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Sample records for acute viral load

  1. Lack of association between viral load and severity of acute bronchiolitis in infants

    PubMed Central

    de Souza, Ana Paula Duarte; Leitão, Lidiane Alves de Azeredo; Luisi, Fernanda; Souza, Rodrigo Godinho; Coutinho, Sandra Eugênia; da Silva, Jaqueline Ramos; Mattiello, Rita; Pitrez, Paulo Márcio Condessa; Stein, Renato Tetelbom; Pinto, Leonardo Araújo

    2016-01-01

    ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants. PMID:27832233

  2. Higher HIV RNA Viral Load in Recent Patients with Symptomatic Acute HIV Infection in Lyon University Hospitals

    PubMed Central

    Girerd-Genessay, Isabelle; Baratin, Dominique; Ferry, Tristan; Chidiac, Christian; Ronin, Vincent; Vanhems, Philippe

    2016-01-01

    Introduction Increased human immunodeficiency virus (HIV) virulence at infection has been suggested by a meta-analysis based on viral load and CD4 T lymphocytes (CD4) count during acute infection. This result was obtained after secondary analyses of large databases, facilitating the detection of differences. Similar finding in cohorts of more modest sample size would indicate that the effect could be more substantial. Methods Change from initial CD4 count and HIV viral load after acute HIV infection by calendar year was explored in patients treated at Lyon University hospitals. All patients admitted to our hospitals with acute HIV infection between 1996 and 2013 were included in our study. Initial CD4 count and viral load before the start of anti-retroviral treatment were analyzed. Trends over time were assessed in linear models. Results Initial CD4 count remained similar over time. However, in 2006–2013, initial viral load rose significantly (+1.12 log10/ml/year, p = 0.01). Conclusion Our data, obtained from a single hospital cohort, confirmed findings from a large meta-analysis, showed increased initial viremia at acute HIV infection since 2006 and suggesting potentially higher HIV virulence in recent years. PMID:26799390

  3. Acute viral myocarditis

    PubMed Central

    Dennert, Robert; Crijns, Harry J.; Heymans, Stephane

    2008-01-01

    Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482

  4. Viral load distribution in SARS outbreak.

    PubMed

    Chu, Chung-Ming; Cheng, Vincent C C; Hung, Ivan F N; Chan, Kin-Sang; Tang, Bone S F; Tsang, Thomas H F; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2005-12-01

    An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribution. Higher nasopharyngeal viral load was found in patients living in adjacent units of the same block inhabited by the index patient, while a lower but detectable nasopharyngeal viral load was found in patients living further away from the index patient. This pattern of nasopharyngeal viral load suggested that airborne transmission played an important part in this outbreak in Hong Kong. Contaminated fomites and rodent pests may have also played a role.

  5. In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.

    PubMed

    Takahashi, Yoshiaki; Byrareddy, Siddappa N; Albrecht, Christina; Brameier, Markus; Walter, Lutz; Mayne, Ann E; Dunbar, Paul; Russo, Robert; Little, Dawn M; Villinger, Tara; Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Villinger, Francois; Ansari, Aftab A

    2014-03-01

    The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8⁺ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4⁺ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a⁺ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses.

  6. Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

    PubMed Central

    2011-01-01

    Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression. PMID:21831310

  7. Hepatitis viral load correlates to glutathione levels.

    PubMed

    1998-01-01

    Several recent scientific articles have found a direct correlation between Glutathione levels and viral activity for hepatitis B and C. When viral load increases, Glutathione decreases. Researchers from Germany report that adding NAC (N-acetyl cysteine) to HBV producing cells lines can reduce hepatitis viral load 50 fold. Glutathione is used by the liver to help break down toxins. Patients who have chronic infection for more than 90 days should ask their physicians to check their Glutathione levels. A test kit is available from ImmunoSciences Labs; contact information is included. An amino acid, L-Glutamine, can be used with Alpha Lipoic Acid and NAC to increase Glutathione levels. Chlorophyll also offers benefits to people with hepatitis and other infections. Instructions on how to use a special retention enema containing chlorophyll, water, and apple cider vinegar are provided.

  8. Lymphocyte populations in acute viral gastroenteritis.

    PubMed Central

    Dolin, R; Reichman, R C; Fauci, A S

    1976-01-01

    Viral gastroenteritis was induced in 16 of 24 normal volunteers after oral administration of either the Norwalk or Hawaii agents. Clinical illness lasted for 24 to 48 h and resolved spontaneously. During acute illness, a transient lymphopenia was noted which involved all lymphocyte subpopulations (thymus-and bone marrow-derived, and null cells). No circulating lymphocytotoxins were detected, and the lymphocytes remaining in the circulation responded normally to mitogenic stimuli. The acute lymphopenia occurred at the time that mononuclear cell infiltration of the jejunal mucosa has been noted. These findings are consistent with the occurrence of a redistribution of circulating lymphocytes during acute illness, with accumulation of lymphocytes at the site of infection in the gut. PMID:1085751

  9. HIV community viral load trends in South Carolina.

    PubMed

    Chakraborty, Hrishikesh; Weissman, Sharon; Duffus, Wayne A; Hossain, Akhtar; Varma Samantapudi, Ashok; Iyer, Medha; Albrecht, Helmut

    2017-03-01

    Community viral load is an aggregate measure of HIV viral load in a particular geographic location, community, or subgroup. Community viral load provides a measure of disease burden in a community and community transmission risk. This study aims to examine community viral load trend in South Carolina and identify differences in community viral load trends between selected population subgroups using a state-wide surveillance dataset that maintains electronic records of all HIV viral load measurements reported to the state health department. Community viral load trends were examined using random mixed effects models, adjusting for age, race, gender, residence, CD4 counts, HIV risk group, and initial antiretroviral regimen during the study period, and time. The community viral load gradually decreased from 2004 to 2013 ( p < 0.0001). The number of new infections also decreased ( p = 0.0001) over time. A faster rate of decrease was seen among men compared to women ( p < 0.0001), men who have sex with men ( p = 0.0001) compared to heterosexuals, patients diagnosed in urban areas compared to that in rural areas ( p = 0.0004), and patients prescribed single-tablet regimen compared to multiple-tablet regimen ( p < 0.0001). While the state-wide community viral load decreased over time, the decline was not uniform among residence at diagnosis, HIV risk group, and single-tablet regimen versus multiple-tablet regimen subgroups. Slower declines in community viral load among females, those in rural areas, and heterosexuals suggest possible disparities in care that require further exploration. The association between using single-tablet regimen and faster community viral load decline is noteworthy.

  10. Viral load: Roche applies for marketing approval for ultrasensitive test.

    PubMed

    1998-08-07

    Roche Molecular Systems has applied for FDA permission to market a more sensitive viral load test. The Amplicor HIV-1 Monitor UltraSensitive Method tests viral load as low as 50 copies; current tests are only accurate to 400 copies. There is a widespread consensus among physicians that testing below 400 copies would be a valuable treatment tool.

  11. Viral loads in dual infection with HIV-1 and cytomegalovirus

    PubMed Central

    Boriskin, Y.; Sharland, M.; Dalton, R.; duMont, G.; Booth, J.

    1999-01-01

    OBJECTIVE—A one year study of the relation between cytomegalovirus (CMV) and human immunodeficiency virus (HIV) viral loads in a cohort of children with vertically acquired HIV-1 infection.
DESIGN—Comparative analysis of viral load measurements for CMV and HIV-1 in peripheral blood leucocytes (PBLs) of individual children in relation to age and clinical staging.
METHODS—Nested polymerase chain reaction (PCR) was used to measure HIV-1 proviral DNA and CMV genomic DNA in PBLs of 56children.
RESULTS—The CMV load was highest in 0-2 year old HIV positive children with stage C disease (range, 1-7143 copies/100 ng DNA; median, 125) and was significantly lower in older children. Although higher in young children, HIV-1 viral load did not show the same marked reduction with age that is seen with CMV. Over a one year period, testing of serial samples for both viruses in a subgroup of children revealed a discordant relation between viral loads for CMV and HIV-1.
CONCLUSIONS—CMV viral load falls much faster than HIV viral load in dually infected children. Screening for clinical CMV disease is most likely to be of benefit in children under 2 years of age with stage C disease. In the few children studied, levels of CMV and HIV replication appear to be independent.

 PMID:10325727

  12. Undiagnosed acute viral febrile illnesses, Sierra Leone.

    PubMed

    Schoepp, Randal J; Rossi, Cynthia A; Khan, Sheik H; Goba, Augustine; Fair, Joseph N

    2014-07-01

    Sierra Leone in West Africa is in a Lassa fever-hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500-700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%-40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%-70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus.

  13. Crimean-Congo hemorrhagic fever: CXCL10 correlates with the viral load.

    PubMed

    Papa, Anna; Yagci Caglayık, Dilek; Christova, Iva; Tsergouli, Katerina; Korukluoglu, Gulay; Uyar, Yavuz

    2015-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a human disease with high fatality rate. Although its pathogenesis is not elucidated yet, it is considered that cytokines play a significant role in the progression and outcome of the disease. Serum CXCL10 levels were estimated in 35 patients with acute CCHF and were correlated with the viral load, and various demographic and clinical parameters. The mean CXCL10 concentration in the patients' group was higher compared to the respective value in the control group (4421.74 pg/ml vs. 28.47 pg/ml, P < 0.05). A strong positive correlation between CXCL10 and viral load was seen (rs = 0.57, P < 0.001), while the outcome of the disease was related with the viral load (rs = 0.47, P = 0.004) and the presence of hemorrhagic manifestations (P < 0.001). The study provides an insight into the strong correlation between CXCL10 and viral load in acute CCHF cases suggesting that it plays an important role in CCHF pathogenesis.

  14. Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

    PubMed

    Ghietto, Lucía María; Majul, Diego; Ferreyra Soaje, Patricia; Baumeister, Elsa; Avaro, Martín; Insfrán, Constanza; Mosca, Liliana; Cámara, Alicia; Moreno, Laura Beatriz; Adamo, Maria Pilar

    2015-01-01

    Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host.

  15. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    PubMed

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-03-11

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS.

  16. Viral Load and CD4+ T-Cell Dynamics in Primary HIV-1 Subtype C Infection

    PubMed Central

    Novitsky, Vladimir; Woldegabriel, Elias; Kebaabetswe, Lemme; Rossenkhan, Raabya; Mlotshwa, Busisiwe; Bonney, Caitlin; Finucane, Mariel; Musonda, Rosemary; Moyo, Sikhulile; Wester, Carolyn; van Widenfelt, Erik; Makhema, Joseph; Lagakos, Stephen; Essex, M.

    2009-01-01

    Background Most knowledge of primary HIV-1 infection is based on subtype B studies, whereas the evolution of viral parameters in the early phase of HIV-1 subtype C infection is not well characterized. Methods The kinetics of viral RNA, proviral DNA, CD4+ T-cell count, and subsets of CD4+ T cells expressing CCR5 or CXCR4 were characterized in 8 acute and 62 recent subtype C infections over the first year postseroconversion. Results The viral RNA peak was 6.25 ± 0.92 log10 copies per milliliter. After seroconversion, heterogeneity among acute cases was evident by patterns of change in viral load and CD4+ T-cell count over time. The patterns were supported by the rate of viral RNA decline from peak (P = 0.022), viral RNA means (P = 0.005), CD4 levels (P <0.001), and CD4 decline to 350 (P = 0.011) or 200 (P = 0.046). Proviral DNA had no apparent peak and its mean was 2.59 ± 0.69 log10 per 106 peripheral blood mononuclear cell. In recent infections, viral RNA set point was 4.00 ± 0.97 log10 and viral RNA correlated inversely with CD4+ T cells (P <0.001) and directly with proviral DNA (P <0.001). Conclusions Distinct patterns of viral RNA evolution may exist shortly after seroconversion in HIV-1 subtype C infection. The study provides better understanding of the early phase of subtype C infection. PMID:19295336

  17. [Cerebrospinal fluid viral load in HIV-1 positive hemophilic patients treated with HAART].

    PubMed

    Corti, M E; Villafañe, M F; Baré, P; Alves Rosa, F; Cermelj, M; Candela, M; Pérez Bianco, R; Tezanos Pinto, M

    2001-01-01

    As HIV seropositive patients with undetectable CSF viral load have a lower likelihood of developing neurologic disease, the determination of CSF viral load levels may be useful to evaluate the efficacy of HAART. We compared plasma viral load levels with HIV-1 RNA CSF levels in 18 hemophilic patients without neurocognitive involvement under HAART. We detected a significant correlation between plasma viral load levels and CSF viral load levels. Fourteen patients with undetectable plasma viral load had undetectable RNA HIV-1 CSF levels as well. Four patients with detectable plasma viral load had detectable HIV-RNA in CSF, but the latter were significantly lower. Viral load is usually lower in non-blood fluids and HAART decreases the viral load in CSF as well as in blood.

  18. Modelling HIV-RNA viral load in vertically infected children.

    PubMed

    Gray, Linsay; Cortina-Borja, Mario; Newell, Marie-Louise

    2004-03-15

    Human immunodeficiency virus (HIV) ribo-nucleic acid (RNA) viral load is a measure of actively replicating virus and is used as a marker of disease progression. For a thorough understanding of the dynamics of the evolution of the virus in the early life of HIV-1 vertically infected children, it is important to elucidate the pattern of HIV-RNA viral load over age. An aspect of assay systems used in the quantification of RNA viral load is that they measure values above particular cut-off values for detection, below which the assays used are not sufficiently sensitive. In this way, measurements are potentially left-censored. Recent adult studies suggest that to adequately model RNA pattern over age, it is necessary to account for within-subject correlation, due to repeated measures, and censoring. The aim of this study, therefore, was to establish whether it is necessary to use complex methods to allow for repeated measures within individuals and censoring of the HIV-RNA viral load in children enrolled in a cohort study. The approach involved the identification of an appropriate model for the basic pattern of RNA viral load by age and subsequent assessment of various estimation procedures accounting for repeated measures and censoring in different ways. Methods developed by Hughes involving the expectation-maximization (EM) algorithm and the Gibbs sampler were taken as the benchmark for comparison of simpler alternatives. Other approaches considered involve linear mixed-effects and ordinary least squares in which censoring is dealt with informally by taking the cut-off value as absolute or taking the mid-point between cut-off and zero. Fractional polynomials provided a substantially superior approach for modelling the dynamics of viral load over age compared to conventional polynomials or change-point models. Allowing for repeated measures was necessary to improve the power of the likelihood ratio tests required to establish the final model, but methods beyond taking

  19. Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load

    PubMed Central

    Ng, Kim Tien; Chook, Jack Bee; Oong, Xiang Yong; Chan, Yoke Fun; Chan, Kok Gan; Hanafi, Nik Sherina; Pang, Yong Kek; Kamarulzaman, Adeeba; Tee, Kok Keng

    2016-01-01

    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5′-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2–7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control. PMID:27721388

  20. The Association of Viral Hepatitis and Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

    1972-01-01

    The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

  1. 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

  2. A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads

    PubMed Central

    Metcalf Pate, Kelly A.; Pohlmeyer, Christopher W.; Walker-Sperling, Victoria E.; Foote, Jeremy B.; Najarro, Kevin M.; Cryer, Catherine G.; Salgado, Maria; Gama, Lucio; Engle, Elizabeth L.; Shirk, Erin N.; Queen, Suzanne E.; Chioma, Stanley; Vermillion, Meghan S.; Bullock, Brandon; Li, Ming; Lyons, Claire E.; Adams, Robert J.; Zink, M. Christine; Clements, Janice E.; Mankowski, Joseph L.; Blankson, Joel N.

    2015-01-01

    Background. Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)–infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification. Methods. Peripheral blood mononuclear cells or purified CD4+ T cells from HIV or simian immunodeficiency virus (SIV)–infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8+ T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody. Results. With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA. Conclusions. Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads. PMID:25883388

  3. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    USGS Publications Warehouse

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  4. Acute viral hepatitis in Hanoi, Viet Nam.

    PubMed

    Corwin, A L; Dai, T C; Duc, D D; Suu, P I; Van, N T; Ha, L D; Janick, M; Kanti, L; Sie, A; Soderquist, R; Graham, R; Wignall, S F; Hyams, K C

    1996-01-01

    A study of acute hepatitis was conducted in Hanoi, Viet Nam, from January 1993 to February 1995; 188 sera from clinical hepatitis cases were screened by enzyme-linked immunosorbent assay for immunoglobulin (Ig) M anti-hepatitis A virus (HAV), IgM anti-hepatitis B core antigen (HBc), IgG anti-hepatitis C virus (HCV), IgG anti-hepatitis E virus (HEV) and IgM anti-HEV. Additionally, 187 sera from control subjects, matched by age, sex and month of admission, with no recent history of hepatitis, were tested for comparative purposes. There was serological evidence of recent HAV (29%) and hepatitis B virus (24%) infection in 53% of cases (2 mixed infections), compared with 2% of controls. HCV infections were detected in 10% of cases (with no IgM anti-HAV or IgM anti-HBc) and in 1% of control sera. There was no significant difference in the proportion of IgG anti-HEV positive sera between cases (in the absence of IgM anti-HAV or IgM anti-HBc) (21%) and controls (14%); 3% of all case sera were IgM anti-HEV positive. Younger cases (< 20 years) were more likely to have recent HAV infections (41%) than those aged > or = 20 years (21%) (P < 0.01). In contrast, a higher percentage of adult cases had IgM anti-HBc, IgG anti-HCV and IgG anti-HEV (in the absence of recent HAV or HBV infection) than did children. No seasonal trend in hepatitis admissions was detected, nor an association between water-borne infections (HAV and HEV) and the warmer months. Hepatitis patients lived throughout Hanoi and surrounding areas, with no identifiable geographical clustering, regardless of serological marker.

  5. Viral load, gene expression and mapping of viral integration sites in HPV16-associated HNSCC cell lines

    PubMed Central

    Olthof, Nadine C.; Huebbers, Christian U.; Kolligs, Jutta; Henfling, Mieke; Ramaekers, Frans C.S.; Cornet, Iris; van Lent-Albrechts, Josefa A.; Stegmann, Sander P.A.; Silling, Steffi; Wieland, Ulrike; Carey, Thomas E.; Walline, Heather M.; Gollin, Susanne M.; Hoffmann, Thomas K.; de Winter, Johan; Kremer, Bernd; Klussmann, Jens-Peter; Speel, Ernst-Jan M.

    2017-01-01

    HPV-related HNSCC generally have a better prognosis than HPV-negative HNSCC. However, a subgroup of HPV-positive tumors with poor prognosis has been recognized, particularly related to smoking, EGFR overexpression and chromosomal instability. Viral integration into the host genome might contribute to carcinogenesis, as is shown for cervical carcinomas. Therefore, all HPV16-positive HNSCC cell lines currently available have been carefully analysed for viral and host genome parameters. The viral integration status, viral load, viral gene expression and the presence of aneusomies was evaluated in the cell lines UD-SCC-2, UM-SCC-047, UM-SCC-104, UPCI:SCC090, UPCI:SCC152, UPCI:SCC154 and 93VU147T. HPV integration was examined using FISH, APOT-PCR and DIPS-PCR. Viral load and the expression of the viral genes E2, E6 and E7 were determined via quantitative PCR. All cell lines showed integration-specific staining patterns and signals indicating transcriptional activity using FISH. APOT- and DIPS-PCR identified integration-derived fusion products in six cell lines, and only episomal products for UM-SCC-104. Despite the observed differences in viral load and the number of viral integration sites, this did not relate to the identified viral oncogene expression. Furthermore, cell lines exhibited EGFR expression, and aneusomy (except UPCI:SCC154). In conclusion, all HPV16-positive HNSCC cell lines showed integrated and/or episomal viral DNA that is transcriptionally active, although viral oncogene expression was independent of viral copy number and the number of viral integration sites. Because these cell lines also contain EGFR expression and aneusomy, which are parameters of poor prognosis, they should be considered suitable model systems for the development of new antiviral therapies. PMID:25082736

  6. Viral load, gene expression and mapping of viral integration sites in HPV16-associated HNSCC cell lines.

    PubMed

    Olthof, Nadine C; Huebbers, Christian U; Kolligs, Jutta; Henfling, Mieke; Ramaekers, Frans C S; Cornet, Iris; van Lent-Albrechts, Josefa A; Stegmann, Alexander P A; Silling, Steffi; Wieland, Ulrike; Carey, Thomas E; Walline, Heather M; Gollin, Susanne M; Hoffmann, Thomas K; de Winter, Johan; Kremer, Bernd; Klussmann, Jens P; Speel, Ernst-Jan M

    2015-03-01

    HPV-related HNSCC generally have a better prognosis than HPV-negative HNSCC. However, a subgroup of HPV-positive tumors with poor prognosis has been recognized, particularly related to smoking, EGFR overexpression and chromosomal instability. Viral integration into the host genome might contribute to carcinogenesis, as is shown for cervical carcinomas. Therefore, all HPV16-positive HNSCC cell lines currently available have been carefully analyzed for viral and host genome parameters. The viral integration status, viral load, viral gene expression and the presence of aneusomies was evaluated in the cell lines UD-SCC-2, UM-SCC-047, UM-SCC-104, UPCI:SCC090, UPCI:SCC152, UPCI:SCC154 and 93VU147T. HPV integration was examined using FISH, APOT-PCR and DIPS-PCR. Viral load and the expression of the viral genes E2, E6 and E7 were determined via quantitative PCR. All cell lines showed integration-specific staining patterns and signals indicating transcriptional activity using FISH. APOT- and DIPS-PCR identified integration-derived fusion products in six cell lines and only episomal products for UM-SCC-104. Despite the observed differences in viral load and the number of viral integration sites, this did not relate to the identified viral oncogene expression. Furthermore, cell lines exhibited EGFR expression and aneusomy (except UPCI:SCC154). In conclusion, all HPV16-positive HNSCC cell lines showed integrated and/or episomal viral DNA that is transcriptionally active, although viral oncogene expression was independent of viral copy number and the number of viral integration sites. Because these cell lines also contain EGFR expression and aneusomy, which are parameters of poor prognosis, they should be considered suitable model systems for the development of new antiviral therapies.

  7. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    PubMed

    Herbeck, Joshua T; Mittler, John E; Gottlieb, Geoffrey S; Mullins, James I

    2014-06-01

    Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  8. Neuroelectric assessment of HIV: EEG, ERP, and viral load.

    PubMed

    Polich, J; Ilan, A; Poceta, J S; Mitler, M M; Darko, D F

    2000-10-01

    The effects of the human immunodeficiency virus (HIV) infection on the central nervous system function were studied with electroencephalographic (EEG) and auditory event-related brain potentials (EPRs) in patients infected with HIV and unaffected young adult control subjects (n=10/group). All subjects were assessed once every 15 min for four trial blocks at the same time of day to assess EEG/ERP changes with time on task-induced fatigue. Spectral analysis was applied to the pre- and post-stimulus EEG segments. ERP values were evaluated with respect to group differences for component amplitude and latency measures. Spectral analysis demonstrated that HIV patients evinced greater pre-stimulus delta power over frontal areas compared to control subjects, and less post-stimulus spectral power for the delta, theta, and alpha bands over the central/parietal areas. P300 amplitude was smaller, and latency was marginally longer for the HIV patients compared to control subjects. P300 latency correlated positively with increases in the patient HIV viral load. Time-on-task generally did not affect EEG or ERP measures for either group other than contributing to an overall decrease in neuroelectric responsivity. Group spectral power effects were consistent with differences in arousal/fatigue level. P300 group differences were consistent with declines in cognitive capability, and P300 latency increased with increased viral load. HIV infection negatively affected central nervous system function as measured by EEG and cognitive ERPs in a manner that suggests decreased arousal and increased fatigue in HIV patients.

  9. The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen

    PubMed Central

    Sadiq, S; McSorley, J; Copas, A; Bennett, J; Edwards, S; Kaye, S; Kirk, S; French, P; Weller, I

    2005-01-01

    Objective: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts. Methods: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20). Results: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either. Conclusions: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen. PMID:16199736

  10. Viral Load Drives Disease in Humans Experimentally Infected with Respiratory Syncytial Virus

    PubMed Central

    DeVincenzo, John P.; Wilkinson, Tom; Vaishnaw, Akshay; Cehelsky, Jeff; Meyers, Rachel; Nochur, Saraswathy; Harrison, Lisa; Meeking, Patricia; Mann, Alex; Moane, Elizabeth; Oxford, John; Pareek, Rajat; Moore, Ryves; Walsh, Ed; Studholme, Robert; Dorsett, Preston; Alvarez, Rene; Lambkin-Williams, Robert

    2010-01-01

    Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immune-mediated rather than being driven by viral load. Objectives: The development of a human experimental wild-type RSV infection model to address these challenges. Methods: Healthy volunteers (n = 35), in five cohorts, received increasing quantities (3.0–5.4 log plaque-forming units/person) of wild-type RSV-A intranasally. Measurements and Main Results: Overall, 77% of volunteers consistently shed virus. Infection rate, viral loads, disease severity, and safety were similar between cohorts and were unrelated to quantity of RSV received. Symptoms began near the time of initial viral detection, peaked in severity near when viral load peaked, and subsided as viral loads (measured by real-time polymerase chain reaction) slowly declined. Viral loads correlated significantly with intranasal proinflammatory cytokine concentrations (IL-6 and IL-8). Increased viral load correlated consistently with increases in multiple different disease measurements (symptoms, physical examination, and amount of nasal mucus). Conclusions: Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics. PMID:20622030

  11. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    PubMed Central

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made. PMID:25709166

  12. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection.

    PubMed

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  13. Severe acute bovine viral diarrhea in Ontario, 1993-1995.

    PubMed

    Carman, S; van Dreumel, T; Ridpath, J; Hazlett, M; Alves, D; Dubovi, E; Tremblay, R; Bolin, S; Godkin, A; Anderson, N

    1998-01-01

    In 1993, noncytopathic bovine viral diarrhea virus (BVDV) strains with enhanced virulence caused unprecedented outbreaks of severe acute bovine viral diarrhea (BVD) in dairy, beef, and veal herds in Ontario (Canada). Fever, pneumonia, diarrhea, and sudden death occurred in all age groups of cattle. Abortions often occurred in pregnant animals. Gross lesions in the alimentary tract were similar to those associated with mucosal disease, especially in animals >6 months of age. Cattle of all age groups had microscopic lesions in the alimentary tract similar to those seen with mucosal disease. The epidemic peaked in the summer of 1993, with 15% of all bovine accessions from diseased cattle presented to the diagnostic laboratory being associated with BVDV. The virus strains involved in the outbreak were analyzed using monoclonal and polyclonal antibodies and the polymerase chain reaction. The virus isolates from these outbreaks of severe disease were determined to be type 2 BVDV. Type 2 BVDV has been present in Ontario at least since 1981 without causing widespread outbreaks of severe acute BVD, which suggests that type 2 designation in itself does not imply enhanced virulence. Cattle properly vaccinated with type 1 BVDV vaccines appear to be protected from clinical disease.

  14. Clinical signs of dysphagia in infants with acute viral bronchiolitis☆

    PubMed Central

    Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

    2014-01-01

    Objective: To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. Methods: This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Results: Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Conclusions: Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. PMID:25479843

  15. Viral load and stochastic mutation in a Monte Carlo simulation of HIV

    NASA Astrophysics Data System (ADS)

    Ruskin, H. J.; Pandey, R. B.; Liu, Y.

    2002-08-01

    Viral load is examined, as a function of primary viral growth factor ( Pg) and mutation, through a computer simulation model for HIV immune response. Cell-mediated immune response is considered on a cubic lattice with four cell types: macrophage ( M), helper ( H), cytotoxic ( C), and virus ( V). Rule-based interactions are used with random sequential update of the binary cellular states. The relative viral load (the concentration of virus with respect to helper cells) is found to increase with the primary viral growth factor above a critical value ( Pc), leading to a phase transition from immuno-competent to immuno-deficient state. The critical growth factor ( Pc) seems to depend on mobility and mutation. The stochastic growth due to mutation is found to depend non-monotonically on the relative viral load, with a maximum at a characteristic load which is lower for stronger viral growth.

  16. Role of the innate immune system in acute viral myocarditis.

    PubMed

    Huang, Chien-Hua; Vallejo, Jesus G; Kollias, George; Mann, Douglas L

    2009-05-01

    Although the adaptive immune system is thought to play an important role in the pathogenesis of viral myocarditis, the role of the innate immune system has not been well defined. To address this deficiency, we employed a unique line of mice that harbor a genomic "knock in" of a mutated TNF gene lacking the AU rich element (TNF(ARE/ARE)) that is critical for TNF mRNA stability and translation, in order to examine the contribution of the innate immune system in encephalomyocarditis-induced myocarditis (EMCV). Heterozygous mice (TNF(ARE/+)) were infected with 500 plaque-forming units of EMCV. TNF(ARE/+)mice had a significantly higher 14-day mortality and myocardial inflammation when compared to littermate control mice. Virologic studies showed that the viral load at 14 days was significantly lower in the hearts of TNF(ARE/+) mice. TNF(ARE/+) mice had an exaggerated proinflammatory cytokine and chemokine response in the heart following EMCV infection. Modulation of the innate immune response in TNF(ARE/+) mice by the late administration of prednisolone resulted in a significant improvement in survival and decreased cardiac inflammation, whereas early administration of prednisolone resulted in a blunted innate response and increased mortality in littermate control mice. Viewed together, these data suggest that the duration and degree of activation of the innate immune system plays a critical role in determining host outcomes in experimental viral myocarditis.

  17. Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy

    PubMed Central

    Ferguson, Deborah; Clarke, Sean; Berry, Neil; Almond, Neil

    2016-01-01

    Objectives: Using simian models, where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated. Design: Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viraemia. Study 1: animals were maintained up to 300 days after inoculation and analysed for viral-induced neuropathology following sustained suppression of chronic viral loads. Study 2: initiation and development of lesion was examined following 3, 10, 21, or 125 days SIVmacC8 infection. Methods: Formalin-fixed, paraffin-embedded brain sections were analysed following immunohistochemical staining for simian immunodeficiency virus (SIV) (KK41), blood–brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation [GFAP, cyclooxygenase (COX)-1, COX-2], microglia and macrophage (Iba-1, CD68, and CD16), oligodendrocytes (CNPase1), MHC class II expression, and T cells (CD3 and CD8). Replicating SIV was detected through in-situ hybridization. Results: Study 1: neuroinflammation was present despite prolonged suppressed viraemia. Study 2: attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naive levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load. Conclusion: Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viraemia to potentially reseed the brain. PMID:27258396

  18. Drivers of Inter-individual Variation in Dengue Viral Load Dynamics

    PubMed Central

    Ben-Shachar, Rotem; Schmidler, Scott; Koelle, Katia

    2016-01-01

    Dengue is a vector-borne viral disease of humans that endemically circulates in many tropical and subtropical regions worldwide. Infection with dengue can result in a range of disease outcomes. A considerable amount of research has sought to improve our understanding of this variation in disease outcomes and to identify predictors of severe disease. Contributing to this research, patterns of viral load in dengue infected patients have been quantified, with analyses indicating that peak viral load levels, rates of viral load decline, and time to peak viremia are useful predictors of severe disease. Here, we take a complementary approach to understanding patterns of clinical manifestation and inter-individual variation in viral load dynamics. Specifically, we statistically fit mathematical within-host models of dengue to individual-level viral load data to test virological and immunological hypotheses explaining inter-individual variation in dengue viral load. We choose between alternative models using model selection criteria to determine which hypotheses are best supported by the data. We first show that the cellular immune response plays an important role in regulating viral load in secondary dengue infections. We then provide statistical support for the process of antibody-dependent enhancement (but not original antigenic sin) in the development of severe disease in secondary dengue infections. Finally, we show statistical support for serotype-specific differences in viral infectivity rates, with infectivity rates of dengue serotypes 2 and 3 exceeding those of serotype 1. These results contribute to our understanding of dengue viral load patterns and their relationship to the development of severe dengue disease. They further have implications for understanding how dengue transmissibility may depend on the immune status of infected individuals and the identity of the infecting serotype. PMID:27855153

  19. Human papillomavirus type 16 viral load measurement as a predictor of infection clearance

    PubMed Central

    Schlecht, Nicolas F.; Ramanakumar, Agnihotram V.; Villa, Luisa L.; Franco, Eduardo L.

    2013-01-01

    Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig–McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman’s rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol. PMID:23677791

  20. Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma

    PubMed Central

    Hsieh, Ai-Ru; Fann, Cathy SJ; Yeh, Chau-Ting; Lin, Hung-Chun; Wan, Shy-Yi; Chen, Yi-Cheng; Hsu, Chia-Lin; Tai, Jennifer; Lin, Shi-Ming; Tai, Dar-In

    2017-01-01

    AIM To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives. METHODS We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis. RESULTS Among 729 relatives enrolled, parent generation (P = 0.0076), index generation (P = 0.0044), mothers positive for HBsAg (P = 0.0007), and HBsAg-positive index cases (P = 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P = 0.0359) and sex (P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P = 0.024) and older siblings were associated with high viral load. CONCLUSION Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations. PMID:28223732

  1. FDA review of viral load test kits. Food and Drug Administration.

    PubMed

    1996-03-01

    Viral load testing, which quantifies the amount of HIV in the blood plasma of infected individuals, may dramatically shorten the time necessary to test drugs prior to approval and marketing. Two manufacturers have applied for approval of their test kits. Hoffman-LaRoche (Roche Molecular Systems) developed a test kit called quantitative competitive polymerase chain reaction (quantitative PCR). Chiron Corporation's product is called branched chain DNA, or bDNA. Both tests give similar results. Viral load is an indicator of the effectiveness of drug therapy, and high viral load is an indicator of disease progression and clinical decline.

  2. Mapping HIV community viral load: space, power and the government of bodies.

    PubMed

    Gagnon, Marilou; Guta, Adrian

    2012-12-01

    HIV plasma viral load testing has become more than just a clinical tool to monitor treatment response at the individual level. Increasingly, individual HIV plasma viral load testing is being reported to public health agencies and is used to inform epidemiological surveillance and monitor the presence of the virus collectively using techniques to measure 'community viral load'. This article seeks to formulate a critique and propose a novel way of theorizing community viral load. Based on the salient work of Michel Foucault, especially the governmentality literature, this article critically examines the use of community viral load as a new strategy of government. Drawing also on the work of Miller and Rose, this article explores the deployment of 'community' through the re-configuration of space, the problematization of viral concentrations in specific microlocales, and the government (in the Foucauldian sense) of specific bodies which are seen as 'risky', dangerous and therefore, in need of attention. It also examines community viral load as a necessary precondition - forming the 'conditions of possibility' - for the recent shift to high impact prevention tactics that are being scaled up across North America.

  3. Mapping HIV community viral load: space, power and the government of bodies

    PubMed Central

    Gagnon, Marilou; Guta, Adrian

    2012-01-01

    HIV plasma viral load testing has become more than just a clinical tool to monitor treatment response at the individual level. Increasingly, individual HIV plasma viral load testing is being reported to public health agencies and is used to inform epidemiological surveillance and monitor the presence of the virus collectively using techniques to measure ‘community viral load’. This article seeks to formulate a critique and propose a novel way of theorizing community viral load. Based on the salient work of Michel Foucault, especially the governmentality literature, this article critically examines the use of community viral load as a new strategy of government. Drawing also on the work of Miller and Rose, this article explores the deployment of ‘community’ through the re-configuration of space, the problematization of viral concentrations in specific microlocales, and the government (in the Foucauldian sense) of specific bodies which are seen as ‘risky’, dangerous and therefore, in need of attention. It also examines community viral load as a necessary precondition — forming the ‘conditions of possibility’ — for the recent shift to high impact prevention tactics that are being scaled up across North America. PMID:23060688

  4. Plasmodium falciparum Infection Does Not Affect Human Immunodeficiency Virus Viral Load in Coinfected Rwandan Adults

    PubMed Central

    Subramaniam, Krishanthi; Plank, Rebeca M.; Lin, Nina; Goldman-Yassen, Adam; Ivan, Emil; Becerril, Carlos; Kemal, Kimdar; Heo, Moonseong; Keller, Marla J.; Mutimura, Eugene; Anastos, Kathryn; Daily, Johanna P.

    2014-01-01

    Background  Plasmodium falciparum infection has been reported to increase human immunodeficiency virus (HIV) viral load (VL), which can facilitate HIV transmission. We prospectively studied the impact of mild P falciparum coinfection on HIV VL in Rwanda. Methods  We measured plasma HIV VL at presentation with malaria infection and weekly for 4 weeks after artemether-lumefantrine treatment in Rwandan adults infected with HIV with P falciparum malaria. Regression analyses were used to examine associations between malaria infection and HIV VL changes. Samples with detectable virus underwent genotypic drug-resistance testing. Results  We enrolled 28 HIV-malaria coinfected patients and observed 27 of them for 5 weeks. Three patients (11%) were newly diagnosed with HIV. Acute P falciparum infection had no significant effect on HIV VL slope over 28 days of follow-up. Ten patients with VL <40 copies/mL at enrollment maintained viral suppression throughout. Seventeen patients had a detectable VL at enrollment including 9 (53%) who reported 100% adherence to ARVs; 3 of these had detectable genotypic drug resistance. Conclusions  Unlike studies from highly malaria-endemic areas, we did not identify an effect of P falciparum infection on HIV VL; therefore, malaria is not likely to increase HIV-transmission risk in our setting. However, routine HIV testing should be offered to adults presenting with acute malaria in Rwanda. Most importantly, we identified a large percentage of patients with detectable HIV VL despite antiretroviral (ARV) therapy. Some of these patients had HIV genotypic drug resistance. Larger studies are needed to define the prevalence and factors associated with detectable HIV VL in patients prescribed ARVs in Rwanda. PMID:25734136

  5. Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

    PubMed

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens D; Eaton, Jeffrey W; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara M; Chakanyuka Musanhu, Christine; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, R Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David P; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa J; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy B; Revill, Paul

    2015-12-03

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

  6. Sustainable HIV Treatment in Africa through Viral Load-Informed Differentiated Care

    PubMed Central

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens; Eaton, Jeff; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara; Musanhu, Christine Chiedza; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy; Revill, Paul

    2016-01-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests. PMID:26633768

  7. Neuroprotection mediated by inhibition of calpain during acute viral encephalitis

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Mirchia, Kanish; Sauer, Brian M.; McGovern, Renee M.; Reid, Joel M.; Buenz, Eric J.

    2016-01-01

    Neurologic complications associated with viral encephalitis, including seizures and cognitive impairment, are a global health issue, especially in children. We previously showed that hippocampal injury during acute picornavirus infection in mice is associated with calpain activation and is the result of neuronal death triggered by brain-infiltrating inflammatory monocytes. We therefore hypothesized that treatment with a calpain inhibitor would protect neurons from immune-mediated bystander injury. C57BL/6J mice infected with the Daniel’s strain of Theiler’s murine encephalomyelitis virus were treated with the FDA-approved drug ritonavir using a dosing regimen that resulted in plasma concentrations within the therapeutic range for calpain inhibition. Ritonavir treatment significantly reduced calpain activity in the hippocampus, protected hippocampal neurons from death, preserved cognitive performance, and suppressed seizure escalation, even when therapy was initiated 36 hours after disease onset. Calpain inhibition by ritonavir may be a powerful tool for preserving neurons and cognitive function and preventing neural circuit dysregulation in humans with neuroinflammatory disorders. PMID:27345730

  8. Transient Viremia, Plasma Viral Load, and Reservoir Replenishment in HIV-Infected Patients on Antiretroviral Therapy

    PubMed Central

    Jones, Laura E.; Perelson, Alan S.

    2008-01-01

    Summary When antiretroviral therapy (ART) is administered for long periods to HIV-1–infected patients, most achieve viral loads that are “undetectable” by standard assay methods (ie, HIV-1 RNA <50 copies/mL). Despite sustaining viral loads lower than the level of detection, a number of patients experience unexplained episodes of transient viremia or viral “blips.” We propose that transient activation of the immune system by infectious agents may explain these episodes of viremia. Using 2 different mathematical models, one in which blips arise because of target cell activation and subsequent infection and another in which latent cell activation generates blips, we establish a nonlinear (power law) relationship between blip amplitude and viral load (under ART) that suggest blips should be of lower amplitude, and thus harder to detect, as increasingly potent therapy is used. This effect can be more profound than is predicted by simply lowering the baseline viral load from which blips originate. Finally, we suggest that sporadic immune activation may elevate the level of chronically infected cells and replenish viral reservoirs, including the latent cell reservoir, providing a mechanism for recurrent viral blips and low levels of viremia under ART. PMID:17496565

  9. Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

    PubMed Central

    2009-01-01

    Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis). Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123). Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

  10. Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring.

    PubMed

    Peter, Trevor; Ellenberger, Dennis; Kim, Andrea A; Boeras, Debrah; Messele, Tsehaynesh; Roberts, Teri; Stevens, Wendy; Jani, Ilesh; Abimiku, Alash'le; Ford, Nathan; Katz, Zachary; Nkengasong, John N

    2017-01-01

    Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.

  11. Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

    PubMed Central

    Nye, Steven; Whitley, Richard J.; Kong, Michele

    2016-01-01

    Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options. PMID:27933286

  12. Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome.

    PubMed

    Nye, Steven; Whitley, Richard J; Kong, Michele

    2016-01-01

    Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in "at risk" populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

  13. Multicenter Comparison of Laboratory Performance in Cytomegalovirus and Epstein-Barr Virus Viral Load Testing using International Standards

    PubMed Central

    Rychert, Jenna; Danziger-Isakov, Lara; Yen-Lieberman, Belinda; Storch, Gregory; Buller, Richard; Sweet, Stewart C.; Mehta, Aneesh K.; Cheeseman, Jennifer A.; Heeger, Peter; Rosenberg, Eric S.; Fishman, Jay A.

    2015-01-01

    Background Infections with cytomegalovirus (CMV) and Epstein Barr Virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation (CTOT/CTOTC). Methods Viral load testing was performed on well-defined viral preparations according to standard operating procedures at each site. Results Among centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. EBV viral load data were more variable and less accurate despite the use of international standards. Conclusions These data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated by using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials. PMID:25303316

  14. Clinical correlations of human cytomegalovirus strains and viral load in kidney transplant recipients.

    PubMed

    Nogueira, Eliana; Ozaki, Kikumi Suzete; Tomiyama, Helena; Câmara, Niels Olsen Saraiva; Granato, Celso Francisco Hernandes

    2009-01-01

    Little is known about clinical differences associated with cytomegalovirus (CMV) infection by distinct strains in renal transplant patients. Different clinical pictures may be associated with specific viral genotypes, viral load, as well as host factors. The objective of this study was to identify CMV strains to determine viral load (antigenemia), and their correlation with clinical data in renal transplant recipients. Seventy-one patients were enrolled, comprising 91 samples. After selection, polymorphonuclear cells were used to amplify and sequence the gB region of CMV DNA. The sequences were analyzed to ascertain the frequency of different genotypes. Additionally, the results of this study showed that the gB coding gene presents a great variability, revealing a variety of patterns: classical gB1 (1.4%), gB1V (46.4%), classical gB2 (35.2%), gB2V (2.8%), gB3 (1.4%), classical gB4 (4.9%) and gB4V (4.9%). The mean viral load in kidney transplant patient was 75.1 positive cells (1-1000). A higher viral load was observed in patients with genotype 4 infection. Statistically significant differences were detected between gB1 and gB4 (p=0.010), and between gB2 and gB4 (p=0.021). The average numbers of positive cells in relation to clinical presentation were: 34.5 in asymptomatic, 49.5 in CMV associated syndrome and 120.7 in patients with invasive disease (p=0.048). As a group, gB1 was the most frequent strain and revealed a potential risk for developing invasive disease. Viral load also seemed to be important as a marker associated with clinical presentation of the disease.

  15. The Paradoxical Effects of Different Hepatitis C Viral Loads on Host DNA Damage and Repair Abilities

    PubMed Central

    Li, Chia-Yang; Chiang, Chi-Shiun; Yu, Guann-Yi; Sakamoto, Naoya; Tu, Wen-Yu; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Chuang, Wan-Long; Dai, Chia-Yen

    2017-01-01

    Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein. We found DNA damage γ-H2AX foci in the HVL population. Comet assays demonstrated that HVL was related to the extent of the DNA strand breaks. Surprisingly, the DNA qPCR arrays and western blotting showed that the damage-related genes GPX2, MRE11, phospho-ATM, and OGG1 were significantly up-regulated in LVL cells but inversely down-regulated or consistently expressed in HVL cells. The colony survival assay to examine the repair abilities of these cells in response to irradiation showed that the LVL cells were more resistant to irradiation and had an increased ability to repair radiation-induced damage. This study found that intracellular viral loads drove cellular DNA damage levels but suppressed damage-related gene expression. However, the increase in damage-related gene expression in the LVL cells may be affected by ROS from the HVL cells. These findings provide new insights into the distinct DNA damage and repair responses resulting from different viral loads in HCV-infected cells. PMID:28052067

  16. The Paradoxical Effects of Different Hepatitis C Viral Loads on Host DNA Damage and Repair Abilities.

    PubMed

    Wang, Shu-Chi; Lai, Kuan-Ru; Li, Chia-Yang; Chiang, Chi-Shiun; Yu, Guann-Yi; Sakamoto, Naoya; Tu, Wen-Yu; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Chuang, Wan-Long; Dai, Chia-Yen; Yu, Ming-Lung

    2017-01-01

    Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein. We found DNA damage γ-H2AX foci in the HVL population. Comet assays demonstrated that HVL was related to the extent of the DNA strand breaks. Surprisingly, the DNA qPCR arrays and western blotting showed that the damage-related genes GPX2, MRE11, phospho-ATM, and OGG1 were significantly up-regulated in LVL cells but inversely down-regulated or consistently expressed in HVL cells. The colony survival assay to examine the repair abilities of these cells in response to irradiation showed that the LVL cells were more resistant to irradiation and had an increased ability to repair radiation-induced damage. This study found that intracellular viral loads drove cellular DNA damage levels but suppressed damage-related gene expression. However, the increase in damage-related gene expression in the LVL cells may be affected by ROS from the HVL cells. These findings provide new insights into the distinct DNA damage and repair responses resulting from different viral loads in HCV-infected cells.

  17. Expression of Interleukin-8, Interleukin-10 and Epstein-Barr Viral-Load as Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Savitri, Eka; Haryana, Mubarika Sofia

    2015-01-01

    Interleukin-8 (IL-8) is angiogeneic chemokine that plays a potential role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). Epstein- Barr virus (EBV) is recognized to be an important etiologic agent of NPC as the viral gene products are frequently detected in NPC tissue along with the elevation of antibody titre to the viral protein (VCA-p18+ EBNA1) of IgA in the majority of patients. Elevated plasma of Viral Load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the level of certain interleukins (IL-8 and IL-10) has also been implicated in NPC progression. The study aimed to investigate the correlations between plasma Viral Load and the level of interleukin (IL-8) and Interleukin (IL-10) in relating these parameters to the stages of NPC. In addition of Viral Load (VCA-p18+EBNA1) IgA, Interleukin-8 and Interleukin-10 before and after therapy will be investigated to seek the possible marker for disease progression. A total of 39 NPC patients and 29 healthy control individuals enrolled in this study. Plasma Viral Load was quantified using real-time quantitative PCR. The Level of plasma interleukins both IL-8 and IL-10 were analyzed using ELISA methods. Results indicated there was a significant decrease in viral load was detected in plasma of NPC patients following therapy. Plasma of viral load was shown to be a good prognosticator for disease progression. There were positive correlation between plasma of viral load and IL-8. These non invasive parameters expressed in blood, could be substitutes of viral load using brushing method, which is invasive. In conclusion that: Viral Load, (VCA-p18+EBNA1) IgA and IL-8 levels are promising markers for the presence of NPC and progression of the disease. PMID:25948470

  18. Multi-scale model for hepatitis C viral load kinetics under treatment with direct acting antivirals.

    PubMed

    Clausznitzer, Diana; Harnisch, Julia; Kaderali, Lars

    2016-06-15

    Hepatitis C virus (HCV) infections are a global health problem, and extensive research over the last decades has been targeted at understanding its molecular biology and developing effective antiviral treatments. Recently, a number of potent direct acting antiviral drugs have been developed targeting specific processes in the viral life cycle. Here, we developed a mathematical multi-scale model of the within-host dynamics of HCV infection by integrating a standard model for viral infection with a detailed model of the viral replication cycle inside infected cells. We use this model to study patient time courses of viral load under treatment with daclatasvir, an inhibitor of the viral non-structural protein NS5A. Model analysis predicts that treatment efficacy can be increased by combining daclatasvir with dedicated viral polymerase inhibitors, corresponding to promising current strategies in drug development. Hence, our model presents a predictive tool for in silico simulations, which can be used to study and optimize direct acting antiviral drug treatment.

  19. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    PubMed Central

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  20. Evaluation of Ag nanoparticle coated air filter against aerosolized virus: Anti-viral efficiency with dust loading.

