Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation.

PubMed

Leung, A Y; Suen, C K; Lie, A K; Liang, R H; Yuen, K Y; Kwong, Y L

2001-09-15

Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 x 10(12) versus 5.7 x 10(7) genome copies/d, P <.001) and larger total amounts of BKV excreted during BMT (4.9 x 10(13) versus 7.7 x 10(8) genome copies, P <.001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT.

Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

PubMed Central

Suess, Thorsten; Remschmidt, Cornelius; Schink, Susanne B.; Schweiger, Brunhilde; Heider, Alla; Milde, Jeanette; Nitsche, Andreas; Schroeder, Kati; Doellinger, Joerg; Braun, Christian; Haas, Walter; Krause, Gérard; Buchholz, Udo

2012-01-01

Background Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany. Methods Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily. Results We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03). Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics. On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status. Conclusion Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was limited. PMID:23240050

Evidence of subclinical foot-and-mouth disease virus infection in young calves born from clinically recovered cow under natural condition

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious and economically important, transboundary viral disease of cloven-hoofed animals. It is known that a chronic, asymptomatic FMD syndrome may occur subsequent to acute FMD in adult ruminants. However, neither asymptomatic nor persistent infection has...

Genital Shedding of Herpes Simplex Virus Among Symptomatic and Asymptomatic Persons with HSV-2 Infection

PubMed Central

Tronstein, Elizabeth; Johnston, Christine; Huang, Meei-Li; Selke, Stacy; Magaret, Amalia; Warren, Terri; Corey, Lawrence; Wald, Anna

2011-01-01

Context Since HSV-2 antibody tests have become commercially available, an increasing number of persons learn that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain. Objective To evaluate the virologic and clinical course of HSV genital shedding among participants with symptomatic and asymptomatic HSV-2 infection. Design, Setting and Participants Cohort of 498 immunocompetent HSV-2 seropositive persons enrolled in prospective studies of genital HSV shedding at the University of Washington Virology Research Clinic, Seattle, Washington, and Westover Heights Clinic in Portland, Oregon, between 1992 and 2008. Each participant obtained daily self-collected swabs of genital secretions for ≥ 30 days. Main Outcome Measurement The rate of viral shedding measured by quantitative real-time fluorescence polymerase chain reaction (PCR) for HSV DNA from genital swabs. Results HSV was detected on 4,753 of 23,683 days (20.1%; 95% CI, 18.3 to 22.0) in persons with symptomatic genital HSV-2 infection compared with 519 of 5,070 days (10.2%; 95% CI, 7.7 to 13.6) in persons with asymptomatic infection, p<0.001. Subclinical shedding rates were higher in persons with symptomatic infection compared with asymptomatic infection (2,708 of 20,735 days (13.1%; 95% CI, 11.5 to14.6) vs. 434 of 4,929 days (8.8%; 95% CI, 6.3 to 11.5), p<0.001. However, the amount of HSV detected during subclinical shedding episodes was similar (median 4.3 [IQR 3.1-5.6] log10 copies in the symptomatic infection group vs. 4.2 [IQR, 2.9-5.5], p=0.27 in the asymptomatic infection group). Days with lesions accounted for 2,045 of 4,753 days (43.0%; 95% CI, 39.8 to 46.5) with genital viral shedding among persons with symptomatic genital HSV-2 infection compared with 85 of 519 days (16.4%; 95% CI, 11.2 to 23.9) among persons with asymptomatic infection, p<0.001. Conclusions Persons with asymptomatic HSV-2 infection shed virus in the genital tract less frequently than persons with symptomatic infection, but much of the difference is attributable to less frequent genital lesions, as lesions are accompanied by frequent viral shedding. PMID:21486977

Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses

PubMed Central

Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G.

2015-01-01

Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID:26139833

First evidence of asymptomatic infection related to the Araucaria (Juquitiba-like) hantavirus.

PubMed

de Borba, Luana; Delfraro, Adriana; Raboni, Sonia M; dos Santos, Claudia Nunes Duarte

2013-08-05

Hantavirus pulmonary syndrome (HPS) is a severe disease, transmitted to humans by inhalation of virus-contaminated aerosols from rodent excreta. Epidemiological, clinical and laboratory data confirmed a fatal HPS case and an asymptomatic infection in a household contact, both caused by Araucaria hantavirus, which has previously been found only in patients with HPS. This is the first report of asymptomatic infection related to a pathogenic hantavirus genotype, highlighting the need for additional studies on characterisation of viral and genetic mechanisms associated with this disease.

Viral infection and antiviral therapy in the neonatal intensive care unit.

PubMed

Barford, Galina; Rentz, Alison C; Faix, Roger G

2004-01-01

Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed. Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease. We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases. Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation.

PubMed

Kourí, Vivian; Correa, Consuelo; Martínez, Pedro A; Sanchez, Lizet; Alvarez, Alina; González, Grehete; Silverio, César E; Hondal, Norma; Florin, Jose; Pérez, Lourdes; Duran, Diana P; Perez, Yardelis; Cazorla, Nancy; Gonzalez, Dalmaris; Jaime, Juan C; Arencibia, Alberto; Sarduy, Sandra; Pérez, Lissette; Soto, Yudira; González, Mabel; Alvarez, Iliana; Dorticós, Elvira; Marchena, Juan J; Solar, Luis; Acosta, Belsy; Savón, Clara; Hengge, Ulrich

2014-01-01

In Cuba, viral monitoring in the post-transplant period was not routinely performed. The aim of this research is to identify the most frequent viruses that affect transplanted Cuban children, by implementing a viral follow-up during the post-transplant period. The study population included all Cuban pediatric patients who underwent solid organ transplantation (SOT) between November 2009 and December 2012. A total of 34 transplanted pediatric patients of kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV) using quantitative real-time polymerase chain reaction (qRT-PCR). Viral genome of at least one virus was detected in 21 of 34 recipients, 18 patients excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%) were the most frequent viruses detected during the follow-up. CMV was the virus mainly associated with clinical symptoms and DNAemia. Its excretion in urine (with cut off value of 219 copies/mL) was associated with detection in plasma (p < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4-29.1, p = 0.001). There was no association between high viral load and clinical complications, due to the prompt initiation of preemptive ganciclovir. This comprehensive viral monitoring program effectively prevents the development of critical viral disease, thus urge the implementation of qRT-PCR as routine for viral monitoring of transplanted Cuban organ recipients.

Influenza A virus infection of healthy piglets in an abattoir in Brazil: animal-human interface and risk for interspecies transmission

PubMed Central

Amorim, Ariane Ribeiro; Fornells, Luz Alba Maria Garcete; Reis, Felicidade da Costa; Rezende, Daiana Jacinto; Mendes, Gabriella da Silva; Couceiro, José Nelson dos Santos Silva; Santos, Norma Suely de Oliveira

2013-01-01

Asymptomatic influenza virus infections in pigs are frequent and the lack of measures for controlling viral spread facilitates the circulation of different virus strains between pigs. The goal of this study was to demonstrate the circulation of influenza A virus strains among asymptomatic piglets in an abattoir in Brazil and discuss the potential public health impacts. Tracheal samples (n = 330) were collected from asymptomatic animals by a veterinarian that also performed visual lung tissue examinations. No slaughtered animals presented with any noticeable macroscopic signs of influenza infection following examination of lung tissues. Samples were then analysed by reverse transcription-polymerase chain reaction that resulted in the identification of 30 (9%) influenza A positive samples. The presence of asymptomatic pig infections suggested that these animals could facilitate virus dissemination and act as a source of infection for the herd, thereby enabling the emergence of influenza outbreaks associated with significant economic losses. Furthermore, the continuous exposure of the farm and abattoir workers to the virus increases the risk for interspecies transmission. Monitoring measures of swine influenza virus infections and vaccination and monitoring of employees for influenza infection should also be considered. In addition regulatory agencies should consider the public health ramifications regarding the potential zoonotic viral transmission between humans and pigs. PMID:23903968

Particulate matter exposure increases JC polyomavirus replication in the human host.

PubMed

Dolci, Maria; Favero, Chiara; Bollati, Valentina; Campo, Laura; Cattaneo, Andrea; Bonzini, Matteo; Villani, Sonia; Ticozzi, Rosalia; Ferrante, Pasquale; Delbue, Serena

2018-05-29

Human polyomaviruses (HPyVs) asymptomatically infect the human population during childhood and establish latency in the host. Viral reactivation and urinary excretion can occur when the immune system is impaired. Exposure to particulate air pollution, including the PM 10 /PM 2.5 components, is a public health problem and has been linked to several disorders. Studies assessing the relationship between PM 10 /PM 2.5 exposure and viral replication are lacking. To investigate the relationship between HPyVs viruria and PM 10 /PM 2.5 exposures. Individual environmental exposure was assessed in 50 healthy adult volunteers using a chemical transport model (CTM) with a municipality resolution for daily PM 10 and monitoring stations data for daily PM 2.5 exposures. For each subject, a urine sample was collected, and HPyVs (JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and HPyV9) loads were determined. Zero-inflated negative binomial (ZINB) regression was used to model the count data, as it contained excessive zeros. Covariates were chosen by stepwise selection. HPyVs DNA was detected in 54% (median:87.6*10 5 copies/ml) of the urine samples. JCPyV was the prevalent (48%, (median viral load:126*10 5 copies/ml). Considering the load of the most frequently measured HPyVs, JCPyV, in the count-part of the ZINB model, every unitary in PM measured 2 days before urine collection (PM Day -2) was associated with an increase in JCPyV load (PM 10 : +4.0%, p-value = 0.002; PM 2.5 : +3.6%, p-value = 0.005). In the zero-part, the significant predictor was the PM 10 measured 5 days before urine collection (+3%, p-value = 0.03). The environmental levels of PM 10 /PM 2.5 increase the JCPyV viruria. Our findings emphasize the need for studies assessing the influence of air pollution exposure on the risk of viral reactivation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of molecular techniques for detection of lymphocystis disease virus in different marine fish species.

PubMed

Cano, I; Ferro, P; Alonso, M C; Bergmann, S M; Römer-Oberdörfer, A; Garcia-Rosado, E; Castro, D; Borrego, J J

2007-01-01

The development and evaluation of a protocol based on polymerase chain reaction (PCR) and nucleic acid hybridization techniques for the specific detection of lymphocystis disease virus (LCDV) in several marine fish species. The pair of primers for PCR, OBL3 and OBL4, was designed based on published nucleotide sequence (LCDV-1) and amplifies a fragment within the major capsid protein. The sensitivity was evaluated using DNA from purified viral particles, as well as from cells inoculated with several viral concentrations. The PCR combined with slot blot was the most sensitive methodology, detecting 2.5 ng of viral DNA. Using this methodology LCDV was detected at 5 days postinoculation from SAF-1 cells initially inoculated with 10(-5) TCID(50) ml(-1). The combination of PCR with membrane hybridization has also been proved to be adequate to detect LCDV from apparently healthy carriers by means of caudal fin sample analysis. This asymptomatic infection was also demonstrated by classical virological methods (cell culture and immunoblot). The protocol described in this study allows the specific detection of LCDV, both in cell cultures and in fin homogenates from asymptomatic fish. The detection of asymptomatic carriers by a rapid molecular method using caudal fin sampling, which does not imply animal killing, could be an important tool to control epizootics caused by LCDV, as fish could be analysed before their introduction and/or mobilization in farm facilities.

Monitoring for HHV-6 infection after renal transplantation: evaluation of risk factors for sustained viral replication.

PubMed

Luiz, Claudia R; Machado, Clarisse M; Canto, Cynthia L M; Christ, Silvia C C; Pestana, Jose O M; Kotton, Camille N; Camargo, Luis F A

2013-03-27

Human herpesvirus-6 (HHV-6) is known to reactivate after renal transplantation and has been associated with several clinical manifestations. Risk factors for sustained viral replication, however, remain unclear. Thirty consecutive kidney transplant patients were prospectively followed for HHV-6 replication between February 2007 and February 2008. Plasma samples for DNA detection were collected from the donor and the recipient before transplantation and from the recipient weekly for the first 2 months after transplantation and then every 2 weeks for 2 additional months. HHV-6 active infection was defined as detection of viral DNA in plasma, by polymerase chain reaction, in at least two consecutive samples over an interval of at least 1 week. Active viral infection was detected in 25% of the recipients before transplantation and 27% (8 of 30) of the patients after transplantation. The mean time to onset of viral replication was 28.1 days after transplantation and 7 of 8 (87.5%) were asymptomatic. Risk factors associated with active HHV-6 infection were receiving an organ from a living donor (P=0.028), recipients with IgM antibodies detected before transplantation (P=0.005), and pretransplantation recipient HHV-6 viral load more than 10,000 copies/mL plasma (P=0.034). Active HHV-6 infection occurs early after renal transplantation and is mostly asymptomatic. Donor or recipient infection may occur at the time of transplantation and are related to higher rates of posttransplantation infections.

Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

PubMed

Medina, Fernando; Quintremil, Sebastián; Alberti, Carolina; Godoy, Fabián; Pando, María E; Bustamante, Andrés; Barriga, Andrés; Cartier, Luis; Puente, Javier; Tanaka, Yuetsu; Valenzuela, María A; Ramírez, Eugenio

2016-03-01

Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+)CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+)CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in non-infected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+)CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers. © 2015 Wiley Periodicals, Inc.

Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children.

PubMed

Monsiváis-Urenda, Adriana; Noyola-Cherpitel, Daniel; Hernández-Salinas, Alba; García-Sepúlveda, Christian; Romo, Neus; Baranda, Lourdes; López-Botet, Miguel; González-Amaro, Roberto

2010-05-01

Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin-like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56-CD3- NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.

A pathological study of the tongues of rabid dogs in the Philippines.

PubMed

Shiwa, Nozomi; Kimitsuki, Kazunori; Manalo, Daria Llenaresas; Inoue, Satoshi; Park, Chun-Ho

2018-06-01

During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner's glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner's glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner's glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner's glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.

Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia

PubMed Central

Madigan, Allison A.; Sobek, Kathryn M.; Cummings, Jessica L.; Green, William R.; Bacich, Dean J.; O’Keefe, Denise S.

2012-01-01

Benign Prostatic Hyperplasia (BPH)is the most common urologic disease in men over age 50. Symptoms include acute urinary retention, urgency to urinate and nocturia. For patients with severe symptoms, surgical treatment is used to remove the affected tissue. Interestingly, the presence of histologic BPH does not always correlate with symptoms. The molecular basis of symptomatic BPH and how it differs from asymptomatic BPH is unknown. Investigation into the molecular players involved in symptomatic BPH will likely give insight into novel therapeutic, and potentially preventative, targets. We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results to prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH). We found that expression of CFI, APOBEC3G, OAS2, and IFIT1, four genes whose protein products are involved in the innate anti-viral immune response, were significantly transcriptionally upregulated in symptomatic BPH. Additionally we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the LINE-1 retrotransposons, in symptomatic BPH when compared to normal prostate tissue. These findings merit further investigation into the anti-viral immune response in symptomatic BPH. PMID:22952051

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

PubMed Central

2013-01-01

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

PubMed

Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

2008-08-01

Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

Vaccine-derived poliovirus from long term excretors and the end game of polio eradication.

PubMed

Martín, Javier

2006-06-01

Seven cases of long-term poliovirus excretion in the UK and Ireland are reviewed in this paper. They include a rare case of long-term virus excretion by a healthy child recently found in Ireland and the case with the longest period of vaccine-derived poliovirus excretion by an immunodeficient individual ever known, 18 years. The evolution of viral properties such as antigenic structure, neurovirulence, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin vaccine strains were studied in detail. The relevance of these cases in the context of the global polio eradication initiative and the design of vaccination strategies for the last stages of eradication and the post-eradication era are discussed.

Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China.

PubMed

Xue, Yu; Jiang, Li; Wan, Wei-Guo; Chen, Yu-Ming; Zhang, Jiong; Zhang, Zhen-Chun

2016-02-05

Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China. Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis. One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P < 0.01; threshold viral loads: 1.75 × 104 copies/ml). Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts (P < 0.01), including CD4+ and CD8+ T-cells (P < 0.01). When CD4+ T-cell count is <0.39 × 109/L, patients are at high risk for pulmonary CMV infection. Patients are prone to be symptomatic with CMV-DNA load >1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells), presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

Association between nasal shedding and fever that influenza A (H3N2) induces in dogs.

PubMed

Song, Daesub; Moon, Hyoungjoon; Jung, Kwonil; Yeom, Minjoo; Kim, Hyekwon; Han, Sangyoon; An, Dongjun; Oh, Jinsik; Kim, Jongman; Park, Bongkyun; Kang, Bokyu

2011-01-05

Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV) H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing) during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5 °C (geometric mean temperature of 39.86 °C ± 0.49) were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID₅₀/ml, which was significantly higher than the viral titer detected in the non fever. The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

Herpesviruses viral loads and levels of proinflammatory cytokines in apical periodontitis.

PubMed

Jakovljevic, A; Knezevic, A; Nikolic, N; Soldatovic, I; Jovanovic, T; Milasin, J; Andric, M

2018-07-01

This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines. A total of 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR. The concentrations of TNF-α, IL-1β and IL-6 were determined by ELISA method. SPSS software was used for statistical analysis. There were no significant differences in the occurrence of EBV and HCMV between symptomatic and asymptomatic periapical lesions (p = .686, p = .879, respectively). Only 12 of 74 EBV (16.2%) and four of 54 HCMV (13.5%) nested PCR-positive samples showed increased viral copy numbers above the limit of 125 copies/ml. There was no significant correlation between the levels of analysed proinflammatory cytokines and herpesviral copy numbers in our sample. The observed low viral loads point to a relatively rare occurrence of active EBV and HCMV infection in our sample. Latent herpesviral infection does not enhance the production of investigated proinflammatory cytokines. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

NASA Astrophysics Data System (ADS)

Wodarz, Dominik

2005-12-01

This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

Impact of rectal gonorrhoea and chlamydia on HIV viral load in the rectum: potential significance for onward transmission.

PubMed

Davies, Olubanke; Costelloe, Sinead; Cross, Gemma; Dew, Tracy; O'Shea, Siobhan; White, John; Fox, Julie

2017-09-01

The aim of this study was to investigate the effect of asymptomatic rectal bacterial sexually transmitted infections (STIs) on rectal HIV viral load (VL). A prospective cohort study of HIV-positive men who have sex with men attending a tertiary centre in London, UK, for their routine HIV care was performed. Forty-two HIV-positive men who have sex with men were recruited between January and August 2014. In participants on antiretroviral therapy (ART), there was no significant difference in rectal VL in those with and without STI ( p = 0.4). All rectal HIV VLs were below the limit of detection (<100 copies/µg of total RNA) whether an STI was present or not. In those not on ART, rectal HIV VL was on average 0.6log 10 lower post STI treatment. The presence of asymptomatic rectal chlamydia and gonorrhoea was not associated with increased rectal HIV VL in those fully suppressed on ART. In the context of effective ART, the presence of rectal gonorrhoea or chlamydia does not appear to increase rectal HIV VL and the risk of increased viral infectivity.

Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.

PubMed

McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G

2012-05-01

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

[Viral and drug-induced liver damage in children with tuberculosis: prevalence, clinical features].

PubMed

Borzakova, S N; Aksenova, V A; Reĭzis, A R

2013-01-01

THE AIM OF THE RESEARCH: Improving the effectiveness of diagnostics and treatment of viral and drug-induced lesions of the liver (DILL) at a tuberculosis in children by identifying the frequency of their distribution, peculiarities of diagnostics and clinics. We examined 242 children in the age from 2 months to 17 years, the patients with different forms of tuberculosis. The prevalence of hepatitis in children with tuberculosis: B - 1,2%, C-0.4%, G - 4,6%, TT - 8,7%. DILL was diagnosed in 67.5% of children - TB patients, in 48% of the children with DILL an asymptomatic course of the disease was noted, however, in 54.4% of the children with DILL cytolitic syndrome was expressed (ALT> standards). The prevalence of viral hepatitis B and C among children with TB is low. The infection with viruses of hepatitis G and TT is more often, but has no significant impact as on the course of tuberculosis, and on the severity of the liver damage. Drug-induced liver damage is a dominant view of pathology of the liver in children - TB patients and is mostly asymptomatic, but with a pronounced cytolitic syndrome.

High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

PubMed Central

Saksela, K; Muchmore, E; Girard, M; Fultz, P; Baltimore, D

1993-01-01

We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and HIV transcription could be rapidly induced in these cells in vitro. These results provide direct evidence of cellular latency of HIV in vivo and suggest that HIV infection in chimpanzees may be a useful model for clinical latency of HIV infection in humans. Images PMID:8230463

Densovirus associated with sea-star wasting disease and mass mortality

USGS Publications Warehouse

Hewson, Ian; Button, Jason B.; Gudenkauf, Brent M.; Miner, Benjamin; Newton, Alisa L.; Gaydos, Joseph K.; Wynne, Janna; Groves, Cathy L.; Hendler, Gordon; Murray, Michael; Fradkin, Steven; Breitbart, Mya; Fahsbender, Elizabeth; Lafferty, Kevin D.; Kilpatrick, A. Marm; Miner, C. Melissa; Raimondi, Peter T.; Lahner, Lesanna L.; Friedman, Carolyn S.; Danielson, Stephen D.; Haulena, Martin; Marliave, Jeffrey; Burge, Colleen A.; Eisenlord, Morgan E.; Harvell, C. Drew

2015-01-01

Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation (“melting”). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus (Parvoviridae). Virus-sized material (i.e., <0.2 μm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality.

Densovirus associated with sea-star wasting disease and mass mortality

PubMed Central

Hewson, Ian; Button, Jason B.; Gudenkauf, Brent M.; Miner, Benjamin; Newton, Alisa L.; Gaydos, Joseph K.; Wynne, Janna; Groves, Cathy L.; Hendler, Gordon; Murray, Michael; Fradkin, Steven; Breitbart, Mya; Fahsbender, Elizabeth; Lafferty, Kevin D.; Kilpatrick, A. Marm; Miner, C. Melissa; Raimondi, Peter; Lahner, Lesanna; Friedman, Carolyn S.; Daniels, Stephen; Haulena, Martin; Marliave, Jeffrey; Burge, Colleen A.; Eisenlord, Morgan E.; Harvell, C. Drew

2014-01-01

Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation (“melting”). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus (Parvoviridae). Virus-sized material (i.e., <0.2 μm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality. PMID:25404293

Densovirus associated with sea-star wasting disease and mass mortality.

PubMed

Hewson, Ian; Button, Jason B; Gudenkauf, Brent M; Miner, Benjamin; Newton, Alisa L; Gaydos, Joseph K; Wynne, Janna; Groves, Cathy L; Hendler, Gordon; Murray, Michael; Fradkin, Steven; Breitbart, Mya; Fahsbender, Elizabeth; Lafferty, Kevin D; Kilpatrick, A Marm; Miner, C Melissa; Raimondi, Peter; Lahner, Lesanna; Friedman, Carolyn S; Daniels, Stephen; Haulena, Martin; Marliave, Jeffrey; Burge, Colleen A; Eisenlord, Morgan E; Harvell, C Drew

2014-12-02

Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation ("melting"). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus (Parvoviridae). Virus-sized material (i.e., <0.2 μm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality.

PREVALENCE AND RISK FACTORS FOR ASYMPTOMATIC INTESTINAL MICROSPORIDIOSIS AMONG ABORIGINAL SCHOOL CHILDREN IN PAHANG, MALAYSIA.

PubMed

Anuar, Tengku Shahrul; Bakar, Nur Hazirah Abu; Al-Mekhlafi, Hesham M; Moktar, Norhayati; Osman, Emelia

2016-05-01

The epidemiology and environmental factors affecting transmission of human microsporidiosis are poorly understood. We conducted the present study to determine the prevalence and risk factors associated with asymptomatic intestinal microsporidiosis among aboriginal school children in the Kuala Krau District, Pahang State, Malaysia. We collected stool samples from 255 school children and examined the samples using Gram-chromotrope Kinyoun stain. We also collected demographic, socioeconomic, environmental and personal hygiene information using a pre-tested questionnaire. Sixty-nine of the children was positive for microsporidia: 72.5% and 27.5% were low (1+) and moderate (2+) excretions of microsporidia spores, respectively. Univariate and multivariate analyses showed being aged 10 years (p = 0.026), using an unsafe water supply as a source for drinking water (p = 0.044) and having close contact with domestic animals (p = 0.031) were all significantly associated with microsporidial infection among study subjects. Our findings suggest asymptomatic intestinal microsporidiosis is common in the study population, more than previously reported. In the study population, control measures need to be implemented, such as good personal hygiene, proper sanitation and safe drinking water supply.

Virus Excretion from Foot-And-Mouth Disease Virus Carrier Cattle and Their Potential Role in Causing New Outbreaks.

PubMed

Parthiban, Aravindh Babu R; Mahapatra, Mana; Gubbins, Simon; Parida, Satya

2015-01-01

The role of foot-and-mouth disease virus (FMDV) carrier cattle in causing new outbreaks is still a matter of debate and it is important to find out these carrier animals by post-outbreak serosurveillance to declare freedom from FMDV infection. In this study we explore the differences in viral shedding between carrier and non-carrier animals, quantify the transmission rate of FMDV infection from carriers to susceptible animals and identify potential viral determinants of viral persistence. We collected nasal and saliva samples from 32 vaccinated and 7 unvaccinated FMDV carrier cattle and 48 vaccinated and 13 unvaccinated non-carrier cattle (total n=100) during the acute phase of infection (up to 28 days post-challenge) and then from limited number of animals up to a maximum 168 days post-challenge. We demonstrate that unvaccinated cattle excrete significantly higher levels of virus for longer periods compared with vaccinated cattle and this is independent of whether or not they subsequently become carriers. By introducing naïve cattle in to the FMDV carrier population we show the risk of new outbreaks is clearly very low in controlled conditions, although there could still be a potential threat of these carrier animals causing new outbreaks in the field situation. Finally, we compared the complete genome sequences of viruses from carrier cattle with the challenge virus and found no evidence for viral determinants of the carrier state.

Shedding and transmission of novel influenza virus A/H1N1 infection in households--Germany, 2009.

PubMed

Suess, Thorsten; Buchholz, Udo; Dupke, Susann; Grunow, Roland; an der Heiden, Matthias; Heider, Alla; Biere, Barbara; Schweiger, Brunhilde; Haas, Walter; Krause, Gérard

2010-06-01

Essential epidemiologic and virologic parameters must be measured to provide evidence for policy/public health recommendations and mathematical modeling concerning novel influenza A/H1N1 virus (NIV) infections. Therefore, from April through August of 2009, the authors collected nasopharyngeal specimens and information on antiviral medication and symptoms from households with NIV infection on a daily basis in Germany. Specimens were analyzed quantitatively by using reverse transcriptase-polymerase chain reaction. In 36 households with 83 household contacts, 15 household contacts became laboratory-confirmed secondary cases of NIV. Among 47 contacts without antiviral prophylaxis, 12 became cases (secondary attack rate of 26%), and 1 (8%) of these was asymptomatic. The mean and median serial interval were 2.6 and 3 days, respectively (range: 1-3 days). On average, the authors detected viral RNA copies for 6.6 illness days (treated in time = 5.7 days, not treated in time = 7.1 days; P = 0.06), but they estimated that most patients cease to excrete viable virus by the fifth illness day. Shedding profiles were consistent with the number and severity of symptoms. Compared with other nasopharyngeal specimen types, nasal wash was the most sensitive. These results support the notion that epidemiologic and virologic characteristics of NIV are in many aspects similar to those of seasonal influenza.

Excretion of Hepatitis A Virus (HAV) in Adults: Comparison of Immunologic and Molecular Detection Methods and Relationship between HAV Positivity and Infectivity in Tamarins

PubMed Central

Polish, Louis B.; Robertson, Betty H.; Khanna, Bhawna; Krawczynski, Krzysztof; Spelbring, John; Olson, Fred; Shapiro, Craig N.

1999-01-01

Fecal excretion of hepatitis A virus (HAV) in 18 patients with HAV infection was evaluated by enzyme immunoassay (EIA) to detect viral antigen and by reverse transcription-PCR amplification followed by ethidium bromide staining (PCR-ETBr) or nucleic acid hybridization (PCR-NA) to detect viral genetic material. A gradation of sensitivity was observed in the detection of virus by the three methods. In persons who had detectable virus, serial stool samples were found to be positive by EIA for up to 24 days after the peak elevation of liver enzymes. Viral genetic material could be detected by PCR-ETBr for up to 34 days and by PCR-NA for up to 54 days after the peak elevation of liver enzymes. After intravenous inoculation of tamarins with stool suspensions categorized as highly reactive for HAV (positive by EIA, PCR-ETBr, and PCR-NA), moderately reactive (positive by PCR-ETBr and PCR-NA), or weakly reactive (positive by PCR-NA), only tamarins infected with highly reactive stool suspensions (EIA positive) developed HAV infection. We conclude that positivity of stool specimens for HAV by PCR-ETBr or PCR-NA indicates a lower potential for infectivity, compared to that of EIA-positive stools. PMID:10523563

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort.

PubMed

Lee, Gwenyth O; McCormick, Benjamin J J; Seidman, Jessica C; Kosek, Margaret N; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A M; Bhutta, Zulfiqar A; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K; Ambikapathi, Ramya; Lang, Dennis R; Gottlieb, Michael; Guerrant, Richard L; Caulfield, Laura E; For The Mal-Ed Network Investigators

2017-07-01

The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort

PubMed Central

Lee, Gwenyth O.; McCormick, Benjamin J. J.; Seidman, Jessica C.; Kosek, Margaret N.; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A. M.; Bhutta, Zulfiqar A.; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J.; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B.; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K.; Ambikapathi, Ramya; Lang, Dennis R.; Gottlieb, Michael; Guerrant, Richard L.; Caulfield, Laura E.

2017-01-01

Abstract. The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function. PMID:28719336

Detection of African swine fever virus DNA in blood samples stored on FTA cards from asymptomatic pigs in Mbeya region, Tanzania.

PubMed

Braae, U C; Johansen, M V; Ngowi, H A; Rasmussen, T B; Nielsen, J; Uttenthal, Å

2015-02-01

The aim of the study was to assess whether blood samples collected onto FTA(®) cards could be used in combination with real-time PCR for the detection of African swine fever virus (ASFV) DNA in samples from resource-poor settings under the assumption that asymptomatically (sub-clinically) infected pigs may be present. Blood samples were collected from clinically healthy pigs from Mbeya Region, Tanzania. The blood samples were stored on FTA(®) cards and analysed by real-time PCR assays in duplicate; three pigs had high levels of viral DNA (Ct values of 27-29), and three pigs had a low level of viral DNA (Ct 36-45). Four pigs were positive in one of the duplicate samples only, but clear products of the expected size were obtained when the reactions were analysed by gel electrophoresis. For comparison, blood samples from pigs experimentally infected with either a pathogenic (OURT T88/1) or a non-pathogenic (OURT T88/3) isolate of ASFV were collected, stored on FTA(®) cards and analysed in the same way. The blood from pigs infected with the OURT T88/1 isolate showed high levels of viral DNA (Ct 22-33), whereas infection with non-pathogenic OURT T88/3 isolate resulted in only low levels of viral DNA (Ct 39) in samples collected at 10-14 days after inoculation. © 2013 Blackwell Verlag GmbH.

Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

PubMed

Gunjan, Deepak; Shalimar; Nadda, Neeti; Kedia, Saurabh; Nayak, Baibaswata; Paul, Shashi B; Gamanagatti, Shivanand Ramachandra; Acharya, Subrat K

2017-06-01

Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

Enhanced inflammation in New Zealand white rabbits when MERS-CoV reinfection occurs in the absence of neutralizing antibody

PubMed Central

Houser, Katherine V.; Gretebeck, Lisa; Vogel, Leatrice; Sutton, Troy; Orandle, Marlene; Moore, Ian N.

2017-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal infection, rabbits developed a transient dose-dependent pulmonary infection with moderately high levels of viral RNA, viral antigen, and perivascular inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed antibodies against viral proteins that lacked neutralizing activity and the animals were not protected from reinfection. In fact, reinfection resulted in enhanced pulmonary inflammation, without an associated increase in viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced inflammation upon infection. We further found this inflammation was accompanied by increased recruitment of complement proteins compared to primary infection. However, reinfection elicited neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a neutralizing antibody response, or persons whose neutralizing antibody titers have waned, may be at risk for severe lung disease on re-exposure to MERS-CoV. PMID:28817732

Blood metabolome profiles of cattle colonized with Escherichia coli O157

USDA-ARS?s Scientific Manuscript database

Metabolomics is being increasingly used for diagnosis of asymptomatic/difficult-to-diagnose diseases in humans including parasitic (i.e. protozoan, schistosomal), viral (i.e. cytomegalovirus), bacterial (i.e. cystic fibrosis caused by Pseudomonas), genetic (i.e. autism) and cancer (i.e. gastric canc...

Passage of an Anterior Odontoid Screw through Gastrointestinal Tract.

PubMed

Leitner, L; Brückmann, C I; Gilg, M M; Bratschitsch, G; Sadoghi, P; Leithner, A; Radl, R

2017-01-01

Purpose . Anterior screw fixation has become a popular surgical treatment method for instable odontoid fractures. Screw loosening and migration are a rare, severe complication following anterior odontoid fixation, which can lead to esophagus perforation and requires revision operation. Methods . We report a case of screw loosening and migration after anterior odontoid fixation, which perforated the esophagus and was excreted without complications in a 78-year-old male patient. Results . A ventral dislocated anterior screw perforated through the esophagus after eight years after implantation and was excreted through the gastrointestinal (GI) tract. At a 6-month follow-up after the event the patient was asymptomatic. Conclusion . Extrusion via the GI tract is not safe enough to be considered as a treatment option for loosened screws. Some improvements could be implemented to prevent such an incident. Furthermore, this case is a fine example that recent preoperative imaging is mandatory before revision surgery for screw loosening.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

PubMed

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

2009-04-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

PubMed Central

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

2009-01-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD. PMID:19390619

[Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing].

PubMed

Calvo, Cristina; Aguado, Isabel; García-García, María Luz; Ruiz-Chercoles, Esther; Díaz-Martinez, Eloisa; Albañil, Rosa María; Campelo, Olga; Olivas, Antonio; Muñóz-Gonzalez, Luisa; Pozo, Francisco; Fernandez-Arroyo, Rosa; Fernandez-Rincón, Adelaida; Calderon, Ana; Casas, Inmaculada

2017-08-01

It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P<.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P<.001 (OR: 2.18; 95% CI: 1.05-4.5). In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Genetic analysis--a diagnostic tool for primary hyperoxaluria type I.

PubMed

Milosevic, Danko; Rinat, Choni; Batinic, Danica; Frishberg, Yaacov

2002-11-01

Primary hyperoxaluria type I is an autosomal recessive metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. The diagnosis may be suspected when clinical signs and increased urinary oxalate and glycolate excretion present, and is confirmed by the measurement of decreased alanine:glyoxylate aminotransferase activity in a liver sample. The enzymatic assay is not readily available to pediatric nephrologists in many parts of the world. We describe three families from Croatia in whom the diagnosis of primary hyperoxaluria was solely based on clinical findings that included nephrolithiasis and nephrocalcinosis accompanied by increased urinary oxalates and glycolate excretion, as enzymatic assays of liver samples could not be performed. Mutation analysis of the AGXT gene encoding the defective enzyme confirmed the diagnosis, revealing three alleles carrying the C156ins mutation and two the G630A mutation. Screening first-degree relatives for the relevant mutation disclosed an asymptomatic affected sibling. Mutation analysis of the AGXT gene is a non-invasive and accurate tool for the diagnosis of type I primary hyperoxaluria that may replace enzymatic assays of liver biopsies.

Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody.

PubMed

Mesenas, Steven J; Chow, Wan C; Zhao, Yi; Lim, Gek K; Oon, Chong J; Ng, Han S

2002-02-01

This study aims to examine the genomic variants of the 'a' epitope in chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Eighteen HBV carriers were studied. Hepatitis B virus (HBV) DNA was extracted and the 'a' epitope region was amplified and sequenced. Eighteen Chinese asymptomatic HBV carriers were studied. There were 13 patients who were positive for both HBsAg and anti-HBs. Of these, one patient had only wild-type HBV, three had a viral mixture, and five had only 'a' epitope variant HBV. Of the three patients with a viral mixture, all had variants in the less conserved region (123-137). Of the five patients with pure HBsAg mutants, three had variants in the less conserved region while two had variants in the highly conserved region. In this study with a limited number of patients, the serum alanine aminotransferase (ALT) levels were higher in patients with wild-type HBV, compared with those with either 'a' epitope variants or a viral mixture consisting of wild type and variants. Eight of the nine (89%) patients positive for both HBsAg and anti-HBs harbored an 'a' epitope variant. The lower ALT levels seen in patients who had either pure 'a' epitope variant or a mixture of wild type and mutants suggest that a closer monitoring of these 'a' epitope variants should be required, as patients carrying these infectious viral strains may remain asymptomatic.

Asymptomatic memory CD8+ T cells

PubMed Central

Khan, Arif Azam; Srivastava, Ruchi; Lopes, Patricia Prado; Wang, Christine; Pham, Thanh T; Cochrane, Justin; Thai, Nhi Thi Uyen; Gutierrez, Lucas; BenMohamed, Lbachir

2014-01-01

Generation and maintenance of high quantity and quality memory CD8+ T cells determine the level of protection from viral, bacterial, and parasitic re-infections, and hence constitutes a primary goal for T cell epitope-based human vaccines and immunotherapeutics. Phenotypically and functionally characterizing memory CD8+ T cells that provide protection against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections, which cause blinding ocular herpes, genital herpes, and oro-facial herpes, is critical for better vaccine design. We have recently categorized 2 new major sub-populations of memory symptomatic and asymptomatic CD8+ T cells based on their phenotype, protective vs. pathogenic function, and anatomical locations. In this report we are discussing a new direction in developing T cell-based human herpes vaccines and immunotherapeutics based on the emerging new concept of “symptomatic and asymptomatic memory CD8+ T cells.” PMID:24499824

[Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection].

PubMed

Alarcón Allen, A; Baquero-Artigao, F

2011-01-01

Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people. Breast milk is the main source of infection, given the high rate of CMV-positive mothers excreting CMV in milk. Freezing reduces the risk of CMV transmission by breastfeeding, although it does not eliminate it completely. Pasteurisation prevents such transmission, but it can alter the immunological properties of breast milk. Postnatal CMV infection is usually asymptomatic, as it normally results from viral reactivation in the mother, and the neonate is born with protective antibodies. However, in the very low birth weight premature infant the amount of transferred antibodies is smaller and a symptomatic infection can occur. Symptomatic post-natal CMV infection in the newborn typically causes hepatitis, neutropenia, thrombocytopenia or sepsis-like syndrome. Pneumonitis and enteritis are less common, but very characteristic. Diagnosis is based on urine virus detection at the time of onset of symptoms. Postnatal CMV infection in the newborn generally resolves spontaneously without antiviral treatment. Ganciclovir should be reserved for severe cases. Unlike congenital CMV disease, post-natal CMV infection in the preterm infant does not seem to be associated with hearing loss or abnormal neuro-development in long term follow-up. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Virus present in the reproductive tract of asymptomatic drones of honey bee (Apis mellifera l.), and possible infection of queen during mating.

PubMed

Da Cruz-Landim, Carminda; Roat, Thaisa C; Fernadez, Fernanda C

2012-07-01

Virus particles and viral inclusions were detected by transmission electron microscopy examination of sections of the seminal vesicles and mucus gland of asymptomatic young drones from colonies of Apis mellifera lightly infested by Varroa mite. In the mucus gland the infection was found in the muscular sheath and epithelium, while in the seminal vesicle in cells of the outer serosa. Isolated viral particles were also observed in the hemolymph occupying the intercellular spaces of the muscular sheath fibers. In the muscle the virus appeared as polygonal crystalloid inclusions, while in the epithelium mainly inside cytoplasmic vesicles. The infected cells apparently are not damaged. The virus particles are present in the hemolymph and forming more mature structures, as crystalloids, in the muscle. This suggests that the virus is liberated in the body fluid and infects the tissues penetrating the cells through endocytosis. The presence of virus in mucus gland epithelial vesicles raise the possibility of its transference to the gland secretion and therefore, to the semen. Copyright © 2012 Wiley Periodicals, Inc.

Lessons from a large norovirus outbreak: impact of viral load, patient age and ward design on duration of symptoms and shedding and likelihood of transmission.

PubMed

Partridge, D G; Evans, C M; Raza, M; Kudesia, G; Parsons, H K

2012-05-01

Hospital norovirus outbreaks cause significant financial and operational disruption which should be minimised by optimal handling of affected areas and use of isolation facilities. To identify factors associated with increased duration of symptoms and viral excretion and increased probability of transmission. Retrospective observational study of a large norovirus outbreak at a UK teaching hospital in the winter of 2009-2010 where patients were diagnosed using a real-time polymerase chain reaction (PCR) assay. Symptom duration was significantly associated with patient age (Spearman rank correlation coefficient: 0.197; P = 0.002) but not with PCR cycle threshold (C(T)) value. Duration of viral excretion was found to be longer in patients with higher viral loads. Transmission within a ward bay was not significantly associated either with age or with C(T) value but was more likely to occur in some ward blocks than others, which may relate to differences in ward design. Transfer of patients into isolation rooms or cohorted area within two days of symptom onset did not significantly influence probability of onward transmission (52% vs 47%; P = 0.67). The presented data suggest that C(T) value may guide timing of repeat sample collection if ongoing gastrointestinal symptoms may relate to other pathologies, and that patients developing symptoms of norovirus may remain in their current bay rather than being moved into isolation facilities. The bay or ward should be closed to new admissions but it should be anticipated that duration of symptoms and therefore closure will be longer when the outbreak involves elderly patients. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Dengue virus life cycle: viral and host factors modulating infectivity.

PubMed

Rodenhuis-Zybert, Izabela A; Wilschut, Jan; Smit, Jolanda M

2010-08-01

Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses.

PubMed

González, Víctor M; Martín, M Elena; Fernández, Gerónimo; García-Sacristán, Ana

2016-12-16

Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers' properties as a real tool for viral infection detection and treatment.

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

PubMed Central

González, Víctor M.; Martín, M. Elena; Fernández, Gerónimo; García-Sacristán, Ana

2016-01-01

Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment. PMID:27999271

Visualization of Arenavirus RNA Species in Individual Cells by Single-Molecule Fluorescence In Situ Hybridization Suggests a Model of Cyclical Infection and Clearance during Persistence.

PubMed

King, Benjamin R; Samacoits, Aubin; Eisenhauer, Philip L; Ziegler, Christopher M; Bruce, Emily A; Zenklusen, Daniel; Zimmer, Christophe; Mueller, Florian; Botten, Jason

2018-06-15

Lymphocytic choriomeningitis mammarenavirus (LCMV) is an enveloped, negative-strand RNA virus that causes serious disease in humans but establishes an asymptomatic, lifelong infection in reservoir rodents. Different models have been proposed to describe how arenaviruses regulate the replication and transcription of their bisegmented, single-stranded RNA genomes, particularly during persistent infection. However, these models were based largely on viral RNA profiling data derived from entire populations of cells. To better understand LCMV replication and transcription at the single-cell level, we established a high-throughput, single-molecule fluorescence in situ hybridization (smFISH) image acquisition and analysis pipeline and examined viral RNA species at discrete time points from virus entry through the late stages of persistent infection in vitro We observed the transcription of viral nucleoprotein and polymerase mRNAs from the incoming S and L segment genomic RNAs, respectively, within 1 h of infection, whereas the transcription of glycoprotein mRNA from the S segment antigenome required ∼4 to 6 h. This confirms the temporal separation of viral gene expression expected due to the ambisense coding strategy of arenaviruses and also suggests that antigenomic RNA contained in virions is not transcriptionally active upon entry. Viral replication and transcription peaked at 36 h postinfection, followed by a progressive loss of viral RNAs over the next several days. During persistence, the majority of cells showed repeating cyclical waves of viral transcription and replication followed by the clearance of viral RNA. Thus, our data support a model of LCMV persistence whereby infected cells can spontaneously clear infection and become reinfected by viral reservoir cells that remain in the population. IMPORTANCE Arenaviruses are human pathogens that can establish asymptomatic, lifelong infections in their rodent reservoirs. Several models have been proposed to explain how arenavirus spread is restricted within host rodents, including the periodic accumulation and loss of replication-competent, but transcriptionally incompetent, viral genomes. A limitation of previous studies was the inability to enumerate viral RNA species at the single-cell level. We developed a high-throughput, smFISH assay and used it to quantitate lymphocytic choriomeningitis mammarenavirus (LCMV) replicative and transcriptional RNA species in individual cells at distinct time points following infection. Our findings support a model whereby productively infected cells can clear infection, including viral RNAs and antigen, and later be reinfected. This information improves our understanding of the timing and possible regulation of LCMV genome replication and transcription during infection. Importantly, the smFISH assay and data analysis pipeline developed here is easily adaptable to other RNA viruses. Copyright © 2018 American Society for Microbiology.

Vanadium release in whole blood, serum and urine of patients implanted with a titanium alloy hip prosthesis.

PubMed

Catalani, S; Stea, S; Beraudi, A; Gilberti, M E; Bordini, B; Toni, A; Apostoli, P

2013-08-01

Vanadium (V) is a minor constituent of the Titanium-Aluminum-Vanadium (TiAlV) alloy currently used in cementless hip prostheses. Present study aimed at verifying the correlation of vanadium levels among different matrices and assessing reference levels of the ion in a population of patients wearing a well-functioning hip prosthesis. Vanadium was measured using Inductive Coupled Plasma Mass Spectrometry (ICP-MS) in whole blood, serum and urine of 129 patients implanted with a TiAlV-alloy hip prosthesis. The values in the serum were above the upper limit of the reference values in 42% of patients (29% in urine and 13% in whole blood). A good correlation among matrices was observed (p < 0.001). The cohort of patients (N = 32) complaining of pain or in which a loosening or damage to the prosthesis was assessed showed a significantly higher excretion of vanadium in urine as compared with the remaining asymptomatic patients (p = 0.001). The 95th percentile distribution of vanadium in the cohort of patients with a well-functioning prosthesis was 0.3 μg/L in whole blood, 0.5 μg/L in serum and 2.8 μg/L in urine, higher that in the unexposed population, especially for urine. The presence of a prosthesis, even though well-functioning, may cause a possible release of vanadium into the blood and a significant urinary excretion. The reference values of vanadium of the asymptomatic patients with titanium alloy hip prostheses supplied information regarding the background exposure level of the ions and their lower and upper limits.

An outbreak of occupational asthma due to chromium and cobalt.

PubMed

Walters, G I; Moore, V C; Robertson, A S; Burge, C B S G; Vellore, A-D; Burge, P S

2012-10-01

Five metal turners employed by an aerospace manufacturer presented to the Birmingham Chest Clinic occupational lung disease unit. Four cases of occupational asthma (OA) due to chromium salt (3) and cobalt (1) were diagnosed by serial peak-expiratory flow measurements and specific inhalation challenge testing. To measure the extent of the outbreak and to provide epidemiological data to ascertain the aetiology. Participants answered a detailed, self-administered questionnaire, designed to detect occupational lung disease. Urine chromium and cobalt excretion, spirometry and exhaled nitric oxide measurements were taken. Those with possible, probable or definite non-OA or OA, after questionnaire, were invited to undertake two-hourly peak flow measurements and received specialist follow-up. A total of 62 workers (95% of workforce) participated. Sixty-one per cent of employees were working in higher metalworking fluid (MWF) exposure areas. Ninety per cent of workers had urinary chromium excretion indicating occupational exposure. Sixty-six per cent of workers reported active respiratory symptoms, although there were no significant differences between exposure groups. Two further workers with probable OA were identified and had significantly higher urinary chromium and cobalt concentration than asymptomatic controls. Eighteen cases of occupational rhinitis (OR) were identified, with significantly raised urinary chromium concentration compared with asymptomatic controls. Chromium salt and cobalt can be responsible for OA and OR in workers exposed to MWF aerosols. Onset of symptoms in those with positive specific challenges followed change in MWF brand. Workers with OA had increased urinary concentrations of chromium and cobalt, and those with OR had increased urinary concentrations of chromium.

Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

PubMed

Bucy, Daniel S; Brown, Mark S; Bielefeldt-Ohmann, Helle; Thompson, Jesse; Bachand, Annette M; Morges, Michelle; Elder, John H; Vandewoude, Sue; Kraft, Susan L

2011-08-01

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells

PubMed Central

Lin, C.; Agnes, J. T.; Behrens, N.; Tagawa, Y.; Gershwin, L. J.; Corbeil, L. B.

2016-01-01

Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2—RSAD2) and ISG15 (IFN-stimulated gene 15—ubiquitin-like modifier) were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo. PMID:26859677

Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

PubMed

Lin, C; Agnes, J T; Behrens, N; Shao, M; Tagawa, Y; Gershwin, L J; Corbeil, L B

2016-01-01

Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2) and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier) were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

Evaluation of Different Antiretroviral Drug Protocols on Naturally Infected Feline Immunodeficiency Virus (FIV) Cats in the late Phase of the Asymptomatic Stage of Infection

PubMed Central

Gómez, Nélida V.; Fontanals, Adriana; Castillo, Víctor; Gisbert, María A.; Suraniti, Adriana; Mira, Graciela; Pisano, Paola B.

2012-01-01

The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV) alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α); ZDV + Lamivudine (3TC) and ZDV + valproic acid (Valp) on naturally feline immunodeficiency virus (FIV)-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP) and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups) only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV. PMID:22816032

Foot-and-mouth disease virus-associated abortion and vertical transmission following acute infection in cattle under natural conditions

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic as well as more than 70 wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. T...

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twite, Nicolas; Andrei, Graciela; Kummert, Caroline

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMVmore » by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.« less

Inflammatory and neurodegeneration markers during asymptomatic HSV-1 reactivation.

PubMed

Martin, Carolina; Aguila, Blanca; Araya, Paulina; Vio, Karin; Valdivia, Sharin; Zambrano, Angara; Concha, Margarita I; Otth, Carola

2014-01-01

Currently, it is unclear whether asymptomatic recurrent reactivations of herpes simplex virus type 1 (HSV-1) occur in the central nervous systems of infected people, and if these events could lead to a progressive deterioration of neuronal function. In this context, HSV-1 constitutes an important candidate to be included among the risk factors for the development of neuropathies associated with chronic neuroinflammation. The aim of this study was to assess in vivo inflammatory and neurodegenerative markers in the brain during productive and latent HSV-1 infection using a mouse model of herpes simplex encephalitis. Neuroinflammation and neurodegeneration markers were evaluated in mice trigeminal ganglia and cerebral cortex during HSV-1 infection, by immunohistochemistry, western blot, and RT-PCR. Neuronal ICP4 viral antigen expression indicative of a reactivation episode during asymptomatic latency of HSV-1 infection in mice was accompanied by upregulation of neuroinflammatory (toll-like receptor-4, interferon α/β, and p-IRF3) and early neurodegenerative markers (phospho-tau and TauC3). HSV-1 reactivation from latency induced neuroinflammatory and neurodegenerative markers in the brain of asymptomatic mice suggesting that recurrent reactivations could be associated with cumulative neuronal dysfunctions.

Cerebrospinal fluid biomarkers of simian immunodeficiency virus encephalitis

PubMed Central

Bissel, Stephanie J.; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R.; Wiley, Clayton A.

2016-01-01

Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease. PMID:27059917

Development and application of a real-time PCR assay for the detection and quantitation of lymphocystis disease virus.

PubMed

Ciulli, Sara; Pinheiro, Ana Cristina de Aguiar Saldana; Volpe, Enrico; Moscato, Michele; Jung, Tae Sung; Galeotti, Marco; Stellino, Sabrina; Farneti, Riccardo; Prosperi, Santino

2015-03-01

Lymphocystis disease virus (LCDV) is responsible for a chronic self-limiting disease that affects more than 125 teleosts. Viral isolation of LCDV is difficult, time-consuming and often ineffective; the development of a rapid and specific tool to detect and quantify LCDV is desirable for both diagnosis and pathogenic studies. In this study, a quantitative real-time PCR (qPCR) assay was developed using a Sybr-Green-based assay targeting a highly conserved region of the MCP gene. Primers were designed on a multiple alignment that included all known LCDV genotypes. The viral DNA segment was cloned within a plasmid to generate a standard curve. The limit of detection was as low as 2.6DNA copies/μl of plasmid and the qPCR was able to detect viral DNA from cell culture lysates and tissues at levels ten-times lower than conventional PCR. Both gilthead seabream and olive flounder LCDV has been amplified, and an in silico assay showed that LCDV of all genotypes can be amplified. LCDV was detected in target and non-target tissues of both diseased and asymptomatic fish. The LCDV qPCR assay developed in this study is highly sensitive, specific, reproducible and versatile for the detection and quantitation of Lymphocystivirus, and may also be used for asymptomatic carrier detection or pathogenesis studies of different LCDV strains. Copyright © 2014 Elsevier B.V. All rights reserved.

Sabin and wild polioviruses from apparently healthy primary school children in northeastern Nigeria.

PubMed

Baba, M M; Oderinde, B S; Patrick, P Z; Jarmai, M M

2012-02-01

Despite significant success of the Global Polio Eradication Initiative (GPEI) in Nigeria, Afghanistan, India, Pakistan, wild poliovirus still occurs due to persistently high proportions of under and unimmunized children. The study aimed at determining the type of poliovirus often excreted into the environment. Four hundred nine fecal samples collected from apparently healthy school children aged 5-16 years in Borno and Adamawa States, northeastern Nigeria, were tested for poliovirus by tissue culture technique. The isolates were characterized further by intratypic differentiation testing and genetic sequencing. Three wild poliovirus type, 11 Sabin type, combination of Sabin-types 1 + 2 and 2 + 3 poliovirus, and 22 non-polio enteroviruses were obtained. The continued excretion of wild-type poliovirus among children above 5 years old vaccinated with oral polio vaccine contributes to the persistent circulation of these viruses in the environment and may limit the population immunity. However, the excreted Sabin poliovirus is capable of immunizing the unvaccinated children and promotes herd immunity. Similarly, the excretion of combination of two polio serotypes indicates the child susceptibility to the missing serotype (s) and therefore indicates an immunity gap. The common unhygienic practices in the environment could aid the spread of these viruses through oral-fecal route. Asymptomatic transmission of wild poliovirus among older oral polio vaccine-vaccinated children poses a serious threat to polio eradication program in Nigeria and therefore, environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria. Copyright © 2011 Wiley Periodicals, Inc.

Emydid herpesvirus 1 infection in northern map turtles (Graptemys geographica) and painted turtles (Chrysemys picta).

PubMed

Ossiboff, Robert J; Newton, Alisa L; Seimon, Tracie A; Moore, Robert P; McAloose, Denise

2015-05-01

A captive, juvenile, female northern map turtle (Graptemys geographica) was found dead following a brief period of weakness and nasal discharge. Postmortem examination identified pneumonia with necrosis and numerous epithelial, intranuclear viral inclusion bodies, consistent with herpesviral pneumonia. Similar intranuclear inclusions were also associated with foci of hepatocellular and splenic necrosis. Polymerase chain reaction (PCR) screening of fresh, frozen liver for the herpesviral DNA-dependent DNA polymerase gene yielded an amplicon with 99.2% similarity to recently described emydid herpesvirus 1 (EmyHV-1). Molecular screening of turtles housed in enclosures that shared a common circulation system with the affected map turtle identified 4 asymptomatic, EmyHV-1 PCR-positive painted turtles (Chrysemys picta) and 1 asymptomatic northern map turtle. Herpesvirus transmission between painted and map turtles has been previously suggested, and our report provides the molecular characterization of a herpesvirus in asymptomatic painted turtles that can cause fatal herpesvirus-associated disease in northern map turtles. © 2015 The Author(s).