    PubMed

    Joe, Yun Haeng; Park, Dae Hoon; Hwang, Jungho

    2016-01-15

    In this study, the effect of dust loading on the anti-viral ability of an anti-viral air filter was investigated. Silver nanoparticles approximately 11 nm in diameter were synthesized via a spark discharge generation system and were used as anti-viral agents coated onto a medium air filter. The pressure drop, filtration efficiency, and anti-viral ability of the filter against aerosolized bacteriophage MS2 virus particles were tested with dust loading. The filtration efficiency and pressure drop increased with dust loading, while the anti-viral ability decreased. Theoretical analysis of anti-viral ability with dust loading was carried out using a mathematical model based on that presented by Joe et al. (J. Hazard. Mater.; 280: 356-363, 2014). Our model can be used to compare anti-viral abilities of various anti-viral agents, determine appropriate coating areal density of anti-viral agent on a filter, and predict the life cycle of an anti-viral filter.

  1. Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics

    PubMed Central

    Lythgoe, Katrina A.; Blanquart, François

    2016-01-01

    The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation. PMID:27706164

  2. Detectable HIV Viral Load in Kenya: Data from a Population-Based Survey

    PubMed Central

    Cherutich, Peter; Kim, Andrea A.; Kellogg, Timothy A.; Sherr, Kenneth; Waruru, Anthony; De Cock, Kevin M.; Rutherford, George W.

    2016-01-01

    Introduction At the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV) transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012) provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART) coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012. Methods Between October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL) was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL ≥ 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non-response. Results Overall, 61·2% (95% CI: 56·4–66·1) of HIV-infected Kenyans aged 15–64 years had not achieved virological suppression. The base10 median (interquartile range [IQR]) and mean (95% CI) VL was 4,633 copies/mL (0–51,596) and 81,750 copies/mL (59,366–104,134), respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0–32.1) had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART. Discussion This report adds to the limited data of nationally-representative surveys to report population- level virological

  3. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  4. Development of a microfluidic system for measuring HIV-1 viral load

    NASA Astrophysics Data System (ADS)

    Wang, Shuqi; Ip, Alexander; Xu, Feng; Giguel, Francoise F.; Moon, SangJun; Akay, Altug; Kuritzkes, Daniel R.; Demirci, Utkan

    2010-04-01

    The World Health Organization (WHO) is rapidly expanding antiretroviral treatment (ART) in sub-Saharan countries. However, virological failure of ART is rarely monitored due to the lack of affordable and sustainable viral load assays suitable for resource-limited settings. Here, we report a prototype of a rapid virus detection method based on microfluidic technologies. In this method, HIV-1 particles from 10 μL whole blood were captured by anti-gp120 antibody coated on the microchannel surface and detected by dual fluorescence signals under microscopy. Next, captured HIV-1 particles were counted using the free software, ImageJ (http://rsbweb.nih.gov/ij/). This rapid HIV-1 detection method has potential to be further developed for viral load monitoring at resource-limited settings.

  5. Comparison of the Abbott Realtime HIV-1 and HCV viral load assays with commercial competitor assays.

    PubMed

    Schutten, Martin

    2008-07-01

    The introduction of commercially available quantitative HIV-1 RNA detection methods at the end of the last century has had a significant impact on the management of patients requiring treatment. Similarly for hepatitis C virus (HCV), clinical decision-making with respect to initiation and prolonging therapy is largely based on data from viral load assays. The methods developed in the early 1990s and further improved since then still have significant drawbacks. For example, they are labor intensive, have a small dynamic range and are contamination sensitive. The development of real-time detection techniques for reverse transcription PCR has in part solved these problems. In the present review the advantages and disadvantages of the recently marketed Abbott Realtime HCV and HIV-1 viral load assays relative to their competitors will be discussed.

  6. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    PubMed

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  7. Comparison of asymptomatic and symptomatic rhinovirus infections in university students: incidence, species diversity, and viral load.

    PubMed

    Granados, Andrea; Goodall, Emma C; Luinstra, Kathy; Smieja, Marek; Mahony, James

    2015-08-01

    Human rhinovirus (HRV) infections are common but poorly characterized in university students. Thus, we characterized asymptomatic and symptomatic HRV infections by incidence, species diversity, and viral load of 502 university students during September and October of 2010 and 2011 from nasal swabs and electronically submitted symptom questionnaires. We tested all symptomatic students and randomly sampled participants who remained asymptomatic (n=25/week, over 8 weeks each study year) on a weekly basis by real-time PCR and sequenced HRV positives. HRV was identified in 33/400 (8.3%) and 85/92 (92.4%) of the asymptomatic and symptomatic students, respectively. We identified a higher than previously reported rate of HRV-B in both groups, although the distribution of HRV species was similar (P=0.37). Asymptomatic viral load averaged 1.2 log10 copies/mL lower than symptomatic HRV (P<0.001). In conclusion, asymptomatic HRV activity preceded peak symptomatic activity in September and October and was associated with lower viral load.

  8. Cigarette Smokers are Less Likely to have Undetectable Viral Loads: Results from Four HIV Clinics

    PubMed Central

    Cropsey, Karen L.; Willig, James H.; Mugavero, Michael J.; Crane, Heidi M.; McCullumsmith, Cheryl; Lawrence, Sarah; Raper, James L.; Mathews, W. Christopher; Boswell, Stephen; Kitahata, Mari M.; Schumacher, Joseph E.; Saag, Michael S.

    2015-01-01

    Background The prevalence of smoking among HIV-infected individuals is 2–3 times that of the general population, increasing the risk of smoking-related morbidity and mortality. We examined characteristics associated with smoking behavior among a large cohort of HIV-infected individuals in care in the US. Methods A convenience sample of 2,952 HIV-infected patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) were assessed during routine clinic visits was included. Multinomial logistic regression was used to examine the relationship between smoking status, depression/panic symptoms, alcohol/substance use, and demographic and clinical characteristics. Results Compared to never smokers, current smokers were more likely to have moderate to severe depression (OR: 1.37), endorse current substance use (OR: 14.09), and less likely to report low risk alcohol use on the AUDIT-C (OR: 0.73). Current smokers were less likely to have an undetectable viral load (OR: 0.75) and more likely to have current substance abuse (OR: 2.81) and moderate to severe depression (OR: 1.50) relative to smokers who had quit smoking. Conclusions HIV-infected smokers are less likely to have undetectable viral loads and frequently have psychosocial co-morbidities including depression and substance abuse that impact ART adherence and viral load suppression. To be effective, smoking cessation interventions need to address the complex underlying concurrent risks in this population. PMID:26656939

  9. Behavioral and Other Characteristics Associated with HIV Viral Load in an Outpatient Clinic

    PubMed Central

    Sacamano, Paul L.; Farley, Jason E.

    2016-01-01

    Persons living with HIV (PLWH) who are engaged in care, yet not virally suppressed, represent a risk for transmission and opportunity for risk reduction interventions. This study describes characteristics of an outpatient clinic cohort of PLWH by laboratory confirmed viral suppression status and examines associations with demographics and sexual and drug use behaviors gathered through questionnaire. From a sample of 500 clinic patients, 438 were prescribed antiretroviral treatment (ART) and 62 were not. Among the 438 on ART, 72 (16.4%) were not virally suppressed at the most recent lab draw. Compared to individuals with a suppressed viral load, those that were unsuppressed were more likely to: be black (79.2% vs. 64.2%; p = 0.014); earn below $25,000/year (88.9% vs. 65.0%; p < 0.001); be of a younger age (47.8 vs. 50.0 mean years; p = 0.009); be on opiate substitution (14.1% vs. 6.3%; p = 0.023); and acknowledge poly-substance (38.9% vs. 24.4%; p = 0.012) and excessive alcohol use (13.9% vs. 6.0%; p = 0.019). Conversely, a smaller proportion of those with an unsuppressed viral load had multiple sex partners in the previous 30 days (39.8% vs. 58.5%; p = 0.003). In multivariable regression of those on ART, the prevalence of an unsuppressed viral load was 3% lower with each increasing year of age (aPR: 0.97; 95% CI: 0.95, 0.99) and 47% lower with income over $25,000/year (aPR: 0.33; 95% CI: 0.16, 0.70). In a separate analysis of all 500 subjects, ART was less frequently prescribed to blacks compared to whites, heterosexuals, those with lower education and income, and persons with active substance use. Findings confirm that a large proportion of PLWH and engaged in care were not virally suppressed and continued behaviors that risk transmission, indicating the need for screening, prevention counseling and access to ancillary services to lower the incidence of HIV infections. PMID:27806109

  10. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  11. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  12. Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men.

    PubMed

    Wu, Chih-Feng; Yu, Ming-Whei; Lin, Chih-Lin; Liu, Chun-Jen; Shih, Wei-Liang; Tsai, Keh-Sung; Chen, Chien-Jen

    2008-01-01

    Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (>/=4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P < 0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in >/=50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at >/=50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load <4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.

  13. Transcriptional Profiling of Banana Shrimp Fenneropenaeus merguiensis with Differing Levels of Viral Load.

    PubMed

    Powell, Daniel; Knibb, Wayne; Nguyen, Nguyen Hong; Elizur, Abigail

    2016-12-01

    Viral pathogens are of serious concern to the culture of penaeid shrimps worldwide. However, little is known about the molecular response of shrimp to viral infection. Selective breeding has been suggested as an effective long-term strategy to manage viral disease, though more information on gene function is needed to help inform breeding programs. The study of cultured banana shrimp (Fenneropenaeus merguiensis) infected with hepatopancreatic parvo-like virus (HPV) provides a unique opportunity to explore the host response to viral infection independent of challenge testing. To gain insight into the genetic mechanisms underlying resistance to high levels of HPV, we examined hepatopancreas tissue from six full-sib groups of banana shrimp with differing levels of HPV infection for differences in gene expression. A total of 404 differentially expressed genes were identified with 180 being over-expressed and 224 under-expressed among high-HPV full-sib groups. Based on homology analysis, a large proportion of these genes were associated with processes reported to be involved in the immune response of crustaceans, including pattern recognition proteins, antimicrobial peptides, components of the prophenoloxidase system, and antiviral activity. The results indicate shrimp from high-HPV full-sib groups appear to have a lower presence of important immune response elements, yet possess upregulated putative antiviral pathways. Within the differentially expressed genes, over 4000 sequence variants were identified to be exclusive to either the high- or low-HPV full-sib groups. To our knowledge, this is the first report of differential expression analysis using RNA-Seq to explore differences in viral load among high- and low-HPV full-sib groups of cultured shrimp. This research has provided additional insight into our understanding of the mechanisms involved in the response of this shrimp species to a naturally occurring viral pathogen. Sequence variants identified in this study

  14. Understanding Determinants of Racial and Ethnic Disparities in Viral Load Suppression.

    PubMed

    Feller, Daniel J; Agins, Bruce D

    Racial and ethnic disparities in viral load suppression (VLS) have been well documented among people living with HIV (PLWH). The authors hypothesized that a contemporary analytic technique could reveal factors underlying these disparities and provide more explanatory power than broad stereotypes. Classification and regression tree analysis was used to detect factors associated with VLS among 11 419 adult PLWH receiving treatment from 186 New York State HIV clinics in 2013. A total of 8885 (77.8%) patients were virally suppressed. The algorithm identified 8 mutually exclusive subgroups characterized by age, housing stability, drug use, and insurance status but neither race nor ethnicity. Our findings suggest that racial and ethnic disparities in VLS exist but likely reflect underlying social and behavioral determinants of health.

  15. Value of serological tests in the diagnosis of viral acute respiratory infections in adults.

    PubMed

    Căruntu, F; Dogaru, D; Stefan, D; Căruntu, V; Angelescu, C; Streinu-Cercel, A; Colţan, G; Petrescu, A L; Tarţă, D; Bârnaure, F

    1986-01-01

    The dynamics of the antibody response to influenza viruses A (H1N1), A (H3N2) and B, to parainfluenza viruses 1, 2, 3, to adenoviruses and respiratory syncytial virus was studied in paired serum samples collected from 110 patients hospitalized with acute respiratory infections (ARI) and in 40 patients suffering from other diseases. Rises in serum antibody titers to 1--5 of the above mentioned antigens were detected in many of the patients of both groups. The fact is most likely due to the presence of some epidemiologically and clinically uncharacteristic viral ARI (influenza included); simultaneous or successive infections with influenza virus and different other viruses were very frequent. A greater efficiency of the etiological diagnosis of viral ARI can be achieved only by the association of epidemiological and clinical criteria with serological data, the visualization of viral antigens and virus isolation.

  16. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  17. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

    PubMed

    Zhai, Yijie; Franco, Luis M; Atmar, Robert L; Quarles, John M; Arden, Nancy; Bucasas, Kristine L; Wells, Janet M; Niño, Diane; Wang, Xueqing; Zapata, Gladys E; Shaw, Chad A; Belmont, John W; Couch, Robert B

    2015-06-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

  18. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    PubMed

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  19. Young Age Predicts Poor Antiretroviral Adherence and Viral Load Suppression Among Injection Drug Users

    PubMed Central

    Hadland, Scott E.; Milloy, M.-J.; Kerr, Thomas; Zhang, Ruth; Guillemi, Silvia; Hogg, Robert S.; Montaner, Julio S.

    2012-01-01

    Abstract Previous studies of adherence to antiretroviral therapy (ART) for HIV among young injection drug users (IDU) have been limited because financial barriers to care disproportionately affect youth, thus confounding results. This study examines adherence among IDU in a unique setting where all medical care is provided free-of-charge. From May 1996 to April 2008, we followed a prospective cohort of 545 HIV-positive IDU of 18 years of age or older in Vancouver, Canada. Using generalized estimating equations (GEE), we studied the association between age and adherence (obtaining ART≥95% of the prescribed time), controlling for potential confounders. Using Cox proportional hazards regression, we also studied the effect of age on time to viral load suppression (<500 copies per milliliter), and examined adherence as a mediating variable. Five hundred forty-five participants were followed for a median of 23.8 months (interquartile range [IQR]=8.5–91.6 months). Odds of adherence were significantly lower among younger IDU (adjusted odds ratio [AOR]=0.76 per 10 years younger; 95% confidence interval [CI], 0.65–0.89). Younger IDU were also less likely to achieve viral load suppression (adjusted hazard ratio [AHR]=0.75 per 10 years younger; 95% CI, 0.64–0.88). Adding adherence to the model eliminated this association with age, supporting the role of adherence as a mediating variable. Despite absence of financial barriers, younger IDU remain less likely to adhere to ART, resulting in inferior viral load suppression. Interventions should carefully address the unique needs of young HIV-positive IDU. PMID:22429003

  20. Progress in Treatment of Viral Infections in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Moschovi, Maria; Adamaki, Maria; Vlahopoulos, Spiros A.

    2016-01-01

    In children, the most commonly encountered type of leukemia is acute lymphoblastic leukemia (ALL). An important source of morbidity and mortality in ALL are viral infections. Even though allogeneic transplantations, which are often applied also in ALL, carry a recognized risk for viral infections, there are multiple factors that make ALL patients susceptible to viral infections. The presence of those factors has an influence in the type and severity of infections. Currently available treatment options do not guarantee a positive outcome for every case of viral infection in ALL, without significant side effects. Side effects can have very serious consequences for the ALL patients, which include nephrotoxicity. For this reason a number of strategies for personalized intervention have been already clinically tested, and experimental approaches are being developed. Adoptive immunotherapy, which entails administration of ex vivo grown immune cells to a patient, is a promising approach in general, and for transplant recipients in particular. The ex vivo grown cells are aimed to strengthen the immune response to the virus that has been identified in the patients’ blood and tissue samples. Even though many patients with weakened immune system can benefit from progress in novel approaches, a viral infection still poses a very significant risk for many patients. Therefore, preventive measures and supportive care are very important for ALL patients. PMID:27471584

  1. Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India.

    PubMed

    Rathore, S K; Dwibedi, B; Kar, S K; Dixit, S; Sabat, J; Panda, M

    2014-12-01

    This study reports clinico-epidemiological features and viral agents causing acute encephalitis syndrome (AES) in the eastern Indian region through hospital-based case enrolment during April 2011 to July 2012. Blood and CSF samples of 526 AES cases were investigated by serology and/or PCR. Viral aetiology was identified in 91 (17·2%) cases. Herpes simplex virus (HSV; types I or II) was most common (16·1%), followed by measles (2·6%), Japanese encephalitis virus (1·5%), dengue virus (0·57%), varicella zoster virus (0·38%) and enteroviruses (0·19%). Rash, paresis and cranial nerve palsies were significantly higher (P < 0·05) with viral AES. Case-fatality rates were 10·9% and 6·2% in AES cases with and without viral aetiology, respectively. Simultaneous infection of HSV I and measles was observed in seven cases. This report provides the first evidence on viral aetiology of AES viruses from eastern India showing dominance of HSV that will be useful in informing the public health system.

  2. The role of viral agents in aetiopathogenesis of acute rheumatic fever.

    PubMed

    Olgunturk, Rana; Okur, Ilyas; Cirak, Meltem Y; Oguz, Ayse Deniz; Akalin, Nursel; Turet, Sevgi; Tunaoglu, Sedef

    2011-01-01

    The reason why abnormal immune response exists in acute rheumatic fever is not exactly explained. The influence of co-pathogens like certain viruses were mentioned regarding the initiation of the immunological reaction in acute rheumatic fever patients by several authors since 1970. This study was designed to find the role or effect of some viral infections in the development of rheumatic fever. In this study, 47 cases with acute rheumatic fever (acute rheumatic arthritis, acute rheumatic carditis, and chorea), 20 cases with chronic rheumatic fever, 20 cases with streptococcal pharyngitis, and 20 healthy age- and gender-matched control cases were involved. Serological and molecular tests were made including hepatitis B virus, hepatitis C virus, rubella virus, herpes simplex virus (HSV group 1), and Epstein-Barr virus (EBV). HBsAg, rubella IgM and EBV IgM positivity were not seen in any of patients with rheumatic fever. Although antiHBs seropositivity was higher in the control group, it was not statistically significant (p > 0.05). There was no difference in rubella IgG, HSV IgM seropositivity, either (p > 0.05). EBV DNA was searched by the polymerase chain reaction technique; due to the latent nature of the virus, no significant difference was found between the control group and the other groups (p > 0.05). In this study, no positive correlation could be found to support the synergism theories regarding the streptoccocus infection and viral infections in the development of acute rheumatic fever. Only EBV DNA positivity was found in all acute rheumatic fever cases but not in the control group may lead to further studies with larger series of patients.

  3. [The pharyngeal viral flora in dystrophic infants 0 to 1 years of age with acute respiratory diseases].

    PubMed

    Pârvu, C; Isaia, G; Moldovan, D; Mârşanu, M; Lăzărescu, P; Sîntimbreanu, C; Mârşanu, A

    1989-01-01

    Pharyngeal viral flora was studied in 0-1-year-old dystrophic children with acute infections of the upper respiratory tract and with interstitial pneumopathy. Influence of the dystrophic factor on the qualitative and quantitative aspects of the viral flora is discussed.

  4. Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy.

    PubMed

    Zivcec, Marko; Safronetz, David; Scott, Dana; Robertson, Shelly; Ebihara, Hideki; Feldmann, Heinz

    2013-06-15

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed viral hemorrhagic fever characterized by rapid onset of flu-like symptoms often followed by hemorrhagic manifestations. CCHF virus (CCHFV), a bunyavirus in the Nairovirus genus, is capable of infecting a wide range of mammalian hosts in nature but so far only causes disease in humans. Recently, immunocompromised mice have been reported as CCHF disease models, but detailed characterization is lacking. Here, we closely followed infection and disease progression in CCHFV-infected interferon α/β receptor knockout (IFNAR(-/-)) mice and age-matched wild-type (WT) mice. WT mice quickly clear CCHFV without developing any disease signs. In contrast, CCHFV infected IFNAR(-/-) mice develop an acute fulminant disease with high viral loads leading to organ pathology (liver and lymphoid tissues), marked proinflammatory host responses, severe thrombocytopenia, coagulopathy, and death. Disease progression closely mimics hallmarks of human CCHF disease, making IFNAR(-/-) mice an excellent choice to assess medical countermeasures.

  5. Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.

    PubMed

    Zabaleta, Aintzane; Riezu-Boj, Jose-Ignacio; Larrea, Esther; Villanueva, Lorea; Lasarte, Juan Jose; Guruceaga, Elizabeth; Fisicaro, Paola; Ezzikouri, Sayeh; Missale, Gabriele; Ferrari, Carlo; Benjelloun, Soumaya; Prieto, Jesús; Sarobe, Pablo

    2016-05-01

    Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses, gene expression was analyzed in DC from patients during acute HCV infection. By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection.

  6. Signs and Symptoms that Differentiate Acute Sinusitis from Viral Upper Respiratory Tract Infection

    PubMed Central

    Shaikh, Nader; Hoberman, Alejandro; Kearney, Diana H.; Colborn, D. Kathleen; Kurs-Lasky, Marcia; Jeong, Jong H.; Haralam, Mary Ann; Bowen, A’Delbert; Flom, Lynda L.; Wald, Ellen R.

    2013-01-01

    Objective Differentiating acute bacterial sinusitis from viral upper respiratory tract infection (URI) is challenging; 20% to 40% of children diagnosed with acute sinusitis based on clinical criteria likely have an uncomplicated URI. The objective of this study was to determine which signs and symptoms could be used to identify the subgroup of children who meet current clinical criteria for sinusitis but who nevertheless have a viral URI. Methods We obtained sinus radiographs in consecutive children meeting a priori clinical criteria for acute sinusitis. We considered the subgroup of children with completely normal sinus radiographs to have an uncomplicated URI despite meeting the clinical diagnostic criteria for sinusitis. We examined the utility of signs and symptoms in identifying children with URI. Results Of 258 children enrolled, 54 (20.9%) children had completely normal radiographs. The absence of green nasal discharge, the absence of disturbed sleep, and mild symptoms were associated with a diagnosis of URI. No physical exam findings were particularly helpful in distinguishing between children with normal vs. abnormal radiographs. Conclusions Among children meeting current criteria for the diagnosis of acute sinusitis, those with mild symptoms are significantly more likely to have a URI than those with severe symptoms. In addition to assessing overall severity of symptoms, practitioners should ask about sleep disturbance and green nasal discharge when assessing children with suspected sinusitis; their absence favors a diagnosis of URI. PMID:23694838

  7. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

    PubMed Central

    de OLIVEIRA, Valter Oberdan Borges; OLIVEIRA, Juliana Passos Rocha; de FRANÇA, Eloy Vianey Carvalho; BRITO, Hugo Leite de Farias; NASCIMENTO, Tereza Virgínia; FRANÇA, Alex

    2016-01-01

    SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7) IU/mL versus 482.8 (± 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment. PMID:27680170

  8. Ebola viral load at diagnosis associates with patient outcome and outbreak evolution

    PubMed Central

    de La Vega, Marc-Antoine; Caleo, Grazia; Audet, Jonathan; Qiu, Xiangguo; Kozak, Robert A.; Brooks, James I.; Kern, Steven; Wolz, Anja; Sprecher, Armand; Greig, Jane; Lokuge, Kamalini; Kargbo, David K.; Kargbo, Brima; Di Caro, Antonino; Grolla, Allen; Kobasa, Darwyn; Strong, James E.; Ippolito, Giuseppe; Van Herp, Michel; Kobinger, Gary P.

    2015-01-01

    BACKGROUND. Ebola virus (EBOV) causes periodic outbreaks of life-threatening EBOV disease in Africa. Historically, these outbreaks have been relatively small and geographically contained; however, the magnitude of the EBOV outbreak that began in 2014 in West Africa has been unprecedented. The aim of this study was to describe the viral kinetics of EBOV during this outbreak and identify factors that contribute to outbreak progression. METHODS. From July to December 2014, one laboratory in Sierra Leone processed over 2,700 patient samples for EBOV detection by quantitative PCR (qPCR). Viremia was measured following patient admission. Age, sex, and approximate time of symptom onset were also recorded for each patient. The data was analyzed using various mathematical models to find trends of potential interest. RESULTS. The analysis revealed a significant difference (P = 2.7 × 10–77) between the initial viremia of survivors (4.02 log10 genome equivalents [GEQ]/ml) and nonsurvivors (6.18 log10 GEQ/ml). At the population level, patient viral loads were higher on average in July than in November, even when accounting for outcome and time since onset of symptoms. This decrease in viral loads temporally correlated with an increase in circulating EBOV-specific IgG antibodies among individuals who were suspected of being infected but shown to be negative for the virus by PCR. CONCLUSIONS. Our results indicate that initial viremia is associated with outcome of the individual and outbreak duration; therefore, care must be taken in planning clinical trials and interventions. Additional research in virus adaptation and the impacts of host factors on EBOV transmission and pathogenesis is needed. PMID:26551677

  9. A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

    PubMed

    Zaas, Aimee K; Burke, Thomas; Chen, Minhua; McClain, Micah; Nicholson, Bradly; Veldman, Timothy; Tsalik, Ephraim L; Fowler, Vance; Rivers, Emanuel P; Otero, Ronny; Kingsmore, Stephen F; Voora, Deepak; Lucas, Joseph; Hero, Alfred O; Carin, Lawrence; Woods, Christopher W; Ginsburg, Geoffrey S

    2013-09-18

    Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.

  10. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

    PubMed Central

    Gaurav, Sharma; Keerthilatha, Pai M.; Archna, Nagpal

    2011-01-01

    The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103). The most common oromucosal lesion was erythematous candidiasis (EC) (38.8%) followed by melanotic hyperpigmentation (35.9%). Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio <0.30. The prevalence of oral manifestations in patients taking ART was lesser (78.6%) as compared to patients not taking ART (82%). Patients having any oral manifestation had a higher HIV viral load as compared to patients not having any oral manifestations (P < 0.05). Pseudomembranous candidiasis (PC) was significantly associated with higher HIV viral loads (>20,000 copies/mL) (P < 0.05). Patients having EC had 4 times greater chance of having CD4/CD8 ratio <0.30. PC can be considered as a marker of immune suppression (HIV viral load >20,000 copies/mL). PMID:22046186

  11. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis.

    PubMed Central

    Maisch, B; Trostel-Soeder, R; Stechemesser, E; Berg, P A; Kochsiek, K

    1982-01-01

    Sera of 177 patients with acute myocarditis (10 coxsackie B 3/4, four influenza, four mumps, 15 cytomegalovirus, 144 undefined) were tested by indirect immunofluorescence for autoantibodies against heart and skeletal muscle and vital or air-dried adult cardiocytes. Antibody-dependent cytolysis, lymphocytotoxicity and antibody-dependent cellular lymphocytotoxicity were assessed using viral adult rat cardiocytes as target cells. Muscle-specific anti-sarcolemmal antibodies of the anti-myolemmal type--often associated with non-organ-specific anti-endothelial antibodies--were demonstrated in nine out of 10 patients with coxsackie B, in all patients with influenza and mumps and in 65 out of 144 patients with undefined myocarditis. In contrast, 13 out of 15 patients with cytomegalovirus myocarditis lacked anti-sarcolemmal antibodies but had low titre anti-inter fibrillary antibodies instead. In the presence of complement, anti-myolemmal antibodies induced cytolysis of vital cardiocytes, whereas hepatocytes remained unaffected. Titres of anti-myolemmal antibodies correlated with the degree of cardiocytolysis. The anti-myolemmal immunofluorescent pattern and the cytolytic serum activity could be absorbed with the respective viral antigens suggesting that these antibodies cross-react with moieties of the virus itself and may be both diagnostic and aetiological markers in acute viral myocarditis. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells could not be observed in our patients with myocarditis of proven viral aetiology. However, lymphocyte-mediated cytotoxicity was demonstrated in 10 ASA-positive and one ASA-negative patient with myocarditis of unknown origin. ASA-positive sera blocked lymphocytotoxicity in three of these patients. PMID:6288291

  12. Baroreflex sensitivity in acute hypoxia and carbohydrate loading.

    PubMed

    Klemenc, Matjaž; Golja, Petra

    2011-10-01

    Hypoxia decreases baroreflex sensitivity (BRS) and can be a sufficient cause for syncope in healthy individuals. Carbohydrate loading enhances efferent sympathetic activity, which affects cardiac contractility, heart rate and vascular resistance, the main determinants of blood pressure. Thus, in both normoxia and hypoxia, carbohydrate loading may be more than simply metabolically beneficial, as it may affect blood pressure regulation. We hypothesised that carbohydrate loading will, in both normoxia and hypoxia, alter the regulation of blood pressure, as reflected in a change in baroreflex sensitivity. Fourteen subjects participated in two experiments, composed of a 15-min normoxic period, after which the subjects ingested water or an equal amount of water with carbohydrates. A 30-min rest period was then followed by a 10-min second normoxic and a 30-min hypoxic period. Blood pressure and heart rate were monitored continuously during the experiment to determine BRS. Despite an increased sympathetic activation, reflected in increased heart rate (P < 0.001) BRS was lower (P < 0.01) after carbohydrate loading, as compared to the water experiment, in both normoxic [23.7 (12.4) versus 28.8 (13.8) ms/mmHg] and hypoxic [16.8 (11.0) versus 24.3 (12.3) ms/mmHg] phases of the present study. As BRS was decreased in acute hypoxic exposure, the results confirm that hypoxia interferes with blood pressure regulation. However, although oral carbohydrate loading induced sympathoexcitation, it did not improve blood pressure regulation in hypoxia, as evident from the BRS data. Baroreflex effects of other forms of carbohydrate loading, not causing postprandial blood shifts to digestive system, should therefore be investigated.

  13. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management.

  14. Dynamics of the Cytotoxic T Cell Response to a Model of Acute Viral Infection

    PubMed Central

    DeWitt, William S.; Emerson, Ryan O.; Lindau, Paul; Vignali, Marissa; Snyder, Thomas M.; Desmarais, Cindy; Sanders, Catherine; Utsugi, Heidi; Warren, Edus H.; McElrath, Juliana; Makar, Karen W.; Wald, Anna

    2015-01-01

    ABSTRACT A detailed characterization of the dynamics and breadth of the immune response to an acute viral infection, as well as the determinants of recruitment to immunological memory, can greatly contribute to our basic understanding of the mechanics of the human immune system and can ultimately guide the design of effective vaccines. In addition to neutralizing antibodies, T cells have been shown to be critical for the effective resolution of acute viral infections. We report the first in-depth analysis of the dynamics of the CD8+ T cell repertoire at the level of individual T cell clonal lineages upon vaccination of human volunteers with a single dose of YF-17D. This live attenuated yellow fever virus vaccine yields sterile, long-term immunity and has been previously used as a model to understand the immune response to a controlled acute viral infection. We identified and enumerated unique CD8+ T cell clones specifically induced by this vaccine through a combined experimental and statistical approach that included high-throughput sequencing of the CDR3 variable region of the T cell receptor β-chain and an algorithm that detected significantly expanded T cell clones. This allowed us to establish that (i) on average, ∼2,000 CD8+ T cell clones were induced by YF-17D, (ii) 5 to 6% of the responding clones were recruited to long-term memory 3 months postvaccination, (iii) the most highly expanded effector clones were preferentially recruited to the memory compartment, and (iv) a fraction of the YF-17D-induced clones could be identified from peripheral blood lymphocytes solely by measuring clonal expansion. IMPORTANCE The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we

  15. Sexual behaviour among people with HIV according to self-reported antiretroviral treatment and viral load status

    PubMed Central

    Lampe, Fiona C.

    2016-01-01

    Objective: To assess, among people with HIV, the association of self-reported antiretroviral treatment (ART) and viral load status with condomless sex with an HIV-serodifferent partner (CLS-D). Design: Cross-sectional study of 3258 HIV-diagnosed adults in the United Kingdom, 2011–2012. Methods: CLS-D in the past 3 months and self-reported ART/viral load were ascertained by questionnaire. Clinic-recorded viral load was documented. HIV-transmission risk sex (CLS-D-HIV-risk) was defined as CLS-D together with either not on ART or clinic-recorded viral load more than 50 copies/ml. Results: Of 3178 participants diagnosed more than 3 months ago, 2746 (87.9%) were on ART, of whom self-reported viral load was ‘50 copies/ml/ or less/undetectable’ for 78.4%; ‘more than 50 copies/ml/detectable’ for 8.3%; ‘do not know/missing’ for 13.3%. CLS-D prevalence was 14.9% (326/2189), 6.4% (23/360) and 10.7% (67/629) among men who have sex with men, heterosexual men and women, respectively. Among men who have sex with men, CLS-D prevalence was 18.8% among those not on ART; 15.2% among those on ART with undetectable self-reported viral load; 9.8% among those on ART without undetectable self-reported viral load. Compared with ‘on ART with undetectable self-reported viral load’, prevalence ratios (95% confidence interval) adjusted for demographic/HIV-related factors were: 0.66 (0.45, 0.95) for ‘on ART without undetectable self-reported viral load’, and 1.08 (0.78, 1.49) for ‘not on ART’ (global P = 0.021). Among heterosexual men and women (combined), ART/self-reported viral load was not associated with CLS-D [corresponding adjusted prevalence ratios: 1.14 (0.73, 1.79) for ‘on ART without undetectable self-reported viral load’; 0.88 (0.44, 1.77) for ‘not on ART’, P = 0.77]. CLS-D-HIV-risk prevalence was 3.2% among all participants; 16.1% for ‘not on ART’; 0.6% for ‘on ART with undetectable self-reported viral load; 4.2% for ‘on ART

  16. Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants

    PubMed Central

    Espinosa, Yazmín; San Martín, Camila; Torres, Alejandro A.; Farfán, Mauricio J.; Torres, Juan P.; Avadhanula, Vasanthi; Piedra, Pedro A.; Tapia, Lorena I.

    2017-01-01

    The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies. PMID:28335547

  17. Someone to count on: social support as an effect modifier of viral load suppression in a prospective cohort study.

    PubMed

    Friedman, M Reuel; Coulter, Robert W S; Silvestre, Anthony J; Stall, Ron; Teplin, Linda; Shoptaw, Steve; Surkan, Pamela J; Plankey, Michael W

    2017-04-01

    Though functional social support has been shown to serve as a protective factor for HIV viral load suppression in other populations, scant research has examined this relationship among men who have sex with men (MSM) in the United States. We assessed characteristics of social support, effects of social support on HIV viral load, and moderation by social support of the relationship between psychosocial indicators of a synergistic epidemic (syndemic) and HIV viral load. We analyzed longitudinal data from HIV-positive MSM using antiretroviral therapy who were enrolled in the Multicenter AIDS Cohort Study between 2002 and 2009 (n = 712). First, we conducted reliability assessments of a one-item social support measure. Then, we conducted a series of generalized longitudinal mixed models to assess our research questions. Moderation was assessed using an interaction term. A three-level (low/medium/high) social support variable demonstrated high reliability (intraclass correlation coefficients  = 0.72; 95% CI: 0.70, 0.75). Black and Hispanic MSM reported lower social support than their White counterparts (p < .0001). Recent sero-conversion was associated with higher social support (p < .05). Higher numbers of concomitant syndemic indicators (depression, polysubstance use, and condomless anal sex) were associated with lower social support (p < .0001). Medium and high social support levels were associated with greater viral load suppression and lower viral load means (p < .0001). Social support moderated the relationships between syndemic and HIV viral load (p < .05). HIV-positive MSM, particularly those of color, may benefit greatly from interventions that can successfully boost functional social support. Creating strengths-based interventions may also have particularly high impact among HIV-positive MSM with the highest psychosocial burdens.

  18. Brief Report: Relationship Among Viral Load Outcomes in HIV Treatment Interruption Trials.

    PubMed

    Treasure, Graham C; Aga, Evgenia; Bosch, Ronald J; Mellors, John W; Kuritzkes, Daniel R; Para, Michael; Gandhi, Rajesh T; Li, Jonathan Z

    2016-07-01

    Viral load (VL) rebound timing and set point were analyzed in 235 participants undergoing analytic treatment interruption (ATI) in 6 AIDS Clinical Trials Group studies. There was no significant association between rebound timing and ATI VL set point for those who rebounded ≤12 weeks. VL set points were lower in participants with rebound >12 weeks (P < 0.001) and participants treated during early infection (P < 0.001). Pre-antiretroviral therapy VL correlated with set point, though 68% of participants had a set point lower than pre-antiretroviral therapy VL. These results illustrate complex relationships between post-ATI virologic outcomes and the potential presence of biological factors mediating rebound timing and set point.

  19. Sensitive and specific nested PCR assay for detection of rotavirus A in samples with a low viral load.

    PubMed

    Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Williams, Alice L; Bowen, Michael D

    2016-10-01

    Techniques such as the real-time reverse transcription-polymerase chain reaction (qRT-PCR) can detect RNA in samples with a low viral load. However, these amplicons typically are either too short or at insufficient concentrations for use in subsequent sequencing reactions for genotyping and detection confirmation. The assay developed in this study detects rotavirus G genotypes and P genotypes with viral loads as low as 6.2 and 8.2 copies per reaction, respectively. The assay was validated using a panel of 91 stool samples, 32 reference rotavirus strains, and 6 non-target enteric virus samples.

  20. Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

    PubMed Central

    Mungaomklang, Anek; Chomcheoy, Jiraruj; Wacharapluesadee, Supaporn; Joyjinda, Yutthana; Jittmittraphap, Akanitt; Rodpan, Apaporn; Ghai, Siriporn; Saraya, Abhinbhen; Hemachudha, Thiravat

    2016-01-01

    In 2014, two unusual peaks of H1N1 influenza outbreak occurred in Nakhon Ratchasima Province, in Thailand. Among 2,406 cases, one of the 22 deaths in the province included a 6-year-old boy, who initially presented with acute necrotizing encephalopathy. On the other hand, his sibling was mildly affected by the same influenza virus strain, confirmed by whole-genome sequencing, with one silent mutation. Absence of acute necrotizing encephalopathy and other neurological illnesses in the family and the whole province, with near identical whole viral genomic sequences from the two siblings, and an absence of concomitant severe lung infection (cytokine storm) at onset suggest nonpermissive infection as an alternative pathogenetic mechanism of influenza virus. PMID:27812294

  1. Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes

    PubMed Central

    Salamon, Douglas; Leber, Amy; Mejias, Asuncion

    2016-01-01

    Background An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. Methods May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. Results In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. Conclusions This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68

  2. Homologous recombinational repair factors are recruited and loaded onto the viral DNA genome in Epstein-Barr virus replication compartments.

    PubMed

    Kudoh, Ayumi; Iwahori, Satoko; Sato, Yoshitaka; Nakayama, Sanae; Isomura, Hiroki; Murata, Takayuki; Tsurumi, Tatsuya

    2009-07-01

    Homologous recombination is an important biological process that facilitates genome rearrangement and repair of DNA double-strand breaks (DSBs). The induction of Epstein-Barr virus (EBV) lytic replication induces ataxia telangiectasia-mutated (ATM)-dependent DNA damage checkpoint signaling, leading to the clustering of phosphorylated ATM and Mre11/Rad50/Nbs1 (MRN) complexes to sites of viral genome synthesis in nuclei. Here we report that homologous recombinational repair (HRR) factors such as replication protein A (RPA), Rad51, and Rad52 as well as MRN complexes are recruited and loaded onto the newly synthesized viral genome in replication compartments. The 32-kDa subunit of RPA is extensively phosphorylated at sites in accordance with those with ATM. The hyperphosphorylation of RPA32 causes a change in RPA conformation, resulting in a switch from the catalysis of DNA replication to the participation in DNA repair. The levels of Rad51 and phosphorylated RPA were found to increase with the progression of viral productive replication, while that of Rad52 proved constant. Furthermore, biochemical fractionation revealed increases in levels of DNA-bound forms of these HRRs. Bromodeoxyuridine-labeled chromatin immunoprecipitation and PCR analyses confirmed the loading of RPA, Rad 51, Rad52, and Mre11 onto newly synthesized viral DNA, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling analysis demonstrated DSBs in the EBV replication compartments. HRR factors might be recruited to repair DSBs on the viral genome in viral replication compartments. RNA interference knockdown of RPA32 and Rad51 prevented viral DNA synthesis remarkably, suggesting that homologous recombination and/or repair of viral DNA genome might occur, coupled with DNA replication to facilitate viral genome synthesis.

  3. Limited efficacy of topical recombinant feline interferon-omega for treatment of cats with acute upper respiratory viral disease.

    PubMed

    Ballin, Anne C; Schulz, Bianka; Helps, Christopher; Sauter-Louis, Carola; Mueller, Ralf S; Hartmann, Katrin

    2014-12-01

    Despite a lack of controlled studies confirming its efficacy, recombinant feline interferon-omega (rfeIFN-ω) is used in the treatment of feline upper respiratory tract disease (FURTD), which is usually caused by feline calicivirus (FCV) or feline herpesvirus-1 (FHV-1). The aims of the present study were to investigate whether administration of rfeIFN-ω improves clinical signs in cats with acute FURTD and whether this treatment reduces shedding of FCV. Thirty-seven cats affected with acute FURTD were recruited into a prospective, randomised, placebo-controlled, double-blinded clinical trial. The presence of FCV and/or FHV-1 was determined by performing quantitative polymerase chain reaction (qPCR) on oropharyngeal and conjunctival swabs. Cats were randomly assigned to treatment groups, receiving either placebo or rfeIFN-ω (2.5 MU/kg) subcutaneously, followed by 0.5 MU topically at 8-h intervals via the conjunctiva, intranasally, and orally for 21 days. All cats received additional treatment with antibiotics, expectorants, and inhalation of nebulised physiological saline with camomile. Clinical signs and FCV shedding were evaluated over 42 days. All cats demonstrated improvement in clinical signs during the course of the study, with no significant difference in any of the assessed variables when comparing the two groups. FCV copy numbers decreased more rapidly in cats receiving rfeIFN-ω. Treatment with rfeIFN-ω was not effective in ameliorating clinical signs of acute viral FURTD compared to placebo, but might accelerate a reduction in FCV load in infected cats.

  4. Nutritional status, breastfeeding, and evolution of Infants with acute viral bronchiolitis.

    PubMed

    Dornelles, Cristina T L; Piva, Jefferson P; Marostica, Paulo J C

    2007-09-01

    Acute viral bronchiolitis is a common respiratory infectious disease of infancy. A prospective study was carried out with 175 infants aged up to six months to evaluate their nutritional and breastfeeding status as possible risk factors for unfavourable evolution of previously-healthy infants from a care hospital. Immunofluorescence test for virus and anthropometric assessment were performed. Outcomes were length of oxygen-use, length of hospital stay, and type of hospital unit needed. Seventy-three percent of the infants were well-nourished, 6% undernourished, 8.6% at a nutritional risk, 10.9% overweight, and 1.7% obese. Eighty-one percent of the undernourished and nutritionally at-risk infants and 72% of the well-nourished, overweight, and obese infants did not receive exclusive breastfeeding. The median length of hospital stay was four days and of oxygen-use was 60 hours. The nutritional status did not affect the clinical course of previously-healthy infants with acute viral brochiolitis. The duration of exclusive breastfeeding, but not type of breastfeeding, was inversely related to the length of oxygen-use and the length of hospital stay. Shorter exclusive breastfeeding was observed in infants who were assigned to a paediatric ward or to an intensive care unit. In conclusion, longer duration of breastfeeding was associated with better clinical outcomes.

  5. Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay

    PubMed Central

    Gous, Natasha; Scott, Lesley; Berrie, Leigh; Stevens, Wendy

    2016-01-01

    Background Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert’s random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Method Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Results Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32–0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. Conclusion The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services. PMID:27992495

  6. Multiple high-risk HPV genotypes are grouped by type and are associated with viral load and risk factors.

    PubMed

    Del Río-Ospina, L; Soto-DE León, S C; Camargo, M; Sánchez, R; Moreno-Pérez, D A; Pérez-Prados, A; Patarroyo, M E; Patarroyo, M A

    2017-02-10

    Investigating whether high-risk human papillomavirus (HR-HPV) types tend to become grouped in a particular way and whether factors are associated with such grouping is important for measuring the real impact of vaccination. In total, 219 women proving positive for HPV as detected by real-time PCR were included in the study. Each sample was analysed for detecting and quantifying six viral types and the hydroxymethylbilane synthase gene. Multiple correspondence analysis led to determining grouping patterns for six HR-HPV types and simultaneous association with multiple variables and whether viral load was related to the coexistence of other viral types. Two grouping profiles were identified: the first included HPV-16 and HPV-45 and the second profile was represented by HPV-31, HPV-33 and HPV-58. Variables such as origin, contraceptive method, births and pregnancies, educational level, healthcare affiliation regime, atypical squamous cells of undetermined significance and viral load were associated with these grouping profiles. Different socio-demographic characteristics were found when coinfection occurred by phylogenetically related HPV types and when coinfection was due to non-related types. Biological characteristics, the number of viral copies, temporality regarding acquiring infection and competition between viral types could influence the configuration of grouping patterns. Characteristics related to women and HPV, influence such interactions between coexisting HPV types reflecting the importance of their evaluation.

  7. Design and implementation of an external quality assessment program for HIV viral load measurements using dried blood spots.

    PubMed

    Prach, Lisa M; Puren, Adrian; Lippman, Sheri A; Carmona, Sergio; Stephenson, Sophie; Cutler, Ewalde; Barnhart, Scott; Liegler, Teri

    2015-03-01

    An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects.

  8. HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis.

    PubMed

    Lyra, A C; Pinho, J R R; Silva, L K; Sousa, L; Saraceni, C P; Braga, E L; Pereira, J E; Zarife, M A S; Reis, M G; Lyra, L G C; Silva, L C da; Carrilho, F J

    2005-05-01

    The aim of the present study was to evaluate the prevalence of HEV, TTV and GBV-C/GBV-C/HGV in patients with acute viral hepatitis A, B and non-A-C. We evaluated sera of 94 patients from a sentinel program who had acute hepatitis A (N = 40), B (N = 42) and non-A-C (N = 12); 71 blood donors served as controls. IgM and anti-HEV IgG antibodies were detected by enzyme immunoassay using commercial kits. TTV and GBV-C/HGV were detected by nested PCR; genotyping was done by sequencing and phylogenetic analysis. Anti-HEV IgG was present in 38, 10 and 17% of patients with hepatitis A, B and non-A-C. Four patients with hepatitis A and 1 with non-A-C hepatitis also had anti-HEV IgM detected in serum. TTV was detected in 21% of patients with acute hepatitis and in 31% of donors. GBV-C/HGV was detected in 9% of patients with hepatitis, and in 10% of donors. We found TTV isolates of genotypes 1, 2, 3, and 4 and GBV-C/HGV isolates of genotypes 1 and 2. Mean aminotransferase levels were lower in patients who were TTV or GBV-C/HGV positive. In conclusion, the detection of anti-HEV IgM in some acute hepatitis A cases suggests co-infection with HEV and hepatitis E could be the etiology of a few cases of sporadic non-A-C hepatitis in Salvador, Brazil. TTV genotype 1, 2, 3 and 4 isolates and GBV-C/HGV genotype 1 and 2 strains are frequent in the studied population. TTV and GBV-C/HGV infection does not appear to have a role in the etiology of acute hepatitis.

  9. Beak and feather disease virus: correlation between viral load and clinical signs in wild Cape parrots (Poicepahlus robustus) in South Africa.

    PubMed

    Regnard, Guy L; Boyes, Rutledge S; Martin, Rowan O; Hitzeroth, Inga I; Rybicki, Edward P

    2015-01-01

    Psittacine beak and feather disease (PBFD), the most prevalent viral disease affecting psittacines, is caused by beak and feather disease virus (BFDV). This study assessed viral load using qPCR in a wild Cape parrot population affected by PBFD and compared it to overall physical condition based on clinical signs attributable to PBFD. A significant inverse correlation between viral load and overall physical condition was found, which confirmed that clinical signs may confidently be used to diagnose the relative severity of BFDV infections in wild populations. This is the first assessment of BFDV viral load in a wild psittacine population.