Association between feline immunodeficiency virus (FIV) plasma viral RNA load, concentration of acute phase proteins and disease severity.

PubMed

Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne

2014-08-01

Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.

Subclinical bovine vaccinia: An important risk factor in the epidemiology of this zoonosis in cattle.

PubMed

Rehfeld, Izabelle Silva; Matos, Ana Carolina Diniz; Guedes, Maria Isabel Maldonado Coelho; Costa, Aristóteles Gomes; Fraiha, Ana Luiza Soares; Lobato, Zélia Inês Portela

2017-10-01

Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV) that mainly affects lactating cows and dairy farm milkers. The epidemiological role(s) of other cattle categories such as dry cows, bulls, and heifers in BV remains unclear. This study was performed to investigate VACV in affected dairy cattle herds and perifocal farms during an outbreak in Brazil. Crusts from lesions of cows' teats were collected from all farms with BV outbreaks. Milk, feces, blood, and serum were collected from symptomatic and asymptomatic lactating cows. Blood and serum were also sampled from other cattle categories (calves, heifers, dry cows, and bulls). The samples were tested for VACV by PCR, and to confirm VACV viability, VACV-positive samples were inoculated in BSC-40 cells and stained using immunoperoxidase. Neutralizing antibodies were investigated using plaque reduction neutralization test. Viral DNA was detected in milk, blood, and feces samples of symptomatic and asymptomatic dairy cows and in blood samples from other cattle categories on farms with and without confirmed BV outbreak. In affected farms, viable virus was identified in feces and milk samples from lactating cows and in blood samples from asymptomatic dry cows. Viable VACV was also identified in feces from lactating cows and one bull's blood sample from perifocal farms. Neutralizing antibodies were detected in 81.6% of the herds affected by BV and in 53.8% of the herds on perifocal farms. The presented data indicate a potential source of viral dissemination, which contributes to the persistence and spread of VACV in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ovine herpesvirus 2 glycoproteins B, H, and L are sufficient for, and viral glycoprotein Ov8 can enhance, cell-cell membrane fusion

USDA-ARS?s Scientific Manuscript database

Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus in the genus Macavirus that is carried asymptomatically by sheep. Infection of poorly adapted animals with OvHV-2 results in sheep associated malignant catarrhal fever, a fatal disease characterized by lymphoproliferation and vasculitis. There is no...

Deep sequencing of viral small-RNAs of citrus tristeza virus (CTV) reveals genomic differences between two Italian isolates of CTV

USDA-ARS?s Scientific Manuscript database

A recent Citrus tristeza virus (CTV) epidemic of quick decline (QD) killed many sweet orange trees grafted on sour orange rootstock in Sicily but left some asymptomatic trees in the same field. Recent reports indicated cross-protection involves exclusion of a severe CTV strain by a mild strain of th...

Molecular Characterization of Polio from Environmental Samples: ISSP, The Israeli Sewage Surveillance Protocol.

PubMed

Shulman, Lester M; Manor, Yossi; Hindiyeh, Musa; Sofer, Danit; Mendelson, Ella

2016-01-01

Polioviruses are enteric viruses that cause paralytic poliomyelitis in less than 0.5 % of infections and are asymptomatic in >90 % infections of naïve hosts. Environmental surveillance monitors polio in populations rather than in individuals. When this very low morbidity to infection ratio, drops drastically in highly vaccinated populations, environmental surveillance employing manual or automatic sampling coupled with molecular analysis carried out in well-equipped central laboratories becomes the surveillance method of choice since polioviruses are excreted by infected individuals regardless of whether or not the infection is symptomatic. This chapter describes a high throughput rapid turn-around time method for molecular characterization of polioviruses from sewage. It is presented in five modules: (1) Sewage collection and concentration of the viruses in the sewage; (2) Cell cultures for identification of virus in the concentrated sewage; (3) Nucleic acid extractions directly from sewage and from tissue cultures infected with aliquots of concentrated sewage; (4) Nucleic Acid Amplification for poliovirus serotype identification and intratypic differentiation (discriminating wild and vaccine derived polioviruses form vaccine strains); and (5) Molecular characterization of viral RNA by qRT-PCR, TR-PCR, and Sequence analysis. Monitoring silent or symptomatic transmission of vaccine-derived polioviruses or wild polioviruses is critical for the endgame of poliovirus eradication. We present methods for adapting standard kits and validating the changes for this purpose based on experience gained during the recent introduction and sustained transmission of a wild type 1 poliovirus in Israel in 2013 in a population with an initial IPV vaccine coverage >90 %.

Hepatitis A: Old and New

PubMed Central

Cuthbert, Jennifer A.

2001-01-01

The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated. PMID:11148002

Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes ▿

PubMed Central

Snooks, Michelle J.; Bhat, Purnima; Mackenzie, Jason; Counihan, Natalie A.; Vaughan, Nicola; Anderson, David A.

2008-01-01

Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of HAV via the apical domain of polarized hepatocytes. We have developed a subclone of hepatocyte-derived HepG2 cells (clone N6) that maintains functional characteristics of polarized hepatocytes but displays morphology typical of columnar epithelial cells, rather than the complex morphology that is typical of hepatocytes. N6 cells form microcolonies of polarized cells when grown on glass and confluent monolayers of polarized cells on semipermeable membranes. When N6 microcolonies were exposed to HAV, infection was restricted to peripheral cells of polarized colonies, whereas all cells could be infected in colonies of nonpolarized HepG2 cells (clone C11) or following disruption of tight junctions in N6 colonies with EGTA. This suggests that viral entry occurs predominantly via the basolateral plasma membrane, consistent with uptake of virus from the bloodstream after enteric exposure, as expected. Viral export was also found to be markedly vectorial in N6 but not C11 cells. However, rather than being exported from the apical domain as expected, more than 95% of HAV was exported via the basolateral domain of N6 cells, suggesting that virus is first excreted from infected hepatocytes into the bloodstream rather than to the biliary tree. Enteric excretion of HAV may therefore rely on reuptake and transcytosis of progeny HAV across hepatocytes into the bile. These studies provide the first example of the interactions between viruses and polarized hepatocytes. PMID:18579610

Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 4. Infective doses and pathogen carriage.

PubMed

Todd, Ewen C D; Greig, Judy D; Bartleson, Charles A; Michaels, Barry S

2008-11-01

In this article, the fourth in a series reviewing the role of food workers in foodborne outbreaks, background information on the presence of enteric pathogens in the community, the numbers of organisms required to initiate an infection, and the length of carriage are presented. Although workers have been implicated in outbreaks, they were not always aware of their infections, either because they were in the prodromic phase before symptoms began or because they were asymptomatic carriers. Pathogens of fecal, nose or throat, and skin origin are most likely to be transmitted by the hands, highlighting the need for effective hand hygiene and other barriers to pathogen contamination, such as no bare hand contact with ready-to-eat food. The pathogens most likely to be transmitted by food workers are norovirus, hepatitis A virus, Salmonella, Shigella, and Staphylococcus aureus. However, other pathogens have been implicated in worker-associated outbreaks or have the potential to be implicated. In this study, the likelihood of pathogen involvement in foodborne outbreaks where infected workers have been implicated was examined, based on infectious dose, carriage rate in the community, duration of illness, and length of pathogen excretion. Infectious dose estimates are based on volunteer studies (mostly early experiments) or data from outbreaks. Although there is considerable uncertainty associated with these data, some pathogens appear to be able to infect at doses as low as 1 to 100 units, including viruses, parasites, and some bacteria. Lengthy postsymptomatic shedding periods and excretion by asymptomatic individuals of many enteric pathogens is an important issue for the hygienic management of food workers.

Estimation model for habitual 24-hour urinary-sodium excretion using simple questionnaires from normotensive Koreans.

PubMed

Kong, Ji-Sook; Lee, Yeon-Kyung; Kim, Mi Kyung; Choi, Mi-Kyeong; Heo, Young-Ran; Hyun, Taisun; Kim, Sun Mee; Lyu, Eun-Soon; Oh, Se-Young; Park, Hae-Ryun; Rhee, Moo-Yong; Ro, Hee-Kyong; Song, Mi Kyung

2018-01-01

This study was conducted to develop an equation for estimation of 24-h urinary-sodium excretion that can serve as an alternative to 24-h dietary recall and 24-h urine collection for normotensive Korean adults. In total, data on 640 healthy Korean adults aged 19 to 69 years from 4 regions of the country were collected as a training set. In order to externally validate the equation developed from that training set, 200 subjects were recruited independently as a validation set. Due to heterogeneity by gender, we constructed a gender-specific equation for estimation of 24-h urinary-sodium excretion by using a multivariable linear regression model and assessed the performance of the developed equation in validation set. The best model consisted of age, body weight, dietary behavior ('eating salty food', 'Kimchi consumption', 'Korean soup or stew consumption', 'soy sauce or red pepper paste consumption'), and smoking status in men, and age, body weight, dietary behavior ('salt preference', 'eating salty food', 'checking sodium content for processed foods', 'nut consumption'), and smoking status in women, respectively. When this model was tested in the external validation set, the mean bias between the measured and estimated 24-h urinary-sodium excretion from Bland-Altman plots was -1.92 (95% CI: -113, 110) mmol/d for men and -1.51 (95% CI: -90.6, 87.6) mmol/d for women. The cut-points of sodium intake calculated based on the equations were ≥4,000 mg/d for men and ≥3,500 mg/d for women, with 89.8 and 76.6% sensitivity and 29.3 and 64.2% specificity, respectively. In this study, a habitual 24-hour urinary-sodium-excretion-estimation model of normotensive Korean adults based on anthropometric and lifestyle factors was developed and showed feasibility for an asymptomatic population.

Estimation model for habitual 24-hour urinary-sodium excretion using simple questionnaires from normotensive Koreans

PubMed Central

Choi, Mi-Kyeong; Heo, Young-Ran; Hyun, Taisun; Kim, Sun Mee; Lyu, Eun-Soon; Oh, Se-Young; Park, Hae-Ryun; Rhee, Moo-Yong; Ro, Hee-Kyong; Song, Mi Kyung

2018-01-01

This study was conducted to develop an equation for estimation of 24-h urinary-sodium excretion that can serve as an alternative to 24-h dietary recall and 24-h urine collection for normotensive Korean adults. In total, data on 640 healthy Korean adults aged 19 to 69 years from 4 regions of the country were collected as a training set. In order to externally validate the equation developed from that training set, 200 subjects were recruited independently as a validation set. Due to heterogeneity by gender, we constructed a gender-specific equation for estimation of 24-h urinary-sodium excretion by using a multivariable linear regression model and assessed the performance of the developed equation in validation set. The best model consisted of age, body weight, dietary behavior (‘eating salty food’, ‘Kimchi consumption’, ‘Korean soup or stew consumption’, ‘soy sauce or red pepper paste consumption’), and smoking status in men, and age, body weight, dietary behavior (‘salt preference’, ‘eating salty food’, ‘checking sodium content for processed foods’, ‘nut consumption’), and smoking status in women, respectively. When this model was tested in the external validation set, the mean bias between the measured and estimated 24-h urinary-sodium excretion from Bland-Altman plots was -1.92 (95% CI: -113, 110) mmol/d for men and -1.51 (95% CI: -90.6, 87.6) mmol/d for women. The cut-points of sodium intake calculated based on the equations were ≥4,000 mg/d for men and ≥3,500 mg/d for women, with 89.8 and 76.6% sensitivity and 29.3 and 64.2% specificity, respectively. In this study, a habitual 24-hour urinary-sodium-excretion-estimation model of normotensive Korean adults based on anthropometric and lifestyle factors was developed and showed feasibility for an asymptomatic population. PMID:29447201

HTLV-III: Intra-BBB IgG Synthesis and Hybridization in CSF Cells

DTIC Science & Technology

1989-01-31

neuropsychologic testing in otherwise asymptomatic individuals [ 9], to a bedridden state marked by global dementia, severe hypokinesis, mutism , incontinence...could result from infection by more than one strain, mutation in vivo, viral adaptation, or host cell selection from a heterogeneous virus population...lower than ours -personal communication, Marshall, Nov. 1988), and their selection by military recruitment personnel for overall good physical health. The

A Cluster of Hepatitis A Viral Infection in HSE South.

PubMed

Ferris, H A; Dillon, A; O'Sullivan, M B

2017-06-09

Hepatitis A is an acute viral infection of the liver that produces clinical features ranging from asymptomatic infection to fulminant hepatitis 1 . The authors report a cluster of 5 serologically-confirmed cases of acute Hepatitis A Virus (HAV), all serum IgM positive for HAV Genotype 1A. This is on a background of only 2 other cases notified to HSE-South in 2016 to date, both travel related. There was a considerable delay in notification in two out of 5 cases. This case report highlights the importance of prompt notification of Hepatitis A, as timely notification would have facilitated prompt contact vaccination and might well have prevented illness in two subsequent household contacts.

Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques

PubMed Central

Graham, Victoria A.; Bewley, Kevin R.; Dennis, Mike; Taylor, Irene; Funnell, Simon G. P.; Bate, Simon R.; Steeds, Kimberley; Tipton, Thomas; Bean, Thomas; Hudson, Laura; Atkinson, Deborah J.; McLuckie, Gemma; Charlwood, Melanie; Roberts, Allen D. G.; Vipond, Julia

2013-01-01

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies. PMID:23658452

[Comparison of clinical and laboratory characteristics of viral hepatitis A and E in Montenegro].

PubMed

Terzić, Dragica; Mijović, Gordana; Dupanović, Brankica; Drasković, Nenad; Svirtlih, Neda

2010-01-01

Hepatitis E has many similarities in with hepatitis A concerning clinical picture, route of transmission and nonexistence of chronicity. Comparison of clinical and laboratory parameters of patients with hepatitis A and E to estimate characteristics of these diseases. Total of 54 patients divided into two groups was investigated: 27 had hepatitis A, others had hepatitis E. Detailed history past, clinical examination, liver function tests and ultrasonography of the upper abdomen, were done in all patients. Aetiology of viral hepatitis was investigated serologically by enzyme immunoassay (ELISA) using commercial kits for following viruses: Hepatitis A-E viruses, cytomegalovirus, and Epstein-Barr virus. Asymptomatic infections (29.6%) and clinical forms without jaundice (59.3%) were more frequent in patients with hepatitis E. Splenomegaly was found more frequent in patients with hepatitis A than in hepatitis E (66.7% vs. 33.3%). Patients with hepatitis E had significantly lower activity of aminotransferases than patients with hepatitis A. A significant increase of gamma-glutamyltranspeptidase was found in patients with hepatitis E (mean value: 120 IU/L). Our results are in concordance with other reports that hepatitis E virus infection is more common asymptomatic disease than hepatitis A. In addition, hepatocyte necrosis in hepatitis E is less extensive than in hepatitis A measured by the activity of aminotransferases. Contrary to that the value of gamma-glutamyltranspeptidase is more increased in hepatitis E than in hepatitis A without exact explanation so far: Viral hepatitis E and A have differences in some clinical features and laboratory parameters although both diseases principally have resolved without consequences after 6-8 weeks.

Excretion of moxidectin into breast milk and pharmacokinetics in healthy lactating women.

PubMed

Korth-Bradley, Joan M; Parks, Virginia; Chalon, Stephan; Gourley, Ian; Matschke, Kyle; Gossart, Sophie; Bryson, Philip; Fleckenstein, Lawrence

2011-11-01

Moxidectin, registered worldwide as a veterinary antiparasitic agent, is currently under development for humans for the treatment of onchocerciasis in collaboration with the World Health Organization. The objective of this study was to assess the pharmacokinetics of moxidectin in healthy lactating women, including the excretion into breast milk. Twelve women, ages 23 to 38 years, weighing 54 to 79 kg, all more than 5 months postpartum, were enrolled, following their plan to wean their infants and provision of informed consent. A single 8-mg, open-label dose was administered orally after consumption of a standard breakfast. Complete milk collection was done for approximately 28 days, and plasma samples were collected for 90 days. Moxidectin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorescence detection, with a validated range of 0.08 to 120 ng/ml. Noncompartmental pharmacokinetic methods were used to find the following results: peak concentration in plasma (C(max)), 87 ± 25 ng/ml; time to C(max) (t(max)), 4.18 ± 1.59 h; terminal-phase elimination half-life (t(1/2)), 832 ± 321 h; total area under the concentration-time curve (AUC), 4,046 ± 1,796 ng · h/ml; apparent oral dose clearance (CL/F), 2.35 ± 1.07 l/h; ratio of CL/F to the terminal-phase disposition rate constant, λ(z) (Vλ(z)/F), 2,526 ± 772 liters; percentage of maternal dose excreted in milk, 0.701 ± 0.299%; absolute amount excreted in milk, 0.056 ± 0.024 mg; relative infant dose, 8.73 ± 3.17% of maternal dose assuming complete absorption; clearance in milk (CL(milk)), 0.016 ± 0.009 liter/h. Nine of 12 subjects reported adverse events, all of which were considered treatment emergent but not drug related and were mostly reported during the long outpatient period 8 to 90 days after dose administration. The most frequently reported adverse events were headache and nausea (n = 4), oropharyngeal pain (n = 2), rhinitis, viral pharyngitis, and viral upper respiratory tract infection (n = 2).

Importance of viruses in acute otitis media.

PubMed

Nokso-Koivisto, Johanna; Marom, Tal; Chonmaitree, Tasnee

2015-02-01

Acute otitis media occurs as a complication of viral upper respiratory tract infection. Bacterial otopathogens and respiratory viruses interact and play important roles in acute otitis media development. A better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease. There has been increasing evidence that acute otitis media occurs during upper respiratory infection, even in the absence of nasopharyngeal bacterial colonization. Among the types of viruses associated with acute otitis media, respiratory syncytial virus continues to be the most commonly detected. It is still unclear whether viral load plays an important role in acute otitis media development, but symptomatic upper respiratory tract infection (as opposed to asymptomatic viral infection) is crucial. Widespread use of bacterial and viral vaccines in young children, including pneumococcal conjugate and influenza vaccines, has led to the reduction in otitis media-related healthcare use between 2001 and 2011. There has been no new vaccine against respiratory viruses other than influenza. Progress has been made toward the reduction of the burden of acute otitis media in the last decade. Success in reducing acute otitis media incidence will rely mainly on prevention of nasopharyngeal otopathogen colonization, as well as reduction in the incidence of viral upper respiratory tract infection.

[Mother-infant and indirect transmission of HSV infection: treatment and prevention].

PubMed

Henrot, A

2002-04-01

Neonatal herpes is a serious condition. The objectives of this critical review of the literature are to: 1) define the modes of mother-infant and indirect transmission of HSV infection; 2) determine current treatments and perspectives for the future. We searched for articles published since 1980 in databases using a series of key words. The articles were classed into three categories by level of scientific proof: good (level 1), fair (level 2), poor (level 3, 4 or 5). General reviews were excluded. We selected 153 articles and retained 96. Man to woman contamination was generally reported: 10p.100 of the couples were serodiscordant. Presence of anti-HSV1 antibodies was partially protective against HSV2 infection. Neonates can be contaminated in utero via transplacental hematogenic transmission, at delivery (the most frequent route), or during the postnatal period (indirect transmission). The risk of neonatal contamination is greatest for primary infection (PI) or non-primary infection occurring the last month of pregnancy (50p.100), but transmission is low for maternal recurrence during the week before delivery (5p.100). Cesarean section is mandatory in case of genital PI or non-primary maternal infection during the last month of pregnancy, especially in case of membrane rupture<6 hr, but does not protect the infant in two-thirds of the cases. The decision for cesarean is controversial in case of recurrence. Antiviral treatment of the mother using aciclovir (ACV) is well tolerated. ACV-cesarean combination provides maximal protection for the neonate. A neonate with proven or suspected HSV infection should be isolated from other neonates but not from the mother. Breastfeeding is contraindicated in case of breast lesions. Parenteral ACV 60 g/kg/d is preferred over vidarabine. It should be started immediately after the first virology samples. The risk of recurrence is estimated at 7p.100 for all neonates and warrants treatment using a high oral dose (90-100mg/kg/d) due to the low bioavailability, if the number of recurrences is>3 in 6 months. Antiviral treatment is formally indicated if: 1) neonate viral cultures are positive at day 1 and day 3, 2) clinical lesions suggest herpes, 3) neurological disorders or signs of sepsis with negative bacteriology are present and the mother has a history of herpes or contact with labial herpes; and can be discussed if: 4) PI is proven at delivery or during the last month of pregnancy (irrespective of the delivery route, even if the mother is treated or if the membranes are intact), 5) late cesarean (membrane rupture>4 h) with clinical herpes at delivery, 6) vaginal delivery and recurrent herpes within the last month with associated clinical risk factor(s). Many points remain to be clarified concerning optimal management of the mother-infant couple in case of maternal herpes during pregnancy or at delivery. New perspectives concerning diagnosis and prevention of neonatal contamination include: identification of asymptomatic primary infections using rapid identification of genital viral antigen during delivery, identification of women with a risk of asymptomatic excretion using specific serology tests for the pregnant woman and her partner, antiviral treatment for men, topical genital treatments, vaccination of women at risk, monoclonal antibodies, new antiviral agents with mechanisms of action independent of viral thymidine kinase.

Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

PubMed Central

DiNapoli, Sarah R.; Hirsch, Vanessa M.

2016-01-01

The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus. PMID:27307568

Detection of Salmonella enterica Serovar Typhimurium by Using a Rapid, Array-Based Immunosensor

PubMed Central

Taitt, Chris Rowe; Shubin, Yura S.; Angel, Roselina; Ligler, Frances S.

2004-01-01

The multianalyte array biosensor (MAAB) is a rapid analysis instrument capable of detecting multiple analytes simultaneously. Rapid (15-min), single-analyte sandwich immunoassays were developed for the detection of Salmonella enterica serovar Typhimurium, with a detection limit of 8 × 104 CFU/ml; the limit of detection was improved 10-fold by lengthening the assay protocol to 1 h. S. enterica serovar Typhimurium was also detected in the following spiked foodstuffs, with minimal sample preparation: sausage, cantaloupe, whole liquid egg, alfalfa sprouts, and chicken carcass rinse. Cross-reactivity tests were performed with Escherichia coli and Campylobacter jejuni. To determine whether the MAAB has potential as a screening tool for the diagnosis of asymptomatic Salmonella infection of poultry, chicken excretal samples from a private, noncommercial farm and from university poultry facilities were tested. While the private farm excreta gave rise to signals significantly above the buffer blanks, none of the university samples tested positive for S. enterica serovar Typhimurium without spiking; dose-response curves of spiked excretal samples from university-raised poultry gave limits of detection of 8 × 103 CFU/g. PMID:14711637

Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric aciduria type I.

PubMed

Herskovitz, Moshe; Goldsher, Dorith; Sela, Ben-Ami; Mandel, Hanna

2013-08-27

Glutaric aciduria type I (GA-I) is an autosomal recessive disease caused by a deficiency of the mitochondrial enzyme glutaryl CoA dehydrogenase (GCDH). This metabolic block causes increased urinary concentrations of glutaric and 3-hydroxyglutaric acids. The accumulation and excretion of glutarylcarnitine esters leads to secondary carnitine deficiency. GA-I has an incidence of 1:30,000. The clinical hallmark of GA-I is an acute encephalopathic crisis, with bilateral striatal necrosis presented by severe dystonic dyskinetic disorder. Most patients have their first symptoms during infancy, but some have a less severe form of the disease and some may even remain asymptomatic.

Fluid control mechanisms in weightlessness

NASA Technical Reports Server (NTRS)

Leach, Carolyn S.

1987-01-01

Experiments performed on Space Shuttle flights have emphasized study of the earliest effects of the cephalad fluid shift resulting from microgravity. Analysis of one subject's urine collected during flight showed that a sharp increase in antidiuretic hormone occurred within 2 h of launch, followed by an increase in cortisol excretion. Although this subject had symptoms of the space adaptation syndrome (SAS), inflight data from Spacelab missions suggested that these transient changes were not caused by SAS. Unpaired t-tests and Mann-Whitney tests showed that before and after flight, plasma thyroxine and urine osmolality were significantly higher in Shuttle crewmembers who exhibited more severe symptoms of SAS than in asymptomatic crewmembers.

Die Virus-induzierten Lebererkrankungen des Menschen

NASA Astrophysics Data System (ADS)

Eisenburg, J.

1982-12-01

Although many viral agents may be associated with inflammatory hepatic changes, the vast majority of clinically important viral hepatitis is caused by hepatitis A, hepatitis B and the non A, non B agents. Infection of the liver of man by these hepatotropic agents is still a major public health problem in all parts of the world and constitutes a major hazard of the transfusion of blood and plasma derivatives. The magnitude of this hepatitis problem is not only documented by the about 200 million carriers of the hepatitis-B virus throughout the world, many of them asymptomatic, but also by the fact, that hepatitis B and non A, non B may progress to chronic liver disease, including cirrhosis and probably primary liver cancer. Potentially important pathogenetic determinants include viral factors such as subtype, dosage and mode of transmission and host factors such as age, sex, preexisting liver disease, coexisting non-liver disease (diabetes etc.), genetics and immune response to viral or autoantigens. As the virus itself seems not directly cytopathic, the diversity of lesions has been attributed to variation in the capacity of the host's response.

Faecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae and Shiga toxin-producing Escherichia coli in asymptomatic nursery children in Lower Saxony (Germany), 2014.

PubMed

Harries, M; Dreesman, J; Rettenbacher-Riefler, S; Mertens, E

2016-09-09

Children may be at higher risk for carriage of antimicrobial-resistant bacteria because of higher usage of antimicrobials. They also have higher rates of Shiga toxin-producing Escherichia coli (STEC) infections than other population groups. Some infections, particularly in children, are asymptomatic, but still lead to the excretion of large numbers of bacteria and viruses that may cause clinical disease in other individuals. That is one reason why, in Lower Saxony as in other German federal states - asymptomatic carriers of STEC are excluded from nurseries and schools until three consecutive stool samples test negative in order to prevent secondary cases. The prevalence of children who are asymptomatic STEC carriers is unknown. But if it is high, this measure would have substantial socioeconomic effects on families. Infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasing problem for public health, especially for hospitals. However, there are no reliable estimates of the prevalence of asymptomatic ESBL-E carriers in Lower Saxony, as there is no mandatory requirement to report these carriers. In order to discuss the exclusion policies for children attending nurseries and ascertain a baseline of ESBL-E carriers, we conducted a cross-sectional study. The aim was to determine the prevalence of ESBL-E and STEC and identify risk factors for carriage in nursery children without diarrhoea (asymptomatic) aged 0-6 years in four selected districts in Northern Germany. During April-September 2014, we collected stool specimens with the support of voluntarily participating nurseries. We tested for STEC by PCR and for ESBL-E on chromogenic agar. Questionnaires answered by parents contained data on eating and drinking habits, outdoor activities, prior antibiotic treatment and animal contact for each participating child. We compared the epidemiological characteristics of ESBL-E carriers vs. non-carriers by using univariable analysis (P value, odds ratio and 95% confidence interval). We could not perform a statistical analysis for STEC carriers due to the low numbers of positive STEC specimens. Of 224 asymptomatic nursery children, we found a prevalence of 2·3% for ESBL-E carriage and 0·5% for STEC carriage. Asymptomatic ESBL-E carriers were more likely to have consumed raw milk, have had contact with pet rodents, or to have taken antibiotics during the preceding 6 months. We also found a high proportion of raw milk consumption (11%). We suggest that the low STEC prevalence in asymptomatic children supports the current practice of excluding STEC carriers from nurseries. The association between ESBL-E carriage and raw milk consumption and contact with pet rodents needs further investigation.

[Detection of West Nile virus in human samples: follow-up studies during the 2015 seasonal period].

PubMed

Nagy, Anna; Nagy, Orsolya; Bán, Enikő; Molnár, Eszter; Müller, Zsófia; Orbán, Márton; Kecskés, Borbála; Harsányi, Emese Henriett; Kővágó, Levente; Jobbágy, Lajos; Németh, Zoltán; Várnai, Zsuzsanna; Takács, Mária

2017-05-01

West Nile virus, a mosquito-borne viral zoonosis is responsible for human infections in Hungary. Laboratory diagnosis is based on serological tests, however the application of molecular methods has been appreciated. The aim of the study was to investigate blood, cerebrospinal-fluid and urine samples of acutely ill patients and to follow-up PCR positive cases to ascertain the length of virus excretion. Clinical specimens were examined by indirect-immunofluorescent, haemagglutination-inhibition, two PCR tests and Sanger-sequencing. Virus isolation in case of two patients was successful. A follow-up study could be carried out in case of 5 patients. Viral nucleic acid was detectable in urine even for several weeks after symptom onset and viral RNA was present at higher concentration compared with other samples. PCR analysis of urine could provide useful epidemiological and diagnostic information. Therefore, it is recommended to collect urine samples in order to supplement the serological diagnosis. Orv Hetil. 2017; 158(20): 791-796.

Viral evolution in HLA-B27-restricted CTL epitopes in human immunodeficiency virus type 1-infected individuals.

PubMed

Setiawan, Laurentia C; Gijsbers, Esther F; van Nuenen, Adrianus C; Kootstra, Neeltje A

2015-08-01

The HLA-B27 allele is over-represented among human immunodeficiency virus type 1-infected long-term non-progressors. In these patients, strong CTL responses targeting HLA-B27-restricted viral epitopes have been associated with long-term asymptomatic survival. Indeed, loss of control of viraemia in HLA-B27 patients has been associated with CTL escape at position 264 in the immunodominant KK10 epitope. This CTL escape mutation in the viral Gag protein has been associated with severe viral attenuation and may require the presence of compensatory mutations before emerging. Here, we studied sequence evolution within HLA-B27-restricted CTL epitopes in the viral Gag protein during the course of infection of seven HLA-B27-positive patients. Longitudinal gag sequences obtained at different time points around the time of AIDS diagnosis were obtained and analysed for the presence of mutations in epitopes restricted by HLA-B27, and for potential compensatory mutations. Sequence variations were observed in the HLA-B27-restricted CTL epitopes IK9 and DR11, and the immunodominant KK10 epitope. However, the presence of sequence variations in the HLA-B27-restricted CTL epitopes could not be associated with an increase in viraemia in the majority of the patients studied. Furthermore, we observed low genetic diversity in the gag region of the viral variants throughout the course of infection, which is indicative of low viral replication and corresponds to the low viral load observed in the HLA-B27-positive patients. These data indicated that control of viral replication can be maintained in HLA-B27-positive patients despite the emergence of viral mutations in HLA-B27-restricted epitopes.

Prevalence and activity of Epstein-Barr virus and human cytomegalovirus in symptomatic and asymptomatic apical periodontitis lesions.

PubMed

Hernádi, Katinka; Szalmás, Anita; Mogyorósi, Richárd; Czompa, Levente; Veress, György; Csoma, Eszter; Márton, Ildikó; Kónya, József

2010-09-01

Apical periodontitis is a polymicrobial inflammation with a dominant flora of opportunistic Gram-negative bacteria; however, a pathogenic role of human herpesviruses such as Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) has been implicated recently. The aims of this study were to determine the prevalence, activity, and disease association of EBV and HCMV in apical periodontitis in an Eastern Hungarian population. Forty samples with apical periodontitis (17 symptomatic and 23 asymptomatic) and 40 healthy pulp controls were collected. EBV and HCMV prevalences were measured by polymerase chain reaction (PCR) detection of the viral DNA and viral activity was tested by reverse-transcription PCR amplification of viral messenger RNA. EBV DNA and EBNA-2 messenger RNA were found in apical periodontitis lesions at significantly (p < 0.0001) higher frequencies (72.5% and 50%, respectively) than in controls (both 2.5%). The occurrence of HCMV infection was rare in both apical lesions (10%) and controls (0%). The presence of EBV DNA in apical lesions was associated significantly with large (> or = 5 mm) lesion size (p = 0.02) but not with symptoms (p = 0.30). Symptomatic manifestation was significantly associated with the co-occurrence (odds ratio [OR], 8.80; 95% confidence interval [CI], 1.69-45.76) but not the sole occurrences of EBNA-2 messenger RNA (OR, 2.29; 95% CI, 0.48-11.06) and large lesion size (OR, 4.02; 95% CI, 0.81-19.89). EBV infection is a frequent event in apical periodontitis, whereas the involvement of HCMV still remains to be elucidated. This study showed that symptomatic manifestation was likely to occur if a large-sized apical periodontitis lesion is aggravated with active EBV infection. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Determinants of monovalent oral polio vaccine mutagenesis in vaccinated elderly people.

PubMed

Boot, Hein J; Sonsma, Jan; van Nunen, Femke; Abbink, Frithjofna; Kimman, Tjeerd G; Buisman, Anne-Marie

2007-06-11

Live oral poliovirus vaccine (OPV) strains can mutate and recombine during replication in the host. Trivalent OPV has long been used to restrain wild-type poliovirus in developing countries. However, recently WHO advocates using monovalent OPV (mOPV) to finally eradicate poliovirus world-wide. We analysed polioviruses recovered from the faeces of 101 elderly patients (divided into three groups by immune status) challenged with mOPV-1 or mOPV-3. A high number of nucleotide mutations was found in the viral capsid-protein-encoding regions. Some of these mutations caused amino acid changes in or near regions with neutralizing epitopes, especially in mOPV-1-derived strains. The quantities of mutations in recovered poliovirus strains correlated with prevaccination immune status (seronegatives have more mutations) and excretion duration. Duration of excretion appears to be the dominant factor for the accumulation of mutations in mOPV-derived strains in vaccinated elderly people.

Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

PubMed

Kállay, Krisztián; Kassa, Csaba; Réti, Marienn; Karászi, Éva; Sinkó, János; Goda, Vera; Stréhn, Anita; Csordás, Katalin; Horváth, Orsolya; Szederjesi, Attila; Tasnády, Szabolcs; Hardi, Apor; Kriván, Gergely

2018-04-01

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

Evaluation of adults with acute viral hepatitis a and review of the literature.

PubMed

Tekin, R; Yolbas, I; Dal, T; Demirpençe, Ö; Kaya, S; Bozkurt, F; Deveci, Ö; Çelen, M K; Tekin, A

2013-01-01

In developing countries HAV infection is very common in the first years of life and it is often asymptomatic. However especially in regions of intermediate endemicity, exposure to the virus may delay and outbreaks of hepatitis A may be encountered in adults. The aim of this study is to evaluate the clinical and laboratory findings and risk factors of adults with acute viral hepatitis A. In present study we evaluated 203 patient with acute viral hepatitis A, who were admitted to four different hospitals of three cities of Turkey between January 2000-December 2011, retrospectively. The diagnosis of acute viral hepatitis A was performed by laboratory findings and clinically. In a total of 203 patients, 120 (59.1%) patients were male and 83 (40.9%) were female. Mean age of cases with acute viral hepatitis A was 24.7 +11.8 years (ranged 15 to 82 years old). Acute viral hepatitis A were seen in patient who were 15-20 years and 21-30 years old, commonly. Jaundice (74%), fatigue (68%), nausea- vomiting (56%) and dark urine (48%) were the most common symptoms in cases. Prolonged cholestasis (6.8%) was the most common atypical manifestation. Prolonged jaundice was more frequent in the cases with positive HBsAg (P < 0.001). Acute viral hepatitis A can cause atypical presentations such as prolonged cholestasis, acute kidney injury and fulminant hepatitis. Some precautions such as routine vaccination program, improvement of hygiene conditions and informing people about it, should be taken for reducing of acute viral hepatitis A infection incidence.

Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

PubMed

Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

2014-10-01

Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

Dengue viruses – an overview

PubMed Central

Bäck, Anne Tuiskunen; Lundkvist, Åke

2013-01-01

Dengue viruses (DENVs) cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF) is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence. PMID:24003364

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load.

PubMed

Hasanoglu, Imran; Guner, Rahmet; Carhan, Ahmet; Kocak Tufan, Zeliha; Yagci-Caglayik, Dilek; Guven, Tumer; Yilmaz, Gul Ruhsar; Tasyaran, Mehmet A

2016-02-01

Crimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5-30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality. To evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF. A total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load. In our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3×10(7)copy/ml and 4.6×10(9)copy/ml in survived and dead patients, respectively (p<0.005). Probability of survival is found to be significantly reduced where AST >1130U/l, ALT >490U/l, CPK >505U/l, LDH >980U/l, platelet count <23×10(3)/l, creatinine >1.4mg/dl, INR >1.3, d-dimer >7100ng/dl, and viral load >1.03×10(8)copy/ml. Patients with 10(8)copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p<0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group. There are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality. Copyright © 2015 Elsevier B.V. All rights reserved.

Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

PubMed

Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

2016-02-29

Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. Copyright © 2016 Elsevier B.V. All rights reserved.

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

PubMed Central

Spengler, Jessica R.; Bergeron, Éric; Rollin, Pierre E.

2016-01-01

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology. PMID:26741652

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spengler, Jessica R.; Bergeron, Eric; Rollin, Pierre E.

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. Furthermore, this review highlights the role of livestock in the maintenancemore » and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.« less

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

PubMed

Spengler, Jessica R; Bergeron, Éric; Rollin, Pierre E

2016-01-01

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

DOE PAGES

Spengler, Jessica R.; Bergeron, Eric; Rollin, Pierre E.; ...

2016-01-07

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. Furthermore, this review highlights the role of livestock in the maintenancemore » and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.« less

Molecular confirmation of Lassa fever imported into Ghana.

PubMed

Bonney, Joseph H K; Nyarko, Edward O; Ohene, Sally-Ann; Amankwa, Joseph; Ametepi, Ralph K; Nimo-Paintsil, Shirley C; Sarkodie, Badu; Agbenohevi, Prince; Adjabeng, Michael; Kyei, Nicholas N A; Bel-Nono, Samuel; Ampofo, William K

2016-01-01

Recent reports have shown an expansion of Lassa virus from the area where it was first isolated in Nigeria to other areas of West Africa. Two Ghanaian soldiers on a United Nations peacekeeping mission in Liberia were taken ill with viral haemorrhagic fever syndrome following the death of a sick colleague and were referred to a military hospital in Accra, Ghana, in May 2013. Blood samples from the soldiers and five asymptomatic close contacts were subjected to laboratory investigations. We report the results of these investigations to highlight the importance of molecular diagnostic applications and the need for heightened awareness about Lassa fever in West Africa. We used molecular assays on sera from the two patients to identify the causative organism. Upon detection of positive signals for Lassa virus ribonucleic material by two different polymerase chain reaction assays, sequencing and phylogenetic analyses were performed. The presence of Lassa virus in the soldiers' blood samples was shown by L-gene segment homology to be the Macenta and las803792 strains previously isolated in Liberia, with close relationships then confirmed by phylogenetic tree construction. The five asymptomatic close contacts were negative for Lassa virus. The Lassa virus strains identified in the two Ghanaian soldiers had molecular epidemiological links to strains from Liberia. Lassa virus was probably responsible for the outbreak of viral haemorrhagic fever in the military camp. These data confirm Lassa fever endemicity in West Africa.

Deep Sequencing Analysis of RNAs from Citrus Plants Grown in a Citrus Sudden Death-Affected Area Reveals Diverse Known and Putative Novel Viruses.

PubMed

Matsumura, Emilyn E; Coletta-Filho, Helvecio D; Nouri, Shahideh; Falk, Bryce W; Nerva, Luca; Oliveira, Tiago S; Dorta, Silvia O; Machado, Marcos A

2017-04-24

Citrus sudden death (CSD) has caused the death of approximately four million orange trees in a very important citrus region in Brazil. Although its etiology is still not completely clear, symptoms and distribution of affected plants indicate a viral disease. In a search for viruses associated with CSD, we have performed a comparative high-throughput sequencing analysis of the transcriptome and small RNAs from CSD-symptomatic and -asymptomatic plants using the Illumina platform. The data revealed mixed infections that included Citrus tristeza virus (CTV) as the most predominant virus, followed by the Citrus sudden death-associated virus (CSDaV), Citrus endogenous pararetrovirus (CitPRV) and two putative novel viruses tentatively named Citrus jingmen-like virus (CJLV), and Citrus virga-like virus (CVLV). The deep sequencing analyses were sensitive enough to differentiate two genotypes of both viruses previously associated with CSD-affected plants: CTV and CSDaV. Our data also showed a putative association of the CSD-symptomatic plants with a specific CSDaV genotype and a likely association with CitPRV as well, whereas the two putative novel viruses showed to be more associated with CSD-asymptomatic plants. This is the first high-throughput sequencing-based study of the viral sequences present in CSD-affected citrus plants, and generated valuable information for further CSD studies.

Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study.

PubMed

Edén, Arvid; Nilsson, Staffan; Hagberg, Lars; Fuchs, Dietmar; Zetterberg, Henrik; Svennerholm, Bo; Gisslén, Magnus

2016-12-15

We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Future of an “Asymptomatic” T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

PubMed Central

Dervillez, Xavier; Gottimukkala, Chetan; Kabbara, Khaled W.; Nguyen, Chelsea; Badakhshan, Tina; Kim, Sarah M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2012-01-01

Summary Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as “asymptomatic” protective epitopes”) could boost local and systemic “natural” protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging “asymptomatic” T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID:22701511

[Research on sexually transmitted infections in asymptomatic heterosexual males whose partners have cervical intraepithelial neoplasia].

PubMed

Varela, José A; Otero, Luis; Junquera, Maria Luisa; Melón, Santiago; del Valle, Asunción; Vázquez, Fernando

2006-06-01

Human papillomaviruses (HPV) are the etiological agents of genital warts and of cervical intraepithelial neoplasia (CIN), and they are sexually transmitted. The aim of this study is to determine the prevalence of sexually transmitted infections (STI) in asymptomatic heterosexual males who consult their physicians seeking advice after their partners have been diagnosed with CIN. 181 asymptomatic males whose partners were women diagnosed with CIN were studied at the STI unit in Gijón over a five-year period (1999-2003). The same diagnostic protocol was used in all cases: clinical exam, genitoscopy and the taking of samples for bacterial, fungus and Trichomonas cultures, as well as samples for the genomic detection of Chlamydia, and syphilis, HIV and viral hepatitis serology. 101 infections were diagnosed in 85 patients (47 %). By order of greatest prevalence, these were: urethritis from Ureaplasma urealyticum (35/181; 19.3 %), genital warts (31/181; 17.1 %), Haemophilus spp. (12 de 181; 6.6 %) and mycotic balanoposthitis (10/181; 5.5 %). The prevalence of STI in the partners of women with CIN is high, and in these cases it is necessary to establish STI detection and control programs in both members of the couple.

Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus.

PubMed

Abou, Magali; Dällenbach, Patrick

2013-04-19

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.

Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus

PubMed Central

Abou, Magali; Dällenbach, Patrick

2013-01-01

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer. PMID:23606387

Identification of Continuous Human B-Cell Epitopes in the VP35, VP40, Nucleoprotein and Glycoprotein of Ebola Virus

PubMed Central

Becquart, Pierre; Mahlakõiv, Tanel; Nkoghe, Dieudonné; Leroy, Eric M.

2014-01-01

Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7–12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods. PMID:24914933

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

PubMed

Pereira, Anna Carolina Toledo da Cunha; de Siqueira, Tatiane Ribeiro; de Oliveira Prado, Andressa Anunciação; da Silva, Camila Almeida Veiga; de Fátima Silva Moraes, Thaís; Aleixo, Alan Alex; de Magalhaes, José Carlos; de Souza, Gabriel Augusto Pires; Drumond, Betânia Paiva; Ferreira, Gustavo Portela; de Mello Silva, Breno; de Brito Magalhães, Cintia Lopes; Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

2018-06-01

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.

Identification of continuous human B-cell epitopes in the VP35, VP40, nucleoprotein and glycoprotein of Ebola virus.

PubMed

Becquart, Pierre; Mahlakõiv, Tanel; Nkoghe, Dieudonné; Leroy, Eric M

2014-01-01

Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7-12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods.

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

PubMed

Johansson, Inger; Andersson, Rune; Friman, Vanda; Selimovic, Nedim; Hanzen, Lars; Nasic, Salmir; Nyström, Ulla; Sigurdardottir, Vilborg

2015-12-24

Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

PubMed

Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

2014-09-01

Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city

PubMed Central

Bhuyan, Golam Sarower; Hossain, Mohammad Amir; Sarker, Suprovath Kumar; Rahat, Asifuzzaman; Islam, Md Tarikul; Haque, Tanjina Noor; Begum, Noorjahan; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Islam, Nafisa Nawal; Islam, Mohammad Sazzadul; Sultana, Nusrat; Jony, Manjur Hossain Khan; Khanam, Farhana; Mowla, Golam; Matin, Abdul; Begum, Firoza; Shirin, Tahmina; Ahmed, Dilruba; Saha, Narayan; Qadri, Firdausi

2017-01-01

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality. PMID:28346512

Gianotti-Crosti syndrome: a case report of a teenager.

PubMed

Pedreira, Renata Leite; Leal, Juliana Martins; Silvestre, Keline Jácome; Lisboa, Alice Paixão; Gripp, Alexandre Carlos

2016-01-01

Gianotti-Crosti syndrome is a rare disease characterized by acral papular eruption with symmetrical distribution. It is a benign and self-limited disease; the symptoms disappear after two to eight weeks, without recurrences or scars. Skin lesions are usually asymptomatic. Prodrome might occur, suggesting upper respiratory infection, or constitutional symptoms. Diagnosis is eminently clinical, and this disease is associated with viral infections. Due to its rarity and low occurrence in adolescents and adults, we report a case of Gianotti-Crosti syndrome of a teenager.

Avian Influenza H7N9/13 and H7N7/13: a Comparative Virulence Study in Chickens, Pigeons, and Ferrets

PubMed Central

Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P.; Starick, Elke; Harder, Timm

2014-01-01

ABSTRACT Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. IMPORTANCE This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk analysis of low-pathogenicity avian influenza viruses of the H7 subtype are provided that could also be used for the risk assessment of zoonotic potentials and necessary biosafety measures. PMID:24899194

Avian influenza H7N9/13 and H7N7/13: a comparative virulence study in chickens, pigeons, and ferrets.

PubMed

Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P; Starick, Elke; Harder, Timm; Beer, Martin

2014-08-01

Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk analysis of low-pathogenicity avian influenza viruses of the H7 subtype are provided that could also be used for the risk assessment of zoonotic potentials and necessary biosafety measures. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations

PubMed Central

Plowright, Raina K.; Peel, Alison J.; Streicker, Daniel G.; Gilbert, Amy T.; McCallum, Hamish; Wood, James; Baker, Michelle L.; Restif, Olivier

2016-01-01

Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife. PMID:27489944

Persistent Bovine Viral Diarrhea Virus Infection in Domestic and Wild Small Ruminants and Camelids Including the Mountain Goat (Oreamnos americanus)

PubMed Central

Nelson, Danielle D.; Duprau, Jennifer L.; Wolff, Peregrine L.; Evermann, James F.

2016-01-01

Bovine viral diarrhea virus (BVDV) is a pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus). PMID:26779126

A Unique Case of Classic Kaposi's sarcoma restricted to the toes.

PubMed

Renteria, Anne S; Marshall, Vickie A; Sun, Yanyu; Chockalingam, Porselvi; Cooper, Jay S; Huang, Yiwu; Whitby, Denise

2013-01-01

Kaposi's sarcoma associated-herpesvirus causes all forms of Kaposi's sarcoma, and six major subtypes have been described based on the amino acid sequences of the open reading frame K1. A 71-year-old man from China, HIV negative, presented with nodules on the dorsal aspect of his toes. Biopsy confirmed the diagnosis of Kaposi's sarcoma and virology studies of his blood and saliva confirmed the presence of Kaposi's sarcoma associated-herpesvirus infection. Viral genotyping was consistent with subtype C3. Intervention has been deferred as our patient has remained clinically asymptomatic and without evident growth of his lesions over a 2-year follow up. We herein report the first known case of Kaposi's sarcoma restricted to the toes caused by the viral subtype C3 in an HIV-negative patient from Harbin, China.

Transmission of Influenza A Viruses

PubMed Central

Neumann, Gabriele; Kawaoka, Yoshihiro

2015-01-01

Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

PubMed

Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

2014-04-16

Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever.

PubMed

Quaresma, Juarez A S; Pagliari, Carla; Medeiros, Daniele B A; Duarte, Maria I S; Vasconcelos, Pedro F C

2013-09-01

Yellow fever is a viral hemorrhagic fever, which affects people living in Africa and South America and is caused by the yellow fever virus, the prototype species in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can produce a wide spectrum of symptoms, ranging from asymptomatic infection or oligosymptomatic illness to severe disease with a high fatality rate. In this review, we focus in the mechanisms associated with the physiopathology of yellow fever in humans and animal models. It has been demonstrated that several factors play a role in the pathological outcome of the severe form of the disease including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte cells in the midzone, and a minimal inflammatory response as well as low-flow hypoxia and cytokine overproduction. New information has filled several gaps in the understanding of yellow fever pathogenesis and helped comprehend the course of illness. Finally, we discuss prospects for an immune therapy in the light of new immunologic, viral, and pathologic tools. Copyright © 2013 John Wiley & Sons, Ltd.

An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination.

PubMed

Bauman, Yoav; Nachmani, Daphna; Vitenshtein, Alon; Tsukerman, Pinchas; Drayman, Nir; Stern-Ginossar, Noam; Lankry, Dikla; Gruda, Raizy; Mandelboim, Ofer

2011-02-17

The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification, using sera from exposed animals, of putative viral antigens in livers of primates with callitrichid hepatitis.

PubMed Central

Stephensen, C B; Montali, R J; Ramsay, E C; Holmes, K V

1990-01-01

Callitrichid hepatitis (CH) is an acute, frequently fatal viral hepatitis which affects members of the primate family Callitrichidae (R. J. Montali, E. C. Ramsay, C. B. Stephensen, M. Worley, J. A. Davis, and K. V. Holmes, J. Infect. Dis. 160:759-765, 1989; E. C. Ramsay, R. J. Montali, M. Worley, C. B. Stephensen, and K. V. Holmes, J. Zoo Wildlife Med. 20:178-183, 1989). Outbreaks of the disease occur in zoos and animal parks. In this study, CH-specific antigens were identified in the livers of infected animals by using immune sera from primates with CH and CH-exposed asymptomatic animals. Three CH-specific antigens with apparent molecular masses of 34, 54, and 65 kDa were identified. A polyclonal antiserum was raised against the 54-kDa antigen. These antigens were not found in the livers of uninfected animals and may be viral proteins. Our results suggest that at least five of the six outbreaks of CH considered here were caused by the same virus or by an antigenically related virus. Images PMID:2123012

The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

PubMed Central

Breman, Joel G.; de Quadros, Ciro A.; Dowdle, Walter R.; Foege, William H.; Henderson, Donald A.; John, T. Jacob; Levine, Myron M.

2011-01-01

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases—smallpox, poliomyelitis, and measles—we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios. PMID:21311582

Diagnosis of genital herpes simplex virus infection in the clinical laboratory

PubMed Central

2014-01-01

Since the type of herpes simplex virus (HSV) infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is always recommended. Although PCR has been the diagnostic standard method for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, could replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, antigen detection—an immunofluorescence test or enzyme immunoassay from samples from symptomatic patients--could be employed, but HSV type determination is of importance. Type-specific serology based on glycoprotein G should be used for detecting asymptomatic individuals but widespread screening for HSV antibodies is not recommended. In conclusion, rapid and accurate laboratory diagnosis of HSV is now become a necessity, given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy. PMID:24885431

IgA is Important for Clearance and Critical for Protection from Rotavirus Infection

PubMed Central

Blutt, Sarah E; Miller, Amber D.; Salmon, Sharon L.; Metzger, Dennis W.; Conner, Margaret E

2012-01-01

Based on a lack of severe phenotype in human IgA deficiency syndromes, the role of IgA in controlling respiratory and gastrointestinal (GI) infections has not been clearly defined. C57BL/6 and BALB/c mice lacking IgA (IgA−/−) were developed and used to address this question. When exposed to a common GI virus, rotavirus, IgA−/− mice exhibited a substantial and significant delay in clearance of the initial infection compared to wild type mice. IgA−/− mice excreted rotavirus in stool up to three weeks after the initial exposure compared to ten days observed in wild type mice. Importantly, IgA−/− mice failed to develop protective immunity against multiple repeat exposures to the virus. All IgA−/− mice excreted virus in the stool upon re-exposure to rotavirus while wild type mice were completely protected against re-infection. These findings clearly indicate a critical role for IgA in the establishment of immunity against a GI viral pathogen. PMID:22739233

Molecular confirmation of Lassa fever imported into Ghana

PubMed Central

Nyarko, Edward O.; Ohene, Sally-Ann; Amankwa, Joseph; Ametepi, Ralph K.; Nimo-Paintsil, Shirley C.; Sarkodie, Badu; Agbenohevi, Prince; Adjabeng, Michael; Kyei, Nicholas N.A.; Bel-Nono, Samuel; Ampofo, William K.

2016-01-01

Background Recent reports have shown an expansion of Lassa virus from the area where it was first isolated in Nigeria to other areas of West Africa. Two Ghanaian soldiers on a United Nations peacekeeping mission in Liberia were taken ill with viral haemorrhagic fever syndrome following the death of a sick colleague and were referred to a military hospital in Accra, Ghana, in May 2013. Blood samples from the soldiers and five asymptomatic close contacts were subjected to laboratory investigations. Objective We report the results of these investigations to highlight the importance of molecular diagnostic applications and the need for heightened awareness about Lassa fever in West Africa. Methods We used molecular assays on sera from the two patients to identify the causative organism. Upon detection of positive signals for Lassa virus ribonucleic material by two different polymerase chain reaction assays, sequencing and phylogenetic analyses were performed. Results The presence of Lassa virus in the soldiers’ blood samples was shown by L-gene segment homology to be the Macenta and las803792 strains previously isolated in Liberia, with close relationships then confirmed by phylogenetic tree construction. The five asymptomatic close contacts were negative for Lassa virus. Conclusions The Lassa virus strains identified in the two Ghanaian soldiers had molecular epidemiological links to strains from Liberia. Lassa virus was probably responsible for the outbreak of viral haemorrhagic fever in the military camp. These data confirm Lassa fever endemicity in West Africa. PMID:28879105

Prevalence and clinical aspects of CMV congenital Infection in a low-income population.

PubMed

Marin, Lauro Juliano; Santos de Carvalho Cardoso, Emanuelle; Bispo Sousa, Sandra Mara; Debortoli de Carvalho, Luciana; Marques Filho, Marcílio F; Raiol, Mônica Regina; Gadelha, Sandra Rocha

2016-08-31

CMV is the most common cause of congenital infection in the whole world (0.2 to 2.2 %). That infection may be symptomatic or asymptomatic at birth and, although asymptomatic cases at birth are more common, some children may develop late sequelae, and require medical intervention. This study aimed to determine the prevalence of CMV congenital infections in children who were born in a public hospital in Ilhéus, Brazil, and to evaluate the clinical progression in infected newborns. CMV congenital infection was determined by detecting viral DNA through nested PCR. The viral DNA was detected in 25 newborns, showing a prevalence of 1.19 % (25/2100) of CMV congenital infection. In regards to the risk factors from mothers, only the variables: age of mothers (p = 0.003), number of children (p = 0.011), and use of medications (p < 0.001) were associated with the congenital infection. Approximately 12 % of children presented symptoms. One death and two auditory alterations were detected during the monitored period. Only 50 % of children diagnosed attended their medical follow. The prevalence found confirms the findings from other studies which involved other poor populations. Two children presented impaired hearing during the monitored period; that was one of the main sequelae from the infection. It is noteworthy that there was low adherence to medical follow-up which may underestimate data on complications of the infection CMV. Late symptoms can be mistaken for other diseases or even go unnoticed.

Prevalence of human herpes virus types 1-7 in the semen of men attending an infertility clinic and correlation with semen parameters.

PubMed

Neofytou, Eirini; Sourvinos, George; Asmarianaki, Maria; Spandidos, Demetrios A; Makrigiannakis, Antonios

2009-06-01

To determine the prevalence of herpes viruses in the semen of an asymptomatic male cohort with and without infertility problems and its association with altered semen parameters. A prospective randomized study. Medical school and IVF clinic. One hundred seventy-two male patients undergoing routine semen analysis: 80 with normal semen parameters (control group) and 92 with abnormal semen parameters. Semen samples were collected by masturbation. The DNA from the Herpesviridae family (herpes simplex virus 1 [HSV-1], herpes simplex virus 2 [HSV-2], Varicella zoster virus [VZV], Epstein-Barr virus [EBV], cytomegalovirus [CMV], human herpes virus type 6 [HHV-6], human herpes virus type 7 [HHV-7]) and routine semen parameters. Viral DNA was detected in 143/172 (83.1%) of the total samples for at least one herpes virus: HSV-1, 2.5%; VZV, 1.2%; EBV, 45%; CMV, 62.5%; HHV-6, 70%; HHV-7, 0% in the normal semen samples and HSV-1, 2.1%; VZV, 3.2%; EBV, 39.1%; CMV, 56.5%; HHV-6, 66.3%; HHV-7, 0% in the abnormal semen samples. No association was found between the presence of viral DNA and semen parameters. Interestingly, a statistical significance between leukocytospermia and the presence of EBV DNA was observed. The DNA of herpes viruses is frequently detected in the semen of asymptomatic fertile and infertile male patients. Further studies are required to investigate the role of herpes viruses in male factor infertility.

[Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners].

PubMed

Bouma, M; van Geldrop, W J; Numans, M E; Wiersma, Tj; Goudswaard, A N

2008-12-06

The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.

Evolving perception on the benefits of vaccination as a foot and mouth disease control policy: contributions of South America.

PubMed

Bergmann, Ingrid E; Malirat, Viviana; Falczuk, Abraham J

2005-12-01

Within the past decade, changes in perceptions on the benefits of vaccination as an appropriate tool to achieve complete foot and mouth disease eradication have become evident. The former negative view was derived from misconceptions, resulting mainly from the belief that vaccines are not entirely effective and that vaccination masks asymptomatic viral circulation. The advent in the 1990s of vaccination policies implemented within a strategic eradication plan in South America, and during recurrence of the disease in disease-free regions contributed towards generating more reliable and visible outcomes of vaccination programs, paving the way towards a new perception. Particularly relevant was the development and application of novel serodiagnostic approaches to assess silent viral circulation, irrespective of vaccination. The use in South America of vaccination allied to serosurveys to accompany viral clarification during eradication campaigns and after emergencies clearly established the importance of this control tool to stop the spread of viral infection. This alliance gave input to break many myths associated with the use of vaccines, including the belief that immunized carrier animals pose an epidemiologic risk. This experience launched new concepts that supported the internationally recognized status of foot and mouth disease-free regions with vaccination and the 'vaccination to live' policy as an alternative to 'stamping out'.

Transmission of lymphocystis disease virus to cultured gilthead seabream, Sparus aurata L., larvae.

PubMed

Cano, I; Valverde, E J; Garcia-Rosado, E; Alonso, M C; Lopez-Jimena, B; Ortiz-Delgado, J B; Borrego, J J; Sarasquete, C; Castro, D

2013-06-01

The transmission of lymphocystis disease virus (LCDV) to gilthead seabream, Sparus aurata L., larvae was investigated using fertilized eggs from a farm with previous reports of lymphocystis disease. LCDV genome was detected by PCR-hybridization in blood samples from 17.5% of the asymptomatic gilthead seabream broodstock analysed. Using the same methodology, eggs spawned from these animals were LCDV positive, as well as larvae hatched from them. The presence of infective viral particles was confirmed by cytopathic effects development on SAF-1 cells. Whole-mount in situ hybridization (ISH) and immunohistochemistry (IHC) showed the presence of LCDV in the epidermis of larvae hatched from LCDV-positive eggs. When fertilized eggs were disinfected with iodine, no viral DNA was detected either in eggs (analysed by PCR-hybridization) or in larvae (PCR-hybridization and ISH). These results suggest the vertical transmission of LCDV, the virus being transmitted on the egg surface. Larvae hatched from disinfected eggs remain LCDV negative during the endotrophic phase, as showed by PCR-hybridization, ISH and IHC. After feeding on LCDV-positive rotifers, viral antigens were observed in the digestive tract, which suggests that viral entry could be achieved via the alimentary canal, and that rotifers can act as a vector in LCDV transmission to gilthead seabream larvae. © 2012 Blackwell Publishing Ltd.

Latent Herpes Viral Reactivation in Astronauts

NASA Technical Reports Server (NTRS)

Pierson, D. L.; Mehta, S. K.; Stowe, R.

2008-01-01

Latent viruses are ubiquitous and reactivate during stressful periods with and without symptoms. Latent herpes virus reactivation is used as a tool to predict changes in the immune status in astronauts and to evaluate associated health risks. Methods: Viral DNA was detected by real time polymerase chain reaction in saliva and urine from astronauts before, during and after short and long-duration space flights. Results and Discussion: EpsteinBarr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivated, and viral DNA was shed in saliva (EBV and VZV) or urine (CMV). EBV levels in saliva during flight were 10fold higher than baseline levels. Elevations in EBV specific CD8+ T-cells, viral antibody titers, and specific cytokines were consistent with viral reactivation. Intracellular levels of cytokines were reduced in EBVspecific Tcells. CMV, rarely present in urine of healthy individuals, was shed in urine of 27% of astronauts during all phases of spaceflight. VZV, not found in saliva of asymptomatic individuals, was found in saliva of 50% of astronauts during spaceflight and 35 days after flight. VZV recovered from astronaut saliva was found to be live, infectious virus. DNA sequencing demonstrated that the VZV recovered from astronauts was from the common European strain of VZV. Elevation of stress hormones accompanied viral reactivation indicating involvement of the hypothalmic-pituitary-adrenal and sympathetic adrenal-medullary axes in the mechanism of viral reactivation in astronauts. A study of 53 shingles patients found that all shingles patients shed VZV DNA in their saliva and the VZV levels correlated with the severity of the disease. Lower VZV levels in shingles patients were similar to those observed in astronauts. We proposed a rapid, simple, and cost-effective assay to detect VZV in saliva of patients with suspected shingles. Early detection of VZV infection allows early medical intervention.

Gallstones in patients with liver cirrhosis: Incidence, etiology, clinical and therapeutical aspects

PubMed Central

Acalovschi, Monica

2014-01-01

Gallstones occur in about one third of the patients having liver cirrhosis. Pigment gallstones are the most frequent type, while cholesterol stones represent about 15% of all stones in cirrhotics. Increased secretion of unconjugated bilirubin, increased hydrolysis of conjugated bilirubin in the bile, reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics. Gallbladder hypomotility also contributes to lithogenesis. The most recent data regarding risk factors for gallstones are presented. Gallstone prevalence increases with age, with a ratio male/female higher than in the general population. Chronic alcoholism, viral C cirrhosis, and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones. Gallstones are often asymptomatic, and discovered incidentally. If asymptomatic, expectant management is recommended, as for asymptomatic gallstones in the general population. However, a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications. For symptomatic stones, laparoscopic cholecystectomy has become the therapy of choice. Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy. Patients with severe liver disease are at highest surgical risk, therefore gallstone complications should be treated using noninvasive or minimally invasive procedures, until stabilization of the patient condition. PMID:24966598

Clinical, biochemical, virological and sonographic profile of incidentally detected asymptomatic HBsAg positive subjects, in Bangladesh.

PubMed

Ishaque, S M; Mahmuduzzaman, M; Rahman, M A; Uddoula, M S; Rahman, M Z; Khan, M R; Chowdhury, M S

2014-01-01

Chronic hepatitis B virus (HBV) is known to be the significant cause of Liver related morbidity and mortality, affecting 400 million people worldwide and a major public health problem in Bangladesh where carrier rates of HBV infection varies from 7.5 to 10%. In Bangladesh prevalence of asymptomatic HBV infection and incidentally detected HBsAg positive subjects were not well studied. The aim of this study is to evaluate the disease activity, replicative status of the virus and to find out the stages of chronic liver disease among incidentally detected asymptomatic HBsAg positive Bangladeshi subjects. Two hundred (200) incidentally detected healthy HBsAg positive subject were evaluated clinically, biochemically, serologically and ultrasonographically from January 2004 to June 2008. HBeAg was found positive in 17(8.5%), anti-HBe was positive in 174(87%), raised serum ALT (>45iu/L) in 45(22.5%), prothrombine time (PT) >3 sec of control in 33(16.5%). Ultrasonography showed coarse hepatic echotexture in 13(6.5%). Evidence of active viral replication and signs of chronic liver disease were observed among incidentally detected healthy HBsAg positive subjects. Such individuals should be followed up at regular interval to evaluate the replicative status of the virus and disease activity so that appropriate measures could be initiated in time.

Illumination of Murine Gammaherpesvirus-68 Cycle Reveals a Sexual Transmission Route from Females to Males in Laboratory Mice

PubMed Central

François, Sylvie; Vidick, Sarah; Sarlet, Mickaël; Desmecht, Daniel; Drion, Pierre; Stevenson, Philip G.; Vanderplasschen, Alain; Gillet, Laurent

2013-01-01

Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68), are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naïve males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent the spread of these viruses in natural populations. PMID:23593002

The impact of viral load and time to onset of cytomegalovirus replication on long-term graft survival after kidney transplantation.

PubMed

Reischig, Tomas; Kacer, Martin; Hruba, Petra; Jindra, Pavel; Hes, Ondrej; Lysak, Daniel; Bouda, Mirko; Viklicky, Ondrej

2017-01-01

Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure. In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood. A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of ≥2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia ≥2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia ≥2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia. Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.

The Fecal Virome of Pigs on a High-Density Farm ▿ †

PubMed Central

Shan, Tongling; Li, Linlin; Simmonds, Peter; Wang, Chunlin; Moeser, Adam; Delwart, Eric

2011-01-01

Swine are an important source of proteins worldwide but are subject to frequent viral outbreaks and numerous infections capable of infecting humans. Modern farming conditions may also increase viral transmission and potential zoonotic spread. We describe here the metagenomics-derived virome in the feces of 24 healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2 different mammalian viruses were shed by healthy piglets, reflecting a high level of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different mammalian viruses. Ninety-nine percent of the viral sequences were related to the RNA virus families Picornaviridae, Astroviridae, Coronaviridae, and Caliciviridae, while 1% were related to the small DNA virus families Circoviridae, and Parvoviridae. Porcine RNA viruses identified, in order of decreasing number of sequence reads, consisted of kobuviruses, astroviruses, enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and teschoviruses. The near-full genomes of multiple novel species of porcine astroviruses and bocaviruses were generated and phylogenetically analyzed. Multiple small circular DNA genomes encoding replicase proteins plus two highly divergent members of the Picornavirales order were also characterized. The possible origin of these viral genomes from pig-infecting protozoans and nematodes, based on closest sequence similarities, is discussed. In summary, an unbiased survey of viruses in the feces of intensely farmed animals revealed frequent coinfections with a highly diverse set of viruses providing favorable conditions for viral recombination. Viral surveys of animals can readily document the circulation of known and new viruses, facilitating the detection of emerging viruses and prospective evaluation of their pathogenic and zoonotic potentials. PMID:21900163

Community-Based Prevalence of Genital Human Papilloma Virus (HPV) Infection: a Systematic Review and Meta-Analysis

PubMed Central

Sabeena, Sasidharanpillai; Bhat, Parvati V; Kamath, Veena; Bhat, Shashikala K; Nair, Sreekumaran; N, Ravishankar; Chandrabharani, Kiran; Arunkumar, Govindakarnavar

2017-01-01

Introduction: Cervical cancer probably represents the best-studied human cancer caused by a viral infection and the causal association of this preventable cancer with human papilloma virus (HPV) is well established. Worldwide there is a scarcity of data regarding HPV prevalence with vast differences existing among populations. Objective: The aim of this meta-analysis was to determine the community-based HPV prevalence estimates among asymptomatic women from urban and rural set ups and in participants of cancer screening clinics. Study design: Systematic review and meta-analysis. Methods: PubMed-Medline, CINAHL, Scopus, and Google scholar were systematically searched for studies providing prevalence data for HPV infection among asymptomatic women between 1986 and 2016. Results: The final analysis included 32 studies comprising a population of 224,320 asymptomatic women. The overall pooled HPV prevalence was 11% (95% confidence interval (CI), 9%-12%). The pooled HPV prevalence of 11% (95% CI, 9%-11%) was observed among women attending cervical cancer screening clinics. The pooled HPV prevalences were 10% (95% CI 8%-12%) and 11% (95% CI 4%-18%) from urban and rural areas respectively, indicating higher infection rates among the rural women with the least access to cancer screening and cancer care. Conclusion: The prevalence rates in this systematic quantitative review provide a reliable estimate of the burden of HPV infection among asymptomatic women from developed as well as developing nations. Rural women and women attending cervical cancer screening programmes feature higher genital HPV prevalences compared to their urban counterparts. PMID:28240509

Community-Based Prevalence of Genital Human Papilloma Virus (HPV) Infection: a Systematic Review and Meta-Analysis

PubMed

Sabeena, Sasidharanpillai; Bhat, Parvati V; Kamath, Veena; Bhat, Shashikala K; Nair, Sreekumaran; n, Ravishankar; Chandrabharani, Kiran; Arunkumar, Govindakarnavar

2017-01-01

Introduction: Cervical cancer probably represents the best-studied human cancer caused by a viral infection and the causal association of this preventable cancer with human papilloma virus (HPV) is well established. Worldwide there is a scarcity of data regarding HPV prevalence with vast differences existing among populations. Objective: The aim of this meta-analysis was to determine the community-based HPV prevalence estimates among asymptomatic women from urban and rural set ups and in participants of cancer screening clinics. Study design: Systematic review and meta-analysis. Methods: PubMed-Medline, CINAHL, Scopus, and Google scholar were systematically searched for studies providing prevalence data for HPV infection among asymptomatic women between 1986 and 2016. Results: The final analysis included 32 studies comprising a population of 224,320 asymptomatic women. The overall pooled HPV prevalence was 11% (95% confidence interval (CI), 9%-12%). The pooled HPV prevalence of 11% (95% CI, 9%-11%) was observed among women attending cervical cancer screening clinics. The pooled HPV prevalences were 10% (95% CI 8%-12%) and 11% (95% CI 4%-18%) from urban and rural areas respectively, indicating higher infection rates among the rural women with the least access to cancer screening and cancer care. Conclusion: The prevalence rates in this systematic quantitative review provide a reliable estimate of the burden of HPV infection among asymptomatic women from developed as well as developing nations. Rural women and women attending cervical cancer screening programmes feature higher genital HPV prevalences compared to their urban counterparts. Creative Commons Attribution License

Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

PubMed

Sharma, Bhawana; Dabur, Rajesh

2016-01-01

Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P < 0.05) was observed but their level get downregulated after TCE intervention. Multivariate analysis of metabolites without missing values showed an increased excretion of 7-dehydrocholesterol, orotic acid, pyridoxine, lipoamide and niacin and TCE intervention depleted their levels (P < 0.05). In contrast, excretion of biotin, xanthine, vitamin D2 and 2-O-p-coumaroyltartronic acid (CA, an internal marker of intestinal absorption) were observed to be decreased in alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Protection Afforded by a Recombinant Turkey Herpesvirus-H5 Vaccine Against the 2014 European Highly Pathogenic H5N8 Avian Influenza Strain.

PubMed

Steensels, M; Rauw, F; van den Berg, Th; Marché, S; Gardin, Y; Palya, V; Lambrecht, B

2016-05-01

A highly pathogenic avian influenza (HPAI) H5N8 (clade 2.3.4.4) virus, circulating in Asia (South Korea, Japan, and southern China) since the beginning of 2014, reached the European continent in November 2014. Germany, the Netherlands, the United Kingdom, Italy, and Hungary confirmed H5N8 infection of poultry farms of different species and of several wild bird species. Unlike the Asian highly pathogenic (HP) H5N1, this HP H5N8 also went transatlantic and reached the American West Coast by the end of 2014, affecting wild birds as well as backyard and commercial poultry. This strain induces high mortality and morbidity in Galliformes, whereas wild birds seem only moderately affected. A recombinant turkey herpesvirus (rHVT) vector vaccine expressing the H5 gene of a clade 2.2 H5N1 strain (rHVT-H5) previously demonstrated a highly efficient clinical protection and reduced viral excretion against challenge with Asian HP H5N1 strains of various clades (2.2, 2.2.1, 2.2.1.1, 2.1.3, 2.1.3.2, and 2.3.2.1) and was made commercially available in various countries where the disease is endemic. To evaluate the protective efficacy of the rHVT-H5 vaccine against the first German H5N8 turkey isolate (H5N8 GE), a challenge experiment was set up in specific-pathogen-free (SPF) chickens, and the clinical and excretional protection was evaluated. SPF chickens were vaccinated subcutaneously at 1 day old and challenged oculonasally at 4 wk of age with two viral dosages, 10(5) and 10(6) 50% egg infective doses. Morbidity and mortality were monitored daily in unvaccinated and vaccinated groups, whereas viral shedding by oropharyngeal and cloacal routes was evaluated at 2, 5, 9, and 14 days postinoculation (dpi). Serologic monitoring after vaccination and challenge was also carried out. Despite its high antigenic divergence of the challenge H5N8 strain, a single rHVT-H5 vaccine administration at 1 day old resulted in a full clinical protection against challenge and a significant reduction of viral shedding in the vaccinated birds.

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort.

PubMed

Arnold, David T; Bentham, Louise M; Jacob, Ruth P; Lilford, Richard J; Girling, Alan J

2011-03-03

Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population.

Pathogenic traits of Salmonella Montevideo in experimental infections in vivo and in vitro

PubMed Central

Lalsiamthara, Jonathan; Lee, John Hwa

2017-01-01

Salmonella serovar Montevideo (SM) is frequently associated with human Salmonella infections and causes gastrointestinal disease, cases are common particularly among individuals who come in close contact with live poultry or poultry meat products. To characterize SM disease in chickens, the pathogenic traits and tissue predilections of the disease were investigated. Dissemination of fluorescent-tagged SM (JOL1575GFP) was monitored after oral and intramuscular mock infections of specific-pathogen-free chickens. The spleen was predominantly affected by intramuscular infection while the cecum, spleen, and minimally liver were affected by oral infection. No conspicuous illness was observed in infected birds, and histopathological examination showed minimal damage of the intestinal epithelium and splenic parenchyma though SM was readily isolated from these tissues. Levels of SM internalization by primary chicken peritoneal macrophages were similar to that of Salmonella Typhimurium. SM was more sensitive to chicken than rabbit serum complement killing. Internal egg contamination of SM mock infected layers also occurred at trace levels and lasted for a week after inoculation. This study also confirmed that SM infection in chickens is sub-clinical and asymptomatic, which suggests that latent asymptomatic carriers may excrete a large number of bacteria and transmit the pathogen by contaminating water or food sources. PMID:28387311

Animal models for influenza virus pathogenesis, transmission, and immunology

PubMed Central

Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

2014-01-01

In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

Crimean-Congo Hemorrhagic Fever.

PubMed

Shayan, Sara; Bokaean, Mohammad; Shahrivar, Mona Ranjvar; Chinikar, Sadegh

2015-01-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.

Association of Depressed Mood With Herpes Simplex Virus-2 Immunoglobulin-G Levels in Pregnancy.

PubMed

Hsu, Pao-Chu; Yolken, Robert H; Postolache, Teodor T; Beckie, Theresa M; Munro, Cindy L; Groer, Maureen W

2016-10-01

Depressed mood is common in pregnancy, is associated with stress, and could result in immune suppression that may lead to latent herpes viral reactivation. This study investigated whether depressed mood is associated with higher herpes viral IgG levels in pregnant women. Complete cross-sectional data from 247 pregnant women were available for this substudy. The data included demographics, scores on the Perceived Stress Scale and Profile of Mood States (POMS), and a panel of serum IgG levels for human herpesviruses. Only the herpes simplex virus type 2 (HSV-2) (genital herpes) IgG level was associated with Perceived Stress Scale and POMS-Depression/Dejection (POMS-D) score. Hierarchical multiple regression analysis was used to examine the association of POMS-D with herpesviral IgG levels adjusting for demographic variables. In the final model, African American race (β = .251, p < .001), older age (β = .199, p = .002), single marital status (β = -.304, p < .001), and depressed mood (β = .122, p = .04) were associated with HSV-2 IgG levels. In logistic regression, the strongest correlates of HSV IgG positivity were single marital status, followed by POMS-D scores and African American race. Genital herpes is a concern in pregnancy. Antibody titers may indicate asymptomatic viral shedding, viral reactivation, or primary viral infection. Antibody levels may be higher because of the immune changes during pregnancy and potential immune effects of depressed mood causing reactivation of latent HSV-2.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

PubMed

Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

2015-06-01

CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

Hyperpotassemia and bradycardia in a bedridden elderly woman with selective hypoaldosteronism associated with low renin activity.

PubMed

Inada, Mitsuo; Iwasaki, Keiko; Imai, Chihiro; Hashimoto, Satoshi

2010-01-01

A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone system and normal adrenoglucocorticoid function. The results were consistent with the abnormalities seen in selective hypoaldosteronism with low renin activity. In addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients with normal serum sodium and potassium levels in our hospital, had diminished plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID reduces renal potassium excretion through the inhibition of renal prostaglandin synthesis. Therefore, the use of NSAID in bedridden elderly patients might intensify the underlying asymptomatic hypoaldosteronism and cause life-threatening hyperpotassemia.

Estimating the Risk of Renal Stone Events during Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Reyes, David; Kerstman, Eric; Gray, Gary; Locke, James

2014-01-01

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Estimating the Risk of Renal Stone Events During Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Reyes, David; Kerstman, Eric; Locke, James

2014-01-01

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

PubMed

Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

2001-08-01

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.

PubMed

Senthilvel, Padmanaban; Lavanya, Pandian; Kumar, Kalavathi Murugan; Swetha, Rayapadi; Anitha, Parimelzaghan; Bag, Susmita; Sarveswari, Sundaramoorthy; Vijayakumar, Vijayaparthasarathi; Ramaiah, Sudha; Anbarasu, Anand

2013-01-01

Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities. ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - - Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - - Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A.

PubMed

Hussain, Zahid; Husain, Syed A; Almajhdi, Fahad N; Kar, Premashis

2011-05-23

Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%). Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.

Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A

PubMed Central

2011-01-01

Background Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. Objective In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Methods Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Results Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%). Conclusions Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity. PMID:21605420

Application of a new real-time polymerase chain reaction assay for surveillance studies of lymphocystis disease virus in farmed gilthead seabream.

PubMed

Valverde, Estefania J; Cano, Irene; Labella, Alejandro; Borrego, Juan J; Castro, Dolores

2016-04-06

Lymphocystis disease (LCD) is the main viral infection reported to affect cultured gilthead seabream (Sparus aurata) in Europe. The existence of subclinical Lymphocystis disease virus (LCDV) infection in this fish species has been recognised by using polymerase chain reaction (PCR)-based methods. Nevertheless, these methods do not provide quantitative results that can be useful in epidemiological and pathological studies. Moreover, carrier fish have been involved in viral transmission, therefore the use of specific and sensitive diagnostic methods to detect LCDV will be relevant for LCD prevention. We have developed a real-time PCR (qPCR) assay to detect and quantify LCDV. The assay was evaluated for viral diagnosis in surveillance studies in gilthead seabream farms, and also to identify viral reservoirs in a hatchery. The prevalence of LCDV infection in the asymptomatic gilthead seabream populations tested varied from 30 to 100 %, including data from one farm without previous records of LCD. Estimated viral load in caudal fin of subclinically infected fish was two to five orders of magnitude lower than in diseased fish. The qPCR assay allowed the detection of carrier fish in broodstock from a farm with a history of clinical LCD in juvenile fish. In addition, the quantitative detection of LCDV was achieved in all samples collected in the hatchery, including fertilized eggs, larvae and fingerlings, and also rotifer cultures and artemia metanauplii and cysts used for larval rearing. The qPCR assay developed in this study has proved to be a rapid, sensitive, and reliable method for LCDV diagnosis, which could be valuable to identify LCDV reservoirs or to study viral replication in gilthead seabream.

Recurrence of CMV Infection and the Effect of Prolonged Antivirals in Organ Transplant Recipients.

PubMed

Natori, Yoichiro; Humar, Atul; Husain, Shahid; Rotstein, Coleman; Renner, Eberhard; Singer, Lianne; Kim, S Joseph; Kumar, Deepali

2017-06-01

Although initial therapy for cytomegalovirus (CMV) is usually successful, a significant subset of patients may have recurrent viremia. However, the epidemiology and risk factors for recurrence have not been fully defined, as well as the utility of prolonged antivirals after initial clearance. Solid organ transplant patients with first episode of CMV disease or asymptomatic viremia (≥1000 IU/mL) requiring treatment were identified by chart review. Clinical and virologic data were collected. The primary outcome was recurrence of CMV viremia or disease within 6 months of treatment discontinuation. The first episode of CMV viremia requiring antiviral therapy was assessed in 282 patients (147 CMV disease and 135 asymptomatic viremia). Cytomegalovirus occurred at 5.6 (0.63-27.7) months posttransplant. Recurrent CMV occurred in 30.5% patients at a median of 51 (0-160) days after discontinuation of therapy. Factors predictive of recurrence were treatment phase viral kinetics (P = 0.005), lung transplant (P = 0.002), CMV donor (D)+/recipient (R)- serostatus(P = 0.04) and recent acute rejection(P = 0.02). Prolonged antiviral therapy was given to 226 (80.1%) of 282 patients. Recurrence occurred in 73 (32.3%) of 226 patients that received prolonged antivirals versus 13 (23.2%) of 56 in those with no prolonged antivirals (P = 0.19). Recurrent CMV occurs in a significant percentage of patients after treatment of the first episode of CMV viremia/disease. CMV D+/R- serostatus, lung transplant, and treatment phase viral kinetics were significant predictors of recurrence. Continuation of prolonged antivirals beyond initial clearance was not associated with a reduced risk of recurrence.

Molecular characterisation of RIG-I-like helicases in the black flying fox, Pteropus alecto.

PubMed

Cowled, Christopher; Baker, Michelle L; Zhou, Peng; Tachedjian, Mary; Wang, Lin-Fa

2012-04-01

The RIG-I like helicases, RIG-I, mda5 and LGP2 are an evolutionarily conserved family of cytosolic pattern recognition receptors important in the recognition of viral RNA, and responsible for the innate induction of interferons and proinflammatory cytokines upon viral infection. Bats are natural reservoir hosts to a variety of RNA viruses that cause significant morbidity and mortality in other species; however the mechanisms responsible for the control of viral replication in bats are not understood. This report describes the molecular cloning and expression analysis of RIG-I, mda5 and LGP2 genes in the fruit bat Pteropus alecto, and is the first description of RIG-I like helicases from any species of bat. Our results demonstrate that P. alecto RIG-I, mda5 and LGP2 have similar primary structures and tissue expression patterns to their counterparts in humans and other mammals. Stimulation of bat kidney cells with synthetic dsRNA (poly I:C) induced high levels of interferon β and rapid upregulation of all three helicases. These findings reveal that the cytoplasmic virus sensing machinery is present and intact in P. alecto. This study provides the foundation for further investigations into the interactions between bat RIG-I-like helicases and viruses to elucidate the mechanisms responsible for the asymptomatic nature of viral infections in bats. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction.

PubMed

De La Cruz-Rivera, Pamela C; Kanchwala, Mohammed; Liang, Hanquan; Kumar, Ashwani; Wang, Lin-Fa; Xing, Chao; Schoggins, John W

2018-01-01

Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox ( Pteropus alecto ) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats. Copyright © 2017 by The American Association of Immunologists, Inc.

Polyomavirus BK non-coding control region rearrangements in health and disease.

PubMed

Sharma, Preety M; Gupta, Gaurav; Vats, Abhay; Shapiro, Ron; Randhawa, Parmjeet S

2007-08-01

BK virus is an increasingly recognized pathogen in transplanted patients. DNA sequencing of this virus shows considerable genomic variability. To understand the clinical significance of rearrangements in the non-coding control region (NCCR) of BK virus (BKV), we report a meta-analysis of 507 sequences, including 40 sequences generated in our own laboratory, for associations between rearrangements and disease, tissue tropism, geographic origin, and viral genotype. NCCR rearrangements were less frequent in (a) asymptomatic BKV viruria compared to patients viral nephropathy (1.7% vs. 22.5%), and (b) viral genotype 1 compared to other genotypes (2.4% vs. 11.2%). Rearrangements were commoner in malignancy (78.6%), and Norwegians (45.7%), and less common in East Indians (0%), and Japanese (4.3%). A surprising number of rearranged sequences were reported from mononuclear cells of healthy subjects, whereas most plasma sequences were archetypal. This difference could not be related to potential recombinase activity in lymphocytes, as consensus recombination signal sequences could not be found in the NCCR region. NCCR rearrangements are neither required nor a sufficient condition to produce clinical disease. BKV nephropathy and hemorrhagic cystitis are not associated with any unique NCCR configuration or nucleotide sequence.

Pathogenic human viruses in coastal waters

USGS Publications Warehouse

Griffin, Dale W.; Donaldson, Kim A.; Paul, J.H.; Rose, Joan B.

2003-01-01

This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and

Prevalence of Asymptomatic Poliovirus Infection in Older Children and Adults in Northern India: Analysis of Contact and Enhanced Community Surveillance, 2009

PubMed Central

Mach, Ondrej; Verma, Harish; Khandait, Devendra W.; Sutter, Roland W.; O'Connor, Patrick M.; Pallansch, Mark A.; Cochi, Stephen L.; Linkins, Robert W.; Chu, Susan Y.; Wolff, Chris; Jafari, Hamid S.

2015-01-01

Background In 2009, enhanced poliovirus surveillance was established in polio-endemic areas of Uttar Pradesh and Bihar, India, to assess poliovirus infection in older individuals. Methods In Uttar Pradesh, stool specimens from asymptomatic household and neighborhood contacts of patients with laboratory-confirmed polio were tested for polioviruses. In Bihar, in community-based surveillance, children and adults from 250 randomly selected households in the Kosi River area provided stool and pharyngeal swab samples that were tested for polioviruses. A descriptive analysis of surveillance data was performed. Results In Uttar Pradesh, 89 of 1842 healthy contacts of case patients with polio (4.8%) were shedding wild poliovirus (WPV); 54 of 85 (63.5%) were ≥5 years of age. Shedding was significantly higher in index households than in neighborhood households (P < .05). In Bihar, 11 of 451 healthy persons (2.4%) were shedding WPV in their stool; 6 of 11 (54.5%) were ≥5 years of age. Mean viral titer was similar in older and younger children. Conclusions A high proportion of persons ≥5 years of age were asymptomatically shedding polioviruses. These findings provide indirect evidence that older individuals could have contributed to community transmission of WPV in India. Polio vaccination campaigns generally target children <5 years of age. Expanding this target age group in polio-endemic areas could accelerate polio eradication. PMID:25316843

HPV/Chlamydia trachomatis co-infection: metagenomic analysis of cervical microbiota in asymptomatic women.

PubMed

Di Pietro, Marisa; Filardo, Simone; Porpora, Maria Grazia; Recine, Nadia; Latino, Maria Agnese; Sessa, Rosa

2018-01-01

HPV and Chlamydia trachomatis are the most common causes of sexually transmitted diseases worldwide. Most infections are asymptomatic and left untreated lead to severe reproductive tract sequelae such as cervical cancer and infertility. Interestingly, C. trachomatis may also increase the susceptibility to HPV infection as well as contribute to viral persistence. Recently, a growing body of evidence has suggested that the composition of the cervico-vaginal microbiota plays a key role in the susceptibility and outcome of genital infections caused by several pathogens, including HPV and C. trachomatis. The aim of our study was to undertake a metagenomic analysis of sequenced 16s rRNA gene amplicons to characterize the cervical microbiota from asymptomatic women with HPV/C. trachomatis co-infection. The composition of the cervical microbiota from HPV-positive or C. trachomatis-positive women was also analysed. The main finding of our study showed that the cervical microbiota in HPV/C. trachomatis co-infected women had a higher microbial diversity than the cervical microbiota in healthy controls (p<0.05). In addition, Aerococcus christensenii was associated with C. trachomatis infection. In conclusion, the increased cervical microbial diversity observed in HPV/C. trachomatis co-infected women and the detection of potential microbiological biomarkers of C. trachomatis infection will open the way to innovative approaches that may be helpful to identify women at risk of co-infection.

Surveillance bronchoscopy in children during the first year after lung transplantation: Is it worth it?

PubMed

Benden, C; Harpur-Sinclair, O; Ranasinghe, A S; Hartley, J C; Elliott, M J; Aurora, P

2007-01-01

Since January 2002, routine surveillance bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy has been performed in all paediatric recipients of lung and heart-lung transplants at the Great Ormond Street Hospital for Children, London, UK, using a newly revised treatment protocol. To report the prevalence of rejection and bacterial, viral or fungal pathogens in asymptomatic children and compare this with the prevalence in children with symptoms. The study population included all paediatric patients undergoing single lung transplantation (SLTx), double lung transplantation (DLTx) or heart-lung transplantation between January 2002 and December 2005. Surveillance bronchoscopies were performed at 1 week, and 1, 3, 6 and 12 months after transplant. Bronchoscopies were classified according to whether subjects had symptoms, defined as the presence of cough, sputum production, dyspnoea, malaise, decrease in lung function or chest radiograph changes. Results of biopsies and BAL were collected, and procedural complications recorded. 23 lung-transplant operations were performed, 12 DLTx, 10 heart-lung transplants and 1 SLTx (15 female patients). The median (range) age of patients was 14.0 (4.9-17.3) years. 17 patients had cystic fibrosis. 95 surveillance bronchoscopies were performed. Rejection (> or =A2) was diagnosed in 4% of biopsies of asymptomatic recipients, and in 12% of biopsies of recipients with symptoms. Potential pathogens were detected in 29% of asymptomatic patients and in 69% of patients with symptoms. The overall diagnostic yield was 35% for asymptomatic children, and 85% for children with symptoms (p < 0.001). The complication rate for bronchoscopies was 3.2%. Many children have silent rejection or subclinical infection in the first year after lung transplantation. Routine surveillance bronchoscopy allows detection and targeted treatment of these complications.

A case-control study of acute respiratory tract infection in general practice patients in The Netherlands.

PubMed

van Gageldonk-Lafeber, Arianne B; Heijnen, Marie-Louise A; Bartelds, Aad I M; Peters, Marcel F; van der Plas, Simone M; Wilbrink, Berry

2005-08-15

Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. During the period of 2000-2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, beta -hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in approximately 30% of control subjects, particularly in the youngest age groups. This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A beta-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.

Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo.

PubMed

Fox, James M; Hilburn, Silva; Demontis, Maria-Antonietta; Brighty, David W; Rios Grassi, Maria Fernanda; Galvão-Castro, Bernardo; Taylor, Graham P; Martin, Fabiola

2016-03-14

Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the "mitotic" spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC) of asymptomatic carriers (ACs) and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukaemia/lymphoma (ATLL). 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

PubMed Central

Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

2015-01-01

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

Age‐related alterations in immune responses to West Nile virus infection

PubMed Central

2016-01-01

Summary West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing. PMID:27612657

Reverse spillover of avian viral vaccine strains from domesticated poultry to wild birds.

PubMed

Rohaim, M A; El Naggar, R F; Helal, A M; Hussein, H A; Munir, Muhammad

2017-06-16

Transmission of viruses from the commercial poultry to wild birds is an emerging paradigm of livestock-wildlife interface. Here, we report the identification and isolation of vaccine strains of avian paramyxovirus serotype 1 (APMV1) and avian coronaviruses (ACoV) from different wild bird species across eight Egyptian governorates between January 2014 and December 2015. Surveillance of avian respiratory viruses in free-ranging wild birds (n=297) identified three species that harboured or excreted APMV1 and ACoVs. Genetic characterization and phylogenetic analysis of recovered viruses revealed a close association with the most widely utilized vaccine strains in the country. These results highlight the potential spillover of vaccine-viruses probably due to extensive use of live-attenuated vaccines in the commercial poultry, and close interaction between domesticated and wild bird populations. Further exploring the full spectrum of vaccine-derived viral vaccine strains in wild birds might help to assess the emergence of future wild-birds origin viruses. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Four-year follow-up of a Wilson disease pedigree complicated with epilepsy and hypopituitarism: Case report with a literature review.

PubMed

Zhang, Qi-Jie; Xu, Liu-Qing; Wang, Chong; Hu, Wei; Wang, Ning; Chen, Wan-Jin

2016-12-01

Wilson's disease (WD) is an autosomal recessive inherited disorder of copper metabolism with excellent prognosis if treated timely. However, WD is usually prone to neglect and misdiagnosis at an early stage. We reported a rare WD pedigree, and the clinical features, laboratory tests, and gene mutations were analyzed in detail. The patient was a 17-year-old and 136-cm-tall girl who presented with limb weakness, combined with multi-organ disorders including blind eye, epilepsy, and hypopituitarism. Clinical tests showed a low serum ceruloplasmin level, high urinary copper excretion and Kayser-Fleischer (K-F) rings. She carried a compound heterozygous mutations in ATP7B gene (c.2828G>A and c.3884C>T). Her younger brother, as an asymptomatic patient, manifested with elevation of transaminases but without neurological and hepatic symptoms. They were diagnosed as WD finally. They were treated with sodium dimercaptosulphonate, supplemented with zinc gluconate, vitamin B6, vitamin C, as well as restriction of dietary copper. The urinary copper excretion and serum transaminase level decreased gradually. The abnormal signals in brainstem and basal ganglia were also remarkably decreased after 4-year of de-copper treatment. As to the patients with complicated clinical manifestations, the extrapyramidal symptom and basal ganglia signals should be concerned. The serum ceruloplasmin detection and ATP7B gene mutation screening are necessary.

Biochemical and clinical studies in Libyan Jewish cystinuria patients and their relatives.

PubMed

Pras, E; Kochba, I; Lubetzky, A; Pras, M; Sidi, Y; Kastner, D L

1998-11-02

Cystinuria is a hereditary disorder manifested by the development of kidney stones. Three subtypes of the disease have been described, based on urinary excretion of cystine and the dibasic amino acids in heterozygotes, and oral loading tests in homozygotes. Cystinuria is very common among Libyan Jews living in Israel. Recently, we mapped the disease-causing gene in Libyan Jews to 19q, and have shown a very strong founder effect. In this report we present the results of biochemical and clinical studies performed on Libyan Jewish cystinuria patients and members of their families. High levels of cystine and the dibasic amino acids in heterozygotes support previous data that cystinuria in Libyan Jews is a non-type I disease. Oral loading tests performed with lysine showed some degree of intestinal absorption, but less than in normal controls. Previous criteria for determining the disease type, based solely on urinary amino acid levels, proved useless due to a very wide range of cystine and the dibasic amino acids excreted by the heterozygotes. Urinary cystine levels were useful in distinguishing between unaffected relatives and heterozygotes, but were unhelpful in differentiating between heterozygotes and homozygotes. Urinary levels of ornithine or arginine, and the sum of urinary cystine and the dibasic amino acids, could distinguish between the last two groups. Among stone formers, 90% were homozygotes and 10% were heterozygotes; 15% of the homozygotes were asymptomatic.

[The spread of the wild Poliovirus in the rural environment, the case of the Adzopé health district, Côte d'Ivoire].

PubMed

Akoua-Koffi, C G; Nekouressi, G; Tieoulou, L; Guillot, S; Faye-Kette, H; Ehouman, A

2004-05-01

Wild Poliovirus spreading in rural environment in Adzopé, Côte d'Ivoire In order to determine the level of wild Poliovirus spreading among rural children in an endemic poliomyelitis country 469 stools samples, from children aged between three weeks and twelve years old were processed according to WHO procedures for transportation, conservation, isolation and identification of Poliovirus. Intratypic differenciation was performed by an antigenic method using monoclonal antibodies and a genomic RFLP (Restriction Fragment Length Polymorphism). 50 Poliovirus strains (10.7%) were isolated and analyzed: 15 vaccine-like Poliovirus type 1 (30%), 30 vaccine-like Poliovirus type 2 (60%), 4 vaccine-like Poliovirus type 3 (8%) and one wild Poliovirus type 3 (2%). As expected, in the major cases the duration of post-vaccinal viral excretion did not exceed two months. However, in 14% of cases, it varied between 3 and 9 months after the third OPV dose. This long excretion could be due to an inefficient local intestinal immunity or no local immunity at all, in spite of the three OPV doses. These results argue in favor of an increase of the number of OPV doses in such endemic zones. Moreover, OPV strains are well-known to revert to pathogenicity in vaccinees, therefore, the long term excretion of pathogenic OPV derived strains by a certain amount of vaccinees needs to be considered quite seriously.

1H NMR-based metabolomic profiling for identification of metabolites in Capsicum annuum cv. mirasol infected by beet mild curly top virus (BMCTV).

PubMed

Villa-Ruano, Nemesio; Velásquez-Valle, Rodolfo; Zepeda-Vallejo, L Gerardo; Pérez-Hernández, Nury; Velázquez-Ponce, Manuel; Arcos-Adame, Victor M; Becerra-Martínez, Elvia

2018-04-01

Beet mild curly top virus (BMCTV) is associated with an outbreak of curly top in chili pepper, tomato and other Solanaceae species, which can cause severe crop losses. The aim of this work was to obtain the 1 H NMR metabolomic profiling of both healthy chili peppers (cv. mirasol) and infected chili peppers with BMCTV in order to find chemical markers associated to the infection process. Significant differences were found between the two groups, according to principal component analysis and orthogonal projections to latent structure discriminant analysis. Compared to the asymptomatic peppers, the symptomatic fruits had higher relative abundance of fructose, isoleucine, histidine, phenylalanine and tryptophan. Contrarily, the asymptomatic samples showed greater amounts of malonate and isobutyrate. These results suggest that in diseased chili peppers there are metabolic changes related to the viral acquisition of energy for replication and capsid assembly. This is the first study describing the chemical profiling of a polar extract obtained from Capsicum annuum infected by BMCTV under open field conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Esophageal papilloma: case report, molecular identification of human papillomavirus and literature review].

PubMed

Barbaglia, Yanina; Jiménez, Félix; Tedeschi, Fabián; Zalazar, Fabián

2013-09-01

sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor of the squamous epithelium consisting of a raised, sessile, small and round (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with a male/female ratio of 3:1. The etiology and pathogenesis appear to be a mechanical or chemical irritation of the mucosa in addition to the presence of human papillomavirus (HPV), important agent in the evolution to a squamous carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of esophageal papilloma whose diagnosis involved endoscopic images, pathological studies and detection of viral DNA by polymerase chain reaction. By using molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been obtained. The patient underwent polypectomy and currently, after 3 years of diagnosis, he remains asymptomatic. This work is one of the first national reports of a patient with esophageal papilloma in which one of the most frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been detected.

Changes in the intraisolate genetic structure of Beet necrotic yellow vein virus populations associated with plant resistance breakdown.

PubMed

Acosta-Leal, Rodolfo; Fawley, Marvin W; Rush, Charles M

2008-06-20

The causal agent of rhizomania disease, Beet necrotic yellow vein virus (BNYVV), typically produces asymptomatic root-limited infections in sugar beets (Beta vulgaris) carrying the Rz1-allele. Unfortunately, this dominant resistance has been recently overcome. Multiple cDNA clones of the viral pathogenic determinant p25, derived from populations infecting susceptible or resistant plants, were sequenced to identify host effects on the viral population structure. Populations isolated from compatible plant-virus interactions (susceptible plant-wild type virus and resistant plant-resistant breaking variants) were large and relatively homogeneous, whereas those from the incompatible interaction (resistant plant-avirulent type virus) were small and highly heterogeneous. All populations from susceptible plants had the same dominant haplotype, whereas those from resistant cultivars had a different haplotype surrounded by a spectrum of mutants. Selection and diversification analyses suggest an evolutionary trajectory of BNYVV with positive selection for changes required to overcome resistance, followed by elimination of hitchhiking mutations through purifying selection.

Antibodies to AIDS-associated retrovirus (HTLV-III/LAV) in drug addicts from Vizcaya, northern Spain.

PubMed

Merino, F; Esparza, B; Aizpiri, J; Fernandez, J; de Masdelval, L; Arrieta, A; Velazquez, M; Volsky, D J; San Cristobal, E; de Izaguirre, A

1986-01-01

Serum samples from 313 asymptomatic intravenous (IV) drug users from Bilbao (Vizcaya, Vasque Country, Spain) were tested for antibodies to HTLV-III/LAV virus, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS). Viral antibodies were assayed by ELISA test. 41.9% of the sera gave positive reactions. No seropositivity was detected among 22 normal blood donors, 58 chronic alcoholics, or 20 members of the Drug Control Center personnel. Virus specific reactions were confirmed by indirect immunofluorescence using an HTLV-III/LAV producer cell line, and by Western blotting. 55% of the ELISA-positive sera were also positive in Western blot assay. No differences in seropositivity by age or sex were observed but it increased with the period of parenteral drug use. Presence of antibody statistically correlated with the frequency of syringe sharing, confirming the transmission of viral infection by blood products. Altered T4/T8 ratios and lower number of T4 positive lymphocytes were detected among HTLV-III/LAV positive drug addicts.

A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda

PubMed Central

Blanquart, François; Grabowski, Mary Kate; Herbeck, Joshua; Nalugoda, Fred; Serwadda, David; Eller, Michael A; Robb, Merlin L; Gray, Ronald; Kigozi, Godfrey; Laeyendecker, Oliver; Lythgoe, Katrina A; Nakigozi, Gertrude; Quinn, Thomas C; Reynolds, Steven J; Wawer, Maria J; Fraser, Christophe

2016-01-01

Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals. DOI: http://dx.doi.org/10.7554/eLife.20492.001 PMID:27815945

Drug-resistant herpes simplex virus in HIV infected patients.

PubMed

Lolis, Margarita S; González, Lenis; Cohen, Philip J; Schwartz, Robert A

2008-01-01

Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations - whether symptomatic or asymptomatic - are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.

African Swine Fever Virus: A Review.

PubMed

Galindo, Inmaculada; Alonso, Covadonga

2017-05-10

African swine fever (ASF) is a highly contagious viral disease of swine which causes high mortality, approaching 100%, in domestic pigs. ASF is caused by a large, double stranded DNA virus, ASF virus (ASFV), which replicates predominantly in the cytoplasm of macrophages and is the only member of the Asfarviridae family, genus Asfivirus . The natural hosts of this virus include wild suids and arthropod vectors of the Ornithodoros genus. The infection of ASFV in its reservoir hosts is usually asymptomatic and develops a persistent infection. In contrast, infection of domestic pigs leads to a lethal hemorrhagic fever for which there is no effective vaccine. Identification of ASFV genes involved in virulence and the characterization of mechanisms used by the virus to evade the immune response of the host are recognized as critical steps in the development of a vaccine. Moreover, the interplay of the viral products with host pathways, which are relevant for virus replication, provides the basic information needed for the identification of potential targets for the development of intervention strategies against this disease.

Transfusion-associated cytomegalovirus mononucleosis.

PubMed Central

Lerner, P I; Sampliner, J E

1977-01-01

Transfusion-associated cytomegalovirus mononucleosis is generally considered only as a complication of extracorporeal circulation following cardiac surgery. Three cases following trauma were recognized in less than one year. Both massive and limited volume blood transfusions were involved. Hectic fever was a characteristic feature in these otherwise remarkably asymptomatic individuals, without the classic features of heterophile-positive infectious mononucleosis. Since the illness developed several weeks into the post-operative period after extensive thoracic or abdominal trauma surgery, the presence of an undrained abscess was naturally the major diagnostic concern. Atypical lymphocytosis, markers of altered immunity (cold agglutinins, rheumatoid factor) and moderate hepatic dysfunction were important laboratory clues. In one case, focal isotope defects in the spleen scan misleadingly suggested a septic complication. A false-positive monospot test initially obscured the correct serologic diagnosis in the same patient. Failure to consider this selflimited viral infection may be a critical factor leading to unnecessary surgery. Other viral agents capable of eliciting a similar syndrome are cited. Images Fig. 1. PMID:190955

Therapeutic approach to respiratory infections in lung transplantation.

PubMed

Clajus, Carolina; Blasi, Francesco; Welte, Tobias; Greer, Mark; Fuehner, Thomas; Mantero, Marco

2015-06-01

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

African Swine Fever Virus: A Review

PubMed Central

Galindo, Inmaculada; Alonso, Covadonga

2017-01-01

African swine fever (ASF) is a highly contagious viral disease of swine which causes high mortality, approaching 100%, in domestic pigs. ASF is caused by a large, double stranded DNA virus, ASF virus (ASFV), which replicates predominantly in the cytoplasm of macrophages and is the only member of the Asfarviridae family, genus Asfivirus. The natural hosts of this virus include wild suids and arthropod vectors of the Ornithodoros genus. The infection of ASFV in its reservoir hosts is usually asymptomatic and develops a persistent infection. In contrast, infection of domestic pigs leads to a lethal hemorrhagic fever for which there is no effective vaccine. Identification of ASFV genes involved in virulence and the characterization of mechanisms used by the virus to evade the immune response of the host are recognized as critical steps in the development of a vaccine. Moreover, the interplay of the viral products with host pathways, which are relevant for virus replication, provides the basic information needed for the identification of potential targets for the development of intervention strategies against this disease. PMID:28489063

Current use of anti-HIV drugs in AIDS.

PubMed

Clumeck, N

1993-07-01

Since 1987 major advances have been made in our understanding of the pathogenesis of infection and the possible inhibition of the HIV virus. Various drugs targeted to the different steps of viral replication have been selected, but drugs such as soluble CD4 or dextran derivatives aimed to inhibit or interfere with the GP120-CD4 attachment step have shown little or no clinical benefit. Protease inhibitors or interferons acting at the post-transcriptional level are currently under phase I to II investigation. The only group of compounds clinically active belong to the nucleosides analogues that act as DNA chain terminators and by inhibiting viral reverse transcriptase. Zidovudine (AZT), didanosine (ddI) and dideoxycytidine (ddC) have been extensively studied, and used on a large clinical scale. Stavudine (D4T), deoxyfluorothymidine (FLT) and 3'thiacytidine (3TC) are entering phase I-II studies. Being the first nucleoside analogue discovered and used since early 1985, zidovudine remains the gold standard of anti-HIV therapy. Zidovudine is indicated at a dosage varying between 500 and 1000 mg in patients with AIDS and ARC, in asymptomatic patients with CD4 < 200/mm3 and in asymptomatic patients with CD4 between 200 and 500 cells/mm3 with a rapid decrease of CD4 cell count or a positive P24 circulating antigen. There is as yet no consensus concerning patients with more than 500 cell/mm3. ddI and ddC are currently indicated for patients intolerant to AZT or in those who have not responded (clinically or biologically) to AZT. Emergence of resistance to AZT has been reported in 30 to 80% of patients at various stages of the disease and after six to nine months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease

PubMed Central

Kim, Yunjeong; Mandadapu, Sivakoteswara Rao; Groutas, William C.; Chang, Kyeong-Ok

2012-01-01

Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC50 in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems. PMID:23219425

HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment

PubMed Central

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W.; Gisslén, Magnus

2010-01-01

Background. Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Methods. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Results. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54–213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Conclusions. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice. PMID:21050119

Identifying predictors of time-inhomogeneous viral evolutionary processes.

PubMed

Bielejec, Filip; Baele, Guy; Rodrigo, Allen G; Suchard, Marc A; Lemey, Philippe

2016-07-01

Various factors determine the rate at which mutations are generated and fixed in viral genomes. Viral evolutionary rates may vary over the course of a single persistent infection and can reflect changes in replication rates and selective dynamics. Dedicated statistical inference approaches are required to understand how the complex interplay of these processes shapes the genetic diversity and divergence in viral populations. Although evolutionary models accommodating a high degree of complexity can now be formalized, adequately informing these models by potentially sparse data, and assessing the association of the resulting estimates with external predictors, remains a major challenge. In this article, we present a novel Bayesian evolutionary inference method, which integrates multiple potential predictors and tests their association with variation in the absolute rates of synonymous and non-synonymous substitutions along the evolutionary history. We consider clinical and virological measures as predictors, but also changes in population size trajectories that are simultaneously inferred using coalescent modelling. We demonstrate the potential of our method in an application to within-host HIV-1 sequence data sampled throughout the infection of multiple patients. While analyses of individual patient populations lack statistical power, we detect significant evidence for an abrupt drop in non-synonymous rates in late stage infection and a more gradual increase in synonymous rates over the course of infection in a joint analysis across all patients. The former is predicted by the immune relaxation hypothesis while the latter may be in line with increasing replicative fitness during the asymptomatic stage.

Cannabinoid administration attenuates the progression of simian immunodeficiency virus.

PubMed

Molina, Patricia E; Winsauer, Peter; Zhang, Ping; Walker, Edith; Birke, Leslie; Amedee, Angela; Stouwe, Curtis Vande; Troxclair, Dana; McGoey, Robin; Varner, Kurt; Byerley, Lauri; LaMotte, Lynn

2011-06-01

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV(mac251); 100 TCID(50)/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIV(mac251) inoculation resulted in measurable viral load, decreased lymphocyte CD4(+)/CD8(+) ratio, and increased CD8(+) proliferation. Δ(9)-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ(9)-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ(9)-THC (10 μm) decreased SIV (10 TCID(50)) viral replication in MT4-R5 cells. These results indicate that chronic Δ(9)-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ(9)-THC-mediated modulation of disease progression that warrant further study.

Treatment of Intestinal Helminths Does Not Reduce Plasma Concentrations of HIV-1 RNA in Coinfected Zambian Adults

PubMed Central

Modjarrad, Kayvon; Zulu, Isaac; Redden, David T.; Njobvu, Lungowe; Lane, H. Clifford; Bentwich, Zvi; Vermund, Sten H.