  10. The role of C5a in acute lung injury induced by highly pathogenic viral infections

    PubMed Central

    Wang, Renxi; Xiao, He; Guo, Renfeng; Li, Yan; Shen, Beifen

    2015-01-01

    The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses. PMID:26060601

  11. Positive Correlation between Epstein-Barr Virus Viral Load and Anti-Viral Capsid Immunoglobulin G Titers Determined for Hodgkin's Lymphoma Patients and Their Relatives

    PubMed Central

    Besson, Caroline; Amiel, Corinne; Le-Pendeven, Catherine; Brice, Pauline; Fermé, Christophe; Carde, Patrice; Hermine, Olivier; Raphael, Martine; Abel, Laurent; Nicolas, Jean-Claude

    2006-01-01

    Markers of Epstein-Barr virus (EBV) infection include measures of specific serological titers and of viral load (VLo) in peripheral blood mononuclear cells. Few studies have investigated the correlation between these two phenotypes. Here, we found that there was no correlation between VLo and either anti-EBV nuclear antigen type 1 or anti-early antigen immunoglobulin G (IgG) titer but that anti-viral capsid antigen (VCA) IgG titer increased with VLo in peripheral blood mononuclear cells in patients with Hodgkin's lymphoma (P = 3.10−3). A similar pattern was observed in healthy first-degree relatives (parents and siblings) of patients (P = 6.10−4). Our results indicate that anti-VCA IgG titers and EBV VLo are specifically correlated EBV phenotypes. PMID:16390946

  12. Characteristics and progression of children with acute viral bronchiolitis subjected to mechanical ventilation

    PubMed Central

    Ferlini, Roberta; Pinheiro, Flávia Ohlweiler; Andreolio, Cinara; Carvalho, Paulo Roberto Antonacci; Piva, Jefferson Pedro

    2016-01-01

    Objective To analyze the characteristics of children with acute viral bronchiolitis subjected to mechanical ventilation for three consecutive years and to correlate their progression with mechanical ventilation parameters and fluid balance. Methods Longitudinal study of a series of infants (< one year old) subjected to mechanical ventilation for acute viral bronchitis from January 2012 to September 2014 in the pediatric intensive care unit. The children's clinical records were reviewed, and their anthropometric data, mechanical ventilation parameters, fluid balance, clinical progression, and major complications were recorded. Results Sixty-six infants (3.0 ± 2.0 months old and with an average weight of 4.7 ± 1.4kg) were included, of whom 62% were boys; a virus was identified in 86%. The average duration of mechanical ventilation was 6.5 ± 2.9 days, and the average length of stay in the pediatric intensive care unit was 9.1 ± 3.5 days; the mortality rate was 1.5% (1/66). The peak inspiratory pressure remained at 30cmH2O during the first four days of mechanical ventilation and then decreased before extubation (25 cmH2O; p < 0.05). Pneumothorax occurred in 10% of the sample and extubation failure in 9%, which was due to upper airway obstruction in half of the cases. The cumulative fluid balance on mechanical ventilation day four was 402 ± 254mL, which corresponds to an increase of 9.0 ± 5.9% in body weight. Thirty-seven patients (56%) exhibited a weight gain of 10% or more, which was not significantly associated with the ventilation parameters on mechanical ventilation day four, extubation failure, duration of mechanical ventilation or length of stay in the pediatric intensive care unit. Conclusion The rate of mechanical ventilation for acute viral bronchiolitis remains constant, being associated with low mortality, few adverse effects, and positive cumulative fluid balance during the first days. Better fluid control might reduce the duration of mechanical

  13. Global cost modeling analysis of HIV-1 and HCV viral load assays.

    PubMed

    Elbeik, Tarek; Chen, Yi-Ming Arthur; Soutchkov, Serguei V; Loftus, Richard A; Beringer, Scott

    2003-08-01

    This review addresses hidden costs associated with the Bayer VERSANT assay, Roche AMPLICOR MONITOR test and COBAS AMPLICOR MONITOR test and how these influence the final per reportable cost to a testing laboratory in resource-rich and -poor countries. An in-depth evaluation and recommendation of the most cost-effective approach for these tests is presented. The analyses demonstrate the need for manufacturers to consider labor and supply costs when marketing a kit in resource-poor countries, noting that marketing strategies need to change. In the absence of any proven monitoring alternative, emphasis is placed on increasing market share to promote significant reduction in kit prices to suit the demands of markets in resource-poor countries. Finally, recommendations are made to improve the overall cost structure of viral load testing. This review is intended as a tool to optimize assay usage in attaining the lowest performance costs by assay and is not to endorse any test, as will become apparent.

  14. Using Exclusion-Based Sample Preparation (ESP) to Reduce Viral Load Assay Cost.

    PubMed

    Berry, Scott M; Pezzi, Hannah M; Williams, Eram D; Loeb, Jennifer M; Guckenberger, David J; Lavanway, Alex J; Puchalski, Alice A; Kityo, Cissy M; Mugyenyi, Peter N; Graziano, Franklin M; Beebe, David J

    2015-01-01

    Viral load (VL) measurements are critical to the proper management of HIV in developing countries. However, access to VL assays is limited by the high cost and complexity of existing assays. While there is a need for low cost VL assays, performance must not be compromised. Thus, new assays must be validated on metrics of limit of detection (LOD), accuracy, and dynamic range. Patient plasma samples from the Joint Clinical Research Centre in Uganda were de-identified and measured using both an existing VL assay (Abbott RealTime HIV-1) and our assay, which combines low cost reagents with a simplified method of RNA isolation termed Exclusion-Based Sample Preparation (ESP).71 patient samples with VLs ranging from <40 to >3,000,000 copies/mL were used to compare the two methods. We demonstrated equivalent LOD (~50 copies/mL) and high accuracy (average difference between methods of 0.08 log, R2 = 0.97). Using expenditures from this trial, we estimate that the cost of the reagents and consumables for this assay to be approximately $5 USD. As cost is a significant barrier to implementation of VL testing, we anticipate that our assay will enhance access to this critical monitoring test in developing countries.

  15. Honey Bee Viruses in Wild Bees: Viral Prevalence, Loads, and Experimental Inoculation.

    PubMed

    Dolezal, Adam G; Hendrix, Stephen D; Scavo, Nicole A; Carrillo-Tripp, Jimena; Harris, Mary A; Wheelock, M Joseph; O'Neal, Matthew E; Toth, Amy L

    2016-01-01

    Evidence of inter-species pathogen transmission from managed to wild bees has sparked concern that emerging diseases could be causing or exacerbating wild bee declines. While some pathogens, like RNA viruses, have been found in pollen and wild bees, the threat these viruses pose to wild bees is largely unknown. Here, we tested 169 bees, representing 4 families and 8 genera, for five common honey bee (Apis mellifera) viruses, finding that more than 80% of wild bees harbored at least one virus. We also quantified virus titers in these bees, providing, for the first time, an assessment of viral load in a broad spectrum of wild bees. Although virus detection was very common, virus levels in the wild bees were minimal-similar to or lower than foraging honey bees and substantially lower than honey bees collected from hives. Furthermore, when we experimentally inoculated adults of two different bee species (Megachile rotundata and Colletes inaequalis) with a mixture of common viruses that is lethal to honey bees, we saw no effect on short term survival. Overall, we found that honey bee RNA viruses can be commonly detected at low levels in many wild bee species, but we found no evidence that these pathogens cause elevated short-term mortality effects. However, more work on these viruses is greatly needed to assess effects on additional bee species and life stages.

  16. Honey Bee Viruses in Wild Bees: Viral Prevalence, Loads, and Experimental Inoculation

    PubMed Central

    Dolezal, Adam G.; Hendrix, Stephen D.; Scavo, Nicole A.; Carrillo-Tripp, Jimena; Harris, Mary A.; Wheelock, M. Joseph; O’Neal, Matthew E.; Toth, Amy L.

    2016-01-01

    Evidence of inter-species pathogen transmission from managed to wild bees has sparked concern that emerging diseases could be causing or exacerbating wild bee declines. While some pathogens, like RNA viruses, have been found in pollen and wild bees, the threat these viruses pose to wild bees is largely unknown. Here, we tested 169 bees, representing 4 families and 8 genera, for five common honey bee (Apis mellifera) viruses, finding that more than 80% of wild bees harbored at least one virus. We also quantified virus titers in these bees, providing, for the first time, an assessment of viral load in a broad spectrum of wild bees. Although virus detection was very common, virus levels in the wild bees were minimal—similar to or lower than foraging honey bees and substantially lower than honey bees collected from hives. Furthermore, when we experimentally inoculated adults of two different bee species (Megachile rotundata and Colletes inaequalis) with a mixture of common viruses that is lethal to honey bees, we saw no effect on short term survival. Overall, we found that honey bee RNA viruses can be commonly detected at low levels in many wild bee species, but we found no evidence that these pathogens cause elevated short-term mortality effects. However, more work on these viruses is greatly needed to assess effects on additional bee species and life stages. PMID:27832169

  17. Molecular viral epidemiology and clinical characterization of acute febrile respiratory infections in hospitalized children in Taiwan.

    PubMed

    Lee, Chun-Yi; Chang, Yu-Fen; Lee, Chia-Lin; Wu, Meng-Che; Ho, Chi-Lin; Chang, Yu-Chuan; Chan, Yu-Jiun

    2015-11-01

    Acute respiratory infection (ARI) is a leading cause of morbidity and hospitalization in children. To profile the viruses causing ARI in children admitted to a community-based hospital in central Taiwan, a cross-sectional study was conducted on children under 14 years of age that were hospitalized with febrile ARI. Viral etiology was determined using conventional cell culture and a commercial respiratory virus panel fast assay (xTAG RVP), capable of detecting 19 different respiratory viruses and subtype targets. Demographic, clinical, and laboratory data were recorded and analyzed. The RVP fast assay identified at least one respiratory virus in 130 of the 216 specimens examined (60.2%) and rose to 137 (63.4%) by combining the results of cell culture and RVP fast assay. In order of frequency, the etiological agents identified were, rhinovirus/enterovirus (24.6%), respiratory syncytial virus (13.8%), adenovirus (11.5%), parainfluenza virus (9.2%), influenza B (8.4%), influenza A (5.4%), human metapneumovirus (4.6%), human coronavirus (2%), and human bocavirus (2%). Co-infection did not result in an increase in clinical severity. The RVP assay detected more positive specimens, but failed to detect 6 viruses identified by culture. The viral detection rate for the RVP assay was affected by how many days after admission the samples were taken (P = 0.03). In conclusion, Rhinovirus/enterovirus, respiratory syncytial virus, and adenovirus were prevalent in this study by adopting RVP assay. The viral detection rate is influenced by sampling time, especially if the tests are performed during the first three days of hospitalization.

  18. Aetiology of acute paediatric gastroenteritis in Bulgaria during summer months: prevalence of viral infections.

    PubMed

    Mladenova, Zornitsa; Steyer, Andrej; Steyer, Adela Fratnik; Ganesh, Balasubramanian; Petrov, Petar; Tchervenjakova, Tanja; Iturriza-Gomara, Miren

    2015-03-01

    Paediatric acute gastroenteritis is a global public health problem. Comprehensive laboratory investigation for viral, bacterial and parasitic agents is helpful for improving management of acute gastroenteritis in health care settings and for monitoring and controlling the spread of these infections. Our study aimed to investigate the role of various pathogens in infantile diarrhoea in Bulgaria outside the classical winter epidemics of rotavirus and norovirus. Stool samples from 115 hospitalized children aged 0-3 years collected during summer months were tested for presence of 14 infectious agents - group A rotavirus, astrovirus, Giardia, Cryptosporidium and Entamoeba using ELISAs; norovirus by real-time RT-PCR; picobirnavirus and sapovirus by RT-PCR; adenovirus using PCR, and Salmonella, Shigella, Escherichia coli, Yersinia and Campylobacter using standard bacterial cultures. Infectious origin was established in a total of 92 cases and 23 samples remained negative. A single pathogen was found in 67 stools, of which rotaviruses were the most prevalent (56.7 %), followed by noroviruses (19.4 %), enteric adenoviruses (7.5 %), astroviruses (6.0 %), bacteria and parasites (4.5 % each) and sapoviruses (1.4 %). Rotavirus predominant genotypes were G4P[8] (46.3 %) and G2P[4] (21.4 %); for astroviruses, type 1a was the most common, while the GII.4/2006b variant was the most prevalent among noroviruses. Bacteria were observed in five cases, with Salmonella sp. as the most prevalent, while parasites were found in ten stool samples, with Giardia intestinalis in five cases. The results demonstrated high morbidity associated with viral infections and that rotavirus and norovirus remain the most common pathogens associated with severe gastroenteritis during summer months in Bulgaria, a country with a temperate climate, and significant molecular diversity among circulating virus strains.

  19. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with HIV in Latin America

    PubMed Central

    Duarte, Horacio A.; Harris, D. Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flavia Faleiro; Cruz, Maria Leticia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan

    2016-01-01

    Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of HIV-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with HIV viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population. PMID:25743569

  20. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community.

    PubMed

    Houben, M L; Coenjaerts, F E J; Rossen, J W A; Belderbos, M E; Hofland, R W; Kimpen, J L L; Bont, L

    2010-07-01

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48-96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi-quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT-value and disease severity was found in all RSV cases (rho = -0.52, P = 0.003) and in cases with RSV as the primary pathogen (rho = -0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection.

  1. Acute volume loading and exercise capacity in postural tachycardia syndrome.

    PubMed

    Figueroa, Rocío A; Arnold, Amy C; Nwazue, Victor C; Okamoto, Luis E; Paranjape, Sachin Y; Black, Bonnie K; Diedrich, Andre; Robertson, David; Biaggioni, Italo; Raj, Satish R; Gamboa, Alfredo

    2014-09-15

    Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate (HR) increases. Acute volume loading with intravenous (iv) saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of iv saline infusion on peak exercise capacity (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential study. VO2peak was measured on two separate study days, following administration of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal effort was achieved. Patients exhibited blood volume deficits (-13.4 ± 1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline 80 ± 8 ml vs. placebo 64 ± 4 ml; P = 0.010), increased cardiac output (saline 6.9 ± 0.5 liter/min vs. placebo 5.7 ± 0.2 liter/min; P = 0.021), and reduced systemic vascular resistance (saline 992.6 ± 70.0 dyn-s/cm(5) vs. placebo 1,184.0 ± 50.8 dyn-s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise, saline did not produce differences in VO2peak (saline 26.3 ± 1.2 mg·kg(-1)·min(-1) vs. placebo 27.7 ± 1.8 mg·kg(-1)·min(-1); P = 0.615), peak HR [saline 174 ± 4 beats per minute (bpm) vs. placebo 175 ± 3 bpm; P = 0.672] or other cardiovascular parameters. These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function.

  2. Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model.

    PubMed

    McLane, Virginia D; Cao, Ling; Willis, Colin L

    2014-04-15

    Chronic opiate abuse accelerates the development of cognitive deficits in human immunodeficiency virus (HIV)-1 patients. To investigate morphine's effects on viral infection of the central nervous system, we applied chronic morphine treatment to the LP-BM5 murine acquired immunodeficiency syndrome (MAIDS) model. LP-BM5 infection induces proinflammatory cytokine/chemokine production, correlating to increased blood-brain barrier permeability. Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe. Morphine reduced the chemokine CCL5 to non-infected levels in the frontal lobe, but not in the hippocampus. These data indicate a region-specific mechanism for morphine's effects on virally-induced neurocognitive deficits.

  3. Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease

    PubMed Central

    Das, Bibhuti; Morrow, Robert; Huang, Rong; Fixler, David

    2016-01-01

    AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder (PTLD) in the presence of persisting high Epstein-Barr virus (EBV) in EBV naïve pediatric heart transplant (HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients (5.5%); 6/91 (6.5%) in those who were EBV seropositive and 2/54 (3.7%) in the EBV naïve group at the time of HT (P = 0.71). We found 32/145 (22%) patients with persistently high EBV load during continuing follow-up; 20/91 (22%) in EBV seropositive group vs 12/54 (22%) in EBV naïve group (P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant (P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15% (3/20) of patients with high EBV vs 4.2% (3/71) of patients with low or undetectable EBV load (P = 0.14) whereas in EBV naïve patients 8.3% (1/12) of those with high EBV load and 2.3% (1/42) with low or undetectable EBV load (P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up (4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort (P = 0.005). At least one episode of acute rejection occurred in 72% (23/32) of patients with high EBV vs 36% (41/113) patients with low or undetectable EBV after HT (P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load

  4. Analysis of plasma viral RNA levels during acute dengue virus infection using quantitative competitor reverse transcription-polymerase chain reaction.

    PubMed

    Sudiro, T M; Zivny, J; Ishiko, H; Green, S; Vaughn, D W; Kalayanarooj, S; Nisalak, A; Norman, J E; Ennis, F A; Rothman, A L

    2001-01-01

    There is increasing recognition of the potential importance of viral burden in the pathogenesis of dengue hemorrhagic fever (DHF). There is little data available, however, describing the kinetics of viral replication in humans with natural dengue virus (DV) infection. Standard procedures for measuring titers of infectious virus in clinical specimens are either laborious or insensitive. We developed a method for measurement of DV RNA in plasma samples based on reverse transcription-polymerase chain reaction (RT-PCR) using a mutant RNA target as a competitor. This technique was reproducible and accurate for samples containing any of the four DV serotypes, and could be applied to samples containing as few as 250 copies of RNA per reaction. We examined plasma viral RNA levels in 80 children with acute DV infection; sequential plasma samples were tested in 34 of these children. Plasma viral RNA levels ranged as high as 10(9) RNA copies/ml, and correlated with titers of infectious virus measured in mosquitoes (r= 0.69). Plasma viral RNA levels fell rapidly during the last several days of the febrile period. We did not find a significant difference in maximal plasma viral RNA levels between children with DHF and children with dengue fever, but peak viral RNA levels were identified in only 16 subjects. We conclude that this quantitative RT-PCR method will be valuable for further studies of natural DV infections.

  5. Acute viral hepatitis, intravascular haemolysis, severe hyperbilirubinaemia and renal failure in glucose-6-phosphate dehydrogenase deficient patients.

    PubMed Central

    Agarwal, R. K.; Moudgil, A.; Kishore, K.; Srivastava, R. N.; Tandon, R. K.

    1985-01-01

    Five patients with acute viral hepatitis developed severe intrasvascular haemolysis and unusually high levels of serum bilirubin (427 to 1368 mumol/l). All 5 had high fever, marked anaemia, reticulocytosis and neutrophilic leucocytosis. Three of them developed acute renal failure, which was of non-oliguric type in 2. The clinical course was protracted, but complete recovery occurred in 4 patients between 4 to 10 weeks. One patient with hepatic coma and oliguric renal failure died. Deficiency of the enzyme G-6-PD was confirmed in 4 cases. Massive haemolysis in the patients was probably induced by the administration of chloroquine and other drugs. Intravascular haemolysis should be suspected in patients with acute viral hepatitis, if they show unexplained anaemia and very high serum bilirubin levels, and measures to prevent renal failure should be instituted in such cases. PMID:4070114

  6. Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus).

    PubMed

    Stanton, Jeffrey J; Zong, Jian-Chao; Eng, Crystal; Howard, Lauren; Flanagan, Joe; Stevens, Martina; Schmitt, Dennis; Wiedner, Ellen; Graham, Danielle; Junge, Randall E; Weber, Martha A; Fischer, Martha; Mejia, Alicia; Tan, Jie; Latimer, Erin; Herron, Alan; Hayward, Gary S; Ling, Paul D

    2013-03-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elphas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions. In three elephants displaying clinical signs of illness, preclinical EEHV1 DNAemia was detectable, and peak whole-blood viral loads occurred 3-8 days after the onset of clinical signs. In two elephants with EEHV1 DNAemia that persisted for 7-21 days, no clinical signs of illness were observed. Detection of EEHV1 DNA in trunk washes peaked approximately 21 days after DNAemia, and viral genotypes detected during DNAemia matched those detected in subsequent trunk washes from the same elephant. In each of the five elephants, two distinct EEHV1 genotypes were identified in whole blood and trunk washes at different time points. In each case, these genotypes represented both an EEHV1A and an EEHV1B subtype. These data suggest that knowledge of viral loads could be useful for the management of elephants before or during clinical illness. Furthermore, sequential infection with both EEHV1 subtypes occurs in Asian elephants, suggesting that they do not elicit cross-protective sterilizing immunity. These data will be useful to individuals involved in the husbandry and clinical care of Asian elephants.

  7. Dried Blood Spots for Viral Load Monitoring in Malawi: Feasible and Effective

    PubMed Central

    Rutstein, Sarah E.; Hosseinipour, Mina C.; Kamwendo, Deborah; Soko, Alice; Mkandawire, Memory; Biddle, Andrea K.; Miller, William C.; Weinberger, Morris; Wheeler, Stephanie B.; Sarr, Abdoulaye; Gupta, Sundeep; Chimbwandira, Frank; Mwenda, Reuben; Kamiza, Steve; Hoffman, Irving; Mataya, Ronald

    2015-01-01

    Objectives To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa. Methods We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation). Results We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (<5,000 copies/ml) on confirmatory testing. Median period between enrollment and specimen testing was 23 days. Adjusting for relevant covariates, participants on ART >4 years were more likely to be failing than participants on therapy 1–4 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11). Conclusions DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy. PMID:25898365

  8. Hepatitis B viral load in dried blood spots: a validation study in Zambia

    PubMed Central

    Vinikoor, Michael J.; Zürcher, Samuel; Musukuma, Kalo; Kachuwaire, Obert; Rauch, Andri; Chi, Benjamin H.; Gorgievski, Meri; Zwahlen, Marcel; Wandeler, Gilles

    2016-01-01

    Background Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons. Objectives To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples. Study design Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by HBV genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL. Results Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98 log IU/ml (interquartile range, 2.04–5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59 log IU/ml lower compared to plasma with 95% limits of agreement of −2.40 to −0.83 log IU/ml. At a plasma VL ≥2,000 IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5–6.6). At plasma VL ≥20,000 IU/ml this probability reduced to 0.2% (95% CI: 0.03–1.7). Conclusions In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000 IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing in SSA settings. PMID:26356987

  9. Acute viral hepatitis in the United States-Mexico border region: data from the Border Infectious Disease Surveillance (BIDS) Project, 2000-2009.

    PubMed

    Spradling, Philip R; Xing, Jian; Phippard, Alba; Fonseca-Ford, Maureen; Montiel, Sonia; Guzmán, Norma Luna; Campuzano, Roberto Vázquez; Vaughan, Gilberto; Xia, Guo-liang; Drobeniuc, Jan; Kamili, Saleem; Cortés-Alcalá, Ricardo; Waterman, Stephen H

    2013-04-01

    Little is known about the characteristics of acute viral hepatitis cases in the United States (US)-Mexico border region. We analyzed characteristics of acute viral hepatitis cases collected from the Border Infectious Disease Surveillance Project from January 2000-December 2009. Over the study period, 1,437 acute hepatitis A, 311 acute hepatitis B, and 362 acute hepatitis C cases were reported from 5 Mexico and 2 US sites. Mexican hepatitis A cases most frequently reported close personal contact with a known case, whereas, US cases most often reported cross-border travel. Injection drug use was common among Mexican and US acute hepatitis B and C cases. Cross-border travel during the incubation period was common among acute viral hepatitis cases in both countries. Assiduous adherence to vaccination and prevention guidelines in the US is needed and strategic implementation of hepatitis vaccination and prevention programs south of the border should be considered.

  10. An Analysis of Viral Testing in non-Acetaminophen (non-APAP) Pediatric Acute Liver Failure (PALF)

    PubMed Central

    Schwarz, Kathleen B.; Olio, Dominic Dell; Lobritto, Steven J.; Lopez, M James; Rodriguez-Baez, Norberto; Yazigi, Nada A.; Belle, Steven H.; Zhang, Song; Squires, Robert H.

    2014-01-01

    Objective Viral infections are often suspected to cause pediatric acute liver failure (PALF) but large-scale studies have not been performed. We analyzed results of viral testing among non-acetaminophen (non APAP) PALF study participants. Methods Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either Causative Viruses (CV) or Associated Viruses (AV). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included “Viral”, “Indeterminate” and “Other”. Results Of 860 participants, 820 had at least one test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among “Viral” [66/80 (82.5%)], “Indeterminate” [52/420 (12.4%)] and “Other” [48/320 (15.0%)] diagnoses. CV accounted for 81/166 (48.8%) positive tests. Herpes Simplex Virus (HSV) was positive in 39/335 (11.6%) who were tested: 26/103 (25.2%) and 13/232 (5.6%) among infants 0 - 6 months and over 6 months, respectively. HSV was not tested in 61.0% and 53% of the over-all cohort and those 0 - 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Conclusions Viral testing in PALF occurs frequently but is often incomplete. Evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation. PMID:25079486

  11. Plasma and Mucosal HIV Viral Loads Are Associated with Genital Tract Inflammation In HIV-Infected Women

    PubMed Central

    Herold, Betsy C.; Keller, Marla J.; Shi, Qiuhu; Hoover, Donald R.; Carpenter, Colleen A.; Huber, Ashley; Parikh, Urvi M.; Agnew, Kathy J.; Minkoff, Howard; Colie, Christine; Nowicki, Marek J.; D’Souza, Gypsyamber; Watts, D. Heather; Anastos, Kathryn

    2013-01-01

    Background Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women’s Interagency HIV Study (WIHS) to explore the hypothesis that compared to HIV-uninfected participants, women with HIV and in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. Methods 19 HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/ml (low viral load) (HIV+-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV+-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). CVL antimicrobial activity was also determined. Results Compared to HIV-uninfected, HIV+-HVL women had higher levels of mucosal, but not systemic pro-inflammatory cytokines and chemokines, higher Nugent scores, and lower E. coli bactericidal activity. In contrast, there were no significant differences between HIV+-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and RANTES and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. Conclusion Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial. PMID:23591635

  12. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  13. Initial viral load determines the magnitude of the human CD8 T cell response to yellow fever vaccination.

    PubMed

    Akondy, Rama S; Johnson, Philip L F; Nakaya, Helder I; Edupuganti, Srilatha; Mulligan, Mark J; Lawson, Benton; Miller, Joseph D; Pulendran, Bali; Antia, Rustom; Ahmed, Rafi

    2015-03-10

    CD8 T cells are a potent tool for eliminating intracellular pathogens and tumor cells. Thus, eliciting robust CD8 T-cell immunity is the basis for many vaccines under development. However, the relationship between antigen load and the magnitude of the CD8 T-cell response is not well-described in a human immune response. Here we address this issue by quantifying viral load and the CD8 T-cell response in a cohort of 80 individuals immunized with the live attenuated yellow fever vaccine (YFV-17D) by sampling peripheral blood at days 0, 1, 2, 3, 5, 7, 9, 11, 14, 30, and 90. When the virus load was below a threshold (peak virus load < 225 genomes per mL, or integrated virus load < 400 genome days per mL), the magnitude of the CD8 T-cell response correlated strongly with the virus load (R(2) ∼ 0.63). As the virus load increased above this threshold, the magnitude of the CD8 T-cell responses saturated. Recent advances in CD8 T-cell-based vaccines have focused on replication-incompetent or single-cycle vectors. However, these approaches deliver relatively limited amounts of antigen after immunization. Our results highlight the requirement that T-cell-based vaccines should deliver sufficient antigen during the initial period of the immune response to elicit a large number of CD8 T cells that may be needed for protection.

  14. Type I Interferon Induced Epigenetic Regulation of Macrophages Suppresses Innate and Adaptive Immunity in Acute Respiratory Viral Infection

    PubMed Central

    Kroetz, Danielle N.; Allen, Ronald M.; Schaller, Matthew A.; Cavallaro, Cleyton; Ito, Toshihiro; Kunkel, Steven L.

    2015-01-01

    Influenza A virus (IAV) is an airborne pathogen that causes significant morbidity and mortality each year. Macrophages (Mϕ) are the first immune population to encounter IAV virions in the lungs and are required to control infection. In the present study, we explored the mechanism by which cytokine signaling regulates the phenotype and function of Mϕ via epigenetic modification of chromatin. We have found that type I interferon (IFN-I) potently upregulates the lysine methyltransferase Setdb2 in murine and human Mϕ, and in turn Setdb2 regulates Mϕ-mediated immunity in response to IAV. The induction of Setdb2 by IFN-I was significantly impaired upon inhibition of the JAK-STAT signaling cascade, and chromatin immunoprecipitation revealed that both STAT1 and interferon regulatory factor 7 bind upstream of the transcription start site to induce expression. The generation of Setdb2LacZ reporter mice revealed that IAV infection results in systemic upregulation of Setdb2 in myeloid cells. In the lungs, alveolar Mϕ expressed the highest level of Setdb2, with greater than 70% lacZ positive on day 4 post-infection. Silencing Setdb2 activity in Mϕ in vivo enhanced survival in lethal IAV infection. Enhanced host protection correlated with an amplified antiviral response and less obstruction to the airways. By tri-methylating H3K9, Setdb2 silenced the transcription of Mx1 and Isg15, antiviral effectors that inhibit IAV replication. Accordingly, a reduced viral load in knockout mice on day 8 post-infection was linked to elevated Isg15 and Mx1 transcript in the lungs. In addition, Setdb2 suppressed the expression of a large number of other genes with proinflammatory or immunomodulatory function. This included Ccl2, a chemokine that signals through CCR2 to regulate monocyte recruitment to infectious sites. Consistently, knockout mice produced more CCL2 upon IAV infection and this correlated with a 2-fold increase in the number of inflammatory monocytes and alveolar Mϕ in the

  15. Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia

    PubMed Central

    Wandeler, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J.; Llenas-García, Jara; Aly, Mussa M.; Mulenga, Lloyd; Chi, Benjamin H.; Ehmer, Jochen; Hobbins, Michael A.; Bolton-Moore, Carolyn; Hoffmann, Christopher J.; Egger, Matthias

    2016-01-01

    Background Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. Methods We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. Results Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192–8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22–5.53) and CD4 cell count below 200/μl (2.58, 1.20–5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. Conclusion One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults. PMID:27032097

  16. Intestinal microbiome in children with severe and complicated acute viral gastroenteritis.

    PubMed

    Chen, Shih-Yen; Tsai, Chi-Neu; Lee, Yun-Shien; Lin, Chun-Yuan; Huang, Kuan-Yeh; Chao, Hsun-Ching; Lai, Ming-Wei; Chiu, Cheng-Hsun

    2017-04-11

    The aim of the present study was to evaluate the microbiota of children with severe or complicated acute viral gastroenteritis (AGE). To that end, next-generation sequencing (NGS) technology was used to sequence the 16S ribosomal RNA (16S rRNA) gene in 20 hospitalized pediatric patients with severe or complicated AGE and a further 20 otherwise healthy children; the fecal microbiome was then assessed. Comparative metagenomics data were analyzed by a Wilcoxon rank-sum test and hierarchical clustering analysis of bacterial reads. The statistical analyses showed a significantly decreased Shannon diversity index (entropy score) of the intestinal microbiota in patients with severe AGE compared with normal controls (P = 0.017) and patients with mild-to-moderate AGE (P = 0.011). The intestinal microbiota score of the 5 patients with rotavirus AGE was significantly lower than that of those with norovirus infection (P = 0.048). Greater richness in Campylobacteraceae (P = 0.0003), Neisseriaceae (P = 0.0115), Methylobacteriaceae (P = 0.0004), Sphingomonadaceae (P = 0.0221), and Enterobacteriaceae (P = 0.0451) was found in patients with complicated AGE compared with normal controls. The data suggest a significant reduction in intestinal microbial diversity in patients with severe AGE, particularly those with rotavirus infection.

  17. Intestinal microbiome in children with severe and complicated acute viral gastroenteritis

    PubMed Central

    Chen, Shih-Yen; Tsai, Chi-Neu; Lee, Yun-Shien; Lin, Chun-Yuan; Huang, Kuan-Yeh; Chao, Hsun-Ching; Lai, Ming-Wei; Chiu, Cheng-Hsun

    2017-01-01

    The aim of the present study was to evaluate the microbiota of children with severe or complicated acute viral gastroenteritis (AGE). To that end, next-generation sequencing (NGS) technology was used to sequence the 16S ribosomal RNA (16S rRNA) gene in 20 hospitalized pediatric patients with severe or complicated AGE and a further 20 otherwise healthy children; the fecal microbiome was then assessed. Comparative metagenomics data were analyzed by a Wilcoxon rank–sum test and hierarchical clustering analysis of bacterial reads. The statistical analyses showed a significantly decreased Shannon diversity index (entropy score) of the intestinal microbiota in patients with severe AGE compared with normal controls (P = 0.017) and patients with mild-to-moderate AGE (P = 0.011). The intestinal microbiota score of the 5 patients with rotavirus AGE was significantly lower than that of those with norovirus infection (P = 0.048). Greater richness in Campylobacteraceae (P = 0.0003), Neisseriaceae (P = 0.0115), Methylobacteriaceae (P = 0.0004), Sphingomonadaceae (P = 0.0221), and Enterobacteriaceae (P = 0.0451) was found in patients with complicated AGE compared with normal controls. The data suggest a significant reduction in intestinal microbial diversity in patients with severe AGE, particularly those with rotavirus infection.

  18. Hepatic immune response in calves during acute subclinical infection with bovine viral diarrhoea virus type 1.

    PubMed

    Risalde, M A; Gómez-Villamandos, J C; Pedrera, M; Molina, V; Cerón, J J; Martínez-Subiela, S; Sánchez-Cordón, P J

    2011-11-01

    Eight colostrum-deprived calves aged 8-12 weeks were inoculated intranasally with a non-cytopathic strain of bovine viral diarrhoea virus (BVDV) genotype-1 and the effects on the hepatic immune response were studied. Two calves were sacrificed at each of 3, 6, 9 and 14 days post-inoculation (dpi) and two uninoculated animals were used as negative controls. BVDV was detected in hepatic macrophages and monocytes from 3 to 14dpi and in Küpffer cells (KCs) from 6 to 14dpi. Increases in the numbers of MAC387(+) KCs and monocytes, but not interstitial macrophages, differentiated by morphological features, were evident in the liver following inoculation with BVDV. There was a substantial increase in the number of monocytes positive for tumour necrosis factor (TNF)-α, but only small increases in the numbers of TNF-α(+) KCs and interstitial macrophages and interleukin (IL)-6(+) monocytes, KCs and interstitial macrophages. There was an increase in the number of interstitial CD3(+) T lymphocytes in the liver, but no substantial changes in the numbers of circulating CD3(+) T lymphocytes, interstitial or circulating CD4(+) or CD8(+) T lymphocytes, or CD79αcy(+) B lymphocytes. Serum haptoglobin and serum amyloid A increased transiently at 12dpi. Upregulation of some pro-inflammatory cytokines by hepatic macrophages is evident in subclinical acute BVDV type 1 infection in calves.

  19. Viral Agents Causing Acute Respiratory Infections in Children under Five: A Study from Eastern India

    PubMed Central

    Mishra, Pravakar; Nayak, Lipika; Dwibedi, Bhagirathi; Singh, Amitabh

    2016-01-01

    Background. Acute respiratory infections (ARIs) are important cause of mortality and morbidity in children under five in developing country. Methods. This observational study was conducted over two-year period in a tertiary care teaching hospital of Eastern India. Nasal and throat swabs were collected, transported to the laboratory at 2–8°C in viral transport media, and then processed for detection of viruses using mono/multiplex real-time polymerase chain reaction. Results. A total of 300 children aged 2–60 months with ARIs were included. The most common age group affected with LRI was 2–12 mo and with URI was >12–60 mo. Viruses were detected in 248 cases. In URI, 77 were positive for single virus and 19 were positive for more than one virus; in LRI, 113 were positive for single virus and 12 were positive for more than one virus. The most common viruses isolated from URI cases were rhinovirus and adenovirus. The most common viruses isolated from LRI cases were respiratory syncytial virus and influenza virus. Most cases occurred in the months of January, December, and August. Conclusion. Viruses constitute a significant cause of ARI in children under five. RSV, ADV, RV, and IFV were the most prevalent viruses isolated. PMID:28018433

  20. Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore

    PubMed Central

    Jiang, Lili; Lee, Vernon Jian Ming; Cui, Lin; Lin, Raymond; Tan, Chyi Lin; Tan, Linda Wei Lin; Lim, Wei-yen; Leo, Yee-Sin; Low, Louie; Hibberd, Martin; Chen, Mark I-Cheng

    2017-01-01

    To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings. PMID:28218288

  1. Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases

    PubMed Central

    Roux, Maria E. B.; Florin-Christensen, A.; Arana, R. M.; Doniach, Deborah

    1974-01-01

    Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha1-fetoprotein, smooth muscle, and mitochondria. Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha1-fetoprotein in one. Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated. In three out of the 18 cases there was a double M-component. Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone. PMID:18668850

  2. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy

    PubMed Central

    Del Prete, Gregory Q.; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W. Gregory; Trubey, Charles M.; Piatak, Michael; Deleage, Claire; Keele, Brandon F.; Estes, Jacob D.; Hesselgesser, Joseph; Geleziunas, Romas

    2015-01-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4+ T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  3. Psychosocial and neurohormonal predictors of HIV disease progression (CD4 cells and viral load): A 4 year prospective study

    PubMed Central

    Ironson, G.; O'Cleirigh, C.; Kumar, M.; Kaplan, L.; Balbin, E.; Kelsch, C. B.; Fletcher, M. A.; Schneiderman, N.

    2015-01-01

    Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to ART. We therefore examine NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws (CD4, viral load (VL)), and a 15-hour urine sample (NE, cortisol) every 6 months over 4 years. HLM was used to model slope in CD4 and viral load controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years. PMID:25234251

  4. Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

    PubMed Central

    Schieffer, Miriam; Jessen, Heiko K.; Oster, Alexander F.; Pissani, Franco; Soghoian, Damien Z.; Lu, Richard; Jessen, Arne B.; Zedlack, Carmen; Schultz, Bruce T.; Davis, Isaiah; Ranasinghe, Srinika; Rosenberg, Eric S.; Alter, Galit; Schumann, Ralf R.

    2014-01-01

    ABSTRACT Effector CD4 T cell responses have been shown to be critically involved in the containment and clearance of viral pathogens. However, their involvement in the pathogenesis of HIV infection is less clear, given their additional role as preferred viral targets. We previously demonstrated that the presence of HIV-specific CD4 T cell responses is somewhat associated with HIV control and that specific CD4 T cell functions, such as direct cytolytic activity, can contribute to control of HIV viremia. However, little is known about how the induction of HIV-specific CD4 T cell responses during acute HIV infection influences disease progression and whether responses induced during the early phase of infection are preferentially depleted. We therefore longitudinally assessed, in a cohort of 55 acutely HIV-infected individuals, HIV-specific CD4 T cell responses from acute to chronic infection. Interestingly, we found that the breadth, magnitude, and protein dominance of HIV-specific CD4 T cell responses remained remarkably stable over time. Moreover, we found that the epitopes targeted at a high frequency in acute HIV infection were recognized at the same frequency by HIV-specific CD4 T cells in chronic HIV infection. Interestingly the induction of Gag-specific CD4 T cell responses in acute HIV infection was significantly inversely correlated with viral set point in chronic HIV infection (R = −0.5; P = 0.03), while the cumulative contribution of Env-specific CD4 T cell responses showed the reverse effect. Moreover, individuals with HIV-specific CD4 T cell responses dominantly targeting Gag over Env in acute HIV infection remained off antiretroviral therapy significantly longer (P = 0.03; log rank). Thus, our data suggest that the induction of HIV-specific CD4 T cell responses during acute HIV infection is beneficial overall and does not fuel disease progression. IMPORTANCE CD4 T cells are critical for the clearance and control of viral infections. However, HIV

  5. Viral load of HPV 16/18 in esophageal squamous cell carcinoma in three ethnic groups living in Xinjiang Autonomous Region, China.

    PubMed

    Liu, Tao; Liu, Qing; Liang, Meng; Zheng, Shutao; Li, Xiu Ling; Lu, Xiaomei; Sheyhidin, Ilyar

    2013-02-01

    To investigate the viral load of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) patients from three ethnic groups in Xinjiang. Using Gp5+/Gp6+ consensus primers, the prevalence of HPV DNA was examined in 253 paraffin-embedded ESCC samples. The presence and viral load of HPV 16 and HPV 18 were detected in Kazakhs, Uygurs and Hans using type-specific primers by quantitative real-time PCR (qRT-PCR). Among the 253 ESCC samples, 52 cases were positive for HPV DNA, all the 52 positive cases displayed HPV 16 infection, and six of the 52 cases were co-infected by HPV 16 and 18. HPV 16-positive rate and viral load were higher in lesions, and was inversely correlated with differentiation grades. However, there was no statistic significance among different differentiation grades. Also, there were no significant difference between detection rates of HPV types, viral load and age, gender, ethnic group, and lymph node metastasis. HPV 16 and HPV 18 genotypes could simultaneously be detected in ESCC specimens in three main ethnic groups in Xinjiang. The viral load of HPV 16 is higher in the ESCC lesions, and is inversely correlated with the differentiation grades. These observations reinforce the suggestion that HPV infection may involved in ESCC carcinogenesis; however, high prevalence or viral load of HPV infection does not seem to be related with high incidence of ESCC in Kazakhs, which may be the one element among the multiple risk factors contributing to ESCC.

  6. IL-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice.

    PubMed

    Loebbermann, Jens; Schnoeller, Corinna; Thornton, Hannah; Durant, Lydia; Sweeney, Nathan P; Schuijs, Martijn; O'Garra, Anne; Johansson, Cecilia; Openshaw, Peter J

    2012-01-01

    Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV) induced IL-10 production by CD4(+) and CD8(+) T cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced IFN-γ. Furthermore, RSV infection of IL-10(-/-) mice resulted in more severe disease with enhanced weight loss, delayed recovery and greater cell infiltration of the respiratory tract without affecting viral load. In addition, IL-10(-/-) mice had a pronounced airway neutrophilia and heightened levels of pro-inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the proportion of lung T cells producing IFN-γ was enhanced, suggesting that IL-10 may act in an autocrine manner to dampen effector T cell responses. Similar findings were made in mice treated with anti-IL-10R antibody and infected with RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with RSV, especially during recovery from infection.

  7. Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

    PubMed Central

    Guenounou, Sarah; Borel, Cécile; Bérard, Emilie; Yon, Edwige; Fort, Marylise; Mengelle, Catherine; Bertoli, Sarah; Sarry, Audrey; Tavitian, Suzanne; Huguet, Françoise; Attal, Michel; Récher, Christian; Huynh, Anne

    2016-01-01

    Abstract Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors. Myeloablative and reduced-intensity conditioning regimen were given to 71 and 65 patients, respectively. Including CMV reactivations, at least 1 viral reactivation was recorded in 76 patients. Viral reactivations were associated with a lower risk of relapse (adjusted HR 0.14; 95% CI 0.07–0.30; P < 0.01), better disease-free survival (aHR 0.29; 95% CI 0.16–0.54; P < 0.01) but higher non relapse mortality. This translated into a better overall survival (aHR 0.44; 95%CI 0.25–0.77; P < 0.01) in patients who experienced viral reactivation. Thus, viral reactivations, including but not limited to CMV reactivation, are associated with a better outcome particularly with regard to the risk of relapse in AML patients undergoing alloSCT. New guidelines regarding the choice of donor according to the CMV serostatus are needed. PMID:27902595

  8. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    PubMed

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  9. Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis

    PubMed Central

    Cade, A; Brownlee, K; Conway, S; Haigh, D; Short, A; Brown, J; Dassu, D; Mason, S; Phillips, A; Eglin, R; Graham, M; Chetcuti, A; Chatrath, M; Hudson, N; Thomas, A; Chetcuti, P

    2000-01-01

    OBJECTIVE—To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis.
DESIGN—A multicentre randomised double blind placebo controlled trial.
SUBJECTS—Infants admitted to hospital with their first episode of RSV positive bronchiolitis.
INTERVENTION—Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12months.
MAIN OUTCOME MEASURES—Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of antiwheeze medication during follow up.
RESULTS—161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), −2 (−14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), −1 (−2 to 0). Percentage of infants receiving at least one prescription for antiwheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), −10 (−26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), −7 (−22 to 8).
CONCLUSIONS—There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

 PMID:10648365

  10. The biofilm electrode sensor system for acute toxicity and viral screening

    SciTech Connect

    Holodnick, S.E.

    1988-01-01

    The biofilm electrode sensor (BFE) is designed for the rapid and sensitive detection of toxic and pathogenic environmental contaminants and industrial effluents. It includes a dissolved oxygen electrode which senses respiration changes induced in a biomass film. This study assessed the effects of five chemical on biofilms of Saccharomyces cerevisiae, and polio virus on biofilms of Buffalo Green Monkey kidney cells (BGMk). Acute toxicity was assessed in 30 min, and viral infectivity in 15-20 hr. Potassium cyanide and cupric nitrate inhibited respiration in a similar manner, 2.5-68.2 %I and 30.2-68.8 %I, respectively. The response of the BFE to cyanide and cupric ions occurred within 5-20 sec. Cadmium ions affected the BFE over the range of 50.0-1000 mg/l, but complexed with components in the support medium at lower concentrations. 2,4-dinitrophenol enhanced respiration in the concentration range of 10.0-50.0 mg/l and inhibited respiration in the concentration range of 85.0-100.0 mg/l. A maximum response of 19 %I was noted at 1200 mg/l phenol, before dissolution of the polysulfone membrane filter occurred. Detection of viruses utilized BGMk cells exposed to 4.7 {times} 10{sup 4}{minus}4.7 {times} 10{sup 8} ID{sub 50}/ml poliovirus for 2 hr prior to immobilization. The response of the BFE was optimal at 15-20 hr, with a %I range of 5-40%.

  11. Acute hepatitis C in a chronically HIV-infected patient: Evolution of different viral genomic regions

    PubMed Central

    Flichman, Diego; Kott, Veronica; Sookoian, Silvia; Campos, Rodolfo

    2003-01-01

    AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up. METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 mo and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced. RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established. CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattern. Most of the nucleotide substitutions observed are non-synonymous and clustered in previously described epitopes, thus suggesting an immune-driven evolutionary process. PMID:12854149

  12. Acute transverse myelitis and subacute thyroiditis associated with dengue viral infection: A case report and literature review

    PubMed Central

    Mo, Zhiming; Dong, Yaxian; Chen, Xiaolian; Yao, Huiyan; Zhang, Bin

    2016-01-01

    Acute transverse myelitis is a rare manifestation of dengue infection. To the best of our knowledge, only 6 cases of acute transverse myelitis as a manifestation of dengue infection have been reported thus far. The present study described a case of acute transverse myelitis complicated with subacute thyroiditis 6 days after the onset of dengue viral infection. In addition, the available literature was searched to identify similar previous cases. Treatment with intravenous pulse methylprednisolone immunoglobulin plasmapheresis and physiotherapy resulted in partial recovery at 3 months post-infection. In conclusion, the involvement of dengue infection should be considered in patients who develop central nervous system manifestations during or after the recovery period of dengue infection. Furthermore, since methylprednisolone and immunoglobulin are effective during the active phase of the infection, prompt diagnosis and initiation of treatment are crucial. PMID:27703498

  13. Induction of anti-viral genes during acute infection with Viral hemorrhagic septicemia virus (VHSV) genogroup IVa in Pacific herring (Clupea pallasii).

    PubMed

    Hansen, John D; Woodson, James C; Hershberger, Paul K; Grady, Courtney; Gregg, Jacob L; Purcell, Maureen K

    2012-02-01

    Infection with the aquatic rhabdovirus Viral hemorrhagic septicemia virus (VHSV) genogroup IVa results in high mortality in Pacific herring (Clupea pallasii) and is hypothesized to be a potential limiting factor for herring recovery. To investigate anti-viral immunity in the Pacific herring, four immune response genes were identified: the myxovirus resistance (Clpa-Mx), a major histocompatibility complex IB (named Clpa-UAA.001), the inducible immunoproteosome subunit 9 (Clpa-PSMB9) and the neutrophil chemotactic factor (Clpa-LECT2). Reverse transcriptase quantitative PCR (RT-qPCR) assays were developed based on these gene sequences to investigate the host immune response to acute VHSV infection following both injection and immersion challenge. Virus levels were measured by both plaque assay and RT-qPCR and peaked at day 6 during the 10-day exposure period for both groups of fish. The interferon stimulated genes (Clpa-Mx, -UAA.001, and -PSMB9) were significantly up-regulated in response to VHSV infection at both 6 and 10 days post-infection in both spleen and fin. Results from this study indicate that Pacific herring mount a robust, early antiviral response in both fin and spleen tissues. The immunological tools developed in this study will be useful for future studies to investigate antiviral immunity in Pacific herring.

  14. Induction of anti-viral genes during acute infection with Viral hemorrhagic septicemia virus (VHSV) genogroup IVa in Pacific herring (Clupea pallasii)

    USGS Publications Warehouse

    Hansen, John D.; Woodson, James C.; Hershberger, Paul K.; Grady, Courtney; Gregg, Jacob L.; Purcell, Maureen K.

    2012-01-01

    Infection with the aquatic rhabdovirus Viral hemorrhagic septicemia virus (VHSV) genogroup IVa results in high mortality in Pacific herring (Clupea pallasii) and is hypothesized to be a potential limiting factor for herring recovery. To investigate anti-viral immunity in the Pacific herring, four immune response genes were identified: the myxovirus resistance (Clpa-Mx), a major histocompatibility complex IB (named Clpa-UAA.001), the inducible immunoproteosome subunit 9 (Clpa-PSMB9) and the neutrophil chemotactic factor (Clpa-LECT2). Reverse transcriptase quantitative PCR (RT-qPCR) assays were developed based on these gene sequences to investigate the host immune response to acute VHSV infection following both injection and immersion challenge. Virus levels were measured by both plaque assay and RT-qPCR and peaked at day 6 during the 10-day exposure period for both groups of fish. The interferon stimulated genes (Clpa-Mx, −UAA.001, and −PSMB9) were significantly up-regulated in response to VHSV infection at both 6 and 10 days post-infection in both spleen and fin. Results from this study indicate that Pacific herring mount a robust, early antiviral response in both fin and spleen tissues. The immunological tools developed in this study will be useful for future studies to investigate antiviral immunity in Pacific herring.