2009-01-01

Background Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)–infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA. Methods We conducted a prospective study of 54 HIV-1– and helminth-coinfected and 57 HIV-1–infected, helminth-uninfected asymptomatic adults living in Lusaka, Zambia, to assess the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA. Results Median baseline viral load was 0.33 log10 copies/mL lower in the helminth-infected group than in the uninfected group. Mean viral load between pretreatment and posttreatment visits increased in the helminth-infected (mean, 4.23 vs. 4.29 log10 copies/mL; P = .6) and helminth-uninfected (mean, 4.39 vs. 4.52 log10 copies/mL; P = .2) groups. Helminth-infected participants with high pretreatment viral loads had a mean 0.25-log10 copies/mL decrease after treatment (P = .3), and helminth-uninfected participants had a mean 0.02-log10 copies/mL decrease (P = .8). Conclusions We did not find an overall association between treatment of intestinal helminth infections and reduction in viral load in coinfected adults. Future studies may need to focus on adults with intense helminth infections who live in rural areas or on adults or children who harbor higher helminth burdens and plasma concentrations of HIV-1 RNA. PMID:16136473

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

PubMed

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine.

PubMed

Mancera Gracia, Jose Carlos; Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

2017-01-01

H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an extensive set of mutations.

Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine

PubMed Central

Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

2017-01-01

H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an extensive set of mutations. PMID:28384328

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

PubMed

Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

2008-06-01

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV-related CLD.

Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

PubMed

Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

2014-01-01

Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

Quasispecies dynamics and the emergence of drug resistance during zidovudine therapy of HIV infection.

PubMed

Frost, S D; McLean, A R

1994-03-01

To investigate the roles of mutation, competition and population dynamics in the emergence of drug resistant mutants during zidovudine therapy. A mathematical model of the population dynamics of the viral quasispecies during zidovudine therapy was investigated. The model was used to simulate changes in the numbers of uninfected and infected cells and the composition of the viral quasispecies in the years following initiation of therapy. Resulting scenarios in asymptomatic and AIDS patients were compared. The model was also used to investigate the efficacy of a treatment regimen involving alternating zidovudine and dideoxyinosine therapy. The behaviour of the model can be divided into three stages. Before therapy, mutation maintains a small pool of resistant mutants, outcompeted to very low levels by sensitive strains. When therapy begins there is a dramatic fall in the total viral load and resistant strains suddenly have the competitive advantage. Thus, it is resistant strains that infect the rising number of uninfected CD4+ cells. During this second stage the rapid effects of population dynamics swamp any effects of mutation between strains. When the populations of infected and uninfected cells approach their treatment equilibrium levels, mutation again becomes important in the slow generation of highly resistant strains. The short-term reduction in viral replication at the initiation of therapy generates a pool of uninfected cells which cause the eventual increase in viral burden. This increase is associated with (but not caused by) a rise in frequency of resistant strains which are at a competitive advantage in the presence of the drug. When therapy is ceased, reversion of resistance is slow as resistant strains are nearly as fit as sensitive strains in the absence of drug.

Clinical Herpes Zoster in Antarctica as a Model for Spaceflight.

PubMed

Reyes, David P; Brinley, Alaina A; Blue, Rebecca S; Gruschkus, Stephen K; Allen, Andrew T; Parazynski, Scott E

2017-08-01

Antarctica is a useful analog for spaceflight, as both environments are remote, isolated, and with limited resources. While previous studies have demonstrated increased asymptomatic viral shedding in both the Antarctic and spaceflight environments, clinical manifestations of reactivated viral disease have been less frequently identified. We sought to identify the incidence of clinical herpes zoster from viral reactivation in the Antarctic winter-over population. Medical records from the 2014 winter season were reviewed for the incidence of zoster in U.S. Antarctic personnel and then compared to the age-matched U.S. Five cases of clinical herpes zoster occurred in the Antarctic Station population of 204 persons, for an incidence of 33.3 per 1000 person-years vs. 3.2 per 1000 person-years in the general population. Four cases were in persons under age 40, yielding an incidence of 106.7 per 1000 person-years in persons ages 30-39 compared to an incidence of 2.0 per 1000 person-years in the same U.S. age group. Immune suppression due to the stressful Antarctic environment may have contributed to the increased incidence of herpes zoster in U.S. Antarctic personnel during the winter of 2014. Working and living in isolated, confined, and extreme environments can cause immune suppression, reactivating latent viruses and increasing viral shedding and symptomatic disease. Such changes have been observed in other austere environments, including spaceflight, suggesting that clinical manifestations of viral reactivation may be seen in future spaceflight.Reyes DP, Brinley AA, Blue RS, Gruschkus SK, Allen AT, Parazynski SE. Clinical herpes zoster in Antarctica as a model for spaceflight. Aerosp Med Hum Perform. 2017; 88(8):784-788.

Generation and Characterization of a Defective HIV-1 Virus as an Immunogen for a Therapeutic Vaccine

PubMed Central

García-Pérez, Javier; García, Felipe; Blanco, Julia; Escribà-García, Laura; Gatell, Jose Maria; Alcamí, Jose; Plana, Montserrat; Sánchez-Palomino, Sonsoles

2012-01-01

Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles. PMID:23144996

Prolonged illness after infectious mononucleosis is associated with altered immunity but not with increased viral load.

PubMed

Cameron, Barbara; Bharadwaj, Mandvi; Burrows, Jacqueline; Fazou, Chrysa; Wakefield, Denis; Hickie, Ian; Ffrench, Rosemary; Khanna, Rajiv; Lloyd, Andrew

2006-03-01

Primary Epstein-Barr virus (EBV) infection causes a spectrum of characteristics that range from asymptomatic seroconversion to severe infectious mononucleosis (IM), sometimes with prolonged symptoms and disability. We examined the relationships between clinical course, number of viral copies, and immunological parameters in a prospective cohort of subjects with recent IM. Eight case patients with at least 6 months of disabling symptoms and 31 matched control subjects who had recovered promptly were included. Symptom scores were recorded at regular intervals over the course of 12 months. Cellular EBV load, EBV-specific antibody responses, lymphocyte subsets, and EBV-specific interferon (IFN)- gamma induction were measured. In case patients with prolonged illness, the severity of acute-phase symptoms was greater, the development of anti-EBV nuclear antigen-1 immunoglobulin G was more rapid, and the time to development of the peak IFN- gamma response to the majority of latent-cycle EBV peptides was generally slower than those in control subjects. However, in both groups, neither viral nor immune parameters correlated with the severity or duration of symptoms. The resolution of symptomatic IM is not determined by control of viremia, nor is it easily explained by altered host responses to EBV infection. The detailed determinants of delayed recovery remain to be elucidated.

Intracerebral Borna Disease Virus Infection of Bank Voles Leading to Peripheral Spread and Reverse Transcription of Viral RNA

PubMed Central

Kinnunen, Paula Maria; Inkeroinen, Hanna; Ilander, Mette; Kallio, Eva Riikka; Heikkilä, Henna Pauliina; Koskela, Esa; Mappes, Tapio; Palva, Airi; Vaheri, Antti; Kipar, Anja; Vapalahti, Olli

2011-01-01

Bornaviruses, which chronically infect many species, can cause severe neurological diseases in some animal species; their association with human neuropsychiatric disorders is, however, debatable. The epidemiology of Borna disease virus (BDV), as for other members of the family Bornaviridae, is largely unknown, although evidence exists for a reservoir in small mammals, for example bank voles (Myodes glareolus). In addition to the current exogenous infections and despite the fact that bornaviruses have an RNA genome, bornavirus sequences integrated into the genomes of several vertebrates millions of years ago. Our hypothesis is that the bank vole, a common wild rodent species in traditional BDV-endemic areas, can serve as a viral host; we therefore explored whether this species can be infected with BDV, and if so, how the virus spreads and whether viral RNA is transcribed into DNA in vivo. We infected neonate bank voles intracerebrally with BDV and euthanized them 2 to 8 weeks post-infection. Specific Ig antibodies were detectable in 41%. Histological evaluation revealed no significant pathological alterations, but BDV RNA and antigen were detectable in all infected brains. Immunohistology demonstrated centrifugal spread throughout the nervous tissue, because viral antigen was widespread in peripheral nerves and ganglia, including the mediastinum, esophagus, and urinary bladder. This was associated with viral shedding in feces, of which 54% were BDV RNA-positive, and urine at 17%. BDV nucleocapsid gene DNA occurred in 66% of the infected voles, and, surprisingly, occasionally also phosphoprotein DNA. Thus, intracerebral BDV infection of bank vole led to systemic infection of the nervous tissue and viral excretion, as well as frequent reverse transcription of the BDV genome, enabling genomic integration. This first experimental bornavirus infection in wild mammals confirms the recent findings regarding bornavirus DNA, and suggests that bank voles are capable of bornavirus transmission. PMID:21935357

An update on the genetic architecture of hyperuricemia and gout.

PubMed

Merriman, Tony R

2015-04-10

Genome-wide association studies that scan the genome for common genetic variants associated with phenotype have greatly advanced medical knowledge. Hyperuricemia is no exception, with 28 loci identified. However, genetic control of pathways determining gout in the presence of hyperuricemia is still poorly understood. Two important pathways determining hyperuricemia have been confirmed (renal and gut excretion of uric acid with glycolysis now firmly implicated). Major urate loci are SLC2A9 and ABCG2. Recent studies show that SLC2A9 is involved in renal and gut excretion of uric acid and is implicated in antioxidant defense. Although etiological variants at SLC2A9 are yet to be identified, it is clear that considerable genetic complexity exists at the SLC2A9 locus, with multiple statistically independent genetic variants and local epistatic interactions. The positions of implicated genetic variants within or near chromatin regions involved in transcriptional control suggest that this mechanism (rather than structural changes in SLC2A9) is important in regulating the activity of SLC2A9. ABCG2 is involved primarily in extra-renal uric acid under-excretion with the etiological variant influencing expression. At the other 26 loci, probable causal genes can be identified at three (PDZK1, SLC22A11, and INHBB) with strong candidates at a further 10 loci. Confirmation of the causal gene will require a combination of re-sequencing, trans-ancestral mapping, and correlation of genetic association data with expression data. As expected, the urate loci associate with gout, although inconsistent effect sizes for gout require investigation. Finally, there has been no genome-wide association study using clinically ascertained cases to investigate the causes of gout in the presence of hyperuricemia. In such a study, use of asymptomatic hyperurcemic controls would be expected to increase the ability to detect genetic associations with gout.

High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya

PubMed Central

Kwarisiima, Dalsone; Kamya, Moses R.; Owaraganise, Asiphas; Mwangwa, Florence; Byonanebye, Dathan M.; Ayieko, James; Plenty, Albert; Black, Doug; Clark, Tamara D.; Nzarubara, Bridget; Snyman, Katherine; Brown, Lillian; Bukusi, Elizabeth; Cohen, Craig R.; Geng, Elvin H.; Charlebois, Edwin D.; Ruel, Theodore D.; Petersen, Maya L.; Havlir, Diane; Jain, Vivek

2017-01-01

Abstract Introduction: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. Methods: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/μL and children (two to fourteen years) with CD4 > 500/μL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events. Results: Overall, 972 HIV-positive adults with CD4+ ≥ 350/μL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28–42), CD4+ 608/μL (IQR, 487–788/μL) and VL 6775 copies/mL (IQR, <500–37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to follow-up). Viral suppression occurred in 778/838 (93%) and 800/972 (82%) in intention-to-treat analysis. Grade III/IV clinical/laboratory adverse events were rare: 95 occurred in 74/972 patients (7.6%). Only 8/972 adults (0.8%) switched ART from EFV to lopinavir (LPV) (n = 2 for dizziness, n = 2 for gynaecomastia, n = 4 for other reasons). Among 83 children, week 48 retention was 89% (74/83), viral suppression was 92% (65/71) and grade III/IV adverse events occurred in 4/83 (4.8%). Conclusions: Using a streamlined care model, viral suppression, retention and ART safety were high among asymptomatic East African adults and children with high CD4+ counts initiating treatment. Clinical Trial Number: NCT01864603 PMID:28770596

Myocarditis in athlete and myocardial bridge: An innocent bystander?

PubMed Central

Quaranta, Federico; Guerra, Emanuele; Sperandii, Fabio; De Santis, Francesco; Pigozzi, Fabio; Calò, Leonardo; Borrione, Paolo

2015-01-01

Myocarditis is a bacterial or viral inflammatory disease, often unnoticed or misdiagnosed. Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sudden death. In the present report, we describe a case of an asymptomatic, apparently healthy, competitive athletes, who was diagnosed a myocarditis and as incidental finding a myocardial bridging. We focused the attention on the importance of anamnesis, electrocardiogram and athletes’ entourage for the diagnosis of such insidious pathologies and we evaluated the follow up, focusing the attention on electrocardiogram changes as well as on restitution ad integrum and prognosis, especially for the athletes. PMID:26015860

Distribution, persistence and interchange of Epstein-Barr virus strains among PBMC, plasma and saliva of primary infection subjects.

PubMed

Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

2015-01-01

Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle.

Distribution, Persistence and Interchange of Epstein-Barr Virus Strains among PBMC, Plasma and Saliva of Primary Infection Subjects

PubMed Central

Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

2015-01-01

Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle. PMID:25807555

Alteration in oligonucleotide fingerprint patterns of the viral genome in poliovirus type 2 isolated from paralytic patients.

PubMed Central

Yoneyama, T; Hagiwara, A; Hara, M; Shimojo, H

1982-01-01

A close relationship was demonstrated by oligonucleotide fingerprinting between genomes of the poliovirus type 2 Sabin vaccine strain and recent isolates from paralytic cases associated with vaccination in Japan. The oligonucleotide maps of isolates from an agammaglobulinemic patient, who continued to excrete poliovirus type 2 for 3.5 years after the administration of oral vaccine, showed that the genomic alteration proceeded gradually, retaining the majority of the oligonucleotides characteristic of the vaccine strain for a long period, indicating vaccine origin for the isolates. The final isolate at month 41, however, lost the majority of these oligonucleotides. The heterologous antigenic relationship between the final isolate and the previous isolates was also observed. The serial alteration in electrophoretic mobility of the major structural proteins (VP1, VP2, and VP3) was observed throughout the excreting period. These results indicate that the population of the virus in this individual changed markedly during the last short period (about 3 months), in which the treatment with secretory immunoglobulin A was carried out. Genome comparisons in oligonucleotide maps show that some oligonucleotides in the genome of the vaccine strain are highly mutable after passage in humans. Images PMID:6179881

Genomic Variability of Serial Human Isolates of Salmonella enterica Serovar Typhimurium Associated with Prolonged Carriage.

PubMed

Octavia, Sophie; Wang, Qinning; Tanaka, Mark M; Sintchenko, Vitali; Lan, Ruiting

2015-11-01

Salmonella enterica serovar Typhimurium is an important foodborne human pathogen that often causes self-limiting but severe gastroenteritis. Prolonged excretion of S. Typhimurium after the infection can lead to secondary transmissions. However, little is known about within-host genomic variation in bacteria associated with asymptomatic shedding. Genomes of 35 longitudinal isolates of S. Typhimurium recovered from 11 patients (children and adults) with culture-confirmed gastroenteritis were sequenced. There were three or four isolates obtained from each patient. Single nucleotide polymorphisms (SNPs) were analyzed in these isolates, which were recovered between 1 and 279 days after the initial diagnosis. Limited genomic variation (5 SNPs or fewer) was associated with short- and long-term carriage of S. Typhimurium. None of the isolates was shown to be due to reinfection. SNPs occurred randomly, and the majority of the SNPs were nonsynonymous. Two nonsense mutations were observed. A nonsense mutation in flhC rendered the isolate nonmotile, whereas the significance of a nonsense mutation in yihV is unknown. The estimated mutation rate is 1.49 × 10(-6) substitution per site per year. S. Typhimurium isolates excreted in stools following acute gastroenteritis in children and adults demonstrated limited genomic variability over time, regardless of the duration of carriage. These findings have important implications for the detection of possible transmission events suspected by public health genomic surveillance of S. Typhimurium infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Management of hyperkalaemia.

PubMed

Maxwell, A P; Linden, K; O'Donnell, S; Hamilton, P K; McVeigh, G E

2013-01-01

Hyperkalaemia, an elevated extracellular fluid potassium concentration, is a common electrolyte disorder and is present in 1-10% of hospitalised patients. Elevated serum potassium concentrations are usually asymptomatic but may be associated with electrocardiogram (ECG) changes. Hyperkalaemia occasionally leads to life-threatening cardiac arrhythmias. Prompt recognition of this disorder, patient risk management and administration of appropriate treatment can prevent serious cardiac complications of hyperkalaemia. Further assessment of the underlying basis for hyperkalaemia usually reveals a problem with renal potassium excretion (rather than transcellular shift of potassium or excess potassium intake). Reduced potassium excretion is typically associated with decreased potassium secretion in the aldosterone-sensitive distal nephron of the kidney. Common causes for hyperkalaemia include kidney failure, limited delivery of sodium and water to the distal nephron and drugs that inhibit the renin-angiotensin-aldosterone system. Treatment of life-threatening hyperkalaemia (particularly those patients with ECG changes) involves administration of intravenous calcium salts to stabilise the resting cardiac membrane potential. The potassium concentration can be lowered by administration of intravenous insulin combined with an infusion of glucose to stimulate intracellular uptake of potassium. Nebulised β-2 adrenoceptor agonists can augment the effects of intravenous insulin and glucose pending more definitive management of the recurrent hyperkalaemia risk. Additional management steps include stopping further potassium intake and careful review of prescribed drugs that may be adversely affecting potassium homeostasis. Changes to prescribing systems and an agreed institutional protocol for management of hyperkalaemia can improve patient safety for this frequently encountered electrolyte disorder.

Albendazole Stimulates the Excretion of Strongyloides stercoralis Larvae in Stool Specimens and Enhances Sensitivity for Diagnosis of Strongyloidiasis▿

PubMed Central

Anamnart, Witthaya; Pattanawongsa, Attarat; Intapan, Pewpan Maleewong; Maleewong, Wanchai

2010-01-01

We succeeded in stimulation of excretion of Strongyloides stercoralis larvae in stool by oral administration of a single dose of 400 mg albendazole to strongyloidiasis patients. This result overcame the false-negative results of stool examination due to low larval numbers. Stool samples were collected from 152 asymptomatic strongyloidiasis patients in the morning, prior to eating. After breakfast, they were given a dose of 400 mg albendazole, and stool samples were collected the following morning. Agar plate culture (APC), modified formalin-ether concentration technique (MFECT), and direct-smear (DS) methods were used to examine stool specimens within 3 h after defecation. The results before and after albendazole was taken were compared. All APCs that were positive became negative after albendazole administration, while MFECT showed a 1.4- to 18.0-fold increase in larval numbers in 97.4% (148/152) of the samples. The DSs were positive in 3 out of 3 smears at a larval number of ≥45 larvae per g (lpg) of stool, and in 1or 2 out of 3 smears at a larval number between 35 and 44 lpg. At a larval number of <35 lpg, the DS became negative. Interestingly 90.5% (19/21) of the samples that were negative by all methods before albendazole administration became positive by MFECT after the treatment. Thus, MFECT can be effectively used for diagnosis of strongyloidiasis with prior administration of albendazole to the subject. PMID:20844212

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-09-03

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general, treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replicatioing a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website ( http://www.hivatis.org ).

Foodborne norovirus outbreak: the role of an asymptomatic food handler.

PubMed

Barrabeig, Irene; Rovira, Ariadna; Buesa, Javier; Bartolomé, Rosa; Pintó, Rosa; Prellezo, Hortènsia; Domínguez, Angela

2010-09-15

In July 2005 an outbreak of acute gastroenteritis occurred on a residential summer camp in the province of Barcelona (northeast of Spain). Forty-four people were affected among residents and employees. All of them had in common a meal at lunch time on 13 July (paella, round of beef and fruit). The aim of this study was to investigate a foodborne norovirus outbreak that occurred in the residential summer camp and in which the implication of a food handler was demonstrated by laboratory tests. A retrospective cohort study was designed. Personal or telephone interview was carried out to collect demographic, clinical and microbiological data of the exposed people, as well as food consumption in the suspected lunch. Food handlers of the mentioned summer camp were interviewed.Ten stool samples were requested from symptomatic exposed residents and the three food handlers that prepared the suspected food. Stools were tested for bacteries and noroviruses. Norovirus was detected using RT-PCR and sequence analysis.Attack rate, relative risks (RR) and its 95% confidence intervals (CI) were calculated to assess the association between food consumption and disease. The global attack rate of the outbreak was 55%. The main symptoms were abdominal pain (90%), nausea (85%), vomiting (70%) and diarrhoea (42.5%). The disease remitted in 24-48 hours. Norovirus was detected in seven faecal samples, one of them was from an asymptomatic food handler who had not eaten the suspected food (round of beef), but cooked and served the lunch. Analysis of the two suspected foods isolated no pathogenic bacteria and detected no viruses. Molecular analysis showed that the viral strain was the same in ill patients and in the asymptomatic food handler (genotype GII.2 Melksham-like). In outbreaks of foodborne disease, the search for viruses in affected patients and all food handlers, even in those that are asymptomatic, is essential. Health education of food handlers with respect to hand washing should be promoted.

A perspective on lyssavirus emergence and perpetuation.

PubMed

Rupprecht, Charles E; Turmelle, Amy; Kuzmin, Ivan V

2011-12-01

Rabies is propagated globally by viruses in the Family Rhabdoviridae, Genus Lyssavirus. These RNA viruses utilize the mammalian central nervous system as their ultimate niche, and exploit routine social mechanisms, as well as host behavioral alterations, to facilitate transmission by neural transport and innervations of the salivary glands, and ultimately excretion via the saliva, towards circulation thereafter in host populations. All mammals are susceptible to infection, but lyssavirus reservoirs are represented by several species of Carnivora, with viral global diversity and distribution in toto driven by a wide variety of the Chiroptera. Pathogen diversity is maintained by multiple faunas, and facilitated by pronounced host vagility, as exemplified by the ease of routine daily and seasonal movements by bats. Viral 'ensembles', or subpopulations associated with productive transmission events, emerge locally in vivo through a combination of naive host infections in some individuals versus acquired immunity by others, using complex metapopulation dynamics. Enhanced surveillance, improved diagnostics, increased pathogen detection, and an integrated One Health approach, targeting human, domestic animal and wildlife interfaces, provide modern insights to the ecology of bat lyssaviruses to augment future prevention and control. Published by Elsevier B.V.

Inactivation of Cytomegalovirus in Breast Milk Using Ultraviolet-C Irradiation: Opportunities for a New Treatment Option in Breast Milk Banking

PubMed Central

Hod, Nurul; Jayaraman, Jothsna; Marchant, Elizabeth A.; Christen, Lukas; Chiang, Peter; Hartmann, Peter; Simmer, Karen

2016-01-01

Pasteurized donor human milk is provided by milk banks to very preterm babies where their maternal supply is insufficient or unavailable. Donor milk is currently processed by Holder pasteurization, producing a microbiologically safe product but significantly reducing immunoprotective components. Ultraviolet-C (UV-C) irradiation at 254 nm is being investigated as an alternative treatment method and has been shown to preserve components such as lactoferrin, lysozyme and secretory IgA considerably better than Holder pasteurization. We describe the inactivation of cytomegalovirus, a virus commonly excreted into breast milk, using UV-C irradiation. Full replication was ablated by various treatment doses. However, evidence of viral immediate early proteins within the cells was never completely eliminated indicating that some viral gene transcription was still occurring. In conclusion, UV-C may be a safe alternative to pasteurisation for the treatment of human donor milk that preserves the bioactivity. However, our data suggests that CMV inactivation will have to be carefully evaluated for each device designed to treat breast milk using UV-C irradiation. PMID:27537346

Inactivation of Cytomegalovirus in Breast Milk Using Ultraviolet-C Irradiation: Opportunities for a New Treatment Option in Breast Milk Banking.

PubMed

Lloyd, Megan L; Hod, Nurul; Jayaraman, Jothsna; Marchant, Elizabeth A; Christen, Lukas; Chiang, Peter; Hartmann, Peter; Shellam, Geoffrey R; Simmer, Karen

2016-01-01

Pasteurized donor human milk is provided by milk banks to very preterm babies where their maternal supply is insufficient or unavailable. Donor milk is currently processed by Holder pasteurization, producing a microbiologically safe product but significantly reducing immunoprotective components. Ultraviolet-C (UV-C) irradiation at 254 nm is being investigated as an alternative treatment method and has been shown to preserve components such as lactoferrin, lysozyme and secretory IgA considerably better than Holder pasteurization. We describe the inactivation of cytomegalovirus, a virus commonly excreted into breast milk, using UV-C irradiation. Full replication was ablated by various treatment doses. However, evidence of viral immediate early proteins within the cells was never completely eliminated indicating that some viral gene transcription was still occurring. In conclusion, UV-C may be a safe alternative to pasteurisation for the treatment of human donor milk that preserves the bioactivity. However, our data suggests that CMV inactivation will have to be carefully evaluated for each device designed to treat breast milk using UV-C irradiation.

Foodborne gastroenteritis outbreak in an Austrian healthcare facility caused by asymptomatic, norovirus-excreting kitchen staff.

PubMed

Schmid, D; Kuo, H-W; Hell, M; Kasper, S; Lederer, I; Mikula, C; Springer, B; Allerberger, F

2011-03-01

An outbreak of norovirus GGII.4 2006b affected an Austrian 600-bed healthcare facility from 15 to 27 March 2009. A total of 204 patients, residents and staff fitted the outbreak case definition; 17 (8.3%) were laboratory-confirmed. Foodborne origin was suspected in the 114 patient and resident cases with onset 15-18 March. A case-cohort study was performed to test the hypothesis that consumption of dishes offered on 14, 15 and 16 March (risk days) was associated with increased risk of infection. Data on food exposure of 62% (317/510) of the patient and resident cohort were available for a simultaneous retrospective cohort study. The case-cohort analysis revealed that consumption of sliced cold sausage offered on 15 March [odds ratio (OR): 3.98; 95% confidence interval (CI): 1.18-14.1], a meat dish with salad (adjusted OR: 2.2; 95% CI: 1.19-4.08) and a rolled spinach pancake (adjusted OR: 2.17; 95% CI: 1.27-3.71) on 16 March were independent risk factors. It is likely that one of the five asymptomatic excretors among the kitchen staff on duty on the risk days was the source of food contamination. The case-cohort study design was found to be a valid alternative to the retrospective cohort study design for the investigation of a suspected foodborne outbreak in a large cohort. Copyright © 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

High-accuracy identification of incident HIV-1 infections using a sequence clustering based diversity measure.

PubMed

Xia, Xia-Yu; Ge, Meng; Hsi, Jenny H; He, Xiang; Ruan, Yu-Hua; Wang, Zhi-Xin; Shao, Yi-Ming; Pan, Xian-Ming

2014-01-01

Accurate estimates of HIV-1 incidence are essential for monitoring epidemic trends and evaluating intervention efforts. However, the long asymptomatic stage of HIV-1 infection makes it difficult to effectively distinguish incident infections from chronic ones. Current incidence assays based on serology or viral sequence diversity are both still lacking in accuracy. In the present work, a sequence clustering based diversity (SCBD) assay was devised by utilizing the fact that viral sequences derived from each transmitted/founder (T/F) strain tend to cluster together at early stage, and that only the intra-cluster diversity is correlated with the time since HIV-1 infection. The dot-matrix pairwise alignment was used to eliminate the disproportional impact of insertion/deletions (indels) and recombination events, and so was the proportion of clusterable sequences (Pc) as an index to identify late chronic infections with declined viral genetic diversity. Tested on a dataset containing 398 incident and 163 chronic infection cases collected from the Los Alamos HIV database (last modified 2/8/2012), our SCBD method achieved 99.5% sensitivity and 98.8% specificity, with an overall accuracy of 99.3%. Further analysis and evaluation also suggested its performance was not affected by host factors such as the viral subtypes and transmission routes. The SCBD method demonstrated the potential of sequencing based techniques to become useful for identifying incident infections. Its use may be most advantageous for settings with low to moderate incidence relative to available resources. The online service is available at http://www.bioinfo.tsinghua.edu.cn:8080/SCBD/index.jsp.

Isolation and characterization of a rhabdovirus from starry flounder (Platichthys stellatus) collected from the northern portion of Puget Sound, Washington, USA

USGS Publications Warehouse

Mork, Christina; Hershberger, Paul K.; Kocan, Richard; Batts, William N.; Winton, James R.

2004-01-01

The initial characterization of a rhabdovirus isolated from a single, asymptomatic starry flounder (Platichthys stellatus) collected during a viral survey of marine fishes from the northern portion of Puget Sound, Washington, USA, is reported. Virions were bullet-shaped and approximately 100 nm long and 50 nm wide, contained a lipid envelope, remained stable for at least 14 days at temperatures ranging from -80 to 5 degrees C and grew optimally at 15 degrees C in cultures of epithelioma papulosum cyprini (EPC) cells. The cytopathic effect on EPC cell monolayers was characterized by raised foci containing rounded masses of cells. Pyknotic and dark-staining nuclei that also showed signs of karyorrhexis were observed following haematoxylin and eosin, May-Grunwald Giemsa and acridine orange staining. PAGE of the structural proteins and PCR assays using primers specific for other known fish rhabdoviruses, including Infectious hematopoietic necrosis virus, Viral hemorrhagic septicemia virus, Spring viremia of carp virus, and Hirame rhabdovirus, indicated that the new virus, tentatively termed starry flounder rhabdovirus (SFRV), was previously undescribed in marine fishes from this region. In addition, sequence analysis of 2678 nt of the amino portion of the viral polymerase gene indicated that SFRV was genetically distinct from other members of the family Rhabdoviridae for which sequence data are available. Detection of this virus during a limited viral survey of wild fishes emphasizes the void of knowledge regarding the diversity of viruses that naturally infect marine fish species in the North Pacific Ocean.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Synergistic effects in the antiviral activity of the three Mx proteins from gilthead seabream (Sparus aurata).

PubMed

Fernández-Trujillo, M A; García-Rosado, E; Alonso, M C; Álvarez, M C; Béjar, J

2015-11-15

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by type I interferon against viral infections. The study on gilthead seabream Mx proteins is especially interesting, since this species is unusually resistant to viral diseases, being asymptomatic carrier of several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems consisting of CHSE-214 cells stably expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV), the European Sheatfish Virus (ESV) and the Lymphocystis Disease Virus (LCDV). A synergistic effect of the Mx proteins was only detected against ESV, no synergy was observed against LCDV, and a negative interference was detected against the two RNA viruses tested, IPNV and VHSV, as viral replication was higher in cells expressing certain Mx combinations than in cells expressing these proteins separately. These results suggest a functional interaction between gilthead seabream Mx isoforms, which results in a higher or lower antiviral activity depending on the virus tested, thus supporting the idea of complex virus-host interactions and finely tuned mechanisms controlling the antiviral activity of Mx proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

An expanded dengue syndrome patient with manifestation myocarditis: case report

NASA Astrophysics Data System (ADS)

Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

2018-03-01

Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

PubMed Central

Niederer, Heather A.; Bangham, Charles R. M.

2014-01-01

Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. PMID:25365582

Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

PubMed Central

Chentoufi, Aziz Alami; BenMohamed, Lbachir

2012-01-01

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed. PMID:23320014

The molecular biology and evolution of feline immunodeficiency viruses of cougars

PubMed Central

Poss, Mary; Ross, Howard; Rodrigo, Allen; Terwee, Julie; VandeWoude, Sue; Biek, Roman

2008-01-01

Feline immunodeficiency virus (FIV) is a lentivirus that has been identified in many members of the family Felidae but domestic cats are the only FIV host in which infection results in disease. We studied FIVpco infection of cougars (Puma concolor) as a model for asymptomatic lentivirus infections to understand the mechanisms of host-virus coexistence. Several natural cougar populations were evaluated to determine if there are any consequences of FIVpco infection on cougar fecundity, survival, or susceptibility to other infections. We have sequenced full length viral genomes and conducted a detailed analysis of viral molecular evolution on these sequences and on genome fragments of serially sampled animals to determine the evolutionary forces experienced by this virus in cougars. In addition, we have evaluated the molecular genetics of FIVpco in a new host, domestic cats, to determine the evolutionary consequences to a host-adapted virus associated with cross-species infection. Our results indicate that there are no significant differences in survival, fecundity or susceptibility to other infections between FIVpco-infected and uninfected cougars. The molecular evolution of FIVpco is characterized by a slower evolutionary rate and an absence of positive selection, but also by proviral and plasma viral loads comparable to those of epidemic lentiviruses such as HIV-1 or FIVfca. Evolutionary and recombination rates and selection profiles change significantly when FIVpco replicates in a new host. PMID:18295904

Notes from the Field: Group A Streptococcal Pharyngitis Misdiagnoses at a Rural Urgent-Care Clinic--Wyoming, March 2015.

PubMed

Harrist, Alexia; Van Houten, Clayton; Shulman, Stanford T; Van Beneden, Chris; Murphy, Tracy

2016-01-01

Group A Streptococcus (GAS) is the most common bacterial cause of pharyngitis, implicated in 20%-30% of pediatric and 5%-15% of adult health care visits for sore throat (1). Along with the sudden onset of throat pain, GAS pharyngitis symptoms include fever, headache, and bilateral tender cervical lymphadenopathy (1,2). Accurate diagnosis and management of GAS pharyngitis is critical for limiting antibiotic overuse and preventing rheumatic fever (2), but distinguishing between GAS and viral pharyngitis clinically is challenging (1). Guidelines for diagnosis and management of GAS pharyngitis have been published by the Infectious Diseases Society of America (IDSA)* (1). IDSA recommends that patients with sore throat be tested for GAS to distinguish between GAS and viral pharyngitis; however, IDSA emphasizes the use of selective testing based on clinical symptoms and signs to avoid identifying GAS carriers rather than acute GAS infections (1). Therefore, testing for GAS usually is not recommended for the following: patients with sore throat and accompanying symptoms (e.g., cough, rhinorrhea) that strongly suggest a viral etiology; children aged <3 years, because acute rheumatic fever is extremely rare in this age group; and asymptomatic household contacts of patients with GAS pharyngitis (1). IDSA recommends penicillin or amoxicillin as the treatment of choice based on effectiveness and narrow spectrum of activity. To date, penicillin-resistant GAS has never been documented (1).

Zika virus infections: An overview of current scenario.

PubMed

Dasti, Javid Iqbal

2016-07-01

Zika virus (ZIKV) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. Until 2007, only 14 cases of human ZIKV infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in Brazil alone, the virus was disseminated to wider South-American territories and travel-associated ZIKV infections were reported in USA, Europe and recently in China. ZIKV infections remain asymptomatic in approximately 80% of the individuals, and no anti-viral treatments were recommended. Yet, neurological complications associated with the infections, such as infant microcephaly and Guillain-Barré syndrome are major cause of the concern. Although, based on small numbers of cases, existing evidence strongly supports an exclusive link of viral infection and observed neurological complications. However, much work remains to assign exact numbers of complications caused by ZIKV. Regarding its structural attributes ZIKV shows remarkable resemblance with dengue virus and West-Nile virus. Despite, genomes of different ZIKV strains have already been decoded; role of the viral components in infection process and particularly pathogenesis of the disease remain widely unclear. In vulnerable areas, most viable strategy to ensure public health safety is vector control and enhanced public awareness about the transmission of the disease. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Epigenetic dysregulation of epstein-barr virus latency and development of autoimmune disease.

PubMed

Niller, Hans Helmut; Wolf, Hans; Ay, Eva; Minarovits, Janos

2011-01-01

Epstein-Barr virus (EBV) is ahumanherpesvirus thatpersists in the memory B-cells of the majority of the world population in a latent form. Primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis. Virus latency is associated with a wide variety of neoplasms whereof some occur in immune suppressed individuals. Virus production does not occur in strict latency. The expression of latent viral oncoproteins and nontranslated RNAs is under epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of a couple of latency promoters in tumor cells, germinal center B cells and lymphoblastoid cells (LCL, transformed by EBV in vitro). Both, latent and lytic EBV proteins elicit a strong immune response. In immune suppressed and infectious mononucleosis patients, an increased viral load can be detected in the blood. Enhanced lytic replication may result in new infection- and transformation-events and thus is a risk factor both for malignant transformation and the development of autoimmune diseases. An increased viral load or a changed presentation of a subset of lytic or latent EBV proteins that cross-react with cellular antigens may trigger pathogenic processes through molecular mimicry that result in multiple sclerosis (MS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Immunogenicity and tolerability of yellow fever vaccination in 23 French HIV-infected patients.

PubMed

Pistone, Thierry; Verdière, Claire-Hélène; Receveur, Marie-Catherine; Ezzedine, Khaled; Lafon, Marie-Edith; Malvy, Denis

2010-09-01

Vaccination of asymptomatic human immunodeficiency virus (HIV)-infected patients with a CD4 cell count ≥ 200/mm³ is strongly suggested prior to travel to a region where yellow fever (YF) is endemic. However, few data describing YF vaccination in such patients are available. In this retrospective observational study of 23 HIV-infected patients, YF antibody titers, CD4 cell counts, and viral loads were measured before and after vaccination. Serologies were performed retrospectively on samples that had been stored as part of routine hospital procedures. Ninety-three percent of patients (13/14) with no baseline immunity, seroconverted after vaccination. Immunogenicity appeared slowly; only 2 of the 5 patients tested within 5 weeks of vaccination had seroconverted. A booster effect was noted in 3 of the 9 patients with baseline immunogenicity. Finally, due to unawareness of his HIV status, one patient was vaccinated and was found later to have a CD4 cell count < 200/mm³.The YF vaccine was well tolerated and no serious adverse events were reported. The impact of vaccination on immunologic and viral parameters was variable. Both decreases (n = 7) and increases (n = 5) in CD4 cell counts were recorded. Viral loads became undetectable in 2 patients and doubled or became positive in 3 patients. Yellow fever vaccination was safe and effective in a large majority of this cohort of stable, HIV-infected patients.

BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist.

PubMed

Priftakis, Peter; Bogdanovic, Gordana; Kokhaei, Parviz; Mellstedt, Håkan; Dalianis, Tina

2003-01-01

Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77-90% of all adult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, a significant overrepresentation of C-->G mutations in the Sp1 binding site in the non-coding control region (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients. We aimed to investigate if this mutation resulted in excessive BKV excretion in HC patients. A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients with HC, with and without the mutations, as well as from patients without HC. Quantification of BKV was successful in 18 of 21 urine patients (six with and six without C-->G mutations) and six patients without HC. A mean of 3.0 x 10(6) BKV copies/microl was detected in urine samples of HC patients with C-->G mutations, compared to a mean of 1.5 x 10(6) BKV copies/microl in HC patients without C-->G mutations and a mean of 1.0 x 10(6) BKV copies/microl in patients without HC. The obtained differences were however not statistically significant, due to one individual non-HC patient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HC groups expressed 1 x 10(6) copies/microl or more, only one of the samples in the non-HC group contained a virus quantity higher than 5 x 10(5) copies. Although we could not confirm that the C-->G mutations in the Sp1 site of BKV were responsible for an increased viral load in patients with HC, our data suggest that levels of BKV above 10(4) copies/microl may indicate a risk for HC.

Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

NASA Technical Reports Server (NTRS)

Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

2003-01-01

OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

Comparative Inactivation of Murine Norovirus, Human Adenovirus, and Human JC Polyomavirus by Chlorine in Seawater

PubMed Central

de Abreu Corrêa, Adriana; Carratala, Anna; Barardi, Celia Regina Monte; Calvo, Miquel; Bofill-Mas, Sílvia

2012-01-01

Viruses excreted by humans affect the commercial and recreational use of coastal water. Shellfish produced in contaminated waters have been linked to many episodes and outbreaks of viral gastroenteritis, as well as other food-borne diseases worldwide. The risk can be reduced by appropriate treatment following harvesting and by depuration. The kinetics of inactivation of murine norovirus 1 and human adenovirus 2 in natural and artificial seawater by free available chlorine was studied by quantifying genomic copies (GC) using quantitative PCR and infectious viral particles (PFU). Human JC polyomavirus Mad4 kinetics were evaluated by quantitative PCR. DNase or RNase were used to eliminate free genomes and assess potential viral infectivity when molecular detection was performed. At 30 min of assay, human adenovirus 2 showed 2.6- and 2.7-log10 GC reductions and a 2.3- and 2.4-log10 PFU reductions in natural and artificial seawater, respectively, and infectious viral particles were still observed at the end of the assay. When DNase was used prior to the nucleic acid extraction the kinetic of inactivation obtained by quantitative PCR was statistically equivalent to the one observed by infectivity assays. For murine norovirus 1, 2.5, and 3.5-log10 GC reductions were observed in natural and artificial seawater, respectively, while no viruses remained infectious after 30 min of contact with chlorine. Regarding JC polyomavirus Mad4, 1.5- and 1.1-log10 GC reductions were observed after 30 min of contact time. No infectivity assays were conducted for this virus. The results obtained provide data that might be applicable to seawater used in shellfish depuration. PMID:22773637

Experimentally Infected Domestic Ducks Show Efficient Transmission of Indonesian H5N1 Highly Pathogenic Avian Influenza Virus, but Lack Persistent Viral Shedding

PubMed Central

Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

2014-01-01

Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2–8 dpi. Viral ribonucleic acid was detected from 1–15 days post inoculation from the oral route and 1–24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection. PMID:24392085

[Mechanisms of lymphopenia in HIV infection].

PubMed

Roger, P M; Pradier, C; Dellamonica, P

1994-01-22

Blood counts of CD4 cells remain the best prognostic factor in patients infected with human immunodeficiency virus (HIV). However, the small number of infected cells contrasts with the importance of lymphocyte depletion. Several mechanisms might explain this depletion including: antibody-dependent cytotoxicity. Twenty to 50% of the antibodies produced in vitro by B lymphocytes are directed against HIV antigens, especially the gp120 and gp41 viral envelope antigen. If this cytotoxicity effect occurs in vivo, it could reduce of lymphocytes carrying the viral genome and partially explain the major lymphopenia in HIV-infected patients. It is not yet known whether the long-term effect of these antibodies is immunoprotective or deleterious, but they may play a protective role at least in the initial stages of the disease. autoimmunity. Sequence homology between the HLA II molecules and the glycoproteins of the viral envelope has been clinically and biologically documented in many manifestations of HIV infection. It has been suggested that alloreactivity, similar to the graft-versus-host reaction could be involved. In addition, programmed cell-death of the CD4 lymphocytes appears to be overactivated in HIV-positive subjects, possibly because the gp120 viral antigen perturbs the CD4-dependent signal for cell death. deleterious effects of cytokines. Tumour necrosis factor, for example, is known to play a role in the regulation of viral replication; it may favour the destruction of contaminated cells but also the initiation of provirus replication and integration into the cell genome. supra-antigens and/or infectious factors. Supra-antigenes, which can link with HLA molecules, are capable of oligoclonal activation without being "processed" in the cell presenting the antigen. This activation might affect cell death. Certain germ toxins could also play a role as cofactors. Cohort studies of asymptomatic HIV patients are needed to improve our understanding of these mechanisms. A therapeutic approach tailored to the stage reached by HIV-infected subjects will then be possible.

Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

PubMed

Korten, Insa; Kieninger, Elisabeth; Klenja, Shkipe; Mack, Ines; Schläpfer, Njima; Barbani, Maria Teresa; Regamey, Nicolas; Kuehni, Claudia E; Hilty, Markus; Frey, Urs; Gorgievski, Meri; Casaulta, Carmen; Latzin, Philipp

2018-01-01

Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity.

PubMed

Kannagi, Mari; Hasegawa, Atsuhiko; Kinpara, Shuichi; Shimizu, Yukiko; Takamori, Ayako; Utsunomiya, Atae

2011-04-01

Human T-cell leukemia virus type 1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-specific T-cell responses elicit antitumor and antiviral effects in experimental models, and are considered to be one of the most important determinants of the disease manifestation, since they are activated in HAM/TSP but not in ATL patients. The combination of low T-cell responses and elevated HTLV-1 proviral loads are features of ATL, and are also observed in a subpopulation of HTLV-1 carriers at the asymptomatic stage, suggesting that these features may be underlying risk factors. These risks may potentially be reduced by vaccination to activate HTLV-1-specific T-cell responses. HAM/TSP and ATL patients also differ in their levels of HTLV-1 mRNA expression, which are generally low in vivo but slightly higher in HAM/TSP patients. Our recent study indicated that viral expression in HTLV-1-infected T-cells is suppressed by stromal cells in culture through type-I IFNs. The suppression was reversible after isolation from the stromal cells, mimicking a long-standing puzzling phenomenon in HTLV-1 infection where the viral expression is very low in vivo and rapidly induced in vitro. Collectively, HTLV-1 is controlled by both acquired and innate immunity in vivo: HTLV-1-specific T-cells survey infected cells, and IFNs suppress viral expression. Both effects would contribute to a reduction in viral pathogenesis, although they may potentially influence or conflict with one another. The presence of double control systems for HTLV-1 infection provides a new concept for understanding the pathogenesis of HTLV-1-mediated malignant and inflammatory diseases. © 2011 Japanese Cancer Association.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ.

PubMed

Giam, Chou-Zen; Semmes, Oliver John

2016-06-16

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10-20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%-5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

PubMed Central

Giam, Chou-Zen; Semmes, Oliver John

2016-01-01

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

Feasibility of Quantitative Environmental Surveillance in Poliovirus Eradication Strategies

PubMed Central

Buisman, A. M.; Rutjes, S. A.; Heijne, J. C.; Teunis, P. F.; de Roda Husman, A. M.

2012-01-01

The progress of the Global Polio Eradication Initiative is monitored by acute flaccid paralysis (AFP) surveillance supplemented with environmental surveillance in selected areas. To assess the sensitivity of environmental surveillance, stools from (re)vaccinated elderly persons with a low seroprevalence and from wastewater were concurrently collected and analyzed in the Netherlands over a prolonged period of time. A total number of 228 healthy individuals with different levels of immunity were challenged with monovalent oral polio vaccine serotype 1 or 3. Poliovirus concentrations were determined by the titration of fecal suspensions on poliovirus-sensitive L20B cells and of sewage concentrates by L20B monolayer plaque assay. Almost half of the individuals (45%) shed poliovirus on day 3 after challenge, which peaked (57%) on day 8 with an average poliovirus excretion of 1.3 × 105 TCID50 per g of feces and gradually decreased to less than 5% on day 42. The virus concentrations in sewage peaked on days 6 to 8 at approximately 100 PFU per liter, remained high until day 14, and subsequently decreased to less than 10 PFU per liter on day 29. The estimated poliovirus concentration in sewage approximated the measured initial virus excretion in feces, within 1 log10 variation, resulting in a sensitivity of detection of 100 infected but mostly asymptomatic individuals in tens of thousands of individuals. An additional second peak observed in sewage may indicate secondary transmission missed by enterovirus or AFP surveillance in patients. This enables the detection of circulating poliovirus by environmental surveillance, supporting its feasibility as an early warning system. PMID:22447593

Super-shedding and the link between human infection and livestock carriage of Escherichia coli O157.

PubMed

Chase-Topping, Margo; Gally, David; Low, Chris; Matthews, Louise; Woolhouse, Mark

2008-12-01

Cattle that excrete more Escherichia coli O157 than others are known as super-shedders. Super-shedding has important consequences for the epidemiology of E. coli O157 in cattle--its main reservoir--and for the risk of human infection, particularly owing to environmental exposure. Ultimately, control measures targeted at super-shedders may prove to be highly effective. We currently have only a limited understanding of both the nature and the determinants of super-shedding. However, super-shedding has been observed to be associated with colonization at the terminal rectum and might also occur more often with certain pathogen phage types. More generally, epidemiological evidence suggests that super-shedding might be important in other bacterial and viral infections.

Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

PubMed

Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

2013-01-01

To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001) and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001) but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27). HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

Effect of Genital Herpes on Cervicovaginal HIV Shedding in Women Co-Infected with HIV AND HSV-2 in Tanzania

PubMed Central

Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A.; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

2013-01-01

Objectives To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Design Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Results Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41–0.60, p<0.001) and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16–0.32, p<0.001) but not the presence of herpetic lesions (β = −0.10, 95%CI:−0.28–0.08, p = 0.27). Conclusions HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility. PMID:23516595

Single-cell analysis of lymphokine imbalance in asymptomatic HIV-1 infection: evidence for a major alteration within the CD8+ T cell subset

PubMed Central

Sousa, A E; Victorino, R M M

1998-01-01

In this study we investigated at single-cell level by flow cytometry the potential of T cell cytokine production in asymptomatic HIV-1-infected subjects with > 200 CD4 counts and possible correlation with T helper cell depletion and viral load. Mitogen-stimulated peripheral blood mononuclear cells from 32 HIV-1+ patients and 16 healthy subjects were intracytoplasmically stained for IL-2, interferon-gamma (IFN-γ), IL-4 or IL-10, and the frequency of cytokine-producing cells was assessed in total T cells, CD4, CD8 and CD45RO subsets as well as in CD69+CD3+ gated lymphocytes. HIV-1+ patients, irrespective of their degree of CD4 depletion, exhibited a major increase in IFN-γ+ CD8 T cells, largely due to CD28− cells, as well as a decrease in the capacity of CD8 T cells to produce IL-2. Patients with > 500 CD4 counts showed a diminished frequency of IL-4 expression in CD4 T cells and a negative correlation was found between this parameter and the ex vivo CD4 counts in the 32 patients. Analysis of patients stratified according to viral load revealed a significantly higher proportion of IL-2-producing CD4 cells in the group with < 5000 RNA copies/ml. In short, using single-cell analysis and an antigen-presenting cell-independent stimulus, we have not been able to find any significant cytokine imbalances in the CD4 subset, suggesting that the well described T helper defects are not due to intrinsic alterations in the potential of CD4 T cells to produce cytokines. On the other hand, the major disturbances in the CD8 T lymphocytes agree with the marked activation and possible replicative senescence of CD8 T cells and emphasize the role of this subset in HIV immunopathogenesis. PMID:9649194

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3

PubMed Central

de Rozières, Sohela; Swan, Christina H; Sheeter, Dennis A; Clingerman, Karen J; Lin, Ying-Chuan; Huitron-Resendiz, Salvador; Henriksen, Steven; Torbett, Bruce E; Elder, John H

2004-01-01

Background The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. Results Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p ≤ 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p ≤ 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. Conclusions The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection. PMID:15555065

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3.

PubMed

de Rozières, Sohela; Swan, Christina H; Sheeter, Dennis A; Clingerman, Karen J; Lin, Ying-Chuan; Huitron-Resendiz, Salvador; Henriksen, Steven; Torbett, Bruce E; Elder, John H

2004-11-19

The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p < or = 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p < or = 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection.

Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases.

PubMed

Niller, Hans Helmut; Wolf, Hans; Minarovits, Janos

2008-05-01

Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosuppressed or immunodeficient individuals, but also in patients with an apparently intact immune system. In memory B cells, tumor cells, and lymphoblastoid cell lines (LCLs, transformed by EBV in vitro) the expression of the viral genes is highly restricted. There is no virus production (lytic viral replication associated with the expression of all viral genes) in tight latency. The expression of latent viral oncogenes and RNAs is under a strict epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of latent promoters in tumor cells, germinal center B cells, and LCLs. Both the latent and lytic EBV proteins are potent immunogens and elicit vigorous B- and T-cell responses. In immunosuppressed and immunodeficient patients, or in individuals with a functional defect of EBV-specific T cells, lytic EBV replication is regularly activated and an increased viral load can be detected in the blood. Enhanced lytic replication results in new infection events and EBV-associated transformation events, and seems to be a risk factor both for malignant transformation and the development of autoimmune diseases. One may speculate that an increased load or altered presentation of a limited set of lytic or latent EBV proteins that cross-react with cellular antigens triggers and perpetuates the pathogenic processes that result in multiple sclerosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In addition, in SLE patients EBV may cause defects of B-cell tolerance checkpoints because latent membrane protein 1, an EBV-encoded viral oncoprotein can induce BAFF, a B-cell activating factor that rescues self-reactive B cells and induces a lupus-like autoimmune disease in transgenic mice.

Multisite outbreak of norovirus associated with a franchise restaurant--Kent County, Michigan, May 2005.

PubMed

2006-04-14

The majority of cases of foodborne gastroenteritis in the United States are caused by noroviruses. This report summarizes an investigation by the Kent County Health Department (KCHD) in Michigan into three norovirus outbreaks and a cluster of community cases that were associated with a national submarine sandwich franchise restaurant during May 3-9, 2005. The investigation identified a potential source, a food handler who had returned to work within a few hours of having symptoms of gastrointestinal illness while he was still excreting norovirus in his stools. To prevent norovirus outbreaks, food service workers should be educated regarding norovirus transmission and control. In 2005, new guidelines for state health departments regarding norovirus containment were published by the Food and Drug Administration (FDA); guidelines for local health departments in Michigan were issued by the state's Department of Community Health and Department of Agriculture. The new guidelines for Michigan recommend that food service workers with suspected norovirus not return to work until they are asymptomatic for 48-72 hours.

[HCV and HBV seropositivity in university students of the State of Nuevo Leòn, Mexico].

PubMed

Flores-Castañeda, M S; García-Méndez, B L; Tijerina-Menchaca, R

1996-01-01

Viral hepatitis is a contagious disease. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), may be either chronically symptomatic or asymptomatic, and suffer cirrhosis and high risk of hepatic carcinoma. Asymptomatic carriers of HBV surface antigen (HBs-Ag) or with anti-HCV antibodies are potentially infectious, and therefore a risk to public health. This work seeks to establish the frequency of seropositivity for HBs-Ag and anti-HCV antibodies in a population of 774 newly accepted students of the Medical School of the Autonomous University of Nuevo Leon, whose average age was 18 years. Second generation ELISA test were used to screen for HBs-Ag and anti-HCV antibodies. HBs-Ag was confirmed by a neutralization test and anti-HCV antibodies were confirmed by a RIBA test. Three sera were positive for HBs-Ag by ELISA and only one serum (0.13% of analyzed samples) was confirmed by the neutralization technique. On the other hand 12 sera were positive for anti-HCV antibodies by ELISA, and eight of these were confirmed by RIBA (1.03% of the analyzed samples). Intensive reactivity bands were found in two sera, and weak reactivity bands were found in six sera. ELISA screening for anti-HCV antibodies showed 0.5% of false positives. This study shows that the frequency of anti-HCV antibodies is 7.95% times higher than that found for HBs-Ag. All seropositive patients were asymptomatic and potentially infective. This demonstrates the need to routinely screen for HBs-Ag and anti-HCV antibodies to establish the prevalence of these diseases in our area.

REACTIVATION OF LATENT VIRUSES IN INDIVIDUALS RECEIVING RITUXIMAB FOR NEW ONSET TYPE 1 DIABETES

PubMed Central

Kroll, Jing Lu; Beam, Craig; Li, Shaobing; Viscidi, Raphael; Dighero, Bonnie; Cho, Alice; Boulware, David; Pescovitz, Mark; Weinberg, Adriana

2013-01-01

Background Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. Objectives To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Study Design Subjects received 4 weekly doses of rituximab (N=57) or placebo (N=30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. Results EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p<0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p<0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Conclusions Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses. PMID:23422292

Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes.

PubMed

Kroll, Jing Lu; Beam, Craig; Li, Shaobing; Viscidi, Raphael; Dighero, Bonnie; Cho, Alice; Boulware, David; Pescovitz, Mark; Weinberg, Adriana

2013-06-01

Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Subjects received 4 weekly doses of rituximab (N = 57) or placebo (N = 30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p < 0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p < 0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses. Copyright © 2013 Elsevier B.V. All rights reserved.

Contributions from the silent majority dominate dengue virus transmission

PubMed Central

Duong, Veasna; Althouse, Benjamin M.; Lloyd, Alun L.; Waller, Lance A.; Morrison, Amy C.; Kitron, Uriel

2018-01-01

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0–146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82–86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0–79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8–1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission. PMID:29723307

HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications

PubMed Central

Hasenkrug, Aaron M.; Jha, Aashish R.; Carvalho, Karina I.; Eccles-James, Ijeoma G.; Bruno, Fernanda R.; Vieira, Raphaella G. S.; York, Vanessa A.; Chew, Glen M.; Jones, R. Brad; Tanaka, Yuetsu; Neto, Walter K.; Sanabani, Sabri S.; Ostrowski, Mario A.; Segurado, Aluisio C.; Nixon, Douglas F.; Kallas, Esper G.

2011-01-01

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially “exhausted” and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8+ and CD4+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3+ and Tim-3− fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications. PMID:21541358

Burden of Chlamydia trachomatis in India: a systematic literature review.

PubMed

Thomas, Pierre; Spaargaren, Joke; Kant, Rajiv; Lawrence, Rubina; Dayal, Arvind; Lal, Jonathan A; Morré, Servaas A

2017-07-31

Chlamydia trachomatis (hereafter CT) is Gram-negative, obligate intracellular pathogen. It causes the world's most common non-viral sexually transmitted disease. India is home to the world's greatest burden of infectious diseases, yet information on prevalence rates of CT is scarce. This article systematically reviews the literature for the prevalence rates and testing methods in India. A total of 27 studies were included. Four main patients groups (symptomatic women, infertile women, pregnant women and asymptomatic population groups) could be identified with varying rates of CT (0.1%-32% using PCR, 2.4%-75% using ELISA serology). Most of the studies originated from urban settings, 11 of them from New Delhi. In-house PCR was the most common diagnostic technique used generating the following ranges in prevalence for the four group studies: symptomatic women 10%-50%, pregnant women 0.1%-2.5% and asymptomatic populations 0.9%-24.5%. The rates among infertile women were 9%-68% based on serology results. The prevalence rates featured in this paper are in line with other locations across the Indian subcontinent. This review highlights the extreme heterogeneity in the limited studies available in India on CT and the need for standardized guidelines for diagnosis and management of CT in India. The availability of resources should be considered in the formulation of recommendations. © FEMS 2017.

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Parvovirus B19 infection as a cause of acute myositis in an adult.

PubMed

Cakirca, Mustafa; Karatoprak, Cumali; Ugurlu, Serdal; Zorlu, Mehmet; Kıskaç, Muharrem; Çetin, Güven

2015-01-01

Parvovirus B19 infection is often asymptomatic, but clinical expressions may include transient aplastic crisis, erythema infectiosum, non-immune hydrops fetalis, and chronic red cell aplasia. This virus has also been associated with rheumatoid arthritis and other autoimmune connective tissue diseases; however, we could not identify any acute adult myositis case developed after a Parvovirus B19 infection in the literature. For this reason, we would like to present a rare case of acute myositis developed after Parvovirus B19 infection. In patients presenting with symptoms of fever, rash on the legs and myositis, viral infections such as Parvovirus B19 should be kept in mind. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Intermittent maple syrup urine disease: two case reports.

PubMed

Axler, Olof; Holmquist, Peter

2014-02-01

The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain α-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or viral gastroenteritis triggers catabolism of muscle protein. Intermittent MSUD should be suspected in cases of common infections with a clinically atypical course, especially in children displaying ataxia or marked drowsiness.

Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis

PubMed Central

Chen, Crystal Y.; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Kouiavskaia, Diana; Nathanson, Neal; Macadam, Andrew J.; Andino, Raul; Kew, Olen; Xu, Junfa

2017-01-01

ABSTRACT Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 107 to 109 50% tissue culture infective doses (TCID50) consistently infected all the animals, and many monkeys receiving 108 or 109 TCID50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 107 to 109 TCID50 Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines. PMID:28356537

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-05-17

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website (http://www.hivatis.org).

Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization.

PubMed

Maschkowitz, Gregor; Gärtner, Sabine; Hofmann-Winkler, Heike; Fickenscher, Helmut; Winkler, Michael

2018-05-01

Human cytomegalovirus (HCMV) is a widespread human pathogen that causes asymptomatic infection in healthy individuals but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC), where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from the trans -Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We have previously shown that the UL35 gene is involved in HCMV assembly, but it is unknown how UL35 proteins regulate viral assembly. Here we show that sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. Expression of wild-type proteins but not mutants defective in SNX5 binding resulted in the cellular redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35 proteins bind and negatively regulate SNX5 to modulate cellular transport pathways. Furthermore, binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant HCMV glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and ppUL35A control the localization of the essential gB through the regulation of a retrograde transport pathway. Thus, this work is the first to define a molecular interaction between a tegument protein and a vesicular transport factor to regulate glycoprotein localization. IMPORTANCE Human cytomegalovirus is ubiquitously present in the healthy population, but reactivation or reinfection can cause serious, life-threatening infections in immunocompromised patients. For completion of its lytic cycle, human cytomegalovirus induces formation of an assembly center where mature virus particles are formed from multiple viral proteins. Viral glycoproteins use separate vesicular pathways for transport to the assembly center, which are incompletely understood. Our research identified a viral structural protein which affects the localization of one of the major glycoproteins. We could link this change in glycoprotein localization to an interaction of the structural protein with a cellular protein involved in regulation of vesicle transport. This increases our understanding of how the virus intersects into cellular regulatory pathways to enhance its own replication. Copyright © 2018 American Society for Microbiology.

Cis-drivers and trans-drivers of bovine leukemia virus oncogenesis.

PubMed

Safari, Roghaiyeh; Hamaidia, Malik; de Brogniez, Alix; Gillet, Nicolas; Willems, Luc

2017-10-01

The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the mechanisms of oncogenesis are still largely unknown, there is clear experimental evidence showing that BLV infection drastically modifies the pattern of gene expression of the host cell. This alteration of the transcriptome in infected B-lymphocytes results first, from a direct activity of viral proteins (i.e. transactivation of gene promoters, protein-protein interactions), second, from insertional mutagenesis by proviral integration (cis-activation) and third, from gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous immune response that indirectly modifies gene transcription in other cell types (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle, insertional mutagenesis and microRNA-associated RNA interference can modify the cell fate without inducing an antiviral immunity. Despite a tight control by the immune response, the permanent attempts of the virus to replicate ultimately induce mutations in the infected cell. Accumulation of these genomic lesions and Darwinian selection of tumor clones are predicted to lead to cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

PubMed

van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

2009-12-15

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

Persistence and infectivity of Zika virus in semen after returning from endemic areas: Report of 5 cases.

PubMed

García-Bujalance, S; Gutiérrez-Arroyo, A; De la Calle, F; Díaz-Menéndez, M; Arribas, Jose R; García-Rodríguez, J; Arsuaga, M

2017-11-01

There are limited data about the persistence and infectivity of Zika virus in semen of symptomatic travelers returning from endemic areas and even less data in asymptomatic cases. We investigated the persistence and infectivity of ZIKA virus in semen in five patients with Zika virus infection returning to Spain from endemic areas. We evaluated the epidemiological, clinical and virological characteristic of the five patients. In semen we detected ZIKA virus by PCR, partial sequencing and cell culture. We also performed phylogenetic analysis. We detected Zika virus RNA (Asian lineage) by PCR in semen samples from day 14th to day 96th since the day of illness onset. Semen viral culture was positive for Zika virus in two patients at days of illness 30 and 69 by virus propagation. Phylogenetic analysis strongly suggested male to female sexual transmission in a couple returning from Maldives. This case series confirms that Zika virus RNA can be detected in semen up to three months after infection. Viral culture of semen samples shows prolonged infectivity that can lead to sexual transmission of Zika virus. Copyright © 2017 Elsevier B.V. All rights reserved.

Feline fecal virome reveals novel and prevalent enteric viruses

PubMed Central

Ng, Terry Fei Fan; Mesquita, João Rodrigo; Nascimento, Maria São José; Kondov, Nikola O.; Wong, Walt; Reuter, Gábor; Knowles, Nick J.; Vega, Everardo; Esona, Mathew D.; Deng, Xutao; Vinjé, Jan; Delwart, Eric

2014-01-01

Humans keep more than 80 million cats worldwide, ensuring frequent contacts with their viruses. Despite such interactions the enteric virome of cats remains poorly understood. We analyzed a fecal sample from a single healthy cat from Portugal using viral metagenomics and detected five eukaryotic viral genomes. These viruses included a novel picornavirus (proposed genus “Sakobuvirus”) and bocavirus (feline bocavirus 2), a variant of feline astrovirus 2 and sequence fragments of a highly divergent feline rotavirus and picobirnavirus. Feline sakobuvirus A represents the prototype species of a proposed new genus in the Picornaviridae family, distantly related to human salivirus and kobuvirus. Feline astroviruses (mamastrovirus 2) are the closest relatives of the classic human astroviruses (mamastrovirus 1), suggestive of past cross-species transmission. Presence of these viruses by PCR among Portuguese cats was detected in 13% (rotavirus), 7% (astrovirus), 6% (bocavirus), 4% (sakobuvirus), and 4% (picobirnavirus) of 55 feline fecal samples. Co-infections were frequent with 40% (4/10) of cats shedding more than one of these viruses. Our study provides an initial unbiased description of the feline fecal virome indicating a high level of asymptomatic infections. Availability of the genome sequences of these viruses will facilitate future tropism and disease association studies. PMID:24793097

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

High production of RANTES and MIP-1alpha in the tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM).

PubMed

Montanheiro, Patricia; Vergara, Maria Paulina Posada; Smid, Jerusa; da Silva Duarte, Alberto José; de Oliveira, Augusto César Penalva; Casseb, Jorge

2007-08-01

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with progressive neurological disorders and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). The pathogenesis of TSP/HAM is considered as immune mediated, involving cytotoxic T cell (CTL) responses to a number of viral proteins and notably the regulation protein Tax. T CD8+ cells produce beta-chemokines, which are important in the anti-viral response. In the present study, we have analyzed the CC chemokines (RANTES, MIP-1beta and MIP-1alpha) production in retrovirus-infected subjects. A total of 191 subjects were studied: 52 healthy controls, 72 asymptomatic HTLV-1-infected carriers and 67 TSP/HAM patients. Peripheral blood mononuclear cells were maintained in the presence or absence of PHA, and supernatant fluids were assayed using EIA. MIP-1beta concentration was not significantly different across groups, but RANTES and MIP-1alpha concentrations showed significant differences when the three groups were compared. In TSP/HAM patients, the increase in the production of chemokines may lead to a recruitment of pro-inflammatory factors, contributing to the membrane's myelin damage.

Epidemiology, transmission, diagnosis, and outcome of Hepatitis C virus infection.

PubMed

Moosavy, Seyed Hamid; Davoodian, Parivash; Nazarnezhad, Mirza Ali; Nejatizaheh, Abdolazim; Eftekhar, Ebrahim; Mahboobi, Hamidreza

2017-10-01

Hepatitis C infection is one of the main causes of chronic liver disorders worldwide. Nearly three percent (3%) of the world population has an HCV infection. Prevalence of HCV infection was higher in some groups such as injected drug users (IDUs) and HIV positive populations. Acute hepatitis has proven asymptomatic in most cases, and delay of diagnosis might lead to late onset of hepatocellular carcinoma and cirrhosis. Some host characteristics such as age, gender, body mass index, and viral properties are associated with HCV outcome hepatitis. Although disease progression is typically slow, some risk factors such as alcohol abuse and coinfection of patients with HBV and HIV can worsen the disease. On the other hand, viral overload is one of the main causes of prediction of HCV infection outcome. Prevalence of HCV infection will increase if we do not consider means of transmission, virus behaviors, and immunologic responses. Rapid diagnostic tests can help us to create preventive strategies among undeveloped villages and prisoners. Screening and training of the high-risk population such as IV drug users, dialysis patients, and hemophiliacs must be one of main HCV preventive programs. The present review is intended to help health policymakers to design suitable preventive and management programs.

Evaluation of an integrated cell culture RT-PCR assay to detect and quantify infectious lymphocystis disease virus.

PubMed

Valverde, Estefania J; Borrego, Juan J; Castro, Dolores

2016-12-01

The lymphocystis disease virus (LCDV), a member of the Iridoviridae family, infects a wide range of fish species including gilthead seabream (Sparus aurata L.), the most important species cultured in the Mediterranean. LCDV is difficult to propagate in cell culture and does not produce clear and consistent cytopathic effects (CPE), especially in samples collected from subclinically infected fish. An integrated cell culture reverse transcription-polymerase chain reaction (ICC-RT-PCR) assay, followed by dot-blot hybridization of the RT-PCR products, was developed to improve the detection of infectious LCDV. The sensitivity of the ICC-RT-PCR assay, which can be performed in 7 d, was at least 100-fold higher than viral diagnosis obtained by CPE development. The developed assay thus allows the determination of infectious titres in samples with low viral loads, including those from asymptomatic carrier fish, in which no CPE was recorded after a 14-d incubation period. The ICC-RT-PCR assay enables rapid, specific and sensitive detection and quantification of infectious LCDV, and may be a valuable tool in the study of aspects of LCDV infection including transmission or epizootiology. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Coxiella burnetii shedding in milk of dairy bovine, caprine, and ovine herds.

PubMed

Rodolakis, A; Berri, M; Héchard, C; Caudron, C; Souriau, A; Bodier, C C; Blanchard, B; Camuset, P; Devillechaise, P; Natorp, J C; Vadet, J P; Arricau-Bouvery, N

2007-12-01

The shedding of Coxiella burnetii in bovine, caprine, and ovine milk was measured using PCR, in 3 herds for each species, the bulk tank milk samples of which were positive at the time of their selection. Milk samples of 95 cows, 120 goats, and 90 ewes were sampled over 16 wk, as was the bulk tank milk. The shedding of C. burnetii in vaginal mucus and feces was checked at the beginning of the experiment and 2 mo later. The clinical signs in the selected herds as well as the duration and the shedding routes differed among the 3 species. The cows were asymptomatic and shed C. burnetii almost exclusively in milk. In one of the caprine herds, abortions due to C. burnetii were reported. The goats excreted the bacteria mainly in milk. In contrast, the ewes, which came from flocks with abortions due to Q fever (C. burnetii infection), shed the bacteria mostly in feces and in vaginal mucus. This could explain why human outbreaks of Q fever are more often related to ovine flocks than to bovine herds. These excretions did not seem more frequent when the samples were taken close to parturition. The samples were taken from 0 to 421 d after parturition in bovine herds and from 5 to 119 d and 11 to 238 d after parturition in the caprine and ovine herds, respectively. The shedding in milk was sometimes intermittent, and several animals shed the bacteria but were negative by ELISA: 80% of the ewes were seronegative, underscoring the lack of sensitivity of the ELISA tests available for veterinary diagnosis. The detection of antibodies in milk seems more sensitive than it is in serum.

Kinetics of Poliovirus Shedding following Oral Vaccination as Measured by Quantitative Reverse Transcription-PCR versus Culture

PubMed Central

Begum, Sharmin; Uddin, Md Jashim; Platts-Mills, James A.; Liu, Jie; Kirkpatrick, Beth D.; Chowdhury, Anwarul H.; Jamil, Khondoker M.; Haque, Rashidul; Petri, William A.; Houpt, Eric R.

2014-01-01

Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in stool samples can provide information about rates of mucosal immunity and allow estimation of the poliovirus reservoir. We developed a multiplex one-step quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin strains 1, 2, and 3 directly in stool samples with an external control to normalize samples for viral quantity and compared its performance with that of viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh, after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350 stool samples were tested, the sensitivity and specificity of the quantitative PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative relationship between culture+/qPCR+ and culture−/qPCR+ stool samples was observed. The kinetics of shedding revealed by qPCR and culture were similar. qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used to identify the culture-positive shedders, as well as the long-duration or high-frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of infants contributed the vast majority (93 to 100%) of the total estimated viral excretion across all subtypes at each time point. This qPCR assay for OPV can simply and quantitatively detect all three Sabin strains directly in stool samples to approximate shedding both qualitatively and quantitatively. PMID:25378579

A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa.

PubMed

Geldenhuys, Marike; Mortlock, Marinda; Weyer, Jacqueline; Bezuidt, Oliver; Seamark, Ernest C J; Kearney, Teresa; Gleasner, Cheryl; Erkkila, Tracy H; Cui, Helen; Markotter, Wanda

2018-01-01

Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.

A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa

PubMed Central

Geldenhuys, Marike; Mortlock, Marinda; Weyer, Jacqueline; Bezuidt, Oliver; Seamark, Ernest C. J.; Kearney, Teresa; Gleasner, Cheryl; Erkkila, Tracy H.; Cui, Helen; Markotter, Wanda

2018-01-01

Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard. PMID:29579103

Diagnosis of Wilson disease in young children: molecular genetic testing and a paradigm shift from the laboratory diagnosis.

PubMed

Seo, Jeong Kee

2012-12-01

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, brain and cornea. Mutations in the WD gene, ATP7B, cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 500 mutations are now recognized, scattered throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. Molecular genetic testing is playing an increasingly important role in the diagnosis of WD in uncertain cases and family screening. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only definite solution for differentiating heterozygote carriers from affected asymptomatic patients. Routine genetic testing, because of the multitude of documented mutations, has been thought to be impractical until recently. However, genetic testing is now being more actively applied to the diagnosis of WD, particularly in young children in whom conventional biochemical diagnosis has much limitation and only genetic testing is able to confirm WD. Because advancement of modern biochemical technology now allows more rapid, easier, and less expensive mutation detection, direct DNA sequencing could be actively considered as the primary mode of diagnostic investigation rather than a supplementary test to the conventional biochemical tests. This review will focus on the recent advancement of molecular genetics and genetic diagnosis of WD in very young children on the basis of research data of the Seoul National University Children's Hospital and recent literature.

Association of pheochromocytoma and ganglioneuroma: unusual finding in neurofibromatosis type 1.

PubMed

Mezitis, Spyros G E; Geller, Mauro; Bocchieri, Elisa; Del Pizzo, Joseph; Merlin, Scott

2007-10-01

To report a rare case of association of pheochromocytoma and ganglioneuroma in an asymptomatic patient with neurofibromatosis type 1 (NF1) and to discuss the importance of annual biochemical and imaging studies. We present the clinical, laboratory, and pathology findings in a 41-year-old woman with NF1 and review the pertinent literature. A 41-year-old woman with NF1 presented for a routine gynecologic examination, at which time a right adrenal mass (4 by 3 cm) was discovered by abdominal ultrasonography and confirmed by abdominal computed tomographic scans and magnetic resonance imaging. The patient was normotensive and complained only of discrete essential tremors. Biochemical studies showed a serum epinephrine level of 195 pg/mL (normal, <100) and a 24-hour urine epinephrine excretion of 55 microg (normal, <20), findings consistent with pheochromocytoma. Metaiodobenzylguanidine scintigraphy revealed uptake in the right adrenal gland, with no evidence of metastatic lesions. Before surgical treatment, the patient received an alpha-adrenergic antagonist for 30 days. Laparoscopic excision of the right adrenal gland yielded excellent postoperative results. Surgical pathology revealed a multinodular mass composed of pheochromocytoma and ganglioneuroma. In patients with NF1 (von Recklinghausen's disease), a tumor consisting of pheochromocytoma and ganglioneuroma is rare and may be more aggressive than pheochromocytoma alone. An asymptomatic catecholamine-producing tumor may cause substantial morbidity and mortality, especially in patients who are undergoing surgical intervention or are under other stressors. The current guidelines for managing patients with NF1 are an annual history and physical examination. Because of the increased prevalence of pheochromocytoma and ganglioneuroma in patients with NF1, and the potential associated adverse effects, we emphasize the importance of periodic clinical evaluation with biochemical testing and imaging studies.

Studies on Infectious Mononucleosis

PubMed Central

Joncas, J.; Lussier, G.; Pavilanis, V.

1966-01-01

Heparinized blood specimens obtained from two patients in the acute phase of infectious mononucleosis and from a healthy technician were injected intravenously into rhesus monkeys (Macaca mulatta) and the animals were observed for three weeks to one month for clinical, hematological and serological signs of infectious mononucleosis. Splenomegaly was the only definite clinical finding after 12 and 16 days, respectively. There were no definite hematological changes. At autopsy, hyperplasia of the germinal centres of lymphoid follicles, occasional foci of lymphocytic infiltration in the red pulp, and abnormal lymphoid cells in venules or arteries of the spleen were noted. The lesions in the spleen suggest that asymptomatic, presumably viral, infections occur in rhesus monkeys after inoculation with material from patients with infectious mononucleosis. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:4957314

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease.

PubMed

Le Calloch, R; Ianotto, J C; Berthou, C; Tempescul, A

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.

Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

PubMed

Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

2011-08-01

Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases.

Viral infections associated with oral cancers and diseases in the context of HIV: Workshop 3B

PubMed Central

Speicher, David J; Ramirez-Amador, Velia; Dittmer, Dirk P; Webster-Cyriaque, Jennifer; Goodman, Marc T; Moscicki, Anna-Barbara

2017-01-01

Human herpesviruses (HHVs) and Human papillomaviruses (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes immunocompromised by age, illness, or HIV infection these dormant viruses can manifest themselves and produce disease. In HIV-positive patients there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses EBV, HHV-8, and HPV. This workshop examined four questions regarding the viruses associated with oral cancers disease in the HIV-positive and -negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required. PMID:27109286

Controversies in HIV-associated neurocognitive disorders

PubMed Central

Nightingale, Sam; Winsto, Alan; Letendre, Scott; Michael, Benedict D; McArthur, Justin C; Khoo, Saye; Solomon, Tom

2015-01-01

Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated. PMID:25316020

Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

PubMed Central

Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

2012-01-01

Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases. PMID:21861620

Faustovirus-Like Asfarvirus in Hematophagous Biting Midges and Their Vertebrate Hosts

PubMed Central

Temmam, Sarah; Monteil-Bouchard, Sonia; Sambou, Masse; Aubadie-Ladrix, Maxence; Azza, Saïd; Decloquement, Philippe; Khalil, Jacques Y. Bou; Baudoin, Jean-Pierre; Jardot, Priscilla; Robert, Catherine; La Scola, Bernard; Mediannikov, Oleg Y.; Raoult, Didier; Desnues, Christelle

2015-01-01

Faustovirus, a new Asfarviridae-related giant virus, was recently isolated in Vermamoeba vermiformis, a protist found in sewage water in various geographical locations and occasionally reported in human eye infection cases. As part of a global metagenomic analysis of viral communities existing in biting midges, we report here for the first time the identification and isolation of a Faustovirus-like virus in hematophagous arthropods and its detection in their animal hosts. The DNA virome analysis of three pools of Culicoides sp., engorged female Culicoides imicola and non-engorged male/female C. imicola biting midges collected in Senegal, revealed the presence of amoeba-infecting giant viruses and, among them, a majority of sequences related to Faustovirus. Phylogenetic analyses conducted on several structural genes of Faustovirus confirmed the clustering of the arthropod-borne Faustovirus with sewage-borne Faustoviruses, with a distinct geographical clustering of Senegalese Faustovirus strains. Transmission electron microscopy identified viral particles with morphologies and diameters which were compatible with Faustovirus. The presence of infectious arthropod-borne Faustovirus was finally confirmed by successful isolation on V. vermiformis amoeba. Global proteomic analysis of biting midges identified that arthropods' blood meal originating from cattle, rodents and humans. Further screening of cattle sera and rodent tissue resulted in prevalence of Faustovirus being estimated at 38% in rodents and 14% in cattle, suggesting a possible origin of Faustovirus presence in arthropods via the ingestion of contaminated blood meal. Viral loads were the highest in rodents' urine and kidney samples, suggesting a possible excretion of viral particles into the environment. Faustovirus DNA polymerase-related sequences were also detected in more than 9 and 11% of febrile patients and healthy Senegalese human sera, respectively. Our study thus, highlights the need to investigate the role of arthropods, wildlife, and domestic animals in the lifecycle of amoeba-infecting giant viruses and, in particular, the environmental cycle of Faustovirus. PMID:26733117

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

PubMed

Gatell, J M

1998-01-01

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a relatively low baseline viral load. Furthermore, components of these protease inhibitor-sparing combinations such as didanosine or nevirapine are suitable for once daily administration.

Fenofibrate causes elevation of betaine excretion but not excretion of other osmolytes by healthy adults.

PubMed

Lever, Michael; McEntyre, Christopher J; George, Peter M; Slow, Sandy; Chambers, Stephen T; Foucher, Christelle

2014-01-01

Cross-sectional data suggest that bezafibrate increases betaine excretion in dyslipidemic patients. We aimed to demonstrate that fenofibrate induces increased betaine excretion in normal subjects and explore whether other 1-carbon metabolites and osmolytes are similarly affected. Urine was collected from 26 healthy adults before and after treatment with fenofibrate (145 mg/day for 6 weeks). Excretions of betaine, N,N-dimethylglycine, free choline, myo-inositol, taurine, trimethylamine-N-oxide, carnitine, and acetylcarnitine were measured by liquid chromatography with mass spectrometric detection. Fenofibrate increased the median betaine excretion from 7.5 to 25.8 mmol/mole creatinine (median increase 3-fold), P < .001. The median increase in N,N-dimethylglycine excretion was 2-fold (P < .001). Median choline excretion increased 12% (significant, P = .029). Participants with higher initial excretions tended to have larger increases (P < .001 in all 3 cases). Fenofibrate did not significantly change the median excretions of myo-inositol, taurine, trimethylamine-N-oxide, and carnitine. The excretion of acetylcarnitine decreased 4-fold on treatment, with no correlation between the baseline and after-treatment excretions. Changes in all urine components tested, except trimethylamine-N-oxide, positively correlated with changes in betaine excretion even when the median excretions before and after were not significantly different. Fibrates increase betaine, and to a lesser extent N,N-dimethylglycine and choline, excretion. Other osmolytes are not elevated. Because the increase in betaine excretion depends on the baseline excretion, large increases in excretion in the metabolic syndrome and diabetes (where baseline excretions are high) could be expected. Replacement with betaine supplements may be considered. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Transmission between Archaic and Modern Human Ancestors during the Evolution of the Oncogenic Human Papillomavirus 16.

PubMed

Pimenoff, Ville N; de Oliveira, Cristina Mendes; Bravo, Ignacio G

2017-01-01

Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes.

PubMed

Bingham, John; Payne, Jean; Harper, Jennifer; Frazer, Leah; Eastwood, Sarah; Wilson, Susanne; Lowther, Sue; Lunt, Ross; Warner, Simone; Carr, Mary; Hall, Roy A; Durr, Peter A

2014-06-01

West Nile virus (WNV; family Flaviviridae; genus Flavivirus) group members are an important cause of viral meningoencephalitis in some areas of the world. They exhibit marked variation in pathogenicity, with some viral lineages (such as those from North America) causing high prevalence of severe neurological disease, whilst others (such as Australian Kunjin virus) rarely cause disease. The aim of this study was to characterize WNV disease in a mouse model and to elucidate the pathogenetic features that distinguish disease variation. Tenfold dilutions of five WNV strains (New York 1999, MRM16 and three horse isolates of WNV-Kunjin: Boort and two isolates from the 2011 Australian outbreak) were inoculated into mice by the intraperitoneal route. All isolates induced meningoencephalitis in different proportions of infected mice. WNVNY99 was the most pathogenic, the three horse isolates were of intermediate pathogenicity and WNVKUNV-MRM16 was the least, causing mostly asymptomatic disease with seroconversion. Infectivity, but not pathogenicity, was related to challenge dose. Using cluster analysis of the recorded clinical signs, histopathological lesions and antigen distribution scores, the cases could be classified into groups corresponding to disease severity. Metrics that were important in determining pathotype included neurological signs (paralysis and seizures), meningoencephalitis, brain antigen scores and replication in extra-neural tissues. Whereas all mice infected with WNVNY99 had extra-neural antigen, those infected with the WNV-Kunjin viruses only occasionally had antigen outside the nervous system. We conclude that the mouse model could be a useful tool for the assessment of pathotype for WNVs. © 2014 CSIRO.

Ecological dynamics of emerging bat virus spillover

PubMed Central

Plowright, Raina K.; Eby, Peggy; Hudson, Peter J.; Smith, Ina L.; Westcott, David; Bryden, Wayne L.; Middleton, Deborah; Reid, Peter A.; McFarlane, Rosemary A.; Martin, Gerardo; Tabor, Gary M.; Skerratt, Lee F.; Anderson, Dale L.; Crameri, Gary; Quammen, David; Jordan, David; Freeman, Paul; Wang, Lin-Fa; Epstein, Jonathan H.; Marsh, Glenn A.; Kung, Nina Y.; McCallum, Hamish

2015-01-01

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. PMID:25392474

A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein.

PubMed

Iwasaki, Masaharu; de la Torre, Juan C

2018-06-01

Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis. To gain a better understanding of how the Z protein exerts its several different functions, we investigated the interaction between Z and viral polymerase L protein using the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated from nonionic detergent-resistant, membrane-rich structures to a subcellular compartment with a different membrane composition susceptible to disruption by nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L) at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did not affect the stability or budding activity of Z when expressed alone, but in the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. IMPORTANCE Several mammarenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose important public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. The mammarenavirus matrix Z protein plays critical roles in different steps of the viral life cycle by interacting with viral and host cellular components. Here we report that alanine substitution of a highly conserved leucine residue, located at position 72 in LCMV Z protein, abrogated Z-L interaction. The L72A mutation did not affect Z budding activity but promoted its rapid degradation in the presence of an active viral ribonucleoprotein (vRNP). Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. Copyright © 2018 American Society for Microbiology.

Burden of Chlamydia trachomatis in India: a systematic literature review

PubMed Central

Spaargaren, Joke; Kant, Rajiv; Lawrence, Rubina; Dayal, Arvind; Lal, Jonathan A.; Morré, Servaas A.

2017-01-01

Abstract Chlamydia trachomatis (hereafter CT) is Gram-negative, obligate intracellular pathogen. It causes the world's most common non-viral sexually transmitted disease. India is home to the world's greatest burden of infectious diseases, yet information on prevalence rates of CT is scarce. This article systematically reviews the literature for the prevalence rates and testing methods in India. A total of 27 studies were included. Four main patients groups (symptomatic women, infertile women, pregnant women and asymptomatic population groups) could be identified with varying rates of CT (0.1%–32% using PCR, 2.4%–75% using ELISA serology). Most of the studies originated from urban settings, 11 of them from New Delhi. In-house PCR was the most common diagnostic technique used generating the following ranges in prevalence for the four group studies: symptomatic women 10%–50%, pregnant women 0.1%–2.5% and asymptomatic populations 0.9%–24.5%. The rates among infertile women were 9%–68% based on serology results. The prevalence rates featured in this paper are in line with other locations across the Indian subcontinent. This review highlights the extreme heterogeneity in the limited studies available in India on CT and the need for standardized guidelines for diagnosis and management of CT in India. The availability of resources should be considered in the formulation of recommendations. PMID:28582495

Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children?

PubMed

Perrin, Eliana Miller; Murphy, Marie Lynd; Casey, Janet R; Pichichero, Michael E; Runyan, Desmond K; Miller, William C; Snider, Lisa A; Swedo, Susan E

2004-09-01

To determine whether group A beta-hemolytic streptococcal infections increase the risk of developing symptoms characteristic of the diagnosis pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Prospective cohort study. Children (N = 814) aged 4 to 11 years seen for sore throat or well-child care in a large pediatric practice in Rochester, NY, were enrolled from October 2001 to June 2002 (group A beta-hemolytic streptococcal [GAS] infected, n = 411; GAS uninfected, n = 403, of whom 207 had a sore throat of presumed viral etiology and 196 were well children). Symptomatic children with GAS infection (n = 399) were treated with antibiotics. At baseline and 2 and 12 weeks following baseline, all parents completed a 20-item questionnaire about the presence/absence of recent PANDAS symptoms in their children, and capable children answered 10 items about worries, obsessions, and compulsions. The relative risk of developing a "mild PANDAS variant" (> or = 2 new PANDAS symptoms) by illness type (GAS positive, presumed viral, or well child) and by parent and child report was determined and adjusted for potential covariates. By parent report, ill children more frequently manifested several PANDAS symptoms at baseline than well children. However, neither new symptoms nor the risk of developing a mild PANDAS variant developed during the subsequent 12 weeks more commonly in children with GAS infection than in those with presumed viral illness or in well children by parent or child report. Ill children with GAS infection, treated for their GAS infection, were not at increased risk for developing PANDAS symptoms or a mild PANDAS variant compared with children with presumed viral illness or well children. The role of antibiotics in the prevention or treatment of PANDAS as well as the investigation of PANDAS in the asymptomatic, infectious host deserves future research.

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

PubMed Central

Jaishankar, Dinesh; Shukla, Deepak

2016-01-01

Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of autophagy and other innate immune mechanisms that are subverted to enhance HSV pathogenesis. This review summarizes our current understanding of HSV-2 and associated diseases and available or upcoming new treatments. PMID:28357380

Genital Herpes: Insights into Sexually Transmitted Infectious Disease.

PubMed

Jaishankar, Dinesh; Shukla, Deepak

2016-06-27

Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of autophagy and other innate immune mechanisms that are subverted to enhance HSV pathogenesis. This review summarizes our current understanding of HSV-2 and associated diseases and available or upcoming new treatments.

Resolution of hypercalcemia and acute kidney injury after treatment for pulmonary tuberculosis without the use of corticosteroids.

PubMed

Araujo, Constance A A; Araujo, Nicole A A; Daher, Elizabeth F; Oliveira, José Daniel B; Kubrusly, Marcos; Duarte, Pastora M A; Silva, Sonia L; Araujo, Sonia M H A

2013-03-01

Abstract. Hypercalcemia caused by tuberculosis is rare and it is usually asymptomatic. Tuberculosis (TB) -related hypercalcemia associated with acute kidney injury (AKI) is rarely reported. We report a case of a 22-year-old immunocompetent man with 1-month history of daily fever, asthenia and weight loss. Laboratory findings on admission included serum calcium 14.9 mg/dL, urinary Ca(2+) 569.6 mg/24 hours, low level of parathyroid hormone, serum creatinine = 2.2 mg/dL and sodium fractional excretion (FeNa) 2.73%. The result of the tuberculin skin test was 17 mm. A chest X-ray revealed micronodular pulmonary infiltrate in the apex of the right lung, which was confirmed by computed tomography scan. The patient was diagnosed with hypercalcemia associated with pulmonary TB and AKI. A general improvement of the hypercalcemia and renal function was observed in the first 2 weeks after effective hydration and treatment of TB without corticosteroids. The patient was discharged with normal calcium levels and renal function.

An epidemiological study of Cryptosporidium parvum in two herds of adult beef cattle.

PubMed

Scott, C A; Smith, H V; Mtambo, M M; Gibbs, H A

1995-04-01

Prevalences of Cryptosporidium parvum oocysts in faeces and of isotype-specific anti-C. parvum antibodies in serum of apparently healthy adult cattle on two farms were determined. On Farm 1 cryptosporidial diarrhoea had been recorded in more than 80% of calves born over the previous 5 years, whereas on Farm 2 cryptosporidiosis had never been reported. No differences were demonstrated in oocyst excretion or presence of antibodies between the two farms. C. parvum oocysts were detected in 62.4% of faecal smears collected from a total of 553 apparently healthy adult cattle. Sucrose flotation was performed on a proportion of the faecal samples. This proved a more sensitive technique, detecting oocysts in 92% of the samples tested, and highlighting the insensitivity of direct smears for detecting oocysts. More than 90% of the cattle had specific anti-C. parvum IgG, IgG1, IgG2 and IgM antibodies and 58% specific anti-C. parvum IgA antibodies. Results suggest that asymptomatic adults may play an important role in the epidemiology of cryptosporidiosis in calves.

Modeling the Lymphocytic Choriomeningitis Virus: Insights into understanding its epidemiology in the wild

NASA Astrophysics Data System (ADS)

Contreras, Christy; McKay, John; Blattman, Joseph; Holechek, Susan

2015-03-01

The lymphocytic choriomenigitis virus (LCMV) is a rodent-spread virus commonly recognized as causing neurological disease that exhibits asymptomatic pathology. The virus is a pathogen normally carried among rodents that can be transmitted to humans by direct or indirect contact with the virus in excretions and secretions from rodents and can cause aseptic meningitis and other conditions in humans. We consider an epidemiological system within rodent populations modeled by a system of ordinary differential equations that captures the dynamics of the diseases transmission and present our findings. The asymptotic nature of the pathogen plays a large role in its spread within a given population, which has motivated us to expand upon an existing SIRC model (Holechek et al in preparation) that accounts for susceptible-, infected-, recovered-, and carrier-mice on the basis of their gender. We are interested in observing and determining the conditions under which the carrier population will reach a disease free equilibrium, and we focus our investigation on the sensitivity of our model to gender, pregnancy related infection, and reproduction rate conditions.

A1AT polymorphisms may be associated with clinical characteristics of retrovirus infections in a mixed ethnic population from the Brazilian Amazon region.

PubMed

Ferreira, Thalita Camêlo da Silva; Queiroz, Maria Alice Freitas; Argañaraz, Gustavo Adolfo; Ishak, Ricardo; Vallinoto, Antonio Carlos Rosário; Argañaraz, Enrique Roberto

2017-12-01

This study investigated the association of alpha-1-antrypsin deficiency (A1AT; S and Z polymorphisms) with HIV-1 and HTLV-1 infection. Blood samples from 201 HIV-1-infected and 115 HTLV-1-infected individuals were examined and compared with those from 300 healthy controls. Genotyping of A1AT (S and Z) and quantification of plasma viral load were performed using RT-PCR, and the CD4+/CD8+ T-cell count was determined by flow cytometry. The wild-type MM genotype showed the highest frequency in each of the three groups investigated. SS and ZZ homozygous genotypes (variants) were observed only among HTLV-1 patients and controls, respectively. Genotype MS was significantly less frequent in HTLV-1-positive persons than in controls. Statistically significant differences were observed when comparing genotype frequencies between symptomatic and asymptomatic HTLV-1-infected persons. The distribution of plasma HIV-1 viral load among individuals with different genotypes of A1AT polymorphism also differed significantly. The results suggest that A1AT polymorphisms may be associated with human retrovirus infections when dealing with an ethnically mixed population from the Amazon region of Brazil. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Laboratory diagnosis and epidemiology of herpes simplex 1 and 2 genital infections.

PubMed

Glinšek Biškup, Urška; Uršič, Tina; Petrovec, Miroslav

2015-01-01

Herpes simplex virus types 1 and 2 are the main cause of genital ulcers worldwide. Although herpes simplex virus type 2 is the major cause of genital lesions, herpes simplex virus type 1 accounts for half of new cases in developed countries. Herpes simplex virus type 2 seroprevalence rises with sexual activity from adolescence through adulthood. Slovenian data in a high-risk population shows 16% seroprevalence of HSV-2. HSV-1 and HSV-2 DNA in genital swabs was detected in 19% and 20.7%, respectively. In most cases, genital herpes is asymptomatic. Primary genital infection with herpes simplex virus types 1 and 2 can be manifested by a severe clinical picture, involving the vesicular skin and mucosal changes and ulcerative lesions of the vulva, vagina, and cervix in women and in the genital region in men. Direct methods of viral genome detection are recommended in the acute stage of primary and recurrent infections when manifest ulcers or lesions are evident. Serological testing is recommended as an aid in diagnosing genital herpes in patients with reinfection in atypical or already healed lesions. When herpes lesions are present, all sexual activities should be avoided to prevent transmission of infection. Antiviral drugs can reduce viral shedding and thus reduce the risk of sexual transmission of the virus.

A novel polyomavirus from the nasal cavity of a giant panda (Ailuropoda melanoleuca).

PubMed

Qi, Dunwu; Shan, Tongling; Liu, Zhijian; Deng, Xutao; Zhang, Zhihe; Bi, Wenlei; Owens, Jacob Robert; Feng, Feifei; Zheng, Lisong; Huang, Feng; Delwart, Eric; Hou, Rong; Zhang, Wen

2017-10-27

Polyomaviruses infect a wide variety of mammalian and avian hosts with a broad spectrum of outcomes including asymptomatic infection, acute systemic disease, and tumor induction. Viral metagenomics and general PCR methods were used to detected viral nucleic acid in the samples from a diseased and healthy giant pandas. A novel polyomavirus, the giant panda polyomavirus 1 (GPPyV1) from the nasal cavity of a dead giant panda (Ailuropoda melanoleuca) was characterized. The GPPyV1 genome is 5144 bp in size and reveals five putative open-reading frames coding for the classic small and large T antigens in the early region, and the VP1, VP2 and VP3 capsid proteins in the late region. Phylogenetic analyses of the large T antigen of the GPPyV1 indicated GPPyV1 belonged to a putative new species within genus Deltapolyomavirus, clustering with four human polyomavirus species. The GPPyV1 VP1 and VP2 clustered with genus Alphapolyomavirus. Our epidemiologic study indicated that this novel polyomavirus was also detected in nasal swabs and fecal samples collected from captive healthy giant pandas. A novel polyomavirus was detected in giant pandas and its complete genome was characterized, which may cause latency infection in giant pandas.

Viruses in bronchiectasis: a pilot study to explore the presence of community acquired respiratory viruses in stable patients and during acute exacerbations.

PubMed

Mitchell, Alicia B; Mourad, Bassel; Buddle, Lachlan; Peters, Matthew J; Oliver, Brian G G; Morgan, Lucy C

2018-05-22

Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently.

Viruses of invasive Argentine ants from the European Main supercolony: characterization, interactions and evolution.

PubMed

Viljakainen, Lumi; Holmberg, Ida; Abril, Sílvia; Jurvansuu, Jaana

2018-06-25

The Argentine ant (Linepithema humile) is a highly invasive pest, yet very little is known about its viruses. We analysed individual RNA-sequencing data from 48 Argentine ant queens to identify and characterisze their viruses. We discovered eight complete RNA virus genomes - all from different virus families - and one putative partial entomopoxvirus genome. Seven of the nine virus sequences were found from ant samples spanning 7 years, suggesting that these viruses may cause long-term infections within the super-colony. Although all nine viruses successfully infect Argentine ants, they have very different characteristics, such as genome organization, prevalence, loads, activation frequencies and rates of evolution. The eight RNA viruses constituted in total 23 different virus combinations which, based on statistical analysis, were non-random, suggesting that virus compatibility is a factor in infections. We also searched for virus sequences from New Zealand and Californian Argentine ant RNA-sequencing data and discovered that many of the viruses are found on different continents, yet some viruses are prevalent only in certain colonies. The viral loads described here most probably present a normal asymptomatic level of infection; nevertheless, detailed knowledge of Argentine ant viruses may enable the design of viral biocontrol methods against this pest.

[Genital herpes and pregnancy: Epidemiology, clinical manifestations, prevention and screening. Guidelines for clinical practice from the French College of Gynecologists and Obstetrician (CNGOF)].

PubMed

Picone, O

2017-12-01

To analyze the consequences of genital herpes infections in pregnant women. The PubMed database and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. The symptomatology of herpes genital rash is often atypical (NP2) and not different during pregnancy (Professional consensus). It is most often due to HSV2 (NP2). Seventy percent of pregnant patients have a history of infection with Herpes simplex virus, without reference to genital or labial localization, and this is in most cases type 1 (NP2). The prevalence of clinical herpes lesions at birth in the event of recurrence is about 16% compared with 36% in the case of initial infection (NP4). In HSV+ patients, asymptomatic herpetic excretion is 4 to 10%. The rate of excretion increases in HIV+ patients (20 to 30%) (NP2). The risk of HSV seroconversion during pregnancy is 1 to 5% (NP2), but can reach 20% in case of sero-discordant couple (NP2). Questioning is not always sufficient to determine the history of herpes infection of a patient and her partner (NP2) and the clinical examination is not always reliable (NP2). Herpetic hepatitis and encephalitis are rare and potentially severe (NP4). These diagnoses should be discussed during pregnancy and antiviral therapy should be started as soon as possible (Professional consensus). There is no established link between herpes infection and miscarriages (NP3). There appears to be an association between untreated herpes infection and premature delivery (NP3) but not in the case of treated infections (NP4). Herpetic fetopathies are exceptional (NP4). There is no argument for recommending specific prenatal diagnosis for herpes infection during pregnancy (Professional consensus). Condom use reduces the risk of initial infection in women who are not pregnant (NP3). There is no evidence to justify routine screening during pregnancy (Professional consensus). There is a strong discrepancy between the prevalence of herpetic excretion at the time of delivery and the scarcity of neonatal infections. There is a lack of data on the impact of herpes infections during pregnancy in France. Fetal and maternal consequences are potentially serious but rare. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Potential spread of highly pathogenic avian influenza H5N1 by wildfowl: dispersal ranges and rates determined from large-scale satellite telemetry

USGS Publications Warehouse

Gaidet, Nicolas; Cappelle, Julien; Takekawa, John Y.; Prosser, Diann J.; Iverson, Samuel A.; Douglas, David C.; Perry, William M.; Mundkur, Taej; Newman, Scott H.

2010-01-01

1. Migratory birds are major candidates for long-distance dispersal of zoonotic pathogens. In recent years, wildfowl have been suspected of contributing to the rapid geographic spread of the highly pathogenic avian influenza (HPAI) H5N1 virus. Experimental infection studies reveal that some wild ducks, geese and swans shed this virus asymptomatically and hence have the potential to spread it as they move. 2. We evaluate the dispersive potential of HPAI H5N1 viruses by wildfowl through an analysis of the movement range and movement rate of birds monitored by satellite telemetry in relation to the apparent asymptomatic infection duration (AID) measured in experimental studies. We analysed the first large-scale data set of wildfowl movements, including 228 birds from 19 species monitored by satellite telemetry in 2006–2009, over HPAI H5N1 affected regions of Asia, Europe and Africa. 3. Our results indicate that individual migratory wildfowl have the potential to disperse HPAI H5N1 over extensive distances, being able to perform movements of up to 2900 km within timeframes compatible with the duration of asymptomatic infection. 4. However, the likelihood of such virus dispersal over long distances by individual wildfowl is low: we estimate that for an individual migratory bird there are, on average, only 5–15 days per year when infection could result in the dispersal of HPAI H5N1 virus over 500 km. 5. Staging at stopover sites during migration is typically longer than the period of infection and viral shedding, preventing birds from dispersing a virus over several consecutive but interrupted long-distance movements. Intercontinental virus dispersion would therefore probably require relay transmission between a series of successively infected migratory birds. 6. Synthesis and applications. Our results provide a detailed quantitative assessment of the dispersive potential of HPAI H5N1 virus by selected migratory birds. Such dispersive potential rests on the assumption that free-living wildfowl will respond analogously to captive, experimentally-infected birds, and that asymptomatic infection will not alter their movement abilities. Our approach of combining experimental exposure data and telemetry information provides an analytical framework for quantifying the risk of spread of avian-borne diseases.

Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and U. urealyticum in men and women? - a Position Statement from the European STI Guidelines Editorial Board.

PubMed

Horner, P; Donders, G; Cusini, M; Gomberg, M; Jensen, J S; Unemo, M

2018-06-20

At present, we have no evidence that we are doing more good than harm detecting and subsequently treating Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum colonisations/infections. Consequently, routine testing and treatment of asymptomatic or symptomatic men and women for M. hominis, U. urealyticum, and U. parvum is not recommended. Asymptomatic carriage of these bacteria is common and the majority of individuals do not develop disease. Although U. urealyticum has been associated with urethritis in men, it is probably not causal unless a high load is present (likely carriage in 40-80% of detected cases). The extensive testing, detection and subsequent antimicrobial treatment of these bacteria performed in some settings may result in selection of antimicrobial resistance, in these bacteria, "true" STI agents, as well as in the general microbiota, and substantial economic cost for society and individuals, particularly women. The commercialisation of many particularly multiplex PCR assays detecting traditional non-viral STIs together with M. hominis, U. parvum and/or U. urealyticum have worsened this situation. Thus, routine screening of asymptomatic men and women or routine testing of symptomatic individuals for M. hominis, U. urealyticum, and U. parvum is not recommended. If testing of men with symptomatic urethritis is undertaken, traditional STI urethritis agents such as Neisseria gonorrhoeae, Chlamydia trachomatis, M. genitalium and, in settings where relevant, Trichomonas vaginalis should be excluded prior to U. urealyticum testing and quantitative species-specific molecular diagnostic tests should be used. Only men with high U. urealyticum load should be considered for treatment, however, appropriate evidence for effective treatment regimens is lacking. In symptomatic women, bacterial vaginosis (BV) should always be tested for and treated if detected. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Zika virus infection in Nicaraguan households.

PubMed

Burger-Calderon, Raquel; Gonzalez, Karla; Ojeda, Sergio; Zambrana, José Victor; Sanchez, Nery; Cerpas Cruz, Cristhiam; Suazo Laguna, Harold; Bustos, Fausto; Plazaola, Miguel; Lopez Mercado, Brenda; Elizondo, Douglas; Arguello, Sonia; Carey Monterrey, Jairo; Nuñez, Andrea; Coloma, Josefina; Waggoner, Jesse J; Gordon, Aubree; Kuan, Guillermina; Balmaseda, Angel; Harris, Eva

2018-05-01

Zika virus (ZIKV) infection recently caused major epidemics in the Americas and is linked to congenital birth defects and Guillain-Barré Syndrome. A pilot study of ZIKV infection in Nicaraguan households was conducted from August 31 to October 21, 2016, in Managua, Nicaragua. We enrolled 33 laboratory-confirmed Zika index cases and their household members (109 contacts) and followed them on days 3-4, 6-7, 9-10, and 21, collecting serum/plasma, urine, and saliva specimens along with clinical, demographic, and socio-economic status information. Collected samples were processed by rRT-PCR to determine viral load (VL) and duration of detectable ZIKV RNA in human bodily fluids. At enrollment, 11 (10%) contacts were ZIKV rRT-PCR-positive and 23 (21%) were positive by IgM antibodies; 3 incident cases were detected during the study period. Twenty of 33 (61%) index households had contacts with ZIKV infection, with an average of 1.9 (range 1-6) positive contacts per household, and in 60% of these households, ≥50% of the members were positive for ZIKV infection. Analysis of clinical information allowed us to estimate the symptomatic to asymptomatic (S:A) ratio of 14:23 (1:1.6) among the contacts, finding 62% of the infections to be asymptomatic. The maximum number of days during which ZIKV RNA was detected was 7 days post-symptom onset in saliva and serum/plasma and 22 days in urine. Overall, VL levels in serum/plasma, saliva, and urine specimens were comparable, with means of 5.6, 5.3 and 4.5 log10 copies/ml respectively, with serum attaining the highest VL peak at 8.1 log10 copies/ml. Detecting ZIKV RNA in saliva over a similar time-period and level as in serum/plasma indicates that saliva could potentially serve as a more accessible diagnostic sample. Finding the majority of infections to be asymptomatic emphasizes the importance of silent ZIKV transmission and helps inform public health interventions in the region and globally.

[Prolonged leucopenia in asymptomatic children].

PubMed

Kaczorowska-Hać, Barbara; Maciejka-Kapuścińska, Lucyna; Reszczyńska, Iwona; Wiśniewski, Jakub; Buchowiecki, Lech; Kozłowska, Marta; Adamkiewicz-Drożyńska, Elżbieta

2014-01-01

The term leucopenia is still a challenge for clinicists in cases of unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons: some drugs, infections, viral mainly, autoimmune diseases, haematological abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this investigation was an analysis of asymptomatic, lasting over three months leucopenia myelograms of childhood. 21 children (6 girls and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The children were referred to our clinic by family physicians to investigate the reason of asymptomatic, lasting over three months leucopenia. These children are still under our observation from one till four years. Despite the fact of lasting over three months leucopenia, the general condition of the patients is good. In all the patients the myelogram analysis was performed after May-Grumwald-Giemsa dying, three slides of one hundred cells were counted. Statistical analysis was made using STATISTICA (Stat Soft Polska) programme. Mean number of leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to 3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l, values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets number were normal. Mean number of marrow cells were within references. However mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than mean number of general population marrow cells (p<0.05). Mean values of myeloblasts, neutrophils, and monocytes were statistically higher than in general population (p<0.05). 1. Hypothesis of obtained differencess in numer of marrow cells would need to be investigated in broad population of patients. 2. Considering that three children presented with positive familial leucopenia history (in one of them grandmother, in two anothers fathers) genetic predisposition can be expected.

Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

PubMed

Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

2017-07-15

Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 10 7 to 10 9 TCID 50 Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines. Copyright © 2017 American Society for Microbiology.

Pathogenicity and Phenotypic Characterization of Enterotoxigenic Escherichia coli Isolates from a Birth Cohort of Children in Rural Egypt

PubMed Central

Shaheen, Hind I.; Amine, Mohamed; Hassan, Khaled; Sanders, John W.; Riddle, Mark S.; Armstrong, Adam W.; Svennerholm, Ann-Mari; Sebeny, Peter J.; Klena, John D.; Young, Sylvia Y. N.; Frenck, Robert W.

2014-01-01

Enterotoxigenic Escherichia coli (ETEC) has consistently been the predominant bacterial cause of diarrhea in many birth cohort- and hospital-based studies conducted in Egypt. We evaluated the pathogenicity of ETEC isolates in a birth cohort of children living in a rural community in Egypt. Between 2004 and 2007, we enrolled and followed 348 children starting at birth until their second year of life. A stool sample and two rectal swabs were collected from children during twice-weekly visits when they presented with diarrhea and were collected every 2 weeks if no diarrhea was reported. From routine stool cultures, five E. coli-like colonies were screened for ETEC enterotoxins using a GM1 enzyme-linked immunosorbent assay (ELISA). The isolates were screened against a panel of 12 colonization factor antigens (CFAs) by a dot blot assay. A nested case-control study evaluated the association between initial or repeat excretion of ETEC and the occurrences of diarrhea. The pathogenicity of ETEC was estimated in symptomatic children compared to that in asymptomatic controls. ETEC was significantly associated with diarrhea (crude odds ratio, 1.37; 95% confidence interval [CI], 1.24 to 1.52). The distribution of ETEC enterotoxins varied between the symptomatic children (44.2% heat-labile toxin [LT], 38.5% heat-stable toxin [ST], and 17.3% LT/ST) and asymptomatic children (55.5% LT, 34.6% ST, and 9.9% LT/ST) (P < 0.001). The CFAs CFA/I (n = 61), CS3 (n = 8), CS1 plus CS3 (n = 24), CS2 plus CS3 (n = 18), CS6 (n = 45), CS5 plus CS6 (n = 11), CS7 (n = 25), and CS14 (n = 32) were frequently detected in symptomatic children, while CS6 (n = 66), CS12 (n = 51), CFA/I (n = 43), and CS14 (n = 20) were detected at higher frequencies among asymptomatic children. While all toxin phenotypes were associated with diarrheal disease after the initial exposure, only ST and LT/ST-expressing ETEC isolates (P < 0.0001) were associated with disease in repeat infections. The role of enterotoxins and pathogenicity during repeat ETEC infections appears to be variable and dependent on the coexpression of specific CFAs. PMID:24478492

Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

PubMed Central

Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

2015-01-01

Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

PubMed Central

Le Calloch, R.; Ianotto, J. C.; Berthou, C.; Tempescul, A.