  15. Kinetics of viral load and erythrocytic inclusion body formation in Pacific herring artificially infected with erythrocytic necrosis virus.

    PubMed

    Glenn, Jolene A; Emmenegger, Eveline J; Grady, Courtney A; Roon, Sean R; Gregg, Jacob L; Conway, Carla M; Winton, James R; Hershberger, Paul K

    2012-09-01

    Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic-a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0-4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

  16. Specimen origin, type and testing laboratory are linked to longer turnaround times for HIV viral load testing in Malawi

    PubMed Central

    Chipungu, Geoffrey; Kim, Andrea A.; Sarr, Abdoulaye; Ali, Hammad; Mwenda, Reuben; Nkengasong, John N.; Singer, Daniel

    2017-01-01

    Background Efforts to reach UNAIDS’ treatment and viral suppression targets have increased demand for viral load (VL) testing and strained existing laboratory networks, affecting turnaround time. Longer VL turnaround times delay both initiation of formal adherence counseling and switches to second-line therapy for persons failing treatment and contribute to poorer health outcomes. Methods We utilized descriptive statistics and logistic regression to analyze VL testing data collected in Malawi between January 2013 and March 2016. The primary outcomes assessed were greater-than-median pretest phase turnaround time (days elapsed from specimen collection to receipt at the laboratory) and greater-than-median test phase turnaround time (days from receipt to testing). Results The median number of days between specimen collection and testing increased 3-fold between 2013 (8 days, interquartile range (IQR) = 6–16) and 2015 (24, IQR = 13–39) (p<0.001). Multivariable analysis indicated that the odds of longer pretest phase turnaround time were significantly higher for specimen collection districts without laboratories capable of conducting viral load tests (adjusted odds ratio (aOR) = 5.16; 95% confidence interval (CI) = 5.04–5.27) as well as for Malawi’s Northern and Southern regions. Longer test phase turnaround time was significantly associated with use of dried blood spots instead of plasma (aOR = 2.30; 95% CI = 2.23–2.37) and for certain testing months and testing laboratories. Conclusion Increased turnaround time for VL testing appeared to be driven in part by categorical factors specific to the phase of turnaround time assessed. Given the implications of longer turnaround time and the global effort to scale up VL testing, addressing these factors via increasing efficiencies, improving quality management systems and generally strengthening the VL spectrum should be considered essential components of controlling the HIV epidemic. PMID:28235013

  17. Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus

    USGS Publications Warehouse

    Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.

    2012-01-01

    Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

  18. Presence, viral load and characterization of Torque teno sus viruses in liver and pork chop samples at retail.

    PubMed

    Leblanc, Danielle; Houde, Alain; Gagné, Marie-Josée; Plante, Daniel; Bellon-Gagnon, Pascale; Jones, Tineke H; Muehlhauser, Victoria; Wilhelm, Barbara; Avery, Brent; Janecko, Nicol; Brassard, Julie

    2014-05-16

    Torque teno viruses (TTV) are widespread in humans, swine as well as in several other animal species. In market ready swine, the reported prevalence ranges between 11% and 100%. Through a national retail sampling plan from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) program, 283 and 599 liver and pork chop samples, respectively, were collected over a 12-month period from commercial establishments in 5 selected geographical regions of Canada to assess the presence of Torque teno sus viruses (TTSuVs) in these products. TTSuVs were detected in 97.9% of pork chops with viral loads ranging between 1×10(4) and 9.9×10(5) genomic copies (gc)/g and 98.6% of liver samples with viral loads ranging from 1×10(5) to 9.9×10(6) gc/g. A selection of 20 positive samples (10 pork chop and 10 liver) from the 5 geographical regions were further tested for the production, of a 305bp fragment for TTSuV1 and a 253bp fragment for TTSuV2 in the non-coding region. TTSuV1 was present in all 10 liver and 10 pork chops samples while TTSuV2 was detected in 10 liver and 9 pork chop samples. Two different TTSuV1 sequences were simultaneously detected from 5 of 20 samples and 2 different TTSuV2 sequences were detected from 6 of 19 samples. The omnipresence of TTSuVs in commercial pork samples may allow its use as a viral indicator to monitor the effectiveness of cleaning and disinfecting process in slaughtering, cutting, slicing and packaging facilities.

  19. Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients—implications for treatment

    PubMed Central

    Pettersson, L; Thunberg, T; Rocklöv, J; Klingström, J; Evander, M; Ahlm, C; Zupanc, T A

    2014-01-01

    Hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in Eurasia and of hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The case fatality rate varies between different hantaviruses and can be up to 40%. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely, both virus-mediated and host-mediated mechanisms are involved. The aim of the present study was to investigate the association among Puumala hantavirus (PUUV) viral RNA load, humoral immune response and disease severity in patients with HFRS. We performed a study of 105 PUUV-infected patients that were followed during the acute phase of disease and for up to 1–3 months later. Fifteen of the 105 patients (14%) were classified as having moderate/severe disease. A low PUUV-specific IgG response (p <0.05) and also a higher white blood cell count (p <0.001) were significantly associated with more severe disease. The PUUV RNA was detected in a majority of patient plasma samples up to 9 days after disease onset; however, PUUV RNA load or longevity of viraemia were not significantly associated with disease severity. We conclude that a low specific IgG response was associated with disease severity in patients with HFRS, whereas PUUV RNA load did not seem to affect the severity of HFRS. Our results raise the possibility of passive immunotherapy as a useful treatment for hantavirus-infected patients. PMID:23742660

  20. Viral arthritides.

    PubMed

    Outhred, Alexander C; Kok, Jen; Dwyer, Dominic E

    2011-05-01

    Viral infections may manifest as acute or chronic arthritis. Joint involvement arises from either direct infection of the joint, through an immunological response directed towards the virus or autoimmunity. Epidemiological clues to the diagnosis include geographic location and exposure to vector-borne, blood-borne or sexually transmitted viruses. Although not always possible, it is important to diagnose the pathogenic virus, usually by serology, nucleic acid tests or rarely, viral culture. In general, viral arthritides are self-limiting and treatment is targeted at symptomatic relief. This article focuses on the causes, clinical features, diagnosis and treatment of viral arthritides.

  1. Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

    DTIC Science & Technology

    2016-07-01

    Acute Respiratory Distress Syndrome PRINCIPAL INVESTIGATOR: Prof. Ariella Oppenheim CONTRACTING ORGANIZATION: Hebrew University of Jerusalem...Lung / 5a. CONTRACT NUMBER Injury/Acute Respiratory Distress Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Prof. Ariella...mechanism elicited by VLPs that attenuate 2CLP-induced sepsis, to be performed as the project continues. 15. SUBJECT TERMS Acute Respiratory Distress

  2. Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection.

    PubMed

    Burdo, Tricia H; Walker, Joshua; Williams, Kenneth C

    2015-06-01

    Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues.

  3. The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections.

    PubMed

    Padaki, Priyadarshini A; Sachithanandham, Jaiprasath; Isaac, Rita; Ramalingam, Veena V; Abraham, Ooriapadickal C; Pulimood, Susanne A; Kannangai, Rajesh

    2016-01-01

    Viral load testing for human immunodeficiency virus 1 (HIV-1) in resource-poor settings continues to be a challenge. Although antiretroviral therapy (ART) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. The purpose of this study was to assess the utility of Cavidi version 3.0, which measures the plasma reverse transcriptase (RT) activity and compare its performance with molecular HIV viral load assays. In all, 125 HIV-1 and 13 HIV-2 positive samples were analyzed. The overall sensitivity of the assay was 86.8% and 94.1% for viral load >1000 copies/ml measured by Qiagen Artus HIV-1 RG RT PCR and Abbott RealTime HIV-1 PCR assays, respectively. Compared with the routine molecular viral load assays, Cavidi version 3.0 is inexpensive, user-friendly, the expenditure on infrastructure is minimal, and it can be used for monitoring of both HIV types.

  4. Cell-mediated immune response during experimental acute infection with bovine viral diarrhoea virus: evaluation of blood parameters.

    PubMed

    Molina, V; Risalde, M A; Sánchez-Cordón, P J; Romero-Palomo, F; Pedrera, M; Garfia, B; Gómez-Villamandos, J C

    2014-02-01

    Acute infections with bovine viral diarrhoea virus (BVDV), a major pathogen of cattle, are often asymptomatic or produce only mild clinical symptoms. However, they may play an important role in the bovine respiratory disease complex by exerting a marked immunosuppressive effect, as a result of the death of the immunocompetent cell populations involved in controlling innate and adaptive immune responses, together with a marked reduction of both cytokine expression and co-stimulatory molecule synthesis. Although experimental research and field studies have shown that acute BVDV infection enhances susceptibility to secondary infection, the precise mechanism involved in BVDV-induced immunosuppression remains unclear. The present study is aimed at measuring a range of blood parameters in a single group of fourteen calves infected with non-cytopathic BVDV-1. Focus has been put on those related to the cell-mediated immune response just as leucocyte populations and lymphocyte subpopulations, serum concentrations of cytokines (IL-1β, TNF-α, IFN-γ, IL-12, IL-4 and IL-10) and acute phase proteins [haptoglobin, serum amyloid A (SAA), fibrinogen and albumin], as well as BVDV-specific antibodies and viremia. After non-cytopathic BVDV-1 infection, clinical signs intensity was never more than moderate coinciding with the presence of viremia and leucocyte and lymphocyte depletion. An early increase in TNF-α, IFN-γ and IL-12 levels in contrast to IL-1β was observed in line with a raise in haptoglobin and SAA levels on the latest days of the study. As regards IL-4 levels, no evidence was found of any changes. However, a slight increase in IL-10 was observed, matching up the TNF-α decline during the acute phase response. These findings would help to increase our knowledge of the immune mechanisms involved in acute infection with non-cytopathic BVDV-1 strains, suggesting the existence of a clear tendency towards a type 1 immune response, thereby enhancing resistance against

  5. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  6. Viral etiology of acute respiratory diseases in Rio de Janeiro: first two years of a longitudinal study

    PubMed Central

    Sutmoller, F.; Nascimento, J. P.; Chaves, J. R. S.; Ferreira, V.; Pereira, M. S.

    1983-01-01

    A two-year study was undertaken to establish the incidence and possible viral etiology of acute respiratory diseases among the child population of a shanty town in Rio de Janeiro, Brazil. The results demonstrated that nearly half of all the illnesses seen were respiratory infections, 10% of them affecting the lower respiratory tract. Viruses were isolated from 20% of the throat swabs collected. Of the viruses identified, 47% were adenoviruses, 25% were enteroviruses, 9% were influenza A, 8% herpes simplex, 7% parainfluenza, 3% respiratory syncytial and 1% influenza B viruses. PMID:6606500

  7. SAMBA HIV semiquantitative test, a new point-of-care viral-load-monitoring assay for resource-limited settings.

    PubMed

    Ritchie, Allyson V; Ushiro-Lumb, Ines; Edemaga, Daniel; Joshi, Hrishikesh A; De Ruiter, Annemiek; Szumilin, Elisabeth; Jendrulek, Isabelle; McGuire, Megan; Goel, Neha; Sharma, Pia I; Allain, Jean-Pierre; Lee, Helen H

    2014-09-01

    Routine viral-load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA semi-Q (simple amplification-based assay semiquantitative test for HIV-1) in London, Malawi, and Uganda. The SAMBA semi-Q can distinguish between patients with VLs above and below 1,000 copies/ml. The SAMBA semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test, v2.0. Testing of 96 2- to 10-fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda yielded an overall accuracy for the SAMBA semi-Q of 99% (95% confidence interval [CI], 93.8 to 99.9%) and 96.9% (95% CI 94.9 to 98.3%), respectively, compared to to the Roche test. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cutoff of 1,000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral loads of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control, defined as either <1,000 copies/ml (SAMBA cutoff) or <5,000 copies/ml (WHO 2010 criterion; WHO, Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a Public Health Approach, 2010). This study suggests that the SAMBA semi-Q has adequate concurrency with the gold standard measurements for viral load. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings.

  8. Plasma viral loads during early HIV-1 infection are similar in subtype C- and non-subtype C-infected African seroconverters.

    PubMed

    Campbell, Mary S; Kahle, Erin M; Celum, Connie; Lingappa, Jairam R; Kapiga, Saidi; Mujugira, Andrew; Mugo, Nelly R; Fife, Kenneth H; Mullins, James I; Baeten, Jared M

    2013-04-01

    Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C-infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa.

  9. Viral arthritis

    PubMed Central

    Marks, Michael; Marks, Jonathan L

    2016-01-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  10. Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients.

    PubMed

    Lopez-Ruz, Miguel A; Navas, Purificación; López-Zúñiga, Miguel A; Gonzalvo, María Carmen; Sampedro, Antonio; Pasquau, Juan; Hidalgo-Tenorio, Carmen; Javier, Rosario; Castilla, José A

    2016-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load <20 copies/mL for at least six months. These patients were given mDRV/r at a dose of 800/100 mg for 48 weeks. At baseline (V0), CD4, CD8, FSH, LH and testosterone levels were measured, together with HIV-1 viral load in plasma and semen. In addition, seminal fluid quality was studied before mDRV/r treatment was prescribed. At week 48 (V1), HIV-1 viral load in plasma and semen and the quality of the seminal fluid were again measured. The results obtained indicate that at V0, 10% of the patients with ART had a positive viral load in seminal fluid (>20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality.

  11. Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

    PubMed Central

    Lopez-Ruz, Miguel A.; Navas, Purificación; López-Zúñiga, Miguel A.; Gonzalvo, María Carmen; Sampedro, Antonio; Pasquau, Juan; Hidalgo-Tenorio, Carmen; Javier, Rosario; Castilla, José A.

    2016-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load <20 copies/mL for at least six months. These patients were given mDRV/r at a dose of 800/100 mg for 48 weeks. At baseline (V0), CD4, CD8, FSH, LH and testosterone levels were measured, together with HIV-1 viral load in plasma and semen. In addition, seminal fluid quality was studied before mDRV/r treatment was prescribed. At week 48 (V1), HIV-1 viral load in plasma and semen and the quality of the seminal fluid were again measured. The results obtained indicate that at V0, 10% of the patients with ART had a positive viral load in seminal fluid (>20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality. PMID:27442068

  12. “Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk: Findings from a Randomized Controlled Trial”

    PubMed Central

    KURTH, Ann E.; SPIELBERG, Freya; CLELAND, Charles M.; LAMBDIN, Barrot; BANGSBERG, David R.; FRICK, Pamela A.; SEVERYNEN, Anneleen O.; CLAUSEN, Marc; NORMAN, Robert G.; LOCKHART, David; SIMONI, Jane M.; HOLMES, King K.

    2014-01-01

    Objective Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design Longitudinal RCT. Settings An academic HIV clinic and a community-based organization in Seattle. Subjects 240 HIV-positive adults on ART; 209 completed nine-month follow-up (87% retention). Intervention Randomization to computerized counseling or assessment-only, 4 sessions over 9 months. Main Outcome Measures HIV-1 viral suppression, and self-reported ART adherence, and transmission risks, compared using generalized estimating equations. Results Overall, intervention participants had reduced viral load (VL): mean 0.17 log10 decline, versus 0.13 increase in controls, p = 0.053, and significant difference in ART adherence baseline to 9 months (p = 0.046). Their sexual transmission risk behaviors decreased (OR = 0.55, p = 0.020), a reduction not seen among controls (OR = 1.1, p = 0.664), and a significant difference in change (p = 0.040). Intervention effect was driven by those most in need: among those with detectable virus at baseline (>30 copies/milliliter, n=89), intervention effect was mean 0.60 log10 VL decline versus 0.15 increase in controls, p=0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, p = 0.038. Conclusions Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior. PMID:24384803

  13. HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

    PubMed Central

    Chen, Fei; Zhang, Jian; Wen, Bo; Luo, Shan; Lin, Yingbiao; Ou, Wensheng; Guo, Fengfan; Tang, Ping; Liu, Wenpei; Qu, Xiaowang

    2016-01-01

    Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection. PMID:28009018

  14. Genomic characterization of a novel human papillomavirus (HPV-117) with a high viral load in a persisting wart.

    PubMed

    Köhler, Anja; Gottschling, Marc; Förster, Jana; Röwert-Huber, Joachim; Stockfleth, Eggert; Nindl, Ingo

    2010-03-30

    Warts from immunosuppressed organ transplant recipients (OTR) persist over years and may progress into non-melanoma skin cancer. Human papillomaviruses (HPV) are considered the causal agents for the development of such warts. We isolated the novel type HPV-117 from a persisting wart by rolling circle amplification. One hundred eighteen warts from immunocompetent patients (IC) and 49 warts from OTR were analyzed by HPV-117 E6 type-specific PCR. As inferred from a phylogenetic analysis, the new type HPV-117 belonged to alpha-PV species 2, including the most similar types HPV-10 and HPV-94. The general prevalence of HPV-117 in warts was 2% in IC (2/118), and 12% in OTR (6/49). The high viral load in dysplastic cells of a Verruca vulgaris was shown by in situ hybridization. Our results suggest an active role of the novel type in the development of cutaneous warts of OTR.

  15. Mutagenesis-Mediated Virus Extinction: Virus-Dependent Effect of Viral Load on Sensitivity to Lethal Defection

    PubMed Central

    Moreno, Héctor; Tejero, Héctor; de la Torre, Juan Carlos; Domingo, Esteban; Martín, Verónica

    2012-01-01

    Background Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results The effect of the mutagenic base analogue 5-fluorouracil (FU) on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV) can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI), or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV), but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV). The increase in mutation frequency and Shannon entropy (mutant spectrum complexity) as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. Conclusions (i) Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii) This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii) The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv) LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v) The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development. PMID:22442668

  16. Evaluation of histopathological changes, viral load and immune function of domestic geese infected with Newcastle disease virus.

    PubMed

    Lu, Ailing; Diao, Youxiang; Chen, Hao; Wang, Jiao; Ge, Pingping; Sun, Xiaoyan; Hao, Dongmin

    2014-01-01

    Outbreaks of Newcastle disease in flocks of geese with high morbidity and mortality in southern and eastern China have been reported frequently since the late 1990s, which broke the traditional view that geese are considered to be the natural reservoir of Newcastle disease virus (NDV) but show few or no clinical signs after infection. In this present study, geese were infected intranasally with a local strain of NDV. Clinical disease and gross pathology were observed. Serum and immune organs were collected from geese sequentially euthanized or after disease-associated death. We studied the histopathology of immune organs by haematoxylin and eosin staining and NDV fusion protein was detected in tissues by immunohistochemistry. At the same time, the SYBR Green I real-time polymerase chain reaction assay was used to detect the viral load from the collected samples. Serum samples were tested for NDV-specific antibodies and avian influenza virus (AIV)-specific antibodies by haemagglutination inhibition (HI) test. The results showed that severe lesions and numerous positive reactions of NDV antigen were detected in the immune organs. High viral loads developed in immune organs of infected geese, correlating with the severity of clinical signs and lesions in the tissues. Furthermore, the infected geese developed low HI antibody titres to both AIV and NDV. The present study showed that the replication and dissemination of the NDV isolate was widespread in immune organs of geese. The study revealed that waterfowl may not only be a natural reservoir of NDV but also become susceptible to disease and may play a major role in the epidemiology of Newcastle disease.

  17. Dry Blood Spots a Reliable Method for Measurement of Hepatitis B Viral Load in Resource-Limited Settings

    PubMed Central

    Stene-Johansen, Kathrine; Yaqoob, Nadeem; Overbo, Joakim; Aberra, Hanna; Desalegn, Hailemichael; Berhe, Nega; Johannessen, Asgeir

    2016-01-01

    Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa. Methods The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4–39 days before shipment to the laboratory. Results Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks. Conclusions This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low- and middle-income countries. PMID:27820845

  18. Patient Use of Electronic Prescription Refill and Secure Messaging and Its Association With Undetectable HIV Viral Load: A Retrospective Cohort Study

    PubMed Central

    Shimada, Stephanie L; Midboe, Amanda M; Nazi, Kim M; Zhao, Shibei; Wu, Justina; Garvey, Casey M; Houston, Thomas K

    2017-01-01

    Background Electronic personal health records (PHRs) can support patient self-management of chronic conditions. Managing human immunodeficiency virus (HIV) viral load, through taking antiretroviral therapy (ART) is crucial to long term survival of persons with HIV. Many persons with HIV have difficulty adhering to their ART over long periods of time. PHRs contribute to chronic disease self-care and may help persons with HIV remain adherent to ART. Proportionally veterans with HIV are among the most active users of the US Department of Veterans Affairs (VA) PHR, called My HealtheVet. Little is known about whether the use of the PHR is associated with improved HIV outcomes in this population. Objective The objective of this study was to investigate whether there are associations between the use of PHR tools (electronic prescription refill and secure messaging [SM] with providers) and HIV viral load in US veterans. Methods We conducted a retrospective cohort study using data from the VA’s electronic health record (EHR) and the PHR. We identified veterans in VA care from 2009-2012 who had HIV and who used the PHR. We examined which ones had achieved the positive outcome of suppressed HIV viral load, and whether achievement of this outcome was associated with electronic prescription refill or SM. From 18,913 veterans with HIV, there were 3374 who both had a detectable viral load in 2009 and who had had a follow-up viral load test in 2012. To assess relationships between electronic prescription refill and viral control, and SM and viral control, we fit a series of multivariable generalized estimating equation models, accounting for clustering in VA facilities. We adjusted for patient demographic and clinical characteristics associated with portal use. In the initial models, the predictor variables were included in dichotomous format. Subsequently, to evaluate a potential dose-effect, the predictor variables were included as ordinal variables. Results Among our sample

  19. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: Need for mucosal viral load measurement

    PubMed Central

    Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

    2015-01-01

    AIM: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). METHODS: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. RESULTS: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/105 cells) than in non-refractory (HCMV 0 and EBV 6 copies/105 cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/105 cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. CONCLUSION: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require

  20. High Viral Load and Respiratory Failure in Adults Hospitalized for Respiratory Syncytial Virus Infections.

    PubMed

    Lee, Nelson; Chan, Martin C W; Lui, Grace C Y; Li, Ran; Wong, Rity Y K; Yung, Irene M H; Cheung, Catherine S K; Chan, Eugenia C Y; Hui, David S C; Chan, Paul K S

    2015-10-15

    A prospective study among adults hospitalized for polymerase chain reaction-confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1-2, 7.29 ± 1.47; day 3-4, 7.28 ± 1.41; day 5-8, 6.66 ± 1.87 log10 copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log10 copies/mL increase, 95% confidence interval, 1.03-1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population.

  1. Viral and Bacterial Etiology of Acute Diarrhea among Children under 5 Years of Age in Wuhan, China

    PubMed Central

    Zhu, Xu-Hui; Tian, Lei; Cheng, Zhong-Ju; Liu, Wei-Yong; Li, Song; Yu, Wei-Ting; Zhang, Wen-Qian; Xiang, Xu; Sun, Zi-Yong

    2016-01-01

    Background: Acute diarrhea remains the serious problem in developing countries, especially among children under 5 years of age. Currently, only two or three common diarrhea pathogens were screened at most hospitals in China. The aim of this study was to provide a wide variety of diarrhea pathogens and their antimicrobial resistance patterns in children under 5 years of age. Methods: Totally 381 stool samples collected from Tongji Hospital between July 1, 2014 and June 30, 2015 were tested by culture and/or polymerase chain reaction for eight kinds of bacteria and five kinds of viruses. An antimicrobial sensitivity test was performed using dilution method recommended by the Clinical and Laboratory Standards Institute. Results: Viral infections were mainly identified in infants (0–11 months), whereas bacterial infections were more prevalent in the age of 24–59 months. About 69.8% of samples were positive for at least one pathogen, 51.7% of samples were virus positive, followed by bacteria positive cases (19.4%), and 12.6% of cases displayed co-infections with two viruses or a virus and a bacterium. Rotavirus was the most prevalent pathogen, followed closely by norovirus, while Salmonella was the most commonly isolated bacteria, followed by diarrheagenic Escherichia coli (DEC) and Campylobacter. More than 40% of Salmonella spp. and DEC isolates were resistant to first-line antibiotics (ampicillin, trimethoprim-sulfamethoxazole, and tetracycline). Around 10% of Salmonella spp. isolates were resistant to ceftriaxone and ciprofloxacin simultaneously. Campylobacter spp. displayed high resistance to ciprofloxacin but kept low resistance to azithromycin and doxycycline. Conclusions: The etiology of acute diarrhea varies in children of different age groups. The high frequency of infection with viruses suggests the urgent demand for new viral vaccine development. Proper use of antibiotics in the treatment of acute diarrhea is crucial due to the high level of antibiotic

  2. Comparison of the Cepheid GeneXpert and Abbott M2000 HIV-1 real time molecular assays for monitoring HIV-1 viral load and detecting HIV-1 infection.

    PubMed

    Ceffa, Susanna; Luhanga, Richard; Andreotti, Mauro; Brambilla, Davide; Erba, Fulvio; Jere, Haswel; Mancinelli, Sandro; Giuliano, Marina; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-03-01

    Assessing treatment efficacy and early infant diagnosis (EID) are critical issues in HIV disease management. Point-of-care assays may greatly increase the possibility to access laboratory monitoring also in rural areas. Recently two new laboratory tests have been developed by Cepheid (Sunnyvale, California) the Xpert HIV-1 Viral Load for viral load determination and the Xpert HIV-1 Qualitative for early infant diagnosis. We conducted a study in Blantyre, Malawi, comparing the 2 methods versus the Abbott real time quantitative and qualitative assays, for viral load and EID respectively. We tested 300 plasma samples for viral load determination and 200 samples for infant diagnosis. HIV-1 RNA values of the 274 samples quantified by both assays were highly correlated (Pearson r=0.95, R(2)=0.90). In 90.9% of the cases the two methods were concordant in defining the HIV-1 RNA levels as detectable or undetectable. For EID, the Xpert HIV-1 Qualitative assay yielded the same identical results as the Abbott assay. Both the quantitative and the qualitative Xpert assays are promising tools to monitor treatment efficacy in HIV patients receiving treatment and for early diagnosis in HIV-exposed infants.

  3. Risk of viral acute gastrointestinal illness from non-disinfected drinking water distribution systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute gastrointestinal illness (AGI) resulting from pathogens directly entering the piping of drinking water distribution systems is insufficiently understood. Here, we estimate AGI incidence attributable to virus intrusions into non-disinfecting municipal distribution systems. Viruses were enumerat...

  4. Acute neuromuscular and hormonal responses during contrast loading: effect of 11 weeks of contrast training.

    PubMed

    Walker, S; Ahtiainen, J P; Häkkinen, K

    2010-04-01

    The purpose of this study was to assess (1) acute neuromuscular and endocrine responses during a contrast loading protocol and (2) how these acute responses are possibly influenced by 11 weeks of contrast training. Contrast loading tests consisting of 4 sets of 80% 1 RM back squat and 4 sets of squat jump (SJ) were performed before and after training. Bilateral isometric leg extension (LE) assessed the impact of loading on isometric variables pre-, mid-, and post-loading. Potentiated SJ performance was observed in set 2 (4.6%, P<0.05), before training only. Greater indications of fatigue were observed in SJ, isometric force, and vastus lateralis (VL) activation after training (P<0.05). Training-induced improvements in SJ height, 80% 1 RM squat load, and maximum isometric LE force were observed (12%, 10%, and 7.7%, P<0.05). In conclusion, potentiated SJ performance occurred during a typical contrast loading protocol before the training period. However, potentiated SJ performance may alter through training, and therefore, the responsiveness of the individual should be periodically monitored and training protocols updated when necessary.

  5. Multiple Human Papillomavirus Infections with High Viral Loads Are Associated with Cervical Lesions but Do Not Differentiate Grades of Cervical Abnormalities

    PubMed Central

    Depuydt, Christophe; Benoy, Ina; Bogers, Johannes; Antoine, Jerome; Arbyn, Marc; Pawlita, Michael

    2013-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n = 100), low-grade squamous intraepithelial lesions (LSIL) (n = 100), and high-grade squamous intraepithelial lesions (HSIL) (n = 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5+/6+-PCR/multiplex HPV genotyping (BSGP5+/6+-PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2+) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4- to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral

  6. Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions.

    PubMed

    Li, Xuelin; Price, Matthew A; He, Dongning; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J; Anzala, Omu; Amornkul, Pauli N; Allen, Susan; Hunter, Eric; Kaslow, Richard A; Gilmour, Jill; Tang, Jianming

    2014-09-01

    Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

  7. Evaluation of Performance of the Gen-Probe Human Immunodeficiency Virus Type 1 Viral Load Assay Using Primary Subtype A, C, and D Isolates from Kenya

    PubMed Central

    Emery, Sandra; Bodrug, Sharon; Richardson, Barbra A.; Giachetti, Cristina; Bott, Martha A.; Panteleeff, Dana; Jagodzinski, Linda L.; Michael, Nelson L.; Nduati, Ruth; Bwayo, Job; Kreiss, Joan K.; Overbaugh, Julie

    2000-01-01

    Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gagp24 antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa. PMID:10878065

  8. Long-term follow up of feline leukemia virus infection and characterization of viral RNA loads using molecular methods in tissues of cats with different infection outcomes.

    PubMed

    Helfer-Hungerbuehler, A Katrin; Widmer, Stefan; Kessler, Yvonne; Riond, Barbara; Boretti, Felicitas S; Grest, Paula; Lutz, Hans; Hofmann-Lehmann, Regina

    2015-02-02

    It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was

  9. Early lymphoid responses and germinal center formation correlates with lower viral load set points and better prognosis of SIV infection

    PubMed Central

    Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth A; Courtney, Cynthia L; Havenar-Daughton, Colin; Crotty, Shane; Ansari, Aftab A; Villinger, Francois

    2014-01-01

    We have investigated the dynamics of germinal center (GC) formation in lymphoid tissues following acute SIV infection. SIV induces a marked follicular hyperplasia, associated with an aberrant accumulation of non-proliferating TFH cells within GCs, but with an abundance of cells producing IL-21, demonstrating that the mechanisms involved for these 2 events appear independent. IL-21 stimulated TFH cells are considered a critical element for GC formation, a physiological process that seems dysregulated and excessive during HIV/SIV infection, contributing to lymphoid pathogenesis. However, the data suggest that the kinetics by which such GC are formed may be an important predictor of the host-pathogen equilibrium, as early GC hyperplasia was associated with better control of viral replication. In contrast, monkeys undergoing fast disease progression upon infection exhibited an involution of GCs without local IL-21 production in GCs. These results provide important clues regarding GC-related hyper immune responses in the context of disease progression within various individuals during HIV/SIV infection and may open novel therapeutic avenues to limit lymphoid dysfunction, post infection. PMID:24907346

  10. Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam.

    PubMed

    Pollack, Todd M; Duong, Hao T; Pham, Thuy T; Do, Cuong D; Colby, Donn

    2017-01-01

    High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1-10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15-3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75-2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among

  11. Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam

    PubMed Central

    Pollack, Todd M.; Duong, Hao T.; Pham, Thuy T.; Do, Cuong D.; Colby, Donn

    2017-01-01

    High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use

  12. Acute viral hepatitis in Lebanon: evidence for a HAV-like non-A non-B hepatitis.

    PubMed

    Shamma'a, M H

    1984-02-01

    Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.

  13. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

    PubMed Central

    Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

    2017-01-01

    Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

  14. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  15. Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease.

    PubMed

    Ito, Yoshinori; Suzuki, Michio; Kawada, Jun-ichi; Kimura, Hiroshi

    2016-04-01

    Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2) IU/μgDNA) compared to the IM (median, 10(2.1) IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0) IU/μgDNA and 10(3.2) IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients.

  16. Characterization of viral loads, strain and state of equine herpesvirus-1 using real-time PCR in horses following natural exposure at a racetrack in California.

    PubMed

    Pusterla, Nicola; Wilson, W David; Mapes, Samantha; Finno, Carrie; Isbell, Diane; Arthur, Rick M; Ferraro, Gregory L

    2009-02-01

    The objective of this study was to determine viral loads, strain (neuropathogenic versus non-neuropathogenic) and state (lytic, non-replicating, latent) of equine herpesvirus-1 (EHV-1) by real-time polymerase chain reaction (PCR) in the blood and nasopharyngeal secretions of adult horses following natural exposure. The index case, a 4-year-old Thoroughbred gelding with confirmed EHV-1 myeloencephalopathy, as well as potentially exposed horses, were sampled over a period of 3 weeks. The study population comprised of 39 adult Thoroughbred horses and 35 adult "pony" and outrider horses of various breeds housed at a racetrack in Northern California. Blood samples and nasopharyngeal secretions (NPS) from all horses were tested on several occasions for EHV-1 DNA viral loads, targeting the glycoprotein B (gB) gene, viral strain, targeting the ORF 30 gene, and transcriptional activity of EHV-1, targeting the gB gene and latency-associated transcripts (LATs). Viral loads and transcriptional activity of the gB gene declined rapidly in the index case following antiviral treatment. The prevalence of EHV-1 infection in NPS determined by PCR slowly decreased over the 22 day study period from 25% to 14%. The initial surveillance showed multiple clusters of exposure, one associated with the index case and two related to horses that had recently returned from a different racetrack. Viral strain differentiation showed that only two horses (the index case and a neighboring horse) were infected with only a neuropathogenic strain, while all other horses were infected with either a non-neuropathogenic strain or were dually infected with both neuropathogenic and non-neuropathogenic strains. In most cases, the virus was present in either a lytic or a non-replicating form, while latent virus was found in blood and NPS much less frequently. The molecular approach used in this study showed promise for assessing the risk of exposing other horses to EHV-1 and for studying viral kinetics in

  17. Combined administration of oseltamivir and hochu-ekki-to (TJ-41) dramatically decreases the viral load in lungs of senescence-accelerated mice during influenza virus infection.

    PubMed

    Ohgitani, Eriko; Kita, Masakazu; Mazda, Osam; Imanishi, Jiro

    2014-02-01

    To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1β and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.

  18. High prevalence of respiratory viral infections in patients hospitalized in an intensive care unit for acute respiratory infections as detected by nucleic acid-based assays.

    PubMed

    Legoff, Jérôme; Guérot, Emmanuel; Ndjoyi-Mbiguino, Angélique; Matta, Mathieu; Si-Mohamed, Ali; Gutmann, Laurent; Fagon, Jean-Yves; Bélec, Laurent

    2005-01-01

    Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia.

  19. High Prevalence of Respiratory Viral Infections in Patients Hospitalized in an Intensive Care Unit for Acute Respiratory Infections as Detected by Nucleic Acid-Based Assays

    PubMed Central

    Legoff, Jérôme; Guérot, Emmanuel; Ndjoyi-Mbiguino, Angélique; Matta, Mathieu; Si-Mohamed, Ali; Gutmann, Laurent; Fagon, Jean-Yves; Bélec, Laurent

    2005-01-01

    Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia. PMID:15635014

  20. Greater numbers of nucleotide substitutions are introduced into the genomic RNA of bovine viral diarrhea virus during acute infections of pregnant cattle than of non-pregnant cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) strains circulating in domestic livestock herds show significant sequence variation. Conventional wisdom states that most sequence variation arises during acute infections in response to immune or other environmental pressures. A recent study showed that more nucle...

  1. Characterization of Viral Load, Viability and Persistence of Influenza A Virus in Air and on Surfaces of Swine Production Facilities

    PubMed Central

    Neira, Victor; Rabinowitz, Peter; Rendahl, Aaron; Paccha, Blanca; Gibbs, Shawn G.; Torremorell, Montserrat

    2016-01-01

    Indirect transmission of influenza A virus (IAV) in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of IAV in swine barns. We characterized viral load, viability and persistence of IAV in air and on surfaces during outbreaks in swine barns. IAV was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98) of oral fluid, 38% (32/84) of pen railing and 43% (35/82) of indoor air samples testing positive by IAV RT-PCR. IAV was isolated from air and oral fluids yielding a mixture of subtypes (H1N1, H1N2 and H3N2). Detection of IAV RNA from air was sustained during the outbreaks with maximum levels estimated between 7 and 11 days from reported onset. Our results indicate that during outbreaks of IAV in swine, aerosols and surfaces in barns contain significant levels of IAV potentially representing an exposure hazard to both swine and people. PMID:26757362

  2. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients.

    PubMed

    Rodriguez-Auad, Juan Pablo; Rojas-Montes, Othon; Maldonado-Rodriguez, Angelica; Alvarez-Muñoz, Ma Teresa; Muñoz, Onofre; Torres-Ibarra, Rocio; Vazquez-Rosales, Guillermo; Lira, Rosalia

    2015-01-01

    Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

  3. Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges

    PubMed Central

    Roberts, Teri; Cohn, Jennifer; Bonner, Kimberly; Hargreaves, Sally

    2016-01-01

    Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed countries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving—including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis—we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges. PMID:26743094

  4. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    PubMed Central

    Rodriguez-Auad, Juan Pablo; Rojas-Montes, Othon; Maldonado-Rodriguez, Angelica; Alvarez-Muñoz, Ma. Teresa; Muñoz, Onofre; Torres-Ibarra, Rocio; Vazquez-Rosales, Guillermo

    2015-01-01

    Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings. PMID:26779533

  5. Use of plasma human herpesvirus-8 viral load measurement: evaluation of practice in three UK HIV treatment centres.

    PubMed

    Nugent, D B; Webster, D; Mabayoje, D; Chung, E; El Bouzidi, K; O'Sullivan, A; Ainsworth, J; Miller, R F

    2017-02-01

    A retrospective audit of plasma human herpesvirus-8 (HHV-8) viral load testing was performed in three HIV treatment centres over 24 months. Reasons for testing (360 tests) were: symptoms of systemic inflammatory response syndrome (SIRS) (fever, lymphadenopathy and raised inflammatory markers); monitoring in known HHV-8 pathology other than Kaposi sarcoma (KS); investigation of known/suspected KS, and other/no reason. Of patients with multicentric Castleman disease (MCD), 14/16 (88%) had detectable plasma HHV-8, as did 27/45 (60%) with biopsy proven or clinically confirmed KS, and 6/19 (32%) with lymphoma. Neither of the two patients with MCD and no detectable HHV-8 had SIRS symptoms at the time of the test. There was wide variation between centres in the indications prompting HHV-8 testing, with a more conservative approach resulting in a higher proportion of positive results. Measuring plasma HHV-8 in the absence of SIRS symptoms, established HHV-8 disease monitoring, or confirmed/suspected KS is unlikely to yield detectable HHV-8 thus allowing potential cost savings.

  6. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

    PubMed Central

    Petersdorf, Nicholas; Ross, Jennifer M; Weiss, Helen A; Barnabas, Ruanne V; Wasserheit, Judith N

    2016-01-01

    Introduction Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control. PMID:27649908

  7. Residential Eviction and Risk of Detectable Plasma HIV-1 RNA Viral Load Among HIV-Positive People Who Use Drugs.

    PubMed

    Kennedy, Mary Clare; Kerr, Thomas; McNeil, Ryan; Parashar, Surita; Montaner, Julio; Wood, Evan; Milloy, M-J

    2017-03-01

    We examined the relationship between residential eviction and exhibiting detectable plasma HIV-1 RNA viral load (VL) among a prospective cohort of antiretroviral therapy (ART)-exposed HIV-seropositive people who use illicit drugs (PWUD) in Vancouver, Canada. We used multivariable generalized estimating equations to estimate the effect of residential eviction on detectable VL and examine ART adherence as a mediating variable. Between June 2007 and May 2014, 705 ART-exposed participants were included in the study, among whom 500 (70.9 %) experienced at least one period of detectable VL. In a time-updated multivariable model, eviction independently increased the odds of detectable VL among those who were homeless [adjusted odds ratio (AOR) = 2.25; 95 % confidence interval (CI) 1.18-4.29] as well as not homeless (AOR = 1.76; 95 % CI 1.17-2.63) post eviction. The results of mediation analyses suggest that this association was mediated by incomplete ART adherence. These findings suggest the need for further development and evaluation of interventions to prevent evictions and promote ART adherence among PWUD facing eviction.

  8. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

    PubMed Central

    Hood, Iris V; Berger, James M

    2016-01-01

    Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of the Staphylococcus aureus replicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association. DOI: http://dx.doi.org/10.7554/eLife.14158.001 PMID:27244442

  9. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America.

    PubMed

    Duarte, Horacio A; Harris, Donald Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flávia Faleiro; Cruz, Maria Letícia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan

    2015-01-01

    Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8-9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in

  10. Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

    PubMed Central

    Garcia-Knight, Miguel A.; Slyker, Jennifer; Payne, Barbara Lohman; Pond, Sergei L. Kosakovsky; de Silva, Thushan I.; Chohan, Bhavna; Khasimwa, Brian; Mbori-Ngacha, Dorothy; John-Stewart, Grace; Rowland-Jones, Sarah L.; Esbjörnsson, Joakim

    2016-01-01

    Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines. PMID:27403940

  11. Cost analysis of centralized viral load testing for antiretroviral therapy monitoring in Nicaragua, a low-HIV prevalence, low-resource setting

    PubMed Central

    2010-01-01

    Background HIV viral load testing as a component of antiretroviral therapy monitoring is costly. Understanding the full costs and the major sources of inefficiency associated with viral load testing is critical for optimizing the systems and technologies that support the testing process. The objective of our study was to estimate the costs associated with viral load testing performed for antiretroviral therapy monitoring to both patients and the public healthcare system in a low-HIV prevalence, low-resource country. Methods A detailed cost analysis was performed to understand the costs involved in each step of performing a viral load test in Nicaragua, from initial specimen collection to communication of the test results to each patient's healthcare provider. Data were compiled and cross referenced from multiple information sources: laboratory records, regional surveillance centre records, and scheduled interviews with the key healthcare providers responsible for HIV patient care in five regions of the country. Results The total average cost of performing a viral load test in Nicaragua varied by region, ranging from US$99.01 to US$124.58, the majority of which was at the laboratory level: $88.73 to $97.15 per specimen, depending on batch size. The average cost to clinics at which specimens were collected ranged from $3.31 to $20.92, depending on the region. The average cost per patient for transportation, food, lodging and lost income ranged from $3.70 to $14.93. Conclusions The quantitative viral load test remains the single most expensive component of the process. For the patient, the distance of his or her residence from the specimen collection site is a large determinant of cost. Importantly, the efficiency of results reporting has a large impact on the cost per result delivered to the clinician and utility of the result for patient monitoring. Detailed cost analysis can identify opportunities for removing barriers to effective antiretroviral therapy monitoring

  12. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey

    PubMed Central

    Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W. B.; Ho, Roger C. M.

    2017-01-01

    Background Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. Methods A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients’ health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients’ WTP for CD4 cell count and viral load testing. Results HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6–8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3–20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. Conclusions These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients. PMID:28199405

  13. Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer.

    PubMed

    Depuydt, Christophe E; Thys, Sofie; Beert, Johan; Jonckheere, Jef; Salembier, Geert; Bogers, Johannes J

    2016-11-01

    Persistent high-risk human papillomavirus (HPV) infection is strongly associated with development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type-specific viral-load measurements predict the natural history of the infection. In infections with multiple HPV-types, the individual type-specific viral-load profile could distinguish progressing HPV-infections from regressing infections. A case-cohort natural history study was established using samples from untreated women with multiple HPV-infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real-time qPCR-assay (18 HPV-types). Using serial type-specific viral-load measurements (≥3) we calculated HPV-specific slopes and coefficient of determination (R(2) ) by linear regression. For each woman slopes and R(2) were used to calculate which HPV-induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV-types, each single HPV-type generated similar increasing (0.27copies/cell/day) and decreasing (-0.27copies/cell/day) viral-load slopes. In CIN3+, at least one of the HPV-types had a clonal progressive course (R(2)  ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type-specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion-producing infections the RNA-staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly-formed virions. RNA-hybridization patterns matched the calculated ongoing processes measured by R(2) and slope in serial type-specific viral-load measurements preceding the biopsy. In women with multiple HPV-types, serial type-specific viral-load measurements predict the natural history of the

  14. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

    2015-10-01

    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  15. Viral hemorrhagic fever cases in the country of Georgia: Acute Febrile Illness Surveillance Study results.

    PubMed

    Kuchuloria, Tinatin; Imnadze, Paata; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Clark, Danielle V; Bautista, Christian T; Abdel Fadeel, Moustafa; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Wölfel, Silke; Wölfel, Roman; Rivard, Robert G

    2014-08-01

    Minimal information is available on the incidence of Crimean-Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia.

  16. Antibody dynamics and spontaneous viral clearance in patients with acute hepatitis C infection in Rio de Janeiro, Brazil

    PubMed Central

    2011-01-01

    Background The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period. Methods We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up. Results Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]. Conclusion Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection. PMID:21226945

  17. Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis

    PubMed Central

    Foureau, D M; Walling, T L; Maddukuri, V; Anderson, W; Culbreath, K; Kleiner, D E; Ahrens, W A; Jacobs, C; Watkins, P B; Fontana, R J; Chalasani, N; Talwalkar, J; Lee, W M; Stolz, A; Serrano, J; Bonkovsky, H L

    2015-01-01

    Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8+ T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD. PMID:25418487

  18. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae

    PubMed Central

    O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-01-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni. PMID:25715048

  19. Interleukin 28B.rs12979860 genotype does not affect hepatitis C viral load in Egyptians with genotype 4 chronic infection.

    PubMed

    Abdelwahab, Sayed F; Zakaria, Zainab; Allam, Walaa R; Hamdy, Shaimaa; Mahmoud, Mohamed A; Sobhy, Maha; Rewisha, Eman; Waked, Imam

    2015-11-01

    Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. Interleukin 28B (IL28B).rs12979860 single nucleotide polymorphism (SNP) was found to predict viral clearance with and without therapy. Subjects with the CC (favorable) genotype of IL28B.rs12979860 were more likely to spontaneously clear the infection and respond favorably to therapy. These data suggest that subjects with the "favorable" CC genotype might have a lower viral load when compared to those with the "unfavorable" TT genotype. Therefore, we examined the effect of IL28B.rs12979860 SNP on HCV viral load and clearance among HCV-infected Egyptians. This cross sectional study was conducted on 375 HCV antibody-positive subjects. Detection and quantification of HCV-RNA was determined by RT-PCR. IL28B.rs12979860 genotyping was performed using SYBR green real-time PCR and specific primers. Of 375 HCV-antibody positive subjects, 239 (63.7%) had chronic HCV infection while the remaining 136 (36.3%) subjects had spontaneously cleared the virus. The frequency of IL28-B CC, CT, and TT genotypes among spontaneous resolvers were 54.4%, 39.0%, and 6.6% while among the chronically infected subjects, they were 31.4%, 49.8%, and 18.8%, respectively. As expected, IL28 genotype predicted spontaneous HCV clearance (p < 0.001). The average HCV viral loads were 1.5 ± 0.69 x 10(6), 0.62 ± 0.11 x 10(6) and 0.51 ± 0.14 x 10(6) IU/ml among chronic subjects with the IL28B.rs12979860 CC, CT and TT genotypes, respectively (p > 0.05). In conclusion, our results show that IL28B.rs12979860 genotype does not affect viral load among chronic HCV infected Egyptians. These findings further confirm the complexity of viral host interactions in determining HCV infection outcome.

  20. Are acute effects of maximal dynamic contractions on upper-body ballistic performance load specific?

    PubMed

    Markovic, Goran; Simek, Sanja; Bradic, Asim

    2008-11-01

    This study investigated the acute effects of upper-body maximal dynamic contractions on maximal throwing speed with 0.55- and 4-kg medicine balls. It was hypothesized that heavy preloading would transiently improve throwing performance only when overcoming the heavier of the two loads. Twenty-three male volunteers were randomly allocated into experimental (n = 11) and control (n = 12) groups. Both groups performed initial and final seated medicine ball throws from the chest, and the maximal medicine ball speed was measured by means of a radar gun. Between the two measurements, the control group rested passively for 15 minutes, and the experimental group performed three sets of three-repetition maximum bench presses. For the 0.55-kg load, a 2 x 2 repeated-measures analysis of variance revealed no significant effect of time x group interaction (p = 0.22), as well as no significant time (p = 0.22) or group (p = 0.72) effects. In contrast, for the 4-kg load, a significant time x group interaction (p = 0.004) and a significant time (p = 0.035) but not group (p = 0.77) effect were observed. Analysis of simple main effects revealed that the experimental group significantly (8.3%; p < 0.01) improved maximal throwing speed with the 4-kg load. These results support our research hypothesis and suggest that the acute effects of heavy preloading on upper-body ballistic performance might be load specific. In a practical sense, our findings suggest that the use of upper-body heavy resistance exercise before ballistic throwing movements against moderate external loads might be an efficient training strategy for improving an athlete's upper-body explosive performance.

  1. Prophylaxis of acute viral hepatitis by immune serum globulin, hepatitis B vaccine, and health education: a sixteen year study of Japan overseas cooperation volunteers.