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy. PMID:22937308

Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

PubMed

Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

2011-01-01

Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

PubMed

Dizdar, Omer; Tapan, Umit; Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Barista, Ibrahim

2008-05-01

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

[Headache case that responded to alendronate treatment in Paget's disease].

PubMed

Bozkurt, Dilek; Hiz, Fazilet; Çinar, Meral; Can, Meltem

2012-01-01

Paget's disease of the bone is a chronic, focal skeletal disease characterized by bone pain and deformity, pathological fractures and neurological symptoms such as headache, hearing loss and tinnitus, etc. The frequency of the disease increases in later ages. Viral and genetical factors play a role in the etiology. The majority of cases are asymptomatic. It is often diagnosed with an incidental finding on radiography or with an unexpected high serum alkaline phosphatase level. Bone fractures or neurological complications can negatively affect the quality of life. Early diagnosis and treatment are thus very important. Bisphosphonates are the most frequently used medication in the treatment. We present a case who sought medical help because of headache and was diagnosed as Paget's disease. Neurological complications and the diagnosis and treatment of Paget's disease are reviewed in the literature.

[Benign ethnic neutropenia; an unrecognised cause of leukopenia in negroid patients].

PubMed

van Rooijen, Cleo R; Slieker, Walentina A T; Simsek, Suat

2012-01-01

Leukopenia has a high incidence and is usually a reason for additional testing. Benign ethnic neutropenia is a relatively common cause of neutropenia in the negroid population. It can be the cause of aberrant laboratory results in negroid patients. A 55-year-old woman from Ghana was referred to the outpatient clinic because of malaise, leukopenia and neutropenia. Viral infection, haematological malignancy, auto-immune disease and vitamin deficiency were considered, but could not be confirmed by additional testing. Upon further investigation, the neutropenia in this patient was found to have existed for years. Moreover, our patient's son also had asymptomatic leukopenia. Therefore, benign ethnic neutropenia was considered the most likely diagnosis. Serological analysis of the patient's erythrocytes revealed the absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b), which is associated with benign ethnic neutropenia.

Partial heterologous protection by low pathogenic H9N2 virus against natural H9N2-PB1 gene reassortant highly pathogenic H5N1 virus in chickens.

PubMed

Dash, Sandeep Kumar; Kumar, Manoj; Kataria, Jag Mohan; Nagarajan, Shanmugasundaram; Tosh, Chakradhar; Murugkar, Harshad V; Kulkarni, Diwakar D

2016-06-01

Low pathogenic avian influenza H9N2 and highly pathogenic avian influenza H5N1 viruses continue to co-circulate in chickens. Prior infection with low pathogenic avian influenza can modulate the outcome of H5N1 infection. In India, low pathogenic H9N2 and highly pathogenic H5N1 avian influenza viruses are co-circulating in poultry. Herein, by using chickens with prior infection of A/chicken/India/04TI05/2012 (H9N2) virus we explored the outcome of infection with H5N1 virus A/turkey/India/10CA03/2012 natural PB1 gene reassortant from H9N2. Four groups (E1-E4) of SPF chickens (n = 6) prior inoculated with 10(6) EID50 of H9N2 virus were challenged with 10(6) EID50 of H5N1 natural reassortant (PB1-H9N2) virus at days 1 (group E1); 3 (group E2); 7 (group E3) and 14 (group E4) post H9N2 inoculation. The survival percentage in groups E1-E4 was 0, 100, 66.6 and 50%, respectively. Virus shedding periods for groups E1-E4 were 3, 4, 7 and 9 days, respectively post H5N1 challenge. Birds of group E1 and E2 were shedding both H9N2 and H5N1 viruses and mean viral RNA copy number was higher in oropharyngeal swabs than cloacal swabs. In group, E3 and E4 birds excreted only H5N1 virus and mean viral RNA copy number was higher in most cloacal swabs than oral swabs. These results indicate that prior infection with H9N2 virus could protect from lethal challenge of reassortant H5N1 virus as early as with three days prior H9N2 inoculation and protection decreased in groups E3 and E4 as time elapsed. However, prior infection with H9N2 did not prevent infection with H5N1 virus and birds continue to excrete virus in oropharyngeal and cloacal swabs. Amino acid substitution K368E was found in HA gene of excreted H5N1 virus of group E3. Hence, concurrent infection can also cause emergence of viruses with mutations leading to virus evolution. The results of this study are important for the surveillance and epidemiological data analysis where both H9N2 and H5N1 viruses are co-circulating. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Intracytoplasmic Domain of the Env Transmembrane Protein Is a Locus for Attenuation of Simian Immunodeficiency Virus SIVmac in Rhesus Macaques

PubMed Central

Shacklett, Barbara L.; Weber, Claudia Jo; Shaw, Karen E. S.; Keddie, Elise M.; Gardner, Murray B.; Sonigo, Pierre; Luciw, Paul A.

2000-01-01

The human and simian immunodeficiency virus (HIV-1 and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis. Here we describe a novel mutant virus, SIVmac-M4, containing multiple mutations in the coding region for the ICD-TM of pathogenic molecular clone SIVmac239. Parental SIVmac239-Nef+ produces high-level persistent viremia and simian AIDS in both juvenile and newborn rhesus macaques. The ICD-TM region of SIVmac-M4 contains three stop codons, a +1 frameshift, and mutation of three highly conserved, charged residues in the conserved C-terminal alpha-helix referred to as lentivirus lytic peptide 1 (LLP-1). Overlapping reading frames for tat, rev, and nef are not affected by these changes. In this study, four juvenile macaques received SIVmac-M4 by intravenous injection. Plasma viremia, as measured by branched-DNA (bDNA) assay, reached a peak at 2 weeks postinoculation but dropped to below detectable levels by 12 weeks. At over 1.5 years postinoculation, all four juvenile macaques remain healthy and asymptomatic. In a subsequent experiment, four neonatal rhesus macaques were given SIVmac-M4 intravenously. These animals exhibited high levels of viremia in the acute phase (2 weeks postinoculation) but are showing a relatively low viral load in the chronic phase of infection, with no clinical signs of disease for 1 year. These findings demonstrated that the intracytoplasmic domain of the transmembrane Env (Env-TM) is a locus for attenuation in rhesus macaques. PMID:10846063

Papillomaviruses: Viral evolution, cancer and evolutionary medicine.

PubMed

Bravo, Ignacio G; Félez-Sánchez, Marta

2015-01-28

Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Prevalence of seroconversion symptoms and relationship to set point viral load: Findings from a subtype C epidemic, 1995–2009

PubMed Central

Sullivan, Patrick S.; Fideli, Ulgen; Wall, Kristin M.; Chomba, Elwyn; Vwalika, Cheswa; Kilembe, William; Tichacek, Amanda; Luisi, Nicole; Mulenga, Joseph; Hunter, Eric; Boeras, Debrah; Allen, Susan

2013-01-01

Objective To describe symptoms, physical exam findings, and set point viral load associated with acute HIV seroconversion in a heterosexual cohort of discordant couples in Zambia. Design We followed HIV serodiscordant couples in Lusaka, Zambia from 1995–2009 with HIV testing of negative partners and symptom inventories 3-monthly, and physical examinations annually. Methods We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical exam [PE] findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting versus HIV-negative or HIV-positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and PE findings predictive of seroconversion versus HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and PE findings at seroconversion and log set-point viral load [VL] using linear regression. Results 2,388 HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor PE findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among non-diarrheic patients (adjusted odds ratio [aOR]=4.0) night sweats (aOR=1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR=2.2), and neck (aOR=2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms was positively associated with set-point VL (p<0.001). Conclusions Though most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion compared with HIV-negative and HIV-positive intervals. When present, symptoms and physical exam findings were non-specific and associated with higher set point viremia. PMID:22089380

Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

DOE PAGES

Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan; ...

2016-12-15

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genomemore » detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle.« less

Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

PubMed Central

Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan; Singh, Karam Pal; Stenfeldt, Carolina; Rodriguez, Luis L.; Pattnaik, Bramhadev; Arzt, Jonathan

2016-01-01

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genome detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle. PMID:27977708

Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genomemore » detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle.« less

Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes

PubMed Central

Garnett, C. T.; Erdman, D.; Xu, W.; Gooding, Linda R.

2002-01-01

The common species C adenoviruses (serotypes Ad1, Ad2, Ad5, and Ad6) infect more than 80% of the human population early in life. Following primary infection, the virus can establish an asymptomatic persistent infection in which infectious virions are shed in feces for several years. The probable source of persistent virus is mucosa-associated lymphoid tissue, although the molecular details of persistence or latency of adenovirus are currently unknown. In this study, a sensitive real-time PCR assay was developed to quantitate species C adenovirus DNA in human tissues removed for routine tonsillectomy or adenoidectomy. Using this assay, species C DNA was detected in Ficoll-purified lymphocytes from 33 of 42 tissue specimens tested (79%). The levels varied from fewer than 10 to greater than 2 × 106 copies of the adenovirus genome/107 cells, depending on the donor. DNA from serotypes Ad1, Ad2, and Ad5 was detected, while the rarer serotype Ad6 was not. When analyzed as a function of donor age, the highest levels of adenovirus genomes were found among the youngest donors. Antibody-coated magnetic beads were used to purify lymphocytes into subpopulations and determine whether viral DNA could be enriched within any purified subpopulations. Separation of T cells (CD4/8- expressing and/or CD3-expressing cells) enriched viral DNA in each of nine donors tested. In contrast, B-cell purification (CD19-expressing cells) invariably depleted or eliminated viral DNA. Despite the frequent finding of significant quantities of adenovirus DNA in tonsil and adenoid tissues, infectious virus was rarely present, as measured by coculture with permissive cells. These findings suggest that human mucosal T lymphocytes may harbor species C adenoviruses in a quiescent, perhaps latent form. PMID:12368303

The cost-effectiveness of directly observed highly-active antiretroviral therapy in the third trimester in HIV-infected pregnant women.

PubMed

McCabe, Caitlin J; Goldie, Sue J; Fisman, David N

2010-04-13

In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.

Avian paramyoxvirus-8 immunization reduces viral shedding after homologous APMV-8 challenge but fails to protect against Newcastle disease.

PubMed

Grund, Christian; Steglich, Constanze; Huthmann, Eva; Beer, Martin; Mettenleiter, Thomas C; Römer-Oberdörfer, Angela

2014-10-08

Protection against infection by Newcastle disease virus (NDV), also designated as avian paramyxovirus subtype-1 (APMV-1), is mediated by immune responses to the two surface glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F) protein. Thus, a chimeric APMV-1 based vaccine that encodes APMV-8 HN- and F-proteins and expresses the hemagglutinin of avian influenza virus (AIV) H5N1, is able to protect against HPAIV H5N1 but fails to protect against NDV [PLoS One8:e72530, 2013]. However, it is unclear whether avirulent APMV-subtypes, like APMV-8 can induce subtype-specific immunity and protect from a homologous challenge. APMV-8 infections of 3- and 6-weeks-old specific pathogen free (SPF)-chickens did not induce any clinical signs but was associated with virus shedding for up to 6 days. Viral replication was only detected in oropharyngeal- and never in cloacal swabs. Upon reinfection with homologous APMV-8, viral shedding was restricted to day 2 and in contrast to naive SPF-chickens, only RNA but no infectious virus was recovered. No protection was induced against virulent NDV challenge, although morbidity and mortality was delayed in APMV-8 primed chickens. This lack of protection is in line with a lack of reactivity of APMV-8 specific sera to APMV-1 HN-protein: Neither by hemagglutin-inhibition (HI) test nor immunoblot analyses, cross-reactivity was detected, despite reactivity to internal proteins. Immune responses mounted during asymptomatic APMV-8 infection limit secondary infection against homologues reinfection and facilitates a delay in the onset of disease in a subtype independent manner but is unable to protect against Newcastle disease, a heterologous APMV-subtype.

Impact of Chloroquine on Viral Load in Breast Milk

PubMed Central

Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

2006-01-01

Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel, chloroquine, sulfadoxine-pyrimethamine, charge virale du lait maternel, fièvre Impacto de la cloroquina en la carga viral de la leche materna El antimalárico cloroquina tiene actividad frente al VIH. Comparamos el efecto de la cloroquina (n = 18) frente a un antimalárico sin actividad anti-VIH conocida, la sulfadoxina-pirimetamina (n = 12), en los niveles de ARN en la leche materna de mujeres infectadas con VIH, en Zambia. Después de ajustar para recuento de CD4 y la carga viral en plasma, se asoció a la cloroquina con una tendencia hacia menores niveles de ARN del VIH en leche materna, comparado con la sulfadoxina pirimetamina (P = 0.05). También se observó una mayor carga viral en la leche materna de mujeres recibiendo tratamiento presuntivo para malaria sintomática, que en los controles asintomáticos y controles que habáan reportado fiebre la semana anterior. Es necesario realizar más estudios para determinar el papel potencial de la cloroquina en la prevención de la trasmisión de VIH a través de la lactancia materna. palabras claveVIH, malaria, lactancia materna, cloroquina, sulfadoxina pirimetamina, transmisión vertical, leche materna, carga viral, fiebre PMID:16772000

The Drosophila Nora virus is an enteric virus, transmitted via feces.

PubMed

Habayeb, Mazen S; Cantera, Rafael; Casanova, Gabriela; Ekström, Jens-Ola; Albright, Shannon; Hultmark, Dan

2009-04-01

The biology of the Drosophila viruses has not been intensely investigated. Here we have investigated the biology of the Nora virus, a persistent Drosophila virus. We find that injected Nora virus is able to replicate in the files, reaching a high titer that is maintained in the next generation. There is a remarkable variation in the viral loads of individual flies in persistently infected stocks; the titers can differ by three orders of magnitude. The Nora virus is mainly found in the intestine of infected flies, and the histology of these infected intestines show increased vacuolization. The virus is excreted in the feces and is horizontally transmitted. The Nora virus infection has a very mild effect on the longevity of the flies, and no significant effect on the number of eggs laid and the percent of eggs that develop to adults.

Experimental study of European bat lyssavirus type-2 infection in Daubenton's bats (Myotis daubentonii).

PubMed

Johnson, Nicholas; Vos, Ad; Neubert, Larissa; Freuling, Conrad; Mansfield, Karen L; Kaipf, Ingrid; Denzinger, Annette; Hicks, Dan; Núñez, Alex; Franka, Richard; Rupprecht, Charles E; Müller, Thomas; Fooks, Anthony R

2008-11-01

European bat lyssavirus type 2 (EBLV-2) can be transmitted from Daubenton's bats to humans and cause rabies. EBLV-2 has been repeatedly isolated from Daubenton's bats in the UK but appears to be present at a low level within the native bat population. This has prompted us to investigate the disease in its natural host under experimental conditions, to assess its virulence, dissemination and likely means of transmission between insectivorous bats. With the exception of direct intracranial inoculation, only one of seven Daubenton's bats inoculated by subdermal inoculation became infected with EBLV-2. Both intramuscular and intranasal inoculation failed to infect the bats. No animal inoculated with EBLV-2 seroconverted during the study period. During infection, virus excretion in saliva (both viral RNA and live virus) was confirmed up to 3 days before the development of rabies. Disease was manifested as a gradual loss of weight prior to the development of paralysis and then death. The highest levels of virus were measured in the brain, with much lower levels of viral genomic RNA detected in the tongue, salivary glands, kidney, lung and heart. These observations are similar to those made in naturally infected Daubenton's bats and this is the first documented report of isolation of EBLV-2 in bat saliva. We conclude that EBLV-2 is most likely transmitted in saliva by a shallow bite.

Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

PubMed

Gringeri, A; Santagostino, E; Mannucci, P M; Siracusano, L; Marinoni, A; Criscuolo, M; Carcagno, M; Fall, L S; M'Bika, J P; Bizzini, B

1995-05-01

A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

Deformed wing virus implicated in overwintering honeybee colony losses.

PubMed

Highfield, Andrea C; El Nagar, Aliya; Mackinder, Luke C M; Noël, Laure M-L J; Hall, Matthew J; Martin, Stephen J; Schroeder, Declan C

2009-11-01

The worldwide decline in honeybee colonies during the past 50 years has often been linked to the spread of the parasitic mite Varroa destructor and its interaction with certain honeybee viruses. Recently in the United States, dramatic honeybee losses (colony collapse disorder) have been reported; however, there remains no clear explanation for these colony losses, with parasitic mites, viruses, bacteria, and fungal diseases all being proposed as possible candidates. Common characteristics that most failing colonies share is a lack of overt disease symptoms and the disappearance of workers from what appears to be normally functioning colonies. In this study, we used quantitative PCR to monitor the presence of three honeybee viruses, deformed wing virus (DWV), acute bee paralysis virus (ABPV), and black queen cell virus (BQCV), during a 1-year period in 15 asymptomatic, varroa mite-positive honeybee colonies in Southern England, and 3 asymptomatic colonies confirmed to be varroa mite free. All colonies with varroa mites underwent control treatments to ensure that mite populations remained low throughout the study. Despite this, multiple virus infections were detected, yet a significant correlation was observed only between DWV viral load and overwintering colony losses. The long-held view has been that DWV is relatively harmless to the overall health status of honeybee colonies unless it is in association with severe varroa mite infestations. Our findings suggest that DWV can potentially act independently of varroa mites to bring about colony losses. Therefore, DWV may be a major factor in overwintering colony losses.

Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

PubMed Central

Alizon, Samuel; Magnus, Carsten

2012-01-01

The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection. PMID:23202449

Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment.

PubMed

Vázquez-Santiago, Fabián; García, Yashira; Rivera-Román, Ivelisse; Noel, Richard J; Wojna, Valerie; Meléndez, Loyda M; Rivera-Amill, Vanessa

Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1-infected people. HIV-1 envelope ( env ) genetic heterogeneity has been detected within the central nervous system (CNS) of individuals with ANI. Changes within env determine co-receptor use, cellular tropism, and neuropathogenesis. We hypothesize that compartmental changes are associated with HIV-1 env C2V4 during ANI and sought to analyze paired HIV-1 env sequences from plasma and cerebrospinal fluid (CSF) of a female subject undergoing long-term cART. Paired plasma and CSF samples were collected at 12-month intervals and HIV-1 env C2V4 was cloned and sequenced. Phylogenetic analysis of paired samples consistently showed genetic variants unique to the CSF. Phenotypic prediction showed CCR5 (R5) variants for all CSF-derived sequences and showed minor X4 variants (or dual-tropic) in the plasma at later time points. Viral compartmentalization was evident throughout the study, suggesting that the occurrence of distinctive env strains may contribute to the neuropathogenesis of HAND. Our study provides new insights about the genetic characteristics within the C2V4 of HIV-1 env that persist after long-term cART and during the course of persistent ANI.

Sodium and potassium excretion are related to bone mineral density in women with coeliac disease.

PubMed

Turner, Kirsty M; Clifton, Peter M; Keogh, Jennifer B

2015-04-01

Women with coeliac disease may have a lower bone mineral density due to the malabsorption of calcium before diagnosis. A high sodium excretion is associated with increased calcium and bone loss. Our aim was to describe the bone mineral density (BMD) and sodium excretion in women with coeliac disease. In a cross-sectional study BMD of the lumbar spine and hip was assessed by dual energy X-ray absorptiometry. Sodium, potassium and calcium excretion were measured from a 24 h urine collection. In 33 women (51 ± 16 yr) BMD was 1.14 ± 0.19 g/cm(2) and 0.94 ± 0.14 g/cm(2) at the lumbar spine and hip respectively. Age matched Z-scores were -0.1 ± 1.2 and -0.3 ± 1.1 at lumbar spine and hip respectively. Sodium excretion was 107 ± 51 mmol/d; 14 (42%) had a sodium excretion >100 mmol Na/d (145 ± 45 mmol/d). Potassium and calcium excretion were 87 ± 25 mmol/d and 4.1 ± 2.0 mmol/d respectively. In women with Na excretion >100 mmol Na/d, Ca excretion was significantly greater than those with <100 mmol/d (4.9 ± 2.0 vs 3.4 ± 1.8, p < 0.05). Sodium excretion and BMI were positively correlated (r = 0.61, p < 0.001) as were sodium and calcium excretion (r = 0.43, p < 0.05). Sodium excretion was inversely related to femoral neck BMD (t = -2.4 p = 0.023) after adjustment for weight, age, years since diagnosis and potassium excretion. Weight, but no other variable, was a predictor of BMD at the lumbar spine (t = 2.58 p = 0.018). Sodium excretion was inversely related and potassium excretion positively related to femoral neck density which was similar to age matched women without coeliac disease. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

An update and review of antiretroviral therapy.

PubMed

Piacenti, Frank J

2006-08-01

The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden, and coformulated dosage forms that contain two or three drugs in one convenient pill. Other improvements include increased potency of newer agents, agents sensitive to a highly resistant virus, improved adverse-effect profile (e.g., less gastrointestinal effects, improved lipid profiles), as well as protease inhibitor boosting with ritonavir, which takes advantage of the potent cytochrome P450 inhibitory action of ritonavir. This review focuses on the concepts of antiretroviral therapy, barriers to successful antiretroviral treatment, developments to limit treatment barriers, and new drug entities for the treatment of HIV.

Evidence of an oncogenic Gammaherpesvirus in domestic Dogs

PubMed Central

Huang, Shih-Hung; Kozak, Philip; Kim, Jessica; Habineza-Ndikuyeze, Georges; Meade, Charles; Gaurnier-Hausser, Anita; Patel, Reema; Robertson, Erle; Mason, Nicola J.

2015-01-01

In humans chronic infection with the gammaherpesvirus, Epstein-Barr Virus is usually asymptomatic however, some infected individuals develop hematological and epithelial malignancies. The exact role of EBV in lymphomagenesis is poorly understood partly because of the lack of clinically relevant animal models. Here we report the detection of serological responses against EBV capsid antigens in healthy dogs and dogs with spontaneous lymphoma and that dogs with the highest antibody titers have B-cell lymphoma. Moreover, we demonstrate the presence of EBV-like viral DNA and RNA sequences and Latent Membrane Protein-1 in malignant lymph nodes of dogs with lymphoma. Finally, electron microscopy of canine malignant B cells revealed the presence of classic herpesvirus particles. These findings suggest that dogs can be naturally infected with an EBV-like gammaherpesvirus that may contribute to lymphomagenesis and that dogs might represent a spontaneous model to investigate environmental and genetic factors that influence gammaherpesvirus-associated lymphomagenesis in humans. PMID:22405628

Skin rash, headache and abnormal behaviour: unusual presentation of intracranial haemorrhage in dengue fever

PubMed Central

Wani, Abdul Majid; Mejally, Mousa Ali Al; Hussain, Waleed Mohd; Maimani, Wail Al; Hanif, Sadia; Khoujah, Amer Mohd; Siddiqi, Ahmad; Akhtar, Mubeena; Bafaraj, Mazen G; Fareed, Khurram

2010-01-01

Dengue viral infections are one of the most important mosquito borne diseases in the world. The dengue virus is a single stranded RNA virus belonging to the Flaviviridae family. There are four serotypes (DEN 1–4) classified according to biological and immunological criteria. Patients may be asymptomatic or their condition may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide and 2.5 billion people are at risk. At present, dengue is endemic in 112 countries. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. We present an interesting case of dengue fever with headache, skin rash and abnormal behaviour who had a massive intracranial haemorrhage with fatal outcome. PMID:22242067

[Unusual location of giant seborrhoeic keratoses].

PubMed

Naciri, Ilhame; Ismaili, Nadia

2017-01-01

Seborrhoeic keratoses (SK) are benign tumors that mainly occur in the head and in the trunk. Their size generally varies from a few millimeters up to a few centimeters. Giant lesions are very rare but pose a problem in terms both of treatment and transformation. Their occurrence in the genital area is even more rare, posing a problem in differential diagnosis of genital warts. Differentiation is only based on histopathology. We report the case of a 80-year old man, with no particular past medical history, who presented with asymptomatic abdominal and genital lesions evolving over the last twenty years. Clinical examination showed four hyperpigmented, humped, well-defined tumors, with warty surface measuring 2-10 cm along its longer axis (A). Dermoscopic examination showed cerebriform convolutions appearance suggesting seborrhoeic keratoses (B). Histology confirmed the diagnosis, without signs of viral infection or malignant transformation. The patient underwent surgical resection resulting in permanent scar.

Outbreak of hepatitis A in Korean military personnel.

PubMed

Lee, Chang-Seop; Lee, Ju-Hyung; Kwon, Keun-Sang

2008-05-01

This report describes a hepatitis A outbreak among Korean military personnel. Each case of hepatitis A in this outbreak was defined as a person who had symptoms compatible with acute viral hepatitis A and had positive HAV IgM between May 2 and August 14, 2007 in Inje district, Gangwon, Korea. We tested 70 cases with symptoms for HAV IgM, and 67 cases showed positive results. They included 4 sergeants, 1 officer and 62 privates. A positive result for HAV IgG among asymptomatic military personnel was seen in 11.8% of cases. This epidemic occurred after a heavy rainfall in the military compound area where drinking water was supplied by the stream water. After the outbreak, the supply of drinking water was switched to a public water system. All of 178 military personnel who had no HAV IgG were vaccinated on July 26, 2007. The outbreak was resolved after the control measures were implemented.

Evolving Character of Chronic Central Nervous System HIV Infection

PubMed Central

Price, Richard W.; Spudich, Serena S.; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

2014-01-01

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. PMID:24715483

Evolving character of chronic central nervous system HIV infection.

PubMed

Price, Richard W; Spudich, Serena S; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

2014-02-01

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Crimean-Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout mice.

PubMed

Bereczky, Sándor; Lindegren, Gunnel; Karlberg, Helen; Akerström, Sara; Klingström, Jonas; Mirazimi, Ali

2010-06-01

Crimean-Congo hemorrhagic fever virus (CCHFV) poses a great threat to public health due to its high mortality, transmission and geographical distribution. To date, there is no vaccine or specific treatment available and the knowledge regarding its pathogenesis is highly limited. Using a small-animal model system, this study showed that adult mice missing the type I interferon (IFN) receptor (IFNAR(-/-)) were susceptible to CCHFV and developed an acute disease with fatal outcome. In contrast, infection of wild-type mice (129 Sv/Ew) was asymptomatic. Viral RNA was found in all analysed organs of the infected mice, but the amount of CCHFV RNA was significantly higher in the IFNAR(-/-) mice than in the wild-type mice. Furthermore, the liver of IFNAR(-/-) mice was enlarged significantly, showing that IFN is important for limiting virus spread and protecting against liver damage in mice.

Neglected Parasitic Infections in the United States: Trichomoniasis

PubMed Central

Secor, W. Evan; Meites, Elissa; Starr, Michelle C.; Workowski, Kimberly A.

2014-01-01

Trichomonas vaginalis is one of the most common human parasitic infections in the United States, as well as the most prevalent non-viral sexually transmitted infection. However, it has long received much less consideration than other parasitic and sexually transmitted diseases. Much of this inattention can be attributed to a poor understanding of the public health impact of trichomoniasis. Increasing recognition of the sequelae of infection, including increased risk of infection with human immunodeficiency virus and adverse outcomes of pregnancy, has led to increased interest in T. vaginalis. Recent innovations include development of diagnostic tests that could improve detection of the parasite. A number of important questions, such as the epidemiology among men and women, the true public health burden of symptomatic and asymptomatic T. vaginalis infections, and whether current treatments will be adequate to reduce the substantial health disparities and costs associated with trichomoniasis, need consideration to remedy neglect of this important disease. PMID:24808247

Rapid and Sensitive Detection of Lymphocystis Disease Virus Genotype VII by Loop-Mediated Isothermal Amplification.

PubMed

Valverde, Estefanía J; Cano, Irene; Castro, Dolores; Paley, Richard K; Borrego, Juan J

2017-03-01

Lymphocystis disease virus (LCDV) infections have been described in gilthead seabream (Sparus aurata L.) and Senegalese sole (Solea senegalensis, Kaup), two of the most important marine fish species in the Mediterranean aquaculture. In this study, a rapid, specific, and sensitive detection method for LCDV genotype VII based on loop-mediated isothermal amplification (LAMP) was developed. The LAMP assay, performed using an apparatus with real-time amplification monitoring, was able to specifically detect LCDV genotype VII from clinically positive samples in less than 12 min. In addition, the assay allowed the detection of LCDV in all asymptomatic carrier fish analysed, identified by qPCR, showing an analytical sensitivity of ten copies of viral DNA per reaction. The LCDV LAMP assay has proven to be a promising diagnostic method that can be used easily in fish farms to detect the presence and spread of this iridovirus.

[Cytomegalovirus-associated infectious mononucleosis-like syndrome accompanied by transient monoclonal expansion of CD8+ T-cells].

PubMed

Yonezawa, Akihito; Onaka, Takashi; Imada, Kazunori

2009-08-01

Most cases of infectious mononucleosis (IM) are caused by Epstein-Barr virus (EBV). Other pathogens have been reported to cause heterophile-negative mononucleosis-like syndrome, including cytomegalovirus (CMV) and human immunodeficiency virus type-1 (HIV-1). Primary CMV infection is often asymptomatic in immunocompetent individuals. In this article, we describe a patient with prolonged fever and fatigue, who developed transient monoclonal CD8+ T-cell lymphocytosis after primary CMV infection. Monoclonal gene rearrangement of T-cell receptor (TCR) beta locus was transiently detected in DNA from peripheral lymphocytes. Monoclonal rearrangement and atypical lymphocytosis disappeared after treatment with anti-viral agents. These observations imply that monoclonal expansion of T-cells could be a reactive phenomenon of primary CMV infection and TCR gene rearrangement is not specific for malignancy. Physicians should carefully follow patients with monoclonal expansion of CD8+ T-cells after CMV-IM in order to rule out T cell malignancy.

Evaluation of COBAS AmpliPrep/COBAS TaqMan CMV Test for use in hematopoietic stem cell transplant recipients.

PubMed

Ramanan, Poornima; Razonable, Raymund R

2017-07-01

Cytomegalovirus (CMV) is a common opportunistic infection that contributes to poor outcomes in hematopoietic stem cell transplant (HSCT) recipients. Prevention of CMV end-organ disease in allogeneic HSCT recipients is commonly achieved by preemptive antiviral therapy of asymptomatic CMV reactivation that is detected by serial nucleic acid testing (NAT). However, there was no standardized CMV NAT until the development of the World Health Organization (WHO) International Standard. Areas covered: This article provides a comprehensive review on COBAS AmpliPrep/TaqMan (CAP/CTM) CMV assay (Roche) and emphasizes the limitations in the clinical use of CMV NAT in HSCT recipients. Expert commentary: The CAP/CTM CMV Test is the first US FDA approved commercial quantitative NAT for CMV viral load monitoring of plasma samples in solid organ transplant and HSCT recipients. The CAP/CTM assay has wide linear range of DNA quantification and demonstrates colinearity to the WHO International Standard. Studies of CAP/CTM CMV assay in HSCT recipients are still limited, but are now being reported to define viral thresholds for diagnosis, surveillance and monitoring. Results from these early studies in HSCT recipients suggest that, while the WHO IS has improved the inter-laboratory result variances, there are still important factors that continue to contribute to assay variability. This lack of harmony among NAT highlights the need for further standardization.

Incidence and characteristics of hepatitis E virus infection in children in Assiut, Upper Egypt.

PubMed

Hasan, Gamal; Assiri, Asaad; Marzuuk, Naglaa; Daef, Enas; Abdelwahab, Sayed; Ahmed, Ahmed; Mohamad, Ismail; Al-Eyadhy, Ayman; Alhaboob, Ali; Temsah, Mohamad-Hani

2016-10-01

Objective To describe the characteristics of hepatitis E virus (HEV) infection in a cohort of children from Upper Egypt using data from a large multicentre prospective study of acute viral hepatitis (AVH). Methods Data from subjects aged 2-18 years with AVH or close contacts of those with AVH found to have asymptomatic AVH were included in the analysis. Information concerning medical history, clinical examination, liver function tests and screening for hepatotropic viruses was recorded and analysed. Results A total of 123 patients (73 boys, 50 girls) were included in the analysis. Of these, 33 (26.8%) had HEV infection, 17 (13.8%) had hepatitis A virus infection, 10 (8.1%) had hepatitis B virus infection, 14 (11.4%) had cytomegalovirus hepatitis, five (4.1%) had autoimmune hepatitis, 11 (8.9%) had hepatitis due to mixed viral infections and 33 (26.8%) had non A-E hepatitis. Overall, 38 (30.9%) had infection with HEV. HEV infection was significantly higher among those using underground wells as a water source compared with tap water. Liver enzymes were significantly raised in patients with non-HEV infection compared with those with HEV infection. Conclusions HEV is a significant cause of AVH among children in Upper Egypt. Contamination of drinking water appears to be a major source of infection. Screening for HEV should be considered in all Egyptian children with AVH.

Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.

PubMed

Zhu, T; Wang, N; Carr, A; Nam, D S; Moor-Jankowski, R; Cooper, D A; Ho, D D

1996-05-01

To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission.

Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission.

PubMed

Biava, Mirella; Caglioti, Claudia; Castilletti, Concetta; Bordi, Licia; Carletti, Fabrizio; Colavita, Francesca; Quartu, Serena; Nicastri, Emanuele; Iannetta, Marco; Vairo, Francesco; Liuzzi, Giuseppina; Taglietti, Fabrizio; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Lalle, Eleonora

2018-01-01

As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.

Avian bornavirus in free-ranging waterfowl: prevalence of antibodies and cloacal shedding of viral RNA.

PubMed

Delnatte, Pauline; Nagy, Éva; Ojkic, Davor; Leishman, David; Crawshaw, Graham; Elias, Kyle; Smith, Dale A

2014-07-01

We surveyed free-ranging Canada Geese (Branta canadensis), Trumpeter Swans (Cygnus buccinator), Mute Swans (Cygnus olor), and Mallards (Anas platyrhynchos) to estimate the prevalence of antibodies to avian bornavirus (ABV) and of cloacal shedding of ABV RNA in southern Ontario, Canada. Blood samples and cloacal swabs were collected from 206 free-ranging Canada Geese, 135 Trumpeter Swans, 75 Mute Swans, and 208 Mallards at 10 main capture sites between October 2010 and May 2012. Sera were assessed for antibodies against ABV by enzyme-linked immunosorbent assay and swabs were evaluated for ABV RNA using real-time reverse-transcription PCR. Serum antibodies were detected in birds from all four species and at each sampling site. Thirteen percent of the geese caught on the Toronto Zoo site shed ABV RNA in feces compared with 0% in geese sampled at three other locations. The proportions of shedders among Mute Swans, Trumpeter Swans, and Mallards were 9%, 0%, and 0%, respectively. Birds that were shedding viral RNA were more likely to have antibodies against ABV and to have higher antibody levels than those that were not, although many birds with antibodies were not shedding. We confirmed that exposure to, or infection with, ABV is widespread in asymptomatic free-ranging waterfowl in Canada; however, the correlation between cloacal shedding, presence of antibodies, and presence of disease is not fully understood.

Molecular typing of enteroviruses associated with viral meningitis in Cyprus, 2000-2002.

PubMed

Richter, Jan; Koptides, Dana; Tryfonos, Christina; Christodoulou, Christina

2006-08-01

Human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. Although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. In this study, samples from 218 patients diagnosed with enteroviral meningitis between January 2000 and December 2002 were analysed in order to assess the epidemiology of human enteroviruses as a cause of viral meningitis in Cyprus. A new typing strategy, based on partial sequencing of the 5' non-coding region (5'NCR), prediction of type, and selection of type-specific primers for sensitive VP1 PCR amplification, was developed. As clustering in the 5'NCR was concordant with clustering in the VP1 region, quick and reliable typing by VP1 sequencing was achieved without virus isolation in cell culture. The most frequent enterovirus serotypes identified were Human echovirus 30 (55.5%), Human echovirus 13 (15.1%), Human echovirus 6 (13.8%) and Human echovirus 9 (8.3%). Human coxsackieviruses B2, B1 and B5, Human echovirus 4, Human enterovirus 71 and Human coxsackievirus A6 represented rather rare serotypes. This is the first molecular epidemiological study of enterovirus meningitis in Cyprus. Serotype distribution corresponded basically with observations in other European countries, suggesting the spread of enteroviruses by tourism.

Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students.

PubMed

Balfour, Henry H; Odumade, Oludare A; Schmeling, David O; Mullan, Beth D; Ed, Julie A; Knight, Jennifer A; Vezina, Heather E; Thomas, William; Hogquist, Kristin A

2013-01-01

University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity. EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8(+) T-cells but not in numbers of CD4(+) T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8(+) lymphocytosis (P = .0003). Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8(+) lymphocytosis correlated with disease severity.

Role of HTLV-1 Tax and HBZ in the Pathogenesis of HAM/TSP

PubMed Central

Enose-Akahata, Yoshimi; Vellucci, Ashley; Jacobson, Steven

2017-01-01

Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. Understanding the interaction between host and HTLV-1 and the molecular mechanisms associated with disease pathogenesis is critical for development efficient therapies. Two HTLV-1 genes, tax and HTLV-1 basic leucine zipper factor (HBZ), have been demonstrated to play important roles in HTLV-1 infectivity and the growth and survival of leukemic cells. Increased HTLV-1 Tax expression induces the expression of various cellular genes such as IL-2 and IL-15, which directly contributes to lymphocyte activation and immunopathogenesis in HAM/TSP patients. However, little is known about the molecular and cellular mechanism of HBZ in development of HAM/TSP. It has been reported that HBZ mRNA expression was detected in HAM/TSP patients higher than in asymptomatic carriers and correlated with proviral load and disease severity. Unlike HTLV-1 tax, HBZ escapes efficient anti-viral immune responses and therefore these reactivities are difficult to detect. Thus, it is important to focus on understanding the function and the role of HTLV-1 tax and HBZ in disease development of HAM/TSP and discuss the potential use of these HTLV-1 viral gene products as biomarkers and therapeutic targets for HAM/TSP. PMID:29312243

Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB

PubMed Central

Yoshida, Yuichi; Okada, Yohei; Suzuki, Akiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Miyasaka, Akio; Takikawa, Yasuhiro; Nishizawa, Tsutomu; Okamoto, Hiroaki

2017-01-01

Abstract Rationale: Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)–associated acute liver failure (ALF) have been reported in low HAV endemic countries annually. Patients concerns: To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described. Diagnoses: This family consisted of five members who all were infected with HAV. Interventions: Four of the five patients hospitalized except for an asymptomatic patient. Outcomes: Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case. Lessons: The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure. PMID:28858094

Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB: A case report.

PubMed

Yoshida, Yuichi; Okada, Yohei; Suzuki, Akiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Miyasaka, Akio; Takikawa, Yasuhiro; Nishizawa, Tsutomu; Okamoto, Hiroaki

2017-09-01

Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)-associated acute liver failure (ALF) have been reported in low HAV endemic countries annually. To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described. This family consisted of five members who all were infected with HAV. Four of the five patients hospitalized except for an asymptomatic patient. Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case. The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure.

Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis

PubMed Central

BLASER, Nello; WETTSTEIN, Celina; ESTILL, Janne; VIZCAYA, Luisa SALAZAR; WANDELER, Gilles; EGGER, Matthias; KEISER, Olivia

2014-01-01

Objectives HIV ‘treatment as prevention’ (TasP) describes early treatment of HIV-infected patients intended to reduce viral load (VL) and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and of the relation of HIV transmission risk to VL. Design Systematic review and meta-analysis. Methods We searched PubMed and Embase databases for studies that established a relationship between VL and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analyzed assumptions about the relationship between VL and transmission risk, and between duration of primary infection and transmission risk. Results We found 36 eligible articles, based on six different study populations. Studies consistently found that larger VLs lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. Conclusions Assumptions and estimates of the relationship between VL and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account. PMID:24691205

Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys.

PubMed

Klatt, Nichole R; Villinger, Francois; Bostik, Pavel; Gordon, Shari N; Pereira, Lara; Engram, Jessica C; Mayne, Ann; Dunham, Richard M; Lawson, Benton; Ratcliffe, Sarah J; Sodora, Donald L; Else, James; Reimann, Keith; Staprans, Silvija I; Haase, Ashley T; Estes, Jacob D; Silvestri, Guido; Ansari, Aftab A

2008-06-01

Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs.

Urinary 24-h creatinine excretion in adults and its use as a simple tool for the estimation of daily urinary analyte excretion from analyte/creatinine ratios in populations.

PubMed

Johner, S A; Boeing, H; Thamm, M; Remer, T

2015-12-01

The assessment of urinary excretion of specific nutrients (e.g. iodine, sodium) is frequently used to monitor a population's nutrient status. However, when only spot urines are available, always a risk of hydration-status-dependent dilution effects and related misinterpretations exists. The aim of the present study was to establish mean values of 24-h creatinine excretion widely applicable for an appropriate estimation of 24-h excretion rates of analytes from spot urines in adults. Twenty-four-hour creatinine excretion from the formerly representative cross-sectional German VERA Study (n=1463, 20-79 years old) was analysed. Linear regression analysis was performed to identify the most important influencing factors of creatinine excretion. In a subsample of the German DONALD Study (n=176, 20-29 years old), the applicability of the 24-h creatinine excretion values of VERA for the estimation of 24-h sodium and iodine excretion from urinary concentration measurements was tested. In the VERA Study, mean 24-h creatinine excretion was 15.4 mmol per day in men and 11.1 mmol per day in women, significantly dependent on sex, age, body weight and body mass index. Based on the established 24-h creatinine excretion values, mean 24-h iodine and sodium excretions could be estimated from respective analyte/creatinine concentrations, with average deviations <10% compared with the actual 24-h means. The present mean values of 24-h creatinine excretion are suggested as a useful tool to derive realistic hydration-status-independent average 24-h excretion rates from urinary analyte/creatinine ratios. We propose to apply these creatinine reference means routinely in biomarker-based studies aiming at characterizing the nutrient or metabolite status of adult populations by simply measuring metabolite/creatinine ratios in spot urines.

Unnatural constituents of breast milk--medication, lifestyle, pollutants, viruses.

PubMed

Golding, J

1997-10-29

It is well recognised that although nutritionally breast milk is the optimal food for babies, there are a number of caveats to this, based on the consequences of the modern lifestyle. Here we have considered ways in which the young breast fed child may be exposed to various environmental and medical contaminants which might cause adverse reactions and to which he/she may not otherwise be exposed. These substances are divided into four different areas: (i) medication taken by the mother; (ii) exposure to possibly addictive drugs taken by the mother; (iii) exposure to pollutants mainly from the maternal diet or as the result of her occupation; (iv) viruses. The infant who consumes breast milk may be exposed to a variety of chemicals which may have untoward effects on his/her immediate health and temperament and future development. Potentially hazardous substances ingested by the breast fed infant include medicaments (or their metabolites) that may have been ingested by the mother, potentially addictive common neurotoxicants such as nicotine, caffeine and alcohol, illicit drugs such as heroin and cocaine, and pollutants such as polychlorinated biphenyls and dichlorodiphenyltrichloroethane (DDT). There is a paucity of good information on which to base reliable estimates of the harm that this may cause the child. Although breast feeding is known to protect against bacterial infection, a number of viruses are excreted in the breast milk which may infect the child asymptomatically (e.g. cytomegalovirus, Epstein-Barr virus) and which are not known to be harmful, as well as human immunodeficiency virus (HIV) excretion which, in contrast, does appear to increase the risk of the child becoming infected. Balancing the risk of infection to the child born to an HIV infected mother, results in the proposition that known HIV positive women in developing countries (where the risk of gastrointestinal infection is high) should continue to breast feed but those in the developed world (where the risk of gastrointestinal infection is lower) are better advised to bottle feed.

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

PubMed Central

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID:26893541

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes.

PubMed

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30-40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO-L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption.

Multicenter, randomized study to optimize bowel preparation for colon capsule endoscopy

PubMed Central

Kastenberg, David; Jr, Wilmot C Burch; Romeo, David P; Kashyap, Pankaj K; Pound, David C; Papageorgiou, Neophytos; Sainz, Ignacio Fernández-Urien; Sokach, Carly E; Rex, Douglas K

2017-01-01

AIM To assess the cleansing efficacy and safety of a new Colon capsule endoscopy (CCE) bowel preparation regimen. METHODS This was a multicenter, prospective, randomized, controlled study comparing two CCE regimens. Subjects were asymptomatic and average risk for colorectal cancer. The second generation CCE system (PillCam® COLON 2; Medtronic, Yoqneam, Israel) was utilized. Preparation regimens differed in the 1st and 2nd boosts with the Study regimen using oral sulfate solution (89 mL) with diatrizoate meglumine and diatrizoate sodium solution (“diatrizoate solution”) (boost 1 = 60 mL, boost 2 = 30 mL) and the Control regimen oral sulfate solution (89 mL) alone. The primary outcome was overall and segmental colon cleansing. Secondary outcomes included safety, polyp detection, colonic transit, CCE completion and capsule excretion ≤ 12 h. RESULTS Both regimens had similar cleansing efficacy for the whole colon (Adequate: Study = 75.9%, Control = 77.3%; P = 0.88) and individual segments. In the Study group, CCE completion was superior (Study = 90.9%, Control = 76.9%; P = 0.048) and colonic transit was more often < 40 min (Study = 21.8%, Control = 4%; P = 0.0073). More Study regimen subjects experienced adverse events (Study = 19.4%, Control = 3.4%; P = 0.0061), and this difference did not appear related to diatrizoate solution. Adverse events were primarily gastrointestinal in nature and no serious adverse events related either to the bowel preparation regimen or the capsule were observed. There was a trend toward higher polyp detection with the Study regimen, but this did not achieve statistical significance for any size category. Mean transit time through the entire gastrointestinal tract, from ingestion to excretion, was shorter with the Study regimen while mean colonic transit times were similar for both study groups. CONCLUSION A CCE bowel preparation regimen using oral sulfate solution and diatrizoate solution as a boost agent is effective, safe, and achieved superior CCE completion. PMID:29358870

Variability of urinary salt excretion estimated by spot urine in treated hypertensive patients.

PubMed

Arakawa, Kimika; Sakaki, Minako; Sakata, Satoko; Oniki, Hideyuki; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

2015-01-01

Among the several methods used to assess salt intake, estimating 24 h urinary salt excretion by spot urine seems appropriate for clinical practice. In this study, we investigated variability in urinary salt excretion using spot urine in hypertensive outpatients. Participants included 200 hypertensive patients who underwent spot urinary salt excretion at least three times during the observation period. Mean urinary salt excretion and the coefficient of the variation were 8.62 ± 1.96 g/day and 19.0 ± 10.2%, respectively. In the analysis of participants who underwent assessment of urinary salt excretion at least eight times (n = 54), a significant reduction in mean urinary salt excretion was found at the 5th measurement. On the contrary, the coefficient of the variation of urinary salt excretion continued to increase until the 5th measurement, and became stable thereafter. Mean urinary salt excretion was positively correlated with mean clinic diastolic blood pressure (r = 0.27, p < 0.05). Clinic diastolic blood pressure in the high urinary salt excretion group (≥ 10 g/day) was significantly higher than that of the low group (76.2 ± 7.5 vs 73.4 ± 8.3 mmHg, p < 0.05). Mean urinary salt excretion in summer was significantly lower than that of the other seasons (7.75 ± 1.94 vs 9.09 ± 2.68 (spring), 8.72 ± 2.12 (autumn), 8.92 ± 2.17 (winter) g/day, p < 0.01). In conclusion, repeated measurements of urinary salt excretion using spot urine are required to assess daily salt intake of hypertensive patients.

Excreting and non-excreting grasses exhibit different salt resistance strategies

PubMed Central

Moinuddin, Muhammad; Gulzar, Salman; Ahmed, Muhammad Zaheer; Gul, Bilquees; Koyro, Hans-Werner; Khan, Muhammad Ajmal

2014-01-01

The combination of traits that makes a plant successful under saline conditions varies with the type of plant and its interaction with the environmental conditions. Knowledge about the contribution of these traits towards salt resistance in grasses has great potential for improving the salt resistance of conventional crops. We attempted to identify differential adaptive response patterns of salt-excreting versus non-excreting grasses. More specifically, we studied the growth, osmotic, ionic and nutrient (carbon/nitrogen) relations of two salt-excreting (Aeluropus lagopoides and Sporobolus tremulus) and two non-excreting (Paspalum paspalodes and Paspalidium geminatum) perennial C4 grasses under non-saline and saline (0, 200 and 400 mM NaCl) conditions. Growth and relative growth rate decreased under saline conditions in the order P. geminatum > S. tremulus = A. lagopoides > P. paspalodes. The root-to-shoot biomass allocation was unaffected in salt-excreting grasses, increased in P. paspalodes but decreased in P. geminatum. Salt-excreting grasses had a higher shoot/root Na+ ratio than non-excreting grasses. K+, Ca2+ and Mg2+ homoeostasis remained undisturbed among test grasses possibly through improved ion selectivity with rising substrate salinity. Salt-excreting grasses increased leaf succulence, decreased ψs and xylem pressure potential, and accumulated proline and glycinebetaine with increasing salinity. Higher salt resistance of P. paspalodes could be attributed to lower Na+ uptake, higher nitrogen-use efficiency and higher water-use efficiency among the test species. However, P. geminatum was unable to cope with salt-induced physiological drought. More information is required to adequately document the differential strategies of salt resistance in salt-excreting and non-excreting grasses. PMID:24996428

Prevalence and genotypes of Enterocytozoon bieneusi in China.

PubMed

Wang, Sha-Sha; Wang, Rong-Jun; Fan, Xian-Cheng; Liu, Ting-Li; Zhang, Long-Xian; Zhao, Guang-Hui

2018-07-01

Enterocytozoon bieneusi has been considered as the most frequently diagnosed microsporidian species in humans and various animal species, accounting for more than 90% of the cases of human microsporidiosis. Spores of this pathogen excreted from both symptomatic and asymptomatic hosts into environment also would be an important source of waterborne outbreak of microsporidiosis. Due to limited effective drugs available but with too much side effects to mammals (eg. toxic), accurate characterization of E. bieneusi in both humans and animals is essential to implement effective control strategies to this pathogen. In China, E. bieneusi infection was presented in humans and some animals with high prevalence. Analysis of genetic variations of the internal transcribed spacer (ITS) sequences found 361 genotypes in China, and some novel genotypes were identified in some specific hosts. Additionally, associations between infections and some risk factors were also observed. In the present article, we reviewed the current status of prevalence, genotypes, multilocus genotypes (MLGs) in humans, various animals and waters in China. These findings will provide basic information for developing effective control strategies against E. bieneusi infection in China as well as other countries. Copyright © 2018 Elsevier B.V. All rights reserved.

Epidemiology of Foodborne Norovirus Outbreak in Incheon, Korea

PubMed Central

Kim, Na-Yeon; Koh, Yeon-Ja; Lee, Hun-Jae

2010-01-01

On June 14, 2008, an outbreak of gastroenteritis occurred among elementary school students in Incheon. We conducted an investigation to identify the source and described the extent of the outbreak. We performed a retrospective cohort study among students, teachers and food handlers exposed to canteen food in the elementary school. Using self-administered questionnaires we collected information on symptoms, days of canteen food eaten, food items consumed. Stool samples were collected from 131 symptomatic people and 11 food handlers. The catering kitchen was inspected and food samples were taken. Of the 1,560 people who ate canteen food, 117 were symptomatic cases, and the attack rate was 7.5%. Consumption of cucumber-crown daisy salad (RR=2.71), fresh cabbage mix (RR=2.23), dried radish salad (RR=3.04) and young radish kimchi (RR=2.52) were associated with illness. Sixty-four (45%) of the 142 stool specimens were positive for Norovirus. Norovirus was detected in 2 food handlers. Interviews with kitchen staff indicated the likelihood of contamination from an infected food handler to the dried radish salad during food processing. The excretion of Norovirus from asymptomatic food handlers may be an infection source of Norovirus outbreaks. PMID:20676321

The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

PubMed Central

Nicolle, Lindsay E.

2016-01-01

Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients. PMID:27104571

The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria.

PubMed

Nicolle, Lindsay E

2016-04-19

Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

Treatment of Athlete's Plantar Warts Using a Botanical Blend: A Case Report.

PubMed

Nelson, Erik O; Kozin, Adam F; Ruiz, Guillermo; Lasku, Arben; Langland, Jeffrey O

2017-05-01

Context • Viral plantar warts, or verruca plantaris, are a benign epithelial tumor caused by various strains of the human papilloma virus (HPV). Current treatments have had mixed degrees of success, are moderately invasive, and are often incompatible with participation in sports. Objective • The study intended to examine the benefits of treating plantar warts with a topical, botanical blend that has had clinical success treating herpes simplex virus cold sores. Methods • A synergistic botanical blend was applied topically. Setting • The case report was completed at the Southwest College of Naturopathic Medicine (Tempe, Arizona, USA). Participant • The participant was a 24-y-old male soccer player, 177.8 cm tall, and weighing 69 kg with previously diagnosed, viral mosaic warts. Intervention • The patient used a pumice stone during bathing for the first week to remove dead tissue and ensure sufficient contact and entry of the botanical gel into infected tissue. After drying the area, the patient applied the botanical gel blend 1 to 2 times daily postshower, spreading it evenly across the surface of the entire lesion. The patient discontinued the exfoliation technique after the first week. Results • Within the first week of treatment, the patient noted changes to the infected area of the hallux epidermal tissue. The combination of exfoliation and application of the gel caused marked, visible differences in presentation by the fifth day of treatment. At 1-mo postintervention, or day 90, the epidermal tissue was asymptomatic and devoid of petechiae, malformations, or visible infection. Conclusions • The results of the current case study directly contrast with the drawbacks of commonly accepted, first-line interventions in the treatment of viral plantar warts and, in many respects, demonstrate better efficacy and fewer side effects than the standard of care. The positive results also highlight the necessity for additional study in the fields of sports medicine and podiatry to further establish the botanical blend when treating viral plantar in athletes, an overall at-risk population for the condition.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

PubMed

Wang, Yang; Hu, Jia-Wen; Qu, Peng-Fei; Wang, Ke-Ke; Yan, Yu; Chu, Chao; Zheng, Wen-Ling; Xu, Xian-Jing; Lv, Yong-Bo; Ma, Qiong; Gao, Ke; Yuan, Yue; Li, Hao; Yuan, Zu-Yi; Mu, Jian-Jun

2018-05-17

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Long-term excretion of vaccine-derived poliovirus by a healthy child.

PubMed

Martín, Javier; Odoom, Kofi; Tuite, Gráinne; Dunn, Glynis; Hopewell, Nicola; Cooper, Gill; Fitzharris, Catherine; Butler, Karina; Hall, William W; Minor, Philip D

2004-12-01

A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+ T Cell Activation during Antiretroviral Treatment

PubMed Central

Massanella, Marta; Richman, Douglas D.; Little, Susan J.; Spina, Celsa A.; Vargas, Milenka V.; Lada, Steven M.; Daar, Eric S.; Dube, Michael P.; Haubrich, Richard H.; Morris, Sheldon R.; Smith, Davey M.

2014-01-01

ABSTRACT Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+ T cells in blood (P < 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+ T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P = 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P = 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+ (P < 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations. IMPORTANCE Almost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in blood, and the size of the HIV DNA reservoir in 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. In support of our primary hypothesis, shedding of CMV DNA in semen was associated with increased activation and proliferation of T cells in blood and also significantly higher levels of HIV DNA in blood cells. These results suggest that CMV reactivation might play a role in the maintenance of the HIV DNA reservoir during suppressive ART and that it could be a target of pharmacologic intervention in future studies. PMID:24789781

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

PubMed

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10. There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Birefringent Crystals and Abdominal Discoloration in the Predatory Mite Phytoseiulus persimilis (Acari: Phytoseiidae)

PubMed

Bjørnson; Steiner; Keddie

1997-03-01

In response to grower complaints of poor performance of Phytoseiulus persimilis, mites from 14 commercial insectaries and research colonies were examined for pathogens. Some were found to have abdominal discolorations, manifested initially as two white stripes along the dorsal sides of the body within the Malpighian tubules. Advanced signs appeared as a large, centrally located, white spot or U-shaped discoloration in the distal opisthosoma within the rectum/anal atrium. White material often accumulated and hardened within the anus and formed a rectal plug that inhibited further excretion. Most affected mites were lethargic. Adults and immatures with abdominal discoloration contained numerous densely packed, birefringent, dumbbell-shaped entities. Though occasionally observed in the colon, they occurred most frequently within the Malpighian tubules and/or rectum and anal atrium. Dumbbells measured 2-4 &mgr;m long and contained prominent concentric rings. When observed by transmission electron microscopy, the entities lacked cellular organelles. Asymptomatic mites contained few or no such entities. Dumbbell-shaped inclusions were observed in P. persimilis from all sources examined. High levels of potassium, low levels of phosphorous and sulfur, and traces of chlorine were detected by energy-dispersive X-ray analysis. Guanine and uric acid, known nitrogenous wastes of arachnids, do not contain these elements. The chemical composition and structure indicate that the dumbbells are crystals. Both asymptomatic mites and those specimens exhibiting abdominal discoloration were examined for pathogens using light and transmission electron microscopy. Microsporidia, virus-like particles, and a rickettsia (genus Wolbachia) were observed in some mites but showed no correlation with white abdominal discoloration or associated crystal formation. Neither were pathogens always detected in symptomatic mites. Although birefringent crystals may be naturally occurring excretory products, the cause of white abdominal signs associated with crystal accumulation in P. persimilis is unknown. These signs indicate overall poor health.

The Contrasting Relationships between Betaine and Homocysteine in Two Clinical Cohorts are Associated with Plasma Lipids and Drug Treatments

PubMed Central

Lever, Michael; George, Peter M.; Atkinson, Wendy; Elmslie, Jane L.; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

2012-01-01

Background Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. Methods The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. Principal findings In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. Conclusions Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. PMID:22396767

Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America.

PubMed

Lipshultz, Steven E; Miller, Tracie L; Wilkinson, James D; Scott, Gwendolyn B; Somarriba, Gabriel; Cochran, Thomas R; Fisher, Stacy D

2013-06-18

Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. Before highly active antiretroviral therapy (HAART), the two-to-five-year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long-term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV-infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late-stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV-infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV-uninfected and HIV-infected children with HIV-infected mothers. In non-HIV-infected infants born to HIV-infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV-infected adults and children as cardiovascular illness has become a part of care for long-term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted.

Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

PubMed

Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R; Galli, M

1976-04-20

Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

Role of vasopressin in regulation of renal kinin excretion in Long-Evans and diabetes insipidus rats.

PubMed Central

Kauker, M L; Crofton, J T; Share, L; Nasjletti, A

1984-01-01

To study the relationship between vasopressin and the renal kallikrein-kinin system we measured the rate of excretion of kinins into the urine of anesthetized rats during conditions of increased and decreased vasopressin level. The excretion of immunoreactive kinins in Brattleboro rats with hereditary diabetes insipidus (DI) (24 +/- 3 pg min-1 kg-1) was lower than in the control Long Evans (LE) rats (182 +/- 22 pg min-1 kg-1; P less than 0.05). The DI rats also exhibited negligible urinary excretion of immunoreactive vasopressin, reduced urine osmolality, and increased urine flow and kininogenase excretion. In LE rats, volume expansion by infusion of 0.45% NaCl-2.5% dextrose to lower vasopressin secretion reduced (P less than 0.05) kinin excretion, vasopressin excretion, and urine osmolality to 41, 26, and 15% of their respective control values, while increasing (P less than 0.05) urine flow and kininogenase excretion. On the other hand, the infusion of 5% NaCl, which promotes vasopressin secretion, increased (P less than 0.05) the urinary excretion of kinins and vasopressin to 165 and 396% of control, while increasing (P less than 0.05) urine flow and kininogenase excretion. Infusion of vasopressin (1.2 mU/h, intravenous) enhanced (P less than 0.05) kinin excretion by two to threefold in DI rats and in LE rats during volume expansion with 0.45% NaCl-2.5% dextrose, while decreasing urine flow and increasing urine osmolality. This study demonstrates that the urinary excretion of immunoreactive kinins varies in relation to the urinary level of vasopressin, irrespective of urine volume and osmolality and of the urinary excretions of sodium and kininogenase. The study suggests a role for vasopressin in promoting the activity of the renal kallikrein-kinin system in the rat. PMID:6561201

Urinary sodium and potassium excretion, mortality, and cardiovascular events.

PubMed

O'Donnell, Martin; Mente, Andrew; Rangarajan, Sumathy; McQueen, Matthew J; Wang, Xingyu; Liu, Lisheng; Yan, Hou; Lee, Shun Fu; Mony, Prem; Devanath, Anitha; Rosengren, Annika; Lopez-Jaramillo, Patricio; Diaz, Rafael; Avezum, Alvaro; Lanas, Fernando; Yusoff, Khalid; Iqbal, Romaina; Ilow, Rafal; Mohammadifard, Noushin; Gulec, Sadi; Yusufali, Afzal Hussein; Kruger, Lanthe; Yusuf, Rita; Chifamba, Jephat; Kabali, Conrad; Dagenais, Gilles; Lear, Scott A; Teo, Koon; Yusuf, Salim

2014-08-14

The optimal range of sodium intake for cardiovascular health is controversial. We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

Vasopressin regulates renal calcium excretion in humans

PubMed Central

Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel

2015-01-01

Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

PubMed

Lever, Michael; McEntyre, Christopher J; George, Peter M; Slow, Sandy; Elmslie, Jane L; Lunt, Helen; Chambers, Stephen T; Parry-Strong, Amber; Krebs, Jeremy D

2014-10-01

Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.

Avian keratin disorder of Alaska black-capped chickadees is associated with Poecivirus infection

USGS Publications Warehouse

Zylberberg, Maxine; Van Hemert, Caroline R.; Handel, Colleen M.; DeRisi, Joseph L.

2018-01-01

BackgroundAvian keratin disorder (AKD) is an epizootic of debilitating beak deformities, first documented in black-capped chickadees (Poecile atricapillus) in Alaska during the late 1990s. Similar deformities have now been recorded in dozens of species of birds across multiple continents. Despite this, the etiology of AKD has remained elusive, making it difficult to assess the impacts of this disease on wild populations. We previously identified an association between infection with a novel picornavirus, Poecivirus, and AKD in a small cohort of black-capped chickadees.MethodsTo test if the association between Poecivirus and AKD holds in a larger study population, we used targeted PCR followed by Sanger sequencing to screen 124 symptomatic and asymptomatic black-capped chickadees for Poecivirus infection. We further compared the efficacy of multiple non-terminal field sampling methods (buccal swabs, cloacal swabs, fecal samples, and blood samples) for Poecivirus screening. Finally, we used both in situ hybridization and a strand-specific expression assay to localize Poecivirus to beak tissue of AKD-positive individuals and to determine if virus is actively replicating in beak tissue.ResultsPoecivirus was detected in 28/28 (100%) individuals with AKD, but only 9/96 (9.4%) asymptomatic individuals with apparently normal beaks (p < 0.0001). We found that cloacal swabs are the most sensitive of these sample types for detecting Poecivirus in birds with AKD, but that buccal swabs should be combined with cloacal swabs in evaluating the infection status of asymptomatic birds. Finally, we used both in situ hybridization and a strand-specific expression assay to localize Poecivirus to beak tissue of AKD-positive individuals and to provide evidence of active viral replication.ConclusionThe data presented here show a strong, statistically significant relationship between Poecivirus infection and AKD, and provide evidence that Poecivirus is indeed an avian virus, infecting and actively replicating in beak tissue of AKD-affected BCCH. Taken together, these data corroborate and extend the evidence for a potential causal association between Poecivirus and AKD in the black-capped chickadee. Poecivirus continues to warrant further investigation as a candidate agent of AKD.

Conservation of the fourth gene among rotaviruses recovered from asymptomatic newborn infants and its possible role in attenuation.

PubMed Central

Flores, J; Midthun, K; Hoshino, Y; Green, K; Gorziglia, M; Kapikian, A Z; Chanock, R M

1986-01-01

RNA-RNA hybridization was performed to assess the extent of genetic relatedness among human rotaviruses isolated from children with gastroenteritis and from asymptomatic newborn infants. 32P-labeled single-stranded RNAs produced by in vitro transcription from viral cores of the different strains tested were used as probes in two different hybridization assays: undenatured genomic RNAs were resolved by polyacrylamide gel electrophoresis, denatured in situ, electrophoretically transferred to diazobenzyloxymethyl-paper (Northern blots), and then hybridized to the probes under two different conditions of stringency; and denatured genomic double-stranded RNAs were hybridized to the probes in solution and the hybrids which formed were identified by polyacrylamide gel electrophoresis. When analyzed by Northern blot hybridization at a low level of stringency, all genes from the strains tested cross-hybridized, providing evidence for some sequence homology in each of the corresponding genes. However, when hybridization stringency was increased, a difference in gene 4 sequence was detected between strains recovered from asymptomatic newborn infants ("nursery strains") and strains recovered from infants and young children with diarrhea. Although the nursery strains exhibited serotypic diversity (i.e., each of the four strains tested belonged to a different serotype), the fourth gene appeared to be highly conserved. Similarly, each of the virulent strains tested belonged to a different serotype; nonetheless, there was significant conservation of sequence among the fourth genes of three of these viruses. Significantly, the conserved fourth genes of the nursery strains were distinct from the fourth gene of each of the virulent viruses. These results were confirmed and extended during experiments in which the RNA-RNA hybridization was carried out in solution and the resulting hybrids were analyzed by polyacrylamide gel electrophoresis. Under these conditions, the fourth genes of the nursery strains were closely related to each other but not to the fourth genes of the virulent viruses. Full-length hybrids did not form between the fourth genes from the nursery strains and the corresponding genes from the strains recovered from symptomatic infants and young children. Images PMID:3023685

Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir

PubMed Central

Marshall, Jason D.; Dorwart, Michael R.; Heeke, Darren S.; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H.; Eisenberg, Roselyn J.

2017-01-01

ABSTRACT Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo. In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection. PMID:28228587

Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

PubMed

Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

2017-05-01

Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection. Copyright © 2017 American Society for Microbiology.

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

PubMed

Huang, Miao-Chan; Hsueh, Thomas Y; Cheng, Yung-Yi; Lin, Lie-Chwen; Tsai, Tung-Hu

2018-06-14

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC conjugate /AUC free-form ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k BE (%) = AUC bile /AUC plasma ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

[Comparative study of infectious diseases in immigrant children from various countries].

PubMed

Huerga Aramburu, H; López-Vélez, R

2004-01-01

Immigrants have a higher risk of contracting some infectious diseases. The aim of this study was to determine and compare the morbidity profile of immigrant children according to their country of origin. We performed a descriptive study of all immigrants aged less than 14 years old who attended the Tropical Medicine Unit of the Ramon y Cajal Hospital in Madrid between 1989 and 2001. A total of 170 children were included (73 % from Africa, 19 % from Latin America, and 5 % from Asia). Seventy-five percent had at least one infectious disease (78 % of Africans and 62 % of Latin Americans) and 27 % were co-infected (> 2 pathogenic agents). The proportion of healthy children was higher (p < 0.05) among Latin Americans (21 %) than among Africans (9 %). The most frequent infectious diseases were malaria (35 %), intestinal parasites (48 %), filariasis (23 %), and viral hepatitis (19 %). Malaria, filariasis and hepatitis were more frequent in Africans than in Americans (p < 0.05). Other helminthic infections (15 %) were more frequent in Americans. In both groups intestinal parasites and tuberculosis (6 %) were prevalent. Of the 36 (21 %) asymptomatic children, 53 % had at least one infectious disease. The most frequently diagnosed diseases in Africans were intestinal parasitosis (35 %), malaria (7 %), cured hepatitis B (15 %), filariasis (12 %) and superficial mycosis (4 %). The most frequent infectious diseases in Latin Americans were intestinal parasitosis (38 %) and visceral toxocariasis (25 %). Infectious diseases and co-infections are frequent in immigrant children, even in those who are asymptomatic. We propose screening of certain infectious diseases in these children according to their country of origin and their length of residence in Spain.

Cholangiocarcinoma in Italy: A national survey on clinical characteristics, diagnostic modalities and treatment. Results from the "Cholangiocarcinoma" committee of the Italian Association for the Study of Liver disease.

PubMed

Alvaro, Domenico; Bragazzi, Maria Consiglia; Benedetti, Antonio; Fabris, Luca; Fava, Giammarco; Invernizzi, Pietro; Marzioni, Marco; Nuzzo, Gennaro; Strazzabosco, Mario; Stroffolini, Tommaso

2011-01-01

Very few studies assessed cholangiocarcinoma clinical characteristics. To evaluate the clinical characteristics of intra-hepatic (IH) and extra-hepatic (EH)-CCA. We performed a national survey based on a questionnaire. 218 cholangiocarcinomas were observed (47% EH-CCA, 53% IH-CCA) with an age at the diagnosis higher for EH-CCA. Coexistence of cirrhosis or viral cirrhosis was more frequent in IH-CCA than EH-CCA. An incidental asymptomatic presentation occurred in 28% of IH-CCA vs 4% EH-CCA whilst, 74% EH-CCA vs 28% IH-CCA presented with jaundice. 91% of IH-CCA presented as a single intra-hepatic mass, whilst 50% of EH-CCA was peri-hilar. In the diagnostic work-up, 70% of all cholangiocarcinoma cases received at least 3 different imaging procedures. Tissue-proven diagnosis was obtained in 80% cholangiocarcinoma. Open surgery with curative intent was performed in 45% of IH-CCA and 29% EH-CCA. 18% IH-CCA vs 4% EH-CCA did not received treatment. In Italy IH-CCA is managed as frequently as EH-CCA. In comparison to EH-CCA, IH-CCA occurs at younger age and is more frequently associated with cirrhosis and with an incidental asymptomatic presentation. In contrast, most EH-CCAs are jaundiced at the diagnosis. Cholangiocarcinoma diagnostic management is cost- and time-consuming with curative surgical treatment applicable more frequently in IH-CCA. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1.

PubMed

Manuel, Sharrón L; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K; Gardner, Jay; Betts, Michael R; Jain, Pooja

2013-10-01

The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. Quality of cytotoxic T lymphocytes (CTLs) is being increasingly associated with the outcome of persistent HTLV-1 infection. In this respect, a patient cohort (from HTLV-1 endemic region) consisting of seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8(+) T cells polyfunctionality in response to the viral antigen Tax. Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8(+) T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8(+) T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy / therapeutic vaccine against HTLV-mediated diseases.

Molecular characterization of double-stranded RNA virus in Trichomonas vaginalis Egyptian isolates and its association with pathogenicity.

PubMed

El-Gayar, Eman K; Mokhtar, Amira B; Hassan, Wael A

2016-10-01

Trichomoniasis is a common human sexually transmitted infection caused by Trichomonas vaginalis. The parasite can be infected with double-stranded RNA viruses (TVV). This viral infection may have important implications on trichomonal virulence and disease pathogenesis. This study aimed to determine the prevalence of T. vaginalis virus among isolates obtained from infected (symptomatic and asymptomatic) women in Ismailia City, Egypt, and to correlate the virus-infected isolates with the clinical manifestations of patients. In addition, the pathogenicity of TVV infected isolates on mice was also evaluated. T. vaginalis isolates were obtained from symptomatic and asymptomatic female patients followed by axenic cultivation in Diamond's TYM medium. The presence of T. vaginalis virus was determined from total extraction of nucleic acids (DNA-RNA) followed by reverse transcriptase-PCR. Representative samples were inoculated intraperitoneally in female albino/BALB mice to assess the pathogenicity of different isolates. A total of 110 women were examined; 40 (36.3 %) samples were positive for T. vaginalis infection. Of these 40 isolates, 8 (20 %) were infected by TVV. Five isolates contained TVV-2 virus species, and the remaining three isolates were infected withTVV-4 variant. A significant association was found between the presence of TVV and particular clinical manifestations of trichomoniasis. Experimental mice infection showed varying degrees of pathogenicity. This is the first report on T. vaginalis infection by TVV in Egypt. The strong association detected between TVV and particular clinical features of trichomoniasis and also the degree of pathogenicity in experimentally infected mice may indicate a possible clinical significance of TVV infection of T. vaginalis isolates.

Virologic and Immunologic Characteristics in Mature Ducks with Acute Duck Hepatitis A Virus 1 Infection.

PubMed

Mao, Sai; Wang, Mingshu; Ou, Xumin; Sun, Di; Cheng, Anchun; Zhu, Dekang; Chen, Shun; Jia, Renyong; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Zhao, Xinxin; Chen, Xiaoyue

2017-01-01

Duck hepatitis A virus 1 (DHAV-1) infection in mature ducks has previously been proposed as a small-animal model for human hepatitis A. However, basic research on the outcome of DHAV-1 infection in mature ducks is limited. Here, we examined the course of viremia, the characteristics of antibody responses, and the profiles of plasma cytokines in mature ducks infected with DHAV-1. During the course of infection, the viremia was detectable soon after infection and persisted for 196 days, however, the ducks presented as clinically asymptomatic. Specific and timely immunoglobulin G (IgG), IgM, and IgA1 responses were elicited. At the same time, extensive inhibition of viral replication was observed with increasing IgG concentration. With respect to pattern-recognition receptors, TLR-7 was mainly involved in triggering the innate defense against the DHAV-1 infection. In addition, plasma immune analytes were measured and were determined to have bidirectional roles in virus clearance. It was concluded that DHAV-1 spreads quickly in blood. The spontaneous clearance of DHAV-1 during asymptomatic infection in mature ducks depends on the cooperation of timely antibody responses and alert innate immune responses. Moreover, the delayed clearance may be associated with a weak interferon-γ-producing CD8+ T cell response. This study allows us to reveal the mechanism of clearance and persistence of DHAV-1 infection in mature ducks. We anticipate that it will provide a basis for future studies focused on defining the nature mechanisms involved in the clearance and persistence of human hepatitis virus.

Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment

PubMed Central

Vázquez-Santiago, Fabián; García, Yashira; Rivera-Román, Ivelisse; Noel, Richard J.; Wojna, Valerie; Meléndez, Loyda M.; Rivera-Amill, Vanessa

2015-01-01

Objective Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1–infected people. HIV-1 envelope (env) genetic heterogeneity has been detected within the central nervous system (CNS) of individuals with ANI. Changes within env determine co-receptor use, cellular tropism, and neuropathogenesis. We hypothesize that compartmental changes are associated with HIV-1 env C2V4 during ANI and sought to analyze paired HIV-1 env sequences from plasma and cerebrospinal fluid (CSF) of a female subject undergoing long-term cART. Methods Paired plasma and CSF samples were collected at 12-month intervals and HIV-1 env C2V4 was cloned and sequenced. Results Phylogenetic analysis of paired samples consistently showed genetic variants unique to the CSF. Phenotypic prediction showed CCR5 (R5) variants for all CSF-derived sequences and showed minor X4 variants (or dual-tropic) in the plasma at later time points. Viral compartmentalization was evident throughout the study, suggesting that the occurrence of distinctive env strains may contribute to the neuropathogenesis of HAND. Conclusions Our study provides new insights about the genetic characteristics within the C2V4 of HIV-1 env that persist after long-term cART and during the course of persistent ANI. PMID:26167513

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1

PubMed Central

Manuel, Sharrón L.; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K.; Gardner, Jay; Goedert, James J.; Betts, Michael R.; Jain, Pooja

2013-01-01

Purpose & methods The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. In this respect, a patient cohort from HTLV-1 endemic region that included seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8+ T cells polyfunctionality in response to the viral antigen Tax. Results Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8+ T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8+ T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Conclusions Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy and therapeutic vaccine against HTLV-mediated diseases. PMID:23888327

Bilirubin metabolism in the fetus

PubMed Central

Bernstein, Ralph B.; Novy, Miles J.; Piasecki, George J.; Lester, Roger; Jackson, Benjamin T.

1969-01-01

Bilirubin metabolism was studied in dog and monkey fetuses. Bilirubin-3H was administered to fetal animals in utero by prolonged intravenous infusion. Fetal plasma disappearance, hepatic uptake, biliary excretion, and placental transfer of bilirubin-3H were measured. Bilirubin metabolism and excretion in the fetus was much less efficient than in the adult. Fetal plasma levels of tritium were elevated for prolonged periods, and the combined rate of placental and fetal hepatic excretion was lower than normal values for adult hepatic excretion. Species differences were noted. Hepatic conjugation and excretion appeared to be the primary mechanism of fetal metabolism in the dog. In contrast, the amounts of conjugated bilirubin-3H excreted in fetal monkey bile were negligible. Small amounts of 3H-labeled bilirubin derivatives were excreted in fetal bile, but 10 times as much of the administered material was transferred intact across the placenta and excreted by the maternal liver. The relationship of this functional difference to known anatomic and biochemical species differences is discussed. Preliminary observations on alternate routes of fetal bilirubin metabolism were obtained. Images PMID:4980771

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.

PubMed

Green, T; Dow, J; Foster, J R; Hext, P M

1998-05-15

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.

The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum creatinine rats: Can creatinine predict renal tubular elimination?

PubMed

Ma, Yan-Rong; Zhou, Yan; Huang, Jing; Qin, Hong-Yan; Wang, Pei; Wu, Xin-An

2018-03-01

The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian rhythmicity of the urinary excretion of mercury, potassium and catecholamines in unconventional shift-work systems.

PubMed

Vokac, Z; Gundersen, N; Magnus, P; Jebens, E; Bakka, T

1980-09-01

The round the clock urinary excretion rates of mercury were assessed for two series of unconventional patterns of activity and sleep in subjects who were not exposed to occupational, medical, or other obvious sources of mercury. In the first series the urine was collected in 3-h periods from six subjects during the first and last 2 d of a four-week, continuous 6-h shift (car ferry, watches either 0800--1400 and 2000--0200 or 1400--2000 and 0200--0800). In the second series the urine was collected in 4-h periods from five subjects working an 8-h experimental rotation shift compressed into 5 d (work two mornings--8-h interval--work two nights--8-h interval--work two afternoons). The mean daily excretion rate of the 11 subjects (48 investigation days, 334 urine samples) was 14.5 pmol of mercury/min (range 5.5--24.4 pmol of mercury/min). The mercury excretion oscillated regularly during 24 h by +/- 20--25% of the individual's daily mean excretion rates. The peak excretion rates were found at 0652 in the first and 0642 in the second series (cosinor treatment). Due to the circadian rhythm the mean 24-h excretion rates were best represented (correlation coefficient 0.92) by analyses of urine produced around noon (spot samples, collection periods 1100--1400 and 1000-1400, respectively). The circadian oscillations of mercury excretion were not influenced by the widely different and varying activity-sleep patterns of the two series. The rhythmicity of potassium excretion (peaks at around 1400) was more irregular. The stable oscillations of mercury excretion contrasted most with the excretion of adrenaline and noradrenaline, which, without losing the basic 24-h rhythmicity, closely followed the unconventional patterns of activity and sleep.

Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection.

PubMed

Bull, Rowena A; Leung, Preston; Gaudieri, Silvana; Deshpande, Pooja; Cameron, Barbara; Walker, Melanie; Chopra, Abha; Lloyd, Andrew R; Luciani, Fabio

2015-05-01

The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required. A major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish the acute infection. This study was made possible through the availability of specimens from a unique cohort of asymptomatic primary infection cases in whom the first available viremic samples were collected approximately 3 weeks postinfection and at regular intervals thereafter. The study included detailed examination of both the evolution of the viral population and the host cellular immune responses against the T/F viruses. The findings here provide the first evidence of host cellular responses targeting T/F variants and imposing a strong selective force toward viral escape. The results of this study provide useful insight on how virus escapes the host response and consequently on future analysis of vaccine-induced immunity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Marine, freshwater and aerially acclimated mangrove rivulus (Kryptolebias marmoratus) use different strategies for cutaneous ammonia excretion

PubMed Central

Cooper, Christopher A.; Wilson, Jonathan M.

2013-01-01

Rhesus (Rh) glycoproteins are ammonia gas (NH3) channels known to be involved in ammonia transport in animals. Because of the different osmoregulatory and ionoregulatory challenges faced by teleost fishes in marine and freshwater (FW) environments, we hypothesized that ammonia excretion strategies would differ between environments. Also, we hypothesized that cutaneous NH3 volatilization in air-acclimated fish is facilitated by base secretion. To test these hypotheses, we used the skin of the euryhaline amphibious mangrove rivulus (Kryptolebias marmoratus). The skin excretes ammonia and expresses Rh glycoproteins. Serosal-to-mucosal cutaneous ammonia flux was saturable (0–16 mmol/l ammonia, Km of 6.42 mmol/l). In FW, ammonia excretion increased in response to low mucosal pH but decreased with pharmacological inhibition of Na+/H+ exchangers (NHE) and H+ ATPase. Conversely, in brackish water (BW), lowering the mucosal pH significantly decreased ammonia excretion. Inhibitors of NHE also decreased ammonia excretion in BW fish. Immunofluorescence microscopy demonstrated that both the Rh isoform, Rhcg1, and NHE3 proteins colocalized in Na+/K+ ATPase expressing mitochondrion-rich cells in the gills, kidney, and skin. We propose that the mechanisms of cutaneous ammonia excretion in FW K. marmoratus are consistent with the model for branchial ammonia excretion in FW teleost fish. NH4+ excretion appeared to play a stronger role in BW. NH4+ excretion in BW may be facilitated by apical NHE and/or diffuse through paracellular pathways. In aerially acclimated fish, inhibition of NHE and H+ ATPase, but not the Cl−/HCO3− exchanger, significantly affected cutaneous surface pH, suggesting that direct base excretion is not critical for NH3 volatilization. Overall, K. marmoratus use different strategies for excreting ammonia in three different environments, FW, BW, and air, and Rh glycoproteins and NHE are integral to all. PMID:23389109

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

PubMed

Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by albuminuria. © 2017 The Author(s)Published by S. Karger AG, Basel.

Antimicrobial Treatment of Asymptomatic Bacteriuria in Healthy Ambulatory Subjects.

ERIC Educational Resources Information Center

Zhanel, George G.

1990-01-01

The treatment of urinary tract infections is discussed. Specific issues considered include the definition of asymptomatic bacteriuria, the prevalence of asymptomatic bacteriuria, the controversies of who should be treated, and antimicrobial treatment of asymptomatic bacteriuria. (MLW)

Asymptomatic bacteriuria in pregnancy.

PubMed

Smaill, Fiona

2007-06-01

Screening for asymptomatic bacteriuria is a standard of obstetrical care and is included in most antenatal guidelines. There is good evidence that treatment of asymptomatic bacteriuria will decrease the incidence of pyelonephritis. All pregnant women should be screened for asymptomatic bacteriuria, and there are no new data that would indicate otherwise. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of preterm delivery or low birth weight, but the methodological quality of the studies means any conclusion about the strength of this association needs to be drawn cautiously. A better understanding of the mechanism by which treatment of asymptomatic bacteriuria could prevent preterm delivery is needed. While several rapid screening tests have been evaluated, none perform adequately to replace urine culture for detecting asymptomatic bacteriuria. Until there are data from well-designed trials that establish the optimal duration of therapy for asymptomatic bacteriuria, standard treatment courses are recommended.

S-phase arrest after vincristine treatment may promote hepatitis B virus replication

PubMed Central

Xu, Lei; Tu, Zeng; Xu, Ge; Hu, Jie-Li; Cai, Xue-Fei; Zhan, Xing-Xing; Wang, Yu-Wei; Huang, Yuan; Chen, Juan; Huang, Ai-Long

2015-01-01

AIM: To observe the effect of vincristine on hepatitis B virus (HBV) replication in vitro and to study its possible mechanisms. METHODS: Vincristine was added to the cultures of two cell lines stably expressing HBV. Then, the levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg) in the supernatants or cytoplasm were examined using by enzyme-linked immunosorbent assay and Western blot. The HBV pregenome RNA (pgRNA) was detected using reverse transcription-PCR and real-time fluorescent quantitative PCR (RT-qPCR), and viral DNA was detected using Southern blot and RT-qPCR. Cell proliferation after drug treatment was detected using the BrdU incorporation test and the trypan blue exclusion assay. Cell cycle and cell apoptosis were examined using flow cytometry and Western blot. RESULTS: Vincristine up-regulated HBV replication directly in vitro in a dose-dependent manner, and 24-h exposure to 0.1 μmol/L vincristine induced more than 4-fold and 3-fold increases in intracellular HBV DNA and the secretion of viral DNA, respectively. The expression of HBV pgRNA, intracellular HBsAg and HBcAg, and the secretion of HBeAg were also increased significantly after drug treatment. Most importantly, vincristine promoted the cell excretion of HBV nucleocapsids instead of HBV Dane particles, and the nucleocapsids are closely related to the HBV pathogenesis. Furthermore, vincristine inhibited the proliferation of cells stably expressing HBV. The higher the concentration of the drug, the more significant the inhibition of the cell proliferation and the stronger the HBV replication ability in cells. Flow cytometry indicated that cell cycle arrest at S-phase was responsible for the cell proliferation inhibition. CONCLUSION: Vincristine has a strong stimulatory effect on HBV replication and induces cell cycle arrest, and cell proliferation inhibition may be conducive to viral replication. PMID:25663769

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

PubMed

van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

2016-01-01

Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

Research progress of asymptomatic bacteriuria before arthroplasty: A systematic review.

PubMed

Zhang, Qingyu; Liu, Lihua; Sun, Wei; Gao, Fuqiang; Cheng, Liming; Li, Zirong

2018-02-01

A high prevalence of asymptomatic bacteriuria exists in patients prior to arthroplasty, and urinary tract infection is considered to be a source of postoperative superficial wound and prosthetic joint infections. There is no consensus whether to screen for and treat asymptomatic bacteriuria before arthroplasty. To summarize the association between asymptomatic bacteriuria and complications after arthroplasty and to evaluate the clinical benefits of treating asymptomatic bacteriuria prior to arthroplasty. We systematically searched PubMed, Embase, and the Cochrane Library to retrieve potentially eligible articles. By screening the titles and abstracts of retrieved records and then reading the full texts of the remaining papers, we finally included 8 English-language articles in this systematic review. Asymptomatic bacteriuria prior to arthroplasty is significantly associated with an increased occurrence of postoperative prosthetic joint and superficial wound infections. However, there is little evidence for direct or hematogenous seeding of urinary infections, and treating asymptomatic bacteriuria before arthroplasty did not decrease the incidence of postoperative infectious complications. Asymptomatic bacteriuria is not a contraindication for arthroplasty, and the practice of routine preoperative screening for and treatment of asymptomatic bacteriuria should not be continued.

The urinary excretion of assayable vitamin B12 and radioactivity after parenteral 58Co B12 in man

PubMed Central

Adams, J. F.

1961-01-01

Evidence is presented that after injection of radioactive vitamin B12 in man, there is a close correlation between the amount of radioactivity excreted and the amount of assayable vitamin B12 excreted, and thus that the amount of radioactivity excreted is a true measure of the vitamin B12 excreted. The possible reasons for this occurrence are discussed and it is suggested that in the body vitamin B12 does not exist as such but as an analogue or active derivative. PMID:13681399

Night-rest urinary catecholamine excretion in relation to aspects of free time, work and background data in a teacher group.

PubMed

Kinnunen, U; Vihko, V

1991-01-01

Free time, work and background data were related to night-rest catecholamine excretion rates in a teacher group (n = 137) during an autumn term. The explained interindividual variance increased slightly towards the end of the term. Adrenaline excretion was predicted better than noradrenaline, notedly by coffee consumption, amount of physical activity, and subjective stress feelings which explained 16% of the variance in adrenaline excretion during night rest. However, the results indicated that the differences in catecholamine excretion during night rest remained mostly unpredictable.

Asymptomatic bacteriuria in adults.

PubMed

Colgan, Richard; Nicolle, Lindsay E; McGlone, Andrew; Hooton, Thomas M

2006-09-15

A common dilemma in clinical medicine is whether to treat asymptomatic patients who present with bacteria in their urine. There are few scenarios in which antibiotic treatment of asymptomatic bacteruria has been shown to improve patient outcomes. Because of increasing antimicrobial resistance, it is important not to treat patients with asymptomatic bacteriuria unless there is evidence of potential benefit. Women who are pregnant should be screened for asymptomatic bacteriuria in the first trimester and treated, if positive. Treating asymptomatic bacteriuria in patients with diabetes, older persons, patients with or without indwelling catheters, or patients with spinal cord injuries has not been found to improve outcomes.

Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high inmore » most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.« less

Desmopressin resistant nocturnal polyuria secondary to increased nocturnal osmotic excretion.

PubMed

Dehoorne, Jo L; Raes, Ann M; van Laecke, Erik; Hoebeke, Piet; Vande Walle, Johan G

2006-08-01

We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Phosphate Starvation Inducible Metabolism in Lycopersicon esculentum1

PubMed Central

Goldstein, Alan H.; Baertlein, Dawn A.; McDaniel, Robert G.

1988-01-01

Both tomato (Lycopersicon esculentum cv VF 36) plants and suspension cultured cells show phosphate starvation inducible (psi) excretion of acid phosphatase (Apase). Apase excretion in vitro was proportional to the level of exogenous orthophosphate (Pi). Intracellular Apase activity remained the same in both Pi-starved and sufficient cells, while Apase excreted by the starved cells increased by as much as six times over unstressed control cells on a dry weight basis. At peak induction, 50% of total Apase was excreted. Ten day old tomato seedlings grown without Pi showed slight growth reduction versus unstressed control plants. The Pi-depleted roots showed psi enhancement of Apase activity. Severely starved seedlings (17 days) reached only one-third of the biomass of unstressed control plants but, because of a combination of psi Apase excretion by roots and a shift in biomass to this organ, they excreted 5.5 times the Apase activity of the unstressed control. Observed psi Apase excretion may be part of a phosphate starvation rescue system in plants. The utility of the visible indicator dye 5-bromo-4-chloro-3-indolyl-phosphate-p-toluidine as a phenotypic marker for plant Apase excretion is demonstrated. Images Fig. 5 PMID:16666212

Sodium and potassium urinary excretion levels of preschool children: Individual, daily, and seasonal differences.

PubMed

Yasutake, Kenichiro; Nagafuchi, Mikako; Izu, Ryoji; Kajiyama, Tomomi; Imai, Katsumi; Murata, Yusuke; Ohe, Kenji; Enjoji, Munechika; Tsuchihashi, Takuya

2017-06-01

In this study, the authors measured sodium and potassium concentrations in spot urine samples of preschool children on multiple days, and evaluated individual, daily, and seasonal effects. A total of 104 healthy preschool children aged 4 to 5 years were studied. Urine samples were collected from the first urine of the day after waking for three consecutive days (Monday-Wednesday) four times a year (spring, summer, autumn, winter). The authors estimated the daily urine volume as 500 mL and daily creatinine excretion as 300 mg, and used these to calculate daily sodium and potassium excretion levels. Daily sodium and potassium excretion levels and sodium to potassium ratios were highly variable. The coefficient variant in the children's excretion levels were also high within and between individuals. Sodium excretion levels and sodium to potassium ratios were higher on Monday (weekend sodium intakes) than Tuesday. Season had no effect on sodium or potassium excretion levels, but the sodium to potassium ratio was higher in summer than in winter. In conclusion, levels of urinary sodium excretion are comparatively high and those of potassium are low in preschool students, with high variability within and between individuals. ©2017 Wiley Periodicals, Inc.

Long-term infection and vertical transmission of a gammaretrovirus in a foreign host species.

PubMed

Sakuma, Toshie; Tonne, Jason M; Malcolm, Jessica A; Thatava, Tayaramma; Ohmine, Seiga; Peng, Kah-Whye; Ikeda, Yasuhiro

2012-01-01

Increasing evidence has indicated natural transspecies transmission of gammaretroviruses; however, viral-host interactions after initial xeno-exposure remain poorly understood. Potential association of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome has attracted broad interests in this topic. Although recent studies have indicated that XMRV is unlikely a human pathogen, further understanding of XMRV xenoinfection would allow in vivo modeling of the initial steps of gammaretroviral interspecies transmission, evolution and dissemination in a new host population. In this study, we monitored the long-term consequences of XMRV infection and its possible vertical transmission in a permissive foreign host, wild-derived Mus pahari mice. One year post-infection, XMRV-infected mice showed no notable pathological changes, while proviral DNA was detected in three out of eight mice. XMRV-infected mice remained seropositive throughout the study although the levels of gp70 Env- and p30 capsid-specific antibodies gradually decreased. When vertical XMRV transmission was assessed, no viremia, humoral immune responses nor endogenization were observed in nine offspring from infected mothers, yet one offspring was found PCR-positive for XMRV-specific sequences. Amplified viral sequences from the offspring showed several mutations, including one amino acid deletion in the receptor binding domain of Env SU. Our results therefore demonstrate long-term asymptomatic infection, low incidence of vertical transmission and limited evolution of XMRV upon transspecies infection of a permissive new host, Mus pahari.

Successful topical respiratory tract immunization of primates against Ebola virus.

PubMed

Bukreyev, Alexander; Rollin, Pierre E; Tate, Mallory K; Yang, Lijuan; Zaki, Sherif R; Shieh, Wun-Ju; Murphy, Brian R; Collins, Peter L; Sanchez, Anthony

2007-06-01

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

PubMed Central

Edén, Arvid; Marcotte, Thomas D.; Heaton, Robert K.; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W.; Grant, Igor; Letendre, Scott L.; Gisslén, Magnus

2016-01-01

Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). Design and Methods We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Results Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Conclusions Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. PMID:27295036

Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment.

PubMed

Edén, Arvid; Marcotte, Thomas D; Heaton, Robert K; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W; Grant, Igor; Letendre, Scott L; Gisslén, Magnus

2016-01-01

Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies.

Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys

PubMed Central

Klatt, Nichole R.; Villinger, Francois; Bostik, Pavel; Gordon, Shari N.; Pereira, Lara; Engram, Jessica C.; Mayne, Ann; Dunham, Richard M.; Lawson, Benton; Ratcliffe, Sarah J.; Sodora, Donald L.; Else, James; Reimann, Keith; Staprans, Silvija I.; Haase, Ashley T.; Estes, Jacob D.; Silvestri, Guido; Ansari, Aftab A.

2008-01-01

Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30–45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs. PMID:18497876

Cerebral embolization in asymptomatic versus symptomatic patients after carotid stenting.

PubMed

Tulip, Hans H; Rosero, Eric B; Higuera, Adriana J; Ilarraza, Adriana; Valentine, R James; Timaran, Carlos H

2012-12-01

Previous studies have investigated the development of new ischemic brain lesions on diffusion-weighted magnetic resonance imaging (DW-MRI) after carotid artery stenting (CAS). The rate of ischemic brain injury after CAS for asymptomatic stenosis has not been extensively studied but is presumed to be less likely than in symptomatic patients. This study assessed the occurrence of cerebral embolization after CAS for asymptomatic vs symptomatic carotid stenosis. During an 18-month period, 40 patients undergoing CAS under filter embolic protection were prospectively evaluated. Transcranial Doppler (TCD) during CAS and preprocedural and 24-hour postprocedural DW-MRI were used to assess cerebral embolization. Univariate and nonparametric analyses were used to compare differences in cerebral embolization after CAS in asymptomatic and symptomatic patients. CAS was performed for 23 asymptomatic (58%) and 17 symptomatic (42%) carotid stenoses. The median microembolic counts detected by TCD were 285 (interquartile range [IQR], 182-376) for asymptomatic and 313 (IQR, 170-426) for symptomatic carotid stenosis (P=.6). DW-MRI was available for assessment in 20 asymptomatic and 14 symptomatic patients. New acute cerebral emboli detected with DW-MRI occurred in 10 asymptomatic (50%) and 7 symptomatic patients (50%) undergoing CAS (P=.9). The ipsilateral and total median number of DW-MRI lesions between groups were not statistically significantly different at, respectively, 1 (IQR, 0-2.5) and 1.5 (IQR, 0-3) for asymptomatic vs 0.5 (IQR, 0-2) and 0.5 (IQR, 0-3) for symptomatic carotid stenosis (P>.5). One asymptomatic patient sustained a minor stroke after CAS. No new neurologic events occurred in symptomatic patients. The 30-day stroke-death rate was 2.5% in this series. Cerebral embolization, as detected by TCD and DW-MRI, occurs with a similar frequency after CAS for asymptomatic and symptomatic carotid stenosis. Because postprocedural ischemic brain injury occurs in approximately half of asymptomatic patients, the safety of CAS under filter embolic protection for asymptomatic carotid stenosis is uncertain and warrants further study. Published by Mosby, Inc.

Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus.

PubMed

Krakowka, S; Ellis, J A; Meehan, B; Kennedy, S; McNeilly, F; Allan, G

2000-05-01

One-day-old gnotobiotic piglets were inoculated intranasally with in vitro passaged porcine circovirus 1 (PCV-1), PCV-2, and porcine parvovirus (PPV) alone or in combination (PCV-1/PCV-2, PCV-1/PPV, and PCV-2/PPV). Piglets were evaluated for 1) the development of porcine postweaning multisystemic wasting syndrome (PMWS), 2) distribution of viral antigens by immunochemistry, and 3) viremia and the presence of viral DNA in nasal and ocular secretions and feces. All single agent-infected piglets and piglets infected with PCV-1/PCV-2 or PCV-1/PPV were clinically asymptomatic. They were transiently viremic and seroconverted to homologous virus(es). At termination of the study on postinfection day (PID) 35, microscopic lesions were restricted to focal inflammatory cell infiltrates in livers and myocardia. One piglet given PCV-1/PPV was PPV viremic for 2 weeks after infection and had lymphangiectasia of the spiral and descending colon associated with granulomatous inflammation. All four PCV-2/PPV-inoculated piglets developed PMWS, characterized by sudden onset of depression and anorexia, icterus, and submucosal edema. One piglet became moribund on PID 27, and the remaining three piglets were euthanatized between PID 27 and PID 30 because of severe disease. Lymph nodes were small and the livers were mottled. Disseminated angiocentric granulomatous inflammation was present in all tissues examined except the brain. Multiple lightly basophilic intracytoplasmic inclusion bodies were identified in macrophages and histiocytes. PCV-2 antigen was widely distributed within macrophages; PPV antigen was sparse. Hepatocellular necrosis and bile retention were prominent. PCV-2 DNA was identified in ocular, fecal, and nasal secretions. Terminal sera contained antibodies to PPV (4/4) and PCV-2 (3/ 4). Production of PMWS in gnotobiotic swine appears to require PCV-2 and additional infectious agents such as PPV for full disease expression in gnotobiotic piglets.

Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression.

PubMed

Tovo, Pier-Angelo; Calitri, Carmelina; Scolfaro, Carlo; Gabiano, Clara; Garazzino, Silvia

2016-01-28

The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques

PubMed Central

Moncla, Louise H.; Weiler, Andrea M.; Barry, Gabrielle; Weinfurter, Jason T.; Dinis, Jorge M.; Charlier, Olivia; Lauck, Michael; Bailey, Adam L.; Wahl-Jensen, Victoria; Nelson, Chase W.; Johnson, Joshua C.; Caì, Yíngyún; Goldberg, Tony L.; O'Connor, David H.; Jahrling, Peter B.

2016-01-01

ABSTRACT Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crab-eating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species. IMPORTANCE Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse pathogenic phenotypes, these viruses may also exhibit distinct patterns of within-host evolution both in vitro and in vivo. PMID:27974564

[Seroprevalence of antibodies against hepatitis A virus and hepatitis B virus in nonvaccinated adult population over 40 years of age].

PubMed

Chlíbek, R; Cecetková, B; Smetana, J; Prymula, R; Kohl, I

2006-08-01

To determine prevalence rates of antibodies against hepatitis A virus (HAV) and hepatitis B virus (HBV) in the general adult male and female population over 40 years of age with no history of viral hepatitis A (VHA) and viral hepatitis B (VHB) who have never been vaccinated against hepatitis and to assess the cost-effectiveness of the pre-vaccination serological screening. In 2003-2004, a total of 972 persons of three age categories: 41-50 years, 51-60 years, 61 and more years, were screened. Persons with a history of VHA and/or VHB and those who had been vaccinated against hepatitis were not included in the study. The following four indicators were determined from a 5 ml specimen of whole venous blood by electrochemiluminiscence assay: total anti-HAV antibodies, total anti-HBc antibodies, anti-HBs antibodies and HBsAg, as the most suitable markers of experienced hepatitis or previous vaccination. The prevalence rates of anti-HAV antibodies were lower in females compared to males for all of the three age categories. These antibodies were detected in 16.8%, 52.9% and 77.5% of 41-50-year-olds, 51-60-year-olds and > or = 61-year-olds, respectively. The total prevalence rate for the three age groups was 61.6%. The anti-HBc antibody seroprevalence rates were 1.9%, 5.3% and 6.1%, respectively. The results show high prevalence of VHA in higher age groups. Such a high seroprevalence of antibodies in nonvaccinated persons with no history of viral hepatitis is suggestive of a very frequent incidence of asymptomatic infection. For this reason, the prevaccination screening of anti-HAV antibodies is cost-effective in the population over 50 years of age but is not justified in persons under 40 years of age. Prevaccination screening for anti-HBc antibodies appears not to be cost-effective regardless of age in view of their low prevalence in the Czech population.

Asymptomatic bacteriuria.

PubMed

Nicolle, Lindsay E

2014-02-01

Asymptomatic bacteriuria is a common finding. Inappropriate antimicrobial treatment of asymptomatic bacteriuria has been identified as a major issue for antimicrobial stewardship programs. This review summarizes and evaluates recent studies which extend our knowledge of the occurrence, management, and outcomes of bacteriuria. The reported prevalence of bacteriuria is higher in some developing countries than generally reported for developed countries, but reasons for this remain unclear. Clinical studies of young women, renal transplant patients, and patients undergoing minor nontraumatic urologic procedures confirm that treatment of asymptomatic bacteriuria for these populations is not beneficial, and may be harmful. There is also no benefit for treatment of asymptomatic bacteriuria prior to orthopedic surgery to decrease postoperative surgical site infection. Studies continue to report substantial inappropriate antimicrobial use for treatment of asymptomatic bacteriuria. Recent publications confirm that asymptomatic bacteriuria is benign in most patients. Management strategies for pregnant women with recurrent bacteriuria require further clarification. There is a continuing problem with inappropriate treatment of asymptomatic bacteriuria, and sustainable strategies to optimize antimicrobial use for this problem are needed.

Research progress of asymptomatic bacteriuria before arthroplasty

PubMed Central

Zhang, Qingyu; Liu, Lihua; Sun, Wei; Gao, Fuqiang; Cheng, Liming; Li, Zirong

2018-01-01

Abstract Background: A high prevalence of asymptomatic bacteriuria exists in patients prior to arthroplasty, and urinary tract infection is considered to be a source of postoperative superficial wound and prosthetic joint infections. There is no consensus whether to screen for and treat asymptomatic bacteriuria before arthroplasty. Objective: To summarize the association between asymptomatic bacteriuria and complications after arthroplasty and to evaluate the clinical benefits of treating asymptomatic bacteriuria prior to arthroplasty. Method: We systematically searched PubMed, Embase, and the Cochrane Library to retrieve potentially eligible articles. By screening the titles and abstracts of retrieved records and then reading the full texts of the remaining papers, we finally included 8 English-language articles in this systematic review. Results: Asymptomatic bacteriuria prior to arthroplasty is significantly associated with an increased occurrence of postoperative prosthetic joint and superficial wound infections. However, there is little evidence for direct or hematogenous seeding of urinary infections, and treating asymptomatic bacteriuria before arthroplasty did not decrease the incidence of postoperative infectious complications. Conclusion: Asymptomatic bacteriuria is not a contraindication for arthroplasty, and the practice of routine preoperative screening for and treatment of asymptomatic bacteriuria should not be continued. PMID:29443741

Tenofovir disoproxil fumarate-associated hypophosphatemia as determined by fractional excretion of filtered phosphate in HIV-infected patients.

PubMed

Cheng, Chien-Yu; Chang, Shu-Yin; Lin, Mei-Hui; Ku, Shin-Yen; Sun, Na-Lee; Cheng, Shu-Hsing

2016-11-01

Tenofovir disoproxil fumarate (TDF) -containing regimens have been associated with nephrotoxicity and hypophosphatemia in HIV-infected patients. The objective of this study was to assess the possible risk factors for hypophosphatemia and evaluate the relationship between fractional excretion of filtered phosphate (FePi) and hypophosphatemia in TDF users. Patients were enrolled in a prospective cohort study between January 2011 and December 2014. We classified experienced HIV-infected patients (individuals maintained on antiretroviral therapy (ART) for 6 months or more) and naïve patients into 3 treatment groups: TDF-containing ART (group 1), non-TDF-containing ART (never received TDF or had not received TDF in the past 6 months; group 2) and naive to antiretroviral therapy (group 3). Specimens from each individual were assessed for serum phosphate, serum creatinine, urine phosphate, and urine creatinine. Multivariable logistic regression was performed to control for the following variables measured at baseline: eGFR, age, sex, sexual orientation, injection drug use (IDUs), HIV-RNA viral load, and CD4 cell count. The frequency of hypophosphatemia in groups 1, 2, and 3 was 20.2%, 7.2%, and 14.6%, respectively (P = 0.002). FePi above 10% also was significantly associated with hypophosphatemia (P = 0.003; adjusted odds ratio = 2.54). Patients with elevated CD4 cell counts (>500 cells/μL) exhibited a lower risk of hypophosphatemia (P = 0.002; adjusted odds ratio = 0.35). Hypophosphatemia is a multifactorial etiology; FePi was confirmed as a suggested method to predict the risk of hypophosphatemia in TDF users. Clinical Trial Number: TYGH103011. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis.

PubMed

Huang, Fen; Li, Yunlong; Yu, Wenhai; Jing, Shenrong; Wang, Jue; Long, Feiyan; He, Zhanlong; Yang, Chenchen; Bi, Yanhong; Cao, Wentao; Liu, Chengbo; Hua, Xiuguo; Pan, Qiuwei

2016-08-01

Hepatitis E virus (HEV) represents the main cause of acute hepatitis worldwide. HEV infection in immunocompromised patients involves a high risk for the development of chronic hepatitis. Because HEV is recognized as a zoonotic pathogen, it is currently believed that swine is the primary reservoir. However, this is not sufficient to justify the strikingly high seroprevalence of HEV in both developing and Western countries. Thus, this study aimed to identify new zoonotic sources that bear a high risk of transmission to humans. We collected fecal, blood, and milk samples of cows in a typical rural region of Yunnan Province in southwest China, where mixed farming of domestic animals is a common practice. HEV RNA was quantified by quantitative real-time polymerase chain reaction, and the whole genome was sequenced. HEV infectivity was assessed in rhesus macaques. We found a high prevalence of active HEV infection in cows as determined by viral RNA positivity in fecal samples. Surprisingly, we discovered that HEV is excreted into milk that is produced by infected cows. Phylogenetic analysis revealed that all HEV isolates from cow/milk belong to genotype 4 and subtype 4h. Gavage with HEV-contaminated raw and even pasteurized milk resulted in active infection in rhesus macaques. Importantly, a short period of boiling, but not pasteurization, could completely inactivate HEV. Infectious HEV-contaminated cow milk is recognized as a new zoonotic source that bears a high risk of transmission to humans; these results call attention to understanding and establishing proper measurement and control of HEV zoonotic transmission, particularly in the setting of mixed farming of domestic animals. (Hepatology 2016;64:350-359). © 2016 by the American Association for the Study of Liver Diseases.

Protection against canine parvovirus type 2 infection in puppies by colostrum-derived antibodies.

PubMed

Mila, Hanna; Grellet, Aurélien; Desario, Costantina; Feugier, Alexandre; Decaro, Nicola; Buonavoglia, Canio; Chastant-Maillard, Sylvie

2014-01-01

During the first weeks of life puppies remain protected against canine parvovirus type 2 (CPV2) infection thanks to maternally derived antibodies (MDA) absorbed with colostrum after birth. The objective of the present study was to present the variability in CPV2-specific passive immune transfer and its consequences in puppies naturally exposed to the parvovirus. Seventy-nine puppies from one breeding kennel were included in the study at birth and followed until 56 d of age. Once per week the MDA titre for CPV2 specific antibodies was determined in blood. Viral excretion was also evaluated on a rectal swab by CPV2 PCR assay and puppies were weighed to determine growth rate. At 2 d of age, thirty-four out of seventy-nine puppies (43 %) had MDA ≤1:160 (designed group A) and forty-five puppies (57 %) had greater MDA titres (designed group B). The level of absorbed maternal antibodies was shown to be associated with breed size and growth rate during the first 48 h of life. The MDA level declined with age in all cases; however, the proportion of puppies with the antibody level considered as protective against CPV2 infection was significantly higher in group B compared with A from day 2 until 42. Among all puppies surviving until 56 d of age, sixty-seven out of seventy (95·7 %) underwent CPV2 infection. However, puppies from group A excreted CPV2 significantly earlier than puppies from group B. The present study demonstrates the link between passive immune transfer, in terms of level of specific MDA absorbed, and length of the protection period against parvovirus infection in weaning puppies.

40 CFR Table Jj-3 to Subpart Jj of... - State-Specific Volatile Solids (VS) and Nitrogen (N) Excretion Rates for Cattle

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false State-Specific Volatile Solids (VS) and Nitrogen (N) Excretion Rates for Cattle JJ Table JJ-3 to Subpart JJ of Part 98 Protection of... Volatile Solids (VS) and Nitrogen (N) Excretion Rates for Cattle State Volatile solids excretion rate (kg...

Association of urinary calcium excretion with serum calcium and vitamin D levels.

PubMed

Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred; Burnier, Michel; Bochud, Murielle

2015-03-06

Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. Copyright © 2015 by the American Society of Nephrology.

The relationship between sodium excretion and blood pressure, urine albumin, central retinal arteriolar equivalent.