    PubMed

    Ohara, H; Ebisawa, I; Naruto, H

    1997-01-01

    From 1978 to 1993 a study of acute viral hepatitis contracted by the Japan Overseas Cooperation Volunteers (JOCV) during their assignments in tropical and subtropical countries was conducted. Of 10,509 subjects in this study, 240 cases of acute viral hepatitis were confirmed (hepatitis A = 139, hepatitis B = 72, and non-A, non-B hepatitis = 29). The annual morbidity was 5.1% in 1978 and 4.9% in 1979, with hepatitis A accounting for 80% of the cases. However, it decreased significantly after the prophylactic inoculation with immune serum globulin (ISG) was started in 1980. A significant decrease of hepatitis B from 1.2% in 1980 to 0.1% in 1990 was also seen after vaccination was introduced for all volunteers in 1988. Health education concerning food and water sanitation, and providing general information on viral hepatitis, was also conducted throughout this period. These results indicate that acute viral hepatitis could be successfully prevented in the JOCV with a combination of ISG, hepatitis B vaccination, and health education.

  2. The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

    PubMed Central

    Mei, Minghua; Mehta, Reena

    2017-01-01

    Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness. PMID:28267794

  3. The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

    PubMed

    Piedra, Felipe-Andrés; Mei, Minghua; Avadhanula, Vasanthi; Mehta, Reena; Aideyan, Letisha; Garofalo, Roberto P; Piedra, Pedro A

    2017-01-01

    Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.

  4. Association between human papillomavirus (HPV) 16, HPV18, and other HR-HPV viral load and the histological classification of cervical lesions: Results from a large-scale cross-sectional study.

    PubMed

    Wu, Zeni; Qin, Yu; Yu, Lulu; Lin, Chunqing; Wang, Hong; Cui, Jianfeng; Liu, Bin; Liao, Yiqun; Warren, De'Andre; Zhang, Xun; Chen, Wen

    2017-03-01

    The relationship between HPV viral load and histological grades in the development of cervical cancer is in argument. It is helpful to better understand the association by quantitatively detecting viral load of HPV16, 18, and a pool of 12 other high-risk HPV type (OT) independently on the samples of precancer and cancer. A cross-sectional study was performed in five medical centers of China. Histological diagnosis made by local pathologists was adjudicated via a pathology expert panel. A fully automated real-time PCR test was used for the measurement of HPV16, 18, OT, and human β-globin gene. A total of 2,513 women [1,341 normal, 209 low grade intraepithelial lesion (LSIL), 392 high grade intraepithelial lesion (HSIL), 520 squamous cell carcinoma (SCC), and 51 adenocarcinoma (ADC)] were included. There is a linear increase in the total 14 HPV viral load with histological grade from normal to SCC. This trend was not observed in HPV18 infection but HPV16. The viral load for OT was low in normal, peaked in LSIL and HSIL, and declined in SCC and ADC. In the co-infection of HPV16 and HPV18, HPV16 viral load was significantly higher than HPV18 in LSIL and HSIL. In co-infection of HPV16 and OT, higher HPV16 viral load was also seen in SCC and ADC. Viral load of HPV16 increases with cervical lesion grade and is predominant in cervical cancer. HPV18 viral load is low in precancer, but going up in cancer. OT viral load shows inverse trend of HPV18. J. Med. Virol. 89:535-541, 2017. © 2016 Wiley Periodicals, Inc.

  5. Rotavirus seasonality in urban sewage from Argentina: effect of meteorological variables on the viral load and the genetic diversity.

    PubMed

    Barril, P A; Fumian, T M; Prez, V E; Gil, P I; Martínez, L C; Giordano, M O; Masachessi, G; Isa, M B; Ferreyra, L J; Ré, V E; Miagostovich, M; Pavan, J V; Nates, S V

    2015-04-01

    In Argentina, the rotavirus disease exhibits seasonal variations, being most prevalent in the fall and winter months. To deepen the understanding of rotavirus seasonality in our community, the influence of meteorological factors on the rotavirus load and the genetic diversity in urban raw sewage from Córdoba city, Argentina were evaluated. Wastewater samples were collected monthly during a three-year study period and viral particles were concentrated by polyethylene glycol precipitation. RT-nested PCR was applied for rotavirus detection, and VP7/VP4 characterization and real-time PCR for rotavirus quantification. Both molecular techniques showed relatively similar sensitivity rates and revealed rotavirus presence in urban wastewater in cold and warm seasons, indicating its circulation in the local community all year round. However, a slight trend for rotavirus circulation was noted by real-time PCR in the fall and winter seasons, showing a significantly higher peak of rotavirus concentration at mean temperatures lower than 18°C and also higher, although not statistically different during drier weather. VP7 and VP4 gene characterization showed that G1 and P[8] genotypes were dominant, and temporal variations in genotype distribution were not observed. Rotavirus spread is complex and our results point out that weather factors alone cannot explain the seasonal quantitative pattern of the rotavirus disease. Therefore, alternative transmission routes, changes in human behavior and susceptibility, and the stability and survivability of the virus might all together contribute to the seasonality of rotavirus. The results obtained here provide evidence regarding the dynamics of rotavirus circulation and maintenance in Argentina.

  6. Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

    PubMed

    Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

    2014-05-01

    Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P < 0.0001), but no significant correlation existed between EBV DNA levels in whole blood and enriched B-cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios.

  7. Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on HIV-1 plasma viral load

    PubMed Central

    Baggaley, Rebecca F.; Griffin, Jamie T.; Chapman, Ruth; Hollingsworth, T. Déirdre; Nagot, Nicolas; Delany, Sinead; Mayaud, Philippe; de Wolf, Frank; Fraser, Christophe; Ghani, Azra C.; Weiss, Helen A.

    2009-01-01

    Objective Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. Design and methods By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. Results Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. Conclusion HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted. PMID:19367154

  8. HIV Viral Load Trends in Six Eastern Caribbean Countries Utilizing a Regional Laboratory Referral Service: Implications for Treatment as Prevention

    PubMed Central

    Landis, R. Clive; Carmichael-Simmons, Kelly; Hambleton, Ian R.; Best, Anton

    2015-01-01

    Objective Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS), Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL) offered by The Ladymeade Reference Unit (LRU) Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service. Methods Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama). VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples. Results A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2%) mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001). Conclusion We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network. PMID:25923741

  9. Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher community viral load?

    PubMed Central

    ABU-RADDAD, Laith J.; BARNABAS, Ruanne V.; JANES, Holly; WEISS, Helen A.; KUBLIN, James G.; LONGINI, Ira M.; WASSERHEIT, Judith N.

    2013-01-01

    Objective The HIV epidemic has carved contrasting trajectories around the world with sub-Saharan Africa (SSA) being most affected. We hypothesized that mean HIV-1 plasma RNA viral loads (VL) are higher in SSA than other areas, and that these elevated levels may contribute to the scale of epidemics in this region. Design and Methods To evaluate this hypothesis, we constructed a database of means of 71,668 VL measurements from 44 cohorts in seven regions of the world. We used linear regression statistical models to estimate differences in VL between regions. We also constructed and analyzed a mathematical model to describe the impact of the regional VL differences on HIV epidemic trajectory. Results We found substantial regional VL heterogeneity. The mean VL in SSA was 0.58 log10 copies/mL higher than in North America (95% CI: 0.45 to 0.71); this represents about a 4-fold increase. The highest mean VLs were found in Southern and East Africa, while in Asia, Europe, North America, and South America, mean VLs were comparable. Mathematical modeling indicated that conservatively 14% of HIV infections in a representative population in Kenya could be attributed to the enhanced infectiousness of subjects with heightened VL. Conclusion We conclude that community VL appears to be higher in SSA than in other regions and this may be a central driver of the massive HIV epidemics in this region. The elevated VLs in SSA may reflect, among other factors, the high burden of co-infections or the preponderance of HIV-1 subtype C infection. PMID:23196933

  10. Modulation of sex hormone secretion in cows by acute infection with bovine viral diarrhoea virus.

    PubMed

    Fray, M D; Mann, G E; Bleach, E C L; Knight, P G; Clarke, M C; Charleston, B

    2002-02-01

    Bovine viral diarrhoea virus (BVDV) is a major pathogen of cattle and is responsible for considerable reproductive loss. In this study, the in vivo responses in six multiparous cows were investigated after a non-cytopathogenic BVDV challenge (strain Pe 515; 5 x 10(6) tissue culture infective dose 50) given 9 days before a synchronized ovulation. Six similar cows challenged with non-infectious culture medium served as controls. The experimental noncytopathogenic BVDV infection was followed by a viraemia and leucopenia at days 5-9 after challenge, but no other clinical signs of infection were detected. However, the BVDV infection altered endocrine function. Mean LH pulse frequency immediately before CIDR withdrawal was lower (P < or = 0.05) in the BVDV-infected (2.17 +/- 0.34 pulses per 8 h) compared with the sham-infected (4.83 +/- 1.04 pulses per 8 h) animals. At day 3 after CIDR withdrawal, plasma oestradiol concentrations remained high (P < 0.05) in the infected cows (2.19 +/- 0.51 pg ml(-1)) compared with the sham-infected controls (0.72 +/- 0.29 pg ml(-1)). However, there was no difference in the peak oestradiol concentration (BVDV: 2.31 +/- 0.29 versus sham: 2.34 +/- 0.41 pg ml(-1)). In addition, non-cytopathogenic BVDV significantly (P < 0.05) increased the duration of the interval between ovulation and onset of the postovulatory progesterone increase (values 1.0 ng ml(-1)) (BVDV: 3.0 +/- 0.26 versus sham: 4.0 +/- 0.26 days). The viral infection also significantly (P < 0.01) decreased mean plasma progesterone concentrations between day 3 and day 11 after ovulation (BVDV: 2.59 +/- 0.32 versus sham: 4.13 +/- 0.27 ng ml(-1)). These data show that non-cytopathogenic BVDV viraemias during the follicular phase can modulate the secretion of gonadotrophins and sex steroids, in particular progesterone, during a synchronized oestrous cycle. Therefore, viraemias during the follicular phase may reduce the fertility of cattle by disrupting the capacity of the ovulatory

  11. HIV Viral Load

    MedlinePlus

    ... used to monitor the effectiveness of antiretroviral treatment (ART) over time. Photo source: CDC / A. Harrison, P. ... the virus may be resistant to that particular ART. The person's treatment will then likely be modified. ...

  12. Viral Load in Infants Hospitalized for Respiratory Syncytial Virus Bronchiolitis Correlates with Recurrent Wheezing at Thirty-Six-Month Follow-Up.

    PubMed

    Nenna, Raffaella; Ferrara, Marianna; Nicolai, Ambra; Pierangeli, Alessandra; Scagnolari, Carolina; Papoff, Paola; Antonelli, Guido; Moretti, Corrado; Midulla, Fabio

    2015-10-01

    The relationship between viral infection, host immune response in infants with respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing is discussed. We measured RSV-RNA load and interferon-λ1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for RSV bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. Higher RSV-RNA load and higher interferon-λ2/3 levels were found in children with recurrent wheezing at 36-month follow-up.

  13. Prompt administration of Crimean-Congo hemorrhagic fever (CCHF) virus hyperimmunoglobulin in patients diagnosed with CCHF and viral load monitorization by reverse transcriptase-PCR.

    PubMed

    Kubar, Ayhan; Haciomeroglu, Mustafa; Ozkul, Aykut; Bagriacik, Umit; Akinci, Esragul; Sener, Kenan; Bodur, Hurrem

    2011-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes a severe disease in humans with high mortality rates. In Turkey, the number of patients with CCHF has increased since 2002. Here, we aimed to treat CCHF patients with CCHFV hyperimmunoglobulin. We prepared a CCHFV hyperimmunoglobulin product from 22 individuals who survived CCHF infection. A total of 26 CCHF patients were enrolled into this study. For CCHFV hyperimmunoglobulin administration, a Kubar Unit (KU) was defined. As a standard therapeutic approach, 400 KU of hyperimmunoglobulin were given to each patient as a single dose before viral load was detected. We used one-step real-time reverse transcriptase-PCR to monitor the viral load of CCHF patients. According to the one-step real-time PCR results, 15 patients with a viral load of 10(8) copies/mL or more were defined as high risk. In this high-risk group, the survival rate was found to be 86.6% (13/15) and 2 patients died despite CCHFV hyperimmunoglobulin administration. CCHF is a very serious and highly fatal infection, particularly for patients in the defined high-risk group. Prompt administration of CCHFV hyperimmunoglobulin might be a very promising new treatment approach, especially for high-risk individuals.

  14. The impact of improved self-efficacy on HIV viral load and distress in culturally diverse women living with AIDS: the SMART/EST Women's Project.

    PubMed

    Ironson, G; Weiss, S; Lydston, D; Ishii, M; Jones, D; Asthana, D; Tobin, J; Lechner, S; Laperriere, A; Schneiderman, N; Antoni, M

    2005-02-01

    The purpose of the present study was to determine whether changes in self-efficacy over time would be related to changes in disease progression markers (CD4, viral load) in a sample of women with AIDS. A self-efficacy measure was developed and two sub-scales emerged via factor analysis of 391 HIV-positive women: AIDS Self-efficacy and Cognitive Behavioral Skills Self-efficacy. Subsequently, the sub-scales and an additional adherence self-efficacy item were given to 56 HIV-positive women who were measured at two time points three months apart. Half of these women were randomly assigned to a CB intervention and half to a low intensity comparison condition. Increases in AIDS Self-efficacy over the three-month period were significantly related to increases in CD4 and decreases in viral load. Similarly, increases in Cognitive Behavioral Skills Self-efficacy were significantly related to decreases in distress over time. Findings were maintained within the intervention group alone. Interestingly, increases in cognitive behavioral skills self-efficacy and increases in the self-efficacy adherence item were also significantly related to decreases in viral load. Implications of the findings and suggestions for future research are discussed.

  15. Transmissible Gastroenteritis MECHANISMS RESPONSIBLE FOR DIARRHEA IN AN ACUTE VIRAL ENTERITIS IN PIGLETS

    PubMed Central

    Butler, D. G.; Gali, D. G.; Kelly, M. H.; Hamilton, J. R.

    1974-01-01

    We studied 3-wk-old piglets 40 h after experimental infection with transmissible gastroenteritis (TGE) virus to identify the mechanisms of diarrhea in this disease and to better understand infectious diarrhea in humans. Using continuous segmental marker perfusion in four regions along the gut, we found significant increases in net intraluminal accumulation of water and electrolytes only in the proximal jejunum, the region infected by the virus. In this jejunal segment studied in vivo, unidirectional sodium flux, extracellular fluid (ECF) to lumen, significantly increased, lumen to ECF significantly decreased, compared with matchfed littermates. The standard perfusate rendered hypertonic by adding mannitol (450 mosmol/kg), in the same segment of normal pigs, caused only an increase in ECF to lumen flux of sodium. TGE did not alter gross villous structure or intraluminal bacteria, bile salts, lactate, pH, or osmolality. Epithelial cell migration was accelerated in the jejunum of infected pigs. Isolated in suspension, these cells from TGE pigs exhibited increased active and passive sodium efflux, cells from mannitol-perfused pigs exhibited only increased active sodium efflux. In this viral enteritis, altered sodium transport occurring in the jejunum, the region of the intestine infected appears to be associated with defective epithelial cell function. The precise nature of the abnormalities in sodium transport, their relationship to disturbances of transport of other solutes, and to virus epithelial cell interaction remain to be defined. Images PMID:4825228

  16. 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

  17. A Complicated Course of Acute Viral Induced Pharyngitis, Icteric Hepatitis, Acalculous Cholecystitis, and Skin Rash

    PubMed Central

    Erfani, Seddigheh Sadat

    2016-01-01

    This case reveals the complexities and challenges in the diagnosis of acute Epstein-Barr virus (EBV) infection, indicating the potential relationship between EBV infection and severe icteric hepatitis, acalculous cholecystitis, and lymphocytic vasculitis. We suggest including EBV infectious mononucleosis in the list of differential diagnoses when any of these clinical syndromes (or a combination thereof) occurs without apparent cause, especially in the presence of lymphocytosis. To our knowledge, this is the first report to suggest the possible role of EBV in the pathogenesis of cutaneous lymphocytic vasculitis. Also it is possible that EBV infection triggered the flare-up of the underlying rheumatologic disease. Therefore, it could be assumed that a part of the clinical syndrome (e.g., dermatologic manifestations) might be related to the flare-up of the underlying rheumatologic disease. PMID:27847520

  18. HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China.

    PubMed

    Li, Xiaoyan; Xue, Yile; Cheng, Hua; Lin, Yi; Zhou, Leiming; Ning, Zhen; Wang, Xuqin; Yu, Xiaolei; Zhang, Wei; Shen, Fangwei; Zheng, Xiaohong; Gai, Jing; Li, Xiaoshan; Kang, Laiyi; Nyambi, Phillipe; Wang, Ying; Zhuang, Minghua; Pan, Qichao; Zhuang, Xun; Zhong, Ping

    2015-01-01

    The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient's immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient's baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines.

  19. HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China

    PubMed Central

    Zhou, Leiming; Ning, Zhen; Wang, Xuqin; Yu, Xiaolei; Zhang, Wei; Shen, Fangwei; Zheng, Xiaohong; Gai, Jing; Li, Xiaoshan; Kang, Laiyi; Nyambi, Phillipe; Wang, Ying; Zhuang, Minghua; Pan, Qichao; Zhuang, Xun; Zhong, Ping

    2015-01-01

    The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient’s immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient’s baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines. PMID:26121491

  20. Accumulation of Pol Mutations Selected by HLA-B*52:01-C*12:02 Protective Haplotype-Restricted Cytotoxic T Lymphocytes Causes Low Plasma Viral Load Due to Low Viral Fitness of Mutant Viruses.

    PubMed

    Murakoshi, Hayato; Koyanagi, Madoka; Chikata, Takayuki; Rahman, Mohammad Arif; Kuse, Nozomi; Sakai, Keiko; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

    2017-02-15

    HLA-B*52:01-C*12:02, which is the most abundant haplotype in Japan, has a protective effect on disease progression in HIV-1-infected Japanese individuals, whereas HLA-B*57 and -B*27 protective alleles are very rare in Japan. A previous study on HLA-associated polymorphisms demonstrated that the number of HLA-B*52:01-associated mutations at four Pol positions was inversely correlated with plasma viral load (pVL) in HLA-B*52:01-negative individuals, suggesting that the transmission of HIV-1 with these mutations could modulate the pVL in the population. However, it remains unknown whether these mutations were selected by HLA-B*52:01-restricted CTLs and also reduced viral fitness. In this study, we identified two HLA-B*52:01-restricted and one HLA-C*12:02-restricted novel cytotoxic T-lymphocyte (CTL) epitopes in Pol. Analysis using CTLs specific for these three epitopes demonstrated that these CTLs failed to recognize mutant epitopes or more weakly recognized cells infected with mutant viruses than wild-type virus, supporting the idea that these mutations were selected by the HLA-B*52:01- or HLA-C*12:02-restricted T cells. We further showed that these mutations reduced viral fitness, although the effect of each mutation was weak. The present study demonstrated that the accumulation of these Pol mutations selected by HLA-B*52:01- or HLA-C*12:02-restricted CTLs impaired viral replication capacity and thus reduced the pVL. The fitness cost imposed by the mutations partially accounted for the effect of the HLA-B*52:01-C*12:02 haplotype on clinical outcome, together with the effect of HLA-B*52:01-restricted CTLs on viral replication, which had been previously demonstrated.

  1. Etiology and Incidence of Viral Acute Respiratory Infections among Refugees Aged 5 Years and Older in Hagadera Camp, Dadaab, Kenya

    PubMed Central

    Mohamed, Gedi A.; Ahmed, Jamal A.; Marano, Nina; Mohamed, Abdinoor; Moturi, Edna; Burton, Wagacha; Otieno, Samora; Fields, Barry; Montgomery, Joel; Kabugi, Willy; Musa, Hashim; Cookson, Susan T.

    2015-01-01

    We used the Centers for Disease Control and Prevention–Kenya Medical Research Institute Acute Respiratory Infection (ARI) Surveillance System data to estimate severe acute respiratory infection (SARI) hospitalization rates, viral etiology, and associated complaints of influenza-like illnesses (ILI) and SARI conditions among those aged 5 years and older in Hagadera, Dadaab refugee camp, Kenya, for 2010–2012. A total of 471 patients aged ≥ 5 years met the case definition for ILI or SARI. SARI hospitalization rates per 10,000 person-years were 14.7 (95% confidence interval [CI] = 9.1, 22.2) for those aged 5–14 years; 3.4 (95% CI = 1.6, 7.2) for those aged 15–24 year; and 3.8 (95% CI = 1.6, 7.2) for those aged ≥ 25 years. Persons between the ages of 5 and 14 years had 3.5 greater odds to have been hospitalized as a result of SARI than those aged ≥ 25 years (odds ratio [OR] = 3.5, P < 0.001). Among the 419 samples tested, 169 (40.3%) were positive for one or more virus. Of those samples having viruses, 36.9% had influenza A; 29.9% had adenovirus; 20.2% had influenza B; and 14.4% had parainfluenza 1, 2, or 3. Muscle/joint pain was associated with influenza A (P = 0.002), whereas headache was associated with influenza B (P = 0.019). ARIs were responsible for a substantial disease burden in Hagadera camp. PMID:26458776

  2. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection

    PubMed Central

    Zhang, Yan; Wallace, Diana L; de Lara, Catherine M; Ghattas, Hala; Asquith, Becca; Worth, Andrew; Griffin, George E; Taylor, Graham P; Tough, David F; Beverley, Peter C L; Macallan, Derek C

    2007-01-01

    Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D2-glucose, CD3– CD16+ NK cells sorted from peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorter (FACS) were analysed for DNA deuterium content by gas chromatography mass spectrometry to yield minimum estimates for proliferation rate (p). In healthy young adults (n = 5), deuterium enrichment was maximal ∼10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (± standard deviation) proliferation rate was 4·3 ± 2·4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 ± 7·6 × 106 cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6·9 ± 4·0%/day; half-life (T½) <10 days]. Healthy elderly subjects (n = 8) had lower proliferation and production rates (P = 2·5 ± 1·0%/day and 7·3 ± 3·7 × 106 cells/l/day, respectively; P = 0·04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P = 3·2 ± 1·9%/day). In acute infectious mononucleosis (n = 5), NK cell numbers were increased but kinetics were unaffected (P = 2·8 ± 1·0%/day) a mean of 12 days after symptom onset. Human NK cells have a turnover time in blood of about 2 weeks. Proliferation rates appear to fall with ageing, remain unperturbed by chronic HTLV-I infection and normalize rapidly following acute Epstein–Barr virus infection. PMID:17346281

  3. Etiology and Incidence of Viral Acute Respiratory Infections Among Refugees Aged 5 Years and Older in Hagadera Camp, Dadaab, Kenya.

    PubMed

    Mohamed, Gedi A; Ahmed, Jamal A; Marano, Nina; Mohamed, Abdinoor; Moturi, Edna; Burton, Wagacha; Otieno, Samora; Fields, Barry; Montgomery, Joel; Kabugi, Willy; Musa, Hashim; Cookson, Susan T

    2015-12-01

    We used the Centers for Disease Control and Prevention-Kenya Medical Research Institute Acute Respiratory Infection (ARI) Surveillance System data to estimate severe acute respiratory infection (SARI) hospitalization rates, viral etiology, and associated complaints of influenza-like illnesses (ILI) and SARI conditions among those aged 5 years and older in Hagadera, Dadaab refugee camp, Kenya, for 2010-2012. A total of 471 patients aged ≥ 5 years met the case definition for ILI or SARI. SARI hospitalization rates per 10,000 person-years were 14.7 (95% confidence interval [CI] = 9.1, 22.2) for those aged 5-14 years; 3.4 (95% CI = 1.6, 7.2) for those aged 15-24 year; and 3.8 (95% CI = 1.6, 7.2) for those aged ≥ 25 years. Persons between the ages of 5 and 14 years had 3.5 greater odds to have been hospitalized as a result of SARI than those aged ≥ 25 years (odds ratio [OR] = 3.5, P < 0.001). Among the 419 samples tested, 169 (40.3%) were positive for one or more virus. Of those samples having viruses, 36.9% had influenza A; 29.9% had adenovirus; 20.2% had influenza B; and 14.4% had parainfluenza 1, 2, or 3. Muscle/joint pain was associated with influenza A (P = 0.002), whereas headache was associated with influenza B (P = 0.019). ARIs were responsible for a substantial disease burden in Hagadera camp.

  4. Noninvasive Detection of New Simian Immunodeficiency Virus Lineages in Captive Sooty Mangabeys: Ability To Amplify Virion RNA from Fecal Samples Correlates with Viral Load in Plasma

    PubMed Central

    Ling, Binhua; Santiago, Mario L.; Meleth, Sreelatha; Gormus, Bobby; McClure, Harold M.; Apetrei, Cristian; Hahn, Beatrice H.; Marx, Preston A.

    2003-01-01

    The sooty mangabey (SM) (Cercocebus atys) is the natural host of a simian immunodeficiency virus, termed SIVsm, which gave rise to human immunodeficiency virus type 2. Data on the geographic distribution, prevalence, and genetic diversity of SIVsm in the wild remains limited. To address this issue, noninvasive strategies based on screening SM fecal and urine specimens for SIVsm-specific antibodies and virion RNA (vRNA) were developed, and the results were correlated with viral loads in plasma. Twenty-three SIVsm-infected and 27 uninfected SMs were evaluated. Time-matched urine, fecal and plasma samples were collected over a 2-month period from 16 captive naturally infected SMs. The remaining 7 infected and 27 uninfected SMs were sampled once. Each specimen was subjected to enhanced chemiluminescence-Western blot analysis and nested reverse transcriptase (RT) PCR. The results showed that urine was highly sensitive (96%) and specific (100%) for detection of SIVsm antibodies, while fecal detection was much less sensitive (16%). Conversely, vRNA detection was more sensitive in feces (50%) than in urine (2%) samples. Fecal-vRNA detection correlated with viral loads in plasma (P < 0.002). SMs with detectable fecal vRNA had a mean viral load in plasma of 458,006 copies/ml, while those with undetectable fecal vRNA had a mean viral load in plasma of 29,428 copies/ml. Moreover, for every log increase in the viral load in plasma, the odds of detecting virus in fecal samples increased 87-fold. Genetic diversity of SIVsm in the SM colony was characterized by sequencing partial gag (846 bp) and gp43 (439 bp) fragments. Surprisingly, four new SIVsm lineages were identified, two of which were initially detected by fecal RT-PCR. This study documents the suitability of noninvasive methods for the detection and molecular characterization of new SIV variants. These assays will be useful for studying the phylogeny and epidemiology of SIVsm infections in the wild, and they hold promise

  5. Filariae-Retrovirus Co-infection in Mice is Associated with Suppressed Virus-Specific IgG Immune Response and Higher Viral Loads

    PubMed Central

    Dietze, Kirsten Katrin; Dittmer, Ulf; Koudaimi, Daniel Karim; Schimmer, Simone; Reitz, Martina

    2016-01-01

    Worldwide more than 2 billion people are infected with helminths, predominantly in developing countries. Co-infections with viruses such as human immunodeficiency virus (HIV) are common due to the geographical overlap of these pathogens. Helminth and viral infections induce antagonistic cytokine responses in their hosts. Helminths shift the immune system to a type 2-dominated immune response, while viral infections skew the cytokine response towards a type 1 immune response. Moreover, chronic helminth infections are often associated with a generalized suppression of the immune system leading to prolonged parasite survival, and also to a reduced defence against unrelated pathogens. To test whether helminths affect the outcome of a viral infection we set up a filarial/retrovirus co-infection model in C57BL/6 mice. Although Friend virus (FV) infection altered the L. sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection. However, reciprocal control of FV infection was clearly impaired by concurrent L. sigmodontis infection. Spleen weight as an indicator of pathology and viral loads in spleen, lymph nodes (LN) and bone marrow (BM) were increased in L. sigmodontis/FV-co-infected mice compared to only FV-infected mice. Numbers of FV-specific CD8+ T cells as well as cytokine production by CD4+ and CD8+ cells were alike in co-infected and FV-infected mice. Increased viral loads in co-infected mice were associated with reduced titres of neutralising FV-specific IgG2b and IgG2c antibodies. In summary our findings suggest that helminth infection interfered with the control of retroviral infection by dampening the virus-specific neutralising antibody response. PMID:27923052

  6. Abuse and resilience in relation to HAART medication adherence and HIV viral load among women with HIV in the United States.

    PubMed

    Dale, Sannisha; Cohen, Mardge; Weber, Kathleen; Cruise, Ruth; Kelso, Gwendolyn; Brody, Leslie

    2014-03-01

    Abuse is highly prevalent among HIV+ women, leading to behaviors, including lower adherence to highly active antiretroviral therapy (HAART) that result in poor health outcomes. Resilience (functioning competently despite adversity) may buffer the negative effects of abuse. This study investigated how resilience interacted with abuse history in relation to HAART adherence, HIV viral load (VL), and CD4+ cell count among a convenience sample of 138 HIV+ women from the Ruth M. Rothstein CORE Center/Cook County Health and Hospital Systems site of the Women's Interagency HIV Study (WIHS). Resilience was measured by the 10-item Connor-Davidson Resilience Scale (CD-RISC). HAART adherence (≥95% vs. <95% self reported usage of prescribed medication) and current or prior sexual, physical, or emotional/domestic abuse, were reported during structured interviews. HIV viral load (≥20 vs. <20 copies/mL) and CD4+ count (200 vs. <200 cells/mm) were measured with blood specimens. Multiple logistic regressions, controlling for age, race, income, enrollment wave, substance use, and depressive symptoms, indicated that each unit increase in resilience was significantly associated with an increase in the odds of having ≥95% HAART adherence and a decrease in the odds of having a detectable viral load. Resilience-Abuse interactions showed that only among HIV+ women with sexual abuse or multiple abuses did resilience significantly relate to an increase in the odds of ≥95% HAART adherence. Interventions to improve coping strategies that promote resilience among HIV+ women may be beneficial for achieving higher HAART adherence and viral suppression.

  7. Abuse and Resilience in Relation to HAART Medication Adherence and HIV Viral Load Among Women with HIV in the United States

    PubMed Central

    Cohen, Mardge; Weber, Kathleen; Cruise, Ruth; Kelso, Gwendolyn

    2014-01-01

    Abstract Abuse is highly prevalent among HIV+ women, leading to behaviors, including lower adherence to highly active antiretroviral therapy (HAART) that result in poor health outcomes. Resilience (functioning competently despite adversity) may buffer the negative effects of abuse. This study investigated how resilience interacted with abuse history in relation to HAART adherence, HIV viral load (VL), and CD4+ cell count among a convenience sample of 138 HIV+ women from the Ruth M. Rothstein CORE Center/Cook County Health and Hospital Systems site of the Women's Interagency HIV Study (WIHS). Resilience was measured by the 10-item Connor-Davidson Resilience Scale (CD-RISC). HAART adherence (≥95% vs. <95% self reported usage of prescribed medication) and current or prior sexual, physical, or emotional/domestic abuse, were reported during structured interviews. HIV viral load (≥20 vs. <20 copies/mL) and CD4+ count (200 vs. <200 cells/mm) were measured with blood specimens. Multiple logistic regressions, controlling for age, race, income, enrollment wave, substance use, and depressive symptoms, indicated that each unit increase in resilience was significantly associated with an increase in the odds of having ≥95% HAART adherence and a decrease in the odds of having a detectable viral load. Resilience-Abuse interactions showed that only among HIV+ women with sexual abuse or multiple abuses did resilience significantly relate to an increase in the odds of ≥95% HAART adherence. Interventions to improve coping strategies that promote resilience among HIV+ women may be beneficial for achieving higher HAART adherence and viral suppression. PMID:24568654

  8. Performance of the SAMBA I and II HIV-1 Semi-Q Tests for viral load monitoring at the point-of-care.

    PubMed

    Goel, Neha; Ritchie, Allyson V; Mtapuri-Zinyowera, Sekesai; Zeh, Clement; Stepchenkova, Tetiana; Lehga, Jesse; De Ruiter, Annemiek; Farleigh, Laura E; Edemaga, Daniel; So, Rosario; Sembongi, Hiroshi; Wisniewski, Craig; Nadala, Lourdes; Schito, Marco; Lee, Helen

    2017-03-06

    Although access to antiretroviral therapy for HIV infection is increasing in resource-poor countries, viral load testing for monitoring of treatment efficacy remains limited, expensive, and confined to centralized laboratories. The SAMBA HIV-1 Semi-Q Test is a nucleic acid-based amplification assay developed for viral load monitoring performed on either the semi-automated SAMBA I system for laboratory use or the fully automated SAMBA II system for point-of care use. We have assessed the performance characteristics of the SAMBA HIV-1 Semi-Q Test on SAMBA I and SAMBA II systems according to the Common Technical Specifications of the European Community's 98/79 In Vitro Diagnostic Medical Devices Directive. The sensitivity, specificity, reproducibility, and viral subtype coverage of the test were similar on the SAMBA I and SAMBA II platforms. The clinical performance on the SAMBA I system was compared with the Roche CAP/CTM assay and evaluated in-house with 130 patient specimens from London as well as in the field with 390 specimens in Kenya and Zimbabwe. The overall concordance between the SAMBA and CAP/CTM assays was 98.1%. The clinical performance of the test on the SAMBA II platform in comparison with the Abbott HIV-1 RealTime Assay was evaluated in-house with 150 specimens from Ukraine, yielding a concordance of 98.0%. The results thus show that the SAMBA HIV-1 Semi-Q Test performs equivalently on SAMBA I and SAMBA II, and they suggest that the test is suitable for implementation at the point-of-care in resource-poor regions where viral load testing is desperately needed but often unavailable.

  9. Acute on-chip HIV detection through label-free electrical sensing of viral nano-lysate.

    PubMed

    Shafiee, Hadi; Jahangir, Muntasir; Inci, Fatih; Wang, Shuqi; Willenbrecht, Remington B M; Giguel, Francoise F; Tsibris, Athe M N; Kuritzkes, Daniel R; Demirci, Utkan

    2013-08-12

    Development of portable biosensors has broad applications in environmental monitoring, clinical diagnosis, public health, and homeland security. There is an unmet need for pathogen detection at the point-of-care (POC) using a fast, sensitive, inexpensive, and easy-to-use method that does not require complex infrastructure and well-trained technicians. For instance, detection of Human Immunodeficiency Virus (HIV-1) at acute infection stage has been challenging, since current antibody-based POC technologies are not effective due to low concentration of antibodies. In this study, we demonstrated for the first time a label-free electrical sensing method that can detect lysed viruses, i.e. viral nano-lysate, through impedance analysis, offering an alternative technology to the antibody-based methods such as dipsticks and Enzyme-linked Immunosorbent Assay (ELISA). The presented method is a broadly applicable platform technology that can potentially be adapted to detect multiple pathogens utilizing impedance spectroscopy for other infectious diseases including herpes, influenza, hepatitis, pox, malaria, and tuberculosis. The presented method offers a rapid and portable tool that can be used as a detection technology at the POC in resource-constrained settings, as well as hospital and primary care settings.

  10. Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri

    PubMed Central

    2013-01-01

    Background Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. Results The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. Conclusions Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs. PMID:23566284

  11. Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis

    PubMed Central

    Long, Qi; Liao, Yu-Hua; Xie, Yu; Liang, Wei; Cheng, Xiang; Yuan, Jing; Yu, Miao

    2016-01-01

    Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC. PMID:28018858

  12. [Investigation of viral nucleic acids in middle-ear effusion specimens from children with acute otitis media].

    PubMed

    Abu Sitteh, Muhammed H; Sener, Kenan; Yapar, Mehmet; Kiliç, Abdullah; Güney, Cakir; Kubar, Ayhan

    2008-07-01

    Acute otitis media with effusion (OME) is one of the major causes of antibiotic use, indication for operation and hearing loss in children. In two third of the cases the etiologic agents are bacteria. Nonetheless, increasing numbers of reports have implicated viruses as etiologic agents that may have some effect on prognosis of OME. The aim of this study was to investigate the presence of nucleic acids of respiratory syncytial virus (RSV) type A and B, influenza type A virus, adenovirus, cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and enteroviruses in the middle ear effusion specimens from children with otitis media by TaqMan real-time PCR. As a result, 18 of 30 (60%) OME samples were found positive in terms of viral nucleic acids by real-time PCR. RSV-A was detected in nine samples (30%), CMV in 3 (10%) samples and HSV-1 in 1 (3.3%) sample. In five of the samples two viruses were detected in the same sample (three were positive for adenovirus and RSV-A, and two were positive for CMV and RSV-A). Our data have supported the importance of viruses as etiologic agents of OME. Additionally, it was thought that TaqMan real-time PCR may be used as a reliable and rapid method for the detection of viruses in the middle ear effusion samples.

  13. Acute viral respiratory infections among children in MERS-endemic Riyadh, Saudi Arabia, 2012-2013.

    PubMed

    Fagbo, Shamsudeen F; Garbati, Musa A; Hasan, Rami; AlShahrani, Dayel; Al-Shehri, Mohamed; AlFawaz, Tariq; Hakawi, Ahmed; Wani, Tariq Ahmad; Skakni, Leila

    2017-02-01

    The emergence of the Middle East Respiratory Syndrome (MERS) in Saudi Arabia has intensified focus on Acute Respiratory Infections [ARIs]. This study sought to identify respiratory viruses (RVs) associated with ARIs in children presenting at a tertiary hospital. Children (aged ≤13) presenting with ARI between January 2012 and December 2013 tested for 15 RVs using the Seeplex(R) RV15 kit were retrospectively included. Epidemiological data was retrieved from patient records. Of the 2235 children tested, 61.5% were ≤1 year with a male: female ratio of 3:2. Viruses were detected in 1364 (61.02%) children, 233 (10.4%) having dual infections: these viruses include respiratory syncytial virus (RSV) (24%), human rhinovirus (hRV) (19.7%), adenovirus (5.7%), influenza virus (5.3%), and parainfluenzavirus-3 (4.6%). Children, aged 9-11 months, were most infected (60.9%). Lower respiratory tract infections (55.4%) were significantly more than upper respiratory tract infection (45.3%) (P < 0.001). Seasonal variation of RV was directly and inversely proportional to relative humidity and temperature, respectively, for non MERS coronaviruses (NL63, 229E, and OC43). The study confirms community-acquired RV associated with ARI in children and suggests modulating roles for abiotic factors in RV epidemiology. However, community-based studies are needed to elucidate how these factors locally influence RV epidemiology. J. Med. Virol. 89:195-201, 2017. © 2016 Wiley Periodicals, Inc.

  14. Risk of viral acute gastrointestinal illness from nondisinfected drinking water distribution systems.

    PubMed

    Lambertini, Elisabetta; Borchardt, Mark A; Kieke, Burney A; Spencer, Susan K; Loge, Frank J

    2012-09-04

    Acute gastrointestinal illness (AGI) resulting from pathogens directly entering the piping of drinking water distribution systems is insufficiently understood. Here, we estimate AGI incidence from virus intrusions into the distribution systems of 14 nondisinfecting, groundwater-source, community water systems. Water samples for virus quantification were collected monthly at wells and households during four 12-week periods in 2006-2007. Ultraviolet (UV) disinfection was installed on the communities' wellheads during one study year; UV was absent the other year. UV was intended to eliminate virus contributions from the wells and without residual disinfectant present in these systems, any increase in virus concentration downstream at household taps represented virus contributions from the distribution system (Approach 1). During no-UV periods, distribution system viruses were estimated by the difference between well water and household tap virus concentrations (Approach 2). For both approaches, a Monte Carlo risk assessment framework was used to estimate AGI risk from distribution systems using study-specific exposure-response relationships. Depending on the exposure-response relationship selected, AGI risk from the distribution systems was 0.0180-0.0661 and 0.001-0.1047 episodes/person-year estimated by Approaches 1 and 2, respectively. These values represented 0.1-4.9% of AGI risk from all exposure routes, and 1.6-67.8% of risk related to drinking water exposure. Virus intrusions into nondisinfected drinking water distribution systems can contribute to sporadic AGI.

  15. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18.

    PubMed

    Fu Xi, Long; Schiffman, Mark; Ke, Yang; Hughes, James P; Galloway, Denise A; He, Zhonghu; Hulbert, Ayaka; Winer, Rachel L; Koutsky, Laura A; Kiviat, Nancy B

    2017-04-15

    Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.

  16. Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.

    PubMed

    Lee, Jia-Yee; Locarnini, Stephen

    2004-05-01

    Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).

  17. Antibody responses and viral load in patients with Crimean-Congo hemorrhagic fever: a comprehensive analysis during the early stages of the infection.

    PubMed

    Ergunay, Koray; Kocak Tufan, Zeliha; Bulut, Cemal; Kinikli, Sami; Demiroz, Ali Pekcan; Ozkul, Aykut

    2014-05-01

    This study was performed to assess viral load, viral nucleocapsid (N), and glycoprotein precursor (GPC) antibodies in consecutive samples obtained from Crimean-Congo hemorrhagic fever patients to reveal viral replication kinetics and antiviral immune responses during the early stages of the infection. Among 116 samples from 20 individuals, 43.9% and 76.7% were positive for viral RNA and IgM/IgG antibodies, respectively, whereas both markers could be detected in 22.4%. Mean duration of viremia was 3 days (range: 1-6 days). N-IgM antibodies were identified as the initial serological marker during the infection, becoming detectable in a median of 2-3 days after disease onset, followed by GPC-IgM (4-6 days) and IgG antibodies (5-6 days). Clearance of viremia followed or coincided N-IgM response. Partial S gene sequences amplified in viremic patients were identical or closely related to previously characterized strains and grouped within European lineage I group II viruses via neighbor-joining analysis without significant amino acid substitutions.

  18. The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June-October 2014.

    PubMed

    Fitzpatrick, Gabriel; Vogt, Florian; Moi Gbabai, Osman B; Decroo, Tom; Keane, Marian; De Clerck, Hilde; Grolla, Allen; Brechard, Raphael; Stinson, Kathryn; Van Herp, Michel

    2015-12-01

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC).Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P < .05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per milliliter (P < .05, odds ratio >10), aged ≥ 50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P < .05) in Ebola patients who died.These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  19. Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load.

    PubMed

    Inaba, Katsuhisa; Fukazawa, Yoshinori; Matsuda, Kenta; Himeno, Ai; Matsuyama, Megumi; Ibuki, Kentaro; Miura, Yoshiharu; Koyanagi, Yoshio; Nakajima, Atsushi; Blumberg, Richard S; Takahashi, Hidemi; Hayami, Masanori; Igarashi, Tatsuhiko; Miura, Tomoyuki

    2010-03-01

    Human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (SHIV) infection generally lead to death of the host accompanied by high viraemia and profound CD4(+) T-cell depletion. SHIV clone KS661-infected rhesus macaques with a high viral load set point (HVL) ultimately experience diarrhoea and wasting at 6-12 months after infection. In contrast, infected macaques with a low viral load set point (LVL) usually live asymptomatically throughout the observation period, and are therefore referred to as asymptomatic LVL (Asym LVL) macaques. Interestingly, some LVL macaques exhibit diarrhoea and wasting similar to the symptoms of HVL macaques and are termed symptomatic LVL (Sym LVL) macaques. This study tested the hypothesis that Sym LVL macaques have the same degree of intestinal abnormalities as HVL macaques. The proviral DNA loads in lymphoid tissue and the intestines of Sym LVL and Asym LVL macaques were comparable and all infected monkeys showed villous atrophy. Notably, the CD4(+) cell frequencies of lymphoid tissues and intestines in Sym LVL macaques were remarkably lower than those in Asym LVL and uninfected macaques. Furthermore, Sym LVL and HVL macaques exhibited an increased number of activated macrophages. In conclusion, intestinal disorders including CD4(+) cell reduction and abnormal immune activation can be observed in SHIV-KS661-infected macaques independent of virus replication levels.

  20. HIV-1 Vpr accelerates viral replication during acute infection by exploitation of proliferating CD4+ T cells in vivo.

    PubMed

    Sato, Kei; Misawa, Naoko; Iwami, Shingo; Satou, Yorifumi; Matsuoka, Masao; Ishizaka, Yukihito; Ito, Mamoru; Aihara, Kazuyuki; An, Dong Sung; Koyanagi, Yoshio

    2013-01-01

    The precise role of viral protein R (Vpr), an HIV-1-encoded protein, during HIV-1 infection and its contribution to the development of AIDS remain unclear. Previous reports have shown that Vpr has the ability to cause G2 cell cycle arrest and apoptosis in HIV-1-infected cells in vitro. In addition, vpr is highly conserved in transmitted/founder HIV-1s and in all primate lentiviruses, which are evolutionarily related to HIV-1. Although these findings suggest an important role of Vpr in HIV-1 pathogenesis, its direct evidence in vivo has not been shown. Here, by using a human hematopoietic stem cell-transplanted humanized mouse model, we demonstrated that Vpr causes G2 cell cycle arrest and apoptosis predominantly in proliferating CCR5(+) CD4(+) T cells, which mainly consist of regulatory CD4(+) T cells (Tregs), resulting in Treg depletion and enhanced virus production during acute infection. The Vpr-dependent enhancement of virus replication and Treg depletion is observed in CCR5-tropic but not CXCR4-tropic HIV-1-infected mice, suggesting that these effects are dependent on the coreceptor usage by HIV-1. Immune activation was observed in CCR5-tropic wild-type but not in vpr-deficient HIV-1-infected humanized mice. When humanized mice were treated with denileukin diftitox (DD), to deplete Tregs, DD-treated humanized mice showed massive activation/proliferation of memory T cells compared to the untreated group. This activation/proliferation enhanced CCR5 expression in memory CD4(+) T cells and rendered them more susceptible to CCR5-tropic wild-type HIV-1 infection than to vpr-deficient virus. Taken together, these results suggest that Vpr takes advantage of proliferating CCR5(+) CD4(+) T cells for enhancing viremia of CCR5-tropic HIV-1. Because Tregs exist in a higher cycling state than other T cell subsets, Tregs appear to be more vulnerable to exploitation by Vpr during acute HIV-1 infection.

  1. Predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.

    PubMed

    Pedraza-Bernal, Angela M; Rodriguez-Martinez, Carlos E; Acuña-Cordero, Ranniery

    2016-05-01

    Although predictors of severe viral acute lower respiratory infections (ALRIs) in children have been reported, there have been few research studies performed in low- and middle-income countries (LMIC). The aim of the present study was to determine predictors of disease severity in a population of Colombian children <5 years of age with ALRI. In a prospective cohort study, we determined independent predictors of severe ALRI in a hospitalized population of children under 5 years old with ALRI during a 1-year period. We included both underlying disease conditions and the infecting respiratory viruses as predictor variables of severe disease. We defined severe disease as the necessity of pediatric intensive care unit admission. Of a total of 1,180 patients admitted with a diagnosis of ALRI, 416 (35.3%) were included because they were positive for any kind of respiratory virus. After controlling for potential confounders, it was found that a history of pulmonary hypertension (RR 3.62; CI 95% 2.38-5.52; P < 0.001) and a history of recurrent wheezing (RR 1.77; CI 95% 1.12-2.79; P = 0.015) were independent predictors of severe disease. The present study shows that respiratory viruses are significant causes of ALRI in infants and young children in Colombia, a typical tropical LMIC, especially during the rainy season. Additionally, the results of the present study show that clinical variables such as a history of pulmonary hypertension and a history of recurrent wheezing are more relevant for predicting ALRI severity than the infecting respiratory viruses.

  2. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2012].

    PubMed

    Guna Serrano, María del Remedio; Orta Mira, Nieves; Latorre Martínez, José-Carlos; Ovies, María Rosario; Poveda, Marta; Ruiz de Gopegui, Enrique; Gimeno Cardona, Concepción

    2014-02-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2012 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (22.3% on average) obtained values out of the accepted range (mean±0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (Δ < 0.5 log10 copias/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 84% in the case of HCV and 88% in the HBV, obtained all the results within the accepted range (mean±1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up.

  3. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2013].

    PubMed

    Orta Mira, Nieves; Del Remedio Guna Serrano, María; Latorre Martínez, José-Carlos; Medina González, Rafael; Rosario Ovies, María; Poveda, Marta; Ruiz de Gopegui, Enrique; Gimeno Cardona, Concepción

    2015-07-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2013 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (25% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (D < 0.5 log10 copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 82% in the case of HCV and 78% in the HBV, obtained all the results within the accepted range (mean ± 1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up.

  4. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2014].

    PubMed

    Medina González, Rafael; Orta Mira, Nieves; Guna Serrano, María Del Remedio; Latorre Martínez, José-Carlos; Gopegui, Enrique Ruiz de; Rosario Ovies, María; Poveda, Marta; Gimeno Cardona, Concepción

    2016-07-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ < 0.5 log10 copies/mL). The HBV and HCV program consisted of 2 standards with different viral load contents. Most of the participants, 83.7% in the case of HCV and 87.9% in the HBV, obtained all the results within the accepted range (mean ± 1.96 standard deviations log10 IU/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up.

  5. Comparison of Auditory Brainstem Response in HIV-1 exposed and unexposed newborns and their correlation with the maternal viral load and CD4 cell counts

    PubMed Central

    FASUNLA, Ayotunde James; OGUNBOSI, Babatunde Oluwatosin; ODAIBO, Georgina Njideka; NWAORGU, Onyekwere George Benjamin; TAIWO, Babafemi; OLALEYE, David Olufemi; OSINUSI, Kikelomo; MURPHY, Robert Leo; ADEWOLE, Isaac Folorunso; AKINYINKA, Olusegun Olusina

    2014-01-01

    Objective The effects of maternal HIV infection and antiretroviral therapy on hearing of HIV-exposed newborns in sub-Saharan Africa have not been investigated. We determined the prevalence of sensorineural hearing loss among HIV-exposed newborns and the association between the hearing threshold and maternal & newborn parameters. Design A cohort audiometric study of newborns between October 2012 and April 2013. Settings Secondary and tertiary hospital based study. Participants Consecutive 126 HIV-exposed and 121 HIV-unexposed newborns. Intervention Hearing screening of the newborns were done with Auditory Brainstem Response and compared with maternal HAART, CD4 cell counts, RNA viral loads and newborn CD4 percent. Main outcome measure Hearing threshold levels of both groups were measured and analyzed. Results 11.1% of HIV-exposed and 6.6% of unexposed newborns had hearing impairment (p=0.2214). 6.4% of HIV-exposed and 2.5% HIV-unexposed newborns had hearing threshold >20dBHL (p = 0.1578). There was no significant association between the hearing thresholds of HIV-exposed newborns and maternal CD4 cell counts (p = 0.059) but there was with maternal viral load (p=0.034). There was significant difference between the hearing thresholds of HIV-exposed newborns with CD4 % of ≤25 and >25. This study showed significant difference in the hearing of the 119 HAART-exposed newborns and 7 unexposed newborns (p=0.002; RR=0.13 [0.05–0.32]). Conclusion There was a trend towards more hearing loss in HIV-exposed newborns. However, hearing thresholds increase with increasing mothers’ viral load. This background information supports the need for further studies on the role of in-utero exposure to HIV and HAART in newborn hearing loss. PMID:25313584

  6. [Analysis of the results of the HIV-1 and HCV viral load of the SEIMC External Quality Control Program. Year 2009].

    PubMed

    Orta Mira, Nieves; del Remedio Guna Serrano, María; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Pérez, José L; Cardona, Concepción Gimeno

    2011-03-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) viral load determinations are among the most important markers in the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarizes the results obtained from the SEIMC's External Quality Control Program for HIV-1 and HCV viral loads in 2009. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log(10) copies/mL; two of these standards were identical, aiming to determine repeatability. A significant proportion of the laboratories (21.5% on average) obtained values outside the accepted range (mean ± 0.2 log(10) copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95 % of laboratories reporting results within the accepted limits (Δ<0.5 log10 copies/mL). Post-analytical errors due to mistranscription of the results were detected for HIV-1. The HCV program consisted of two standards with different viral load contents. Most of the participants (79.7%) obtained results within the accepted range (mean ± 1.96 SD log(10) UI/mL). Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to marked interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable.

  7. [Analysis of the results of the HIV-1, HCV and HBV viral load of the SEIMC External Quality Control Program. Year 2011].

    PubMed

    Orta Mira, Nieves; Guna Serrano, María del Remedio; Latorre Martínez, José-Carlos; Ovies, María Rosario; Poveda, Marta; Ruiz de Gopegui, Enrique; Gimeno Cardona, Concepción

    2013-02-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers in the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarizes the results of the 2011 SEIMC External Quality Control Program for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients in the range of 2-5 log10 copies/mL; to determine repeatability, two of these standards were identical. A significant proportion of the laboratories (52.1% on average) obtained values outside the accepted range (mean ± 0,25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 94.9% of laboratories reporting results within the accepted range (Δ<0,5 log10 copies/ mL). The HBV and HCV program consisted of two standards with different viral load contents. In most of the participating laboratories (90% in the case of HCV and 86% in that of HBV), all the results were within the accepted range (mean ± 1.96 SD log10UI/mL). Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to the marked interlaboratory variability found, use of the same method and the same laboratory for patient follow-up is advisable.

  8. Viral load detection using dried blood spots in a cohort of HIV-1-infected children in Uganda: correlations with clinical and immunological criteria for treatment failure.

    PubMed

    Costenaro, Paola; Lundin, Rebecca; Petrara, Maria Raffaella; Penazzato, Martina; Massavon, William; Kizito, Susan; Nabachwa, Sandra Monica; Nannyonga Musoke, Maria; Namisi, Charles; Morelli, Erika; Bilardi, Davide; Mazza, Antonio; Zanchetta, Marisa; Giaquinto, Carlo; De Rossi, Anita

    2014-07-01

    Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of <1,000, 1,000 to 5,000, and >5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.

  9. Distribution of human papillomavirus genotypes, assessment of HPV 16 and 18 viral load and anal related lesions in HIV positive patients: a cross-sectional analysis.

    PubMed

    Tamalet, Catherine; Obry-Roguet, Veronique; Ressiot, Emmanuelle; Bregigeon, Sylvie; Del Grande, Jean; Poizot-Martin, Isabelle

    2014-03-01

    Natural history of anal intraepithelial neoplasia and anal cancer is not fully understood. Factors associated with cytological abnormalities and predictors of progression to high-grade anal intraepithelial neoplasia still deserve investigation. The aim of this cross-sectional study was to assess the prevalence of HPV types, the relationship between HPV genotypes, HPV 16/18 viral load and cytological abnormalities in male and female HIV-infected patients. One hundred and twenty-two (72.6%) patients were infected with HPV, 75 (61%) had multiple HPV infection, and 94 (77%) had high-risk HPV infection. The most frequently identified HPV types were HPV 16 (64%), HPV 6 (39%), HPV 18 (31%), HPV 53 (14.7%), HPV 33 (10.6%), HPV 11 (8.2%), HPV 70 (5.7%), and HPV 61 (4.9%). The HPV types which were most frequently found in combination were HPV 6 + 16 (9.8%), 6 + 16 + 18 (8.2%), 16 + 18 (6.6%), 6 + 18 (4.9%), 16 + 33 (3.3%), 16 + 53 (3.3%). Median HPV16 and 18 viral loads were 6.1 log10 copies/10(6) cells [IQR 5.0-7.3] and 6.1 log10 copies/10(6) cells [IQR 5.7-6.0], respectively. Male gender (P = 0.03, OR: 1.2 [1.0-1.4]) and homo/bisexual transmission routes (P = 0.044, OR: 1.4 [1.0-1.9]) were associated with HPV 16 infection. An HPV 16 viral load cut-off ≥5.3 log10 copies/10(6) cells and a CD4+ cell count ≤200/µl were independent factors associated with abnormal cytology. In the absence of national consensus guidelines, a strict regular follow-up at shorter intervals is recommended for HIV-infected patients with abnormal cytology, especially low grade squamous intraepithelial lesions, an HPV 16 viral load ≥5.3 log/10(6) cells and a CD4+ cell count ≤200/µl.

  10. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

    PubMed

    Ande, Anusha; McArthur, Carole; Ayuk, Leo; Awasom, Charles; Achu, Paul Ngang; Njinda, Annette; Sinha, Namita; Rao, P S S; Agudelo, Marisela; Nookala, Anantha Ram; Simon, Stephen; Kumar, Anil; Kumar, Santosh

    2015-01-01

    Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible

  11. Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: results from a multicenter study.

    PubMed

    Broccolo, Francesco; Fusetti, Lisa; Rosini, Sandra; Caraceni, Donatella; Zappacosta, Roberta; Ciccocioppo, Lucia; Matteoli, Barbara; Halfon, Philippe; Malnati, Mauro S; Ceccherini-Nelli, Luca

    2013-03-01

    High-risk human papillomavirus (HR-HPV) genotype viral load and E6/E7 mRNA detection are proposed as surrogate markers of malignant cervical lesion progression. Currently, the use of commercially available DNA-based or mRNA-based tests is under investigation. In this study, the viral DNA load and E6/E7 mRNA detection of the five most common HR-HPV types detected in cervical cancer worldwide were compared in 308 cervical samples by using in-house type-specific quantitative real-time PCR assays and PreTect HPV-Proofer test, respectively. Sensitivity and negative predictive values were higher for the HPV-DNA assays combined (95.0% and 96.0%, respectively) than the RNA assays (77.0% and 88.0%, respectively); conversely, the mRNA test showed a higher specificity and higher positive predictive value (81.7% and 66.9%, respectively) than the DNA test (58.6% and 52.5%, respectively) for detecting histology-confirmed high-grade cervical intraepithelial neoplasia. A significantly higher association between viral DNA load and severity of disease was observed for HPV 16 and 31 (γ = 0.62 and γ = 0.40, respectively) than for the other HPV types screened. A good degree of association between the two assays was found for detection of HPV 16 (k = 0.83), HPV 18 (k = 0.72), HPV 33 (k = 0.66), and HPV 45 (k = 0.60) but not for HPV 31 (k = 0.24). Sequence analysis in L1 and E6-LCR regions of HPV 31 genotypes showed a high level of intra-type variation. HR-HPV viral DNA load was significantly higher in E6/E7 mRNA positive than negative samples (P < 0.001), except for HPV 31. These findings suggest that transcriptional and replicative activities can coexist within the same sample.

  12. Epstein-Barr viral load in whole blood of adults with posttransplant lymphoproliferative disorder after solid organ transplantation does not correlate with clinical course.

    PubMed

    Oertel, Stephan; Trappe, Ralf Ulrich; Zeidler, Kristin; Babel, Nina; Reinke, Petra; Hummel, Manfred; Jonas, Sven; Papp-Vary, Matthias; Subklewe, Marion; Dörken, Bernd; Riess, Hanno; Gärtner, Barbara

    2006-07-01

    Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary Epstein-Barr virus (EBV) infection. A defect of EBV specific cellular immunity is postulated to play a pivotal role in the etiology of PTLD, but there is some debate as to whether EBV load in the peripheral blood of transplant patients predicts onset of PTLD or relapse after treatment. The current prospective, single-center study was undertaken to investigate the impact of therapy on EBV load in adult patients with PTLD. Fifteen patients with PTLD after solid organ transplantation were included and of these, seven had EBV-associated PTLD. All 15 patients received Rituximab as primary therapy. In cases of treatment failure or relapse after Rituximab treatment, patients received polychemotherapy according to the cyclophosphamide, vincristine, doxorubicin, and prednisone regimen. At onset of PTLD, the median EBV load in the peripheral blood of patients was higher in EBV-associated PTLD than PTLD with no associated EBV infection. After Rituximab therapy, four of seven patients with EBV-associated PTLD achieved long-lasting complete remissions. However, in two of these patients, EBV load increased to reach levels as high as those recorded at onset of PTLD. Another patient showed a dramatic decline of EBV load after the first dose of Rituximab while suffering from progressive disease. The other patient relapsed after Rituximab monotherapy, but his viral load stayed low. In total, discordance in EBV load and clinical course was observed in five of the seven patients with EBV-associated PTLD. We conclude that in adult patients with PTLD, EBV load does not correlate with treatment response and is not suitable as a predictive marker for PTLD relapse.

  13. High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis.

    PubMed

    Weiss, Eric R; Alter, Galit; Ogembo, Javier Gordon; Henderson, Jennifer L; Tabak, Barbara; Bakiş, Yasin; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Luzuriaga, Katherine

    2017-01-01

    The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM.

  14. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  15. Viral Dose and Immunosuppression Modulate the Progression of Acute BVDV-1 Infection in Calves: Evidence of Long Term Persistence after Intra-Nasal Infection

    PubMed Central

    Strong, Rebecca; La Rocca, Severina Anna; Paton, David; Bensaude, Emmanuelle; Sandvik, Torstein; Davis, Leanne; Turner, Jane; Drew, Trevor; Raue, Rudiger; Vangeel, Ilse; Steinbach, Falko

    2015-01-01

    Bovine viral diarrhoea virus (BVDV) infection of cattle causes a diverse range of clinical outcomes from being asymptomatic, or a transient mild disease, to producing severe cases of acute disease leading to death. Four groups of calves were challenged with a type 1 BVDV strain, originating from a severe outbreak of BVDV in England, to study the effect of viral dose and immunosuppression on the viral replication and transmission of BVDV. Three groups received increasing amounts of virus: Group A received 102.55TCID50/ml, group B 105.25TCID50/ml and group C 106.7TCID 50/ml. A fourth group (D) was inoculated with a medium dose (105.25TCID50/ml) and concomitantly treated with dexamethasone (DMS) to assess the effects of chemically induced immunosuppression. Naïve calves were added as sentinel animals to assess virus transmission. The outcome of infection was dose dependent with animals given a higher dose developing severe disease and more pronounced viral replication. Despite virus being shed by the low-dose infection group, BVD was not transmitted to sentinel calves. Administration of dexamethasone (DMS) resulted in more severe clinical signs, prolonged viraemia and virus shedding. Using PCR techniques, viral RNA was detected in blood, several weeks after the limit of infectious virus recovery. Finally, a recently developed strand-specific RT-PCR detected negative strand viral RNA, indicative of actively replicating virus, in blood samples from convalescent animals, as late as 85 days post inoculation. This detection of long term replicating virus may indicate the way in which the virus persists and/or is reintroduced within herds. PMID:25955849

  16. Acute coronal plane scaphoid fracture and scapholunate dissociation from an axial load: a case report.

    PubMed

    Shin, Alexander Y; Horton, Todd; Bishop, Allen T

    2005-03-01

    Coronal fractures of the scaphoid are rare and can be difficult to diagnose. Axial load injuries that result in a complete coronal fracture of the scaphoid associated with an acute scapholunate dissociation are exceedingly rare. In our patient the radiographic finding of wide scapholunate dissociation was obvious; however, the coronal scaphoid fracture was not recognized initially nor suspected. During surgery the coronal scaphoid fracture was identified, reduced anatomically, and fixed with a compression screw. The scapholunate ligament also was repaired. A good result was obtained with return to sports with extension of 60 degrees and flexion of 70 degrees , grip strength equal to that of the uninjured wrist, and no radiographic problems (arthrosis, avascular necrosis, nonunion).

  17. Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Scotto, P.; Riedel, C.; Avasthi, P.; Koshukosky, V.; Chick, T. W.

    1991-01-01

    Cardiopulmonary responses to acute hypoxia (HY), fluid loading by saline infusion (FL), and head-down tilt (HD) of mechanically ventilated anesthetized dogs were investigated by measuring thermodynamics and pulmonary gas exchange. It was found that HD decreased the total respiratory compliance both during HY and normoxia (NO) and that the reduction in compliance by FL was twice as large as by HD. Superimposing HD on HY doubled the increase in vascular resistance due to HY alone. In the systemic circulation, HD lowered the resistance to below NO levels. There was a significant positive correlation between the changes in blood volume and in pulmonary artery pressure for experimental transitions, suggesting that a shift in blood volume from systemic to pulmonary circulations and changes in the total blood volume may contribute substantially to these apparent changes in resistance.

  18. Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma.

    PubMed

    Rosty, Christophe; Sheffer, Michal; Tsafrir, Dafna; Stransky, Nicolas; Tsafrir, Ilan; Peter, Martine; de Crémoux, Patricia; de La Rochefordière, Anne; Salmon, Rémy; Dorval, Thierry; Thiery, Jean Paul; Couturier, Jérôme; Radvanyi, François; Domany, Eytan; Sastre-Garau, Xavier

    2005-10-27

    Specific HPV DNA sequences are associated with more than 90% of invasive carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators in cell transformation by disrupting TP53 and RB pathways. To investigate molecular mechanisms involved in the progression of invasive cervical carcinoma, we performed a gene expression study on cases selected according to viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting Points Into Neighbourhoods methods, we identified a 'cervical cancer proliferation cluster' composed of 163 highly correlated transcripts. Most of these transcripts corresponded to E2F pathway genes controlling cell division or proliferation, whereas none was known as TP53 primary target. The average expression level of the genes of this cluster was higher in tumours with an early relapse than in tumours with a favourable course (P = 0.026). Moreover, we found that E6/E7 mRNA expression level was positively correlated with the expression level of the cluster genes and with viral DNA load. These findings suggest that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV expression level may thus provide a biological marker useful for prognosis assessment and specific therapy of the disease.

  19. Mechanistic evaluation of the pros and cons of digital RT-LAMP for HIV-1 viral load quantification on a microfluidic device and improved efficiency via a two-step digital protocol.

    PubMed

    Sun, Bing; Shen, Feng; McCalla, Stephanie E; Kreutz, Jason E; Karymov, Mikhail A; Ismagilov, Rustem F

    2013-02-05

    Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient's HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful

  20. Experimental infection of European flat oyster Ostrea edulis with ostreid herpesvirus 1 microvar (OsHV-1μvar): Mortality, viral load and detection of viral transcripts by in situ hybridization.

    PubMed

    López Sanmartín, Monserrat; Power, Deborah M; de la Herrán, Roberto; Navas, José I; Batista, Frederico M

    2016-06-02

    Ostreid herpesvirus 1 (OsHV-1) infections have been reported in several bivalve species. Mortality of Pacific oyster Crassostrea gigas spat has increased considerably in Europe since 2008 linked to the spread of a variant of OsHV-1 called μvar. In the present study we demonstrated that O. edulis juveniles can be infected by OsHV-1μvar when administered as an intramuscular injection. Mortality in the oysters injected with OsHV-1μvar was first detected 4 days after injection and reached 25% mortality at day 10. Moreover, the high viral load observed and the detection of viral transcripts by in situ hybridization in several tissues of dying oysters suggested that OsHV-1μvar was the cause of mortality in the O. edulis juveniles. This is therefore the first study to provide evidence about the pathogenicity of OsHV-1μvar in a species that does not belong to the Crassostrea genus. Additionally, we present a novel method to detect OsHV-1 transcripts in infected individuals' using in situ hybridization.

  1. Depression, Substance Use, Viral Load, and CD4+ Count among Patients who continued or left Antiretroviral Therapy for HIV in St. Petersburg, Russian Federation

    PubMed Central

    Pecoraro, Anna; Mimiaga, Matthew; O'Cleirigh, Conall; Safren, Steven A.; Blokhina, Elena; Verbitskaya, Elena; Yaroslavtseva, Tatiana; Ustinov, Andrey; Lioznov, Dmitry A.; Zvartau, Edwin; Krupitsky, Evgeny; Woody, George E.

    2014-01-01

    Antiretroviral therapy (ART) became more widely available in the Russian Federation in 2006 when the Global Fund made a contribution to purchase ART with a mandate to increase numbers of patients receiving it. Funds were distributed to AIDS Centers and selected hospitals, and numbers quickly increased. Though ART is highly effective for adherent patients, dropout has been a problem; thus understanding characteristics of patients who remain on ART vs. those who leave treatment may provide information to facilitate engagement. We retrospectively assessed depression, hopelessness, substance use, viral load, and CD4+ counts of 120 patients who dropped out of ART for >12 months (Lost-to-Care; LTCs) and 120 who continued for >12 months (Engaged-in-Care; EICs). As expected, LTCs had higher viral loads and depression, lower CD4+ counts, and more alcohol, heroin, and injection drug use in the past 30 days. A binary logistic regression with Center for Epidemiologic Studies Depression score, Beck Hopelessness score, whether drugs/alcohol had ever prevented them from taking ART, and past 30 days’ alcohol use [X2(4)=64.27, p=.0.000] correctly classified 74.5% of participants as LTC or EIC, suggesting that integrated treatment for substance use, psychiatric, and HIV could reduce dropout and improve outcomes. PMID:25264710

  2. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    PubMed

    Chang, Hsuen-Wen; Lin, Yi-Wen; Ho, Hui-Min; Lin, Min-Han; Liu, Chia-Chyi; Shao, Hsiao-Yun; Chong, Pele; Sia, Charles; Chow, Yen-Hung

    2013-01-01

    Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  3. Valine, a branched-chain amino Acid, reduced HCV viral load and led to eradication of HCV by interferon therapy in a decompensated cirrhotic patient.

    PubMed

    Kawaguchi, Takumi; Torimura, Takuji; Takata, Akio; Satomi, Susumu; Sata, Michio

    2012-09-01

    A decreased serum level of branched-chain amino acid (BCAA) is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV) load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.

  4. Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase.

    PubMed

    Adedeji, Adeyemi O; Singh, Kamalendra; Calcaterra, Nicholas E; DeDiego, Marta L; Enjuanes, Luis; Weiss, Susan; Sarafianos, Stefan G

    2012-09-01

    Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC(50)s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC(50)] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC(50)] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.

  5. Acute Effects of Elastic Bands on Kinetic Characteristics During the Deadlift at Moderate and Heavy Loads.

    PubMed

    Galpin, Andrew J; Malyszek, Kylie K; Davis, Kyle A; Record, Shaina M; Brown, Lee E; Coburn, Jared W; Harmon, RoQue A; Steele, Jeff M; Manolovitz, Adam D

    2015-12-01

    Loading a barbell with variable resistance positively alters kinetic characteristics during the back squat and bench press but has never been studied during the deadlift. The purpose of this project was to examine the acute effects of combining elastic bands and free weights during the deadlift at moderate and heavy loads. Twelve trained men (age: 24.08 ± 2.35 years, height: 175.94 ± 5.38 cm, mass: 85.58 ± 12.49 kg, deadlift 1 repetition maximum (RM): 188.64 ± 16.13 kg) completed 2 variable resistance (B1 and B2) and 1 traditional free-weight (NB) condition at both 60 and 85% 1RM on a force plate. B1 had 15% resistance from bands, with the remaining 85% from free weights. B2 had 35% bands and 65% free weights. NB used free weights only. Average resistance was equated for all conditions. Power and velocity generally increased, whereas force decreased with the addition of bands. The amount of band tension (B1 or B2) had little impact on power when lifting at 60% 1RM. However, greater resistance from bands resulted in greater peak and relative power when lifting at 85% 1RM. Adding elastic bands decreased time to peak force (PF), time between PF and peak power (PP), and time between PF and peak velocity (PV) when compared with NB at 60% 1RM (NB > B1 > B2). These differences only reached significance for NB > B2 when lifting at 85% 1RM. These same differences existed for time between PP and PV. Thus, the amount of tension from bands has less impact on interpeak variables at heavier absolute loads. Practitioners should consider using heavy bands when prescribing the deadlift for speed or power, but not maximal force.

  6. Protective effect of magnolol-loaded polyketal microparticles on lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Tsai, Tsuimin; Kao, Chen-Yu; Chou, Chun-Liang; Liu, Lu-Chun; Chou, Tz-Chong

    2016-08-01

    Magnolol has shown inhibitory effects on NO production and TNF-alpha production in lipopolysaccharide (LPS)-activated macrophages and LPS-induced acute lung injury; however, the poor solubility of magnolol has hindered its clinical success. In this study, magnolol-loaded microparticles were prepared via single emulsion method from a polyketal polymer, termed PK3. The particle sizes of magnolol-loaded PK3 microparticle is 3.73 ± 0.41 μm, and was suitable for phagocytosis by macrophages and pulmonary drug delivery. PK3 microparticles exhibited excellent biocompatibility both in vitro and in vivo. More importantly, intratracheal delivery of these magnolol-loaded microparticles significantly reduced the lung inflammatory responses at low dosage of magnolol (0.5 mg/kg), and have great clinical potential in treating acute lung injury.

  7. Impact of genotype-specific herd immunity on the circulatory dynamism of norovirus: a 10-year longitudinal study of viral acute gastroenteritis.

    PubMed

    Sakon, Naomi; Yamazaki, Kenji; Nakata, Keiko; Kanbayashi, Daiki; Yoda, Tomoko; Mantani, Masanobu; Kase, Tetsuo; Takahashi, Kazuo; Komano, Jun

    2015-03-15

    Human norovirus is a major cause of viral acute gastroenteritis worldwide. However, the transition of endemic norovirus genotypes remains poorly understood. The characteristics of natural immunity against norovirus are unclear because few studies have been performed in the natural infection setting. This prospective 10-year surveillance study of acute gastroenteritis in the province of Osaka, Japan, revealed that norovirus spread shows temporal, geographic, and age group-specific features in the humans. Genogroup II genotype 4 (GII.4) was detected in most sporadic pediatric cases, as well as in foodborne and nursing home outbreaks, respectively. The dominant genotypes in outbreaks at childcare facilities and schools shifted every season and involved GI, GII.2, GII.3, GII.4, and GII.6. Evidence at both the facility and individual levels indicated that genotype-specific herd immunity lasted long enough to influence the endemic norovirus genotype in the next season. Thus, norovirus circulates through human populations in a uniquely dynamic fashion.

  8. Contractile function and sarcolemmal permeability after acute low-load resistance exercise with blood flow restriction.

    PubMed

    Wernbom, Mathias; Paulsen, Gøran; Nilsen, Tormod S; Hisdal, Jonny; Raastad, Truls

    2012-06-01

    Conflicting findings have been reported regarding muscle damage with low-intensity resistance exercise with blood flow restriction (BFR) by pressure cuffs. This study investigated muscle function and muscle fibre morphology after a single bout of low-intensity resistance exercise with and without BFR. Twelve physically active subjects performed unilateral knee extensions at 30% of their one repetition maximum (1RM), with partial BFR on one leg and the other leg without occlusion. With the BFR leg, five sets were performed to concentric torque failure, and the free-flow leg repeated the exact same number of repetitions and sets. Biopsies were obtained from vastus lateralis before and 1, 24 and 48 h after exercise. Maximum isometric torque (MVC) and resting tension were measured before and after exercise and at 4, 24, 48, 72, 96 and 168 h post-exercise. The results demonstrated significant decrements in MVC (lasting ≥48 h) and delayed onset muscle soreness in both legs, and increased resting tension for the occluded leg both acutely and at 24 h post-exercise. The percentage of muscle fibres showing elevated intracellular staining of the plasma protein tetranectin, a marker for sarcolemmal permeability, was significantly increased from 9% before exercise to 27-38% at 1, 24 and 48 h post-exercise for the BFR leg. The changes in the free-flow leg were significant only at 24 h (19%). We conclude that an acute bout of low-load resistance exercise with BFR resulted in changes suggesting muscle damage, which may have implications both for safety aspects and for the training stimulus with BFR exercise.

  9. Spatiotemporal Interplay of Severe Acute Respiratory Syndrome Coronavirus and Respiratory Mucosal Cells Drives Viral Dissemination in Rhesus Macaques

    PubMed Central

    Liu, Li; Wei, Qiang; Nishiura, Kenji; Peng, Jie; Wang, Haibo; Midkiff, Cecily; Alvarez, Xavier; Qin, Chuan; Lackner, Andrew; Chen, Zhiwei

    2015-01-01

    Innate immune responses play a critical role in the control of early virus replication and dissemination. It remains unknown, however, how SARS-CoV evades respiratory innate immunity to establish a systemic infection. Here, we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387+ and CD163+ monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells (LCs) and migrated into the tonsils and/or draining lymph nodes (LNs) within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages and the dendritic cell network in mucosal tissues and highlights the fact that while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically. PMID:26647718

  10. Dust-metal Loadings and the Risk of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Whitehead, Todd P.; Ward, Mary H.; Colt, Joanne S.; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B.; Hammond, S. Katharine; Rappaport, Stephen M.; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001–2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively-coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in less than 15% of homes. Relationships between dust-metal loadings (μg metal per m2 carpet) and ALL risk were modeled using multivariable logistic regression, adjusting for the child’s age, sex, and race/ethnicity and confounders, including household annual income. A doubling of dust-metal loadings was not associated with significant changes in ALL risk [odds ratio (95% confidence interval): arsenic: 0.94 (0.83, 1.05), cadmium: 0.91 (0.80, 1.04), chromium: 0.99 (0.87, 1.12), copper: 0.96 (0.90, 1.03), lead: 1.01 (0.93, 1.10), nickel: 0.92 (0.80, 1.07), tin: 0.93 (0.82, 1.05), and zinc: 0.91 (0.81, 1.02)]. Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL. PMID:25736162

  11. Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

    PubMed

    Whitehead, Todd P; Ward, Mary H; Colt, Joanne S; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B; Katharine Hammond, S; Rappaport, Stephen M; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in <15% of homes. Relationships between dust metal loadings (μg metal per m(2) carpet) and ALL risk were modeled using multivariable logistic regression, adjusting for the child's age, sex, and race/ethnicity and confounders, including household annual income. A doubling of dust metal loadings was not associated with significant changes in ALL risk (odds ratio (95% confidence interval): arsenic: 0.96 (0.86, 1.07), cadmium: 0.92 (0.81, 1.05), chromium: 1.01 (0.90, 1.14), copper: 0.97 (0.91, 1.03), lead: 1.01 (0.93, 1.10), nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.

  12. The effectiveness of session rating of perceived exertion to monitor resistance training load in acute burns patients.

    PubMed

    Grisbrook, Tiffany L; Gittings, Paul M; Wood, Fiona M; Edgar, Dale W

    2017-02-01

    Session-rating of perceived exertion (RPE) is a method frequently utilised in exercise and sports science to quantify training load of an entire aerobic exercise session. It has also been demonstrated that session-RPE is a valid and reliable method to quantify training load during resistance exercise, in healthy and athletic populations. This study aimed to investigate the effectiveness of session-RPE as a method to quantify exercise intensity during resistance training in patients with acute burns. Twenty burns patients (mean age=31.65 (±10.09) years), with a mean TBSA of 16.4% (range=6-40%) were recruited for this study. Patients were randomly allocated to the resistance training (n=10) or control group (n=10). All patients completed a four week resistance training programme. Training load (session-RPE×session duration), resistance training session-volume and pre-exercise pain were recorded for each exercise session. The influence of; age, gender, %TBSA, exercise group (resistance training vs. control), pre-exercise pain, resistance training history and session-volume on training load were analysed using a multilevel mixed-effects linear regression. Session-volume did not influence training load in the final regression model, however training load was significantly greater in the resistance training group, compared with the control group (p<0.001). Pre-exercise pain significantly influenced training load, where increasing pain was associated with a higher session-RPE (p=0.004). Further research is indicated to determine the exact relationship between pain, resistance training history, exercise intensity and session-RPE and training load before it can be used as a method to monitor and prescribe resistance training load in acute burns patients.

  13. High-intensity cannabis use associated with lower plasma HIV-1 RNA viral load among recently-infected people who use injection drugs

    PubMed Central

    Milloy, M-J; Marshall, Brandon; Kerr, Thomas; Richardson, Lindsey; Hogg, Robert; Guillemi, Silvia; Montaner, Julio SG; Wood, Evan

    2015-01-01

    Introduction and Aims Cannabis use is common among people who are living with HIV/AIDS. While there is growing pre-clinical evidence of the immunomodulatory and anti-viral effects of cannabinoids, their possible effects on HIV disease parameters in humans is largely unknown. Thus, we sought to investigate the possible effects of cannabis use on plasma HIV-1 RNA viral loads among recently-seroconverted illicit drug users. Design and Methods We used data from two linked longitudinal observational cohorts of people who use injection drugs. Using multivariable linear mixed-effects modeling, we analysed the relationship between pVL and high-intensity cannabis use among participants who seroconverted following recruitment. Results Between May, 1996 and March, 2012, 88 individuals seroconverted after recruitment and were included in these analyses. Median pVL in the first 365 days among all seroconverters was 4.66 log10 c/mL. In a multivariable model, at least daily cannabis use was associated with 0.51 log10 c/mL lower pVL (β = −0.51, Standard Error = 0.170, p-value = 0.003). Discussion Consistent with the findings from recent in vitro and in vivo studies, including one conducted among lentiviral-infected primates, we observed a strong association between cannabis use and lower pVL following seroconversion among illicit drug-using participants. Conclusion Our findings support the further investigation of the immunomodulatory or anti-viral effects of cannabinoids among individuals living with HIV/AIDS. PMID:25389027

  14. Activation of intrahepatic CD4+CXCR5+ T and CD19+ B cells is associated with viral clearance in a mouse model of acute hepatitis B virus infection.

    PubMed

    Song, Xiao-Fei; Hu, Ting-Ting; Lei, Yu; Li, Hu; Zhang, Li; Zhang, Miao; Liu, Bin; Chen, Min; Hu, Huai-Dong; Ren, Hong; Hu, Peng

    2016-08-09

    The role of immunity in the pathogenesis of acute hepatitis B virus (HBV) infection is poorly understood. The purpose of this research was to define the intrahepatic immune factors responsible for viral clearance during acute HBV infection. The model of acute HBV infection was established by hydrodynamically transfecting mice with pCDNA3.1-HBV1.3 plasmids which contained a supergenomic HBV1.3-length transgene. The frequency of CD4+ CXCR5+ T cells, CD19+ B cells and their surface molecules in livers, spleens and peripheral blood were detected using flow cytometry. The lymphomononuclear cells isolated from the livers of transfected mice were further stimulated by HBc-derived peptides and then the frequency and cytokine secretion of HBV-specific CD4+CXCR5+ T cells were detected. We found that the frequency of CXCR5+ in CD4+ T cells was specifically increased; the expression of PD-1 was decreased while the expression of ICOS was increased on intrahepatic CD4+CXCR5+ T cells. Although the frequency of CD19+ B cells was not affected, the expression of PDL-1, ICOSL and IL-21R on B cells was increased in the livers of mice. The frequency of HBV-specific CD4+CXCR5+ T cells and the production of IL-21 by intrahepatic CD4+CXCR5+ T cells of mice with acute HBV infection were increased after stimulation. Furthermore, the expression of function-related molecules of intrahepatic CD4+CXCR5+ T, including Bcl-6, CXCR5, IL-6, IL-6R, IL-21 and IL-4 in the liver was increased during acute HBV infection. In conclusion, the activation of intrahepatic CD4+CXCR5+ T cells and B cells was associated with the clearance of HBV during acute infection.

  15. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells

    PubMed Central

    Waguespack, Yan; Figliozzi, Robert W.; Kharel, Madan K.; Zhang, Qiaojuan; Martin-Caraballo, Miguel

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  16. Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response.

    PubMed Central

    Missale, G; Bertoni, R; Lamonaca, V; Valli, A; Massari, M; Mori, C; Rumi, M G; Houghton, M; Fiaccadori, F; Ferrari, C

    1996-01-01

    The anti-viral T cell response is believed to play a central role in the pathogenesis of hepatitis C virus infection. Since chronic evolution occurs in > 50% of HCV infections, the sequential analysis of the T cell response from the early clinical stages of disease may contribute to define the features of the T cell response associated with recovery or chronic viral persistence. For this purpose, 21 subjects with acute hepatitis C virus infection were sequentially followed for an average time of 44 wk. Twelve patients normalized transaminase values that remained normal throughout the follow-up period; all but two cleared hepatitis C virus-RNA from serum. The remaining nine patients showed persistent viremia and elevated transaminases. Analysis of the peripheral blood T cell proliferative response to core, E1, E2, NS3, NS4, and NS5 recombinant antigens and synthetic peptides showed that responses to all hepatitis C virus antigens, except E1, were significantly more vigorous and more frequently detectable in patients who normalized transaminase levels than in those who did not. By sequential evaluation of the T cell response, a difference between the two groups of patients was already detectable at the very early stages of acute infection and then maintained throughout the follow-up period. The results suggest that the vigor of the T cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection. PMID:8698862

  17. A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen®) in the Clinical Management of Acute Viral Diarrhea in Children

    PubMed Central

    García-Menor, Emilia; García-Marín, Fátima; Vecino-López, Raquel; Horcajo-Martínez, Gloria; de Ibarrondo Guerrica-Echevarría, María-José; Gómez-González, Pedro; Velasco-Ortega, Syra; Suárez-Almarza, Javier; Nieto-Magro, Concepción

    2016-01-01

    This randomized, open-label study evaluated the additional benefits of the synbiotic Prodefen® in the clinical management of acute diarrhea of suspected viral origin in children between 6 months and 12 years of age. Study outcomes included the duration of diarrhea, the recovery from diarrhea, and the tolerability and acceptance of the treatment. The proportion of patients without diarrhea over the study period was greater in the synbiotic group than in the control group at all study time points, showing a statistically significant difference on the fifth day (95% vs 79%, p < 0.001). The duration of diarrhea (median and interquartile range) was reduced by 1 day in the synbiotic-treated patients (3 [2-5] vs 4 [3-5], p = 0.377). The tolerability of the treatment regimen, as evaluated by the parents, was significantly better in those receiving the synbiotic than in the control group. Overall, 96% of the parents of children receiving the synbiotic reported being satisfied to very satisfied with the treatment regimen. The results of this study indicate that the addition of the synbiotic Prodefen® is a well-tolerated and well-accepted approach that provides an additional benefit to the standard supportive therapy in the management of acute viral diarrhea in children. PMID:28229091

  18. Principles of quantitation of viral loads using nucleic acid sequence-based amplification in combination with homogeneous detection using molecular beacons

    PubMed Central

    Weusten, Jos J. A. M.; Carpay, Wim M.; Oosterlaken, Tom A. M.; van Zuijlen, Martien C. A.; van de Wiel, Paul A.

    2002-01-01

    For quantitative NASBA-based viral load assays using homogeneous detection with molecular beacons, such as the NucliSens EasyQ HIV-1 assay, a quantitation algorithm is required. During the amplification process there is a constant growth in the concentration of amplicons to which the beacon can bind while generating a fluorescence signal. The overall fluorescence curve contains kinetic information on both amplicon formation and beacon binding, but only the former is relevant for quantitation. In the current paper, mathematical modeling of the relevant processes is used to develop an equation describing the fluorescence curve as a function of the amplification time and the relevant kinetic parameters. This equation allows reconstruction of RNA formation, which is characterized by an exponential increase in concentrations as long as the primer concentrations are not rate limiting and by linear growth over time after the primer pool is depleted. During the linear growth phase, the actual quantitation is based on assessing the amplicon formation rate from the viral RNA relative to that from a fixed amount of calibrator RNA. The quantitation procedure has been successfully applied in the NucliSens EasyQ HIV-1 assay. PMID:11884645

  19. Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance.

    PubMed

    Back, Helena; Ullman, Karin; Treiberg Berndtsson, Louise; Riihimäki, Miia; Penell, Johanna; Ståhl, Karl; Valarcher, Jean-François; Pringle, John

    2015-09-30

    The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492 (74%) positive for EHV-5. Furthermore, 176 (27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters.

  20. Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

    PubMed Central

    Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

    2016-01-01

    Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

  1. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    PubMed Central

    Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

    2014-01-01

    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

  2. Triclosan and triclosan-loaded liposomal nanoparticles in the treatment of acute experimental toxoplasmosis.

    PubMed

    El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Shereen F; Ramadan, Heba S; Younis, Salwa S

    2015-02-01

    Efficacy of triclosan (TS) and TS-loaded liposomes against the virulent strain of Toxoplasma gondii (T. gondii) was evaluated. Swiss albino mice were intraperitoneally infected with 10(4) tachyzoites of RH HXGPRT(-) strain of T. gondii, then were orally treated with 150 mg/kg TS or 100 mg/kg TS liposomes twice daily for 4 days. Mice mortality, peritoneal and liver parasite burdens, viability, infectivity and ultrastructural changes of peritoneal tachyzoites of infected treated mice were studied, in comparison with those of infected non-treated controls. Drug safety was biochemically assessed by measuring liver enzymes and thyroxin. Both TS and TS liposomes induced significant reduction in mice mortality, parasite burden, viability and infectivity of tachyzoites harvested from infected treated mice. Scanning electron microscopy of treated tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion. Transmission electron microscopy showed that treated tachyzoites were intracellularly distorted, had cytoplasmic vacuolation, discontinuous plasma membranes, nuclear abnormalities and disrupted internal structures. Besides, in TS liposomes-treated subgroup, most tachyzoites were seen intracellularly with complete disintegration of the parasite plasma and nuclear membranes, with complete destruction of the internal structures. Biochemical safety of TS and TS liposomes was proven. Accordingly, TS can be considered as a promising alternative to the standard therapy for treating acute murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use in a lower dose.

  3. Novel Use of Surveillance Data to Detect HIV-Infected Persons with Sustained High Viral Load and Durable Virologic Suppression in New York City

    PubMed Central

    Terzian, Arpi S.; Bodach, Sara D.; Wiewel, Ellen W.; Sepkowitz, Kent; Bernard, Marie-Antoinette; Braunstein, Sarah L.; Shepard, Colin W.

    2012-01-01

    Background Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL) surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA) in New York City (NYC) with sustained high VL (SHVL) and durably suppressed VL (DSVL). Methods/Principal Findings Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU) risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. Conclusions/Significance Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone. PMID:22291892

  4.  Evaluation of serum HBV viral load, transaminases and histological features in chronic HBeAg-negative hepatitis B patients

    PubMed Central

    Esmaeelzadeh, Abbas; Saadatnia, Hassan; Memar, Bahram; Mokhtari Amirmajdi, Elham; Ganji, Azita; Goshayeshi, Ladan; Meshkat, Zahra; Pasdar, Alireza; Vosoughinia, Hassan; Farzanehfar, Mohammadreza; Tehranian, Shahrzad; Ghaffarzadehgan, Kamran; Rajabzadeh, Farnood; Ahadi, Mitra

    2017-01-01

    Aim: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). Background: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. Methods: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled. Alcohol consumption, liver mass, fatty liver and positive results of Anti HDV, Anti HCV or Anti HIV were excluded. The relationship between viral loads, liver enzymes (old and new cutoffs) and histopathological features was analyzed using descriptive and analytic statistical methods. Results: A total of 150 HBeAg-negative CHB (males=110, mean age=38.44±11.34 years) were assessed. ALT had a significant relation with the logarithm of serum HBV-DNA (P<0.0001), grade and stage on liver biopsy (P<0.001, P=0.034, respectively). Serum viral load, AST and ALT were independent predictors of histological grade, age was the only independent predictor of the stage of liver fibrosis. There was a significant relationship between serum ALT and stage of liver fibrosis (P<0.0001) when new cutoff values for ALT were considered. We found that age had a significant relation with histological grade but it showed a reverse relation with ALT levels (P=0.009). Conclusion: In HBeAg-negative CHB, AST had a better prediction for liver necrosis and inflammation. Age could be an independent predictor for liver fibrosis. New cutoff values for ALT had superiority over conventional values to identify higher risk of liver fibrosis. PMID:28331563

  5. Evaluation of Two Techniques for Viral Load Monitoring Using Dried Blood Spot in Routine Practice in Vietnam (French National Agency for AIDS and Hepatitis Research 12338)

    PubMed Central

    Taieb, Fabien; Tram, Tran Hong; Ho, Hien Thi; Pham, Van Anh; Nguyen, Lan; Pham, Ban Hien; Tong, Linh An; Tuaillon, Edouard; Delaporte, Eric; Nguyen, Anh Tuan; Bui, Duc Duong; Do, NhanThi; Madec, Yoann

    2016-01-01

    Background. Although it is the best method to detect early therapeutic failure, viral load (VL) monitoring is still not widely available in many resource-limited settings because of difficulties in specimen transfer, personnel shortage, and insufficient laboratory infrastructures. Dried blood spot (DBS) use, which was introduced in the latest World Health Organization recommendations, can overcome these difficulties. This evaluation aimed at validating VL measurement in DBS, in a laboratory without previous DBS experience and in routine testing conditions. Methods. Human immunodeficiency virus (HIV)-infected adults were observed in a HIV care site in Hanoi, and each patient provided 2 DBS cards with whole blood spots and 2 plasma samples. Viral load was measured in DBS and in plasma using the COBAS Ampliprep/TaqMan and the Abbott RealTime assays. To correctly identify those with VL ≥ 1000 copies/mL, sensitivity and specificity were estimated. Results. A total of 198 patients were enrolled. With the Roche technique, 51 plasma VL were ≥1000 copies/mL; among these, 28 presented a VL in DBS that was also ≥1000 copies/mL (sensitivity, 54.9; 95% confidence interval [CI], 40.3–68.9). On the other hand, all plasma VL < 1000 copies/mL were also <1000 copies/mL in DBS (specificity, 100; 95% CI, 97.5–100). With the Abbott technique, 45 plasma VL were ≥1000 copies/mL; among these, 42 VL in DBS were also ≥1000 copies/mL (sensitivity, 93.3%; 95% CI, 81.7–98.6); specificity was 94.8 (95% CI, 90.0–97.7). Conclusions. The Abbott RealTime polymerase chain reaction assay provided adequate VL results in DBS, thus allowing DBS use for VL monitoring. PMID:27704001

  6. Short Communication: Atazanavir-Based Therapy Is Associated with Higher Hepatitis C Viral Load in HIV Type 1-Infected Subjects with Untreated Hepatitis C

    PubMed Central

    Rivero-Juarez, Antonio; Mira, Jose A.; Santos-Gil, Ignacio; Lopez-Cortes, Luis F.; Girón-Gonzalez, Jose A; Marquez, Manuel; Merino, Dolores; Tellez, Francisco; Caruz, Antonio; Pineda, Juan A

    2013-01-01

    Abstract We assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal–Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9–6.8) log IU/ml] than those who received LPV [6.1 (5.5–6.5) log IU/ml], EFV [6.1 (5.6–6.4) log IU/ml], NVP [5.8 (5.5–5.9) log IU/ml], or other PIs [6.1 (5.7–6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients. PMID:22966845

  7. Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

    PubMed

    Bell, H; Hellum, K; Harthug, S; Maeland, A; Ritland, S; Myrvang, B; von der Lippe, B; Raknerud, N; Skaug, K; Gutigard, B G; Skjaerven, R; Prescott, L E; Simmonds, P

    1997-01-01

    Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

  8. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein

    PubMed Central

    Sainz, Bruno; Mossel, Eric C.; Gallaher, William R.; Wimley, William C.; Peters, C.J.; Wilson, Russell B.; Garry, Robert F.

    2008-01-01

    Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002–2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40–70% at concentrations of 15–30 μM. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2–4 μM) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions. PMID:16616792

  9. The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.

    PubMed

    El Kholy, A A; Mostafa, N A; Ali, A A; Soliman, M M S; El-Sherbini, S A; Ismail, R I; El Basha, N; Magdy, R I; El Rifai, N; Hamed, D H

    2016-10-01

    Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

  10. Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection

    PubMed Central

    2013-01-01

    Background HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). Findings Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint. Conclusions The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function. PMID:24245727

  11. Acute bovine viral diarrhea associated with extensive mucosal lesions, high morbidity, and mortality in a commercial feedlot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2008, a northwest Texas feedlot underwent an outbreak of bovine viral diarrhea virus (BVDV) disease causing high morbidity and mortality involving two lots of calves (Lots A and B). Severe mucosal surface lesions were observed grossly in the oral cavity, larynx and esophagus. Mucosal lesions vari...

  12. Acute immunological responses to a combined viral-bacterial respiratory disease challenge in feedlot heifers supplemented with yeast

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune responses to a combined viral-bacterial respiratory challenge. Thirty-two beef heifers (325 +/- 19.2 kg BW) were selected and randomly assigned to one of two treatments, and fed for 3...

  13. HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype

    PubMed Central

    Moura, Tuane Carolina Ferreira; Araújo, Mauro Sérgio; Freitas Queiroz, Maria Alice; Conde, Simone Regina Souza da Silva; Demachki, Sâmia; Martins-Feitosa, Rosimar Neris; Machado, Luiz Fernando Almeida; Cayres-Vallinoto, Izaura Maria Vieira; Ishak, Ricardo

    2017-01-01

    The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

  14. Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus

    PubMed Central

    Hosie, Margaret J.; Dunsford, Thomas; Klein, Dieter; Willett, Brian J.; Cannon, Celia; Osborne, Robert; MacDonald, Julie; Spibey, Norman; Mackay, Nancy; Jarrett, Oswald; Neil, James C.

    2000-01-01

    It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIVPET) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIVAM6 and FIVGL8. This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIVGL8-infected cats. In contrast, DNA vaccines based on either FIVPET or FIVGL8, which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIVPET but had no measurable effect on virus load when the infecting virus was FIVGL8. These results indicate that the more virulent FIVGL8 is intrinsically more resistant to vaccinal immunity than the FIVPET strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development. PMID:11000209

  15. Acute sodium bicarbonate loading has negligible effects on resting and exercise blood pressure but causes gastrointestinal distress.