PubMed

Huang, Feng; Yu, Peng; Yuan, Yin; Li, Qiaowei; Lin, Fan; Gao, Zhonghai; Chen, Falin; Zhu, Pengli

2016-10-11

Many studies showed an association between dietary salt intake, blood pressure and increased CVD risk. The potential reason may be related to vascular structural and functional changes, through alterations in endothelial function. The central retinal arteriolar equivalent and urinary albumin reflected vascular endothelial dysfunction in different part of the body. The urinary sodium-creatinine ratio of causal urine specimens could represent the 24-h urinary sodium intake to estimate sodium intake. The 24-h sodium excretion was estimated by urinary sodium-creatinine ratio. Urinary albumin-creatinine ratio (UACR), reflecting renal arterial damage, was also determined. The central retinal arteriolar equivalent (CRAE) was detected by fundus photography and was further analyzed by semi-quantitative software. Participants included 951 hypertensive patients with the average sodium excretion of 11.62 ± 3.01 g. The sodium excretion was significantly higher (P < 0.01) in the hypertensive as compared to that of the non-hypertensive participants. Prevalence of hypertension was increased with increasing sodium excretion. The sodium excretion was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively (r = 0.20 and 0.14; P < 0.01). Furthermore, UACR and CRAE were significantly (P < 0.01) different within the sodium excretion quartiles (Q1-Q4). After adjusting the confounding variables, such as age and sex, the binary logistic regression analysis showed that sodium excretion was an independent factor of UACR and CRAE (P < 0.01). Our results suggest that sodium excretion in the hypertensive participants were higher. The high sodium excretion was related with the renal arterial damage as well as retinal arteriolar changes.

Improving the efficiency of feed utilization in poultry by selection. 2. Genetic parameters of excretion traits and correlations with anatomy of the gastro-intestinal tract and digestive efficiency.

PubMed

de Verdal, Hugues; Narcy, Agnès; Bastianelli, Denis; Chapuis, Hervé; Même, Nathalie; Urvoix, Séverine; Le Bihan-Duval, Elisabeth; Mignon-Grasteau, Sandrine

2011-08-17

Poultry production has been widely criticized for its negative environmental impact related to the quantity of manure produced and to its nitrogen and phosphorus content. In this study, we investigated which traits related to excretion could be used to select chickens for lower environmental pollution.The genetic parameters of several excretion traits were estimated on 630 chickens originating from 2 chicken lines divergently selected on apparent metabolisable energy corrected for zero nitrogen (AMEn) at constant body weight. The quantity of excreta relative to feed consumption (CDUDM), the nitrogen and phosphorus excreted, the nitrogen to phosphorus ratio and the water content of excreta were measured, and the consequences of such selection on performance and gastro-intestinal tract (GIT) characteristics estimated. The genetic correlations between excretion, GIT and performance traits were established. Heritability estimates were high for CDUDM and the nitrogen excretion rate (0.30 and 0.29, respectively). The other excretion measurements showed low to moderate heritability estimates, ranging from 0.10 for excreta water content to 0.22 for the phosphorus excretion rate. Except for the excreta water content, the CDUDM was highly correlated with the excretion traits, ranging from -0.64 to -1.00. The genetic correlations between AMEn or CDUDM and the GIT characteristics were very similar and showed that a decrease in chicken excretion involves an increase in weight of the upper part of the GIT, and a decrease in the weight of the small intestine. In order to limit the environmental impact of chicken production, AMEn and CDUDM seem to be more suitable criteria to include in selection schemes than feed efficiency traits.

Ethosuximide: liver enzyme induction and D-glucaric acid excretion.

PubMed

Gilbert, J C; Scott, A K; Galloway, D B; Petrie, J C

1974-06-01

1 A study has been carried out to determine if ethosuximide induces liver enzymes. 2 Ethosuximide did not affect the urinary excretion of D-glucaric acid by healthy adult subjects nor was the mean daily D-glucaric acid excretion of three epileptic children on long term ethosuximide therapy different from that of three matched controls. 3 Ethosuximide (10 mg/kg or 50 mg/kg daily) did not influence D-glucaric acid excretion or liver microsomal protein and cytochrome P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it increased liver microsomal protein and cytochrome P450 without altering D-glucaric acid excretion. 4 These results suggest that at anticonvulsant doses ethosuximide is unlikely to induce liver enzymes. The precise relationship between D-glucaric acid excretion and liver enzyme induction remains in doubt.

Interplay of biopharmaceutics, biopharmaceutics drug disposition and salivary excretion classification systems

PubMed Central

Idkaidek, Nasir M.

2013-01-01

The aim of this commentary is to investigate the interplay of Biopharmaceutics Classification System (BCS), Biopharmaceutics Drug Disposition Classification System (BDDCS) and Salivary Excretion Classification System (SECS). BCS first classified drugs based on permeability and solubility for the purpose of predicting oral drug absorption. Then BDDCS linked permeability with hepatic metabolism and classified drugs based on metabolism and solubility for the purpose of predicting oral drug disposition. On the other hand, SECS classified drugs based on permeability and protein binding for the purpose of predicting the salivary excretion of drugs. The role of metabolism, rather than permeability, on salivary excretion is investigated and the results are not in agreement with BDDCS. Conclusion The proposed Salivary Excretion Classification System (SECS) can be used as a guide for drug salivary excretion based on permeability (not metabolism) and protein binding. PMID:24493977

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

PubMed

Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

2017-03-01

A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Ammonia excretion increased and urea excretion decreased in urine of a new world nectarivorous bat with decreased nitrogen intake.

PubMed

Herrera M, L Gerardo; Ramirez P, Nicte; Miron M, Leticia

2006-01-01

We determined the effect of water and nitrogen intake on nitrogenous waste composition in the nectarivorous Pallas's long-tongued bat Glossophaga soricina (Phyllostomidae) to test the hypothesis that bats reduce excretion of urea nitrogen and increase the excretion of ammonia nitrogen as nitrogen intake decreases and water intake decreases. Because changes in urine nitrogen composition are expected only in animals whose natural diets are low in nitrogen and high in water content, we also measured maintenance nitrogen requirements (MNR). We hypothesized that, similar to other plant-eating vertebrates, nectarivorous bats have low MNR. Our nitrogen excretion hypothesis was partly proved correct. There was an increase in the proportion of N excreted as ammonia and a decrease in the proportion excreted as urea in low-nitrogen diets. The proportion of N excreted as ammonia and urea was independent of water intake. Most individuals were ureotelic (n = 28), and only a few were ureo-ammonotelic (n = 3) or ammonotelic (n = 2). According to our nitrogen requirement hypothesis, apparent MNR (60 mg kg(-0.75) d(-1)) and truly digestible MNR (54 mg N kg(-0.75) d(-1)) were low. A decrease in urea excretion in low-nitrogen diets may result from urea recycling from liver to the gut functioning as a nitrogen salvage system in nectarivorous bats. This mechanism probably contributes to the low MNR found in Pallas's long-tongued bats.

Excretion of Avenanthramides, Phenolic Acids and their Major Metabolites Following Intake of Oat Bran

PubMed Central

Schär, Manuel Y.; Corona, Giulia; Soycan, Gulten; Dine, Clemence; Kristek, Angelika; Alsharif, Sarah N. S.; Behrends, Volker; Lovegrove, Alison; Shewry, Peter R.

2017-01-01

Scope Wholegrain has been associated with reduced chronic disease mortality, with oat intake particularly notable for lowering blood cholesterol and glycemia. To better understand the complex nutrient profile of oats, we studied urinary excretion of phenolic acids and avenanthramides after ingestion of oat bran in humans. Methods and results After a 2‐d (poly)phenol‐low diet, seven healthy men provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 μmol avenanthramides, 139.2 μmol phenolic acids) or a phenolic‐low (traces of phenolics) control in a crossover design. Analysis by ultra‐high performance liquid chromatography (UPLC)–MS/MS showed that oat bran intake resulted in an elevation in urinary excretion of 30 phenolics relative to the control, suggesting that they are oat bran‐derived. Mean excretion levels were elevated between 0–2 and 4–8 h, following oat bran intake, and amounted to a total of 33.7 ± 7.3 μmol total excretion (mean recovery: 22.9 ± 5.0%), relative to control. The predominant metabolites included: vanillic acid, 4‐ and 3‐hydroxyhippuric acids, and sulfate‐conjugates of benzoic and ferulic acids, which accounted collectively for two thirds of total excretion. Conclusion Oat bran phenolics follow a relatively rapid urinary excretion, with 30 metabolites excreted within 8 h of intake. These levels of excretion suggest that bound phenolics are, in part, rapidly released by the microbiota. PMID:29024323

Ecdysteroid excretion by adult Hymenolepis diminuta in vitro.

PubMed

Mercer, J G; Munn, A E; Arme, C; Rees, H H

1987-12-01

Both patent and prepatent adult Hymenolepis diminuta excreted 20-hydroxyecdysone into the culture medium when maintained in vitro. Patent worms also excreted ecdysone and comparatively large quantities of unidentified immunoreactive material of a relatively apolar nature. This latter material was shown to be depleted from the endogenous free ecdysteroids of patent adults during the culture period. Ecdysteroid excretion was affected both qualitatively and quantitatively when culturing conditions were varied.

Effects of chronic lithium administration on renal acid excretion in humans and rats

PubMed Central

Weiner, I. David; Leader, John P.; Bedford, Jennifer J.; Verlander, Jill W.; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J.

2014-01-01

Abstract Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium‐treated and control humans. There were no significant differences between lithium‐treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium‐treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium‐treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg. PMID:25501430

Greater bile acid excretion with soy bean than with cow milk in infants.

PubMed

Potter, J M; Nestel, P J

1976-05-01

The excretion of fecal sterols and bile acids was measured in five infants from the 1st week of life to 2 or 3 months of age as the composition of their diet was changed from cow milk to soy bean milk. Bile acid excretion, adjusted for body weight, was initially lower during the 1st than during the 3rd week, when it reached adult values. The average excretion of bile acids was 6.8 mg/kg per day with soy bean milk and 3.6 mg/kg per day with cow milk. Net sterol excretion (total sterol output minus cholesterol intake) was also twice as high with soy bean milk and probably reflected enhancement of cholesterol re-excretion as well as of synthesis since the cholesterol content of soy beans is nil. However, net sterol excretion remained higher with soy bean than with cow milk even when egg yolk cholesterol was added to the soy bean milk. It is concluded that the substitution of soy bean milk for cow milk, which lowered the plasma cholesterol in all infants (even in the presence of dietary cholesterol) leads to an increase in bile acids and probably also in cholesterol excretion in young infants.

Renal Function of Rats in Response to 37 Days of Head-Down Tilt

NASA Technical Reports Server (NTRS)

Wang, Tommy J.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

Asymptomatic bacteriuria: review and discussion of the IDSA guidelines.

PubMed

Nicolle, Lindsay E

2006-08-01

Asymptomatic bacteriuria is a common finding, but is usually benign. Screening and treatment of asymptomatic bacteriuria is only recommended for pregnant women, or for patients prior to selected invasive genitourinary procedures. Healthy women identified with asymptomatic bacteriuria on population screening subsequently experience more frequent episodes of symptomatic infection, but antimicrobial treatment of asymptomatic bacteriuria does not decrease the occurrence of these episodes. Clinical trials in spinal-cord injury patients, diabetic women, patients with indwelling urethral catheters, and elderly nursing home residents have consistently found no benefits with treatment of asymptomatic bacteriuria. Negative outcomes with antimicrobial treatment do occur, including adverse drug effects and re-infection with organisms of increasing resistance. Optimal management of asymptomatic bacteriuria requires appropriate implementation of screening strategies to promote timely identification of the selected patients for whom treatment is beneficial, and avoidance of antimicrobial therapy where no benefit has been shown.

Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments

PubMed Central

Geng, Lingyun; Wang, Xin

2015-01-01

Epstein-Barr Virus (EBV), the first human virus related to oncogenesis, was initially identified in a Burkitt lymphoma cell line in 1964. EBV infects over 90% of the world’s population. Most infected people maintain an asymptomatic but persistent EBV infection lifelong. However, in some individuals, EBV infection has been involved in the development of cancer and autoimmune disease. Nowadays, oncogenic potential of EBV has been intensively studied in a wide range of human neoplasms, including Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphoma (NHL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), etc. EBV encodes a series of viral protein and miRNAs, promoting its persistent infection and the transformation of EBV-infected cells. Although the exact role of EBV in the oncogenesis remains to be clarified, novel diagnostic and targeted therapeutic approaches are encouraging for the management of EBV-related malignancies. This review mainly focuses on the experimental and clinical advances of EBV-associated lymphoproliferative disorders. PMID:26628948

[Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infection. Competition of the subtypes in acute and inapparent infection].

PubMed

Gerasimov, S G; Pogodina, V V; Koliasnikova, N M; Karan', L S; Malenko, G V; Levina, L S

2011-01-01

Long-term monitoring of natural tick-borne encephalitis virus (TBEV) populations could reveal the change of TBEV subtypes, the displacement of the Far Eastern (FE) subtype, and its substitution for the Siberian (Sib) subtype. Acute and inapparent mixed infections were studied in Syrian hamsters to understand this phenomenon. The animals were inoculated with the Sib subtype and then with the FE one of TBEV (JQ845440-YaroslavI-Aver-08 and Fj214132-Kemerovo-Phateev-1954 strains). The inapparent form developed more frequently in mixed infection. Viral progeny was genotyped by reverse transcription polymerase chain reaction and hybridization fluorescence detection using genotype-specific probes. Independent reproduction of strains in the brain gave way to competition. The FE subtype dominated in hamster youngsters with acute infection. The Sib subtype had selective benefits in asymptomatic infection (adult hamsters infected intracerebrally and subcutaneously and youngsters infected subcutaneously). The competition of the subtypes was imperfect.

Evidence of an oncogenic gammaherpesvirus in domestic dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Shih-Hung, E-mail: ncku309@gmail.com; Kozak, Philip J., E-mail: philj@vet.upenn.edu; Kim, Jessica, E-mail: jesskim820@gmail.com

In humans, chronic infection with the gammaherpesvirus Epstein-Barr virus is usually asymptomatic; however some infected individuals develop hematological and epithelial malignancies. The exact role of EBV in lymphomagenesis is poorly understood partly because of the lack of clinically relevant animal models. Here we report the detection of serological responses against EBV capsid antigens in healthy dogs and dogs with spontaneous lymphoma and that dogs with the highest antibody titers have B cell lymphoma. Moreover, we demonstrate the presence of EBV-like viral DNA and RNA sequences and Latent Membrane Protein-1 in malignant lymph nodes of dogs with lymphoma. Finally, electron microscopymore » of canine malignant B cells revealed the presence of classic herpesvirus particles. These findings suggest that dogs can be naturally infected with an EBV-like gammaherpesvirus that may contribute to lymphomagenesis and that dogs might represent a spontaneous model to investigate environmental and genetic factors that influence gammaherpesvirus-associated lymphomagenesis in humans.« less

The management of HCV-infected pregnant women.

PubMed

Valladares, Guillermo; Chacaltana, Alfonso; Sjogren, Maria H

2010-01-01

Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

Coxsackie Virus A16 Infection of Placenta with Massive Perivillous Fibrin Deposition Leading to Intrauterine Fetal Demise at 36 Weeks Gestation.

PubMed

Yu, Weiming; Tellier, Raymond; Wright, James R

2015-01-01

Massive perivillous fibrin deposition (MPFD) is an uncommon placental disorder, associated with significant fetal morbidity, mortality, and recurrence; its etiology is unknown. We describe a 31-year-old mother, diagnosed with Coxsackievirus infection and hand-foot-and-mouth disease at 35 weeks gestation. Ultrasound at 35 weeks revealed a normal fetus and placenta. One week later, the mother experienced decreased fetal movement and ultrasound demonstrated intrauterine demise. The autopsy showed mild, acute pericarditis and hypoxic-ischemic encephalopathy. Placenta examination showed MPFD involving 80% of the parenchyma. Molecular viral analysis and serotyping showed Coxsackie A16 virus. The mother had an uneventful pregnancy 15 months later. Coxsackievirus infections in pregnant mothers are often asymptomatic. Transplacental Coxsackievirus infection is very rare but is associated with spontaneous abortion, intrauterine demise, or serious neonatal morbidity. Mild, nonspecific histologic changes have been reported in the placenta. To our knowledge, this is the first report of MPFD associated with Coxsackievirus infection.

Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area1

PubMed Central

Weiss, Greta E; Crompton, Peter D.; Li, Shanping; Walsh, Laura A.; Moir, Susan; Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Ogobara K.; Pierce, Susan K.

2009-01-01

Epidemiological observations in malaria endemic areas have long suggested a deficiency in the generation and maintenance of B cell memory to Plasmodium falciparum (Pf) in individuals chronically reinfected with the parasite. Recently, a functionally and phenotypically distinct population of FCRL4+ hypo-responsive memory B cells (MBCs) was reported to be expanded in HIV-infected individuals with high viral loads. Here we provide evidence that a phenotypically similar atypical MBC population is significantly expanded in Pf-exposed Malian adults and children as young as two years of age as compared to healthy U.S. adult controls. The number of these atypical MBCs was higher in children with chronic asymptomatic Pf infections compared to uninfected children suggesting that the chronic presence of the parasite may drive expansion of these distinct MBCs. This is the first description of an atypical MBC phenotype associated with malaria. Understanding the origin and function of these MBCs could be important in informing the design of malaria vaccines. PMID:19592645

[Reactivation of parvovirus B19 infection in an HIV-infected woman].

PubMed

Sterpu, R; Ichou, H; Mahé, I; Mortier, E

2014-06-01

Infection by human parvovirus B19 (erythrovirus B19) is common and usually asymptomatic during childhood conferring lasting protection against a new infection. Parvovirus B19 infection may cause erythema infectiosum (5th disease) and aplastic crisis. Secondary symptomatic parvovirus B19 infection in the same patient is rare and its physiopathology is not always clear. A 48-year-old HIV-infected female patient presented within 5 years two acute episodes of parvovirus B19 infection although her CD4 cells count was above 500/mm(3). Absence of specific antibodies production after the first episode and persisting parvovirus viremia suggested viral reactivation rather than re-infection. During the second episode, specific antibodies were produced. Similarly to most DNA viruses, parvovirus B19 reactivation is possible in HIV-infected patients while effectively treated by antiretroviral therapy. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Molecular studies with Aedes (Stegomyia) aegypti (Linnaeus, 1762), mosquito transmitting the dengue virus.

PubMed

Pereira, Luciana Patrícia Lima Alves; Brito, Maria Cristiane Aranha; Araruna, Felipe Bastos; de Andrade, Marcelo Souza; Moraes, Denise Fernandes Coutinho; Borges, Antônio Carlos Romão; do Rêgo Barros Pires Leal, Emygdia Rosa

2017-08-01

Dengue is an infectious viral disease, which can present a wide clinical picture, ranging from oligo or asymptomatic forms, to bleeding and shock, and can progress to death. The disease problem has increased in recent years, especially in urban and suburban areas of tropical and subtropical regions. There are five dengue viruses, called serotypes (DEN-1, DEN-2, DEN-3, DEN-4, and DEN-5), which belong to the Flaviviridae family and are transmitted to humans through infected mosquito bites, with the main vector the Aedes aegypti mosquito (Linnaeus, 1762). Studies performed with Ae. aegypti, aimed at their identification and analysis of their population structure, are fundamental to improve understanding of the epidemiology of dengue, as well for the definition of strategic actions that reduce the transmission of this disease. Therefore, considering the importance of such research to the development of programs to combat dengue, the present review considers the techniques used for the molecular identification, and evaluation of the genetic variability of Ae. aegypti.

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

PubMed Central

Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

2014-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

PubMed

Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

2015-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. Copyright © 2014 Elsevier Inc. All rights reserved.

HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers.

PubMed

Di Domenico, Marina; Giovane, Giancarlo; Kouidhi, Soumaya; Iorio, Rosamaria; Romano, Maurizio; De Francesco, Francesco; Feola, Antonia; Siciliano, Camilla; Califano, Luigi; Giordano, Antonio

2017-03-31

Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

PubMed

Peluso, Michael J; Spudich, Serena

2014-09-01

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

Acute diarrhea in West African children: diverse enteric viruses and a novel parvovirus genus.

PubMed

Phan, Tung G; Vo, Nguyen P; Bonkoungou, Isidore J O; Kapoor, Amit; Barro, Nicolas; O'Ryan, Miguel; Kapusinszky, Beatrix; Wang, Chunling; Delwart, Eric

2012-10-01

Parvoviruses cause a variety of mild to severe symptoms or asymptomatic infections in humans and animals. During a viral metagenomic analysis of feces from children with acute diarrhea in Burkina Faso, we identified in decreasing prevalence nucleic acids from anelloviruses, dependoviruses, sapoviruses, enteroviruses, bocaviruses, noroviruses, adenoviruses, parechoviruses, rotaviruses, cosavirus, astroviruses, and hepatitis B virus. Sequences from a highly divergent parvovirus, provisionally called bufavirus, were also detected whose NS1 and VP1 proteins showed <39% and <31% identities to those of previously known parvoviruses. Four percent of the fecal samples were PCR positive for this new parvovirus, including a related bufavirus species showing only 72% identity in VP1. The high degree of genetic divergence of these related genomes from those of other parvoviruses indicates the presence of a proposed new Parvoviridae genus containing at least two species. Studies of the tropism and pathogenicity of these novel parvoviruses will be facilitated by the availability of their genome sequences.

Acute Diarrhea in West African Children: Diverse Enteric Viruses and a Novel Parvovirus Genus

PubMed Central

Phan, Tung G.; Vo, Nguyen P.; Bonkoungou, Isidore J. O.; Kapoor, Amit; Barro, Nicolas; O'Ryan, Miguel; Kapusinszky, Beatrix; Wang, Chunling

2012-01-01

Parvoviruses cause a variety of mild to severe symptoms or asymptomatic infections in humans and animals. During a viral metagenomic analysis of feces from children with acute diarrhea in Burkina Faso, we identified in decreasing prevalence nucleic acids from anelloviruses, dependoviruses, sapoviruses, enteroviruses, bocaviruses, noroviruses, adenoviruses, parechoviruses, rotaviruses, cosavirus, astroviruses, and hepatitis B virus. Sequences from a highly divergent parvovirus, provisionally called bufavirus, were also detected whose NS1 and VP1 proteins showed <39% and <31% identities to those of previously known parvoviruses. Four percent of the fecal samples were PCR positive for this new parvovirus, including a related bufavirus species showing only 72% identity in VP1. The high degree of genetic divergence of these related genomes from those of other parvoviruses indicates the presence of a proposed new Parvoviridae genus containing at least two species. Studies of the tropism and pathogenicity of these novel parvoviruses will be facilitated by the availability of their genome sequences. PMID:22855485

Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities.

PubMed

Seferovic, Maxim; Martín, Claudia Sánchez-San; Tardif, Suzette D; Rutherford, Julienne; Castro, Eumenia C C; Li, Tony; Hodara, Vida L; Parodi, Laura M; Giavedoni, Luis; Layne-Colon, Donna; Tamhankar, Manasi; Yagi, Shigeo; Martyn, Calla; Reyes, Kevin; Suter, Melissa A; Aagaard, Kjersti M; Chiu, Charles Y; Patterson, Jean L

2018-05-01

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

Avian influenza: public health and food safety concerns.

PubMed

Chmielewski, Revis; Swayne, David E

2011-01-01

Avian influenza (AI) is a disease or asymptomatic infection caused by Influenzavirus A. AI viruses are species specific and rarely cross the species barrier. However, subtypes H5, H7, and H9 have caused sporadic infections in humans, mostly as a result of direct contact with infected birds. H5N1 high pathogenicity avian influenza (HPAI) virus causes a rapid onset of severe viral pneumonia and is highly fatal (60% mortality). Outbreaks of AI could have a severe economic and social impact on the poultry industry, trade, and public health. Surveillance data revealed that H5N1 HPAI has been detected in imported frozen duck meat from Asia, and on the surface and in contaminated eggs. However, there is no direct evidence that AI viruses can be transmitted to humans via the consumption of contaminated poultry products. Implementing management practices that incorporate biosecurity principles, personal hygiene, and cleaning and disinfection protocols, as well as cooking and processing standards, are effective means of controlling the spread of the AI viruses.

Role of the HLA system in the association between multiple sclerosis and infectious mononucleosis.

PubMed

Ramagopalan, Sreeram V; Meier, Ute C; Conacher, Margaret; Ebers, George C; Giovannoni, Gavin; Crawford, Dorothy H; McAulay, Karen A

2011-04-01

To determine whether multiple sclerosis (MS) and infectious mononucleosis (IM) share common HLA associations. A prospective cohort study was conducted from October 1, 1999, through September 30, 2003. University of Edinburgh Richard Verney Health Centre, Edinburgh, Scotland. Participants included 179 individuals who underwent asymptomatic Epstein-Barr virus seroconversion and 175 patients who developed IM. Genotyping for 5 classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1). Diagnosis of IM and allele frequency. Allelic analysis showed that HLA-DRB1*01:01 was significantly associated with the development of IM (odds ratio, 3.2; P < .001). Patients with IM and HLA-DRB1*01:01 had a lower Epstein-Barr virus viral load compared with those without the allele (median, 783 vs 7366 copies/10(6) peripheral blood mononuclear cells; P = .03). HLA-DRB1*01:01 is protective against developing MS; thus, a common genetic basis between IM and MS is not supported.

Effects of age and sex on hormonal responses to weightlessness simulation

NASA Technical Reports Server (NTRS)

Larochelle, F.; Leach, C.; Vernikos-Danellis, J.

1982-01-01

The effects of horizontal bedrest on the excretion of catecholamines, aldosterone, and cortisol by human subjects grouped by age and sex are examined. The responses are assessed by assays of 24-hr urine samples collected throughout the studies. In 36-45-yr-olds, the excretion of epinephrine increases, whereas it decreases in the 46-55- and 56-65-yr-old groups. Norepinephrine excretion decreases (5-27%) in all groups during bedrest. Aldosterone excretion increases in the younger two groups of both males (19 and 6%) and females (47 and 9%). A slight decrease is observed in 56-65-yr-old males (6%), whereas excretion in females is unchanged. Cortisol excretion increases in the youngest groups of both men (12%) and women (13%) but decreases in the 56-65-yr-old groups (6 and 5%). For the two groups of intermediate age (46-55 yr), excretion in females decreases (15%), whereas in males it increases (19%). It is believed that hormone measurements may be of value in explaining variation in stress tolerance due to age and/or sex during space flight.

Effects of diet on titratable acid-base excretion in grasshoppers.

PubMed

Frazier, M R; Harrison, J F; Behmer, S T

2000-01-01

Despite the potential for diet to affect organismal acid-base status, especially in herbivores, little is known about the effects of diet on acid-base loading and excretion. We tested the effects of diet on acid-base loading and excretion in grasshoppers by (a) comparing the fecal acid-base content of 15 grasshopper species collected from the field and (b) comparing fecal acid-base excretion rates of Schistocerca americana grasshoppers fed vegetable diets that differed in their ashed and raw acid-base contents. The field experiments indicated that grass-feeding species excrete fairly neutral fecal pellets, while forb/mixed-feeding species vary widely in their fecal acid-base contents. In the laboratory experiment, acid-base excretion rates were positively correlated with dietary ashed base intake rates but were not correlated with the acid-base content of raw, unashed diet or feeding rate. These experiments suggest that some diets could strongly challenge the acid-base homeostasis of herbivores; in some grasshoppers, dietary acid-base loads could produce certainly lethal 1-unit changes in average body pH within 6 h if they were not excreted.

Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi.

PubMed

Buchwald, Andrea G; Sixpence, Alick; Chimenya, Mabvuto; Damson, Milius; Sorkin, John D; Wilson, Mark L; Seydel, Karl; Hochman, Sarah; Mathanga, Don P; Taylor, Terrie E; Laufer, Miriam K

2018-05-16

Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs.

The human polyomavirus BK: Potential role in cancer.

PubMed

Fioriti, D; Videtta, M; Mischitelli, M; Degener, A M; Russo, G; Giordano, A; Pietropaolo, V

2005-08-01

In human cancer, a role has been suggested for the human polyomavirus BK, primarily associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients, and with hemorrhagic cystitis in bone marrow transplant (BMT) recipients. After the initial infection, primarily unapparent and without clinical signs, the virus disseminates and establishes a persistent infection in the urinary tract and lymphocytes. There is correlative evidence regarding potential role of polyomavirus BK in cancer. In fact, the BK virus (BKV) DNA (complete genome and/or subgenomic fragments containing the early region) is able to transform embryonic fibroblasts and cells cultured from kidney and brain of hamster, mouse, rat, rabbit, and monkey. Nevertheless, transformation of human cells by BKV is inefficient and often abortive. Evidence supporting a possible role for BKV in human cancer has accumulated slowly in recent years, after the advent of polymerase chain reaction (PCR). BKV is known to commonly establish persistent infections in people and to be excreted in the urine by individuals who are asymptomatic, complicating the evaluation of its potential role in development of human cancer. Therefore, there is no certain proof that human polyomavirus BK directly causes the cancer in humans or acts as a cofactor in the pathogenesis of some types of human cancer. (c) 2005 Wiley-Liss, Inc.

Campylobacteriosis, Salmonellosis, Yersiniosis, and Listeriosis as Zoonotic Foodborne Diseases: A Review

PubMed Central

Chlebicz, Agnieszka; Śliżewska, Katarzyna

2018-01-01

Zoonoses are diseases transmitted from animals to humans, posing a great threat to the health and life of people all over the world. According to WHO estimations, 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. Campylobacter, Salmonella, as well as Yersinia enterocolitica and Listeria monocytogenes may dwell in livestock (poultry, cattle, and swine) but are also found in wild animals, pets, fish, and rodents. Animals, often being asymptomatic carriers of pathogens, excrete them with faeces, thus delivering them to the environment. Therefore, pathogens may invade new individuals, as well as reside on vegetables and fruits. Pathogenic bacteria also penetrate food production areas and may remain there in the form of a biofilm covering the surfaces of machines and equipment. A common occurrence of microbes in food products, as well as their improper or careless processing, leads to common poisonings. Symptoms of foodborne infections may be mild, sometimes flu-like, but they also may be accompanied by severe complications, some even fatal. The aim of the paper is to summarize and provide information on campylobacteriosis, salmonellosis, yersiniosis, and listeriosis and the aetiological factors of those diseases, along with the general characteristics of pathogens, virulence factors, and reservoirs. PMID:29701663

Duration of carriage and transmission of Yersinia enterocolitica biotype 4, serotype 0:3 in dogs.

PubMed Central

Fenwick, S. G.; Madie, P.; Wilks, C. R.

1994-01-01

Human infections with pathogenic strains of Yersinia enterocolitica have been linked to contact with dogs excreting these microorganisms. This study examines the carriage and transmission of Y. enterocolitica biotype 4, serotype 03 in dogs. Fourteen 6-month-old cross-bred dogs were separated into 5 groups, 2 containing 4 dogs (I and II) and the others 2 dogs (III-V). Each of the 4 dogs in Group I and 2 of the dogs in Group II were inoculated orally with the test strain. Bacteriological examination of faecal samples showed that dogs can be readily infected and can carry the organism for up to 23 days. The two in-contact dogs in Group II started to shed the test organism after 5 days. Subsequent transfer of these dogs to Group III and those in Group III to Group IV showed that Y. enterocolitica biotype 4, serotype 03 can be readily transmitted between dogs. At no time did any of the dogs show clinical signs of infection. Group V served as a negative control for the trial. These findings suggest that dogs can carry Y. enterocolitica biotype 4, serotype 03 asymptomatically and hence might act as a potential source of infection for people. PMID:7995357

Experimentally infected human body lice (pediculus humanus humanus) as vectors of Rickettsia rickettsii and Rickettsia conorii in a rabbit model.

PubMed

Houhamdi, Linda; Raoult, Didier

2006-04-01

The human body louse, the natural vector of Rickettsia prowazekii, is able to experimentally transmit the normally flea-borne rickettsia R. typhi, suggesting that the relationships between the body louse and rickettsiae are not specific. We used our experimental infection model to test the ability of body lice to transmit two prevalent tick-borne rickettsiae. Each of two rabbits was made bacteremic by injecting intravenously 2 x 10(6) plaque-forming units of either R. rickettsii or R. conorii. Four hundred body lice were infected by feeding on the bacteremic rabbit and were compared with 400 uninfected lice. Each louse group was fed once a day on a separate seronegative rabbit. The survival of infected lice was not different from that of uninfected controls. Lice remained infected for their lifespan, excreted R. rickettsii and R. conorii in their feces, but did not transmit the infection to their progeny. The nurse rabbit of uninfected lice remained asymptomatic and seronegative. Those rabbits used to feed infected lice developed bacteremia and seroconverted. Although the body louse is not a known vector of spotted fevers, it was able in our study to acquire, maintain, and transmit both R. rickettsii and R. conorii.

Identification and chromosomal localization of ecogenetic components of electrolyte excretion.

PubMed

Dumas, Pierre; Kren, Vladimír; Krenová, Drahomíra; Pravenec, Michal; Hamet, Pavel; Tremblay, Johanne

2002-02-01

To determine to what extent urinary excretion of blood pressure-modulating electrolytes is genetically determined, and to identify their chromosomal localization. Twenty-six rat recombinant inbred strains (RIS) originating from reciprocal crosses of normotensive Brown Norway (BN.Lx) and spontaneously hypertensive rats (SHR) were used. A pilot experiment on a subset of strains determined that fasting decreases the impact of environmental noise and increases that of heritability. Twenty-four-hour urinary collections were obtained from fasting rats aged 6-12 weeks (3-8 rats per strain). Sodium (Na), potassium (K) and calcium (Ca) excretions were measured, and the Na/K ratio calculated. These phenotypes served as quantitative traits for the search of quantitative trait loci (QTLs) by scanning the RIS genome that was mapped with 475 polymorphic markers. Constant Na intake resulted in a low heritability for Na excretion, reflecting the environmental impact (intake = excretion), whereas fasting revealed a gradient among RIS indicative of the genetic component of the traits. In the fasting state, a locus on chromosome 14 was found to be significantly associated with K excretion (Alb, P = 0.00002, r = -0.69, logarithm of the odds score (LOD) 3.9), whereas another locus on chromosome 10 (D10Cebrp97s5, P = 0.0003, r = -0.69, LOD 3.0) and one on chromosome 6 (D6Cebrp97s14, P = 0.0007, r = -0.65, LOD 1.9) were more significantly associated with Na excretion and the Na/K ratio respectively. The observed correlations were all negative for Na, K and Na/K, indicating a higher excretion of Na and K and a greater Na/K ratio in rats bearing BN.Lx alleles at these loci, i.e. salt retention in fasting SHR. These three loci accounted for 47-55% of variance of their associated trait, suggesting that they are the main genetic determinants for these phenotypes in basal fasting conditions. Rats bearing the Y chromosome of SHR origin had significantly higher K excretion that, in turn, led to a significantly lower Na/K ratio. Finally, a locus on chromosome 7 was linked to Ca excretion, explaining 46% of the trait variance (D7Mit10, LOD score 3.0). RIS enabled us to determine QTLs for environmentally modulated traits such as Na, K and Ca excretions. We demonstrated that whereas urinary electrolytes are determined mainly by intake (environment) in a steady state, their excretion in an adaptive state (fasting) is predominantly genetically determined by distinct QTL on autosomes as well as the Y chromosome. Furthermore, the loci responsible for Na and K excretions act independently of the locus governing the relative excretion of Na/K. Thus, the salt-retaining aspects of some hypertensives may be, in large part, determined by genes responsible for renal excretion, the impact of which is predominant over the environment under acute challenge.

Asymptomatic malaria, growth status, and anaemia among children in Lao People's Democratic Republic: a cross-sectional study.

PubMed

Akiyama, Takeshi; Pongvongsa, Tiengkham; Phrommala, Souraxay; Taniguchi, Tomoyo; Inamine, Yuba; Takeuchi, Rie; Watanabe, Tadashi; Nishimoto, Futoshi; Moji, Kazuhiko; Kano, Shigeyuki; Watanabe, Hisami; Kobayashi, Jun

2016-10-18

Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People's Democratic Republic (Lao PDR), malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. The mean age of participants (n = 319) was 88.3 months old (Standard Deviation: 20.6, ranged from 30-119 months old), and 20 participants (6.3 %) had an asymptomatic malaria infection, 92 (28.8 %) were anaemic, 123 (38.6 %) were underweight, and 137 (42.9 %) were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR) 3.34, 95 % confidence interval (CI) 1.25-8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99-13.43]. These results suggest a significant association between asymptomatic malaria and anaemia in children. Furthermore, stunted children were more likely to have lower Hb levels and to be infected with asymptomatic malaria than children without stunting. However, further studies examining the impact of asymptomatic malaria infection on children's nutritional and development status are necessary.

Carotid artery stiffness in patients with symptomatic carotid artery disease with contralateral asymptomatic carotid artery disease and in patients with bilateral asymptomatic carotid artery disease: a cine phase-contrast carotid MR study.

PubMed

Sadat, Umar; Usman, Ammara; Howarth, Simon P S; Tang, Tjun Y; Alam, Fahreyar; Graves, Martin J; Gillard, Jonathan H

2014-04-01

Atherosclerosis is a systemic inflammatory disease that may affect multiple arterial beds simultaneously. Vascular distensibility is increasingly used in the clinical assessment of patients with atherosclerotic disease. In this study, we assess distensibility of symptomatic atherosclerotic carotid artery and of contralateral asymptomatic side. We also investigate the distensibility of bilaterally asymptomatic atherosclerotic carotid arteries using cine phase-contrast carotid magnetic resonance (MR) imaging. Nineteen patients with bilateral carotid artery disease underwent cine phase-contrast carotid imaging on a 1.5 T MR system. Ten patients had ipsilateral symptomatic carotid artery disease and contralateral asymptomatic stenosis. Nine additional patients with bilateral asymptomatic carotid artery disease constituted historical control group. Cine phase-contrast MR imaging acquired at the common carotid artery, maximum luminal stenosis, and internal carotid artery was used to determine carotid distensibility bilaterally for carotid arteries in both patient groups. Symptomatic carotid arteries were found to be significantly less distensible (mean distensibility coefficient [DC] 35.4 ± 6.12 × 10(-3)/kPa) than the contralateral asymptomatic vessels (mean DC 54.4 ± 7.88 × 10(-3)/kPa, P = .03) at the level of the common carotid artery. A similar trend of high distensibility for asymptomatic side in the area of maximum stenosis and the internal carotid artery was seen, but it was not found to be statistically significant. Plaque burden was comparable between the 2 groups at all locations. DC was comparable for patients with bilateral asymptomatic carotid artery stenoses. Distensibility of bilaterally asymptomatic carotid arteries was greater than that of asymptomatic carotid artery contralateral to the symptomatic side. Symptomatic carotid artery is stiffer than the contralateral asymptomatic side, despite comparable plaque burden. Patients with bilateral asymptomatic carotid artery disease have comparable stiffness. Larger studies are warranted to further investigate the findings of this MR study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effect of monofluoroacetate on renal H+ excretion in the rat.

PubMed

Simonnet, H; Gauthier, C; Pellet, M V

1979-05-01

In order to investigate the effect of monofluoroacetate (MFA) on renal H+ excretion, anesthetized rats under mannitol diuresis were given intraperitoneally MFA and some of the acido-basic status parameters were determined. Urinary pH and pCO2 did not change after MFA administration, while urinary flow rate increased. MFA induced a decrease in H+ net excretion and in ammonia excretion. Titratable acidity did not change significantly within the experiment.

The excretion of biotrace elements using the multitracer technique in tumour-bearing mice.

PubMed

Wang, X; Tian, J; Yin, X M; Zhang, X; Wang, Q Z

2000-12-01

A radioactive multitracer solution obtained from the nuclear reaction of selenium with 25 MeV/nucleon 40Ar ions was used for investigation of trace element excretion into the faeces and urine of cancerous mice. The excretion rates of 22 elements (Na, K, Rb, Mg, Ca, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Mo, Nb, Tc, Ru, Ag and In) were simultaneously measured under strictly identical experimental conditions, in order to clarify the excretion behavior of these elements in cancerous mice. The faecal and urinary excretion rates of Mg, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Nb, Ru and Mo in cancerous mice, showed the in highest value at 0-8 hours. The accumulative excretion of Ca, Mo, Y and Zr was decreased and Na, Fe, Mn and Co increased in tumour-bearing mice, when compared to normal mice.

Reference limits for urinary fractional excretion of electrolytes in adult non-racing Greyhound dogs.

PubMed

Bennett, S L; Abraham, L A; Anderson, G A; Holloway, S A; Parry, B W

2006-11-01

To determine reference limits for urinary fractional excretion of electrolytes in Greyhound dogs. Urinary fractional excretion was calculated using a spot clearance method preceded by a 16 to 20 hour fast in 48 Greyhound dogs. Raw data analysed using the bootstrap estimate was used to calculate the reference limits. The observed range for urinary fractional excretion in Greyhound dogs was 0.0 to 0.77% for sodium, 0.9 to 14.7% for potassium, 0 to 0.66% for chloride, 0.03 to 0.22% for calcium and 0.4 to 20.1% for phosphate. Expressed as percentages, the suggested reference limits for fractional excretion in Greyhound dogs are as follows: sodium < or = 0.72, potassium < or = 12.2, chloride < or = 0.55, calcium < or = 0.13 and phosphate < or = 16.5. Veterinary practitioners may use these reference limits for urinary electrolyte fractional excretion when investigating renal tubular disease in Greyhound dogs.

Assessment of urinary betaine as a marker of diabetes mellitus in cardiovascular patients.

PubMed

Schartum-Hansen, Hall; Ueland, Per M; Pedersen, Eva R; Meyer, Klaus; Ebbing, Marta; Bleie, Øyvind; Svingen, Gard F T; Seifert, Reinhard; Vikse, Bjørn E; Nygård, Ottar

2013-01-01

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus.

Iodine Excretion in 24-hour Urine Collection and Its Dietary Determinants in Healthy Japanese Adults

PubMed Central

Katagiri, Ryoko; Asakura, Keiko; Uechi, Ken; Masayasu, Shizuko; Sasaki, Satoshi

2016-01-01

Background Since seaweed is a common component of the Japanese diet, iodine intake in Japanese is expected to be high. However, urinary iodine excretion, measured using 24-hour urine samples, and its dietary determinants are not known. Methods Apparently healthy adults aged 20 to 69 years living in 20 areas throughout Japan were recruited in February and March, 2013. Urinary iodine excretion was evaluated using 24-hour urine collected from 713 subjects (362 men and 351 women), and the difference among age groups was assessed. The association between dietary intake of food groups and urinary iodine excretion was assessed among 358 subjects who completed a semi-weighed 4-day diet record (DR) and urine collection. The correlations between iodine intake and iodine excretion were also evaluated, and correlation coefficients were calculated for iodine intake in the DR of the overlapping day or the DR 1 day before and after urine collection. Results Median iodine excretion in 24-hour urine was 365 µg, and excretion was significantly higher in older subjects. Iodine intake estimated by the DRs was significantly correlated with urinary iodine excretion when DRs and urine collection were obtained on the same day (r = 0.37). After adjustment for confounding factors, iodine excretion was significantly associated with intakes of kelp and soup stock from kelp and fish. Conclusions Although multiple measurements for urinary iodine are required to confirm our results, this study showed the current iodine status of healthy Japanese adults. The results suggest that kelp and fish are the main contributors to Japanese iodine status measured by 24-hour urine. PMID:27374137

Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study.

PubMed

Normén, L; Laerke, H N; Jensen, B B; Langkilde, A M; Andersson, H

2001-01-01

The ketohexose D-tagatose is a new sweetener with a low energy content. This low energy content may be due to either low absorption of the D-tagatose or decreased absorption of other nutrients. The aims of this study were to measure the excretion of D-tagatose from the human small bowel, to calculate the apparent absorption of D-tagatose, and to study the effects of D-tagatose on the small-bowel excretion of other carbohydrates. A controlled diet was served for 2 periods of 2 d during 3 consecutive weeks to 6 ileostomy subjects. In one of the periods, 15 g D-tagatose was added to the diet daily. Duplicate portions of the diet and ileostomy effluents were freeze-dried and analyzed to calculate the apparent net absorption of D-tagatose and carbohydrates. Median D-tagatose excretion was 19% (range: 12-31%), which corresponded to a calculated apparent absorption of 81% (69-88%). Of the total amount of D-tagatose excreted [2.8 g (1.7-4.4 g)], 60% (8-88%) was excreted within 3 h. Between 3 and 5 h, 32% (11-82%) was excreted. Excretion of wet matter increased by 41% (24-52%) with D-tagatose ingestion. Sucrose and D-glucose excretion increased to a small extent, whereas no significant changes were found in the excretion of dry matter, energy, starch, or D-fructose. The apparent absorption of 15 g D-tagatose/d was 81%. D-Tagatose had only a minor influence on the apparent absorption of other nutrients.

Association between 24-h urinary sodium excretion and obesity in Korean adults: A multicenter study.

PubMed

Nam, Ga Eun; Kim, Seon Mee; Choi, Mi-Kyeong; Heo, Young-Ran; Hyun, Tai-Sun; Lyu, Eun-Soon; Oh, Se-Young; Park, Hae-Ryun; Ro, Hee-Kyong; Han, Kyungdo; Lee, Yeon Kyung

2017-09-01

The aim of this study was to explore the association between sodium intake, as assessed by 24-h urinary sodium excretion, and various obesity parameters among South Korean adults. The associations of 24-h urinary sodium excretion and sodium intake calculated from the dietary questionnaire with obesity parameters also were compared. This multicenter, cross-sectional study analyzed data of 640 healthy adults from eight provinces in South Korea. Obesity was assessed by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Mean 24-h urinary sodium excretion was calculated from repeatedly collected 24-h urine samples. Participants' dietary intake was assessed by 24-h dietary recall interview on the days before 24-h urine collection. In both sexes, the means of all anthropometric measurements tended to increase proportionally with 24-h urinary sodium excretion quartiles, regardless of adjustment. Men in the highest quartile (Q4) of 24-h urinary sodium excretion had increased odds of obesity (as assessed by BMI, WC, WHR, and WHtR) compared with men in the three lower quartiles (Q1-Q3) of 24-h urinary sodium excretion. Women in Q4 of 24-h urinary sodium excretion exhibited a higher chance of general obesity and abdominal obesity. Sodium intake calculated from the dietary questionnaire was not significantly associated with obesity in either sex. In Korean adults, there was a positive association between higher sodium intake as assessed by 24-h urinary sodium excretion and obesity independent of energy intake. Copyright © 2017 Elsevier Inc. All rights reserved.

Population-based association between urinary excretion of sodium, potassium and its ratio with albuminuria in Chinese.

PubMed

Yan, Liuxia; Guo, Xiaolei; Wang, Huicheng; Zhang, Jiyu; Tang, Junli; Lu, Zilong; Cai, Xiaoning; Liu, Longjian; Gracely, Edward J; Ma, Jixiang

2016-12-01

Albuminuria is a risk factor for cardiovascular and renal disease. However, little is known about the association of 24 h urinary sodium and potassium excretion with albuminuria in China. The aim of this study was to examine this association by analyzing the data from 1,975 Chinese adults living in north China. Excretion of urinary sodium, potassium and albumin was assessed in a single 24-h urine sample for each participant. Height, weight, waist circumference and blood pressure were measured and body mass index was determined as weight divided by square height. Fasting blood sample was collected and fasting glucose was measured. The average 24-h urinary sodium and potassium excretion were 232 mmol and 40.8 mmol, resulting a mean sodium to potassium ratio of 6.7. The median (Q1-Q3) 24-h urinary albuminuria excretion was 6.1 mg (4.5-8.7 mg). Overall, urinary sodium excretion was positively associated with albumin excretion (β=0.029, p<0.001). This association was independent of major cardiovascular risk factors including age, gender, systolic blood pressure, body mass index, fasting glucose, waist circumference, hypertensive drug treatment, and smoking. Moreover, the relation of sodium and albumin was similar in the subgroups stratified by gender, adiposity and diabetic status. No significant associations of potassium excretion or sodium to potassium ratio with urinary albumin excretion were observed. In cross-sectional analyses, high sodium intake was shown to be associated with increased urinary albuminuria in the general Chinese adult population, supporting salt restriction for renal and cardiovascular health benefit.

Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I).

PubMed

Asami, Akitoshi; Shimada, Tsutomu; Mizuhara, Yasuharu; Asano, Takayuki; Takeda, Shuichi; Aburada, Takashi; Miyamoto, Ken-Ichi; Aburada, Masaki

2010-07-01

To investigate the pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe, the pharmacokinetic parameters were determined by using (14)C-[6]-shogaol (labeled compound) and [6]-shogaol (non-labeled compound). When the labeled compound was orally administered to rats, the maximum plasma concentration (C (max)) and the area under the curve (AUC) of plasma radioactivity concentration increased in a dose-dependent manner. When the labeled compound was orally administered at a dose of 10 mg/kg, 20.0 + or - 1.8% of the radioactivity administered was excreted into urine, 64.0 + or - 12.9% into feces, and 0.2 + or - 0.1% into breath. Thus, more of the radioactivity was excreted into feces than into urine, and almost no radioactivity was excreted into breath. Furthermore, when the labeled compound was orally administered at a dose of 10 mg/kg, cumulative biliary radioactivity excretion over 48 h was 78.5 + or - 4.5% of the radioactivity administered, and cumulative urinary radioactivity excretion over 48 h was 11.8 + or - 2.7%, showing that about 90% of the dose administered orally was absorbed from the digestive tract and most of the fecal excretion was via biliary excretion. On the other hand, when the non-labeled compound [6]-shogaol was orally administered, the plasma concentration and biliary excretion of the unchanged form were extremely low. When these results are combined with those obtained with the labeled compound, it would suggest that [6]-shogaol is mostly metabolized in the body and excreted as metabolites.

EXCRETION OF P$sup 32$ AFTER THERAPY FOR POLYCYTHEMIA RUBRA VERA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weijer, D.L.; Duggan, H.E.; Scott, D.B.

1962-09-01

Fifteen subjects undergoing treatment for polycythemia rubra vera were given P/sup 32/. Carrier-free P/sup 32/ was administered intravenously in 11 and orally in 6. Total excretion studies were carried out in each case for periods of 5 to 22 days. Average urinary excretion of P/sup 32/, as a percentage of the initial dose to the end of 3 days for the entire series, was 14.3%, with limits of 6.4 and 18.7%. The corresponding 5-day average amounted to 17.8%, with limits of 7.5 and 22.5%. In the six patients treated orally, the average 3-day urinary excretion was 11.2% and for 5more » days was 14.2%. For the 11 patients treated intravenously, the average 3-day excretion was 16.1%, the average 5-day excretion 19.8%. The average fecal excretion as a percentage of the initial dose to the end of 3 days was 1.7%, with limits of 0.1 and 5.5%, and the average 5-day excretion was 2.5%, with limits 0.5 and 5.9%. In the orally treated fasting group the total stool excretion to the end of 3 days was 2.0 and 2.5% at the end of 5 days. Of the 10 polycythemia patients treated intravenously, the stool excretion to the end of 3 days was 1.5% and at 5 days 2.5%. Under fasting conditions (both before and after the administration of P/sup 32/) with little or no carrier added, the fecal excretion of P/sup 32/is small. Thus, the total excretion of P/sup 32/ does not differ significantly for oral and intravenous administration. Hence, despite contrary reports, it appears that under fasting conditions of administration it is not necessary to increase the oral dose of P/ sup 32/ to 4/3 of the intravenous dose in order to obtain equivalent absorption of the administered dose. It is concluded that the P/sup 32/ content of urine in the first 24 hr after therapy, by either route of administration, indicates whether or not a particular patient will retain the dose within normal limits. (BBB)« less

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

PubMed Central

Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R.

2017-01-01

Abstract Background. Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. Methods. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR. Results. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. Conclusion. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. PMID:28181657

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia.

PubMed

Boeckh, Michael; Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R

2017-05-15

Quantitative cytomegalovirus (CMV) DNA-specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA-specific PCR. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6-6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0-2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Biliary excretion of intravenous (/sup 14/C) omeprazole in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lind, T.; Andersson, T.; Skanberg, I.O.

1987-11-01

We have studied the biliary excretion of (/sup 14/C) omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of (/sup 14/C) omeprazole. These data suggest a minimal spillover of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted formore » by biliary excretion.« less

Vitamin C modulates lead excretion in rats.

PubMed

Lihm, Hoseob; Kim, Hyun; Chang, Heekyung; Yoon, Myunghee; Lee, Kayoung; Choi, Jongsoon

2013-12-01

Lead, one of the most toxic heavy metals, takes longer time to be excreted from the body than other heavy metals. The purpose of this study is, by measuring lead excretion via urine and feces, to find out the effect of vitamin C in lead chelation. Thirty-six rats were randomly assorted into four groups. All 33 rats except for the control group were administered with lead, before orally administered with different doses of vitamin C per kilogram of body weight. The lead excretion levels in urine and feces as well as the survival rate were then measured for each group. The rats with lead administrations (10/13, 76.9%) with lead administrations only, 10/11 rats (90.9%) with lead administrations and low dose of vitamin C, 9/9 rats (100%) with lead administrations and high dose of vitamin C survived. Among the 29 surviving rats, low vitamin C intake group exhibited higher urinary excretion than the lead only group. The urinary excretion level in high dose vitamin C intakegroup was significantly higher than the lead only group. In addition, fecal lead excretion seemed to be increased in the high dose vitamin C intake group, compared to the group with lead administrations only with statistical significance. Through animal experiment, it was found out that administrating high dose of vitamin C accelerated the excretion of lead in body compared to low dose of vitamin C.

Influence of hypernatraemia and urea excretion on the ability to excrete a maximally hypertonic urine in the rat

PubMed Central

Cheema-Dhadli, Surinder; Halperin, Mitchell L

2002-01-01

Rats normally excrete 20-25 mmol of sodium (Na+) + potassium (K+) per kilogram per day. To minimize the need for a large water intake, they must excrete urine with a very high electrolyte concentration (tonicity). Our objective was to evaluate two potential factors that could influence the maximum urine tonicity, hypernatraemia and the rate of urea excretion. Balance studies were carried out in vasopressin-treated rats fed a low-electrolyte diet. In the first series, the drinking solution contained an equivalent sodium chloride (NaCl) load at 150 or 600 mmol l−1. In the second series, the maximum urine tonicity was evaluated in rats consuming 600 mmol l−1 NaCl with an 8-fold range of urea excretion. Hypernatraemia (148 ± 1 mmol l−1) developed in all rats that drank 600 mmol l−1 saline. Although the rate of Na+ + K+ excretion was similar in both saline groups, the maximum urine total cation concentration was significantly higher in the hypernatraemic group (731 ± 31 vs. 412 ± 37 mmol l−1). Only when the rate of excretion of urea was very low, was there a further increase in the maximum urine total cation concentration (1099 ± 118 mmol l−1). Thus hypernatraemia was the most important factor associated with a higher urine tonicity. PMID:12068051

Dietary intake and urinary excretion of lignans in Finnish men.

PubMed

Nurmi, Tarja; Mursu, Jaakko; Peñalvo, José L; Poulsen, Henrik E; Voutilainen, Sari

2010-03-01

Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100 Finnish men consuming their habitual omnivorous diet, and measured the 24 h urinary excretion of plant and enterolignans to compare the intake and metabolism. Dietary determinants of lignan intake and their urinary excretion were also determined. The mean intake of lignans was 1224 (sd 539) mug/d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion of plant lignans was explained 14 % by the intake of rye products and intake of coffee, and consequently 3-7 % by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11 % by the intake of vegetables and rye products, 14 % by the intake of water-soluble fibre and only 4 % by the intake of lariciresinol. Although the assessed intake of lignans corresponded well with the urinary excretion of lignans, the enterolactone production in the human body depended more on the dietary sources of lignans than the absolute intake of lignans.