    PubMed

    Kahle, Laura E; Kelly, Patrick V; Eliot, Kathrin A; Weiss, Edward P

    2013-06-01

    Oral ingestion of sodium bicarbonate (bicarbonate loading) has acute ergogenic effects on short-duration, high-intensity exercise. Because sodium bicarbonate is 27% sodium, ergogenic doses (ie, 300 mg∙kg⁻¹) result in sodium intakes well above the Dietary Reference Intakes upper limit of 2300 mg/day. Therefore, it is conceivable that bicarbonate loading could have hypertensive effects. Therefore, we performed a double-blind crossover trial to evaluate the hypothesis that bicarbonate loading increases resting and exercise blood pressure (BP). A secondary hypothesis was that bicarbonate loading causes gastrointestinal distress. Eleven endurance-trained men and women (exercise frequency, 4.6 ± 0.4 sessions/wk; duration, 65 ± 6 min/session) underwent testing on two occasions in random sequence: once after bicarbonate loading (300 mg∙kg⁻¹) and once after placebo ingestion. BP and heart rate were measured before bicarbonate or placebo consumption, 30 minutes after consumption, during 20 min of steady state submaximal cycling exercise, and during recovery. Bicarbonate loading did not affect systolic BP during rest, exercise, or recovery (P = .38 for main treatment effect). However, it resulted in modestly higher diastolic BP (main treatment effect, +3.3 ± 1.1 mmHg, P = .01) and higher heart rate (main treatment effect, +10.1 ± 2.4 beats per minute, P = .002). Global ratings of gastrointestinal distress severity (0-10 scale) were greater after bicarbonate ingestion (5.1 ± 0.5 vs 0.5 ± 0.2, P < .0001). Furthermore, 10 of the 11 subjects (91%) experienced diarrhea, 64% experience bloating and thirst, and 45% experienced nausea after bicarbonate loading. In conclusion, although a single, ergogenic dose of sodium bicarbonate does not appear to have acute, clinically important effects on resting or exercise BP, it does cause substantial gastrointestinal distress.

  16. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading.

    PubMed

    Theodorou, A S; Cooke, C B; King, R F; Hood, C; Denison, T; Wainwright, B G; Havenetidis, K

    1999-11-01

    We investigated the effect of an acute creatine loading (25 g per day for 4 days) and longer-term creatine supplementation (5 g of creatine or 5 g of placebo per day for 2 months) on the performance of 22 elite swimmers during maximal interval sessions. After the acute creatine loading, the mean of the average interval swim times for all swimmers (n = 22) improved (44.3+/-16.5 s before vs. 43.7+/-16.3 s after supplementation; P<0.01). Three of the 22 swimmers did not respond positively to supplementation. After 2 months of longer-term creatine supplementation or placebo, neither group showed a significant change in swimming performance (38.7+/-13.5 s before vs. 38.7+/-14.1 s after for the creatine group; 48.7+/-18.0 s before vs. 48.7+/-18.1 s after for the placebo group). We conclude that, in elite swimmers, 4 days of acute creatine loading improves swimming performance significantly when assessed by maximal interval sessions. However, longer-term supplementation for 2 months (5 g of creatine per day) did not benefit significantly the creatine group compared with the placebo group.

  17. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

    PubMed Central

    Gill, Upkar S.; Peppa, Dimitra; Micco, Lorenzo; Singh, Harsimran D.; Carey, Ivana; Foster, Graham R.; Maini, Mala K.; Kennedy, Patrick T. F.

    2016-01-01

    NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB. PMID:27487232

  18. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women

    PubMed Central

    Borgdorff, Hanneke; Tsivtsivadze, Evgeni; Verhelst, Rita; Marzorati, Massimo; Jurriaans, Suzanne; Ndayisaba, Gilles F; Schuren, Frank H; van de Wijgert, Janneke HHM

    2014-01-01

    Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting ‘Rwanda') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (Ptrend=0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding. PMID:24599071

  19. Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania.

    PubMed

    Kilewo, Charles; Karlsson, Katarina; Swai, Andrew; Massawe, Augustine; Lyamuya, Eligius; Mhalu, Fred; Biberfeld, Gunnel

    2005-04-15

    The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in

  20. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  1. Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study

    PubMed Central

    Gill, Michelle M.; Hoffman, Heather J.; Bobrow, Emily A.; Mugwaneza, Placidie; Ndatimana, Dieudonne; Ndayisaba, Gilles F.; Baribwira, Cyprien; Guay, Laura; Asiimwe, Anita

    2016-01-01

    There are limited viral load (VL) data available from programs implementing “Option B+,” lifelong antiretroviral treatment (ART) to all HIV-positive pregnant and postpartum women, in resource-limited settings. Extent of viral suppression from a prevention of mother-to-child transmission of HIV program in Rwanda was assessed among women enrolled in the Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) Study. ARV drug resistance testing was conducted on women with VL>2000 copies/ml. In April 2013-January 2014, 608 pregnant or early postpartum HIV-positive women were enrolled in 14 facilities. Factors associated with detectable enrollment VL (>20 copies/ml) were examined using generalized estimating equations. The most common antiretroviral regimen (56.7%, 344/607) was tenofovir/lamivudine/efavirenz. Median ART duration was 13.5 months (IQR 3.0–48.8); 76.1% of women were on ART at first antenatal visit. Half of women (315/603) had undetectable RNA-PCR VL and 84.6% (510) had <1,000 copies/ml. Detectable VL increased among those on ART > 36 months compared to those on ART 4–36 months (72/191, 37.7% versus 56/187, 29.9%), though the difference was not significant. The odds of having detectable enrollment VL decreased significantly as duration on ART at enrollment increased (AOR = 0.99, 95% CI: 0.9857, 0.9998, p = 0.043). There was a higher likelihood of detectable VL for women with lower gravidity (AOR = 0.90, 95% CI: 0.84, 0.97, p = 0.0039), no education (AOR = 2.25, (95% CI: 1.37, 3.70, p = 0.0004), nondisclosure to partner (AOR = 1.97, 95% CI: 1.21, 3.21, p = 0.0063) and side effects (AOR = 2.63, 95% CI: 1.72, 4.03, p<0.0001). ARV drug resistance mutations were detected in all of the eleven women on ART > 36 months with genotyping available. Most women were receiving ART at first antenatal visit, with relatively high viral suppression rates. Shorter ART duration was associated with higher VL, with a concerning increasing

  2. Effects of acute creatine loading with or without carbohydrate on repeated bouts of maximal swimming in high-performance swimmers.

    PubMed

    Theodorou, Apostolos S; Havenetidis, Konstantinos; Zanker, Cathy L; O'Hara, John P; King, Roderick F G J; Hood, Colin; Paradisis, Giorgios; Cooke, Carlton B

    2005-05-01

    The addition of carbohydrate (CHO) to an acute creatine (Cr) loading regimen has been shown to increase muscle total creatine content significantly beyond that achieved through creatine loading alone. However, the potential ergogenic effects of combined Cr and CHO loading have not been assessed. The purpose of this study was to compare swimming performance, assessed as mean swimming velocity over repeated maximal intervals, in high-performance swimmers before and after an acute loading regimen of either creatine alone (Cr) or combined creatine and carbohydrate (Cr + CHO). Ten swimmers (mean +/- SD of age and body mass: 17.8 +/- 1.8 years and 72.3 +/- 6.8 kg, respectively) of international caliber were recruited and were randomized to 1 of 2 groups. Each swimmer ingested five 5 g doses of creatine for 4 days, with the Cr + CHO group also ingesting approximately 100 g of simple CHO 30 minutes after each dose of creatine. Performance was measured on 5 separate occasions: twice at "baseline" (prior to intervention, to assess the repeatability of the performance test), within 48 hours after intervention, and then 2 and 4 weeks later. All subjects swam faster after either dietary loading regimen (p < 0.01, both regimens); however, there was no difference in the extent of improvement of performance between groups. In addition, all swimmers continued to produce faster swim times for up to 4 weeks after intervention. Our findings suggest that no performance advantage was gained from the addition of carbohydrate to a creatine-loading regimen in these high-caliber swimmers.

  3. Comparison of the health-related quality of life, CD4 count and viral load of AIDS patients and people with HIV who have been on treatment for 12 months in rural South Africa

    PubMed Central

    Igumbor, Jude; Stewart, Aimee; Holzemer, William

    2013-01-01

    This study compared the level of CD4 count, viral load and health-related quality of life (HRQOL) between treatment-naïve AIDS patients and a cohort of people living with HIV who have been on treatment for 12 months. This study is based on a secondary data analysis of the records of 642 people with HIV consisting of 311 treatment-naïve AIDS patients and 331 people with HIV who have been on treatment for 12 months. The study findings are mostly presented in tables and analysed using the t-test to compare HRQOL scores, CD4 count and viral load in the two groups. The study generally noted poor financial capacity and low activity tolerance among the participants. Significant changes were noted in all the domains of HRQOL compared between the treatment-naïve patients and the 12 months treatment cohort. In the same manner, the median CD4 cell count and viral load differed significantly between both groups. The treatment-naïve and the 12 months treatment cohorts consistently reported much lower quality of life scores in the level of dependence domain which includes the measures of mobility, activity of daily living, dependence on medication and work capacity. There were little or no associations between the biomedical markers (CD4 count and viral load) and HRQOL indicators. However, the quality of life tended to increase with increase in the CD4 cell count. The poor to no association between the biomedical markers and HRQOL indicators show that these cannot be direct proxies of each other and that the CD4 cell count and viral load alone may be inadequate eligibility criteria for social support. PMID:23777555

  4. Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

    PubMed Central

    Peterson, Ingrid; Bar-Zeev, Naor; Kennedy, Neil; Ho, Antonia; Newberry, Laura; SanJoaquin, Miguel A.; Menyere, Mavis; Alaerts, Maaike; Mapurisa, Gugulethu; Chilombe, Moses; Mambule, Ivan; Lalloo, David G.; Anderson, Suzanne T.; Katangwe, Thembi; Cunliffe, Nigel; Nagelkerke, Nico; McMorrow, Meredith; Widdowson, Marc-Allain; French, Neil; Everett, Dean; Heyderman, Robert S.

    2017-01-01

    Background We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. Methods From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. Results Hospital-attended influenza virus–positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)–infected children aged 5–9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4–3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3–3.0) and rainy season (aRR, 2.4; 95% CI, 1.6–3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. Conclusions Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance. PMID:27630199

  5. Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

    PubMed

    Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

    2011-10-01

    This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution.

  6. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  7. Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4+ Level

    PubMed Central

    de Freitas, Vera Lúcia Teixeira; da Silva, Sheila Cristina Vicente; Sartori, Ana Marli; Bezerra, Rita Cristina; Westphalen, Elizabeth Visone Nunes; Molina, Tatiane Decaris; Teixeira, Antonio R. L.; Ibrahim, Karim Yaqub; Shikanai-Yasuda, Maria Aparecida

    2011-01-01

    Background Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4+ cells or the CD4+/CD8+ ratio. Conclusions qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4+ cells/mm3 and the CD4+/CD8+ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy. PMID

  8. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women

    PubMed Central

    Ondoa, Pascale; Gautam, Raju; Rusine, John; Lutter, Rene; Jurriaans, Suzanne; Kootstra, Neeltje; Karita, Etienne; van de Wijgert, Janneke

    2015-01-01

    Background Genital viral load (GVL) is the main determinant of sexual transmission of human immune-deficiency virus (HIV). The effect of antiretroviral therapy (ART) on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda. Materials and Methods All participants were evaluated for GVL, plasma viral load (PVL), CD4 count, various sexually-transmitted infections (STIs) at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥40copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate. Results 96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15) and at month 12 with MIP-1β (95% CI 0.96-21.32) after controlling for baseline GVL, PVL and month 12 IL-8. Conclusion Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART. PMID:26010956

  9. Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard.

    PubMed

    Semenova, Touyana; Lupo, Julien; Alain, Sophie; Perrin-Confort, Gwladys; Grossi, Laurence; Dimier, Julie; Epaulard, Olivier; Morand, Patrice; Germi, Raphaële

    2016-07-01

    The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases.

  10. Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard

    PubMed Central

    Semenova, Touyana; Lupo, Julien; Alain, Sophie; Perrin-Confort, Gwladys; Grossi, Laurence; Dimier, Julie; Epaulard, Olivier; Morand, Patrice

    2016-01-01

    The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases. PMID:27076661

  11. Vaccination with inactivated virus but not viral DNA reduces virus load following challenge with a heterologous and virulent isolate of feline immunodeficiency virus.

    PubMed

    Hosie, M J; Dunsford, T; Klein, D; Willett, B J; Cannon, C; Osborne, R; Macdonald, J; Spibey, N; Mackay, N; Jarrett, O; Neil, J C

    2000-10-01

    It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIV(PET)) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIV(AM6) and FIV(GL8). This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIV(GL8)-infected cats. In contrast, DNA vaccines based on either FIV(PET) or FIV(GL8), which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIV(PET) but had no measurable effect on virus load when the infecting virus was FIV(GL8). These results indicate that the more virulent FIV(GL8) is intrinsically more resistant to vaccinal immunity than the FIV(PET) strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.

  12. Acute effects of a loaded warm-up protocol on change of direction speed in professional badminton players.

    PubMed

    Maloney, Sean J; Turner, Anthony N; Miller, Stuart

    2014-10-01

    It has previously been shown that a loaded warm-up may improve power performances. We examined the acute effects of loaded dynamic warm-up on change of direction speed (CODS), which had not been previously investigated. Eight elite badminton players participated in three sessions during which they performed vertical countermovement jump and CODS tests before and after undertaking the dynamic warm-up. The three warm-up conditions involved wearing a weighted vest (a) equivalent to 5% body mass, (b) equivalent to 10% body mass, and (c) a control where a weighted vest was not worn. Vertical jump and CODS performances were then tested at 15 seconds and 2, 4, and 6 minutes post warm-up. Vertical jump and CODS significantly improved following all warm-up conditions (P < .05). Post warm-up vertical jump performance was not different between conditions (P = .430). Post warm-up CODS was significantly faster following the 5% (P = .02) and 10% (P < .001) loaded conditions compared with the control condition. In addition, peak CODS test performances, independent of recovery time, were faster than the control condition following the 10% loaded condition (P = .012). In conclusion, the current study demonstrates that a loaded warm-up augmented CODS, but not vertical jump performance, in elite badminton players.

  13. Evaluation of viral load thresholds for predicting new WHO Stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy

    PubMed Central

    Siberry, George K; Harris, D. Robert; Oliveira, Ricardo Hugo; Krauss, Margot R.; Hofer, Cristina B.; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C.; Abreu, Thalita; Negra, Marinella Della; Mofenson, Lynne M.; Hazra, Rohan

    2012-01-01

    Background This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly-active antiretroviral therapy (HAART). Methods Cox proportional hazards modeling was used to assess the adjusted risk of World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥ 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies/mL, with model fit evaluated on the basis of the minimum Akaike Information Criterion (AIC) value, a standard model fit statistic. Results Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cutpoints of > 2600 copies/mL and > 32,000 copies/mL corresponded to the lowest AIC values and were associated with the highest hazard ratios [2.0 (p = 0.015) and 2.1 (p = 0.0058), respectively] for WHO events. Conclusions In HIV-infected Latin American children on stable HAART, two distinct VL thresholds (> 2,600 copies/mL and > 32,000 copies/mL) were identified for predicting children at significantly increased risk of HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors. PMID:22343177

  14. A Self-Reported Adherence Measure to Screen for Elevated HIV Viral Load in Pregnant and Postpartum Women on Antiretroviral Therapy

    PubMed Central

    Brittain, Kirsty; Mellins, Claude A.; Zerbe, Allison; Remien, Robert H.; Abrams, Elaine J.; Myer, Landon; Wilson, Ira B.

    2016-01-01

    Maternal adherence to antiretroviral therapy (ART) is a concern and monitoring adherence presents a significant challenge in low-resource settings. We investigated the association between self-reported adherence, measured using a simple three-item scale, and elevated viral load (VL) among HIV-infected pregnant and postpartum women on ART in Cape Town, South Africa. This is the first reported use of this scale in a non-English speaking setting and it achieved good psychometric characteristics (Cronbach α = 0.79). Among 452 women included in the analysis, only 12 % reported perfect adherence on the self-report scale, while 92 % had a VL <1000 copies/mL. Having a raised VL was consistently associated with lower median adherence scores and the area under the curve for the scale was 0.599, 0.656 and 0.642 using a VL cut-off of ≥50, ≥1000 and ≥10000 copies/mL, respectively. This simple self-report adherence scale shows potential as a first-stage adherence screener in this setting. Maternal adherence monitoring in low resource settings requires attention in the era of universal ART, and the value of this simple adherence scale in routine ART care settings warrants further investigation. PMID:27278548

  15. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials.

    PubMed

    Simoni, Jane M; Pearson, Cynthia R; Pantalone, David W; Marks, Gary; Crepaz, Nicole

    2006-12-01

    Adherence to highly active antiretroviral therapy (HAART) is generally suboptimal, limiting the effectiveness of HAART. This meta-analytic review examined whether behavioral interventions addressing HAART adherence are successful in increasing the likelihood of a patient attaining 95% adherence or an undetectable HIV-1 RNA viral load (VL). We searched electronic databases from January 1996 to September 2005, consulted with experts in the field, and hand searched reference sections from relevant articles. Nineteen studies (with a total of 1839 participants) met the selection criteria of describing a randomized controlled trial among adults evaluating a behavioral intervention with HAART adherence or VL as an outcome. Random-effects models indicated that across studies, participants in the intervention arm were more likely than those in the control arm to achieve 95% adherence (odds ratio [OR] = 1.50, 95% confidence interval [CI]: 1.16 to 1.94); the effect was nearly significant for undetectable VL (OR = 1.25; 95% CI: 0.99 to 1.59). The intervention effect for 95% adherence was significantly stronger in studies that used recall periods of 2 weeks or 1 month (vs.

  16. Effects of different accentuated eccentric loads on acute neuromuscular, growth hormone, and blood lactate responses during a hypertrophic protocol.

    PubMed

    Ojasto, Timo; Häkkinen, Keijo

    2009-05-01

    This study monitored acute neuromuscular responses and growth hormone (GH) and blood lactate (La) concentrations in the eccentric-concentric (ECC-CON) hypertrophic protocol by using various dynamic accentuated external resistance (DAER) loads in the bench press exercise. Male subjects (age = 32 +/- 4 years; n = 11) performed 4 sets of 10 repetitions with 2 minutes of recovery between the sets. The loads were 70, 80, 90, and 100% of 1 repetition maximum (RM) for the ECC phase, whereas 70% RM was constantly used for the CON phase. Electromyographic activity (EMG), ECC, CON, and isometric (ISOM) forces, serum GH and blood La, were measured at pre- and postloading. Significant reductions occurred in ISOM and CON pre- to postforces in all loading conditions (p < 0.01 - 0.001). Pre- to postchange in blood La in the 90/70% condition (9.5 +/- 2.3 mmolxL) was greater (p < 0.05) than in the control 70/70% condition (7.7 +/- 1.1 mmolxL). The highest individual pre- to postchange in blood La was larger after the 90/70% (p < 0.001) condition compared with the 70/70% condition. The post-GH concentration in the 90/70% loading was 8.7 +/- 1.9 microgxL and in the abstract. --> 3.5 +/- 1.5 microgxL in the control condition, but the difference did not reach statistical significance. ECC EMG of the agonists increased with the increase in load but significantly only in the deltoid anterior (p < 0.01). A significant relationship was observed between the "optimal" ECC load and 1RM per body mass (BM)-ratio (r = 0.85; p < 0.05). The findings suggest that the acute metabolic and GH responses in the 90/70% condition were more favourable compared with the 70/70% condition, and a significant correlation between the optimal ECC load and 1RM per BM-ratio was observed. The findings can be applied into practice in designing exercise protocols in training for muscle hypertrophy and suggest the importance of individualized load selection for DAER exercises.

  17. Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases

    PubMed Central

    Hernández, Carolina; Cucunubá, Zulma; Flórez, Carolina; Olivera, Mario; Valencia, Carlos; Zambrano, Pilar; León, Cielo; Ramírez, Juan David

    2016-01-01

    Background The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases. Methodology/Principal Findings Samples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml). Conclusions/Significance The molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic

  18. Acute Stress and Perceptual Load Consume the Same Attentional Resources: A Behavioral-ERP Study

    PubMed Central

    Tiferet-Dweck, Chen; Hensel, Michael; Kirschbaum, Clemens; Tzelgov, Joseph; Friedman, Alon; Salti, Moti

    2016-01-01

    Stress and perceptual load affect selective attention in a paradoxical manner. They can facilitate selectivity or disrupt it. This EEG study was designed to examine the reciprocal relations between stress, load and attention. Two groups of subjects, one that performed the Trier Social Stress Test (TSST), and a control group, were asked to respond to a target letter under low and high perceptual load in the absence or presence of a distractor. In the control group, the distractor increased response times (RTs) for high and low load. In the TSST group, distractor increased RTs under low load only. ERPs showed that distractor’s presentation attenuated early visual P1 component and shortened its latency. In the TSST group, distractor reduced P1 component under high load but did not affect its latency. Source localization demonstrated reduced activation in V1 in response to distractors presence in the P1 time window for the TSST group compared to the control group. A behavioral replication revealed that in the TSST group distractors were less perceived under high load. Taken together, our results show that stress and perceptual load affect selectivity through the early stages of visual processing and might increase selectivity in a manner that would block conscious perception of irrelevant stimuli. PMID:27196027

  19. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence.

    PubMed

    Schulze Zur Wiesch, Julian; Ciuffreda, Donatella; Lewis-Ximenez, Lia; Kasprowicz, Victoria; Nolan, Brian E; Streeck, Hendrik; Aneja, Jasneet; Reyor, Laura L; Allen, Todd M; Lohse, Ansgar W; McGovern, Barbara; Chung, Raymond T; Kwok, William W; Kim, Arthur Y; Lauer, Georg M

    2012-01-16

    Vigorous proliferative CD4(+) T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4(+) T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4(+) T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4(+) T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4(+) T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4(+) T cells. Instead, broadly directed HCV-specific CD4(+) T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4(+) T cell responses through antiviral therapy.

  20. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  1. Changes in MR Relaxation Times of the Meniscus With Acute Loading: An In Vivo Pilot Study in Knee Osteoarthritis

    PubMed Central

    Subburaj, Karupppasamy; Souza, Richard B.; Wyman, Bradley T.; Le Graverand-Gastineau, Marie-Pierre Hellio; Li, Xiaojuan; Link, Thomas M.; Majumdar, Sharmila

    2014-01-01

    Purpose To prospectively evaluate changes in T1ρ and T2 relaxation times in the meniscal body with acute loading using MRI in osteoarthritic knees and to compare these findings with those of age-matched healthy controls. Materials and Methods Female subjects above 40 years of age with (N1 = 20) and without osteoarthritis (OA) (N2 = 10) were imaged on a 3 Tesla MR scanner using a custom made loading device. MR images were acquired, with the knee flexed at 20°, with and without a compressive load of 50% of the subject's bodyweight. The subjects were categorized based on the radiographic evidence of OA. Three different zones (outer, middle, and inner) of meniscus body were defined (each occupying 1/3rd the width). After adjusting for age and body mass index in the general linear regression model, repeated measures analysis of variance was used to detect significant differences in T1ρ and T2 with and without loading. Results In the unloaded condition, the average T1ρ and T2 times were elevated in the outer and middle zones of the medial meniscus in OA subjects compared with the controls. In the loaded condition, T1ρ and T2 times of the outer zone of the medial meniscus was significantly elevated in OA subjects compared with controls. Finally the change (from unloaded to loaded) was significantly higher in controls than OA subjects (15.1% versus 8.3%; P = 0.039 for ΔT1ρ, and 11.5% versus 6.9%, P = 0.049 for ΔT2). Conclusion These findings suggest that while the OA process appears to affect the relaxation times of all regions within the meniscus, it may affect some regions sooner or to a greater degree. Furthermore, the differences in the change in relaxation times between unloaded and loaded conditions may reveal evidence about load transmission failure of the outer zone of the medial meniscus in subjects with knee OA. It is possible that these metrics (ΔT1ρ and ΔT2) may be valuable as an early biomechanical biomarker, which could be used to predict load

  2. Comparison of the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test v1.0 with v2.0 in HIV-1 viral load quantification.

    PubMed

    Tung, Yi-Ching; Ke, Liang-Yin; Lu, Po-Liang; Lin, Kuei-Hsiang; Lee, Su-Chen; Lin, Yi-Ying; Chou, Li-Chiu; Tsai, Wen-Chan

    2015-04-01

    Roche modified the COBAS AmpliPrep/COBAS TaqMan human immunodeficiency virus type 1 (HIV-1) test version 1.0 (CAP/CTM v1.0), resulting in the COBAS AmpliPrep/COBAS TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0). The aim of this study was to evaluate the performance of the CAP/CTM v2.0 and to compare this performance with that of the CAP/CTM v1.0. The study was conducted in a small local study group in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. A total of 86 plasma samples from HIV-1-seropositive patients were tested using the two assays. The correlation and concordance of results between the two assays were calculated. The CAP/CTM v2.0 generated higher values than did the CAP/CTM v1.0, and five samples (5.8%) yielded a difference of > 1 log10 copies/mL. In addition, our data show that CAP/CTM v1.0 and CAP/CTM v2.0 yielded relatively consistent values for 23 samples with low viral loads (< 200 copies/mL). Furthermore, when viral loads were in a medium range (2-5 log10 copies/mL), the results of the two assays were more compatible. This study shows a good correlation between CAP/CTM v1.0 and v2.0 in HIV-1 viral load measurement. Further attention must be paid to those cases in which measured viral loads present larger differences between the two assays.

  3. Second-generation Cobas AmpliPrep/Cobas TaqMan HCV quantitative test for viral load monitoring: a novel dual-probe assay design.

    PubMed

    Zitzer, Heike; Heilek, Gabrielle; Truchon, Karine; Susser, Simone; Vermehren, Johannes; Sizmann, Dorothea; Cobb, Bryan; Sarrazin, Christoph

    2013-02-01

    Hepatitis C virus (HCV) RNA viral load (VL) monitoring is a well-established diagnostic tool for the management of chronic hepatitis C patients. HCV RNA VL results are used to make treatment decisions with the goal of therapy to achieve an undetectable VL result. Therefore, a sensitive assay with high specificity in detecting and accurately quantifying HCV RNA across genotypes is critical. Additionally, a lower sample volume requirement is desirable for the laboratory and the patient. This study evaluated the performance characteristics of a second-generation real-time PCR assay, the Cobas AmpliPrep/Cobas TaqMan HCV quantitative test, version 2.0 (CAP/CTM HCV test, v2.0), designed with a novel dual-probe approach and an optimized automated extraction and amplification procedure. The new assay demonstrated a limit of detection and lower limit of quantification of 15 IU/ml across all HCV genotypes and was linear from 15 to 100,000,000 IU/ml with high accuracy (<0.2-log(10) difference) and precision (standard deviation of 0.04 to 0.22 log(10)). A specificity of 100% was demonstrated with 600 HCV-seronegative specimens without cross-reactivity or interference. Correlation to the Cobas AmpliPrep/Cobas TaqMan HCV test (version 1) was good (n = 412 genotype 1 to 6 samples, R(2) = 0.88; R(2) = 0.94 without 105 genotype 4 samples). Paired plasma and serum samples showed similar performance (n = 25, R(2) = 0.99). The sample input volume was reduced from 1 to 0.65 ml in the second version. The CAP/CTM HCV test, v2.0, demonstrated excellent performance and sensitivity across all HCV genotypes with a smaller sample volume. The new HCV RNA VL assay has performance characteristics that make it suitable for use with currently available direct-acting antiviral agents.

  4. Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

    PubMed Central

    2010-01-01

    Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

  5. Elevated granzyme B+ B-cell level in SIV-infection correlate with viral load and low CD4 T-cell count

    PubMed Central

    Kotb, Ahmad; Klippert, Antonina; Daskalaki, Maria; Sauermann, Ulrike; Stahl-Hennig, Christiane; Neumann, Berit

    2017-01-01

    Granzyme B-expressing (GrB+) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB+ B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts. When investigating GrB+ B cells in different compartments, levels were highest in blood, spleen and bone marrow, but considerably lower in lymph nodes and tonsils. Analysis of expression of various surface markers on this particular B-cell subset in SIV-infected macaques revealed differences between the phenotype in macaques and in humans. GrB+ B cells in SIV-infected rhesus macaques exhibit an elevated expression of CD5, CD10, CD25 and CD27, while expression of CD19, CD185 and HLA-DR is reduced. In contrast to human GrB+ B cells, we did not observe a significantly increased expression of CD43 and CD86. B-cell receptor stimulation in combination with IL-21 of purified B cells from healthy animals led to the induction of GrB expression. Furthermore, initial functional analyses indicated a regulatory role on T-cell proliferation. Overall, our data pave the way for longitudinal analyses including studies on the functionality of GrB+ B cells in the nonhuman primate model for AIDS. PMID:27779180

  6. Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection

    PubMed Central

    Noh, Ran; Lee, Doo Hyuck; Kwon, Byoung Woon; Kim, Yong Hyun

    2016-01-01

    Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality. PMID:27656205

  7. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.

    PubMed

    Towner, Jonathan S; Rollin, Pierre E; Bausch, Daniel G; Sanchez, Anthony; Crary, Sharon M; Vincent, Martin; Lee, William F; Spiropoulou, Christina F; Ksiazek, Thomas G; Lukwiya, Mathew; Kaducu, Felix; Downing, Robert; Nichol, Stuart T

    2004-04-01

    The largest outbreak on record of Ebola hemorrhagic fever (EHF) occurred in Uganda from August 2000 to January 2001. The outbreak was centered in the Gulu district of northern Uganda, with secondary transmission to other districts. After the initial diagnosis of Sudan ebolavirus by the National Institute for Virology in Johannesburg, South Africa, a temporary diagnostic laboratory was established within the Gulu district at St. Mary's Lacor Hospital. The laboratory used antigen capture and reverse transcription-PCR (RT-PCR) to diagnose Sudan ebolavirus infection in suspect patients. The RT-PCR and antigen-capture diagnostic assays proved very effective for detecting ebolavirus in patient serum, plasma, and whole blood. In samples collected very early in the course of infection, the RT-PCR assay could detect ebolavirus 24 to 48 h prior to detection by antigen capture. More than 1,000 blood samples were collected, with multiple samples obtained from many patients throughout the course of infection. Real-time quantitative RT-PCR was used to determine the viral load in multiple samples from patients with fatal and nonfatal cases, and these data were correlated with the disease outcome. RNA copy levels in patients who died averaged 2 log(10) higher than those in patients who survived. Using clinical material from multiple EHF patients, we sequenced the variable region of the glycoprotein. This Sudan ebolavirus strain was not derived from either the earlier Boniface (1976) or Maleo (1979) strain, but it shares a common ancestor with both. Furthermore, both sequence and epidemiologic data are consistent with the outbreak having originated from a single introduction into the human population.

  8. B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

    PubMed

    Oballah, Peter; Flach, Britta; Eller, Leigh A; Eller, Michael A; Ouma, Benson; de Souza, Mark; Kibuuka, Hannah N; Wabwire-Mangen, Fred; Brown, Bruce K; Michael, Nelson L; Robb, Merlin L; Montefiori, David; Polonis, Victoria R

    2011-01-01

    To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.

  9. Partner Disclosure of PrEP Use and Undetectable Viral Load on Geosocial Networking Apps: Frequency of Disclosure and Decisions about Condomless Sex

    PubMed Central

    Newcomb, Michael E.; Mongrella, Melissa C.; Weis, Benjamin; McMillen, Samuel J.; Mustanski, Brian

    2015-01-01

    Background Recent advances in biomedical prevention strategies, including pre-exposure prophylaxis (PrEP) and achieving an undetectable viral load (UVL) among HIV-infected persons, show promise in curbing the rising incidence of HIV among men who have sex with men (MSM) in the United States. This mixed methods study aimed to investigate the frequency with which MSM encounter potential sex partners on geosocial networking apps who disclose biomedical prevention use, and how MSM make decisions about condom use after these disclosures. Method Participants were recruited via adverstiments placed on a large geosocial networking app for MSM. A total of 668 and 727 participants, respectively, responded to questionnaires assessing partner disclosure of PrEP use and UVL. Each questionnaire included an open-ended item assessing reasons for condomless anal sex (CAS) with partners using biomedical prevention. Results Across both surveys, a majority of respondents encountered potential sex partners who disclosed PrEP use or UVL, and the majority of those who met up with these partners engaged in CAS at least once. Qualitative analyses found that most participants who reported CAS did so after making a calculated risk about HIV transmission. We also describe a novel risk reduction strategy, “biomed-matching,” or having CAS only when both individuals use PrEP or have UVL. We report serostatus differences in both quantitative and qualitative findings. Conclusions Disclosure of PrEP use and UVL is not uncommon among MSM. Many MSM make accurate appraisals of the risks of CAS with biomedical prevention, and mobile apps may aid with disclosing biomedical prevention use. PMID:26761520

  10. Select Neurocognitive Impairment in HIV-Infected Women: Associations with HIV Viral Load, Hepatitis C Virus, and Depression, but Not Leukocyte Telomere Length

    PubMed Central

    Giesbrecht, Chantelle J.; Thornton, Allen E.; Hall-Patch, Clare; Maan, Evelyn J.; Côté, Hélène C. F.; Money, Deborah M.; Murray, Melanie; Pick, Neora

    2014-01-01

    Background Through implementation of combination antiretroviral therapy (cART) remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection), to characterize impairments in predominately male HIV-infected populations. Methods Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+) women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV−) women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning) and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL), a marker of cellular aging, did not significantly differ between HIV+ and HIV− women, nor was LTL associated with overall neurocognition in the HIV+ group. Conclusions The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments. PMID:24595021

  11. Triphasic multinutrient supplementation during acute resistance exercise improves session volume load and reduces muscle damage in strength-trained athletes.

    PubMed

    Bird, Stephen P; Mabon, Tom; Pryde, Mitchell; Feebrey, Sarah; Cannon, Jack

    2013-05-01

    We hypothesized that triphasic multinutrient supplementation during acute resistance exercise would enhance muscular performance, produce a more favorable anabolic profile, and reduce biochemical markers of muscle damage in strength-trained athletes. Fifteen male strength-trained athletes completed two acute lower-body resistance exercise sessions to fatigue 7 days apart. After a 4-hour fast, participants consumed either a multinutrient supplement (Musashi 1-2-3 Step System, Notting Hill, Australia) (SUPP) or placebo (PLA) beverage preexercise (PRE), during (DUR), and immediately postexercise (IP). Session volume loads were calculated as kilograms × repetitions. Lower-body peak power was measured using unloaded repeated countermovement jumps, and blood samples were collected to assess biochemistry, serum hormones, and muscle damage markers at PRE, DUR, IP, 30 minutes postexercise (P30), and 24 hours postexercise (P24h). The SUPP demonstrated increased glucose concentrations at DUR and IP compared with at PRE (P < .01), whereas PLA demonstrated higher glucose at P30 compared with at PRE (P < .001). Session volume load was higher for SUPP compared with PLA (P < .05). Cortisol increased at DUR, IP, and P30 compared with at PRE in both treatments (P < .05); however, SUPP also displayed lower cortisol at P24h compared with at PRE and PLA (P < .01). The total testosterone response to exercise was higher for PLA compared with SUPP (P < .01); however, total creatine kinase and C-reactive protein responses to exercise were lower for SUPP compared with PLA (P < .05). These data indicate that although triphasic multinutrient supplementation did not produce a more favorable anabolic profile, it improved acute resistance exercise performance while attenuating muscle damage in strength-trained athletes.

  12. Garlic oil and DDB, comprised in a pharmaceutical composition for the treatment of patients with viral hepatitis, prevents acute liver injuries potentiated by glutathione deficiency in rats.

    PubMed

    Park, Eun Young; Ki, Sung Hwan; Ko, Myong Sok; Kim, Choon Won; Lee, Min Ho; Lee, Young Sok; Kim, Sang Geon

    2005-06-30

    A pharmaceutical composition PENNEL comprising garlic oil (GO) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) as ingredients active for phase II enzyme induction and liver protection, respectively, has been used as a curative preparation for patients with acute or chronic viral hepatitis. In spite of the wide clinical use of PENNEL in Asian and Middle Eastern countries, whether GO+DDB treatment synergistically protects the liver from injuries potentiated by GSH deficiency compared to the individual treatment has not been determined. This study investigated the effects of GO+DDB in comparison with each ingredient alone on chemical-induced liver injury potentiated by a GSH depleting agent. Rats that had been daily pretreated with GO+DDB, GO, DDB, ursodesoxycholic acid or silymarin for 6 days were exposed to buthionine sulfoximine (BSO) and then injected with a single dose of CCl4. The effects of the agents on acute liver toxicities induced by BSO, CCl4 or BSO+CCl4 were assessed by blood biochemistry and histopathology. GO+DDB pretreatment effectively prevented increases in plasma aminotransferases or lactate dehydrogenase activities in rats exposed to BSO+CCl4, compared to GO or DDB treatment alone. Whereas BSO potentiated CCl4-induced liver injuries as evidenced by elevations in central necrosis, hepatocyte degeneration and inflammation, pretreatment with GO+DDB abrogated BSO+CCl4-induced liver injuries more efficaciously than did that with GO or DDB. The hepatoprotective effect of GO+DDB was superior to that of ursodesoxycholic acid or silymarin. Also, blood biochemistry indicated that GO+DDB pretreatment prevented increases in plasma triglyceride contents in rats insulted with CCl4 or BSO+CCl4. The present study demonstrated that GO+DDB, when daily pretreated for six consecutive days, exerted synergistic protection of the liver from chemical-induced injury potentiated by the condition of GSH deficiency, and has additional

  13. Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers.

    PubMed

    Tandon, Ravi; Chew, Glen M; Byron, Mary M; Borrow, Persephone; Niki, Toshiro; Hirashima, Mitsuomi; Barbour, Jason D; Norris, Philip J; Lanteri, Marion C; Martin, Jeffrey N; Deeks, Steven G; Ndhlovu, Lishomwa C

    2014-07-01

    Galectin-9 (Gal-9) is a β-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and IL-1β. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r=0.29; p=0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3 pg/ml) and in elite controllers (263.3 pg/ml) compared to age-matched HIV-uninfected controls (54 pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.

  14. Viral Meningitis

    MedlinePlus

    ... have severe illness from viral meningitis. Causes Non-polio enteroviruses are the most common cause of viral ... following viruses spread by visiting CDC’s websites: Non-polio enteroviruses Mumps virus Herpesviruses, including Epstein-Barr virus , ...

  15. Viral Infections

    MedlinePlus

    ... from medicines, which usually move through your bloodstream. Antibiotics do not work for viral infections. There are a few antiviral medicines available. Vaccines can help prevent you from getting many viral diseases. NIH: National Institute of Allergy and Infectious Diseases

  16. Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

    PubMed Central

    Li, Lihong; Li, Zhuoran; Wang, Erlin; Yang, Rui; Xiao, Yu; Han, Hongbo; Lang, Fengchao; Li, Xin; Xia, Yujie; Gao, Feng; Li, Qihan; Fraser, Nigel W.

    2015-01-01

    ABSTRACT Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG

  17. Viral pneumonia

    MedlinePlus

    ... Names Pneumonia - viral; Walking pneumonia - viral Images Lungs Respiratory system References Lee FE, Treanor JJ. Viral infections. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  18. The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Zheng, Jingtong; Shi, Yue; Zhang, Weijie; Li, Ying; Gibson, Peter G.; Zhang, Chao; Lu, Junying; Sai, Jingying; Wang, Guoqiang

    2017-01-01

    Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD. PMID:28352642

  19. Duox2 is required for the transcription of pattern recognition receptors in acute viral lung infection: An interferon-independent regulatory mechanism.

    PubMed

    Hong, Seung-No; Kim, Ji Young; Kim, Hanna; Kim, Dong-Young; Won, Tae-Bin; Han, Doo Hee; Rhee, Chae-Seo; Kim, Hyun Jik

    2016-10-01

    The innate immune response, which constitutes the first line of defense against influenza A virus (IAV) infection, is activated by pattern recognition receptors (PRRs) that recognize viral structures. We found that the PRRs, retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), which have been implicated as interferon (IFN)-stimulated genes, were dominantly responsible for the recognition of IAV in lungs of mice at 3 and 7 days post infection (dpi). Intranasal administration of IFNs enhanced RIG-I and MDA5 gene expression after IAV infection and mRNA levels of RIG-I and MDA5 were significantly reduced at 7 dpi in mice with neutralization of secreted IFNs. However, blockade of IFNs did not alter the transcription of RIG-I and MDA5 at 3 dpi. We studied the antiviral effect of Duox2 in vivo lung to elucidate the role of Duox2 in respiratory mucosa. RIG-I and MDA5 mRNA levels were induced to a lower extent in lungs of mice that were inoculated with Duox2 small hairpin RNA regardless of secreted IFNs at 3 dpi. We propose that Duox2 is responsible for IFN-independent signaling for induction of PRRs transcription and can control acute IAV lung infection at the beginning of infection.

  20. Israeli acute paralysis virus associated paralysis symptoms, viral tissue distribution and Dicer-2 induction in bumblebee workers (Bombus terrestris).

    PubMed

    Wang, Haidong; Meeus, Ivan; Smagghe, Guy

    2016-08-01

    Although it is known that Israeli acute paralysis virus (IAPV) can cause bee mortality, the symptoms of paralysis and the distribution of the virus in different body tissues and their potential to respond with an increase of the siRNA antiviral immune system have not been studied. In this project we worked with Bombus terrestris, which is one of the most numerous bumblebee species in Europe and an important pollinator for wild flowers and many crops in agriculture. Besides the classic symptoms of paralysis and trembling prior to death, we report a new IAPV-related symptom, crippled/immobilized forelegs. Reverse-transcriptase quantitative PCR showed that IAPV accumulates in different body tissues (midgut, fat body, brain and ovary). The highest levels of IAPV were observed in the fat body. With fluorescence in situ hybridization (FISH) we detected IAPV in the Kenyon cells of mushroom bodies and neuropils from both antennal and optic lobes of the brain in IAPV-infected workers. Finally, we observed an induction of Dicer-2, a core gene of the RNAi antiviral immune response, in the IAPV-infected tissues of B. terrestris workers. According to our results, tissue tropism and the induction strength of Dicer-2 could not be correlated with virus-related paralysis symptoms.

  1. Incidence and viral aetiologies of acute respiratory illnesses (ARIs) in the United States: a population-based study.

    PubMed

    Szilagyi, P G; Blumkin, A; Treanor, J J; Gallivan, S; Albertin, C; Lofthus, G K; Schnabel, K C; Donahue, J G; Thompson, M G; Shay, D K

    2016-07-01

    We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.

  2. Impact of acute malaria on pre-existing antibodies to viral and vaccine antigens in mice and humans.

    PubMed

    Banga, Simran; Coursen, Jill D; Portugal, Silvia; Tran, Tuan M; Hancox, Lisa; Ongoiba, Aissata; Traore, Boubacar; Doumbo, Ogobara K; Huang, Chiung-Yu; Harty, John T; Crompton, Peter D

    2015-01-01

    Vaccine-induced immunity depends on long-lived plasma cells (LLPCs) that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies--raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B) before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies.

  3. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    PubMed

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission.

  4. Viral causes of diarrhea.

    PubMed

    Goodgame, R W

    2001-09-01

    Viruses are important causes of diarrhea. In healthy adults, the main clinical manifestation is acute, self-limited gastroenteritis. Advances in molecular diagnostics have shown that epidemics of acute gastroenteritis most frequently are due to caliciviruses spread through contaminated food or through person-to-person contact. Application of similar technology is needed to make a definitive statement about the role of such candidate viruses as rotavirus, astrovirus, and adenovirus as the cause of nonepidemic acute gastroenteritis in adults. Rarely a previously healthy adult gets acute CMV colitis. CMV and EBV mainly cause diarrhea in immunocompromised patients, however. Advances in prophylaxis and treatment have reduced the frequency and severity of these diseases. Acute infantile gastroenteritis is caused by rotavirus, calcivirus, astrovirus, and adenovirus. These viral diseases of the gut are seen by the physician as routine and rare clinical problems.

  5. Acute Effects of Low-Load/High-Repetition Single-Limb Resistance Training in COPD.

    PubMed

    Nyberg, André; Saey, Didier; Martin, Mickaël; Maltais, François

    2016-12-01

    Exercising small muscle groups at a time allows higher muscle specific workloads compared with whole body aerobic exercises in people with chronic obstructive pulmonary disease (COPD). Whether similar effects also occur with partitioning exercise during low load/high-repetition resistance exercises is uncertain.

  6. Durability of lopinavir/ritonavir dual-therapies in individuals with viral load <50 copies/mL in the observational setting

    PubMed Central

    Gianotti, Nicola; Cozzi-Lepri, Alessandro; Antinori, Andrea; Di Biagio, Antonio; Cristina Moioli, Maria; Nozza, Silvia; Cingolani, Antonella; De Luca, Andrea; Madeddu, Giordano; Bonora, Stefano; Ceccherini-Silberstein, Francesca; d'Arminio Monforte, Antonella

    2014-01-01

    Introduction We aimed at evaluating the efficacy and durability of a lopinavir/ritonavir-based dual regimen (LPV/r-DR) in virologically controlled HIV-infected individuals in current clinical practice. Methods Patients who have initiated for the first time a LPV/r-DR with HIV-RNA<50 copies/mL were included in this observational study. The main endpoints were: time to virological rebound [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to experience either a single VL>200 copies/mL or discontinuation/intensification (= treatment failure, TF). Individuals’ follow-up accrued from the date of starting the LPV/r-DR to event or last available VL. Kaplan-Meier curves and Cox regression analysis were used. Covariates included in the multivariable analysis were gender, age, route of transmission, hepatitis co-infection, calendar year of starting the DR, nadir CD4+ count, VL at initiation of first cART, previous failures to protease inhibitors (PIs), time with undetectable VL before starting the DR and the type of DR [nucleoside reverse transcriptase (NRTI), non-NRTI (NNRTI), raltegravir or maraviroc, with NRTI as reference group]. Results are presented as median (Q1, Q3) or frequency (%) as appropriate. Results 108 individuals followed for 18 (7, 30) months were included; baseline (BL) characteristics are detailed in Table 1. LPV/r was associated with a NRTI in 51, with a NNRTI in 10, with raltegravir in 29, and with maraviroc in 18 individuals. By 36 months from switching to the LPV/r-DR, the proportion of individuals with VR and TF was 10% (95% CI 3–17%) and 36% (95% CI 22–50%), respectively. We did not find any factor independently associated with the risk of VR. Older age (ARH=0.49 (95% CI 0.30–0.78) per 10 years older; p=0.003) was found to be protective from TF. Mean (SE) CD4+ cells/µL increase from BL to month 36 resulted significant: 195 (40.1) cells/µL (p=0.0028). We did not observe significant changes in AST, ALT, eGFR (MDRD

  7. Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

    NASA Astrophysics Data System (ADS)

    Walshe, R.; Ruskin, H. J.; Callaghan, A.

    Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

  8. RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) for Identifying Acute Viral Upper Respiratory Tract Infections

    PubMed Central

    Chen, Kuan-Fu; Blyn, Lawrence; Rothman, Richard E.; Ramachandran, Padmini; Valsamakis, Alexandra; Ecker, David; Sampath, Rangarajan; Gaydos, Charlotte A.

    2010-01-01

    Diagnosis of respiratory viruses traditionally relies on culture or antigen detection.We aimed to demonstrate capacity of the RT-PCR/ESI-MS platform to identify clinical relevant respiratory viruses in nasopharyngeal aspirate (NPA) samples and compare the diagnostic performance characteristics relative to conventional culture- and antigen-based methods. A RT-PCR/ESI-MS respiratory virus surveillance kit designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus was evaluated using both mock-ups and frozen archived NPA (N=280), 95 of which were positive by clinical virology methods. RT-PCR/ESI-MS detected 74/95 (77.9%) known positive samples and identified an additional 13/185 (7%) from culture negative samples. Viruses that are non-detectable with conventional methods were also identified. Viral load was semi-quantifiable and ranged from 2,400 to >320,000copies/ml. Time to results was 8hrs. RT-PCR/ESI-MS showed promise in rapid detection of respiratory viruses, merits further evaluation for use in clinical settings. PMID:21251562

  9. Outcomes after viral load rebound on first-line antiretroviral therapy in HIV-infected children in the UK/Ireland: an observational cohort study

    PubMed Central

    CHILDS, Tristan; SHINGADIA, Delane; GOODALL, Ruth; DOERHOLT, Katja; LYALL, Hermione; DUONG, Trinh; JUDD, Ali; GIBB, Di M; COLLINS, Intira Jeannie

    2015-01-01

    Background Approximately one-third of HIV-infected children experience virological failure within two years of initiating antiretroviral therapy (ART). We determined the probability of switch to second-line ART or viral load (VL) re-suppression without switch among children who experienced VL rebound on first-line ART in an observational cohort in the UK/Ireland. Methods Children with VL rebound (confirmed VL>400c/ml following suppression <400c/ml) on first-line ART were included. Competing risk analysis estimated the probability of: switch to second-line; confirmed re-suppression (two consecutive VL<400c/ml) without switch; and continued VL>400c/ml without switch. Predictors of time to switch were assessed. Findings Of 900 children starting first-line ART who had VL<400c/ml by one year, 170 (19%) experienced VL rebound by median [IQR] 20·6 months [9·7-40·5]. At rebound, median age was 10·6 years [5·6-13·4], VL 3·6 log10c/ml [3·1-4·2], and CD4% 24 [17-32]. Eighty-nine (52%) switched to second-line ART at median 4·9 months [1·7-13·4] after VL rebound, 53 (31%) re-suppressed without switch (61% of those on PI-based and 24% of those on NNRTI-based first-line regimens), while 28 (16%) neither re-suppressed nor switched. At 12 months after rebound, probabilities of switch or re-suppression without switch were 38% (95% CI 30-45) and 27% (95% CI 21-34), respectively. Faster time to switch was associated with higher VL (p<0·0001), later calendar year (p=0·02) at VL rebound, and NNRTI- or triple NRTI- versus PI-based first-line (p=0·001). Interpretation One-third of children with VL rebound re-suppressed without switch. The possibility of re-suppression with adherence support should be considered prior to switching. Funding NHS England PMID:26413561

  10. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

    PubMed Central

    Lamers, Susanna L.; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J.; Fogel, Gary B.; Salemi, Marco; Garcia, Debra L.; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H.; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A.; Singer, Elyse J.

    2016-01-01

    ABSTRACT HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV+) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. IMPORTANCE It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An

  11. First-line cART regimen impacts the course of CD8+ T-cell counts in HIV-infected patients that achieve sustained undetectable viral load.

    PubMed Central

    Poizot-Martin, Isabelle; Allavena, Clotilde; Delpierre, Cyrille; Duvivier, Claudine; Obry-Roguet, Véronique; Cano, Carla E.; Guillouet de Salvador, Francine; Rey, David; Dellamonica, Pierre; Cheret, Antoine; Cuzin, Lise; Katlama, Christine; Cabié, André; Hoen, Bruno

    2016-01-01

    Abstract The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8+ T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT’AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8+ T-cell counts according to cART regimen was assessed. CD8+ T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8+ T-cell count compared with NNRTI-containing regimens (–10.2 cells/μL in 3NRTIs vs –105.1 cells/μL; P=0.02) but not compared with PI-containing regimens (10.2 vs –60.9 cells/μL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8+ T-cell count and % compared with PI/r- and NNRTI-containing regimens (0.2 in 3NRTIs vs –9.9 with PI/r-regimens, P=0.001, and vs –11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8+ T-cell count of –155 [inter quartile range: –302; –22] cells/μL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. PMID:27741125

  12. CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time

    PubMed Central

    Cori, Anne; Pickles, Michael; van Sighem, Ard; Gras, Luuk; Bezemer, Daniela; Reiss, Peter; Fraser, Christophe

    2015-01-01

    Background: CD4+ cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4+ cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4+ decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. Methods: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4+ cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4+ cell counts and an observation model relating actual CD4+ measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4+ cell counts through categories CD4+ above 500, 350–500, 200–350 and 200 cells/μl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. Results: Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4+ cell count above 500 cells/μl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4+ cell count less than 200 cells/μl compared with 15.76 years for SPVL less than 4 log10 copies/ml. Conclusion: Many individuals already have CD4+ cell count below 500 cells/μl after seroconversion. SPVL strongly influences the rate of CD4+ decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification. PMID

  13. Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving Antiretroviral Therapy in Africa and Asia

    PubMed Central

    Monleau, Marjorie; Eymard-Duvernay, Sabrina; Dagnra, Anoumou; Kania, Dramane; Ngo-Giang-Huong, Nicole; Touré-Kane, Coumba; Truong, Lien X. T.; Chaix, Marie-Laure; Delaporte, Eric; Ayouba, Ahidjo; Peeters, Martine

    2014-01-01

    Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at −20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory

  14. Prompt increases in retinol-binding protein 4 and endothelial progenitor cells during acute exercise load in diabetic subjects.

    PubMed

    Aoki, Atsushi; Murata, Miho; Asano, Tomoko; Ikoma, Aki; Sasaki, Masami; Saito, Tomoyuki; Otani, Taeko; Jinbo, Sachimi; Ikeda, Nahoko; Kawakami, Masanobu; Ishikawa, San-E

    2012-01-01

    The present study was undertaken to determine whether acute exercise load alters serum retinol-binding protein 4 (RBP4) and numbers of endothelial progenitor cells (EPC) in diabetic subjects. Sixty-two subjects with type 2 diabetes mellitus were enrolled in the present study. They were 50 males and 12 females with the ages of 65.1±8.1 (mean ± SD) years. Cardio-pulmonary exercise stress test (CPX) was carried out, and the numbers of EPC and serum RBP4 levels before and after the CPX were measured. RBP4 is a cytokine synthesized in hepatocytes, white adipose tissues and skeletal muscles, and serum RBP4 was determined by ELISA. EPC was determined as CD34(+)/133(+) cells by FACS. The subjects were subgrouped into two groups with or without nephropathy. Serum RBP4 levels promptly increased from 48.2±4.3 (mean±SEM) to 54.3±4.2 μg/mL after the CPX (mean exercise time of 8 min) in the diabetic subjects without nephropathy (p=0.0006), but did not in those with nephropathy. There was a positive correlation between changes in serum RBP4 during the exercise and estimated glomerular filtration rate (r=0.30, p=0.018). Also, an acute exercise load promptly increased the number of EPCs in the diabetic subjects with and without nephropathy. These findings suggest that a prompt increase in exercise-induced RBP4 is retarded by progression of nephropathy, and that an exercise-induced mobilization of EPCs could maintain endothelial cells in diabetic subjects.

  15. Quantification and determination of spread mechanisms of bovine viral diarrhoea virus in blood and tissues from colostrum-deprived calves during an experimental acute infection induced by a non-cytopathic genotype 1 strain.

    PubMed

    Pedrera, M; Gómez-Villamandos, J C; Molina, V; Risalde, M A; Rodríguez-Sánchez, B; Sánchez-Cordón, P J

    2012-10-01

    To detect and monitor the sequential changes in virus levels, a reverse transcription quantitative real-time polymerase chain reaction assay using a TaqMan probe was carried out on frozen blood and tissues samples collected from calves experimentally infected with a non-cytopathic Bovine viral diarrhoea virus (BVDV) genotype 1 strain. Blood samples were collected among days 1-14 post-inoculation (p.i). On day 3 p.i, viral RNA was detected in blood samples from six of the eight inoculated animals. Viral RNA was detected in all remaining inoculated animals between 5 and 12 days p.i. The levels of viral RNA increased along the experiment, with a maximal peak between 6 and 9 days p.i. Analysis of virus load in tissues collected from calves euthanized on days 3, 6, 9 and 14 p.i displayed that BVDV was detected on day 3 p.i, being especially abundant in tonsils and ileocaecal valve, highlighting the role of tonsils as the main earliest viral replication sites as well as the principal source for virus spread to other lymphoid tissues and visceral organs. Coinciding with the highest viraemia levels, the highest viral loads were recorded at 9 days p.i. in tonsils, ileal lymph nodes, distal ileum and spleen, showing the main role of these secondary lymphoid organs in the pathogenic mechanisms of BVDV. However, virus levels in the liver and lung increased only towards the end of the infection. This fact could influence in the appearance of bovine respiratory diseases because of the capacity of BVDV for enhancing susceptibility to secondary infections.

  16. Viral and Atypical Bacterial Etiology of Acute Respiratory Infections in Children under 5 Years Old Living in a Rural Tropical Area of Madagascar

    PubMed Central

    Hoffmann, Jonathan; Rabezanahary, Henintsoa; Randriamarotia, Martin; Ratsimbasoa, Arsène; Najjar, Josette; Vernet, Guy; Contamin, Bénédicte; Paranhos-Baccalà, Gláucia

    2012-01-01

    Background In Madagascar, very little is known about the etiology and prevalence of acute respiratory infections (ARIs) in a rural tropical area. Recent data are needed to determine the viral and atypical bacterial etiologies in children with defined clinical manifestations of ARIs. Methods During one year, we conducted a prospective study on ARIs in children between 2 to 59 months in the community hospital of Ampasimanjeva, located in the south-east of Madagascar. Respiratory samples were analyzed by multiplex real-time RT-PCR, including 18 viruses and 2 atypical bacteria. The various episodes of ARI were grouped into four clinical manifestations with well-documented diagnosis: “Community Acquired Pneumonia”(CAP, group I), “Other acute lower respiratory infections (Other ALRIs, group II)”, “Upper respiratory tract infections with cough (URTIs with cough, group III)”and “Upper respiratory tract infections without cough (URTIs without cough, group IV)”. Results 295 children were included in the study between February 2010 and February 2011. Viruses and/or atypical bacteria respiratory pathogens were detected in 74.6% of samples, the rate of co-infection was 27.3%. Human rhinovirus (HRV; 20.5%), metapneumovirus (HMPV A/B, 13.8%), coronaviruses (HCoV, 12.5%), parainfluenza virus (HPIV, 11.8%) and respiratory syncytial virus A and B (RSV A/B, 11.8%) were the most detected. HRV was predominantly single detected (23.8%) in all the clinical groups while HMPV A/B (23.9%) was mainly related to CAP (group I), HPIV (17.3%) to the “Other ALRIs” (group II), RSV A/B (19.5%) predominated in the group “URTIs with cough” (group III) and Adenovirus (HAdV, 17.8%) was mainly detected in the “without cough” (group IV). Interpretation This study describes for the first time the etiology of respiratory infections in febrile children under 5 years in a malaria rural area of Madagascar and highlights the role of respiratory viruses in a well clinically defined

  17. Acute neuromuscular and metabolic responses to combined strength and endurance loadings: the "order effect" in recreationally endurance trained runners.

    PubMed

    Taipale, Ritva S; Schumann, Moritz; Mikkola, Jussi; Nyman, Kai; Kyröläinen, Heikki; Nummela, Ari; Häkkinen, Keijo

    2014-01-01

    The study examined the acute neuromuscular and metabolic responses and recovery (24 and 48 h) to combined strength and endurance sessions (SEs). Recreationally endurance trained men (n = 12) and women (n = 10) performed: endurance running followed immediately by a strength loading (combined endurance and strength session (ES)) and the reverse order (SE). Maximal strength (MVC), countermovement jump height (CMJ), and creatine kinase activity were measured pre-, mid-, post-loading and at 24 and 48 h of recovery. MVC and CMJ were decreased (P < 0.05) at post-ES and SE sessions in men. Only MVC decreased in ES and SE women (P < 0.05). During recovery, no order differences in MVC were observed between sessions in men, but MVC and CMJ remained decreased. During recovery in women, a delayed decrease in CMJ was observed in ES but not in SE (P < 0.01), while MVC returned to baseline at 24 h. Creatine kinase increased (P < 0.05) during both ES and SE and peaked in all groups at 24 h. The present combined ES and SE sessions induced greater neuromuscular fatigue at post in men than in women. The delayed fatigue response in ES women may be an order effect related to muscle damage.

  18. Acute Effects of Loaded Half-Squat Jumps on Sprint Running Speed in Track and Field Athletes and Soccer Players.

    PubMed

    Vanderka, Marián; Krčmár, Matúš; Longová, Katarína; Walker, Simon

    2016-06-01

    The purpose of the study was to determine the acute responses to a jump squat protocol designed to induce postactivation potentiation on sprint running performance in experienced track and field athletes and soccer players. Twenty-five regional level athletes (12 track and field: ∼17 years; ∼177 cm; ∼73 kg and 13 soccer: ∼18 years; ∼175 cm; ∼72 kg) performed 2 test sessions assessing 40-m sprint running performance in a balanced, crossover design. Dual-beam light timing gates measured 0-20 and 20-40 m sprint times before and after either 9 minutes of sitting (control) or 2 sets of 6 repetition half-squat jump with the load eliciting maximum power (experimental) conditions. Sprint performance was significantly enhanced over both 0-20 m (3.09 ± 0.07 to 3.04 ± 0.08 seconds; Δ ∼1.5%; p ≤ 0.05) and 20-40 m (2.42 ± 0.09 to 2.39 ± 0.09 seconds; Δ ∼1%; p ≤ 0.05) in track and field athletes only. Also, the magnitude of enhanced sprint performance was related to baseline 0-20 m sprint performance (r = 0.44; p = 0.028; n = 25). It seems that using loaded half-squat jumps to enhance sprint performance could be used in training of high-level young athletes.

  19. Prolonged Treadmill Load Carriage: Acute Injuries and Changes in Foot Anthropometry

    DTIC Science & Technology

    1990-06-01

    associated with load carriage include upper and lower back strain, metatarsalgia, plantar fasciitis , knee and ankle pain (2,3), stress fractures (5) and...and foot powder was applied to their feet on a daily basis to minimize blistering. All subjects wore the standard plastic mesh ve ,dlating insert ... Fasciitis (feet) 3 3.6% Tendonitis (knee) 3 3.6% Toenail Injury 3 3.6% Groin Strain 2 2.5% Low Back Strain 1 1.2% Hip Pain 1 1.2% Ankle Sprain 1 1.2% Foot

  20. Cloning of the rhesus lymphocryptovirus viral capsid antigen and Epstein-Barr virus-encoded small RNA homologues and use in diagnosis of acute and persistent infections.

    PubMed

    Rao, P; Jiang, H; Wang, F

    2000-09-01

    Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with the development of several human malignancies. A closely related herpesvirus in the same lymphocryptovirus (LCV) genera as EBV naturally infects rhesus monkeys and provides an important animal model for studying EBV pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to determine whether epitopes in the rhesus LCV sVCA are a reliable indicator of rhesus LCV infection. In order to define a "gold standard" for rhesus LCV infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2 homologues from rhesus LCV and developed a reverse transcription (RT)-PCR assay to detect persistent LCV infection in rhesus monkey peripheral blood lymphocytes. Animals from a conventional and a hand-reared colony were studied to compare the prevalence of rhesus LCV infection in the two groups. There was a 100% correlation between the peptide ELISA and EBER RT-PCR results for rhesus LCV infection. In addition, specificity for LCV infection and exclusion of potential cross-reactivity to the rhesus rhadinovirus sVCA homologue could be demonstrated using sera from experimentally infected animals. These studies establish two novel assays for reliable diagnosis of acute and persistent rhesus LCV infections. The rhesus LCV sVCA peptide ELISA provides a sensitive and reliable assay for routine screening, and these studies of the hand-reared colony confirm the feasibility of raising rhesus LCV-naive animals.

  1. Cloning of the Rhesus Lymphocryptovirus Viral Capsid Antigen and Epstein-Barr Virus-Encoded Small RNA Homologues and Use in Diagnosis of Acute and Persistent Infections

    PubMed Central

    Rao, Pasupuleti; Jiang, Hua; Wang, Fred

    2000-01-01

    Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with the development of several human malignancies. A closely related herpesvirus in the same lymphocryptovirus (LCV) genera as EBV naturally infects rhesus monkeys and provides an important animal model for studying EBV pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to determine whether epitopes in the rhesus LCV sVCA are a reliable indicator of rhesus LCV infection. In order to define a “gold standard” for rhesus LCV infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2 homologues from rhesus LCV and developed a reverse transcription (RT)-PCR assay to detect persistent LCV infection in rhesus monkey peripheral blood lymphocytes. Animals from a conventional and a hand-reared colony were studied to compare the prevalence of rhesus LCV infection in the two groups. There was a 100% correlation between the peptide ELISA and EBER RT-PCR results for rhesus LCV infection. In addition, specificity for LCV infection and exclusion of potential cross-reactivity to the rhesus rhadinovirus sVCA homologue could be demonstrated using sera from experimentally infected animals. These studies establish two novel assays for reliable diagnosis of acute and persistent rhesus LCV infections. The rhesus LCV sVCA peptide ELISA provides a sensitive and reliable assay for routine screening, and these studies of the hand-reared colony confirm the feasibility of raising rhesus LCV-naive animals. PMID:10970361

  2. Acute effects of heavy- and light-load squat exercise on the kinetic measures of vertical jumping.

    PubMed

    Hanson, Erik D; Leigh, Steve; Mynark, Richard G

    2007-11-01

    This study examined the acute performance enhancing effects of a single light-load, high-velocity or heavy-load, low-velocity squat intervention set (SIS) on stimulating activity-dependent postactivation potentiation and thereby increasing vertical jumping performance. Jump performance was assessed using 4 dependent variables: net impulse, time of ground contact, and normalized peak and normalized minimum vertical ground reaction force. Resistance-trained subjects (n = 30) attended 3 independent sessions separated by 3 to 7 days. The first session served for familiarization and to determine each subject's 1 repetition maximum (1RM) in the squat. In the 2 testing sessions, subjects performed 2 countermovement jump (CMJ) sets, followed by a single SIS and then a final CMJ set. A CMJ set consisted of 3 maximal effort jumps. The testing sessions were identical except for SIS intensity, which was 40% of 1RM for 1 session and 80% of 1RM for the other. The order of the 2 testing sessions was counterbalanced within subjects. The 4 dependent variables were reduced for every jump. No significant changes were observed from pre- to post-testing in either SIS condition, nor were there any differences between the heavy and light SIS loading condition. Reasons for the lack of performance enhancement can be attributed to postactivation potentiation stimulated by the SIS being insufficient in magnitude or dissipating before post-testing. This may have been due to a submaximal workload of 50% during the SIS, insufficient movement pattern specificity between the squat exercise and a CMJ, or rest intervals of excess duration. A single SIS provides no benefit to a warm-up protocol under the current conditions.

  3. Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation

    PubMed Central

    Foo, Suan-Sin; Chen, Weiqiang; Taylor, Adam; Sheng, Kuo-Ching; Yu, Xing; Teng, Terk-Shin; Reading, Patrick C.; Blanchard, Helen; Garlanda, Cecilia; Mantovani, Alberto; Ng, Lisa F. P.; Herrero, Lara J.; Mahalingam, Suresh

    2015-01-01

    The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3-/-) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis. PMID:25695775

  4. From hepatic diseases and jaundice to viral hepatitis: the configuration of a kaleidoscope.

    PubMed

    Gaze, Rosangela; Carvalho, Diana Maul de; Santoro-Lopes, Guilherme; Tura, Luiz Fernando Rangel

    2013-02-01

    Viral hepatitis A, B, C, D and E--systemic hepatotropic viral infections--present as acute hepatitis that, depending on the etiological agent, viral load and host conditions, may evolve into chronic hepatitis, cirrhosis, liver cancer and acute fulminant disease. The ecological versatility of these viruses, their spectrum of transmission in time and space, potentialized by the sub-clinical course of a large proportion of infections, comprise an epidemiological challenge. This essay describes scenarios and tendencies in the socioepidemiologic profile, based on the history of these infections, and indicates the need to overcome patterns, models, and protocols and instead investigate each particular situation. In other words, it highlights the need to explore singularities in order to be able to develop new proposals for general actions tailored to local specificities.

  5. Acute effect of Snus on physical performance and perceived cognitive load on amateur footballers.

    PubMed

    Morente-Sánchez, J; Zandonai, T; Mateo-March, M; Sanabria, D; Sánchez-Muñoz, C; Chiamulera, C; Zabala Díaz, M

    2015-08-01

    Smokeless tobacco (Snus) is a substance that contains nicotine, which has been placed on World Anti-Doping Agency's 2014 Monitoring Program. A proliferation of nicotine use in sport has been observed in recent years, but little is known regarding its effects, especially on football players' performance. Therefore, the aim of this study was to assess the effect of Snus on physical performance, heart rate variability, subjective activation, mental fatigue, and perceived readiness before a physical test in non-smoker, non-Snus user, amateur football players. Participants were administered either Snus or placebo 40 min prior to a fitness test battery (handgrip test, countermovement jump, agility test, and Yo-Yo intermittent recovery test). Results showed that Snus intake (compared with placebo) increased perceived mental fatigue level and mental load, and reduced perceived readiness level and heart rate variability. No significant differences between the two experimental conditions were found in either performance in the physical tests or perceived physical fatigue levels. In light of these results, Snus could not be considered an ergogenic substance. On the contrary, based on the extant evidence linking mental load and fatigue with physical performance, we argue that the observed negative effects on mental fatigue, perceived readiness, and heart rate variability should be considered.

  6. [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads].

    PubMed

    Orta Mira, Nieves; Serrano, María del Remedio Guna; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Cardona, Concepción Gimeno

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean ± 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Δ<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean ± 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable.

  7. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naïve HIV-mono-infected and HIV/HCV-co-infected Chinese.

    PubMed

    He, Lai; Zhao, Jin; Wang, Maggie Haitian; Siu, Kenny K Y; Gan, Yong-Xia; Chen, Lin; Zee, Benny C Y; Yang, Li; Kung, Hsiang-Fu; Yang, Zheng-Rong; He, Ming-Liang

    2014-01-01

    Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  8. Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

    PubMed Central

    Ribeiro, Ana P.; Sacco, Isabel C. N.; Dinato, Roberto C.; João, Silvia M. A.

    2016-01-01

    BACKGROUND: The risk factors for the development of plantar fasciitis (PF) have been associated with the medial longitudinal arch (MLA), rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain) and 15 with previous chronic PF (without pain). The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R 2=0.15 for acute phase PF; R 2=0.17 for chronic PF) and maximum force (R 2=0.35 for chronic PF) over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R 2=0.18) and chronic (R 2=0.45). The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R 2=0.19) and chronic (R 2=0.40). CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot. PMID:26786073

  9. Comparison of Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0) with other real-time PCR assays in HIV-1 monitoring and follow-up of low-level viral loads.

    PubMed

    Wojewoda, Christina M; Spahlinger, Timothy; Harmon, Marlene Louise; Schnellinger, Brian; Li, Qing; Dejelo, Corazon; Schmotzer, Christine; Zhou, Lan

    2013-01-01

    Viral load monitoring of HIV-1 has become standard of care in HIV-1 positive patients. In this study, we evaluated the performance characteristics of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0) in comparison with Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 1.0 (CAP/CTM v1.0) and Abbott RealTime HIV-1 assay (m2000), with special emphasis on the quantitation of clinically controversial low-level viral loads. The performance characteristics of CAP/CTM v2.0 were confirmed by the validation study. All three assays performed comparably, with Abbott m2000 showing slightly decreased sensitivity for detection of viral loads close to the lower limit of quantitation. Follow-up of patients with low-level viral loads revealed that some of those represent single viral blips; however, a significant portion of these patients have intermittent or persistent low-positive viremia. We conclude that CAP/CTM v2.0 is an accurate and reliable assay for HIV-1 viral load monitoring.

  10. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens by activating natural killer cells (NK), cytotoxic T lymphocytes, and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such i...

  11. Acute effects of blood flow restriction on muscle activity and endurance during fatiguing dynamic knee extensions at low load.

    PubMed

    Wernbom, Mathias; Järrebring, Rickard; Andreasson, Mikael A; Augustsson, Jesper

    2009-11-01

    The purpose of this study was to investigate muscle activity and endurance during fatiguing low-intensity dynamic knee extension exercise with and without blood flow restriction. Eleven healthy subjects with strength training experience performed 3 sets of unilateral knee extensions with no relaxation between repetitions to concentric torque failure at 30% of the 1 repetition maximum. One leg was randomized to exercise with cuff occlusion and the other leg to exercise without occlusion. The muscle activity in the quadriceps was recorded with electromyography (EMG). Ratings of perceived exertion (RPE) and acute pain were collected immediately, and delayed onset muscle soreness (DOMS) was rated before and at 24, 48, and 72 hours after exercise. The results demonstrated high EMG levels in both experimental conditions, but there were no significant differences regarding maximal muscle activity, except for a higher EMG in the eccentric phase in set 3 for the nonoccluded condition (p = 0.005). Significantly more repetitions were performed with the nonoccluded leg in every set (p < 0.05). The RPE and acute pain ratings were similar, but DOMS was higher in the nonoccluded leg (p < 0.05). We conclude that blood flow restriction during low-intensity dynamic knee extension decreases the endurance but does not increase the maximum muscle activity compared with training without restriction when both regimes are performed to failure. The high levels of muscle activity suggest that performing low-load dynamic knee extensions in a no-relaxation manner may be a useful method in knee rehabilitation settings when large forces are contraindicated. However, similarly to fatiguing blood flow restricted exercise, this method is associated with ischemic muscle pain, and thus its applications may be limited to highly motivated individuals.

  12. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

    PubMed Central

    Ong, Yong Sze; Saiful Yazan, Latifah; Ng, Wei Keat; Noordin, Mustapha M; Sapuan, Sarah; Foo, Jhi Biau; Tor, Yin Sim

    2016-01-01

    Background Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes. Conclusion For long-term oral consumption, TQ and

  13. Acute and long-term effects after single loading of functionalized multi-walled carbon nanotubes into zebrafish (Danio rerio)

    SciTech Connect

    Cheng Jinping; Chan, C.M.; Veca, L. Monica; Poon, W.L.; Chan, P.K.; Qu Liangwei; Sun Yaping Cheng, S.H.

    2009-03-01

    Carbon nanotubes (CNTs) are widely explored for biomedical applications, but there is very limited information regarding their in vivo biodistribution and biocompatibility. Here, we report the in vivo biodistribution and long-term effects of functionalized multi-walled carbon nanotubes (MWCNTs) in developing zebrafish. The fluorescent-labeled MWCNTs were introduced into zebrafish embryos at 1-cell stage and at 72 h post fertilization through microinjection. After single injection, both acute and long-term interactions between zebrafish and functionalized MWCNTs were studied. The injected FITC-BSA-MWCNTs (at 1-cell stage) were allocated to all blastoderm cells of the embryos through proliferation, and were distinctively excluded from the yolk cell. When introduced into the circulation system, FITC-BSA-MWCNTs moved easily in the compartments and finally were cleaned out by the body at 96 h after the loading. At early stages, the treated zebrafish embryos generated immune response by accumulating circulating white blood cells at the trunk region. Under transmission electron microscope, many lysosome-like vesicles were observed in the blastoderm cells of the treated embryos. The zebrafish loaded with MWCNTs had normal primordial germ cells at early stage and produced second generation later on. However, the larvae of the second generation had obviously lower survival rates as compared to the untreated groups, suggesting a negative effect on the reproduction potential. These results suggest that extensive purification and functionalization processes can help improve the biocompatibility of CNTs. This study also indicates that purified CNTs may have long-term toxicity effects when they were delivered into the body.

  14. Reduction of viral load in whitefly (Bemisia tabaci Gen.) feeding on RNAi-mediated bean golden mosaic virus resistant transgenic bean plants.

    PubMed

    de Paula, Nayhanne T; de Faria, Josias C; Aragão, Francisco J L

    2015-12-02

    The RNAi concept was explored to silence the rep gene from the bean golden mosaic virus (BGMV) and a genetically modified (GM) bean immune to the virus was previously generated. We investigated if BGMV-viruliferous whiteflies would reduce viral amount after feeding on GM plants. BGMV DNA amount was significantly reduced in whiteflies feeding in GM-plants (compared with insects feeding on non-GM plants) for a period of 4 and 8 days in 52% and 84% respectively.

  15. Expression of profibrotic growth factors and their receptors by mouse lung macrophages and fibroblasts under conditions of acute viral inflammation in influenza A/H5N1 virus.

    PubMed

    Anikina, A G; Shkurupii, V A; Potapova, O V; Kovner, A V; Shestopalov, A M

    2014-04-01

    Morphological signs of early interstitial fibrosis, developing under conditions of acute viral inflammation (postinfection days 1-14), were observed in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The development of fibrosis was confirmed by an increase in the number of lung cells expressing TNF-α. These changes were recorded in the presence of a many-fold increase in the counts of macrophages and fibroblasts expressing FGF, EGF, and their receptors.

  16. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus

    PubMed Central

    Morgan, Sophie B.; Hemmink, Johanneke D.; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E.; Brookes, Sharon M.; Bailey, Michael; Townsend, Alain M.; Charleston, Bryan

    2016-01-01

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

  17. Viral quasispecies.

    PubMed

    Andino, Raul; Domingo, Esteban

    2015-05-01

    New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.

  18. Molecular biology of bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are arguably the most important viral pathogen of ruminants worldwide and can cause severe economic loss. Clinical symptoms of the disease caused by BVDV range from subclinical to severe acute hemorrhagic syndrome, with the severity of disease being strain depend...

  19. Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1+ patients

    PubMed Central

    Papasavvas, Emmanouil; Foulkes, Andrea; Yin, Xiangfan; Joseph, Jocelin; Ross, Brian; Azzoni, Livio; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

    2015-01-01

    The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1+ patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3+ CD4− perforin+ IFN-γ+ cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R2 = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3+ CD4− CSFElo CD107a+ cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies. PMID:25684333

  20. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  1. Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies

    PubMed Central

    Miceli-Richard, Corinne; Gestermann, Nicolas; Amiel, Corinne; Sellam, Jérémie; Ittah, Marc; Pavy, Stephan; Urrutia, Alejandra; Girauld, Isabelle; Carcelain, Guislaine; Venet, Alain; Mariette, Xavier

    2009-01-01

    Introduction There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. Methods Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNγ-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. Results The EBV load and the number of IFNγ-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. Conclusions These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded. PMID:19470150

  2. Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells

    PubMed Central

    Haatveit, Hanne Merethe; Wessel, Øystein; Markussen, Turhan; Lund, Morten; Thiede, Bernd; Nyman, Ingvild Berg; Braaen, Stine; Dahle, Maria Krudtaa; Rimstad, Espen

    2017-01-01

    Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon (Salmo salar) and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1–2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription. Globular viral factories organized by the non-structural protein µNS were also observed initially, but were not evident at later stages. Interactions between µNS and the PRV structural proteins λ1, µ1, σ1 and σ3 were demonstrated. Different size variants of µNS and the outer capsid protein µ1 appeared at specific time points during infection. Maximal viral protein load was observed five weeks post cohabitant challenge and was undetectable from seven weeks post challenge. In contrast, viral RNA at a high level could be detected throughout the eight-week trial. A proteolytic cleavage fragment of the µ1 protein was the only viral protein detectable after seven weeks post challenge, indicating that this µ1 fragment may be involved in the mechanisms of persistent infection. PMID:28335455

  3. The contribution of viral genotype to plasma viral set-point in HIV infection.

    PubMed

    Hodcroft, Emma; Hadfield, Jarrod D; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J

    2014-05-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.

  4. Development and optimization of a sensitive TaqMan® real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load.

    PubMed

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; de Figueiredo, Glauciane Garcia; Yamamoto, Aparecida Yulie; Mussi-Pinhata, Marisa Marcia; Kashima, Simone; Covas, Dimas Tadeu

    2016-09-01

    Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan® real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan® PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry-over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan® real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. © 2016 Wiley Periodicals, Inc.

  5. Human viral gastroenteritis.

    PubMed Central

    Christensen, M L

    1989-01-01

    During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young children, whereas the small caliciviruses and unclassified astroviruses, and possibly enteric coronaviruses, are responsible for significantly fewer cases overall. In addition to electron microscopy, enzyme immunoassays and other rapid antigen detection systems have been developed to detect rotaviruses and fastidious fecal adenoviruses in the stool specimens of both nonhospitalized patients and those hospitalized for dehydration and electrolyte imbalance. Experimental rotavirus vaccines have also been developed, due to the prevalence and seriousness of rotavirus infection. The small, unclassified Norwalk virus and morphologically similar viruses are responsible for large and small outbreaks of acute gastroenteritis in older children, adolescents, and adults. Hospitalization of older patients infected with these viruses is usually not required, and their laboratory diagnoses have been limited primarily to research laboratories. Images PMID:2644024

  6. Reduced Frequencies and Activation of Regulatory T Cells After the Treatment of HIV-1-Infected Individuals with the CCR5 Antagonist Maraviroc Are Associated with a Reduction in Viral Loads Rather Than a Direct Effect of the Drug on Regulatory T Cells.

    PubMed

    Joedicke, Jara J; Dirks, Miriam; Esser, Stefan; Verheyen, Jens; Dittmer, Ulf

    2016-04-01

    Regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1 infection and they frequently express the chemokine receptor CCR5. We therefore investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc affected Tregs in chronically HIV-1-infected individuals. HIV-1-infected patients with high viral loads had elevated frequencies of activated Tregs in the peripheral blood compared with healthy controls. In patients successfully treated with antiretroviral drugs (undetectable viral loads), the frequency and the activation status of Tregs were comparable with healthy controls without any specific effect related to the treatment with Maraviroc. These results indicate that the control of viral replication in general rather than a direct binding of Maraviroc to CCR5-positive Tregs influences Treg responses in successfully treated chronically HIV-1-infected individuals.

  7. Importance of Viruses in Acute Otitis Media

    PubMed Central

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

    2015-01-01

    Purpose of review Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infection (URI). Bacterial otopathogens and respiratory viruses interact and play important roles in AOM development. Better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease. Recent findings There has been increasing evidence that AOM occurs during URI, even in the absence of nasopharyngeal bacterial colonization. Among the types of viruses associated with AOM, respiratory syncytial virus continues to be the most commonly detected. It is still unclear whether viral load plays an important role in AOM development, but symptomatic URI (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 health care use between 2001 and 2011. There has been no new vaccine against respiratory viruses other than influenza. Summary Progress has been made towards reduction of the burden of AOM in the last decade. Success in reducing AOM incidence will rely mainly on prevention of nasopharyngeal otopathogen colonization, as well as reduction in the incidence of viral URI. PMID:25514574

  8. The inter-relation of maternal immune competence, HIV-1 viral load, and nutritional status in preventing vertical transmission: an alternative to chemoprophylaxis?

    PubMed

    Moran, P J; Welles, S L; Williams, M A

    1998-11-01

    As the human immunodeficiency virus (HIV) global pandemic moves towards the end of its second decade, women of reproductive age throughout the world have been shown to be increasingly at risk for acquiring HIV-1 infection. Recently, the focus for preventive measures has expanded to include preventing the perinatal transmission of HIV-1 to fetuses and newborns. This manuscript reviews the available literature that examines risk factors for perinatal transmission, immunopathogenesis of HIV-1 infection, and the role that antioxidant micronutrients play in modulating immune response to HIV-1 disease progression. The available information provides a compelling case for the design of studies that evaluate the extent to which maternal HIV-1 viremia and disease progression are modulated by her nutritional status. Should results from these studies confirm that antioxidant micronutrient status is inversely related to HIV-1 RNA load, particularly in economically vulnerable populations, carefully designed and executed supplementation trials would be warranted.

  9. A comparison of quantitative-competitive and realtime PCR assays using an identical target sequence to detect Epstein-Barr virus viral load in the peripheral blood.

    PubMed

    Xu, Shushen; Green, Michael; Kingsley, Laurence; Webber, Steven; Rowe, David

    2006-11-01

    Monitoring the load of Epstein-Barr virus (EBV) in the peripheral blood by quantitative PCR has been accepted as a useful tool for predicting the onset of EBV related diseases, confirming an EBV disease diagnosis and following the response to treatment interventions. In the present study, the use of a realtime polymerase chain reaction (rt-PCR) assay developed for unpurified cell preparations was examined and the results of the realtime assay were compared to an EBV quantitative-competitive PCR assay (QC-PCR). Both assays use the same target sequence and the same method for determining the standard value for the copy number of EBV genomes present. A comparison of 572 PCR results reveals that the realtime assay gave 5-10-fold higher values than the QC-PCR. Fifty-one results (8.9%) were discordant between the two sets of data. The most commonly encountered discordant result was detection of low amounts of EBV DNA by the rt-PCR assay that were not detected in specimens by QC-PCR. The two assays had a high degree of correlation across the range of load detection allowing clinically relevant threshold values determined in the QC-PCR assay to be inferred for the rt-PCR assay. External normalization of the rt-PCR assay was determined to be an important tool for monitoring the quality and/or quantity of human DNA in the starting material. rt-PCR assays with unpurified cell lysates compare favorably with quantitative-competitive assays and when normalized offer real advantages in specimen preparation, assay manipulations and reproducibility over both quantitative-competitive assays and realtime assays that require purified nucleic acid inputs.

  10. Arrhythmias in viral myocarditis and pericarditis.

    PubMed

    Baksi, A John; Kanaganayagam, G Sunthar; Prasad, Sanjay K

    2015-06-01

    Acute viral myocarditis and acute pericarditis are self-limiting conditions that run a benign course and that may not involve symptoms that lead to medical assessment. However, ventricular arrhythmia is frequent in viral myocarditis. Myocarditis is thought to account for a large proportion of sudden cardiac deaths in young people without prior structural heart disease. Identification of acute myocarditis either with or without pericarditis is therefore important. However, therapeutic interventions are limited and nonspecific. Identifying those at greatest risk of a life-threatening arrhythmia is critical to reducing the mortality. This review summarizes current understanding of this challenging area in which many questions remain.

  11. Viral epigenetics.

    PubMed

    Milavetz, Barry I; Balakrishnan, Lata

    2015-01-01

    DNA tumor viruses including members of the polyomavirus, adenovirus, papillomavirus, and herpes virus families are presently the subject of intense interest with respect to the role that epigenetics plays in control of the virus life cycle and the transformation of a normal cell to a cancer cell. To date, these studies have primarily focused on the role of histone modification, nucleosome location, and DNA methylation in regulating the biological consequences of infection. Using a wide variety of strategies and techniques ranging from simple ChIP to ChIP-chip and ChIP-seq to identify histone modifications, nuclease digestion to genome wide next generation sequencing to identify nucleosome location, and bisulfite treatment to MeDIP to identify DNA methylation sites, the epigenetic regulation of these viruses is slowly becoming better understood. While the viruses may differ in significant ways from each other and cellular chromatin, the role of epigenetics appears to be relatively similar. Within the viral genome nucleosomes are organized for the expression of appropriate genes with relevant histone modifications particularly histone acetylation. DNA methylation occurs as part of the typical gene silencing during latent infection by herpesviruses. In the simple tumor viruses like the polyomaviruses, adenoviruses, and papillomaviruses, transformation of the cell occurs via integration of the virus genome such that the virus's normal regulation is disrupted. This results in the unregulated expression of critical viral genes capable of redirecting cellular gene expression. The redirected cellular expression is a consequence of either indirect epigenetic regulation where cellular signaling or transcriptional dysregulation occurs or direct epigenetic regulation where epigenetic cofactors such as histone deacetylases are targeted. In the more complex herpersviruses transformation is a consequence of the expression of the viral latency proteins and RNAs which again can

  12. Measures of Viral Load using Abbott Real-Time HIV-1 Assay on Venous and Fingerstick Dried Blood Spots from Provider-Collected Specimens in Malawian District Hospitals

    PubMed Central

    Rutstein, Sarah E.; Kamwendo, Deborah; Lugali, Lebah; Thengolose, Isaac; Tegha, Gerald; Fiscus, Susan A.; Nelson, Julie A. E.; Hosseinipour, Mina C.; Sarr, Abdoulaye; Gupta, Sundeep; Chimbwandira, Frank; Mwenda, Reuben; Mataya, Ronald

    2014-01-01

    Background Viral suppression is a key indicator of antiretroviral therapy (ART) response among HIV-infected patients. Dried blood spots (DBS) are an appealing alternative to conventional plasma-based virologic testing, improving access to monitoring in resource-limited settings. However, validity of DBS obtained from fingerstick in field settings remains unknown. Objectives Investigate feasibility and accuracy of DBS vs plasma collected by healthcare workers in real-world settings of remote hospitals in Malawi. Compare venous DBS to fingerstick DBS for identifying treatment failure. Study design We recruited patients from ART clinics at two district hospitals in Malawi, collecting plasma, venous DBS (vDBS), and fingerstick DBS (fsDBS) cards for the first 149 patients, and vDBS and fsDBS only for the subsequent 398 patients. Specimens were tested using Abbott RealTime HIV-1 Assay (lower detection limit 40 copies/ml (plasma) and 550 copies/ml (DBS)). Results 21/149 (14.1%) had detectable viremia (>1.6 log copies/ml), 13 of which were detectable for plasma, vDBS, and fsDBS. Linear regression demonstrated high correlation for plasma vs. DBS (vDBS: β=1.19, R2 0.93 (p<0.0001); fsDBS β=1.20, R2 0.90 (p<0.0001)) and vDBS vs. fsDBS (β=0.88, R2 0.73, (p<0.0001)). Mean difference between plasma and vDBS was 0.51 log copies/ml [SD: 0.33] and plasma and fsDBS 0.46 log copies/ml [SD: 0.30]. At 5000 copies/ml, sensitivity was 100%, and specificity was 98.6% and 97.8% for vDBS and fsDBS, respectively, compared to plasma. Conclusions DBS from venipuncture and fingerstick perform well at the failure threshold of 5000 copies/ml. Fingerstick specimen source may improve access to virologic treatment monitoring in resource-limited settings given task-shifting in high-volume, low-resource facilities. PMID:24906641

  13. P-glycoprotein (ABCB1) activity decreases raltegravir disposition in primary CD4+P-gphigh cells and correlates with HIV-1 viral load

    PubMed Central

    Minuesa, Gerard; Arimany-Nardi, Cristina; Erkizia, Itziar; Cedeño, Samandhy; Moltó, José; Clotet, Bonaventura; Pastor-Anglada, Marçal; Martinez-Picado, Javier

    2016-01-01

    Objectives To evaluate the role of P-glycoprotein (P-gp) and multidrug-resistant-protein 1 (MRP1) on raltegravir intracellular drug disposition in CD4+ T cells, investigate the effect of HIV-1 infection on P-gp expression and correlate HIV-1 viraemia with P-gp activity in primary CD4+ T cell subsets. Methods The cellular accumulation ratio of [3H]raltegravir was quantified in CD4+ T cell lines overexpressing either P-gp (CEM-P-gp) or MRP1 (CEM-MRP1) and in primary CD3+CD4+ T cells with high (P-gphigh) and low P-gp activity (P-gplow); inhibition of efflux transporters was confirmed by the intracellular retention of calcein-AM. The correlation of P-gp activity with HIV-1 viraemia was assessed in naive and memory T cell subsets from 21 HIV-1-infected treatment-naive subjects. Results [3H]Raltegravir cellular accumulation ratio decreased in CEM-P-gp cells (P < 0.0001). XR9051 (a P-gp inhibitor) and HIV-1 PIs reversed this phenomenon. Primary CD4+P-gphigh cells accumulated less raltegravir (38.4% ± 9.6%) than P-gplow cells, whereas XR9051 also reversed this effect. In vitro HIV-1 infection of PBMCs and stimulation of CD4+ T cells increased P-gp mRNA and P-gp activity, respectively, while primary CD4+P-gphigh T cells sustained a higher HIV-1 replication than P-gplow cells. A significant correlation between HIV-1 viraemia and P-gp activity was found in different CD4+ T cell subsets, particularly memory CD4+ T cells (r = 0.792, P < 0.0001). Conclusions Raltegravir is a substrate of P-gp in CD4+ T cells. Primary CD4+P-gphigh T cells eliminate intracellular raltegravir more readily than P-gplow cells and HIV-1 viraemia correlates with P-gp overall activity. Specific CD4+P-gphigh T cell subsets could facilitate the persistence of viral replication in vivo and ultimately promote the appearance of drug resistance. PMID:27334660

  14. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.

    PubMed

    Addo, M M; Yu, X G; Rathod, A; Cohen, D; Eldridge, R L; Strick, D; Johnston, M N; Corcoran, C; Wurcel, A G; Fitzpatrick, C A; Feeney, M E; Rodriguez, W R; Basgoz, N; Draenert, R; Stone, David R; Brander, C; Goulder, P J R; Rosenberg, E S; Altfeld, M; Walker, B D

    2003-02-01

    Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

  15. In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading.

    PubMed

    Lu, W; Locke, S J; Brauer, M

    1994-05-01

    The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.

  16. [Effect of intracoronary and intravenous administration of tirofiban loading dose in patients underwent percutaneous coronary interventions because of acute coronary syndrome].

    PubMed

    Turkmen, S; Fettser, D V; Kagliian, K É; Serchelik, A; Arystanova, A Zh; Tekin, K; Balli, M; Batyraliev, T A; Samko, A N; Sidorenko, B A

    2013-01-01

    Aim of this multicenter retrospective study was assessment of effect of intracoronary administration of tirofiban loading dose in troponin positive patients with acute coronary syndrome (ACS). We analyzed multicenter data base of patients subjected to percutaneous coronary interventions (PCI) because of ST-elevation or non-ST elevation ACS from October 2010 to October 2011. Patients who received loading doses of aspirin (300 mg) and clopidogrel (600 mg) before PCI and tirofiban (10 mg/kg bolus with subsequent infusion 0.15 mg/kg/min for 24 h) were selected for the study (n=133, 89 with intravenous and 44 - intracoronary administration of tirofiban loading dose). We assessed hospital mortality, myocardial reinfarctions (reMI), necessity of target vessel revascularization (TVR) and pronounced bleedings. There were no significant differences in mortality, reMI, and TVR between two groups. However major adverse cardiac events was significantly less in patients who received intracoronary tirofiban (6.8 vs. 21.3% in i.v. group; p=0.046). Hospital stay was significantly shorter in intracoronary compared with i.v. group (3.84+/-0.96 vs. 4.55+/-1.11 days; p=0.001). Rates of bleedings did not differ significantly between groups. Thus compared with i.v. intracoronary administration of tirofiban loading dose allows lower rate of major adverse cardiac events as well as to shorten length of hospital stay of patients with ACS.

  17. Rapid identification viruses from nasal pharyngeal aspirates in acute viral respiratory infections by RT-PCR and electrospray ionization mass spectrometry.

    PubMed

    Chen, Kuan-Fu; Rothman, Richard E; Ramachandran, Padmini; Blyn, Lawrence; Sampath, Rangarajan; Ecker, David J; Valsamakis, Alexandra; Gaydos, Charlotte A

    2011-04-01

    Diagnosis of the etiologic agent of respiratory viral infection relies traditionally on culture or antigen detection. This pilot evaluation compared performance characteristics of the RT-PCR and electrospray ionization mass spectrometry (RT-PCR/ESI-MS) platform to conventional virologic methods for identifying multiple clinically relevant respiratory viruses in nasopharyngeal aspirates. The RT-PCR/ESI-MS respiratory virus surveillance kit was designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus. Patients (N=192) attending an emergency department during the 2007-2008 respiratory season consented, and "excess" frozen archived nasopharyngeal aspirates were analysed; 46 were positive by conventional virology and 69 by RT-PCR/ESI-MS, among which there were six samples with multiple viral pathogens detected. The sensitivity and specificity of the assay were 89.1% and 80.3%, respectively. Additional viruses that were not identified by conventional virology assays were detected (4 human bocaviruses and 7 coronaviruses). Samples in which the RT-PCR/ESI-MS results disagreed with conventional virology were sent for analysis by a third method using a commercial RT-PCR-based assay, which can identify viruses not detectable by conventional virologic procedures. Time to first result of RT-PCR/ESI-MS was 8h. RT-PCR/ESI-MS demonstrated capacity to detect respiratory viruses identifiable and unidentifiable by conventional methods rapidly.

  18. Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS.

    PubMed

    Callendret, Benoît; Lorin, Valérie; Charneau, Pierre; Marianneau, Philippe; Contamin, Hugues; Betton, Jean-Michel; van der Werf, Sylvie; Escriou, Nicolas

    2007-07-05

    The SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS. Upon immunization of mice with low doses (2 microg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. Our observations are likely to be useful for the construction of plasmid and viral vectors designed for optimal expression of intronless genes derived from cytoplasmic RNA viruses.

  19. Effects of acute heat exposure on prosencephalic c-Fos expression in normohydrated, water-deprived and salt-loaded rats.

    PubMed

    Santana, Rejane; de De Castro E Silva, Emilio; Reis de Oliveira, Irismar; Fregoneze, Josmara B

    2007-04-13

    In the present study, the distribution pattern of c-Fos protein immunoreactivity (Fos-IR) in prosencephalic areas of the brain involved in thermoregulatory and osmoregulatory responses was investigated, in rats exposed or not exposed to a hyperthermic environment, under three different conditions: normohydration, dehydration induced by water deprivation and hyperosmolarity induced by an acute intragastric salt load. Normohydrated, water-deprived or salt-loaded male Wistar rats (270+/-30 g) were submitted or not to acute heat exposure (33 degrees C for 45 min). A separate group of animals was submitted to the same experimental protocol and had blood samples collected before and after the heating period to measure serum osmolarity and sodium. The brains were processed for c-Fos immunohistochemistry using the avidin-biotin peroxidase method. After analyzing Fos-IR in the brains of animals in the present study, three different types of prosencephalic areas were identified: (1) those that respond to hydrational and to heat conditions, with an interaction between these two factors (PaMP and SON); (2) those that respond to hydrational and to heat conditions, but with no interaction between these factors (MnPO, LSV and OVLT); and (3) those that respond only to hydrational status (SFO and PaLM).

  20. Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1(+) γδ T cells in lymphoid tissues of beef calves.

    PubMed

    Palomares, Roberto A; Sakamoto, Kaori; Walz, Heather L; Brock, Kenny V; Hurley, David J

    2015-10-15

    The objective of this study was to determine the abundance and distribution of γδ T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n=10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n=10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n=10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1(+) γδ T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of γδ T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P<0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1(+) γδ T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in γδ T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues.