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Sample records for newly infected individuals

  1. High Percentage of Recent HIV Infection Among HIV-Positive Individuals Newly Diagnosed at Voluntary Counseling and Testing Sites in Poland

    PubMed Central

    Marzec-Bogustawska, Anna; Janiec, Janusz; Smoleń-Dzirba, Joanna; Wąsik, Tomasz; Gniewosz, Joanna; Zalewska, Małgorzata; Murphy, Gary; McKinney, Elaine; Porter, Kholoud

    2013-01-01

    Abstract To gain insight into HIV transmission we estimated the proportion of those recently infected. We examined data from HIV-positive patients and a random 10% sample of HIV-negative patients tested at Voluntary Counseling and Testing sites in Poland in 2006. Archived samples from positive patients were tested by three assays to differentiate recent from long-standing infection. Using logistic regression, we examined the association of recent infection (at least one assay) with age, sex, HIV exposure category, and the interval between self-reported HIV exposure and previous HIV test. Of 13,511 tests, 154 (1.1%) were HIV positive, representing 19.7% (n=783) of new diagnoses in Poland in 2006. Demographic and behavioral data were linked for 95, of whom 45 (47%) were recently infected and 1,001 were HIV negative. New diagnoses were more likely to be injectors (17% vs. 2%), men who have sex with men (MSM) (37% vs. 12%), and less frequent condom users (7.8% vs. 14% always) compared to HIV negatives. The median number of partners during the past 12 months was one and two among positives and negatives, but was higher among MSM—four and three, respectively. Ever injectors were less likely to be recently infected (adjusted OR=0.15, 95%CI=0.03–0.73). Having two or more sexual partners in the past 12 months was an independent predictor of recent infection (4.01, 1.4–11.49). We found no evidence that age or sex predicted recent infection. These data reinforce health education campaigns for safe sex messages, especially among MSM. They also suggest, albeit based on a subset of new diagnoses, that interventions should not be limited to selected age/sex groups. PMID:23343475

  2. Death Concerns among Individuals Newly Diagnosed with Lung Cancer

    ERIC Educational Resources Information Center

    Lehto, Rebecca; Therrien, Barbara

    2010-01-01

    Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

  3. Multiple Epstein-Barr virus infections in healthy individuals

    NASA Technical Reports Server (NTRS)

    Walling, Dennis M.; Brown, Abigail L.; Etienne, Wiguins; Keitel, Wendy A.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2003-01-01

    We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

  4. Determinants of Newly Detected Human Papillomavirus Infection in HIV-Infected and HIV-Uninfected Injection Drug Using Women

    PubMed Central

    Phelan, Darcy F.; Gange, Stephen J.; Ahdieh-Grant, Linda; Mehta, Shruti H.; Kirk, Gregory D.; Shah, Keerti; Gravitt, Patti

    2009-01-01

    Background We sought to identify factors associated with newly detected human papillomavirus (HPV) infection in a high-risk cohort of injection drug using women in Baltimore, MD. Methods We studied 146 HIV-infected and 73 HIV-uninfected female participants in a 5-year prospective HIV natural history study. We examined the association of sexual and nonsexual risk factors and newly detected type-specific HPV infection as determined by consensus PCR between consecutive visits. Results Newly detected HPV was more common among HIV-infected versus HIV-uninfected women (30% and 6%, respectively; P <0.01). Among the entire cohort, recent crack use (OR, 1.7; 95% CI, 1.1−2.6) and HIV infection/CD4 cell count were independent predictors for new HPV detection (HIV-uninfected as reference, OR, 4.6; 95% CI, 2.3−8.9, OR, 5.4; 95% CI, 2.8−10.3, and OR, 10.9; 95% CI, 5.5−21.7 for HIV-infected CD4 >500, 200−500, and <200, respectively). Among HIV-uninfected women, recent marijuana use was an independent predictor of newly detected HPV infection (OR, 3.5; 95% CI, 1.3−9.5). Conclusions Newly detected HPV clearly increased with greater immunosuppression in HIV-infected injection drug users. Larger studies of HIV-uninfected and infected high-risk individuals are needed to clarify the independent associations of crack and marijuana use with new (or reactivated) HPV infection. PMID:19174735

  5. Transmission of resistant HIV type 1 variants and epidemiological chains in Italian newly diagnosed individuals.

    PubMed

    Lai, Alessia; Violin, Michela; Ebranati, Erika; Franzetti, Marco; Micheli, Valeria; Gismondo, Maria Rita; Capetti, Amedeo; Meraviglia, Paola; Simonetti, Francesco Roberto; Bozzi, Giorgio; Ciccozzi, Masimo; Galli, Massimo; Zehender, Gianguglielmo; Balotta, Claudia

    2012-08-01

    Transmission of HIV-1 and drug resistance continue to occur at a considerable level in Italy, influenced mainly by changes in modality of infection. However, the long period of infectivity makes difficult the interpretation of epidemiological networks, based on epidemiological data only. We studied 510 naive HIV-1-infected individuals, of whom 400 (78.4%) were newly diagnosed patients with an unknown duration of infection (NDs), with the aim of identifying sexual epidemiological networks and transmitted drug resistance (TDR) over a 7-year period. Clusters were identified by Bayesian methods for 412 patients with B subtype; 145 individuals (35.2%) clustered in 34 distinct clades. Within epidemiological networks males were 93.1% (n=135); the same proportion of patients has been infected by the sexual route; 62.1% (n=90) were men having sex with men (MSM) of whom 67.8% (n=61) were NDs. Among heterosexuals (n=44), males were predominant (79.5%, n=35) and 77.3% (n=34) were NDs. TDR in clusters was 11.7 % (n=17), of whom 76.5% (n=13) was found in MSM. TDR was predominantly associated with NRTI resistance in individuals with chronic infection (n=11). A high prevalence of epidemiological networks has been found in the metropolitan area of Milan, indicating a high frequency of transmission events. The cluster analysis of networks suggested that the source of new infections was mainly represented by males and MSM who have long lasting HIV-1 infection. Notably, the prevalence of resistance-conferring mutations was higher in chronically infected patients, carrying mainly resistance to thymidine analogs, the backbone of first antiretroviral (ARV) generation. Intervention strategies of public health are needed to limit HIV-1 transmission and the associated TDR.

  6. A national surveillance system for newly acquired HIV infection in Australia. National HIV Surveillance Committee.

    PubMed Central

    McDonald, A M; Gertig, D M; Crofts, N; Kaldor, J M

    1994-01-01

    OBJECTIVES. The purpose of this study was to describe the establishment of a national surveillance system for newly acquired human immunodeficiency virus (HIV) infection and present the first 3 years' results. METHODS. All new cases of diagnosed HIV infection were reported to the national HIV surveillance center through state and territory health authorities. Information sought on each case included evidence of whether the infection had been newly acquired, defined by the diagnosis of HIV seroconversion illness or by the report of a negative or indeterminate HIV antibody test result occurring within the 12 months prior to diagnosis of infection. RESULTS. Of 3602 reported cases of HIV infection in adults and adolescents newly diagnosed in Australia between 1991 and 1993, 11.4% were identified as newly acquired. The majority (85%) of cases of newly diagnosed HIV infection occurred among men who reported homosexual contact, and 15% of these cases were identified as newly acquired. Average age at diagnosis was 31 years for cases of newly acquired infection and 34 years for other cases. CONCLUSIONS. Surveillance for newly acquired HIV infection has been established at a national level in Australia and provides valuable information for planning primary HIV prevention programs. PMID:7998631

  7. Autoantibodies in nonautoimmune individuals during infections.

    PubMed

    Berlin, Tatiana; Zandman-Goddard, Gisele; Blank, Miri; Matthias, Torsten; Pfeiffer, Sascha; Weis, Ingrid; Toubi, Elias; Singh, Sham; Asherson, Ronald; Fraser, Abigail; Gilburd, Boris; Sapir, Tal; Levy, Yair; Lukac, Janja; Rozman, Blaz; Kveder, Tanja; Shoenfeld, Yehuda

    2007-06-01

    Infections can act as environmental triggers inducing or promoting autoimmune disease in genetically predisposed individuals. Identification of microbial peptides similar to self-tissues may by molecular mimicry, provide the inducing mechanism for an immune response. The aim of this study was to identify autoantibodies (autoAbs) in nonautoimmune individuals during acute bacterial, viral, or parasitic infections. Specific Abs or specific infections with an increased autoAb load may shed insight into the mechanisms of autoimmune disease. Sera from 88 patients with acute infections (41 bacterial, 23 viral, 17 parasitic, and 7 rickettsial) were tested by the ELISA method for antinuclear antibodies (ANA) 8 Pro, and Abs to thyroid peroxidase (TPO), thyroglobulin, phospholipids, annexin-V, laminin, anti-Saccharomyces cervisiae (ASCA), and prothrombin, along with 80 normal controls. Elevated titers of Abs to annexin-V and prothrombin were the most prevalent in viral, parasitic, and rickettsial infections and to laminin in viral and parasitic infections. Elevated titers of ASCA and ANA were found in viral and bacterial infections. Antiphospholipid Abs were found in parasitic and Q-fever infections. Thirty-four individuals harbored elevated titers of at least two Abs. An autoAb burden was detected in individuals with hepatitis A, hepatitis B, toxoplasma or Q-fever infections. In nonautoimmune individuals with various (bacterial, viral, parasitic, and rickettsial) infections, elevated titers of Abs to annexin-V, prothrombin, laminin, ASCA, ANA, and phospholipids were most frequently detected. PMID:17894023

  8. Immunotherapeutic restoration in HIV-infected individuals.

    PubMed

    Kim, June Myung; Han, Sang Hoon

    2011-02-01

    While the development of combined active antiretroviral therapy (cART) has dramatically improved life expectancies and quality of life in HIV-infected individuals, long-term clinical problems, such as metabolic complications, remain important constraints of life-long cART. Complete immune restoration using only cART is normally unattainable even in cases of sufficient plasma viral suppression. The need for immunologic adjuncts that complement cART remains, because while cART alone may result in the complete recovery of peripheral net CD4+ T lymphocytes, it may not affect the reservoir of HIV-infected cells. Here, we review current immunotherapies for HIV infection, with a particular emphasis on recent advances in cytokine therapies, therapeutic immunization, monoclonal antibodies, immune-modulating drugs, nanotechnology-based approaches and radioimmunotherapy.

  9. Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children

    PubMed Central

    Ebonyi, Augustine O.; Oguche, Stephen; Ejeliogu, Emeka U.; Agbaji, Oche O.; Shehu, Nathan Y.; Abah, Isaac O.; Sagay, Atiene S.; Ugoagwu, Placid O.; Okonkwo, Prosper I.; Idoko, John A.; Kanki, Phyllis J.

    2016-01-01

    Introduction Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. Methods We performed a retrospective analysis of 876 children, aged 2 months – 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. Results The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). Conclusion In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes. PMID:27019829

  10. The role of infections and coinfections with newly identified and emerging respiratory viruses in children

    PubMed Central

    2012-01-01

    Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza viruses (PIVs), adenovirus, rhinovirus (HRV), have repeatedly been detected in acute lower respiratory tract infections (LRTI) in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV), coronaviruses NL63 (HcoV-NL63) and HKU1 (HcoV-HKU1), human Bocavirus (HBoV), new enterovirus (HEV), parechovirus (HpeV) and rhinovirus (HRV) strains, polyomaviruses WU (WUPyV) and KI (KIPyV) and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood. PMID:23102237

  11. HIV-1 envelope replication and α4β7 utilization among newly infected subjects and their corresponding heterosexual partners

    PubMed Central

    2013-01-01

    Background Previous studies suggest that active selection limits the number of HIV-1 variants acquired by a newly infected individual from the diverse variants circulating in the transmitting partner. We compared HIV-1 envelopes from 9 newly infected subjects and their linked transmitting partner to explore potential mechanisms for selection. Results Recipient virus envelopes had significant genotypic differences compared to those present in the transmitting partner. Recombinant viruses incorporating pools of recipient and transmitter envelopes showed no significant difference in their sensitivity to receptor and fusion inhibitors, suggesting they had relatively similar entry capacity in the presence of low CD4 and CCR5 levels. Aggregate results in primary cells from up to 4 different blood or skin donors showed that viruses with envelopes from the transmitting partner as compared to recipient envelopes replicated more efficiently in CD4+ T cells, monocyte derived dendritic cell (MDDC) – CD4+ T cell co-cultures, Langerhans cells (LCs) – CD4+ T cell co-cultures and CD4+ T cells expressing high levels of the gut homing receptor, α4β7, and demonstrated greater binding to α4β7 high / CD8+ T cells. These transmitter versus recipient envelope virus phenotypic differences, however, were not always consistent among the primary cells from all the different blood or skin donation volunteers. Conclusion Although genotypically unique variants are present in newly infected individuals compared to the diverse swarm circulating in the chronically infected transmitting partner, replication in potential early target cells and receptor utilization either do not completely dictate this genetic selection, or these potential transmission phenotypes are lost very soon after HIV-1 acquisition. PMID:24369910

  12. Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection.

    PubMed

    Varmuzova, Karolina; Kubasova, Tereza; Davidova-Gerzova, Lenka; Sisak, Frantisek; Havlickova, Hana; Sebkova, Alena; Faldynova, Marcela; Rychlik, Ivan

    2016-01-01

    Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID:27379083

  13. Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection

    PubMed Central

    Varmuzova, Karolina; Kubasova, Tereza; Davidova-Gerzova, Lenka; Sisak, Frantisek; Havlickova, Hana; Sebkova, Alena; Faldynova, Marcela; Rychlik, Ivan

    2016-01-01

    Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID:27379083

  14. Recent Infection, Sexually Transmitted Infections and Transmission Clusters Frequently Observed Among Persons Newly-Diagnosed with HIV in San Francisco

    PubMed Central

    Truong, Hong-Ha M.; Pipkin, Sharon; O’Keefe, Kara J.; Louie, Brian; Liegler, Teri; McFarland, Willi; Grant, Robert M.; Bernstein, Kyle; Scheer, Susan

    2015-01-01

    There were 1,311 newly-diagnosed HIV cases in San Francisco between 2005 and 2011 that were linked to care at publicly-funded facilities and had viral sequences available for analysis. Of the 214 cases characterized as recently-infected with HIV at time of diagnosis, 25% had a recent sexually transmitted infection (STI) diagnosis (vs. 10% among longer-standing HIV infections, p<0.001) and 57% were part of a phylogenetic transmission cluster (vs. 42% among longer-standing HIV infection, p<0.001). The association observed between recent HIV infection and having a STI diagnosis during the interval overlapping likely HIV acquisition points to potential opportunities to interrupt HIV transmission. PMID:25967271

  15. A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China.

    PubMed

    Chen, Y; Wang, Z; Huang, A; Yuan, J; Wei, D; Ye, H

    2016-06-01

    Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients.

  16. Human Immunodeficiency Virus Infection Newly Diagnosed at Autopsy in New York City, 2008-2012.

    PubMed

    Ramaswamy, Chitra; Ellman, Tanya M; Myers, Julie; Madsen, Ann; Sepkowitz, Kent; Shepard, Colin

    2015-12-01

    Background.  Studying the most extreme example of late diagnosis, new HIV diagnoses after death, may be instructive to HIV testing efforts. Using the results of routine HIV testing of autopsies performed by the Office of Chief Medical Examiner (OCME), we identified new HIV diagnoses after death in New York City (NYC) from 2008 to 2012. Methods.  Population-based registries for HIV and deaths were linked to identify decedents not known to be HIV-infected before death. Multivariable logistic regression models were constructed to determine correlates of a new HIV diagnosis after death among all persons newly diagnosed with HIV and among all HIV-infected decedents receiving an OCME autopsy. Results.  Of 264 893 deaths, 24 426 (9.2%) were autopsied by the NYC OCME. Of these, 1623 (6.6%) were infected with HIV, including 142 (8.8%) with a new HIV diagnosis at autopsy. This represents 0.8% (142 of 18 542) of all new HIV diagnoses during the 5-year period. Decedents newly diagnosed with HIV at OCME autopsy were predominantly male (73.9%), aged 13-64 years (85.9%), non-white (85.2%), unmarried (81.7%), less than college educated (83.8%), and residents of an impoverished neighborhood (62.0%). Of all HIV-infected OCME decedents aged ≥65 years (n = 71), 22.0% were diagnosed at autopsy. The strongest independent correlate of new HIV diagnosis at autopsy in both multivariable models was age ≥65 years. Conclusions.  Human immunodeficiency virus diagnoses first made after death are rare, but, when observed, these diagnoses are more commonly found among persons ≥65 years, suggesting that despite highly visible efforts to promote HIV testing community-wide, timely diagnosis among older adults living in impoverished, high-prevalence neighborhoods may require additional strategies. PMID:26566538

  17. Newly Emerged Populations of Plasmopara halstedii Infecting Rudbeckia Exhibit Unique Genotypic Profiles and Are Distinct from Sunflower-Infecting Strains.

    PubMed

    Rivera, Yazmín; Salgado-Salazar, Catalina; Gulya, Thomas J; Crouch, Jo Anne

    2016-07-01

    The oomycete Plasmopara halstedii emerged at the onset of the 21st century as a destructive new pathogen causing downy mildew disease of ornamental Rudbeckia fulgida (rudbeckia) in the United States. The pathogen is also a significant global problem of sunflower (Helianthus annuus) and is widely regarded as the cause of downy mildew affecting 35 Asteraceae genera. To determine whether rudbeckia and sunflower downy mildew are caused by the same genotypes, population genetic and phylogenetic analyses were performed. A draft genome assembly of a P. halstedii isolate from sunflower was generated and used to design 15 polymorphic simple sequence repeat (SSR) markers. SSRs and two sequenced phylogenetic markers measured differentiation between 232 P. halstedii samples collected from 1883 to 2014. Samples clustered into two main groups, corresponding to host origin. Sunflower-derived samples separated into eight admixed subclusters, and rudbeckia-derived samples further separated into three subclusters. Pre-epidemic rudbeckia samples clustered separately from modern strains. Despite the observed genetic distinction based on host origin, P. halstedii from rudbeckia could infect sunflower, and exhibited the virulence phenotype of race 734. These data indicate that the newly emergent pathogen populations infecting commercial rudbeckia are a different species from sunflower-infecting strains, notwithstanding cross-infectivity, and genetically distinct from pre-epidemic populations infecting native rudbeckia hosts. PMID:27003506

  18. Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina

    PubMed Central

    Rodriguez-Rodrigues, Nahuel; Duran, Adriana; Bouzas, María Belen; Zapiola, Ines; Vila, Marcelo; Indyk, Debbie; Bissio, Emiliano; Salomon, Horacio; Dilernia, Dario A

    2013-01-01

    Objective Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years. Design We carried out a multi-site resistance surveillance study according to WHO HIV resistance guidelines, using a weighted sampling technique based on annual HIV case reports per site. Methods Blood samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed between March 2010 and August 2011 at 20 HIV voluntary counselling and testing centres in Buenos Aires. Clinical records of enrolled patients at the time of diagnosis were compiled. Viral load and CD4 counts were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis. Results We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations were largely the most prevalent (5.9%), accounting for 75% of all primary resistance and exhibiting a significant increase (p=0.0072) in prevalence during the past 10 years as compared to our previous study performed in 1997–2000 and in 2003–2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor primary resistance were low and similar to the one previously reported. Conclusions Levels of primary NNRTI resistance in Buenos Aires appear to be increasing in the context of a sustained ARV coverage and a high proportion of undiagnosed HIV-positive individuals. PMID:24093951

  19. Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges

    PubMed Central

    Nissapatorn, Veeranoot; Sawangjaroen, Nongyao

    2011-01-01

    After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leismaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. PMID:22310820

  20. Incidence and Risk Factors of Nasal Carriage of Staphylococcus aureus in HIV-Infected Individuals in Comparison to HIV-Uninfected Individuals: A Case-Control Study.

    PubMed

    Kotpal, Ruchi; S, Krishna Prakash; Bhalla, Preena; Dewan, Richa; Kaur, Ravinder

    2016-01-01

    The study was conducted to evaluate the prevalence of nasal colonization of Staphylococcus aureus in individuals with HIV infection attending the Integrated Counselling and Testing Centre in a teaching hospital and compare the prevalence with HIV-uninfected individuals. A case-control study was conducted among newly diagnosed HIV-infected individuals and an equal number of age-group and sex-matched HIV-uninfected individuals, and nasal swabs were collected from both the samples. Sociodemographic and clinical data were collected through individual interviews. Ethical aspects were respected. A total of 100 individuals participated in the study, and 22 (44%) of the 50 HIV-infected cases were colonized by S aureus, including 19 (86.4%) methicillin-sensitive S aureus (MSSA) and 3 (13.6%) methicillin-resistant S aureus (MRSA). Only 12 (24%) strains were isolated from 50 HIV-uninfected individuals, with 11 being MSSA and 1 being MRSA. This difference in the isolation rate was statistically significant (P = .035). The 2 most commonly encountered risk factors in both the groups appeared to be history of tuberculosis and history of surgical procedures but none being statistically significant (P = .093 and P = .996). All the strains of S aureus were sensitive to mupirocin. The study concluded that HIV-infected individuals are at a higher risk of carriage as compared to HIV-uninfected individuals. By eliminating carriage in immunocompromised individuals, infections due to S aureus can also be minimized.

  1. Expansion of the E138A mutation in newly diagnosed HIV-infected patients in Gran Canaria.

    PubMed

    Chamizo, Francisco; Gilarranz, Raúl; Tosco, Tomás; Carrillo, Deyanira; Holguín, África; Santana, Évora; Pérez-Arellano, Jose Luís; Hernández, Michele; Francés, Adela; Cárdenes, Miguel Ángel; Zarzalejos, Jose María; Pena-López, María José

    2016-09-01

    Molecular epidemiology allows us to know local HIV transmission and to design strategies of prevention. We studied 25 HIV newly diagnosed patients with the E138A mutation since the year 2010. Most transmission networks involved young and promiscuous men who have sex with men. Recent infection was only documented in patients grouped into the smaller clusters. PMID:27352730

  2. Individual consistency in the behaviors of newly-settled reef fish.

    PubMed

    White, James R; Meekan, Mark G; McCormick, Mark I

    2015-01-01

    Flexibility in behavior is advantageous for organisms that transition between stages of a complex life history. However, various constraints can set limits on plasticity, giving rise to the existence of personalities that have associated costs and benefits. Here, we document a field and laboratory experiment that examines the consistency of measures of boldness, activity, and aggressive behavior in the young of a tropical reef fish, Pomacentrus amboinensis (Pomacentridae) immediately following their transition between pelagic larval and benthic juvenile habitats. Newly-settled fish were observed in aquaria and in the field on replicated patches of natural habitat cleared of resident fishes. Seven behavioral traits representing aspects of boldness, activity and aggression were monitored directly and via video camera over short (minutes), medium (hours), and long (3 days) time scales. With the exception of aggression, these behaviors were found to be moderately or highly consistent over all time scales in both laboratory and field settings, implying that these fish show stable personalities within various settings. Our study is the first to examine the temporal constancy of behaviors in both field and laboratory settings in over various time scales at a critically important phase during the life cycle of a reef fish. PMID:26020013

  3. Individual consistency in the behaviors of newly-settled reef fish

    PubMed Central

    Meekan, Mark G.; McCormick, Mark I.

    2015-01-01

    Flexibility in behavior is advantageous for organisms that transition between stages of a complex life history. However, various constraints can set limits on plasticity, giving rise to the existence of personalities that have associated costs and benefits. Here, we document a field and laboratory experiment that examines the consistency of measures of boldness, activity, and aggressive behavior in the young of a tropical reef fish, Pomacentrus amboinensis (Pomacentridae) immediately following their transition between pelagic larval and benthic juvenile habitats. Newly-settled fish were observed in aquaria and in the field on replicated patches of natural habitat cleared of resident fishes. Seven behavioral traits representing aspects of boldness, activity and aggression were monitored directly and via video camera over short (minutes), medium (hours), and long (3 days) time scales. With the exception of aggression, these behaviors were found to be moderately or highly consistent over all time scales in both laboratory and field settings, implying that these fish show stable personalities within various settings. Our study is the first to examine the temporal constancy of behaviors in both field and laboratory settings in over various time scales at a critically important phase during the life cycle of a reef fish. PMID:26020013

  4. Individual Plasmodium vivax msp1 Variants within Polyclonal P. vivax Infections Display Different Propensities for Relapse

    PubMed Central

    Juliano, Jonathan J.; Kharabora, Oksana; Sem, Rithy; Lin, Feng-Chang; Muth, Sinuon; Ménard, Didier; Wongsrichanalai, Chansuda; Rogers, William O.; Meshnick, Steven R.

    2012-01-01

    Using a newly developed Plasmodium vivax merozoite surface protein 1 gene (Pvmsp1) heteroduplex tracking assay, we genotyped 107 P. vivax infections in individuals from Cambodia, 45 of whom developed recurrent parasitemia within 42 days. The majority of isolates were polyclonal, but recurrent parasitemias displayed fewer variants compared to initial parasitemias. Two Pvmsp1 gene variants occurred more frequently in the initial genotypes of those who developed recurrent parasitemia, representing the first time P. vivax variants associated with a higher risk of relapse have been described. PMID:22205791

  5. Individual Correlates of Infectivity of Influenza A Virus Infections in Households

    PubMed Central

    Tsang, Tim K.; Fang, Vicky J.; Chan, Kwok-Hung; Ip, Dennis K. M.; Leung, Gabriel M.; Peiris, J. S. Malik; Cauchemez, Simon

    2016-01-01

    Background Identifying individual correlates of infectivity of influenza virus is important for disease control and prevention. Viral shedding is used as a proxy measure of infectivity in many studies. However, the evidence for this is limited. Methods In a detailed study of influenza virus transmission within households in 2008–12, we recruited index cases with confirmed influenza infection from outpatient clinics, and followed up their household contacts for 7–10 days to identify secondary infections. We used individual-based hazard models to characterize the relationship between individual viral shedding and individual infectivity. Results We analyzed 386 households with 1147 household contacts. Index cases were separated into 3 groups according to their estimated level of viral shedding at symptom onset. We did not find a statistically significant association of virus shedding with transmission. Index cases in medium and higher viral shedding groups were estimated to have 21% (95% CI: -29%, 113%) and 44% (CI: -16%, 167%) higher infectivity, compared with those in the lower viral shedding group. Conclusions Individual viral load measured by RT-PCR in the nose and throat was at most weakly correlated with individual infectivity in households. Other correlates of infectivity should be examined in future studies. PMID:27153194

  6. Identification of Siglec-1 null individuals infected with HIV-1.

    PubMed

    Martinez-Picado, Javier; McLaren, Paul J; Erkizia, Itziar; Martin, Maureen P; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M; Penugonda, Sudhir; Günthard, Huldrych F; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-01-01

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. PMID:27510803

  7. Identification of Siglec-1 null individuals infected with HIV-1

    PubMed Central

    Martinez-Picado, Javier; McLaren, Paul J.; Erkizia, Itziar; Martin, Maureen P.; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M.; Penugonda, Sudhir; Günthard, Huldrych F.; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-01-01

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. PMID:27510803

  8. Dyslipidemia in HIV-infected individuals: from pharmacogenetics to pharmacogenomics.

    PubMed

    Tarr, Philip E; Rotger, Margalida; Telenti, Amalio

    2010-04-01

    HIV-infected individuals may have accelerated atherogenesis and an increased risk for premature coronary artery disease. Dyslipidemia represents a key pro-atherogenic mechanism. In HIV-infected patients, dyslipidemia is typically attributed to the adverse effects of antiretroviral therapy. Nine recent genome-wide association studies have afforded a comprehensive, unbiased inventory of common SNPs at 36 genetic loci that are reproducibly associated with dyslipidemia in the general population. Genome-wide association study-validated SNPs have now been demonstrated to contribute to dyslipidemia in the setting of HIV infection and antiretroviral therapy. In a Swiss HIV-infected study population, a similar proportion of serum lipid variability was explained by antiretroviral therapy and by genetic background. In the individual patient, both antiretroviral therapy and the cumulative effect of SNPs contribute to the risk of high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol and hypertriglyceridemia. Genetic variants presumably contribute to additional major metabolic complications in HIV-infected individuals, including diabetes mellitus and coronary artery disease. In an effort to explain an increasing proportion of the heritability of complex metabolic traits, ongoing large-scale gene resequencing studies are focusing on the effects of rare SNPs and structural genetic variants.

  9. Tobacco use and cessation in HIV-infected individuals

    PubMed Central

    Wewers, Mary Ellen; Ferketich, Amy; Diaz, Philip

    2013-01-01

    Synopsis The smoking prevalence estimates among HIV-infected individuals range from 40%-84%; much higher than the overall adult prevalence in the United States. Characteristics that are associated with smokers who are HIV-positive include drug and alcohol abuse, psychiatric comorbidities, and lower education and socioeconomic status. There are important health implications for HIV-infected smokers, including bacterial and Pneumocystis pneumonia, tuberculosis, COPD, lung cancer and coronary artery disease. To date, there have been few tobacco dependence treatment trials conducted among HIV-infected smokers. Most have used nicotine replacement therapy but abstinence rates were low. A recent preliminary study found the use of varenicline to be well tolerated and it may increase abstinence rates with HIV-infected individuals. Recommendations for future research include examining underlying factors that contribute to persistent smoking and barriers to abstinence, identifying ways to increase motivation for quit attempts, increasing the number of multi-centered, two-arm tobacco dependence treatment trials, and using highly efficacious first-line pharmacotherapy in tobacco dependence treatment intervention studies. Addressing the above-mentioned research gaps will help to reduce the tobacco-related disease burden of HIV-infected individuals in the future. PMID:23702169

  10. Intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt.

    PubMed

    Shehata, Amany I; Hassanein, Faika

    2015-01-01

    This cross-sectional study was carried to determine the prevalence of intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt, in the period from December 2012 till November 2013. The study was conducted on 200 institutionalized and non-institutionalized mentally handicapped individuals. Fresh stool samples were subjected to different stains including; trichrome for detecting intestinal protozoa, modified acid fast stain for intestinal coccidia and quick hot gram chromotrope stain for Microsporidia. Also they were processed by Kato-Katz and formol ethyl acetate techniques for intestinal helminths. Additionally, blood samples were collected for measuring hemoglobin levels. Out of 200 mentally handicapped individuals, 87 (43.5%) were infected. The infection rates were 44.6% and 42.6% for non-institutionalized and institutionalized people, respectively. Regarding gender, 46.7% and 38.5% were reported for the males and females respectively. The most common parasites detected were: Cryptosporidium sp. (23.5%), microsporidia (15%), Giardia lamblia (8.5%), Dientamoeba fragilis (8%), Cyclospora cyatanensis (7.5%), Blastocystis hominis (6.5%), Entamoeba histolytica (5.5%) and Entamoeba coli (2.5%). Rates for Isospora belli and Enterobius vermicularis were estimated to be 1.5% for each, while lower rate was reported for Iodamoeba butschlii (1.0%). Prevalence of infections among mentally handicapped individuals are indications for several risk factors, including improper sanitary hygiene and illiteracy about personal hygiene. Therefore, frequent investigations, health care and medical intervention are needed. PMID:26878626

  11. Intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt.

    PubMed

    Shehata, Amany I; Hassanein, Faika

    2015-01-01

    This cross-sectional study was carried to determine the prevalence of intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt, in the period from December 2012 till November 2013. The study was conducted on 200 institutionalized and non-institutionalized mentally handicapped individuals. Fresh stool samples were subjected to different stains including; trichrome for detecting intestinal protozoa, modified acid fast stain for intestinal coccidia and quick hot gram chromotrope stain for Microsporidia. Also they were processed by Kato-Katz and formol ethyl acetate techniques for intestinal helminths. Additionally, blood samples were collected for measuring hemoglobin levels. Out of 200 mentally handicapped individuals, 87 (43.5%) were infected. The infection rates were 44.6% and 42.6% for non-institutionalized and institutionalized people, respectively. Regarding gender, 46.7% and 38.5% were reported for the males and females respectively. The most common parasites detected were: Cryptosporidium sp. (23.5%), microsporidia (15%), Giardia lamblia (8.5%), Dientamoeba fragilis (8%), Cyclospora cyatanensis (7.5%), Blastocystis hominis (6.5%), Entamoeba histolytica (5.5%) and Entamoeba coli (2.5%). Rates for Isospora belli and Enterobius vermicularis were estimated to be 1.5% for each, while lower rate was reported for Iodamoeba butschlii (1.0%). Prevalence of infections among mentally handicapped individuals are indications for several risk factors, including improper sanitary hygiene and illiteracy about personal hygiene. Therefore, frequent investigations, health care and medical intervention are needed.

  12. Urinary tract infection in individuals with spinal cord lesion.

    PubMed

    Biering-Sørensen, Fin

    2002-01-01

    Urinary tract infection is the most frequently reported secondary impairment in individuals with spinal cord lesion. The most prevalent risk indicator is an indwelling catheter. Hydrophilic catheters for clean intermittent catheterization may induce lower rates of bacteriuria and long-term urethral complications. Due to chronic bacterial infection within biofilms, an antibacterial treatment based on a urinary culture of bacteria in the urine and its antimicrobial susceptibility may fail to eradicate catheter-associated urinary tract infection. No commercially available drugs are sufficiently active against the bacteria in a mature biofilm. Biomaterials may be modified to decrease the formation of a biofilm. Silver alloy catheters are effective in preventing urinary tract infection when indwelling urinary catheterization is necessary. The risk of systemic argyria in long-term use needs to be evaluated. Suprapubic cystostomy drainage in patients with neurogenic bladder is preferred to an indwelling urethral catheter. In cases of recurring urinary tract infection in patients with a permanent urinary catheter, it may be beneficial to change the catheter every 1 or 2 weeks. There is some evidence that cranberry products may prevent urinary tract infection. In the future, bacterial interference and vaccination may be a possibility for prevention of urinary tract infection.

  13. Behavior of susceptible-vaccinated-infected-recovered epidemics with diversity in the infection rate of individuals

    NASA Astrophysics Data System (ADS)

    Cai, Chao-Ran; Wu, Zhi-Xi; Guan, Jian-Yue

    2013-12-01

    We study a susceptible-vaccinated-infected-recovered (SVIR) epidemic-spreading model with diversity of infection rate of the individuals. By means of analytical arguments as well as extensive computer simulations, we demonstrate that the heterogeneity in infection rate can either impede or accelerate the epidemic spreading, which depends on the amount of vaccinated individuals introduced in the population as well as the contact pattern among the individuals. Remarkably, as long as the individuals with different capability of acquiring the disease interact with unequal frequency, there always exist a cross point for the fraction of vaccinated, below which the diversity of infection rate hinders the epidemic spreading and above which expedites it. The overall results are robust to the SVIR dynamics defined on different population models; the possible applications of the results are discussed.

  14. Clinical management considerations for dyslipidemia in HIV-infected individuals.

    PubMed

    Kirchner, Jeffrey T

    2012-01-01

    Dyslipidemia is common in patients with human immunodeficiency virus (HIV) and may result in significant morbidity, including coronary heart disease (CHD). Treatment of dyslipidemia in these patients is generally based on the National Cholesterol Education Program Adult Treatment Panel III goals for individuals without HIV. For individuals with ≥ 2 cardiovascular risk factors, the risk of CHD should be evaluated using the Framingham risk calculator and managed accordingly. Switching to an antiretroviral regimen with a favorable lipid profile should be considered before pharmacologic management if virologic suppression can be maintained. Statins are the first-choice therapy for elevated low-density lipoprotein cholesterol, but in HIV-infected individuals, special consideration must be given to drug-drug interactions, specifically those between protease inhibitors and statins. Management of dyslipidemia in HIV-infected individuals is a challenging but important aspect of chronic disease management. Additional research, specifically related to the role of chronic inflammation, is needed to better define the relationship between HIV infection and cardiovascular disease.

  15. Infection Dynamics and Immune Response in a Newly Described Drosophila-Trypanosomatid Association

    PubMed Central

    Votýpka, Jan; Dostálová, Anna; Yurchenko, Vyacheslav; Bird, Nathan H.; Lukeš, Julius; Lemaitre, Bruno

    2015-01-01

    ABSTRACT Trypanosomatid parasites are significant causes of human disease and are ubiquitous in insects. Despite the importance of Drosophila melanogaster as a model of infection and immunity and a long awareness that trypanosomatid infection is common in the genus, no trypanosomatid parasites naturally infecting Drosophila have been characterized. Here, we establish a new model of trypanosomatid infection in Drosophila—Jaenimonas drosophilae, gen. et sp. nov. As far as we are aware, this is the first Drosophila-parasitic trypanosomatid to be cultured and characterized. Through experimental infections, we find that Drosophila falleni, the natural host, is highly susceptible to infection, leading to a substantial decrease in host fecundity. J. drosophilae has a broad host range, readily infecting a number of Drosophila species, including D. melanogaster, with oral infection of D. melanogaster larvae resulting in the induction of numerous immune genes. When injected into adult hemolymph, J. drosophilae kills D. melanogaster, although interestingly, neither the Imd nor the Toll pathway is induced and Imd mutants do not show increased susceptibility to infection. In contrast, mutants deficient in drosocrystallin, a major component of the peritrophic matrix, are more severely infected during oral infection, suggesting that the peritrophic matrix plays an important role in mediating trypanosomatid infection in Drosophila. This work demonstrates that the J. drosophilae-Drosophila system can be a powerful model to uncover the effects of trypanosomatids in their insect hosts. PMID:26374124

  16. Copro-diagnosis of Echinococcus granulosus infection in dogs by amplification of a newly identified repeated DNA sequence.

    PubMed

    Abbasi, Ibrahim; Branzburg, Anna; Campos-Ponce, Maiza; Abdel Hafez, Sami K; Raoul, Francis; Craig, Philip S; Hamburger, Joseph

    2003-09-01

    Diagnosis of Echinococcus granulosus infection in dogs by detecting adult worms recovered post mortem or purged from the intestines after treatment with arecoline is not suitable for mass screening. Large-scale diagnosis by detection of copro-antigens is useful but only with relatively high intensity infections, and only by genus. To provide a more sensitive and specific diagnosis, a polymerase chain reaction (PCR) assay was developed, that amplified a target repeated sequence (EgG1 Hae III) newly identified in the genome of the common sheep strain of E. granulosus. This repeated sequence consists of approximately 6,900 copies, arranged in tandem, in groups of 2-6 repeats. The corresponding primers used in the PCR easily detected a single egg with no cross-amplification of DNA from closely related cestodes, including E. multilocularis and Taenia spp. Fecal samples from naturally infected dogs, with 2-10,000 E. granulosus worms at necropsy, were all PCR positive, while E. multilocularis or Taenia spp. positive controls as well as non-endemic controls were all PCR negative. This copro-PCR assay was demonstrated to be 100% specific and also detected all necropsy-positive E. granulosus-infected dogs. It is suggested that this copro-PCR assay has the potential for pre-mortem diagnosis of E. granulosus infection even in areas where E. granulosus and E. multilocularis are co-endemic.

  17. The interplay of infections, function and length of stay (LOS) in newly admitted geriatric psychiatry patients.

    PubMed

    Malyuk, Rhonda E; Wong, Carol; Buree, Barbara; Kang, Arvind; Kang, Nirmal

    2012-01-01

    The purpose of this study was to determine the impact of identifying and treating infections on functional outcomes and length of stay (LOS). Our retrospective naturalistic study reviewed all new admissions to a tertiary geriatric psychiatry teaching hospital from 2003 to 2007. Over this four-year period, 390 patients were admitted and discharged with 21% (85) of patients identified as having infections on admission. Those with infections were compared to the group without to determine and compare clinical characteristics. Factors included in analysis were: age, gender, diagnoses, medical comorbidity, neuropsychiatric symptoms, functional outcomes, medications and LOS. Both groups were similar in gender, psychiatric diagnoses and severity of dementia. Those requiring antibiotics for treatment of infections on admission, were older (p=0.003), had poorer baseline function (p=0.005) and higher medical comorbidity (p<0.001). At discharge, the group with infections showed greater functional improvement (p<0.001), particularly in mobility (p=0.005) and cognition (p=0.046), and had a shorter LOS (p=0.02). We conclude that a significant number of patients in tertiary geriatric services continue to have infections on admission. Early identification and treatment of infections can result in improved function and decreased LOS. PMID:21377222

  18. Psychiatric Disorders in HTLV-1-Infected Individuals with Bladder Symptoms

    PubMed Central

    Orge, Glória O.; Dellavechia, Thais R.; Carneiro-Neto, José Abraão; Araújo-de-Freitas, Lucas; Daltro, Carla H. C.; Santos, Carlos T.; Quarantini, Lucas C.

    2015-01-01

    Background Previous studies have reported high rates of depression and anxiety in HTLV-1 infected individuals with the neurological disease and in the asymptomatic phase. No study has investigated the rates in individuals that already show bladder symptoms without severe neurological changes; that is, during the oligosymptomatic phase. The present study investigated patients in this intermediate form on the spectrum of the infection. Methodology/Principal Findings Participants answered a sociodemographic questionnaire, the Mini International Neuropsychiatric Interview Brazilian Version 5.0.0 (MINI PLUS) and the Hospital Anxiety and Depression Scale (HADS). Data analysis was performed in STATA statistical software (version 12.0). Depressive disorder was the most frequent comorbidity. Current depressive disorder was higher in the group of overactive bladder subjects (11.9%), and lifelong depression was more frequent in the HAM/TSP group (35%). The three groups had similar frequencies of anxiety disorders. Increased frequency and severity of anxiety and depression symptoms were observed in the overactive bladder group. Conclusion/Significance The results suggest that individuals with overactive bladders need a more thorough assessment from the mental health perspective. These patients remain an understudied group regarding psychiatric comorbidities. PMID:26018525

  19. The Role of Helminth Infection and Environment in the Development of Allergy: A Prospective Study of Newly-Arrived Ethiopian Immigrants in Israel.

    PubMed

    Stein, Miguel; Greenberg, Zalman; Boaz, Mona; Handzel, Zeev T; Meshesha, Mesfin K; Bentwich, Zvi

    2016-01-01

    Helminth infection may be protective against allergy and account for the low prevalence of allergy in developing countries. We studied prospectively the prevalence of allergy in Ethiopian immigrants with heavy helminth infection on arrival in Israel, and again after a year of adjustment to an urban industrialized setting, to explore the roles of helminth infection, changed environment and background immunity on the manifestations of allergy. 126 newly arrived Ethiopian immigrants were studied at baseline and 115 after a year of follow up in Israel. Allergic symptoms, Skin prick tests (SPT), Tuberculin (PPD) skin tests, stool and blood samples were obtained for determining parasites, blood IgE and eosinophil levels, respectively. Anti-helminthic therapy was offered to the entire infected individuals, but only 50/108 (46.3%) took the medication. At baseline, there was a significant negative association between helminth infection and allergy, 4/18 (22.2%) of uninfected participants were allergic compared to 7/108 (6.5%) of helminth-infected participants (p = 0.028), as well as between helminth infection and SPT reactivity, 12/18 (66.6%) of uninfected participants compared to 43/108 (39.8%) of helminth-infected participants (p = 0.033). After one year, a significant general increase in allergy and SPT was observed. While only 11/126 (8.7%) were allergic at baseline, 30/115 (26.1%) became allergic at follow-up (p<0.0001), and while 55/126 (43.7%) were SPT+ at baseline, 79/115 (68.7%) became SPT+ at follow-up (p<0.001). A twofold increase in allergen sensitization was also observed after one year in Israel, particularly for dust mites, grasses and olive tree (p<0.001). These results show that: a) Helminth infection is significantly associated with low allergy and low SPT reactivity; b) One year after immigration to Israel, allergy and SPT reactivity increased significantly in all immigrants; c) Higher increases in positive SPT and allergy were observed after a year in

  20. The Role of Helminth Infection and Environment in the Development of Allergy: A Prospective Study of Newly-Arrived Ethiopian Immigrants in Israel

    PubMed Central

    Stein, Miguel; Greenberg, Zalman; Boaz, Mona; Handzel, Zeev T.; Meshesha, Mesfin K.; Bentwich, Zvi

    2016-01-01

    Helminth infection may be protective against allergy and account for the low prevalence of allergy in developing countries. We studied prospectively the prevalence of allergy in Ethiopian immigrants with heavy helminth infection on arrival in Israel, and again after a year of adjustment to an urban industrialized setting, to explore the roles of helminth infection, changed environment and background immunity on the manifestations of allergy. 126 newly arrived Ethiopian immigrants were studied at baseline and 115 after a year of follow up in Israel. Allergic symptoms, Skin prick tests (SPT), Tuberculin (PPD) skin tests, stool and blood samples were obtained for determining parasites, blood IgE and eosinophil levels, respectively. Anti-helminthic therapy was offered to the entire infected individuals, but only 50/108 (46.3%) took the medication. At baseline, there was a significant negative association between helminth infection and allergy, 4/18 (22.2%) of uninfected participants were allergic compared to 7/108 (6.5%) of helminth-infected participants (p = 0.028), as well as between helminth infection and SPT reactivity, 12/18 (66.6%) of uninfected participants compared to 43/108 (39.8%) of helminth-infected participants (p = 0.033). After one year, a significant general increase in allergy and SPT was observed. While only 11/126 (8.7%) were allergic at baseline, 30/115 (26.1%) became allergic at follow-up (p<0.0001), and while 55/126 (43.7%) were SPT+ at baseline, 79/115 (68.7%) became SPT+ at follow-up (p<0.001). A twofold increase in allergen sensitization was also observed after one year in Israel, particularly for dust mites, grasses and olive tree (p<0.001). These results show that: a) Helminth infection is significantly associated with low allergy and low SPT reactivity; b) One year after immigration to Israel, allergy and SPT reactivity increased significantly in all immigrants; c) Higher increases in positive SPT and allergy were observed after a year in

  1. The Role of Helminth Infection and Environment in the Development of Allergy: A Prospective Study of Newly-Arrived Ethiopian Immigrants in Israel.

    PubMed

    Stein, Miguel; Greenberg, Zalman; Boaz, Mona; Handzel, Zeev T; Meshesha, Mesfin K; Bentwich, Zvi

    2016-01-01

    Helminth infection may be protective against allergy and account for the low prevalence of allergy in developing countries. We studied prospectively the prevalence of allergy in Ethiopian immigrants with heavy helminth infection on arrival in Israel, and again after a year of adjustment to an urban industrialized setting, to explore the roles of helminth infection, changed environment and background immunity on the manifestations of allergy. 126 newly arrived Ethiopian immigrants were studied at baseline and 115 after a year of follow up in Israel. Allergic symptoms, Skin prick tests (SPT), Tuberculin (PPD) skin tests, stool and blood samples were obtained for determining parasites, blood IgE and eosinophil levels, respectively. Anti-helminthic therapy was offered to the entire infected individuals, but only 50/108 (46.3%) took the medication. At baseline, there was a significant negative association between helminth infection and allergy, 4/18 (22.2%) of uninfected participants were allergic compared to 7/108 (6.5%) of helminth-infected participants (p = 0.028), as well as between helminth infection and SPT reactivity, 12/18 (66.6%) of uninfected participants compared to 43/108 (39.8%) of helminth-infected participants (p = 0.033). After one year, a significant general increase in allergy and SPT was observed. While only 11/126 (8.7%) were allergic at baseline, 30/115 (26.1%) became allergic at follow-up (p<0.0001), and while 55/126 (43.7%) were SPT+ at baseline, 79/115 (68.7%) became SPT+ at follow-up (p<0.001). A twofold increase in allergen sensitization was also observed after one year in Israel, particularly for dust mites, grasses and olive tree (p<0.001). These results show that: a) Helminth infection is significantly associated with low allergy and low SPT reactivity; b) One year after immigration to Israel, allergy and SPT reactivity increased significantly in all immigrants; c) Higher increases in positive SPT and allergy were observed after a year in

  2. Combination of Antiretroviral Drugs and Radioimmunotherapy Specifically Kills Infected Cells from HIV-Infected Individuals

    PubMed Central

    Tsukrov, Dina; McFarren, Alicia; Morgenstern, Alfred; Bruchertseifer, Frank; Dolce, Eugene; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Berman, Joan W.; Schoenbaum, Ellie; Zingman, Barry S.; Casadevall, Arturo; Dadachova, Ekaterina

    2016-01-01

    Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs) were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal antibody to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: 10 on ART and 5 ART-naïve. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART and supports continued development of 213Bi-2556 for co-administration with ART toward an HIV eradication strategy. PMID:27725930

  3. Drug resistance among newly-diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis

    PubMed Central

    Kuhn, Louise; Hunt, Gillian; Technau, Karl-Günter; Coovadia, Ashraf; Ledwaba, Johanna; Pickerill, Sam; Penazzato, Martina; Bertagnolio, Silvia; Mellins, Claude A.; Black, Vivian; Morris, Lynn; Abrams, Elaine J.

    2015-01-01

    Background In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. Methods HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly-diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy (cART) for pregnant women, were being implemented. Results Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had non-nucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor (PI) mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures but resistance to NNRTI was detected in 24.0%, NRTI in 10.7% and PI in 1.3%. Conclusion The new PMTCT strategies dramatically reduce the number of children who acquire infection but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pre-treatment drug resistance. Our results support the use of PI-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history. PMID:24785949

  4. Mortality in HIV infected individuals in Pune, India

    PubMed Central

    Ghate, Manisha; Deshpande, Swapna; Tripathy, Srikanth; Godbole, Sheela; Nene, Madhura; Thakar, Madhuri; Risbud, Arun; Bollinger, Robert; Mehendale, Sanjay

    2011-01-01

    Background & objectives: With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India Methods: A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death. Results: Median CD4 count in study participants was 218 cells/µl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/µl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively]. Interpretation & conclusions: High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme. PMID:21537095

  5. A Comparison of Individual-Level and Community-Level Predictors of Marijuana and Cocaine Use among a Sample of Newly Arrested Juvenile Offenders

    ERIC Educational Resources Information Center

    Childs, Kristina; Dembo, Richard; Belenko, Steven; Wareham, Jennifer; Schmeidler, James

    2011-01-01

    Variations in drug use have been found across individual-level factors and community characteristics, and by type of drug used. Relatively little research, however, has examined this variation among juvenile offenders. Based on a sample of 924 newly arrested juvenile offenders, two multilevel logistic regression models predicting marijuana test…

  6. OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia.

    PubMed

    Hirano, Taizou; Kikuchi, Toshiaki; Tode, Naoki; Santoso, Arif; Yamada, Mitsuhiro; Mitsuhashi, Yoshiya; Komatsu, Riyo; Kawabe, Takeshi; Tanimoto, Takeshi; Ishii, Naoto; Tanaka, Yuetsu; Nishimura, Hidekazu; Nukiwa, Toshihiro; Watanabe, Akira; Ichinose, Masakazu

    2016-01-01

    Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 deficiency, resulting in decreased susceptibility to influenza viral infection. Upon infection, bronchiolar progenitors increase in number for repairing the influenza-damaged epithelia. The OX40L expression is induced on the progenitors for the antiviral immunity during the infectious process. However, these defense-like host responses lead to more extensive infection owing to the induced OX40L with α-2,6 sialic acid modification, which augments the interaction with the viral hemagglutinin. In fact, the specific antibody against the sialylated site of OX40L exhibited therapeutic potency in mitigating the OX40L-mediated susceptibility to influenza. Our data illustrate that the influenza-induced expression of OX40L on bronchiolar progenitors has pathogenic value to develop a novel therapeutic approach against influenza. PMID:26976612

  7. Hepatitis B Vaccination and Risk of Hepatitis B Infection in HIV-Infected Individuals

    PubMed Central

    Landrum, Michael L.; Hullsiek, Katherine Huppler; Ganesan, Anuradha; Weintrob, Amy C.; Crum-Cianflone, Nancy F.; Barthel, Vincent R.; O’Connell, Robert J.; Fieberg, Ann; Chun, Helen M.; Marconi, Vincent C.; Dolan, Matthew J.; Agan, Brian K.

    2009-01-01

    Objective To assess the association of HBV vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees. Design Observational cohort study Methods Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models. Results During 11,632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75–2.27) /100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted HR 0.86, 95% CI 0.7–1.1; adjusted HR 1.08, 95% CI 0.8–1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (HR 0.96; 95% CI 0.56–1.64). Among 409 vaccinees with HBsAb <10 IU/L, 46 (11.2%) developed HBV infection compared to 11 of 217 (5.1%) vaccinees with HBsAb ≥10 IU/L (HR 0.51; 95% CI 0.3–1.0). In participants with initial HBsAb <10 IU/L, 16/46 (35%) infections were chronic, compared to 0/11 in those with initial HBsAb ≥10 IU/L (p=0.02). Conclusion Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients. PMID:19487908

  8. Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections.

    PubMed

    Ferreira, João Leandro de Paula; Thomaz, Mariana; Rodrigues, Rosangela; Harrad, David; Oliveira, Cristina Mendes; Oliveira, Carmem Aparecida de Freitas; Batista, João Paulo Gervasio; Ito, Tomoko Sezazake; Brigido, Luis Fernando de Macedo

    2008-12-01

    As in many areas of Brazil, the AIDS epidemic in Curitiba is relatively stable, but surveillance is important to support public policy. The molecular characteristics of HIV may be instrumental for monitoring epidemic trends. We evaluated plasma HIV-1 RNA (n = 37) from 38 cases presenting with positive serology, who were among 820 consenting volunteers visiting the downtown counselling and serology testing centre. Seroprevalence was 4.6% (CI 95% 3.2-6.3) and the estimated HIV incidence, as defined by the BED assay, was 2.86 persons/years (CI 95% 1.04-4.68). An additional set of contemporaneous, anonymous samples from a local laboratory was also analysed (n = 20). Regions of the HIV-1 polymerase (n = 57) and envelope (n = 34) were evaluated for subtyping, determination of mosaic structure, primary drug resistance mutations (pDRM), envelope V3 loop motifs and amino acid signatures related to viral tropism. HIV-1 clade B was observed in 53% of cases; HIV-1C in 30% and BC mosaics in 14%, with one F genome and one CF mosaic. Clade C infection was associated with recent infections among males (p < 0.03). Stanford surveillance pDRM was observed in 8.8% of sequences, with 7% showing high level resistance to at least one antiretroviral drug. Tropism for CXCR4 co-receptor was predicted in 18% of envelope sequences, which were exclusively among clade B genomes and cases with serological reactivity to chronic infection.

  9. Detection of classical and newly described staphylococcal superantigen genes in coagulase-negative staphylococci isolated from bovine intramammary infections

    PubMed Central

    Park, Joo Youn; Fox, Lawrence K.; Seo, Keun Seok; McGuire, Mark A.; Park, Yong Ho; Rurangirwa, Fred R.; Sischo, William M.; Bohach, Gregory A.

    2013-01-01

    The coagulase negative staphylococci (CNS) are the most prevalent mastitis pathogen group yet their virulence characteristics have not been well described. We investigated the presence of 19 classical and newly described staphylococcal superantigen (SAg) genes in CNS isolates from bovine intramammary infections (IMI). A total of 263 CNS representing 11 different Staphylococcus spp. were examined, and 31.2% (n = 82) of CNS isolates had one or more SAg genes; there were 21 different SAg gene combinations. The most prevalent combination of SAg genes (seb, seln, and selq; n = 45) was found in S. chromogenes, S. xylosus, S. haemolyticus, S. sciuri subsp. carnaticus, S. simulans and S. succinus. The genes for SAgs appear to be widely distributed amongst CNS isolated from bovine IMI. PMID:20667668

  10. Detection of classical and newly described staphylococcal superantigen genes in coagulase-negative staphylococci isolated from bovine intramammary infections.

    PubMed

    Park, Joo Youn; Fox, Lawrence K; Seo, Keun Seok; McGuire, Mark A; Park, Yong Ho; Rurangirwa, Fred R; Sischo, William M; Bohach, Gregory A

    2011-01-10

    The coagulase-negative staphylococci (CNS) are the most prevalent mastitis pathogen group yet their virulence characteristics have not been well described. We investigated the presence of 19 classical and newly described staphylococcal superantigen (SAg) genes in CNS isolates from bovine intramammary infections (IMI). A total of 263 CNS representing 11 different Staphylococcus spp. were examined, and 31.2% (n=82) of CNS isolates had one or more SAg genes; there were 21 different SAg gene combinations. The most prevalent combination of SAg genes (seb, seln and selq; n=45) was found in S. chromogenes, S. xylosus, S. haemolyticus, S. sciuri subsp. carnaticus, S. simulans and S. succinus. The genes for SAgs appear to be widely distributed amongst CNS isolated from bovine IMI. PMID:20667668

  11. The needs of AIDS-infected individuals in rural China.

    PubMed

    Lu, Yun Luke; Trout, Shirley K; Lu, Katarina; Creswell, John W

    2005-11-01

    The purpose of this exploratory case study was to describe the needs and present the voices of 21 AIDS-infected individuals who contracted the disease through the selling of blood in rural China. Data sources included interviews, field notes, and letters. Three themes emerged: living in a vicious circle, awakening from the dead end, and escaping the vicious circle through education. Education emerged as an overarching theme and was identified as the catalyst that would either keep the families of those affected trapped in the vicious circle or rescue them from it. Findings are explained within the theoretical contexts of social capital, motivation theory, and Confucius's philosophy on education. The authors discuss implications for researchers, educators, relief workers, human service workers, policy makers, and human rights advocates. They conclude with suggestions for further study.

  12. Short Communication: Neutralizing Antibodies in HIV-1-Infected Brazilian Individuals

    PubMed Central

    Morgado, Mariza Gonçalvez; Côrtes, Fernanda Heloise; Guimarães, Monick Lindermeyer; Mendonça-Lima, Leila; Pilotto, Jose Henrique; Grinsztejn, Beatriz; Veloso, Valdiléa Gonçalves; Bongertz, Vera

    2013-01-01

    Abstract Tests for the detection of the humoral immune response to HIV-1 have to be standardized and established, demanding regional efforts. For this purpose the neutralizing antibody (NAb) assay for HIV-1 in TZM-bl cells was introduced in Brazil. Twenty plasma samples from HIV-1-infected individuals were assayed: 10 progressors and 10 long-term nonprogressors. These were tested against eight env-pseudotyped viruses (psVs) in the TZM-bl NAb assay and against HIV-1 strain HTLV/IIIB (HIV-1 IIIB) in primary lymphocytes. Forty-four percent of the samples showed neutralizing titers for psVs and 55% for HIV-1 IIIB. Plasma from progressors showed a broader neutralization and a higher potency. The introduction of these reference reagents encourages the participation of Brazil in future comparative assessments of anti-HIV-1 antibodies. PMID:23145941

  13. Differential Gene Expression in HIV-Infected Individuals Following ART

    PubMed Central

    Massanella, Marta; Singhania, Akul; Beliakova-Bethell, Nadejda; Pier, Rose; Lada, Steven; White, Cory H.; Pérez-Santiago, Josué; Blanco, Julià; Richman, Douglas D.; Little, Susan J.; Woelk, Christopher H.

    2013-01-01

    Previous studies of the effect of ART on gene expression in HIV-infected individuals have identified small numbers of modulated genes. Since these studies were underpowered or cross-sectional in design, a paired analysis of peripheral blood mononuclear cells (PBMCs), isolated before and after ART, from a robust number of HIV-infected patients (N=32) was performed. Gene expression was assayed by microarray and 4,157 differentially expressed genes (DEGs) were identified following ART using multivariate permutation tests. Pathways and Gene Ontology (GO) terms over-represented for DEGs reflected the transition from a period of active virus replication before ART to one of viral suppression (e.g., repression of JAK-STAT signaling) and possible prolonged drug exposure (e.g. oxidative phosphorylation pathway) following ART. CMYC was the DEG whose product made the greatest number of interactions at the protein level in protein interaction networks (PINs), which has implications for the increased incidence of Hodgkin’s lymphoma (HL) in HIV-infected patients. The differential expression of multiple genes was confirmed by RT-qPCR including well-known drug metabolism genes (e.g., ALOX12 and CYP2S1). Targets not confirmed by RT-qPCR (i.e., GSTM2 and RPL5) were significantly confirmed by droplet digital (ddPCR), which may represent a superior method when confirming DEGs with low fold changes. In conclusion, a paired design revealed that the number of genes modulated following ART was an order of magnitude higher than previously recognized. PMID:23933117

  14. Perturbations in the Lipid Profile of Individuals with Newly Diagnosed Type 1 Diabetes Mellitus: Lipidomics Analysis of a Diabetes Antibody Standardization Program Sample Subset

    SciTech Connect

    Sorensen, Christina M.; Ding, Jie; Zhang, Qibin; Alquier, Thierry; Zhao, Rui; Mueller, Patricia W.; Smith, Richard D.; Metz, Thomas O.

    2010-08-01

    Objectives: To characterize the lipid profile of individuals with newly diagnosed type 1 diabetes mellitus using LC-MS-based lipidomics and the accurate mass and time (AMT) tag approach. Design and methods: Lipids were extracted from plasma and sera of 10 subjects from the Diabetes Antibody Standardization Program (years 2000-2005) and 10 non-diabetic subjects and analyzed by capillary liquid chromatography coupled with a hybrid ion-trap-Fourier transform ion cyclotron resonance mass spectrometer. Lipids were identified and quantified using the AMT tag approach. Results: Five hundred sixty lipid features differentiated (q < 0.05) diabetic from healthy individuals in a partial least-squares analysis, characterizing of individuals with recently diagnosed type 1 diabetes mellitus. Conclusions: A lipid profile associated with newly diagnosed type 1 diabetes may aid in further characterization of biochemical pathways involved in lipid regulation or mobilization and lipotoxicity of pancreatic beta-cells.

  15. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract.

  16. Splenic tuberculosis in a patient with newly diagnosed advanced HIV infection.

    PubMed

    Tiri, B; Saraca, L M; Luciano, E; Burkert, F R; Cappanera, S; Cenci, E; Francisci, D

    2016-01-01

    The extra-pulmonary tuberculosis (TB) constitutes to about 20% of all TB cases. Among extra-pulmonary form, splenic TB is very rare clinical condition especially as initial manifestation in a developed country. Diagnosis of splenic TB is challenging because it presents no specific symptoms or typical imaging findings and microbiological confirmation is not straight forward. We describe the case of a 55 year old Italian female with advanced HIV infection whose first AIDS clinical manifestation was a TB splenic abscess.On CT, the lesion was multilocular, hypovascular, 34 mm large, and presented contrast enhancement and a spoke wheel pattern; it was initially considered a cystic formation of parasitic nature. In this patient clinical manifestations were nonspecific (nightly fever, weight loss, and fatigue); as diagnostic imaging could not pinpoint the underlying etiology, microbiological and molecular examinations of spleen abscess drainage proved pivotal for the diagnosis. The patient improved clinically with antitubercular therapy. The rarityof splenic tuberculosis in an European patient coupled with the involvement of the spleen in isolation and outside the "miliary" setting prompted us to report this case. PMID:27635384

  17. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract. PMID:27346304

  18. Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India.

    PubMed

    Chaaithanya, I K; Bhattacharya, D; Muruganandam, N; Thamizhmani, R; Babu, B V Suresh; Sundaram, S G; Matta, M; Singh, S S; Vijayachari, P

    2012-10-01

    Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.

  19. Auditory impairments in HIV-infected individuals in Tanzania

    PubMed Central

    Maro, Isaac I.; Moshi, Ndeserua; Clavier, Odile H.; MacKenzie, Todd A.; Kline-Schoder, Robert J.; Wilbur, Jed C.; Chambers, Robert D.; Fellows, Abigail M.; Jastrzembski, Benjamin G.; Mascari, John E.; Bakari, Muhammad; Matee, Mecky; Musiek, Frank E.; Waddell, Richard D.; von Reyn, C. Fordham; Buckey, Jay C.

    2014-01-01

    Objectives Abnormal hearing tests have been noted in HIV-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. We performed a cross-sectional study of both HIV+ and HIV− individuals in Tanzania using an audiological test battery. We hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared to HIV− controls. Additionally, we anticipated that the prevalence of abnormal hearing assessments would increase with anti-retroviral therapy (ART) use, and treatment for tuberculosis (TB). Design Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV− in the U.S., plus 651 in Dar es Salaam Tanzania including 449 HIV+ [130 ART− and 319 ART+], and 202 HIV−, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+, and 23 of the HIV−, subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing as well as a health history questionnaire. Results HIV+ subjects had reduced DPOAE levels compared to HIV− subjects, but their hearing thresholds, tympanometry results, and gap detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech-in-noise, and were significantly more likely to report that they had difficulty understanding speech than the ART− group. The ART+ group had a significantly higher mean gap detection threshold compared to the ART− group. No effects of TB treatment were seen. Conclusions The fact that the ART+/ART− groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and higher gap detection thresholds

  20. Changes in plasma cytokines after treatment of ascaris lumbricoides infection in individuals with HIV-1 infection.

    PubMed

    Blish, Catherine A; Sangaré, Laura; Herrin, Bradley R; Richardson, Barbra A; John-Stewart, Grace; Walson, Judd L

    2010-06-15

    Albendazole treatment of individuals with human immunodeficiency virus type 1 (HIV-1) and Ascaris lumbricoides co-infection has led to significantly improved CD4(+) cell counts and a trend for lower plasma HIV-1 RNA levels in a previous randomized placebo-controlled trial. To define mechanisms by which deworming contributed to changes in markers of HIV-1 disease progression, plasma cytokine levels were evaluated. Albendazole treatment, compared with placebo, was associated with significantly decreased plasma interleukin (IL) 10 levels (P = .01)ot associated with significant changes in levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12p70, IL-13, interferon gamma, tumor necrosis factor alpha, or thymic stromal lymphopoietin. Treatment of A. lumbricoides co-infection may delay HIV-1 disease progression by reducing helminth-induced, IL-10-mediated immunosuppression.

  1. Changes in plasma cytokines after treatment of ascaris lumbricoides infection in individuals with HIV-1 infection.

    PubMed

    Blish, Catherine A; Sangaré, Laura; Herrin, Bradley R; Richardson, Barbra A; John-Stewart, Grace; Walson, Judd L

    2010-06-15

    Albendazole treatment of individuals with human immunodeficiency virus type 1 (HIV-1) and Ascaris lumbricoides co-infection has led to significantly improved CD4(+) cell counts and a trend for lower plasma HIV-1 RNA levels in a previous randomized placebo-controlled trial. To define mechanisms by which deworming contributed to changes in markers of HIV-1 disease progression, plasma cytokine levels were evaluated. Albendazole treatment, compared with placebo, was associated with significantly decreased plasma interleukin (IL) 10 levels (P = .01)ot associated with significant changes in levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12p70, IL-13, interferon gamma, tumor necrosis factor alpha, or thymic stromal lymphopoietin. Treatment of A. lumbricoides co-infection may delay HIV-1 disease progression by reducing helminth-induced, IL-10-mediated immunosuppression. PMID:20441516

  2. Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection

    PubMed Central

    Marzinke, Mark A.; Clarke, William; Wang, Lei; Cummings, Vanessa; Liu, Ting-Yuan; Piwowar-Manning, Estelle; Breaud, Autumn; Griffith, Sam; Buchbinder, Susan; Shoptaw, Steven; del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Fields, Sheldon D.; Mayer, Kenneth H.; Wheeler, Darrell P.; Koblin, Beryl A.; Eshleman, Susan H.; Fogel, Jessica M.

    2014-01-01

    In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)–infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly diagnosed and previously diagnosed HIV infection. PMID:24092804

  3. [Anti HTLV-I antibody titers in seropositive infected individuals].

    PubMed

    Galeno, H; Ramírez, E; Mora, J; Ojeda, M; Cartier, L

    1994-09-01

    The aim of this study was to determine anti HTLV-I antibody titers in seropositive symptomatic and asymptomatic infected subjects. One hundred seven infected subjects (47 with spastic paraparesis and 60 asymptomatic) were studied. HTLV-I antibodies were determined using indirect immunofluorescence in cells infected with the retrovirus. The mean titer was 1/234 in asymptomatic subjects and 1/2138 in symptomatic patients (p < 0.001). These results suggest an association between HTLV-I antibody titers and clinical stage of infected subjects.

  4. Risk of Newly Detected Infections and Cervical Abnormalities in Women Seropositive for Naturally Acquired Human Papillomavirus Type 16/18 Antibodies: Analysis of the Control Arm of PATRICIA

    PubMed Central

    Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M.; Germar, Maria Julieta V.; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M.; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C.; Skinner, S. Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Peters, Klaus; Tjalma, Wiebren A. A.; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

    2014-01-01

    Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15–25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242–794), 204 (95% CI, 129–480), and 480 (95% CI, 250–5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. PMID:24610876

  5. Mortality and Risk Stratification of HIV Infected Individuals.

    PubMed

    Heltemes, Bradley R

    2015-01-01

    For the first decade and a half after the Human Immunodeficiency Virus (HIV) was first identified, the prognosis for most people infected with HIV was quite poor. Life insurance companies responded accordingly and insurance laboratories developed new means to test for the infection. However, it is now clear that people with HIV infection are living longer and that the majority of deaths occurring among those on treatment are now no longer due to AIDS-defining illnesses. This review examines the results of selected studies which analyzed mortality outcomes in those with HIV infection, the many factors which influence those outcomes, and the limitations in the data and in their applicability to an insurance population. PMID:27584921

  6. Effects of tobacco smoking on HIV-infected individuals.

    PubMed

    Calvo, Marta; Laguno, Montserrat; Martínez, María; Martínez, Esteban

    2015-01-01

    A longer life expectancy and a high prevalence of tobacco smoking among HIV patients have led to an increasing cumulative exposure to tobacco in this community. Clinical recommendations for smoking cessation in HIV patients are mainly based on the body of evidence from the general population plus few available data from HIV cohort studies. The assumption that the pathophysiology of tobacco-related diseases in HIV-infected patients is similar to that in the general population may be questionable. This article reviews the pathophysiological mechanisms underlying health problems attributable to tobacco in HIV patients, and how these mechanisms may interact with those of HIV infection. Tobacco smoking exerts a greater health impact on HIV-infected patients than on uninfected smokers. Components of tobacco smoke and HIV infection induce complex interrelated pathophysiological changes through different pathways, affecting various organ systems with a cumulative or synergistic effect. This review supports the contention that HIV infection may confer an increased susceptibility to the harmful effects of smoking. Tobacco-related harm in the setting of HIV infection is still underestimated. A better understanding of the pathophysiological interaction between tobacco smoking and HIV will help to promote smoking cessation in this specific population.

  7. The prevalence and correlates of receiving confirmatory HIV test results among newly diagnosed HIV-positive individuals at a community-based testing center.

    PubMed

    Feldman, Matthew; Wu, Elwin; Mendoza, Moira; Lowry, Blakely; Ford, Lynnette; Holloway, Ian

    2012-10-01

    This study examined the prevalence and correlates of completing the HIV testing process-specifically receiving a confirmatory HIV test and returning for the results-in a sample of newly diagnosed HIV-positive individuals at an HIV testing center in New York City. Of the 213 individuals who received a reactive rapid HIV test result, 82% received a confirmatory HIV test. Of the 236 individuals who received a positive result on a rapid or traditional HIV test that was validated by a positive confirmatory HIV test, 65% returned for the confirmatory test results. Multivariate analyses revealed that being a non-U.S. citizen, homeless/living in transitional housing, being uninsured, and testing off-site were significantly associated with completing the HIV testing process. The findings indicate the need to explore strategies that address obstacles to receiving confirmatory HIV testing and returning for the results, in addition to the feasibility of a rapid confirmatory HIV test. PMID:23016505

  8. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

    PubMed Central

    Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A.; Atti El Mekki, Misk El Yemen A.; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E.

    2016-01-01

    Background In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways

  9. A newly developed tool for intra-tracheal temperature and humidity assessment in laryngectomized individuals: the Airway Climate Explorer (ACE).

    PubMed

    Zuur, J K; Muller, S H; de Jongh, F H C; van der Horst, M J; Shehata, M; van Leeuwen, J; Sinaasappel, M; Hilgers, F J M

    2007-08-01

    The aim of this study is to develop a postlaryngectomy airway climate explorer (ACE) for assessment of intratracheal temperature and humidity and of influence of heat and moisture exchangers (HMEs). Engineering goals were within-device condensation prevention and fast response time characteristics. The ACE consists of a small diameter, heated air-sampling catheter connected to a heated sensor house, containing a humidity sensor. Air is sucked through the catheter by a controlled-flow pump. Validation was performed in a climate chamber using a calibrated reference sensor and in a two-flow system. Additionally, the analyser was tested in vivo. Over the clinically relevant range of humidity values (5-42 mg H2O/l air) the sensor output highly correlates with the reference sensor readings (R2 > 0.99). The 1-1/e response times are all <0.5 s. A first in vivo pilot measurement was successful. The newly developed, verified, fast-responding ACE is suitable for postlaryngectomy airway climate assessment.

  10. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  11. Utility of a partner communication scale and a personal meaning scale in newly diagnosed HIV-infected persons.

    PubMed

    Buscher, April; Latini, David M; Hartman, Christine; Kallen, Michael; Sansgiry, Shubhada; Giordano, Thomas P

    2013-01-01

    No studies to our knowledge have examined the Lepore Social Constraint Scale or Fife Constructed Meaning Scale in recently diagnosed HIV-infected persons. Twenty-four participants in a prospective observational cohort completed the social-constraint measure, and 47 completed the constructed-meaning scale at either 3 or 9 months after diagnosis. Participants completed a 4-week visual analogue scale to assess adherence to antiretroviral therapy, and validated depression and self-efficacy scales. Spearman correlation coefficients compared measures. In cross-sectional analyses, participants with higher social-constraint scores had lower constructed meaning and adherence. Higher social constraint correlated negatively with self-efficacy and positively with depression. Higher constructed-meaning scores did not correlate with adherence but correlated positively with self-efficacy and negatively with depression. The quality of HIV-infected individuals' discussions of HIV with their partners and positive constructed meaning were associated with better mental health and could be targets for improving medication adherence.

  12. Evaluation of newly installed SWEPOS mast stations, individual vs. type PCV antenna models and comparison with pillar stations

    NASA Astrophysics Data System (ADS)

    Nilfouroushan, Faramarz; Jivall, Lotti; Lilje, Christina; Steffen, Holger; Lidberg, Martin; Johansson, Jan; Jarlemark, Per

    2016-04-01

    For about two decades, SWEPOS (the Swedish Permanent GNSS network) pillar stations have been used in different geodetic and geodynamic studies. To keep continuous measurements of these long lived pillar stations and at the same time modernizing the SWEPOS network, it has been decided to install new truss mast stations, equipped with modern and individually calibrated antennas and radomes, capable of tracking all new GNSS satellites. Installation of mast stations started in 2011. Today, each pillar station in the SWEPOS permanent GNSS network has a close-by truss mast station, mostly in 10 meters distance with individual calibrated Leica choke ring antenna and its attachment (LEIAR25.R3, LEIT). Due to their closeness to pillars, the modern mast stations may provide additional information for the analysis of ground movements in Sweden e.g. to distinguish between tectonic and geodynamic processes (e.g. land uplift in Sweden). In this study, we have used two datasets from two different seasons for 21 pillars and 21 mast stations and formed different networks. The mast network has been processed using both IGS standard (type) and individually calibrated PCV (Phase Center Variation) models and therefore the effect of these two different PCV models on height components has been investigated. In a combined network, we processed all 42 stations (21 pillars+21 mast) to see how this multi-baseline network (861 baselines) combination differs from independent mast or pillar networks with much less baselines (210 baselines). For our analysis, we used the GAMIT-GLOBK software and compared different networks. Ambiguity resolutions, daily coordinate repeatability and differences between height components in different solutions are presented. Moreover, the GAMIT and BERNESE solutions for combined mast and pillar networks are compared. Our results suggest that the SWEPOS truss mast stations can reliably be used for crustal deformation studies. The comparison between pillar and mast

  13. Dataset generated using hyperplexing and click chemistry to monitor temporal dynamics of newly synthesized macrophage secretome post infection by mycobacterial strains.

    PubMed

    Kumar, Ajay; Jamwal, Shilpa; Midha, Mukul Kumar; Hamza, Baseerat; Aggarwal, Suruchi; Yadav, Amit Kumar; Rao, Kanury V S

    2016-12-01

    Here we provide data for SILAC and iTRAQ based hyperplexing combined with BONCAT based click chemistry for selective enrichment of newly synthesized proteins secreted by THP1 macrophages at various time points after infection with four different strains of Mycobacterium tuberculosis. The macrophages were infected with H37Ra, H37Rv, BND433 and JAL2287 strains of M. tuberculosis. Newly-synthesized secreted host proteins were observed, starting from six hours post-infection till 26 h, at 4 h intervals. We have combined BONCAT with hyperplexing (18-plex), which blends SILAC and iTRAQ, for the first time. Two sets of triplex SILAC were used to encode the strains of M. tuberculosis - H37Ra & H37Rv in one and BND433 & JAL2287 in another with a control in each. BONCAT was used to enrich the secretome for newly synthesized proteins while 6-plex iTRAQ labeling was employed to quantify the temporal changes in the captured proteome. Each set of 18-plex was run in 4 MS replicates with two linear and two non-linear separation modes. This new variant of hyperplexing method, combining triplex SILAC with 6-plex iTRAQ, achieves 18-plex quantitation in a single MS run. Hyperplexing enables large scale spatio-temporal systems biology studies where large number of samples can be processed simultaneously and in quantitative manner. Data are available via ProteomeXchange with identifier ProteomeXchange: PXD004281. PMID:27672675

  14. Prevalence of hepatitis B and C viral co-infections among HIV-1 infected individuals in Nairobi, Kenya

    PubMed Central

    2013-01-01

    Background Hepatitis B virus (HBV) and Hepatitis C virus (HCV) co-infections among HIV-1 infected individuals are growing worldwide health problems characterized by lack of effective vaccines, need for expensive treatment, chronicity of morbidity and associated mortality. Their prevalence and distribution patterns continue to vary across geographical locations with high prevalence being detected among high risk populations. To determine the prevalence of HBV and HCV among HIV-1 infected individuals, blood samples were collected from consenting study subjects visiting comprehensive HIV clinics in Nairobi during the period between October and December 2009. Methods Blood samples from volunteers were screened with ELISA tests for detecting HIV, HBV surface antigen (HBsAg) and anti-HCV antibodies. Results In a total of three (300) hundred infected individuals consisting of 129 (43%) males and 171 (57%) females 15.3% (46/300) were HIV-1 co-infected with either HBV or HCV or both, 10.3% (31/300) with HIV-1 and HCV and 6% (18/300) with HIV-1 and HBV infections. However, only three individuals (1%) were coinfected with the three viruses (HIV/HBV/HCV). Conclusion Though, low levels of co-infection with all three viruses were reported, there could be higher prevalence rates than reported here especially among high risk populations. PMID:24016453

  15. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    PubMed

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

  16. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    PubMed

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity. PMID:22235298

  17. Analysis of Wuchereria bancrofti infections in a village community in northern Nigeria: increased prevalence in individuals infected with Onchocerca volvulus.

    PubMed

    Engelbrecht, Fred; Oettl, Tobias; Herter, Ursula; Link, Claudia; Philipp, Diana; Edeghere, Henry; Kaliraj, P; Enwezor, Felicia

    2003-03-01

    Infections with Wuchereria bancrofti causing lymphatic filariasis still represent one of the major health problems in the tropics, with 120 million people infected and over 750 million exposed to this filarial parasite. We have studied lymphatic filariasis infections as part of a multi-parasite survey in a village community in the savannah of northern Nigeria. We analysed serum samples from 341 individuals aged 5-70 years, detecting a W. bancrofti circulating antigen using the commercially available ICT Filariasis card test. The prevalence of infections was 10% and clearly age-dependent, increasing from below 2% in children to over 20% in subjects older than 40 years. Measuring IgG4 antibodies against the recombinant W. bancrofti antigen SXP1 showed that 36% of all tested individuals had been at least exposed to the parasite. Antibody levels also increased very significantly with age. A further analysis measuring Onchocerca volvulus-specific IgG4 antibodies showed a very significant association between infections with O. volvulus and those with W. bancrofti. Our data show that infections with W. bancrofti in Nigeria are still a frequently occurring health problem, since they are more prevalent than previously reported, and that individuals with an O. volvulus infection are more often infected with W. bancrofti than expected statistically. PMID:12543143

  18. Identification of Germinal Center B Cells in Blood from HIV-infected Drug-naive Individuals in Central Africa

    PubMed Central

    Béniguel, Lydie; Bégaud, Evelyne; Cognasse, Fabrice; Gabrié, Philippe; Mbolidi, Christophe D.; Sabido, Odile; Marovich, Mary A.; deFontaine, Christiane; Frésard, Anne; Lucht, Frédéric; Genin, Christian; Garraud, Olivier

    2004-01-01

    To better understand the pathophysiology of B cell populations—the precursors of antibody secreting cells—during chronic human immunodeficiency virus (HIV) infection, we examined the phenotype of circulating B cells in newly diagnosed Africans. We found that all African individuals displayed low levels of naive B cells and of memory-type CD27+ B cells, and high levels of differentiated B cells. On the other hand, HIV-infected African patients had a population of germinal center B cells (i.e. CD20+, sIgM-, sIgD+, CD77+, CD138±), which are generally restricted to lymph nodes and do not circulate unless the lymph node architecture is altered. The first observations could be linked to the tropical environment whereas the presence of germinal center B cells may be attributable to chronic exposure to HIV as it is not observed in HIV-negative African controls and HAART treated HIV-infected Europeans. It may impact the management of HIV infection in countries with limited access to HIV drugs and urges consideration for implementation of therapeutic vaccines. PMID:15154608

  19. Latent Toxoplasma gondii Infection and Associated Risk Factors among HIV-Infected Individuals at Arba Minch Hospital, South Ethiopia

    PubMed Central

    2014-01-01

    Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii (T. gondii). The parasite has cosmopolitan distribution, infecting almost all species of warm-blooded animals. Latent T. gondii infection in HIV/AIDS patients is a risk for development of cerebral toxoplasmosis (CT). The aim of this study is to determine seroprevalence of latent T. gondii infection and assess its associated factors among individuals infected with HIV in Arba Minch Hospital, south Ethiopia. A facility-based cross-sectional study involving 170 HIV-infected individuals attending Arba Minch Hospital antiretroviral therapy (ART) clinic was conducted from April to June 2013. Data on demographic profile of the study participants and factors associated with T. gondii infection were gathered using a questionnaire. Serum was tested for IgG anti-T. gondii antibody by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS version 20 software. Seroprevalence of latent T. gondii infection among the study participants was 88.2%. Consumption of raw meat (AOR = 4.361; 95% CI: 1.409–13.496) and involvement in farming/gardening activities (AOR = 4.051; 95% CI: 1.112–14.758) were independent predictors of T. gondii seropositivity. This study revealed high prevalence of latent T. gondii infection, similar to other studies. Monitoring of the patients to prevent reactivation of the latent T. gondii infection is recommended. PMID:25431660

  20. Long-term Bone Mineral Density Changes in Antiretroviral-Treated HIV-Infected Individuals.

    PubMed

    Grant, Philip M; Kitch, Douglas; McComsey, Grace A; Collier, Ann C; Koletar, Susan L; Erlandson, Kristine M; Yin, Michael T; Bartali, Benedetta; Ha, Belinda; Melbourne, Kathy; Brown, Todd T

    2016-08-15

    We compared adjusted bone mineral density (BMD) changes between human immunodeficiency virus (HIV)-infected individuals during the first approximately 7.5 years after antiretroviral therapy (ART) initiation and HIV-uninfected controls. HIV-infected individuals (n = 97) had significantly greater adjusted BMD decline than controls (n = 614) during the first 96 weeks of ART. Subsequently, the rate of BMD decline slowed in HIV-infected individuals but remained greater than the rate of decline in HIV-uninfected individuals at the lumbar spine but not at the hip. In HIV-infected individuals after 96 weeks, no HIV- or treatment-related characteristic was associated with BMD loss, but lower lean body mass was associated with greater BMD loss at both lumbar spine and hip. PMID:27330053

  1. Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals

    PubMed Central

    Shaviya, Nathan; Budambula, Valentine; Webale, Mark K.; Were, Tom

    2016-01-01

    Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ = −0.849; P < 0.0001), body mass index (ρ = 0.664; P = 0.013), hip girth (ρ = −0.579; P = 0.038), and plateletcrit (ρ = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ = −0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (ρ = −0.560; P = 0.047), body mass index (ρ = −0.604; P = 0.029), and plateletcrit (ρ = 0.793; P = 0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients. PMID:26880909

  2. Spirituality and religion among HIV-infected individuals.

    PubMed

    Szaflarski, Magdalena

    2013-12-01

    Spirituality and religion are important to many people living with HIV (PLWH). Recent research has focused on special populations (ethnic-minorities, women, and youth), spirituality/religion measurement, mediating/moderating mechanisms, and individual and community-level interventions. Spirituality/religion in PLWH has been refined as a multidimensional phenomenon, which improves health/quality of life directly and through mediating factors (healthy behaviors, optimism, social support). Spirituality/religion helps people to cope with stressors, especially stigma/discrimination. Spiritual interventions utilizing the power of prayer and meditation and addressing spiritual struggle are under way. Faith-based community interventions have focused on stigma and could improve individual outcomes through access to spiritual/social support and care/treatment for PLWA. Community engagement is necessary to design/implement effective and sustainable programs. Future efforts should focus on vulnerable populations; utilize state-of-the-art methods (randomized clinical trials, community-based participatory research); and, address population-specific interventions at individual and community levels. Clinical and policy implications across geographic settings also need attention.

  3. Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms

    PubMed Central

    Schüpbach, Jörg; Niederhauser, Christoph; Yerly, Sabine; Regenass, Stephan; Gorgievski, Meri; Aubert, Vincent; Ciardo, Diana; Klimkait, Thomas; Dollenmaier, Günter; Andreutti, Corinne; Martinetti, Gladys; Brandenberger, Marcel; Gebhardt, Martin D.

    2015-01-01

    Background HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. Methods and Results Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship ‘incident = true incident + false incident’, (ii) based on the window-periods of the algorithms and utilizing the relationship ‘Prevalence = Incidence x Duration’. From 2008—2013, 3’851 HIV notifications were received. Adult HIV-1 infections amounted to 3’809 cases, and 3’636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1’755 (95% confidence interval, 1588—1923) and 1’790 cases (95% CI, 1679—1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008—2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008—2013 were of similar extent among the major transmission groups. Conclusions Inno-Lia based incident HIV-1 infection surveillance proved useful and

  4. Prevalence of Intestinal Parasite Infections among Individuals with Mental Retardation in New York State.

    ERIC Educational Resources Information Center

    Schupf, Nicole; And Others

    1995-01-01

    Prevalence of intestinal parasite infection among program participants of the New York State Office of Mental Retardation and Developmental Disabilities for 1986-87 was estimated at 7.3%, suggesting that management of parasitic infection is improving. Males and individuals with severe/profound mental retardation were twice as likely to have…

  5. Clinical Characteristics and Outcomes Among Individuals With Spinal Implant Infections: A Descriptive Study

    PubMed Central

    Baxi, Sanjiv M.; Robinson, Makeda L.; Grill, Marie F.; Schwartz, Brian S.; Doernberg, Sarah B.; Liu, Catherine

    2016-01-01

    Little is known about the clinical presentation and outcomes associated with spinal implant infections. Here, we describe a single center's experience in a retrospective cohort of 109 individuals with spinal implant infections, including clinical, microbiological, therapeutic, and outcome data. PMID:27704027

  6. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    PubMed

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. PMID:26971243

  7. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    PubMed

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.

  8. Estimating Time of Infection Using Prior Serological and Individual Information Can Greatly Improve Incidence Estimation of Human and Wildlife Infections

    PubMed Central

    Hens, Niel; Beutels, Philippe; Leirs, Herwig; Reijniers, Jonas

    2016-01-01

    Diseases of humans and wildlife are typically tracked and studied through incidence, the number of new infections per time unit. Estimating incidence is not without difficulties, as asymptomatic infections, low sampling intervals and low sample sizes can introduce large estimation errors. After infection, biomarkers such as antibodies or pathogens often change predictably over time, and this temporal pattern can contain information about the time since infection that could improve incidence estimation. Antibody level and avidity have been used to estimate time since infection and to recreate incidence, but the errors on these estimates using currently existing methods are generally large. Using a semi-parametric model in a Bayesian framework, we introduce a method that allows the use of multiple sources of information (such as antibody level, pathogen presence in different organs, individual age, season) for estimating individual time since infection. When sufficient background data are available, this method can greatly improve incidence estimation, which we show using arenavirus infection in multimammate mice as a test case. The method performs well, especially compared to the situation in which seroconversion events between sampling sessions are the main data source. The possibility to implement several sources of information allows the use of data that are in many cases already available, which means that existing incidence data can be improved without the need for additional sampling efforts or laboratory assays. PMID:27177244

  9. A new approach to prevent HIV transmission: Project Protect intervention for recently infected individuals.

    PubMed

    Vasylyeva, T I; Friedman, S R; Smyrnov, P; Bondarenko, K

    2015-01-01

    Past research suggests that as many as 50% of onward human immunodeficiency virus (HIV) transmissions occur during acute and recent HIV infection. It is clearly important to develop interventions which focus on this highly infectious stage of HIV infection to prevent further transmission in the risk networks of acutely and recently infected individuals. Project Protect tries to find recently and acutely infected individuals and prevents HIV transmission in their risk networks. Participants are recruited by community health outreach workers at community-based HIV testing sites and drug users' community venues, by coupon referrals and through referrals from AIDS clinics. When a network with acute/recent infection is identified, network members are interviewed about their risky behaviors, network information is collected, and blood is drawn for HIV testing. Participants are also educated and given prevention materials (condoms, syringes, educational materials); HIV-infected participants are referred to AIDS clinics and are assisted with access to care. Community alerts about elevated risk of HIV transmission are distributed within the risk networks of recently infected. Overall, 342 people were recruited to the project and screened for acute/recent HIV infection. Only six index cases of recent infection (2.3% of all people screened) were found through primary screening at voluntary counseling and testing (VCT) sites, but six cases of recent infection were found through contact tracing of these recently infected participants (7% of network members who came to the interview). Combining screening at VCT sites and contact tracing the number of recently infected people we located as compared to VCT screening alone. No adverse events were encountered. These first results provide evidence for the theory behind the intervention, i.e., in the risk networks of recently infected people there are other people with recent HIV infection and they can be successfully located without

  10. Depressive Symptoms and Their Impact on Health-seeking Behaviors in Newly-diagnosed HIV-infected Patients in Durban, South Africa

    PubMed Central

    Regan, Susan; Giddy, Janet; Chetty, Senica; Ross, Douglas; Katz, Jeffrey N.; Freedberg, Kenneth A.; Walensky, Rochelle P.; Losina, Elena; Bassett, Ingrid V.

    2012-01-01

    We evaluated the prevalence and correlates of depressive symptoms prior to HIV diagnosis and determined the effect of these symptoms on seeking HIV care at an urban and rural clinic in Durban, South Africa. Adults were administered a questionnaire which included the 5-item Mental Health Index (MHI-5) before HIV testing. We determined the depressive symptoms among HIV-infected subjects. Of 1,545 newly-diagnosed HIV-infected subjects, 55% had depressive symptoms by MHI-5 score. Enrolling at the urban clinic and decreasing functional activity score were associated with depressive symptoms. Subjects with depressive symptoms who were referred for HIV testing by a healthcare provider were less likely to obtain a CD4 count than those without depressive symptoms who self-referred for testing. Depressive symptoms were common among newly-diagnosed HIV-infected participants and impacted CD4 uptake. Depression screening at the time of HIV diagnosis is critical for improving linkage to mental health and HIV services in South Africa. PMID:22451351

  11. Differential Pathological and Immune Responses in Newly Weaned Ferrets Are Associated with a Mild Clinical Outcome of Pandemic 2009 H1N1 Infection

    PubMed Central

    Huang, Stephen S. H.; Banner, David; Degousee, Norbert; Leon, Alberto J.; Xu, Louling; Paquette, Stephane G.; Kanagasabai, Thirumagal; Fang, Yuan; Rubino, Salvatore; Rubin, Barry; Kelvin, Alyson A.

    2012-01-01

    Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses. PMID:23055557

  12. Frequency and Determinants of Preventive Care Counseling by HIV Medical Care Providers during Encounters with Newly Diagnosed and Established HIV-Infected Patients.

    PubMed

    Mgbere, Osaro; Rodriguez-Barradas, Maria C; Bell, Tanvir K; Khuwaja, Salma; Arafat, Raouf; Essien, Ekere J; Singh, Mamta; Simmons, Paul; Aguilar, Jonathan

    2016-05-01

    This study evaluates the frequency and determinants of preventive care counseling by HIV medical care providers (HMCPs) during encounters with newly diagnosed and established HIV-infected patients. Data used were from a probability sample of HMCPs in Houston/Harris County, Texas, surveyed in 2009. Overall, HMCPs offered more preventive care counseling to newly diagnosed than the established patients (adjusted odds ratio [AOR] = 7.28; 95% confidence interval [CI] = 2.86-16.80). They were more likely to counsel newly diagnosed patients than the established ones on medication and adherence (AOR = 14.70; 95% CI = 1.24-24.94), HIV risk reduction (AOR = 5.91; 95% CI = 0.48-7.13), and disease screening (AOR = 7.20; 95% CI = 0.72-11.81). HIV medical care providers who were less than 45 years of age, infectious disease specialists, and had less than 30 minutes of encounter time were less likely to counsel patients regardless of the status. Our findings suggest the need for HMCPs to improve their preventive care counseling efforts, in order to help patients build skills for adopting and maintaining safe behavior that could assist in reducing the risk of HIV transmission.

  13. Newly Diagnosed?

    MedlinePlus

    ... Suggestions Examine Your Skin Newly Diagnosed? Understanding Your Pathology Biopsy: The First Step Sentinel Node Biopsy Melanoma ... start this journey: Get a copy of your pathology report. We can help you understand the report ...

  14. Nodule Worm Infection in Humans and Wild Primates in Uganda: Cryptic Species in a Newly Identified Region of Human Transmission

    PubMed Central

    Ghai, Ria R.; Chapman, Colin A.; Omeja, Patrick A.; Davies, T. Jonathan; Goldberg, Tony L.

    2014-01-01

    Introduction Soil-transmitted helminths (STHs) are a major health concern in tropical and sub-tropical countries. Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda, East Africa, among primates (including humans). However, the taxonomy and ecology of Oesophagostomum in Uganda have not been studied, except for in chimpanzees (Pan troglodytes), which are infected by both O. bifurcum and O. stephanostomum. Methods and Findings We studied Oesophagostomum in Uganda in a community of non-human primates that live in close proximity to humans. Prevalence estimates based on microscopy were lower than those based on polymerase chain reaction (PCR), indicating greater sensitivity of PCR. Prevalence varied among host species, with humans and red colobus (Procolobus rufomitratus) infected at lowest prevalence (25% and 41% by PCR, respectively), and chimpanzees, olive baboons (Papio anubis), and l'hoest monkeys (Cercopithecus lhoesti) infected at highest prevalence (100% by PCR in all three species). Phylogenetic regression showed that primates travelling further and in smaller groups are at greatest risk of infection. Molecular phylogenetic analyses revealed three cryptic clades of Oesophagostomum that were not distinguishable based on morphological characteristics of their eggs. Of these, the clade with the greatest host range had not previously been described genetically. This novel clade infects humans, as well as five other species of primates. Conclusions Multiple cryptic forms of Oesophagostomum circulate in the people and primates of western Uganda, and parasite clades differ in host range and cross-species transmission potential. Our results expand knowledge about human Oesophagostomum infection beyond the West African countries of Togo and Ghana, where the parasite is a known public health concern. Oesophagostomum infection in humans may be common throughout Sub-Saharan Africa, and the transmission of this neglected

  15. Diabetes mellitus among HIV-infected individuals in follow-up care at University of Gondar Hospital, Northwest Ethiopia

    PubMed Central

    Abebe, Solomon Mekonnen; Getachew, Assefa; Fasika, Solomon; Bayisa, Mulugeta; Girma Demisse, Abayneh; Mesfin, Nebiyu

    2016-01-01

    Objective To assess the prevalence of diabetes mellitus (DM) and associated factors among HIV-infected adults in northwest Ethiopia. Design Hospital-based cross-sectional study. Setting HIV clinic of the University of Gondar Hospital, Ethiopia. Participants All HIV-infected adults who visited the HIV clinic from December 2013 to the end of February 2014 were the source population. Measures A structured and pretested questionnaire incorporating the WHO STEPwise approach was used. A multivariate logistic regression analysis was applied to assess factors associated with DM. Results The overall prevalence of type 2 DM was 8% (95% CI 5.5% to 10.5%). The prevalence of DM was higher (13.2%; 95% CI 8.0% to 18.3%) among subjects receiving pre-antiretroviral treatment (pre-ART) than among those taking ART (5.1%; 95% CI 2.6% to 7.6%). Thirteen (35.1%) of the DM cases were newly identified during the study. Obesity (adjusted OR (AOR) 6.55; 1.20 to 35.8), hypertension (AOR 3.45; 1.50 to 7.90), being in the pre-ART group (AOR 4.47; 1.80 to 11.08), hypertriglyceridaemia (AOR 2.24; 1.02 to 49.5) and tertiary-level education (AOR 11.8; 2.28 to 61.4) were associated with DM. Conclusions Overall DM prevalence was high, particularly among subjects in the pre-ART group. More educated, hypertensive and obese HIV-infected adults were more likely to have DM as a comorbidity. Health policy and the clinical management of HIV-infected individuals should take into account the rising DM. PMID:27540099

  16. Clinical spectrum of infections due to the newly described Actinomyces species A. turicensis, A. radingae, and A. europaeus.

    PubMed

    Sabbe, L J; Van De Merwe, D; Schouls, L; Bergmans, A; Vaneechoutte, M; Vandamme, P

    1999-01-01

    Over a 7-year period, we isolated 294 Actinomyces-like organisms (ALOs) which were not clearly identifiable. Using well-defined probes coding for sequences specific for recently described Actinomyces species (A. turicensis, A. radingae, and A. europaeus), we were able to identify 128 strains. The majority belonged to the A. turicensis species. A. radingae was found only in patients with skin-related pathologies. A. europaeus was also detected in patients with urinary tract infections. The main sources of A. turicensis were genital infections, followed by skin-related and urinary tract infections. Additional clinical pictures were appendicitis, cholecystitis, ear, nose, and throat infections, and bacteremia. In a small number of patients these ALOs were found as the only pathogen. Strains of the three species were tested by two widely used biochemical identification methods. A. turicensis was easily identifiable by both these methods. We conclude that these ALOs are not infrequent pathogens and are found in a wide range of human infections. At least A. turicensis is easily identifiable by clinical diagnostic laboratories.

  17. Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed hiv-infected adults: a prospective, clinic-based study

    PubMed Central

    2014-01-01

    Background A rapid diagnostic test for active tuberculosis (TB) at the clinical point-of-care could expedite case detection and accelerate TB treatment initiation. We assessed the diagnostic accuracy of a rapid urine lipoarabinomannan (LAM) test for TB screening among HIV-infected adults in a TB-endemic setting. Methods We prospectively enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 outpatient clinics in Durban from Oct 2011-May 2012, excluding those on TB therapy. A physician evaluated all participants and offered CD4 cell count testing. Trained study nurses collected a sputum sample for acid-fast bacilli smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing using Determine™ TB LAM in the clinic. The presence of a band regardless of intensity on the urine LAM test was considered positive. We defined as the gold standard for active pulmonary TB a positive sputum culture for Mycobacterium tuberculosis. Diagnostic accuracy of urine LAM was assessed, alone and in combination with smear microscopy, and stratified by CD4 cell count. Results Among 342 newly-diagnosed HIV-infected participants, 190 (56%) were male, mean age was 35.6 years, and median CD4 was 182/mm3. Sixty participants had culture-positive pulmonary TB, resulting in an estimated prevalence of 17.5% (95% CI 13.7-22.0%). Forty-five (13.2%) participants were urine LAM positive. Mean time from urine specimen collection to LAM test result was 40 minutes (95% CI 34–46 minutes). Urine LAM test sensitivity was 28.3% (95% CI 17.5-41.4) overall, and 37.5% (95% CI 21.1-56.3) for those with CD4 count <100/mm3, while specificity was 90.1% (95% CI 86.0-93.3) overall, and 86.9% (95% CI 75.8-94.2) for those with CD4 < 100/mm3. When combined with sputum AFB (either test positive), sensitivity increased to 38.3% (95% CI 26.0-51.8), but specificity decreased to 85.8% (95% CI 81.1-89.7). Conclusions In this prospective, clinic-based study with trained nurses, a rapid

  18. A Cross Section Study to Determine the Prevalence of Antibodies against HIV Infection among Hepatitis B and C Infected Individuals.

    PubMed

    Flores, Geane L; de Almeida, Adilson J; Miguel, Juliana C; Cruz, Helena M; Portilho, Moyra M; Scalioni, Letícia de P; Marques, Vanessa A; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Villar, Livia Melo

    2016-03-01

    (1) BACKGROUND: There are limited data regarding human immunodeficiency virus (HIV) prevalence among hepatitis B virus (HBV) or hepatitis C virus (HCV) infected individuals. The aim of this cross-sectional study is to determine the prevalence of HBV and HCV infection among HIV individuals; (2) METHODS: A total of 409 patients (126 HBV+ and 283 HCV+) referred to the Brazilian Reference Laboratory for Viral Hepatitis from 2010 to 2013 donated serum samples. Anti-HIV, HBsAg, anti-HBc, anti-HBs, anti-HBcIgM, anti-HBe, HBeAg, and anti-HCV antibodies were measured, and anti-HCV positive samples were tested for viral RNA and genotype; (3) RESULTS: The anti-HIV antibody prevalence was 10.31% and 4.59% among HBV+ and HCV+ patients, respectively. The HCV mean (SD) viral load was log 5.14 ± 1.64 IU/mL, and genotype I was most prevalent (163/283). Anti-HBs and anti-HBc were detected in 40% and 26% of HCV+ individuals, respectively. Among the HBV+ population, the presence of anti-HIV antibodies was associated with male gender, marital status (married), tattoo, sexual orientation, sexual practices (oral sex and anal sex), history of sexually transmitted diseases (STDs), history of viral hepatitis treatment, and a sexual partner with hepatitis or HIV. For the HCV+ group, the presence of anti-HIV antibodies was associated with female gender, marital status (married), anal intercourse, previous history of STDs, and number of sexual partners; (4) CONCLUSION: A high prevalence of anti-HIV antibodies was found among individuals with HBV and HCV, showing the importance of education programmes towards HIV infection among HBV- and HCV-infected individuals. PMID:26978383

  19. A Cross Section Study to Determine the Prevalence of Antibodies against HIV Infection among Hepatitis B and C Infected Individuals

    PubMed Central

    Flores, Geane L.; de Almeida, Adilson J.; Miguel, Juliana C.; Cruz, Helena M.; Portilho, Moyra M.; de P. Scalioni, Letícia; Marques, Vanessa A.; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Melo Villar, Livia

    2016-01-01

    (1) Background: There are limited data regarding human immunodeficiency virus (HIV) prevalence among hepatitis B virus (HBV) or hepatitis C virus (HCV) infected individuals. The aim of this cross-sectional study is to determine the prevalence of HBV and HCV infection among HIV individuals; (2) Methods: A total of 409 patients (126 HBV+ and 283 HCV+) referred to the Brazilian Reference Laboratory for Viral Hepatitis from 2010 to 2013 donated serum samples. Anti-HIV, HBsAg, anti-HBc, anti-HBs, anti-HBcIgM, anti-HBe, HBeAg, and anti-HCV antibodies were measured, and anti-HCV positive samples were tested for viral RNA and genotype; (3) Results: The anti-HIV antibody prevalence was 10.31% and 4.59% among HBV+ and HCV+ patients, respectively. The HCV mean (SD) viral load was log 5.14 ± 1.64 IU/mL, and genotype I was most prevalent (163/283). Anti-HBs and anti-HBc were detected in 40% and 26% of HCV+ individuals, respectively. Among the HBV+ population, the presence of anti-HIV antibodies was associated with male gender, marital status (married), tattoo, sexual orientation, sexual practices (oral sex and anal sex), history of sexually transmitted diseases (STDs), history of viral hepatitis treatment, and a sexual partner with hepatitis or HIV. For the HCV+ group, the presence of anti-HIV antibodies was associated with female gender, marital status (married), anal intercourse, previous history of STDs, and number of sexual partners; (4) Conclusion: A high prevalence of anti-HIV antibodies was found among individuals with HBV and HCV, showing the importance of education programmes towards HIV infection among HBV- and HCV-infected individuals. PMID:26978383

  20. Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales.

    PubMed

    Ezenwa, Vanessa O; Jolles, Anna E

    2015-01-01

    Parasitic worms modulate host immune responses in ways that affect microbial co-infections. For this reason, anthelmintic therapy may be a potent tool for indirectly controlling microbial pathogens. However, the population-level consequences of this type of intervention on co-infecting microbes are unknown. We evaluated the effects of anthelmintic treatment on bovine tuberculosis (BTB) acquisition, mortality after infection, and pathogen fitness in free-ranging African buffalo. We found that treatment had no effect on the probability of BTB infection, but buffalo survival after infection was ninefold higher among treated individuals. These contrasting effects translated into an approximately eightfold increase in the reproductive number of BTB for anthelmintic-treated compared with untreated buffalo. Our results indicate that anthelmintic treatment can enhance the spread of microbial pathogens in some real-world situations.

  1. Systematic review of the pharmacological treatment of alcohol use disorders in individuals infected with hepatitis C.

    PubMed

    Thibault, Alexis; Brissette, Suzanne; Jutras-Aswad, Didier

    2015-01-01

    Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological treatment is effective for decreasing alcohol consumption and promoting abstinence. However, unique factors belonging to HCV-infected individuals, such as baseline hepatic vulnerability and possible ongoing hepatitis C treatment, complicate AUD drug therapy. The goal of this review is to systematically identify, summarize, and evaluate the existing evidence on the pharmacological management of AUD in HCV-infected individuals. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for English- and French-language articles published from 1993 to December 2013. The search criteria focused on clinical trials and observational studies assessing the efficacy and/or safety of pharmacological management of AUD in patients infected with HCV. Of 421 identified studies, three were included for analysis. Two were observational studies assessing the safety of disulfiram. One was a randomized controlled trial assessing the efficacy and safety of baclofen. There is paucity of data regarding the efficacy and safety of pharmacological treatment of AUD in HCV-infected individuals, with studies being small series and showing significant heterogeneity. No strong recommendations can be made based on the current studies as to which pharmacological option should be preferred in this sub-population. PMID:25928362

  2. Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports

    NASA Astrophysics Data System (ADS)

    Jiao, Jianjun; Cai, Shaohong; Li, Limei

    2016-05-01

    To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.

  3. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  4. Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

    PubMed Central

    Lau, Bryan; Justice, Amy C.; Engels, Eric; Gill, M. John; Goedert, James J.; Kirk, Gregory D.; D’Souza, Gypsyamber; Bosch, Ronald J.; Brooks, John T.; Napravnik, Sonia; Hessol, Nancy A.; Jacobson, Lisa P.; Kitahata, Mari M.; Klein, Marina B.; Moore, Richard D.; Rodriguez, Benigno; Rourke, Sean B.; Saag, Michael S.; Sterling, Timothy R.; Gebo, Kelly A.; Press, Natasha; Martin, Jeffrey N.; Dubrow, Robert

    2012-01-01

    Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued. PMID:22291097

  5. Alcohol Drinking Pattern: A Comparison between HIV-Infected Patients and Individuals from the General Population

    PubMed Central

    Ikeda, Maria Leticia R.; Barcellos, Nemora T.; Alencastro, Paulo R.; Wolff, Fernando H.; Moreira, Leila B.; Gus, Miguel; Brandão, Ajacio B. M.; Fuchs, Flavio D.; Fuchs, Sandra C.

    2016-01-01

    Background Alcohol consumption is highly prevalent in the general population and among HIV-infected population. This study aimed to compare the pattern of alcohol consumption and to describe characteristics associated with heavy alcohol consumption in individuals from the general population with patients infected with HIV. Methods Participants for this analysis came from a population-based cross-sectional study and from a consecutive sampling of patients infected with HIV. Participants aged 18 years or older were interviewed using similar questionnaires with questions pertaining to socio-demographic characteristics, alcohol consumption, smoking, physical activity, and HIV-related characteristics, among others. Blood pressure and anthropometric measures were measured using standardized procedures. Results Weekly alcohol consumption was more prevalent among individuals from the general population than HIV-infected patients: 57.0 vs. 31.1%, P<0.001. The prevalence of heavy episodic drinking was higher in the population sample as well: 46.1 vs. 17.0%, P<0.001. In the general population, heavy alcohol consumption was more prevalent in men. Cigarette smoking was independently associated with heavy alcohol consumption among HIV infected (Prevalence Ratio; PR = 5.9; 95%CI 2.6–13.9; P<0,001) and general population (PR = 2.6; 95%CI 1.9–3.0; P<0.001). Years at school were inversely associated with heavy alcohol consumption among HIV-infected patients and directly associated among participants from the general population, even after controlling for sex, age, skin color, and smoking. Conclusions Heavy alcohol consumption is more prevalent in the general population than among HIV-infected patients. Individuals aware about their disease may reduce the amount of alcoholic beverages consumption comparatively to healthy individuals from the general population. PMID:27362541

  6. Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals

    PubMed Central

    Firth, C.; Harrison, R.; Ritchie, S.; Wardlaw, J.; Ferro, C.J.; Starr, J.M.; Deary, I.J.

    2016-01-01

    Background: Cytomegalovirus (CMV) is a chronic infection that is widely distributed in the population. CMV infects a range of tissues, including endothelium, and viral replication is suppressed by the host immune system. Infection is associated with increased risk of mortality from vascular disease in older people, but the mechanisms behind this have not been determined. Aim: We investigated the association between CMV infection and cardiovascular phenotype in a cohort of healthy elderly donors. Design: CMV serostatus and cardiovascular parameters were determined in the Lothian Birth cohort, which comprises 1091 individuals aged 70 years in whom many environmental, biochemical and radiological correlates of vascular function have been determined. Methods: CMV serostatus was determined by enzyme-linked immunosorbant assay and correlated with a range of biochemical and phenotypic measures. Results: Sixty-five percent of participants were CMV seropositive, which indicates chronic infection. The mean sitting systolic blood pressure (SBP) was 149.2 mmHg in CMV seropositive individuals compared with 146.2 mmHg in CMV seronegative subjects (SD 18.7 vs. 19.7; P < 0.017). This association between CMV infection and SBP was not attenuated after adjustment for a wide range of biological and socio-economic factors. Conclusions: These data show that CMV infection is associated with an increase in SBP in individuals at age 70 years. The magnitude is comparable to environmental variables such as obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension. PMID:27071749

  7. Enteric opportunistic parasites among HIV infected individuals: associated risk factors and immune status.

    PubMed

    Dwivedi, Kaushal Kumar; Prasad, Ganga; Saini, Sanjeev; Mahajan, Surbhi; Lal, Shiv; Baveja, Usha Krishan

    2007-05-01

    Data on various etiologic agents causing diarrhea in human immunodeficiency virus type-1 (HIV-1) infected individuals are sparse in Delhi, India. The present study was undertaken to identify various causative agents, the role of associated risk factors and immune status. A case-control study was conducted among 75 HIV-1 infected individuals, 50 with and 25 without diarrheal infection. Fecal samples were screened for coccidian parasites, enteric protozoa, and helminthes by using various staining techniques. The CD4+ T-lymphocyte count was estimated. Enteric parasites were identified among 62.7% individuals, of which Cryptosporidium emerged as the single largest pathogen predominant among 33% of the individuals (P < 0.025). Other parasites diagnosed that were significantly associated with diarrhea were Giardia lamblia (13.3%), microsporidia (6.7%), and Isospora belli (2.7%). Chronic infected diarrheal cases were found to have polyparasitic infections. The mean CD4+ cell count was found to be lower among the diarrheal cases when compared with the non-diarrheal cases (mean, 141 cells/mm(3) versus 390 cells/mm(3)). Similarly, among diarrheal individuals, the chronic diarrheal cases had a comparatively lower CD4+ cell count than the acute cases (mean, 123 cells/mm(3) versus 265 cells/mm(3)). Risk factors found significant during multivariate analysis were: residence in a slum, exposure to pets and animals, use of public toilets, and practice of unsafe homosexual activity. Enteric coccidian parasites were identified as significant agents associated with diarrhea, especially among those with improper hygiene, multiple infections and a lower CD4+ cell count. Thus, this study emphasizes the need for routine screening of enteric parasites as well as education about practicing personal hygiene and taking timely and appropriate prophylactic measures. PMID:17515636

  8. Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells

    PubMed Central

    Santos, Steven; Obukhov, Yuri; Nekhai, Sergei; Pushkarsky, Tatiana; Brichacek, Beda; Bukrinsky, Michael; Iordanskiy, Sergey

    2016-01-01

    The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. Our data suggest that incorporation of physiological amounts of MCM5 promotes aberrant reverse transcription, leading to partial incapacitation of cDNA, whereas increased MCM5 abundance leads to reduced reverse transcription and infection. Therefore, MCM5 has the properties of an inhibitory factor that interferes with production of an integration-competent cDNA product. PMID:27414250

  9. Seropositive individuals willingness to communicate, self-efficacy, and assertiveness prior to HIV infection.

    PubMed

    Crowell, Tara L

    2004-01-01

    The purpose of this study was to examine possible communication similarities between human immunodeficiency virus (HIV) positive and HIV negative individuals. Forty HIV positive heterosexuals, who were infected through heterosexual sex, completed an on-line questionnaire to assess their safer sexual communication, willingness to communicate, condom self-efficacy, and assertiveness prior to HIV infection. Results indicate that prior to infection, HIV positive heterosexuals reported having similar safer sexual communication behaviors to those not infected with the virus. Participants in this study reported high levels of willingness to engage in safer sex communication, but low levels of actual communication. Further, results reveal that participants who engaged more often in safer sex communication were more likely to use condoms. Additionally, participants reported high levels of condom self-efficacy and moderate levels of assertiveness; both variables positively correlated with condom use. Finally, participants reported that they believed they did not need to discuss using condoms because they were not at risk. Previous safer sexual communication research reveals HIV negative individuals reported engaging in the same behaviors and holding the same beliefs reported by seropositive individuals. Hence, discussion of the importance of safer sexual communication and the utility of personalization to increase the communication of HIV negative individuals is explored.

  10. Treatment uptake by individuals infected with Plasmodium falciparum in rural Gambia, West Africa.

    PubMed Central

    von Seidlein, Lorenz; Clarke, Sian; Alexander, Neâl; Manneh, Fandingding; Doherty, Tom; Pinder, Margaret; Walraven, Gijs; Greenwood, Brian

    2002-01-01

    OBJECTIVE: To find out what proportion of Plasmodium falciparum infections are treated in rural Gambia. METHODS: Subjects from four villages in the Gambia were followed over nine months through visits to village health workers. Monthly cross-sectional malaria surveys measured the prevalence of P. falciparum infection. Linked databases were searched for treatment requests. Treated cases were individuals with parasitaemia who requested treatment during narrow or extended periods (14 or 28 days, respectively) before or after a positive blood film was obtained. FINDINGS: Parasite prevalence peaked in November 1998, when 399/653 (61%) individuals had parasitaemia. Parasite prevalence was highest throughout the study in children aged 5-10 years. Although access to treatment was better than in most of sub-Saharan Africa, only 20% of infected individuals sought medical treatment up to 14 days before or after a positive blood film. Within two months of a positive blood film, 199/726 (27%) individuals with parasitaemia requested treatment. Despite easy access to health care, less than half (42%) of those with parasite densities consistent with malaria attacks (5000/ l) requested treatment. High parasite density and infection during October-November were associated with more frequent treatment requests. Self-treatment was infrequent in study villages: in 3/120 (2.5%) households antimalarial drugs had been used in the preceding malaria season. CONCLUSION: Many P. falciparum infections may be untreated because of their subclinical nature. Intermittent presumptive treatment may reduce morbidity and mortality. It is likely that not all untreated infections were asymptomatic. Qualitative research should explore barriers to treatment uptake, to allow educational interventions to be planned. PMID:12471399

  11. Bacterial endosymbiont-derived lipopolysaccharides and a protein on symbiosome membranes in newly infected amoebae and their roles in lysosome-symbiosome fusion.

    PubMed

    Kim, K J; Na, Y E; Jeon, K W

    1994-01-01

    Experimental results are presented to support the view that symbiont-derived lipopolysaccharides are involved in the prevention of lysosome-symbiosome fusion in xD amoebae harboring bacterial endosymbionts. Monoclonal antibodies against lipopolysaccharides and a 96-kDa protein present on symbiosome membranes of amoebae were used to monitor the appearance of the membrane-specific components in newly infected amoebae with endosymbionts from xD amoebae. The lipopolysaccharides and protein appeared on the newly forming symbiosome membranes within 3 to 7 days, as detected by indirect immunofluorescence staining with monoclonal antibodies. The lysosome-symbiosome fusion was followed by double staining of two antigens with different monoclonal antibodies applied to the same amoeba. Antilipopolysaccharide monoclonal antibodies were detected by staining with a fluorescein isothiocyanate-conjugated secondary antibody, and a biotinylated anti-lysosomal protein monoclonal antibody was detected by staining with Texas Red-conjugated streptavidin. In xD amoebae injected with an antilipopolysaccharide antibody, lysosomes fused with some of the symbiosomes that did not fuse with lysosomes in noninjected cells. PMID:8262651

  12. Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals

    PubMed Central

    Galiani, M D; Aguado, E; Tarazona, R; Romero, P; Molina, I; Santamaria, M; Solana, R; PeñA, J

    1999-01-01

    Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals. PMID:10193420

  13. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients. PMID:25407519

  14. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

  15. Neurocognitive Impairment in HIV-1 Clade C versus B Infected Individuals in Southern Brazil

    PubMed Central

    de Almeida, Sergio Monteiro; Ribeiro, Clea Elisa; de Pereira, Ana Paula; Badiee, Jayraan; Cherner, Mariana; Smith, Davey; Maich, Ingrid; Raboni, Sonia Mara; Rotta, Indianara; Barbosa, Francisco Jaime; Heaton, Robert K.; Umlauf, Anya; Ellis, Ronald J.

    2014-01-01

    HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV- participants were recruited from the same geographic region in southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale; IHDS), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T-scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid (CSF) were collected from all HIV+ participants. HIV+ and HIV- participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV- by the IHDS and the GDS. Clade B and C infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis. PMID:24277437

  16. Dermatological Manifestations of Individuals Infected with Human T-cell Lymphotropic Virus type 1

    PubMed Central

    Dantas, Lorena; Netto, Eduardo; Glesby, Marshall; Carvalho, Edgar; Machado, Paulo

    2013-01-01

    Background Human T-cell lymphotropic virus - type 1 (HTLV-1) is associated with specific manifestations such as adult T-cell lymphoma/leukemia (ATLL), HTLV-1-associated myelopathy / tropical spastic paraparesis (HAM/TSP), HTLV-1-associated uveitis and infective dermatitis associated with HTLV-1 (IDH). Although ATLL and IDH are considered specific manifestations of HTLV-1 infection, several dermatological manifestations have been described in HTLV-1-infected patients. Methods A prevalence study was conducted between 2008 and 2010 with two groups of individuals, 179 HTLV-1 seropositive (positive ELISA and positive Western Blot) and 193 seronegative individuals (ELISA negative). The subjects were selected at a random basis and evaluated using a questionnaire to obtain epidemiological and clinical data. A physical examination was performed to verify the presence of skin lesions. Results Superficial mycoses were found in 54 HTLV-1-positive subjects (30.2%) and in 26 (13.5%) of the seronegative group (p<0.001). Xerosis was found in 39.1% of HTLV-1 infected subjects and in 9.3% of seronegative controls (p<0.001). Ichthyosis was diagnosed in 9 HTLV-1 positive cases (5%) whereas absent in the control group (p=0.001). A seborrheic dermatitis diagnosis was made in 43 HTLV-1 infected subjects (24%) and in 24 seronegative controls (12.4%) (p=0.004). Furthermore, the dermatological manifestations were more intense in the HTLV-1 group. Conclusions Several dermatological manifestations are more common and more severe in HTLV-1 subjects. The presence of these manifestations in an endemic area for HTLV- 1 infection may be a clue for the investigation of this infection. PMID:24111739

  17. Diagnosis of human immunodeficiency virus (HIV) infection: multicenter evaluation of a newly developed anti-HIV 1 and 2 enzyme immunoassay.

    PubMed Central

    Hess, G; Avillez, F; Lourenco, M H; D'Agostino, F; Cambie, G; Piot, P; Vercauteren, G; Michl, U; Melchior, W; Bayer, H

    1994-01-01

    A new anti-human immunodeficiency virus type 1 and 2 (anti-HIV 1 and 2) test is described. It uses recombinant p24 and peptides covering gp32, gp41, and gp120 to identify HIV-1 and HIV-2 infections. This test has been shown to be specific (99.5%) and sensitive (99.8%). In this respect, the assay was equal or superior to anti-HIV 1 and 2 tests run as references. The test was able to discriminate sera from patients with HIV infections from those from uninfected individuals with excellence; it also exerted high intra- and interassay precisions. The "modular" concept of the test allows the use of single components (gp32 or gp41) to separate between HIV-2 and HIV-1 infections, respectively. PMID:8150950

  18. First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China.

    PubMed

    Zhang, Yibo; Sun, Jingyong; Mi, Chenrong; Li, Wenhui; Zhao, Shengyuan; Wang, Qun; Shi, Dake; Liu, Luo; Ding, Bingyu; Chang, Yung-Fu; Guo, Hongxiong; Guo, XiaoKui; Li, Qingtian; Zhu, Yongzhang

    2015-01-01

    Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2-3 weeks will be also vital for successfully preventing hvKP reinfection or relapse. PMID:26257712

  19. Evaluation of the Microbicidal Activity and Cytokines/Chemokines Profile Released by Neutrophils from HTLV-1-Infected Individuals

    PubMed Central

    Bezerra, Caroline A.; Cardoso, Thiago M.; Giudice, Angela; Porto, Aurélia F.; Santos, Silvane B.; Carvalho, Edgar M.; Bacellar, Olívia

    2011-01-01

    Human T cell lymphotropic virus type-1 (HTLV-1) induces activation and spontaneous proliferation of T cells with production of type-1 pro-inflammatory cytokines. It modifies the immune response to other antigens and increases susceptibility to infectious diseases. However, little is known about innate immunity in HTLV-1 infection. HTLV-1-infected individuals have higher spontaneous neutrophil activation than HTLV-1-seronegative individuals, as shown by the nitroblue tetrazolium (NBT) assay. This study was conducted to evaluate neutrophil function in HTLV-1-infected individuals. Participants in the study included 18 HTLV-1-infected individuals and 14 HTLV-1-seronegative controls. We evaluated the ability of neutrophils (PMNs) to control a parasite infection, to produce peroxynitrite, cytokines and chemokines and to express activation markers in cultures when stimulated with LPS or infected with Leishmania. When compared with the control group, there was no difference in the percentage of PMNs infected with Leishmania or in the number of amastigotes/100 PMNs in HTLV-1-infected individuals. The microbicidal activity of the PMNs and the levels of CXCL8 and CCL4 released by these cells did not show a difference between HTLV-1-infected individuals and the control group. In both the HTLV-1 group and the control group, infection with Leishmania or stimulation of PMNs led to cellular activation. These observations suggest that neutrophils from HTLV-1-infected individuals have preserved their ability to become activated and to produce chemokines and peroxynitrite after stimulation and that the susceptibility to infection by intracellular Leishmania amazonensis in HTLV-1-infected individuals does not depend on impairment of neutrophil function. PMID:21595736

  20. Systemic dissemination as a result of oral infection in individuals 50 years of age and older.

    PubMed

    Navazesh, M; Mulligan, R

    1995-01-01

    The oral pathosis caused by systemic disorders in middle-aged and elderly adults has been the focus of many publications in recent years. The intraoral soft and hard tissue changes associated with systemic disorders, medications, chemotherapy, and radiation treatment have been well-investigated and -documented. Far less attention has been paid to the role of oral infection as the etiology of systemic disorders. A literature review (1980-1994) is provided here focusing on well-documented cases in which systemic disorders were caused by oral foci of infections. This paper attempts to raise the level of awareness of practitioners in considering possible systemic complications caused by oral infection. It also emphasizes the need for further longitudinal studies in this field involving healthy and medically compromised elderly individuals.

  1. The Serostatus Approach to Fighting the HIV Epidemic: prevention strategies for infected individuals.

    PubMed Central

    Janssen, R S; Holtgrave, D R; Valdiserri, R O; Shepherd, M; Gayle, H D; De Cock, K M

    2001-01-01

    In the United States, HIV prevention programs have historically tailored activities for specific groups primarily on the basis of behavioral risk factors and demographic characteristics. Through the Serostatus Approach to Fighting the Epidemic (SAFE), the Centers for Disease Control and Prevention is now expanding prevention programs, especially for individuals with HIV, to reduce the risk of transmission as a supplement to current programs that primarily focus on reducing the risk of acquisition of the virus. For individuals with HIV, SAFE comprises action steps that focus on diagnosing all HIV-infected persons, linking them to appropriate high-quality care and prevention services, helping them adhere to treatment regimens, and supporting them in adopting and sustaining HIV risk reduction behavior. SAFE couple a traditional infectious disease control focus on the infected person with behavioral interventions that have been standard for HIV prevention programs. PMID:11441723

  2. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.

    PubMed

    Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor

    2009-04-01

    Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

  3. Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals

    PubMed Central

    Lange, David C.; Glidden, David; Secemsky, Eric A.; Ordovas, Karen; Deeks, Steven G.; Martin, Jeffrey N.; Bolger, Ann F.; Hsue, Priscilla Y.

    2015-01-01

    Background HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals. Methods and Results We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell’s C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all). Conclusion In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death. PMID:26132465

  4. Seroprevalence of Human Herpesvirus-8 in HIV-1 Infected and Uninfected Individuals in Cameroon

    PubMed Central

    Mbondji-Wonje, Christelle; Ragupathy, Viswanath; Lee, Sherwin; Wood, Owen; Awazi, Bih; Hewlett, Indira K.

    2013-01-01

    We evaluated the prevalence of HHV-8 antibodies in 516 plasma samples collected from HIV positive and negative patients from blood banks and urban areas of Cameroon. Among HIV-1 positive samples, HHV-8 seropositivity rate was 61% based on combined reactivity using both ELISA and IFA techniques. HIV negative samples showed 62% seropositivity rate for HHV-8 antibodies. Our results indicate a high HHV-8 prevalence rate in both HIV infected and uninfected individuals in Cameroon. PMID:24056671

  5. Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population.

    PubMed

    Katoh, Jiro; Kawana-Tachikawa, Ai; Shimizu, Akihisa; Zhu, Dayong; Han, Chungyong; Nakamura, Hitomi; Koga, Michiko; Kikuchi, Tadashi; Adachi, Eisuke; Koibuchi, Tomohiko; Gao, George F; Brumme, Zabrina L; Iwamoto, Aikichi

    2016-01-01

    HIV-1 escape from CTL is predictable based on the Human Leukocyte Antigen (HLA) class I alleles expressed by the host. As such, HIV-1 sequences circulating in a population of hosts will harbor escape mutations specific to the HLA alleles of that population. In theory, this should increase the frequency of escape mutation transmission to persons expressing the restricting HLA allele, thereby compromising host immunity to the incoming HIV-1 strain. However, the clinical impact of infection with HIV-1 containing immune escape mutations has not conclusively been demonstrated. Japan's population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. As such, Japan is an ideal population in which to examine this phenomenon. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. Over a ~5 year follow-up, these individuals exhibited significantly lower CD4 counts compared to individuals inferred to have been infected with wild-type HIV-1. Our results support a significant negative clinical impact of pathogen adaptation to host pressures at the population level. PMID:26953793

  6. Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population.

    PubMed

    Katoh, Jiro; Kawana-Tachikawa, Ai; Shimizu, Akihisa; Zhu, Dayong; Han, Chungyong; Nakamura, Hitomi; Koga, Michiko; Kikuchi, Tadashi; Adachi, Eisuke; Koibuchi, Tomohiko; Gao, George F; Brumme, Zabrina L; Iwamoto, Aikichi

    2016-01-01

    HIV-1 escape from CTL is predictable based on the Human Leukocyte Antigen (HLA) class I alleles expressed by the host. As such, HIV-1 sequences circulating in a population of hosts will harbor escape mutations specific to the HLA alleles of that population. In theory, this should increase the frequency of escape mutation transmission to persons expressing the restricting HLA allele, thereby compromising host immunity to the incoming HIV-1 strain. However, the clinical impact of infection with HIV-1 containing immune escape mutations has not conclusively been demonstrated. Japan's population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. As such, Japan is an ideal population in which to examine this phenomenon. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. Over a ~5 year follow-up, these individuals exhibited significantly lower CD4 counts compared to individuals inferred to have been infected with wild-type HIV-1. Our results support a significant negative clinical impact of pathogen adaptation to host pressures at the population level.

  7. Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population

    PubMed Central

    Shimizu, Akihisa; Zhu, Dayong; Han, Chungyong; Nakamura, Hitomi; Koga, Michiko; Kikuchi, Tadashi; Adachi, Eisuke; Koibuchi, Tomohiko; Gao, George F.; Brumme, Zabrina L.; Iwamoto, Aikichi

    2016-01-01

    HIV-1 escape from CTL is predictable based on the Human Leukocyte Antigen (HLA) class I alleles expressed by the host. As such, HIV-1 sequences circulating in a population of hosts will harbor escape mutations specific to the HLA alleles of that population. In theory, this should increase the frequency of escape mutation transmission to persons expressing the restricting HLA allele, thereby compromising host immunity to the incoming HIV-1 strain. However, the clinical impact of infection with HIV-1 containing immune escape mutations has not conclusively been demonstrated. Japan’s population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. As such, Japan is an ideal population in which to examine this phenomenon. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. Over a ~5 year follow-up, these individuals exhibited significantly lower CD4 counts compared to individuals inferred to have been infected with wild-type HIV-1. Our results support a significant negative clinical impact of pathogen adaptation to host pressures at the population level. PMID:26953793

  8. Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

    PubMed Central

    2012-01-01

    The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays. PMID:22455516

  9. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

    PubMed Central

    Das, Partha Pratim; Saikia, Lahari; Nath, Reema; Phukan, Sanjib Kumar

    2016-01-01

    Background & objectives: The changing spectrum of Candida species in causation of oropharyngeal candidiasis and their antifungal susceptibility pattern among the HIV infected individuals has made the identification to species level mandatory and detection of drug resistance necessary for patient care. The present study was carried out to determine the species distribution and antifungal susceptibility profile of oral Candida isolates colonizing or infecting both HIV seropositive and seronegative individuals. Methods: A case-control study was conducted including 141 consecutive, non-repeat HIV-seropositive individuals and an equal number of sex and age matched HIV-seronegative control. Speciation of the oropharyngeal Candida isolates was done using standard yeast identification protocol. Antifungal susceptibility testing was done by the disk-diffusion method as well as by Fungitest method. Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candida albicans (n=47, 77.0%), C. dubliniensis (n=9, 14.7%), C. parapsilosis (n=2, 3.2%), C. glabrata (n=2, 3.2%), and C. famata (n=1, 1.6%). Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control) group. Antifungal susceptibility testing revealed (n=6, 9.3%) C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country. PMID:27377507

  10. Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

    PubMed Central

    Tippett, Emma; Cheng, Wan-Jung; Westhorpe, Clare; Cameron, Paul U.; Brew, Bruce J.; Lewin, Sharon R.; Jaworowski, Anthony; Crowe, Suzanne M.

    2011-01-01

    CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163

  11. Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1-Infected Individuals

    PubMed Central

    Aziz, Najib; Detels, Roger; Chang, L Cindy; Butch, Anthony W

    2016-01-01

    Objective Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described. Methods We determined the serum levels of MIP-3α, and IFN-γ, in 167 HIV-1-infected and 27 HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers were measured using enzyme-linked immunosorbent assays (ELISA) and the cell phenotypes using flow cytometry. Results Median serum levels of MIP-3α in HIV-1-infected and uninfected men was significantly different (p<0.0001) and were 21.3 pg/mL and 6.4 pg/mL respectively. The HIV-1-infected men with CD4+ T cell count <200 cells/μL showed the highest median serum MIP-3α (23.1 pg/mL). Serum levels of MIP-3α in HIV-1 infected (n=167) were negatively correlated with absolute number of CD4+ T cell (p=0.01) and were positively correlated with CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-γ (0.006). Conclusion Serum levels of MIP-3α concomitantly increase with plasma levels of IFN-γ, CD38 expression on CD8+ T cells, and decreased of absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3α may be representation of locally high level of MIP-3α and more recruitment of immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and epithelial cells at the recto-colonel level may enhance sexual transmission of HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and AIDS. PMID:27617163

  12. Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1-Infected Individuals

    PubMed Central

    Aziz, Najib; Detels, Roger; Chang, L Cindy; Butch, Anthony W

    2016-01-01

    Objective Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described. Methods We determined the serum levels of MIP-3α, and IFN-γ, in 167 HIV-1-infected and 27 HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers were measured using enzyme-linked immunosorbent assays (ELISA) and the cell phenotypes using flow cytometry. Results Median serum levels of MIP-3α in HIV-1-infected and uninfected men was significantly different (p<0.0001) and were 21.3 pg/mL and 6.4 pg/mL respectively. The HIV-1-infected men with CD4+ T cell count <200 cells/μL showed the highest median serum MIP-3α (23.1 pg/mL). Serum levels of MIP-3α in HIV-1 infected (n=167) were negatively correlated with absolute number of CD4+ T cell (p=0.01) and were positively correlated with CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-γ (0.006). Conclusion Serum levels of MIP-3α concomitantly increase with plasma levels of IFN-γ, CD38 expression on CD8+ T cells, and decreased of absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3α may be representation of locally high level of MIP-3α and more recruitment of immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and epithelial cells at the recto-colonel level may enhance sexual transmission of HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and AIDS.

  13. Electron-microscopic and chemical identification of an individual grain in the newly formed cementite in spheroidized pearlitic 12Kh1MF steel

    NASA Astrophysics Data System (ADS)

    Gerasimov, V. V.

    2015-12-01

    The microstructure of pearlitic 12Kh1MF steel having spent its service life is studied with a Neophot-32 optical microscope. A cementite grain is identified and its elemental composition is determined using a multipurpose EVO-50 scanning electron microscope equipped with an EDS/WDS X-ray spectrometer. A newly formed grain of alloyed cementite is detected at a triple junction. The diffusion processes that occur in loaded steel are refined.

  14. Mitochondrial Haplogroup Influences Motor Function in Long-Term HIV-1-Infected Individuals

    PubMed Central

    Azar, Ashley; Giovannetti, Tania; Pirrone, Vanessa; Nonnemacher, Michael R.; Passic, Shendra; Kercher, Katherine; Williams, Jean W.; Wigdahl, Brian; Dampier, William; Libon, David J.; Sell, Christian

    2016-01-01

    Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes. Stepwise regression analysis showed that the best model for predicting both working memory and declarative memory were age and years since diagnosis. In contrast, years since diagnosis and sub-haplogroup were significantly predictive of psychomotor speed. Consistent with this, patients with haplogroup L3e obtained better scores on psychomotor speed and dexterity tasks when compared to the remainder of the cohort, suggesting that this haplogroup provides a protective advantage when faced with the combined stress of HIV-1 infection and long-term antiretroviral therapies. Differential performance on declarative memory tasks was noted for individuals with other sub-L haplogroups, but these differences were not as robust as the association between L3e and psychomotor speed and dexterity tasks. This work provides evidence that mitochondrial haplogroup is related to neuropsychological test performance among patients in chronic disease settings such as HIV-1 infection. PMID:27711166

  15. Variations in the Role of Social Support on Disclosure Among Newly Diagnosed HIV-Infected People Who Inject Drugs in Vietnam.

    PubMed

    Go, Vivian F; Latkin, Carl; Le Minh, Nguyen; Frangakis, Constantine; Ha, Tran Viet; Sripaipan, Teerada; Mo, Tran Thi; Davis, Wendy W; Vu, Pham The; Quan, Vu Minh

    2016-01-01

    Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option.

  16. Variations in the Role of Social Support on Disclosure Among Newly Diagnosed HIV-Infected People Who Inject Drugs in Vietnam.

    PubMed

    Go, Vivian F; Latkin, Carl; Le Minh, Nguyen; Frangakis, Constantine; Ha, Tran Viet; Sripaipan, Teerada; Mo, Tran Thi; Davis, Wendy W; Vu, Pham The; Quan, Vu Minh

    2016-01-01

    Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option. PMID:25972071

  17. Risk factors for West Nile virus Infection and Disease in Populations and Individuals

    PubMed Central

    Montgomery, Ruth R.; Murray, Kristy O.

    2016-01-01

    Summary West Nile virus (WNV) is a mosquito-borne enveloped positive-strand RNA virus that emerged in North America in 1999 in New York City. Over the past 15 years, WNV has become established throughout the USA and has spread into Canada, Mexico and the Caribbean. CDC reports indicate >41,000 clinical cases, including more than 1,700 fatalities. An estimated 3 million people in the USA may have been infected to date. Infection with WNV is dependent on many factors including climate, mosquito habitats and immunologically-naïve bird populations. In addition, variations within individuals contribute to the risk of severe disease, in particular, advanced age, hypertension, immunosuppression and critical elements of the immune response. Recent advances in technology now allow detailed analysis of complex immune interactions relevant to disease susceptibility. PMID:25637260

  18. Antibodies to CD4 in individuals infected with human immunodeficiency virus type 1.

    PubMed Central

    Kowalski, M; Ardman, B; Basiripour, L; Lu, Y C; Blohm, D; Haseltine, W; Sodroski, J

    1989-01-01

    The attachment of human immunodeficiency virus type 1 (HIV-1) to target cells is mediated by a specific interaction between the viral envelope glycoprotein (gp120) and the CD4 receptor. Here we report that approximately 10% of HIV-1-infected individuals produce antibodies that recognize the extracellular portion of the CD4 molecule. Carboxyl-terminal deletions of CD4 that do not affect HIV-1 gp120 binding eliminate recognition of CD4 by patient antisera. In contrast, mutations in the amino-terminal domain of CD4 that attenuate HIV-1 gp120 binding do not diminish CD4 recognition by patient antisera. These results suggest that HIV-1 infection can generate antibodies directed against a region of the viral receptor distinct from the virus-binding domain. Images PMID:2541442

  19. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.

    2010-01-01

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretroviral therapy, adherence with therapy, and long-term persistence in care. Substance abuse treatment appears to facilitate engagement in HIV care, and access to evidence-based treatment for substance abuse is central to addressing the HIV epidemic. Strategies that show promise for HIV-infected substance abusers include integrated treatment models, directly observed therapy, and incentive-based interventions. PMID:20888839

  20. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

    PubMed Central

    Achkar, Jacqueline M.; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O.; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-01-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  1. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals.

    PubMed

    Achkar, Jacqueline M; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-09-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV(-)) and co-infected (HIV(+)) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV(-) individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV(+) individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV(-) TB, 0.95 for HIV(+) TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  2. Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a “special population”?

    PubMed Central

    Karageorgopoulos, Drosos E; Allen, Joanna; Bhagani, Sanjay

    2015-01-01

    A substantial proportion of individuals with chronic hepatitis C virus (HCV) are co-infected with human immunodeficiency virus (HIV). Co-infected individuals are traditionally considered as one of the “special populations” amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals (DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the “special population” designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users. PMID:26244068

  3. Depressive symptoms, lifestyle structure, and ART adherence among HIV-infected individuals: a longitudinal mediation analysis.

    PubMed

    Magidson, Jessica F; Blashill, Aaron J; Safren, Steven A; Wagner, Glenn J

    2015-01-01

    Despite the well-documented relationship between depression and antiretroviral therapy (ART) nonadherence, few studies have identified explanatory pathways through which depression affects adherence. The current study tested lifestyle structure-the degree of organization and routinization of daily activities-as a mediator of this relationship, given previous evidence of lifestyle structure being associated with both depression and ART nonadherence. HIV-infected individuals starting or re-starting ART in the California Collaborative Treatment Group 578 study (n = 199) were assessed over 48 weeks. Adherence was measured using electronic monitoring caps to determine dose timing and doses taken, and viral load was assessed. The mediating role of lifestyle structure was tested using generalized linear mixed-effects modeling and bootstrapping. Lifestyle significantly mediated the relationship between depression and both measures of ART adherence behavior. Interventions that minimize disruptions to lifestyle structure and link adherence to daily activities may be useful for individuals with depression and ART nonadherence.

  4. The Wide Range Achievement Test-4 Reading Subtest “Holds” in HIV-infected Individuals

    PubMed Central

    Casaletto, K. B.; Cattie, J.; Franklin, D. R.; Moore, D. J.; Woods, S. P.; Grant, I.; Heaton, R. K.

    2014-01-01

    Background In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals’ premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population. Methods The Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants at baseline; a subset of 48 HIV+ individuals completed a second study visit (M=14.4 months), in which the alternate version of the WRAT-4 was administered. Results Although HIV+ individuals evidenced worse current neurocognitive functioning than HIV- participants, WRAT-4 Reading performance was comparable between groups. Longitudinally, HIV+ participants evidenced improved disease and neuropsychological functioning, yet WRAT-4 Reading demonstrated strong test-retest reliability, no practice effect, and did not differ between the initial and follow-up assessments. Test-retest differences in reading performance were minor and not associated with changes in neurocognitive performance or changes in HIV disease. Conclusions We found no evidence of WRAT-4 Reading performance decline in HIV infection, despite HIV+/HIV- group differences in neurocognitive functioning. Additionally, reading performances among HIV+ individuals demonstrated consistency across study visits. These results begin to support the validity of the WRAT-4 Reading subtest as an indicator of premorbid cognitive functioning in HIV+ individuals. PMID:25283135

  5. Conceptual models for Mental Distress among HIV-infected and uninfected individuals: A contribution to clinical practice and research in primary-health-care centers in Zambia

    PubMed Central

    2011-01-01

    Background Mental distress is common in primary care and overrepresented among Human Immunodeficiency virus (HIV)-infected individuals, but access to effective treatment is limited, particularly in developing countries. Explanatory models (EM) are contextualised explanations of illnesses and treatments framed within a given society and are important in understanding an individual's perspective on the illness. Although individual variations are important in determining help-seeking and treatment behaviour patterns, the ability to cope with an illness and quality of life, the role of explanatory models in shaping treatment preferences is undervalued. The aim was to identify explanatory models employed by HIV-infected and uninfected individuals and to compare them with those employed by local health care providers. Furthermore, we aimed to build a theoretical model linking the perception of mental distress to treatment preferences and coping mechanisms. Methods Qualitative investigation nested in a cross-sectional validation study of 28 (male and female) attendees at four primary care clinics in Lusaka, Zambia, between December 2008 and May 2009. Consecutive clinic attendees were sampled on random days and conceptual models of mental distress were examined, using semi-structured interviews, in order to develop a taxonomic model in which each category was associated with a unique pattern of symptoms, treatment preferences and coping strategies. Results Mental distress was expressed primarily as somatic complaints including headaches, perturbed sleep and autonomic symptoms. Economic difficulties and interpersonal relationship problems were the most common causal models among uninfected individuals. Newly diagnosed HIV patients presented with a high degree of hopelessness and did not value seeking help for their symptoms. Patients not receiving anti-retroviral drugs (ARV) questioned their effectiveness and were equivocal about seeking help. Individuals receiving ARV were

  6. Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals.

    PubMed

    Serrano-Villar, Sergio; Rojo, David; Martínez-Martínez, Mónica; Deusch, Simon; Vázquez-Castellanos, Jorge F; Bargiela, Rafael; Sainz, Talía; Vera, Mar; Moreno, Santiago; Estrada, Vicente; Gosalbes, María José; Latorre, Amparo; Seifert, Jana; Barbas, Coral; Moya, Andrés; Ferrer, Manuel

    2016-06-01

    While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host. PMID:27428431

  7. Neuronal number and volume alterations in the neocortex of HIV infected individuals.

    PubMed Central

    Everall, I P; Luthert, P J; Lantos, P L

    1993-01-01

    Substantial neuronal loss in the superior frontal gyrus in patients who have died of AIDS have been reported previously. This investigation examined the distribution of neuronal loss in three other neocortical areas and, alteration in neuronal volume in four neocortical areas. This was carried out using two stereological probes, the "disector" and the "nucleator". These recently developed methods provide estimations, regardless of size and shape, in real three-dimensional space, and are more efficient than conventional quantitation. The study was performed on 12 HIV infected individuals and nine controls. The HIV group had no neuropathological evidence of opportunistic infections or neoplasms, five had HIV encephalitis and the remaining seven had only minimal pathology. There was significant neuronal loss of 30% (p = 0.018) in the calcarine cortex (primary visual area), and loss of 18% in the superior parietal lobule which just failed to reach significance. This loss was not related to the presence of HIV encephalitis. The mean neuronal volume was increased in the occipital area by 29% (p = 0.028) and the frequency of large neurons (over 2000 microns 3) doubled in the frontal (p < 0.05) and parietal (p < 0.02) areas. The results confirm the hypothesis that HIV infection is associated with neuronal injury and death, and suggest that increase in neuronal size may be a feature of the cytopathology of this condition. PMID:8505639

  8. Anopheles darlingi (Diptera: Culicidae) displays increased attractiveness to infected individuals with Plasmodium vivax gametocytes

    PubMed Central

    2014-01-01

    Background Most hematophagous insects use host odours as chemical cues. The odour components, some physiological parameters and host attractiveness are affected by several conditions, including infection by parasites, e.g., plasmodia and, therefore, change the epidemiological scenario. This study evaluated the attractiveness of individuals with vivax malaria before, during (7 days) and after treatment (14 days) with specific antimalarial drugs. Findings Mosquito attractiveness to vivax-infected patients was assessed using a vertical olfactometer using the foot as a source of body odour. The ratio of Anopheles darlingi mosquitoes in the lower chamber of the olfactometer was used to calculate the attractiveness, and patient temperature was measured using a digital thermometer. An increased attractiveness was found only in patients bearing vivax gametocytes during the first experiment (early infection) (P < 0.001). Patients in the first experiment tended to have a higher body temperature, but grouping patients into fever and non-fever resulted in a higher attractiveness only in the fever group of gametocyte carriers, suggesting a synergistic effect of temperature and gametocytes in the host attractiveness to A. darlingi. Conclusions Gametocyte presence and fever in vivax malaria patients increased short distance host attractiveness to An. darlingi. PMID:24885914

  9. Impaired antibody response after immunization of HIV-infected individuals with the polysaccharide vaccine against Salmonella typhi (Typhim-Vi).

    PubMed

    Kroon, F P; van Dissel, J T; Ravensbergen, E; Nibbering, P H; van Furth, R

    1999-08-01

    Infections with Salmonella species, including Salmonella typhi, are more frequently observed in HIV-infected individuals than in healthy individuals. HIV-infected individuals were vaccinated with polysaccharide vaccine against Salmonella typhi (Typhim-Vi) which is assumed to be a T-cell-independent antigen. We found that the antibody response in patients with < 200 x 10(6)/l CD4+ T lymphocytes was significantly lower compared with patients with > or = 200 x 10(6)/l CD4+ T lymphocytes and healthy controls. The antibody response after vaccination with the polysaccharide salmonella Vi-antigen was correlated with the number of CD4+ T lymphocytes and therefore Typhim-Vi can be considered to be a T-cell-independent type 2 antigen. The results of this study indicate that after vaccination the proportion of HIV-infected individuals with protective antibody concentrations against Salmonella typhi will be lower than in healthy controls.

  10. On the correlation between variance in individual susceptibilities and infection prevalence in populations.

    PubMed

    Margheri, Alessandro; Rebelo, Carlota; Gomes, M Gabriela M

    2015-12-01

    The hypothesis that infection prevalence in a population correlates negatively with variance in the susceptibility of its individuals has support from experimental, field, and theoretical studies. However, its generality has never been formally demonstrated. Here we formulate an endemic SIS model with individual susceptibility distributed according to a discrete or continuous probability function to assess the generality of such hypothesis. We introduce an ordering among susceptibility distributions with the same mean, analogous to that considered in Katriel (J Math Biol 65:237-262, 2012) to order the attack rates in an epidemic SIR model with heterogeneity. It turns out that if one distribution dominates another in this order then it has greater variance and corresponds to a lower infection prevalence for R0 varying in a suitable maximal interval of the form ]1, R0*]. We show that in both the discrete and continuous frameworks R0* can be finite, so that the expected correlation among variance and prevalence does not always hold. For discrete distributions this fact is demonstrated analytically, and the proof introduces a constructive procedure to find ordered pairs for which R0* is arbitrarily close to 1. For continuous distributions our conclusion is based on numerical studies with the beta distribution. Finally, we present explicit partial orderings among discrete susceptibility distributions and among symmetric beta distributions which guarantee that R0* = +∞.

  11. Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

    PubMed

    Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

    2015-07-31

    Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir<200c/μl was associated with increased pertussis seropositivity (OR 12.2, 95% CI 1.2 to 121). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. In patients with a CD4 count>200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases.

  12. Factors Associated with D-Dimer Levels in HIV-Infected Individuals

    PubMed Central

    Borges, Álvaro H.; O’Connor, Jemma L.; Phillips, Andrew N.; Baker, Jason V.; Vjecha, Michael J.; Losso, Marcelo H.; Klinker, Hartwig; Lopardo, Gustavo; Williams, Ian; Lundgren, Jens D.

    2014-01-01

    Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. PMID:24626096

  13. Indirect effects of parasitism: costs of infection to other individuals can be greater than direct costs borne by the host

    PubMed Central

    Granroth-Wilding, Hanna M. V.; Burthe, Sarah J.; Lewis, Sue; Herborn, Katherine A.; Takahashi, Emi A.; Daunt, Francis; Cunningham, Emma J. A.

    2015-01-01

    Parasitic infection has a direct physiological cost to hosts but may also alter how hosts interact with other individuals in their environment. Such indirect effects may alter both host fitness and the fitness of other individuals in the host's social network, yet the relative impact of direct and indirect effects of infection are rarely quantified. During reproduction, a host's social environment includes family members who may be in conflict over resource allocation. In such situations, infection may alter how resources are allocated, thereby redistributing the costs of parasitism between individuals. Here, we experimentally reduce parasite burdens of parent and/or nestling European shags (Phalacrocorax aristotelis) infected with Contracaecum nematodes in a factorial design, then simultaneously measure the impact of an individual's infection on all family members. We found no direct effect of infection on parent or offspring traits but indirect effects were detected in all group members, with both immediate effects (mass change and survival) and longer-term effects (timing of parents’ subsequent breeding). Our results show that parasite infection can have a major impact on individuals other than the host, suggesting that the effect of parasites on population processes may be greater than previously thought. PMID:26156765

  14. Natural Selection on Individual Variation in Tolerance of Gastrointestinal Nematode Infection

    PubMed Central

    Hayward, Adam D.; Nussey, Daniel H.; Wilson, Alastair J.; Berenos, Camillo; Pilkington, Jill G.; Watt, Kathryn A.; Pemberton, Josephine M.; Graham, Andrea L.

    2014-01-01

    Hosts may mitigate the impact of parasites by two broad strategies: resistance, which limits parasite burden, and tolerance, which limits the fitness or health cost of increasing parasite burden. The degree and causes of variation in both resistance and tolerance are expected to influence host–parasite evolutionary and epidemiological dynamics and inform disease management, yet very little empirical work has addressed tolerance in wild vertebrates. Here, we applied random regression models to longitudinal data from an unmanaged population of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. On average, individuals lost weight as parasite burden increased, but whereas some lost weight slowly as burden increased (exhibiting high tolerance), other individuals lost weight significantly more rapidly (exhibiting low tolerance). We then investigated associations between tolerance and fitness using selection gradients that accounted for selection on correlated traits, including body weight. We found evidence for positive phenotypic selection on tolerance: on average, individuals who lost weight more slowly with increasing parasite burden had higher lifetime breeding success. This variation did not have an additive genetic basis. These results reveal that selection on tolerance operates under natural conditions. They also support theoretical predictions for the erosion of additive genetic variance of traits under strong directional selection and fixation of genes conferring tolerance. Our findings provide the first evidence of selection on individual tolerance of infection in animals and suggest practical applications in animal and human disease management in the face of highly prevalent parasites. PMID:25072883

  15. Characterization of Human Endogenous Retroviral Elements in the Blood of HIV-1-Infected Individuals

    PubMed Central

    Contreras-Galindo, Rafael; Kaplan, Mark H.; Contreras-Galindo, Angie C.; Gonzalez-Hernandez, Marta J.; Ferlenghi, Ilaria; Giusti, Fabiola; Lorenzo, Eric; Gitlin, Scott D.; Dosik, Michael H.; Yamamura, Yasuhiro

    2012-01-01

    We previously reported finding the RNA of a type K human endogenous retrovirus, HERV-K (HML-2), at high titers in the plasma of HIV-1-infected and cancer patients (R. Contreras-Galindo et al., J. Virol. 82:9329–9236, 2008.). The extent to which the HERV-K (HML-2) proviruses become activated and the nature of their activated viral RNAs remain important questions. Therefore, we amplified and sequenced the full-length RNA of the env gene of the type 1 and 2 HERV-K (HML-2) viruses collected from the plasma of seven HIV-1-infected patients over a period of 1 to 3 years and from five breast cancer patients in order to reconstruct the genetic evolution of these viruses. HERV-K (HML-2) RNA was found in plasma fractions of HIV-1 patients at a density of ∼1.16 g/ml that contained both immature and correctly processed HERV-K (HML-2) proteins and virus-like particles that were recognized by anti-HERV-K (HML-2) antibodies. RNA sequences from novel HERV-K (HML-2) proviruses were discovered, including K111, which is specifically active during HIV-1 infection. Viral RNA arose from complete proviruses and proviruses devoid of a 5′ long terminal repeat, suggesting that the expression of HERV-K (HML-2) RNA in these patients may involve sense and antisense transcription. In HIV-1-infected individuals, the HERV-K (HML-2) viral RNA showed evidence of frequent recombination, accumulation of synonymous rather than nonsynonymous mutations, and conserved N-glycosylation sites, suggesting that some of the HERV-K (HML-2) viral RNAs have undergone reverse transcription and are under purifying selection. In contrast, HERV-K (HML-2) RNA sequences found in the blood of breast cancer patients showed no evidence of recombination and exhibited only sporadic viral mutations. This study suggests that HERV-K (HML-2) is active in HIV-1-infected patients, and the resulting RNA message reveals previously undiscovered HERV-K (HML-2) genomic sequences. PMID:22031938

  16. Longitudinal analysis of antigen specific response in individuals with Schistosoma mansoni infection in an endemic area of Minas Gerais, Brazil

    PubMed Central

    Matoso, Leonardo Ferreira; Oliveira-Prado, Roberta; Abreu, Mery Natali Silva; Fujiwara, Ricardo Toshio; LoVerde, Philip T.; Kloos, Helmut; Gazzinelli, Andréa; Correa-Oliveira, Rodrigo

    2013-01-01

    Background Immunoepidemiologic studies have shown a relationship between IgE and IgG4 antibodies with age and with resistance and susceptibility to infection. It is believed that the IgE and IgG4 responses to soluble egg antigen (SEA) can be used for serological analysis of infection and post-treatment status. This study aimed to evaluate the association between Schistosoma mansoni infection and anti-SEA IgG4 and IgE reactivities, and determine whether these reactivities could be used as biomarkers of infection. Methods Between 2001 and 2009, a longitudinal study was performed in which parasitologic and blood specimens and socioeconomic and water-contact information were collected from 127 individuals. All patients positive for S. mansoni infection were treated. Results Schistosomiasis prevalence and the geometric mean of the egg count in 2001 were 59% and 61.05, respectively, decreasing to 26.8% and 8.78 in 2009. IgG4 anti-SEA reactivity in infected individuals was significantly higher than that in uninfected individuals at all time points. Analysis of receiver-operating characteristic (ROC) area showed that the IgG4 anti-SEA antibodies were able to predict infection by S. mansoni at each time point. Conclusion IgG4 anti-SEA reactivity can be used as a biomarker for immune monitoring of the presence of infection with S. mansoni in endemic areas. PMID:24189480

  17. Neutralization breadth and potency of serum derived from recently human immunodeficiency virus type 1-infected Thai individuals.

    PubMed

    Chaitaveep, Nithinart; Utachee, Piraporn; Chuenchitra, Thippawan; Karasavvan, Nicos; Takeda, Naokazu; Kameoka, Masanori

    2016-05-01

    Neutralizing antibody responses play important roles in controlling several viral infections including human immunodeficiency virus type 1 (HIV-1). Potent and broad neutralizing antibody responses have been reported in some HIV-1-infected individuals; therefore, elucidating the mechanisms underlying neutralizing antibody responses will provide important information for the development of anti-HIV-1 vaccines. We herein performed a comparative study on the neutralization breadth and potency of serum samples collected from Thai individuals recently and chronically infected with HIV-1. Neutralization tests using a series of envelope glycoproteins (Env)-recombinant viruses revealed that although several serum samples derived from recently infected individuals did not show any HIV-1-specific neutralizing activity, the remaining serum samples exhibited neutralizing activity not only for recombinant viruses with CRF01_AE Env, but also for viruses with subtypes B and C Env. Furthermore, some serum samples derived from recently infected individuals showed the neutralization potency. Our results may provide a deeper insight into the characteristics of neutralizing antibody responses that develop during the course of HIV-1 infection among individuals in Thailand.

  18. HIV Prevalence and Risks Associated with HIV Infection among Transgender Individuals in Cambodia

    PubMed Central

    Ngak, Song; Srean, Chhim; Sansothy, Neth; Mills, Stephen; Ferradini, Laurent

    2016-01-01

    = 3.25 [1.35,7.85]) were independently associated with HIV infection. Conclusions This study confirms transgender individuals as one of the highest-risk groups for HIV infection in Cambodia. It suggests the need for programmatic strategies that mitigate identified associated risks and facilitate access to HIV care for this population. PMID:27070152

  19. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

    PubMed Central

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-01-01

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  20. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics.

    PubMed

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-08-12

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  1. Food Insecurity, Depression, and Social Support in HIV-infected Hispanic Individuals

    PubMed Central

    Kapulsky, Leonid; Tang, Alice M

    2014-01-01

    Background Previous research has identified an association between food insecurity and depression in a variety of world regions in both healthy and HIV-infected individuals. We examined this association in 183 HIV-infected Hispanic adults from the Greater Boston area. Methods We measured depression with the Burnam Depression Screen and food insecurity with the Radimer/Cornell Questionnaire. Dietary intake was assessed with an adapted version of the Block Food Frequency Questionnaire. Logistic regression models were created with depression as the outcome variable and food insecurity as the main predictor. Results In bivariate analyses, food insecurity was significantly associated with depression (odds ratio [OR] = 2.5; 95% confidence interval [CI]: 1.1, 5.5; P = 0.03). When we accounted for social support, food insecurity was no longer significant. We found no differences in the quality or quantity of dietary intake between the food insecure and food secure groups. Discussion Our findings highlight the importance of social support in the association between food insecurity and depression. Food insecurity may reflect social support more than actual dietary intake in this population. PMID:25047405

  2. Low prevalence of primary antiretroviral resistance mutations and predominance of HIV-1 clade C at polymerase gene in newly diagnosed individuals from south Brazil.

    PubMed

    Rodrigues, Rosangela; Scherer, Luciene C; Oliveira, Cristina M; Franco, Heitor Moreira; Sperhacke, Rosa Dea; Ferreira, Joao Leandro Paula; Castro, Simone Martins; Stella, Isete Maria; Brigido, Luis Fernando Macedo

    2006-03-01

    We describe preliminary molecular characterization of HIV-1 pol from 108 consecutive HIV seropositive users of a Voluntary Counseling and Testing (VCT) site of Porto Alegre city, the major metropolitan area in the south of Brazil. Protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and sequenced after direct nested PCR. Principal antiretroviral resistance mutations (ARM) were observed in 3% of the samples, two cases with K103N and one with M41L, L210W and T215Y, all in HIV-1 clade B infected men. At protease region, no principal mutations were observed, but polymorphisms at secondary codons were frequent. Contrary to other areas in the country where clade B dominates, HIV-1 clade C genomes predominated in this study (58%), clade B (32%) and clade F1 (3%). Of the genomes clustering in clade C, almost half (43%) had a small clade B segment at reverse transcriptase, forming a sub-cluster within clade C with a similar recombinant structure and carrying new amino acid signatures. Other mosaic genomes were also observed (7%). The low prevalence of resistance mutations is consistent with previous observations at this geographical location but the high frequency of HIV-1 clade C and CB mosaics seems pre-eminent and warns close monitoring.

  3. Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual.

    PubMed

    Khan, Lubina; Makhdoomi, Muzamil Ashraf; Kumar, Sanjeev; Nair, Ambili; Andrabi, Raiees; Clark, Brenda E; Auyeung, Kate; Bhattacharya, Jayanta; Vajpayee, Madhu; Wig, Naveet; Pantophlet, Ralph; Luthra, Kalpana

    2015-01-01

    Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.

  4. HIV infection duration, social support and the level of trauma symptoms in a sample of HIV-positive Polish individuals.

    PubMed

    Rzeszutek, Marcin; Oniszczenko, Włodzimierz; Żebrowska, Magdalena; Firląg-Burkacka, Ewa

    2015-01-01

    The aim of this study was to investigate the relationship between the average HIV infection duration and the level of quantitatively rated post-traumatic stress disorder (PTSD) symptoms and social support dimensions in a sample of 562 Polish HIV+ adults. Possible moderating effects of social support on the relationship between the average HIV infection duration and the level of PTSD symptoms were also analysed. The results of this study suggest that the average HIV infection duration may intensify PTSD symptoms and deteriorate the perceived availability of social support in HIV+ individuals. However, a positive relationship between HIV infection duration and the level of trauma symptoms was observed only in the group of HIV+ individuals with low perceived available social support, but not in the group of HIV-infected individuals with high perceived available social support. This research provided some new insight into the psychological and social aspects of living with HIV. In particular, our results suggest that although HIV infection duration may intensify trauma symptoms and deteriorate social support, perceived available social support may act as a buffer against HIV-related trauma symptoms.

  5. Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers.

    PubMed

    Luquetti, Alejandro O; Tavares, Suelene Brito do Nascimento; Siriano, Liliane da Rocha; Oliveira, Rozângela Amaral de; Campos, Dayse Elizabeth; de Morais, Cicilio Alves; de Oliveira, Enio Chaves

    2015-05-01

    Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruzi infection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruzi infection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruzi and the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region.

  6. Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers

    PubMed Central

    Luquetti, Alejandro O; Tavares, Suelene Brito do Nascimento; Siriano, Liliane da Rocha; de Oliveira, Rozângela Amaral; Campos, Dayse Elizabeth; de Morais, Cicilio Alves; de Oliveira, Enio Chaves

    2015-01-01

    Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruzi infection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruzi infection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruzi and the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region. PMID:25993506

  7. Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls.

    PubMed

    Biselli, R; Mariotti, S; Sargentini, V; Sauzullo, I; Lastilla, M; Mengoni, F; Vanini, V; Girardi, E; Goletti, D; D' Amelio, R; Nisini, R

    2010-08-01

    Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.

  8. Increased Endoparasite Infection in Late-Arriving Individuals of a Trans-Saharan Passerine Migrant Bird

    PubMed Central

    López, Guillermo; Muñoz, Joaquín; Soriguer, Ramón; Figuerola, Jordi

    2013-01-01

    Earlier migration in males than in females is the commonest pattern in migrating passerines and is positively related to size dimorphism and dichromatism. The early arrival of males is a costly trait that may confer reproductive advantages in terms of better territories and/or mates. Given the physiological cost of migration, early migrants are those in best condition and accordingly the prevalence, load, and/or diversity of parasites is expected to increase in both sexes for late migrants. To test this hypothesis, we sampled 187 trans-Saharan migrant garden warblers Sylvia borin and 64 resident serins Serinus serinus (as a control for potential circannual patterns in parasite load) during spring migration in Spain. We assessed the prevalence of blood parasites (Haemoproteus, Plasmodium, and Leucocytozoon) and the prevalence and load of intestinal parasites (mainly coccidians and spirurids). The relationship between parasite (prevalence, load, and richness) and the timing of passage through a stopover area was tested using generalized linear models. Protandry occurs in the monomorphic garden warbler and males migrated on average 5.5 days before females. Intestinal parasite richness increased with the date of migration. The timing of migration was unrelated to the presence or load of the other parasite groups analyzed. Our results support the idea that the timing of migration is a condition-dependent trait and suggests that multiple intestinal parasite infestations could delay migration in birds. Even in monomorphic species parasites may play a role in sexual selection by delaying the arrival of the most infected individuals at breeding grounds, thereby further increasing the benefits of mating with early-arriving individuals. PMID:23620731

  9. Clinical correlates of suicidality among individuals with HIV infection and AIDS disease in Mbarara, Uganda.

    PubMed

    Rukundo, Godfrey Zari; Kinyanda, Eugene; Mishara, Brian

    2016-09-01

    The association between suicidality and HIV/AIDS has been demonstrated for three decades, but little is know about risk factors that can help understand this association and help identify who is most at risk. Few research studies have been conducted in sub-Saharan Africa, a region that accounts for more than 70% of the HIV global burden. This paper describes clinical risk factors for suicidality among individuals with HIV infection and AIDS disease in Mbarara, Uganda. In this study, suicidality includes both suicidal ideation and suicidal attempts. A cross-sectional survey was conducted with 543 HIV-positive individuals aged 15 years and above, recruited from 2 HIV specialised clinics in Mbarara. Using logistic regression analysis, factors significantly associated with suicidality at 95% confidence interval were identified. The rate of suicidality was 10% (n = 54; 95% CI: 5.00-15.00). Risk factors for suicidality were: perception of poor physical health (OR 2.22, 95% CI 1.23-3.99, p = 0.007), physical pain (OR 1.83, 95% CI 1.01-3.30, p = 0.049), reducing work due to illness (OR = 2.22, 95% CI 1.23-3.99, p = 0.004) and recent HIV diagnosis (OR 1.02, 95% CI 1.01-1.03, p = 0.001). These findings suggest that HIV/AIDS in south-western Uganda is associated with a considerable burden of suicidality. HIV is associated with several clinical factors that increase vulnerability to suicidality. There is need for more appropriate interventions targeting these clinical risk factors, systematic suicide risk assessment and management of suicidal ideation and behaviours in HIV care. PMID:27681146

  10. The Individualized Genetic Barrier Predicts Treatment Response in a Large Cohort of HIV-1 Infected Patients

    PubMed Central

    Beerenwinkel, Niko; Montazeri, Hesam; Schuhmacher, Heike; Knupfer, Patrick; von Wyl, Viktor; Furrer, Hansjakob; Battegay, Manuel; Hirschel, Bernard; Cavassini, Matthias; Vernazza, Pietro; Bernasconi, Enos; Yerly, Sabine; Böni, Jürg; Klimkait, Thomas; Cellerai, Cristina; Günthard, Huldrych F.

    2013-01-01

    The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests. PMID:24009493

  11. Gender disparities in latent tuberculosis infection in high-risk individuals: a cross-sectional study.

    PubMed

    Ting, Wen-Ying; Huang, Shiang-Fen; Lee, Ming-Che; Lin, Yung-Yang; Lee, Yu-Chin; Feng, Jia-Yih; Su, Wei-Juin

    2014-01-01

    Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ≥ 55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors. PMID:25369472

  12. Gender Disparities in Latent Tuberculosis Infection in High-Risk Individuals: A Cross-Sectional Study

    PubMed Central

    Ting, Wen-Ying; Huang, Shiang-Fen; Lee, Ming-Che; Lin, Yung-Yang; Lee, Yu-Chin

    2014-01-01

    Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ≥55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors. PMID:25369472

  13. H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix(®) vaccination.

    PubMed

    Ambati, Aditya; Valentini, Davide; Montomoli, Emanuele; Lapini, Guilia; Biuso, Fabrizio; Wenschuh, Holger; Magalhaes, Isabelle; Maeurer, Markus

    2015-07-01

    A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix(®) vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.

  14. Assessment of the Microbial Constituents of the Home Environment of Individuals with Cystic Fibrosis (CF) and Their Association with Lower Airways Infections

    PubMed Central

    Heirali, Alya; McKeon, Suzanne; Purighalla, Swathi; Storey, Douglas G.; Rossi, Laura; Costilhes, Geoffrey; Drews, Steven J.; Rabin, Harvey R.; Surette, Michael G.; Parkins, Michael D.

    2016-01-01

    Introduction Cystic fibrosis (CF) airways are colonized by a polymicrobial community of organisms, termed the CF microbiota. We sought to define the microbial constituents of the home environment of individuals with CF and determine if it may serve as a latent reservoir for infection. Methods Six patients with newly identified CF pathogens were included. An investigator collected repeat sputum and multiple environmental samples from their homes. Bacteria were cultured under both aerobic and anaerobic conditions. Morphologically distinct colonies were selected, purified and identified to the genus and species level through 16S rRNA gene sequencing. When concordant organisms were identified in sputum and environment, pulsed-field gel electrophoresis (PFGE) was performed to determine relatedness. Culture-independent bacterial profiling of each sample was carried out by Illumina sequencing of the V3 region of the 16s RNA gene. Results New respiratory pathogens prompting investigation included: Mycobacterium abscessus(2), Stenotrophomonas maltophilia(3), Pseudomonas aeruginosa(3), Pseudomonas fluorescens(1), Nocardia spp.(1), and Achromobacter xylosoxidans(1). A median 25 organisms/patient were cultured from sputum. A median 125 organisms/home were cultured from environmental sites. Several organisms commonly found in the CF lung microbiome were identified within the home environments of these patients. Concordant species included members of the following genera: Brevibacterium(1), Microbacterium(1), Staphylococcus(3), Stenotrophomonas(2), Streptococcus(2), Sphingomonas(1), and Pseudomonas(4). PFGE confirmed related strains (one episode each of Sphinogomonas and P. aeruginosa) from the environment and airways were identified in two patients. Culture-independent assessment confirmed that many organisms were not identified using culture-dependent techniques. Conclusions Members of the CF microbiota can be found as constituents of the home environment in individuals with

  15. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals.

  16. Treatment Considerations for HIV-Infected Individuals with Severe Mental Illness

    PubMed Central

    Himelhoch, Seth; Walkup, James; Eisenberg, Marlene M.

    2013-01-01

    There has been a general recognition of a syndemic that includes HIV/AIDS and serve mental illnesses including schizophrenia, major depression, bipolar disorder, post-traumatic stress disorder, and others. The pathophysiology and direction of effects between severe mental illness and HIV infection is less clear however, and relatively little work has been done on prevention and treatment for people with these complex, co-occurring conditions. Here we present the most recent work that has been published on HIV and mental illness. Further, we describe the need for better treatments for “triply diagnosed persons”; those with HIV, mental illness, and substance abuse and dependence. Finally, we describe the potential drug-drug interactions between psychotropic medications and anti-retrovirals, and the need for better treatment guidelines in this area. We describe one example of an individually tailored intervention for persons with serious mental illness and HIV (PATH+) that shows that integrated community-based treatments using advanced practice nurses (APNs) as health navigators can be successful in improving health-related quality of life and reducing the burden of disease in these persons. PMID:24158425

  17. Influence of Antiretroviral Drugs on the Pharmacokinetics of Prednisolone in HIV-Infected Individuals

    PubMed Central

    Busse, Kristin H.; Formentini, Elizabeth; Alfaro, Raul M.; Kovacs, Joseph A.; Penzak, Scott R.

    2009-01-01

    Background Corticosteroids are cytochrome P450 3A4 substrates, which have been associated with toxicities in patients receiving cytochrome P450 3A4 inhibitors such as human immunodeficiency virus protease inhibitors. In a study in healthy volunteers, ritonavir significantly increased prednisolone exposure. Methods We investigated the influence of antiretroviral (ARV) medications on prednisolone pharmacokinetics in 3 groups of 10 human immunodeficiency virus–infected subjects. One group received lopinavir/ritonavir, and another efavirenz, as part of their ARV regimen; a third group did not receive ARV medications. Each subject received a single 20-mg prednisone dose followed by serial blood sampling for prednisolone. Prednisolone pharmacokinetics were compared among the groups. Results Area under the concentration–time curve was significantly lower in efavirenz recipients versus subjects receiving lopinavir/ritonavir (geometric mean ratio = 0.60, P = 0.01). Average prednisolone area under the concentration–time curve was higher in subjects taking lopinavir/ritonavir versus subjects not on ARVs; however, this difference was not significant (P > 0.05). Conclusions These data indicate that prednisolone concentrations may fluctuate widely when human immunodeficiency virus–positive individuals established on efavirenz therapy change to lopinavir/ritonavir or vice versa. PMID:18645517

  18. HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals.

    PubMed Central

    Pontesilli, O; Carlesimo, M; Varani, A R; Ferrara, R; Guerra, E C; Bernardi, M L; Ricci, G; Mazzone, A M; D'Offizi, G; Aiuti, F

    1995-01-01

    In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens. PMID:7774051

  19. Individual interferon regulatory factor-3 thiol residues are not critical for its activation following virus infection.

    PubMed

    Zucchini, Nicolas; Williams, Virginie; Grandvaux, Nathalie

    2012-09-01

    The interferon regulatory factor (IRF)-3 transcription factor plays a central role in the capacity of the host to mount an efficient innate antiviral immune defense, mainly through the regulation of type I Interferon genes. A tight regulation of IRF-3 is crucial for an adapted intensity and duration of the response. Redox-dependent processes are now well known to regulate signaling cascades. Recent reports have revealed that signaling molecules upstream of IRF-3, including the mitochondrial antiviral-signalling protein (MAVS) and the TNF receptor associated factors (TRAFs) adaptors, are sensitive to redox regulation. In the present study, we assessed whether redox regulation of thiol residues contained in IRF-3, which are priviledged redox sensors, play a role in its regulation following Sendai virus infection, using a combination of mutation of Cysteine (Cys) residues into Alanine and thiols alkylation using N-ethyl maleimide. Alkylation of IRF-3 on Cys289 appears to destabilize IRF-3 dimer in vitro. However, a detailed analysis of IRF-3 phosphorylation, dimerization, nuclear accumulation, and induction of target gene promoter in vivo led us to conclude that IRF-3 specific, individual Cys residues redox status does not play an essential role in its activation in vivo.

  20. Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa

    PubMed Central

    Azevedo, Tiago Castro Lopes; Zwahlen, Marcel; Rauch, Andri; Egger, Matthias; Wandeler, Gilles

    2016-01-01

    Introduction Although hepatitis C virus (HCV) screening is recommended for all HIV-infected patients initiating antiretroviral therapy, data on epidemiologic characteristics of HCV infection in resource-limited settings are scarce. Methods We searched PubMed and EMBASE for studies assessing the prevalence of HCV infection among HIV-infected individuals in Africa and extracted data on laboratory methods used. Prevalence estimates from individual studies were combined for each country using random-effects meta-analysis. The importance of study design, population and setting as well as type of test (anti-HCV antibody tests and polymerase chain reactions) was examined with meta-regression. Results Three randomized controlled trials, 28 cohort studies and 121 cross-sectional analyses with 108,180 HIV-infected individuals from 35 countries were included. The majority of data came from outpatient populations (55%), followed by blood donors (15%) and pregnant women (14%). Based on estimates from 159 study populations, anti-HCV positivity prevalence ranged between 3.3% (95% confidence interval (CI) 1.8–4.7) in Southern Africa and 42.3% (95% CI 4.1–80.5) in North Africa. Study design, type of setting and age distribution did not influence this prevalence significantly. The prevalence of replicating HCV infection, estimated from data of 29 cohorts, was 2.0% (95% CI 1.5–2.6). Ten studies from nine countries reported the HCV genotype of 74 samples, 53% were genotype 1, 24% genotype 2, 14% genotype 4 and 9% genotypes 3, 5 or 6. Conclusions The prevalence of anti-HCV antibodies is high in HIV-infected patients in Africa, but replicating HCV infection is rare and varies widely across countries. PMID:27293220

  1. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials

    PubMed Central

    Palumbo, Antonio; Waage, Anders; Hulin, Cyrille; Beksac, Meral; Zweegman, Sonja; Gay, Francesca; Gimsing, Peter; Leleu, Xavier; Wijermans, Pierre; Sucak, Gülsan; Pezzatti, Sara; Juliusson, Gunnar; Pégourié, Brigitte; Schaafsma, Martijn; Galli, Monica; Turesson, Ingemar; Kolb, Brigitte; van der Holt, Bronno; Baldi, Ileana; Rolke, Jürgen; Ciccone, Giovannino; Wetterwald, Marc; Lokhorst, Henk; Boccadoro, Mario; Rodon, Philippe; Sonneveld, Pieter

    2013-01-01

    Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival. PMID:22875621

  2. Current Practices of Screening for Incident Hepatitis C Virus (HCV) Infection Among HIV-Infected, HCV-Uninfected Individuals in Primary Care

    PubMed Central

    Freiman, J. Morgan; Huang, Wei; White, Laura F.; Geng, Elvin H.; Hurt, Christopher B.; Taylor, Lynn E.; Overton, E. Turner; Cachay, Edward R.; Kitahata, Mari M.; Moore, Richard D.; Rodriguez, Benigno; Mayer, Kenneth H.; Linas, Benjamin P.

    2014-01-01

    Background. Human immunodeficiency virus (HIV)-infected, hepatitis C virus (HCV)-uninfected patients are at risk for incident HCV infection, but little is known about screening practices for incident HCV among HIV-infected individuals in HIV primary care clinics. Methods. We used data from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) to investigate historical trends in screening for incident HCV infection among HIV-infected patients who were HCV-uninfected at enrollment in care. We used descriptive measures and Poisson regression to identify factors associated with screening for HCV infection (using HCV antibody or RNA), performed temporal analyses to assess changes in screening over time, and investigated the frequency with which elevated alanine aminotransferase (ALT) levels were followed by diagnostic HCV testing. Results. Among 17 090 patients registered at CNICS sites between 2000 and 2011, 14 534 (85%) received HCV antibody screening within 3 months of enrolling in care, and 9077 met all of the inclusion criteria. Only 55.6% ever received additional HCV screening. HCV screening increased over time, but not uniformly at all sites. Only 26.7% of first-time ALT elevations to >100 IU/L were followed up within 12 months by HCV antibody or RNA testing. Conclusions. Although most HIV-infected patients were screened for prevalent HCV infection at enrollment in care, only half who were HCV uninfected were screened again. Screening varied between sites, even when controlling for demographics and risk behaviors. Patients with new ALT elevations to >100 IU/L were seldom assessed for incident HCV infection. Guidelines are needed to help HIV providers know whom to screen, how frequently to screen, and which screening test to use. PMID:25186591

  3. Light scattering and morphology of the lymphocyte as applied to flow cytometry for distinguishing healthy and infected individuals.

    PubMed

    Ruban, Gennady I; Berdnik, Vladimir V; Marinitch, Dmitry V; Goncharova, Natalia V; Loiko, Valery A

    2010-01-01

    A simple optical model of single lymphocytes with smooth and nonsmooth surfaces has been developed for healthy and infected individuals. The model can be used for rapid (in the real-time scale) solution of the inverse light-scattering problem on the basis of optical data measured by label-free flow cytometry. Light scattering patterns have been calculated for the model developed. It has been shown that the smooth and nonsmooth cells can be resolved using the intensities of the sideward- and backward-scattered light. We have found by calculations and validated by the flow cytometer experiments that intensity distributions for the cells of lymphocyte populations can be used as a preliminary signatures of some virus infections. Potential biomedical applications of the findings for label-free flow cytometry detection of individuals infected with viruses of hepatitis B or C and some others viruses are presented. PMID:21054124

  4. High Genotypic Discordance of Concurrent Mycobacterium tuberculosis Isolates from Sputum and Blood of HIV-Infected Individuals

    PubMed Central

    Ssengooba, Willy; Cobelens, Frank G.; Nakiyingi, Lydia; Mboowa, Gerald; Armstrong, Derek T.; Manabe, Yukari C.; Joloba, Moses L.; de Jong, Bouke C.

    2015-01-01

    Background Among HIV-infected individuals with CD4 less than 200 cells/mm3, tuberculosis often has an atypical presentation, is more likely to be disseminated and is diagnostically challenging. We sought to understand the genotypic discordance of concurrent sputum and blood M. tuberculosis (MTB) isolates from HIV-infected individuals. Methods From a prospective diagnostic accuracy study with 182 HIV-infected culture-positive TB adults, isolates were obtained from 51 of 66 participants who were MTB culture-positive by both sputum and blood. Isolates were subjected to susceptibility testing to 1st line drugs, spoligotyping and 24 locus- MIRU-VNTR. Results The median age of the participants was 31 (IQR; 27–38) years and 51% were male. The median CD4 count was 29 (IQR; 10–84) cells/mm3 with 20% taking ART; 8.0% were previously treated for TB, and 63% were AFB smear-negative. The isolates belonged to two of the main global MTB-lineages; East-African-Indian (L3) 17 (16.7%) and Euro-American (L4) 85 (83.3%). We identified 26 (51.0%) participants with discordant MTB-genotypes between sputum and blood, including two patients with evidence of mixed infection in either compartment. Having discordant MTB-genotypes was not predicted by the MTB-lineage in either blood or sputum, CD4 cell count, or any other clinical characteristic. Conclusions There is a high genotypic discordance among M. tuberculosis concurrently isolated from sputum and blood of HIV-infected individuals. These findings suggest that infection with more than one strain of M. tuberculosis occurs in at least half of patients with advanced HIV infection. PMID:26176604

  5. Analysis of HLA association among North Indian HIV-positive individuals co-infected with Mycobacterium tuberculosis

    PubMed Central

    Saikia, Biman; Wanchu, Ajay; Mahakur, Sobhana; Bind, Mahendra; Sarkar, Krishnakali; Minz, Ranjana W

    2015-01-01

    Background: Genetic variation in HLA genes influence the immune response and may thus contribute to differential development of tuberculosis (TB) in HIV-infected individuals. The study was designed to determine whether HLA polymorphisms influence the development of Mycobacterium tuberculosis infection in HIV-infected individuals. Materials and Methods: Fifty HIV-positive individuals without TB (HIV+TB−), 50 HIV patients co-infected with TB (HIV+TB+) and 50 control subjects (HIV-TB-) were analyzed for HLA Class I and II polymorphisms. Results: In HLA Class II, frequency of occurrence of DRB1*13 (OR 3.165, CI 1.176–8.518, P value 0.019), DRB5 (OR 2.253, CI 1.011–5.019, P value 0.045) and DQB1*06 (OR 2.705, CI 1.197–6.113, P value 0.016) were increased in HIV+TB+compared to HIV+TB−. HLA DQB1*02 (OR 0.436, CI 0.185–1.029, P value 0.05) on the other hand conferred a protective role. In HLA Class I, frequency of B*15 (OR 2.705, CI 1.040–7.036, P value 0.038) was increased, whereas B*51 (OR 0.148, CI 0.031–0.706, P value 0.007) was decreased in HIV+TB+group compared to HIV+TB−. These differences however were not significant when compared with healthy controls. Conclusion: HLA polymorphisms independently did not account for the susceptibility to either of the disease mostly, although they seem to play a role once the infection(s) has established in a particular individual. Further studies are needed on a larger sample size to confirm these observations. PMID:26628757

  6. Individuals infected with JC polyomavirus do not present detectable JC virus DNA in oropharyngeal fluids.

    PubMed

    Matos, Ana; Duque, Vitor; Luxo, Cristina; Meliço-Silvestre, António; Major, Eugene O

    2012-04-01

    JC virus (JCV) is ubiquitous in the human population. Primary infection normally occurs during childhood and is followed by a lifelong persistent infection. The main mode of transmission remains unknown. Several authors have hypothesized that JCV transmission occurs through the respiratory route, and that respiratory secretions could represent a possible source of viral particles. The present study intended to evaluate oropharyngeal fluids from patients infected with JCV, in order to ascertain if respiratory secretions could indeed constitute a source of exposure to this polyomavirus. Oropharyngeal washing samples from 25 patients co-infected with JCV and human immunodeficiency virus type 1 were evaluated for the presence of JCV DNA. Regardless of the titre of antibodies or the presence of viral urinary excretion, JCV genome was not detected in oropharyngeal samples collected from any of the patients infected with JCV included in this study, which may suggest that oropharyngeal fluids are an unlikely source for JCV infection.

  7. Reactive arthritis responding to antiretroviral therapy in an HIV-1-infected individual.

    PubMed

    Scott, C; Brand, A; Natha, M

    2012-05-01

    Reactive arthritis (ReA) is an autoimmune seronegative spondyloarthropathy that occurs in response to a urogenital or enteric infection. Several studies have reported a link between ReA and HIV infection. We report a case of an HIV-1-infected patient diagnosed with a disabling ReA who failed to respond to conventional therapy but whose symptoms resolved rapidly after starting antiretroviral therapy (ART). Clinicians may not be cognizant to this phenomenon and so this case report serves to remind clinicians that initiation of antiretroviral therapy should be considered in HIV-infected patients with ReA who are refractory to standard therapy.

  8. KLRG1 negatively regulates natural killer cell functions through the Akt pathway in individuals with chronic hepatitis C virus infection.

    PubMed

    Wang, Jia M; Cheng, Yong Q; Shi, Lei; Ying, Ruo S; Wu, Xiao Y; Li, Guang Y; Moorman, Jonathan P; Yao, Zhi Q

    2013-11-01

    In this study, we demonstrate that killer cell lectin-like receptor subfamily G member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is highly expressed on CD56(+) NK cells, which are significantly reduced in their numbers and functions in the peripheral blood of patients with chronic hepatitis C virus (HCV) infection compared to subjects without infection. KLRG1 expression is also upregulated on healthy NK cells exposed to Huh-7 hepatocytes infected with HCV in vitro. Importantly, the expression levels of KLRG1 are inversely associated with the capacity of NK cells to proliferate and to produce gamma interferon (IFN-γ) but positively associated with apoptosis of NK cells in response to inflammatory cytokine stimulation. KLRG1(+) NK cells, including CD56(bright) and CD56(dim) subsets, exhibit impaired cell activation and IFN-γ production but increased apoptosis compared to KLRG1(-) NK cells, particularly in HCV-infected individuals. Importantly, blockade of KLRG1 signaling significantly recovered the impaired IFN-γ production by NK cells from HCV-infected subjects. Blockade of KLRG1 also enhanced the impaired phosphorylation of Akt (Ser473) in NK cells from HCV-infected subjects. Taken together, these results indicate that KLRG1 negatively regulates NK cell numbers and functions via the Akt pathway, thus providing a novel marker and therapeutic target for HCV infection.

  9. Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy

    PubMed Central

    Zhang, Linqi; Lewin, Sharon R.; Markowitz, Martin; Lin, Hsi-Hsun; Skulsky, Eva; Karanicolas, Rose; He, Yuxian; Jin, Xia; Tuttleton, Sarah; Vesanen, Mika; Spiegel, Hans; Kost, Rhonda; van Lunzen, Jan; Stellbrink, Hans-Juergen; Wolinsky, Steven; Borkowsky, William; Palumbo, Paul; Kostrikis, Leondios G.; Ho, David D.

    1999-01-01

    The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 10–15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, α1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in α1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as α1 circle numbers are normal in a substantial subset of HIV-1–infected individuals. PMID:10477556

  10. Risk Factors for Oral Human Papillomavirus Infection in Healthy Individuals: A Systematic Review and Meta-Analysis

    PubMed Central

    Shigeishi, Hideo; Sugiyama, Masaru

    2016-01-01

    Background Oral human papillomavirus (HPV) infection is associated with oral cancer development. However, few epidemiologic investigations have focused on oral HPV prevalence in healthy individuals. The objective of this study was to provide updated information regarding oral HPV prevalence in patients without oral cancer worldwide. Methods We systematically reviewed 29 studies reporting the prevalence of oral HPV infection that included 22,756 subjects (10,124 males, 12,623 females, and nine unknown gender; age range 2 - 89 years) and were published from January 2012 to June 2015. Results The prevalence of overall HPV, low-risk type HPV, high-risk type HPV, and HPV16 in the reported cases was 5.5%, 2.2%, 2.7%, and 1.0%, respectively. The prevalence of overall HPV was considerably higher in males who had sex with males (12.2%) as compared to heterosexual males (4.7%) and females (2.9%). A meta-analysis was performed to elucidate significant risk factors for oral HPV infection, which revealed a significant statistical association for oral sex and smoking with oral HPV infection (odds ratio (OR): 1.90, 95% confidence interval (CI): 1.51 - 2.39, P < 0.0001; OR: 2.13, 95% CI: 1.32 - 3.43, P = 0.002). Conclusions Our findings suggest that sexual behavior and smoking are importantly related to oral HPV infection in healthy individuals.

  11. Risk Factors for Oral Human Papillomavirus Infection in Healthy Individuals: A Systematic Review and Meta-Analysis

    PubMed Central

    Shigeishi, Hideo; Sugiyama, Masaru

    2016-01-01

    Background Oral human papillomavirus (HPV) infection is associated with oral cancer development. However, few epidemiologic investigations have focused on oral HPV prevalence in healthy individuals. The objective of this study was to provide updated information regarding oral HPV prevalence in patients without oral cancer worldwide. Methods We systematically reviewed 29 studies reporting the prevalence of oral HPV infection that included 22,756 subjects (10,124 males, 12,623 females, and nine unknown gender; age range 2 - 89 years) and were published from January 2012 to June 2015. Results The prevalence of overall HPV, low-risk type HPV, high-risk type HPV, and HPV16 in the reported cases was 5.5%, 2.2%, 2.7%, and 1.0%, respectively. The prevalence of overall HPV was considerably higher in males who had sex with males (12.2%) as compared to heterosexual males (4.7%) and females (2.9%). A meta-analysis was performed to elucidate significant risk factors for oral HPV infection, which revealed a significant statistical association for oral sex and smoking with oral HPV infection (odds ratio (OR): 1.90, 95% confidence interval (CI): 1.51 - 2.39, P < 0.0001; OR: 2.13, 95% CI: 1.32 - 3.43, P = 0.002). Conclusions Our findings suggest that sexual behavior and smoking are importantly related to oral HPV infection in healthy individuals. PMID:27635177

  12. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

  13. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART. PMID:26475399

  14. Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.

    PubMed Central

    Franchini, M; Walker, C; Henrard, D R; Suter-Gut, D; Braun, P; Villiger, B; Suter, M

    1995-01-01

    The lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung asymptomatic' patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease. PMID:7586671

  15. Epidemiological studies on guinea-worm in some newly discovered villages of Jhabua District (M.P.) and test of carica papaya leaves of guinea worm infection.

    PubMed

    Sanghvi, P K

    1989-05-01

    Epidemiological survey was carried out for prevalence of guinea worm infection in 12 villages having a total population of 10281 persons in Jhabua district of M.P. The prevalence of 2.85 percent. Infection was more common in males. A paste of leaves of carica papya with opium and common salt applied for 3 days was helpful in relief of symptoms and easy extraction of worm from the body.

  16. Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

    PubMed

    Papuchon, Jennifer; Pinson, Patricia; Guidicelli, Gwenda-Line; Bellecave, Pantxika; Thomas, Réjean; LeBlanc, Roger; Reigadas, Sandrine; Taupin, Jean-Luc; Baril, Jean Guy; Routy, Jean Pierre; Wainberg, Mark; Fleury, Hervé

    2014-01-01

    In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013) showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2) and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

  17. Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria

    PubMed Central

    Royal, Walter; Cherner, Mariana; Burdo, Tricia H.; Umlauf, Anya; Letendre, Scott L.; Jumare, Jibreel; Abimiku, Alash’le; Alabi, Peter; Alkali, Nura; Bwala, Sunday; Okwuasaba, Kanayo; Eyzaguirre, Lindsay M.; Akolo, Christopher; Guo, Ming; Williams, Kenneth C.; Blattner, William A.

    2016-01-01

    The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes. PMID:26829391

  18. Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

    PubMed

    Royal, Walter; Cherner, Mariana; Burdo, Tricia H; Umlauf, Anya; Letendre, Scott L; Jumare, Jibreel; Abimiku, Alash'le; Alabi, Peter; Alkali, Nura; Bwala, Sunday; Okwuasaba, Kanayo; Eyzaguirre, Lindsay M; Akolo, Christopher; Guo, Ming; Williams, Kenneth C; Blattner, William A

    2016-01-01

    The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes. PMID:26829391

  19. Prototheca algaemia: a rare but fatal opportunistic infection among immunocompromised individuals.

    PubMed

    Yeh, Chun-Ting; Li, Ming-Chi; Chuang, Yin-Ching; Hsu, Hui-Jine; Lee, Mei-Feng; Zhang, Chun-Cheng; Ko, Wen-Chien; Tang, Hung-Jen

    2013-01-01

    Infections due to Prototheca spp. are ubiquitous in nature, occurring in both immunocompetent and immunocompromised patients. The study cohort consisted of 14 cases of Prototheca algaemia reported over the past 5 decades and 2 recent cases from study hospitals. Prototheca wickerhamii was the most common species. The overall mortality rate was 62.5%. Prototheca algaemia, a healthcare-associated infection, was observed in immunocompromised patients and was associated with a poor prognosis. PMID:24270142

  20. Anti-Infective Metabolites of a Newly Isolated Bacillus thuringiensis KL1 Associated with Kalmegh (Andrographis paniculata Nees.), a Traditional Medicinal Herb.

    PubMed

    Roy, Sudipta; Yasmin, Sahana; Ghosh, Subhadeep; Bhattacharya, Somesankar; Banerjee, Debdulal

    2016-01-01

    This study was conducted to isolate endophytic bacteria possessing anti-infective property from Kalmegh (Andrographis paniculata Nees.), a well-known medicinal plant. A total of 23 strains were isolated from this plant among which the strain KL1, isolated from surface-sterilized leaf of this medicinal herb, showed broad-spectrum antagonism against an array of Gram-positive and -negative bacterial pathogens. Ethyl acetate extract of KL1-fermented media yielded a greenish amorphous substance retaining anti-infective property. Solvent-extracted crude material was separated by thin-layer chromatography, and the active ingredient was located by autobiogram analysis. The purified anti-infective compound was found as anthracene derivative as analyzed by ultraviolet and Fourier transform infrared spectroscopy. The strain was identified as Bacillus thuringiensis KL1 from cultural, physiochemical, and molecular aspects. The above results indicate the pharmaceutical potential of the candidate isolate.

  1. Anti-Infective Metabolites of a Newly Isolated Bacillus thuringiensis KL1 Associated with Kalmegh (Andrographis paniculata Nees.), a Traditional Medicinal Herb

    PubMed Central

    Roy, Sudipta; Yasmin, Sahana; Ghosh, Subhadeep; Bhattacharya, Somesankar; Banerjee, Debdulal

    2016-01-01

    This study was conducted to isolate endophytic bacteria possessing anti-infective property from Kalmegh (Andrographis paniculata Nees.), a well-known medicinal plant. A total of 23 strains were isolated from this plant among which the strain KL1, isolated from surface-sterilized leaf of this medicinal herb, showed broad-spectrum antagonism against an array of Gram-positive and -negative bacterial pathogens. Ethyl acetate extract of KL1-fermented media yielded a greenish amorphous substance retaining anti-infective property. Solvent-extracted crude material was separated by thin-layer chromatography, and the active ingredient was located by autobiogram analysis. The purified anti-infective compound was found as anthracene derivative as analyzed by ultraviolet and Fourier transform infrared spectroscopy. The strain was identified as Bacillus thuringiensis KL1 from cultural, physiochemical, and molecular aspects. The above results indicate the pharmaceutical potential of the candidate isolate. PMID:26997870

  2. Thymic Function Is Most Severely Impaired in Chronic HIV-1 Infection, but Individuals With Faster Disease Progression During Early HIV-1 Infection Expressed Lower Levels of RTEs.

    PubMed

    He, Sijia; Zhang, Zining; Fu, Yajing; Qin, Chaolong; Li, Sha; Han, Xiaoxu; Xu, Junjie; Liu, Jing; Jiang, Yongjun; Shang, Hong

    2015-12-15

    In HIV disease course, the decline of peripheral CD4 T-cell count correlates with rapid disease progression. The supply of peripheral naive T cells by the thymus requires precursor T-cell proliferation within the thymus. In the setting of HIV-1 infection, when both naive and memory T cells are progressively depleted, the contribution of thymic dysfunction in CD4 depletion needs to be studied. Previous research has shown that thymic function may also be impaired in HIV-1 infection. However, it is inconclusive regarding whether this impairment occurred at the early time or during the chronic phase. In addition, the relationship between thymic dysfunction and disease progression remains unknown. In this study, we examined the thymic function in 65 HIV-infected individuals. Among them, 17 were in acute phase, 15 were in early chronic phase, 15 were in chronic phase with no ART (antiretroviral therapy), and 18 were on ART. We also included 11 uninfected individuals as controls. We measured the peripheral blood levels of T-cell receptor rearrangement excision circles and PTK7 and CD31 expressions for the frequency of circulating recent thymic emigrants. We observed that the 2 indicators of thymic function, sj/β-TREC and PTK7, seemed to be lower in the chronic infection group than those in the acute and early chronic groups. Both indicators returned to the normal level after ART. However, after 1-year follow-up of patients with early HIV-1 infection, rapid progressors (n = 4) had lower PTK7 and CD31 expressions than chronic progressors (n = 6). PMID:26569175

  3. Thymic Function Is Most Severely Impaired in Chronic HIV-1 Infection, but Individuals With Faster Disease Progression During Early HIV-1 Infection Expressed Lower Levels of RTEs.

    PubMed

    He, Sijia; Zhang, Zining; Fu, Yajing; Qin, Chaolong; Li, Sha; Han, Xiaoxu; Xu, Junjie; Liu, Jing; Jiang, Yongjun; Shang, Hong

    2015-12-15

    In HIV disease course, the decline of peripheral CD4 T-cell count correlates with rapid disease progression. The supply of peripheral naive T cells by the thymus requires precursor T-cell proliferation within the thymus. In the setting of HIV-1 infection, when both naive and memory T cells are progressively depleted, the contribution of thymic dysfunction in CD4 depletion needs to be studied. Previous research has shown that thymic function may also be impaired in HIV-1 infection. However, it is inconclusive regarding whether this impairment occurred at the early time or during the chronic phase. In addition, the relationship between thymic dysfunction and disease progression remains unknown. In this study, we examined the thymic function in 65 HIV-infected individuals. Among them, 17 were in acute phase, 15 were in early chronic phase, 15 were in chronic phase with no ART (antiretroviral therapy), and 18 were on ART. We also included 11 uninfected individuals as controls. We measured the peripheral blood levels of T-cell receptor rearrangement excision circles and PTK7 and CD31 expressions for the frequency of circulating recent thymic emigrants. We observed that the 2 indicators of thymic function, sj/β-TREC and PTK7, seemed to be lower in the chronic infection group than those in the acute and early chronic groups. Both indicators returned to the normal level after ART. However, after 1-year follow-up of patients with early HIV-1 infection, rapid progressors (n = 4) had lower PTK7 and CD31 expressions than chronic progressors (n = 6).

  4. [HPV infection might play a role in the development of non-melanoma skin cancer in immunocompetent individuals].

    PubMed

    Birch-Johansen, Fatima; Norrild, Bodil; Olesen, Anne Braae; Jensen, Allan; Kjær, Susanne Krüger

    2012-02-13

    Human papillomavirus (HPV) is necessary for the development of cervical cancer and is also involved in vulvar, anus, penis and head and neck cancer. Little is known about the role of HPV infection in non-melanoma skin cancer (NMSC). Through a systematic review of the literature, we studied the HPV prevalence in immunocompetent individuals in relation to NMSC. We found that HPV, including multiple HPV types, tended to be more prevalent in NMSC, especially in squamous cell carcinoma (SCC) compared to basal cell carcinoma and healthy skin, indicating a potential link between HPV and SCC in immunocompetent individuals.

  5. Protocol for a randomised trial on the effect of group education on skin-protective behaviour versus treatment as usual among individuals with newly notified occupational hand eczema – the Prevention of Hand Eczema (PREVEX) Trial

    PubMed Central

    2013-01-01

    Background The incidence of occupational hand eczema is approximately 0.32 per 1,000 person years. The burden of the disease is high, as almost 60% has eczema-related sick leave during the first year after notification, and 15% are excluded from the workforce 12 years after disease onset. New treatments and prevention strategies are needed. Methods/Design Trial design: The PREVEX trial is a randomised, parallel-group, superiority trial. Participants: All individuals from the Capital Region of Denmark and Region Zealand with a suspected occupational skin disorder notified to the National Board of Industrial Injuries between June 2012 and December 2013 are invited to participate in the trial. Inclusion criteria are: self-reported hand eczema and informed consent. Exclusion criteria are: age <18 years or >65 years; permanent exclusion from the workforce; inability to understand the Danish language; any serious medical condition; and lack of written informed consent. We plan to randomise 742 participants. Interventions: The experimental intervention is an educational course in skin-protective behaviour and written information about skin care related to the participants' specific occupation. Also, a telephone hotline is available and a subgroup will be offered a work-place visit. The experimental and the control group have access to usual care and treatment. All participants are contacted every eighth week with questions regarding number of days with sick leave or other absence from work. 12 months after randomisation follow-up is completed. Objective: To assesses the effect of an educational course versus treatment as usual in participants with newly notified occupational hand eczema. Randomisation: Participants are centrally randomised according to a computer-generated allocation sequence with a varying block size concealed to investigators. Blinding: It is not possible to blind the participants and investigators, however, data obtained from registers, data entry

  6. Individual Monitoring of Immune Response in Atlantic Salmon Salmo salar following Experimental Infection with Infectious Salmon Anaemia Virus (ISAV).

    PubMed

    Collet, Bertrand; Urquhart, Katy; Monte, Milena; Collins, Catherine; Garcia Perez, Sandro; Secombes, Chris J; Hall, Malcolm

    2015-01-01

    Monitoring the immune response in fish over the progression of a disease is traditionally carried out by experimental infection whereby animals are killed at regular intervals and samples taken. We describe here a novel approach to infectiology for salmonid fish where blood samples are collected repeatedly in a small group of PIT-tagged animals. This approach contributes to the reduction of animals used in research and to improved data quality. Two groups of 12 PIT-tagged Atlantic salmon (Salmo salar) were i.p infected with Infectious Salmon Anaemia Virus (ISAV) or culture medium and placed in 1 m3 tanks. Blood samples were collected at 0, 4, 8, 12, 16, 21 and 25 days post infection. The viral load, immune and stress response were determined in individual fish by real-time quantitative PCR (QPCR) on the blood cells, as well as the haematocrit used as an indicator of haemolysis, a clinical consequence of ISAV infection. "In-tank" anaesthesia was used in order to reduce the stress related to chase and netting prior to sampling. The data were analysed using a statistical approach which is novel with respect to its use in fish immunology. The repeated blood collection procedure did not induce stress response as measured by HSP70 and HSP90 gene expression in the un-infected animals. A strong increase in viraemia as well as a significant induction of Mx and γIP gene expression were observed in the infected group. Interleukin 10 was found induced at the later stage of the infection whereas no induction of CD8 or γ IFN could be detected. These results and the advantages of this approach are discussed. PMID:26397117

  7. Individual Monitoring of Immune Response in Atlantic Salmon Salmo salar following Experimental Infection with Infectious Salmon Anaemia Virus (ISAV).

    PubMed

    Collet, Bertrand; Urquhart, Katy; Monte, Milena; Collins, Catherine; Garcia Perez, Sandro; Secombes, Chris J; Hall, Malcolm

    2015-01-01

    Monitoring the immune response in fish over the progression of a disease is traditionally carried out by experimental infection whereby animals are killed at regular intervals and samples taken. We describe here a novel approach to infectiology for salmonid fish where blood samples are collected repeatedly in a small group of PIT-tagged animals. This approach contributes to the reduction of animals used in research and to improved data quality. Two groups of 12 PIT-tagged Atlantic salmon (Salmo salar) were i.p infected with Infectious Salmon Anaemia Virus (ISAV) or culture medium and placed in 1 m3 tanks. Blood samples were collected at 0, 4, 8, 12, 16, 21 and 25 days post infection. The viral load, immune and stress response were determined in individual fish by real-time quantitative PCR (QPCR) on the blood cells, as well as the haematocrit used as an indicator of haemolysis, a clinical consequence of ISAV infection. "In-tank" anaesthesia was used in order to reduce the stress related to chase and netting prior to sampling. The data were analysed using a statistical approach which is novel with respect to its use in fish immunology. The repeated blood collection procedure did not induce stress response as measured by HSP70 and HSP90 gene expression in the un-infected animals. A strong increase in viraemia as well as a significant induction of Mx and γIP gene expression were observed in the infected group. Interleukin 10 was found induced at the later stage of the infection whereas no induction of CD8 or γ IFN could be detected. These results and the advantages of this approach are discussed.

  8. Individual Monitoring of Immune Response in Atlantic Salmon Salmo salar following Experimental Infection with Infectious Salmon Anaemia Virus (ISAV)

    PubMed Central

    Collet, Bertrand; Urquhart, Katy; Monte, Milena; Collins, Catherine; Garcia Perez, Sandro; Secombes, Chris J.; Hall, Malcolm

    2015-01-01

    Monitoring the immune response in fish over the progression of a disease is traditionally carried out by experimental infection whereby animals are killed at regular intervals and samples taken. We describe here a novel approach to infectiology for salmonid fish where blood samples are collected repeatedly in a small group of PIT-tagged animals. This approach contributes to the reduction of animals used in research and to improved data quality. Two groups of 12 PIT-tagged Atlantic salmon (Salmo salar) were i.p infected with Infectious Salmon Anaemia Virus (ISAV) or culture medium and placed in 1 m3 tanks. Blood samples were collected at 0, 4, 8, 12, 16, 21 and 25 days post infection. The viral load, immune and stress response were determined in individual fish by real-time quantitative PCR (QPCR) on the blood cells, as well as the haematocrit used as an indicator of haemolysis, a clinical consequence of ISAV infection. “In-tank” anaesthesia was used in order to reduce the stress related to chase and netting prior to sampling. The data were analysed using a statistical approach which is novel with respect to its use in fish immunology. The repeated blood collection procedure did not induce stress response as measured by HSP70 and HSP90 gene expression in the un-infected animals. A strong increase in viraemia as well as a significant induction of Mx and γIP gene expression were observed in the infected group. Interleukin 10 was found induced at the later stage of the infection whereas no induction of CD8 or γ IFN could be detected. These results and the advantages of this approach are discussed. PMID:26397117

  9. Incidence of HIV Type 1 Infection, Antiretroviral Drug Resistance, and Molecular Characterization in Newly Diagnosed Individuals in Argentina: A Global Fund Project

    PubMed Central

    Gómez-Carrillo, M.; Vignoles, M.; Rubio, A.E.; dos Ramos Farias, M.S.; Vila, M.; Rossi, D.; Ralón, G.; Marone, R.; Reynaga, E.; Sosa, J.; Torres, O.; Maestri, M.; Ávila, M.M.; Salomón, H.

    2011-01-01

    Abstract An HIV incidence estimation was performed among men who have sex with men (MSM), drug users (DUs), sex workers (SWs), and pregnant women (PW) from Argentina. Volunteers older than 18 years old without a previous HIV-positive diagnosis were included. HIV-positive samples were analyzed by the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS) to estimate incidence. By partial RT-PCR and sequencing of the HIV pol gene, an HIV subtype and resistance profile were determined. A total of 12,192 volunteers were recruited from October 2006 to September 2008. A higher HIV prevalence was detected among trans SWs (33.9%, 38/112), male SWs (10.8%, 12/111), and MSM 10.4% (161/1549). HIV incidence estimates by STARHS was also higher on trans SWs (11.31 per 100 person-years), male SWs (6.06 per 100 person-years), and MSM (6.36 per 100 person-years). Antiretroviral primary resistant mutations were detected in 8.4% of the study group, with a higher frequency in female DUs (33.3%). Phylogenetic analysis showed that 124 (57.9%) samples were subtype B, 84 (39.3%) intersubtype BF recombinants, 5 (2.3%) subtype C, and 1 (0.5%) subtype F in the pol region. Subtype B was most commonly found in MSM and male SWs whereas the intersubtype BF recombinant was more prevalent in female DUs, female SWs, and PW. Given the high HIV prevalence and incidence found in most of these groups, monitoring the continuing spread of the HIV epidemic is essential for determining public health priorities, assessing the impact of interventions, and estimating current and future health care needs. PMID:20860532

  10. Comparison of a newly developed enzyme-linked immunosorbent assay with complement fixation and neutralisation tests for serology of bovine respiratory syncytial virus infections.

    PubMed

    Westenbrink, F; Brinkhof, J M; Straver, P J; Quak, J; De Leeuw, P W

    1985-05-01

    An indirect double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed for the detection and titration of serum antibodies to bovine respiratory syncytial virus (BRSV). The ELISA was compared with a complement fixation (CF) test and a test for virus neutralising antibody in serum (virus neutralisation [VN] test). Testing sera collected in dairy herds revealed the closest correlation between the results of the ELISA and the CF test with respect to BRSV antibody titres. The VN test detected BRSV antibodies in a higher percentage of acute phase sera compared to the other two tests in field samples and in early bleedings of experimentally infected calves. However, the VN test was less effective in making a diagnosis of BRSV infections on the basis of a significant titre increase in paired sera. For this purpose the ELISA was found to be the most sensitive test.

  11. The Confidentiality Rights of HIV-Infected Individuals within a School.

    ERIC Educational Resources Information Center

    Adams-Nepote, Sue

    The right of Human Immunodeficiency Virus (HIV) infected students and staff members to continue in the public school system without disruption has been legally established. However, the question now lies in the legal implications of confidentiality. School districts must implement policies and procedures to ensure medical record confidentiality of…

  12. A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette–Guérin-vaccinated Individuals

    PubMed Central

    Peña, Delfina; Rovetta, Ana I.; Hernández Del Pino, Rodrigo E.; Amiano, Nicolás O.; Pasquinelli, Virginia; Pellegrini, Joaquín M.; Tateosian, Nancy L.; Rolandelli, Agustín; Gutierrez, Marisa; Musella, Rosa M.; Palmero, Domingo J.; Gherardi, María M.; Iovanna, Juan; Chuluyan, H. Eduardo; García, Verónica E.

    2015-01-01

    IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette–Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people. PMID:26425695

  13. The Concept of Ecthyma Gangrenosum Illustrated by a Fusarium oxysporum Infection in an Immunocompetent Individual.

    PubMed

    Jiang, Yanping; Al-Hatmi, Abdullah M S; Xiang, Yining; Cao, Yu; van den Ende, Albert H G Gerrits; Curfs-Breuker, Ilse; Meis, Jacques F; Lu, Hongguang; de Hoog, G Sybren

    2016-10-01

    Ecthyma gangrenosum (EG) involves necrotic cutaneous lesions caused by bacteria, mainly Pseudomonas aeruginosa, and is usually seen in immunocompromised patients with septicemia. However, clinically similar infections have been published with fungi as etiologic agents. We present a case of an EG-like lesion due to Fusarium oxysporum confirmed by clinical diagnosis, culture and molecular identification and discuss the definition of EG. PMID:27324372

  14. The use of pharmacogenetics in clinical practice for the treatment of individuals with HIV infection in Thailand

    PubMed Central

    Bushyakanist, Asalaysa; Puangpetch, Apichaya; Sukasem, Chonlaphat; Kiertiburanakul, Sasisopin

    2015-01-01

    Objectives The objectives of this study were to describe the use of pharmacogenetics in clinical practice for the treatment of individuals with human immunodeficiency virus (HIV) infection and to determine the treatment outcomes of HIV-infected patients in whom pharmacogenetic testing was performed. Methods This study involves a retrospective collection of medical records of HIV-infected patients who attended Ramathibodi Hospital during January 2011 to November 2014 and in whom pharmacogenetic testing was performed. We reviewed patients’ characteristics, reasons for pharmacogenomic testing, results of human leukocyte antigen-B* (HLA-B*) 5701, HLA-B*3505, HLA-B*4001, CYP2B6, and antiretroviral drug (ARV) levels, treatment planning after the physicians were informed the results, and outcome after changing the treatment. Results A total of 103 HIV-infected patients with a median age of 46 (range, 20–85) years were enrolled, and 68.9% of them were male. The reasons for pharmacogenomic testing were having adverse drug reactions besides rash (37.9%), screening before prescribing ARV (36.9%), choice of next ARV (19.4%), and confirmation of the cause of skin rash (5.8%). After the physicians knew the results, they adjusted the treatment plan including changing the regimens, changing the ARV dose for avoiding toxicity, and stopping ARV. Among 45 patients, side effects, such as dizziness from efavirenz or rash from abacavir, were improved in 96.4%. Among 27 patients, abnormal laboratory results, such as renal insufficiency from tenofovir or anemia from zidovudine, were improved and some returned to normal in 59.3%. HIV RNA was undetectable after treatment adjustment in 94.9%. Conclusion The benefits of pharmacogenetic testing are either guiding the initial drug regimen or individualizing regimen, increasing efficacy, and simultaneously avoiding adverse drug reactions. Use of pharmacogenetic testing in HIV-infected Thai adults should be considered. PMID:26604812

  15. Haemostatic trends in HIV-infected individuals in Yaoundé, Cameroon: a pilot study

    PubMed Central

    Tene, Larissa; Tagny, Claude T.; Mintya-Ndoumba, Annick; Fossi, Vincent N.; Mbanya, Dora

    2016-01-01

    Bleeding disorders are haematological manifestations that are frequently observed during HIV infection. This study intends to describe the haemostatic trends in HIV-infected patients in Cameroon. This cross-sectional descriptive study was carried out at the haematology unit of the Yaoundé University Teaching Hospital from March to June 2012. It included consenting HIV-positive patients, aged 18 years and above, naive to antiretroviral treatment or not. The coagulation profile was measured with Stago reagents (Stago Diagnostics, Asnières sur Seine, France) using a chronometric technique on a semi-automate (Stago Diagnostics). Platelets count was estimated on a human count automate (Human diagnostic, Wiesbaden, Germany) by flow cytometry. A total of 139 HIV-infected patients were included in this study, out of which 106 were females (76.3%) against 33 (23.7%) males, giving a sex ratio of 0.3 (M/F). Mean age was 38.85 years (range 22–73 years) and median CD4 count was 353 cells/μl (Interquartile range 200–500 cells/μl). Hyperfibrinogenaemia was the most frequent bleeding disorder in the studied population [40 of 139 (28.78%)], followed by low prothrombin time (PT) [22 of 139 (15.83%)], thrombocytopenia [19 of 139 (13.67%)], hypofibrinogenaemia [18 of 139 (12.95)], prolonged activated partial thromboplastin time (7.91) and by thrombocytosis which was less frequent [6 of 139 (4.32%)]. Out of the six haemostatic disorders, only low PT was significantly associated with CD4 count (P=0.02). This study showed that bleeding disorders are very frequent in the HIV-infected patients studied. Low PT was significantly associated with CD4 count, hence it may be recommended to systematic screen for bleeding disorders in severe immune-depressed (CD4 ≤ 200) HIV-infected patients. PMID:24469390

  16. Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus).

    PubMed

    Atkins, Lisa; Zong, Jian-Chao; Tan, Jie; Mejia, Alicia; Heaggans, Sarah Y; Nofs, Sally A; Stanton, Jeffrey J; Flanagan, Joseph P; Howard, Lauren; Latimer, Erin; Stevens, Martina R; Hoffman, Daryl S; Hayward, Gary S; Ling, Paul D

    2013-03-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause acute hemorrhagic disease with high mortality rates in Asian elephants (Elephas maximus). Recently, a new EEHV type known as EEHV5 has been described, but its prevalence and clinical significance remain unknown. In this report, an outbreak of EEHV5 infection in a herd of captive Asian elephants in a zoo was characterized. In February 2011, a 42-yr-old wild-born female Asian elephant presented with bilaterally swollen temporal glands, oral mucosal hyperemia, vesicles on the tongue, and generalized lethargy. The elephant had a leukopenia and thrombocytopenia. She was treated with flunixin meglumine, famciclovir, and fluids. Clinical signs of illness resolved gradually over 2 wk, and the white blood cell count and platelets rebounded to higher-than-normal values. EEHV5 viremia was detectable starting 1 wk before presentation and peaked at the onset of clinical illness. EEHV5 shedding in trunk secretions peaked after viremia resolved and continued for more than 2 mo. EEHV5 trunk shedding from a female herd mate without any detectable viremia was detected prior to onset of clinical disease in the 42-yr-old elephant, indicating reactivation rather than primary infection in this elephant. Subsequent EEHV5 viremia and trunk shedding was documented in the other five elephants in the herd, who remained asymptomatic, except for 1 day of temporal gland swelling in an otherwise-healthy 1-yr-old calf. Unexpectedly, the two elephants most recently introduced into the herd 40 mo previously shed a distinctive EEHV5 strain from that seen in the other five elephants. This is the first report to document the kinetics of EEHV5 infection in captive Asian elephants and to provide evidence that this virus can cause illness in some animals.

  17. Functional profile of CD4+ and CD8+ T cells in latently infected individuals and patients with active TB.

    PubMed

    Marín, Nancy D; París, Sara C; Rojas, Mauricio; García, Luis F

    2013-03-01

    Tuberculosis (TB) is one of the most important infectious diseases around the world. Several studies have focused on the identification of correlates of protection against TB. Most of them have concentrated on the study of IFN-γ due to its robust association with protection against TB. However, given the complexity of the immune response elicited after Mtb infection, other cytokines should also be considered. In the present study, we evaluated Th1 and Th17 responses and their association with the protection or development of active disease. Therefore, non infected individuals (nonTBi), latently infected individuals (LTBi) and patients with active TB (ATB) were studied. The evaluation of the number of cytokine producing cells by ELISPOT showed a higher number of IFN-γ-producing cells in ATB patients, but no differences were found regarding the number of IL-17 producing cells among studied groups. The evaluation of IFN-γ, IL-2, TNF-α and IL-17 producing CD4+ and CD8+ T cells at 1 day and 6 days of stimulation with mycobacterial antigens suggests the presence of functional signatures associated with latency or active TB. The results presented herein suggest the possible use of the evaluation of Th1-type cytokines, such as IFN-γ and/or TNF-α, as a correlate of protection against TB; however, these results need to be validated for other groups.

  18. IFN-gamma-release assays to diagnose TB infection in the immunocompromised individual.

    PubMed

    Domínguez, Jose; Latorre, Irene; Altet, Neus; Mateo, Lourdes; De Souza-Galvão, Malú; Ruiz-Manzano, Juan; Ausina, Vicente

    2009-06-01

    The tuberculin skin test (TST) is used for diagnosing latent TB infection (LTBI). The main limitation of TST is its low sensitivity in populations with the highest risk of progression to active TB: immunosuppressed patients and young children. New IFN-gamma-based tests appear as an alternative to the TST. IFN-gamma-based tests seem more specific than the TST, being closely associated with LTBI factors, and not being affected by bacillus Calmette-Guérin vaccination. Indeterminate results are mainly related to immunosuppression. Looking at the available data, it seems prudent to recommend the utilization of IFN-gamma-based tests after a negative TST result, in order to increase the sensitivity of detecting LTBI cases in severely immunosuppressed patients. In summary, IFN-gamma-based tests appear to be a valuable tool, in combination with the TST, for diagnosing TB infection in immunosuppressed patients.

  19. Asymptomatic Tuberculosis-Induced Ileal Perforation in an HIV- Infected Individual; A Case Report

    PubMed Central

    Tahmasebi, Sedigheh; Moslemi, Sam; Tahamtan, Maryam; Taheri, Lohrasb; Davarpanah, Mohammad Ali

    2013-01-01

    The co-existence of acquired immune deficiency syndrome (AIDS) and tuberculosis is a major cause of morbidity and mortality because of a widespread organ involvement. The gastrointestinal tract is a common site for localization of opportunistic microorganisms in AIDS. However, surgical abdominal emergencies such as intestinal perforation resulted from tuberculosis are uncommon in these patients. The asymptomatic occurrence of such intestinal perforation has not been reported our knowledge. We represent an HIV and HCV co-infected man with miliary tuberculosis and an incidentally detected free air under  diaphragm in the chest X-ray eventually resulting in exploratory laparotomy which then revealed two tubercular-induced intestinal perforations. It seems that as the tuberculosis is increasing in incidence, mostly due to reactivation in HIV-infected patients especially in developing countries, we should not underestimate its acute abdominal emergencies such as bowel perforation. PMID:27162854

  20. Thirty-Day Postoperative Mortality Among Individuals With HIV Infection Receiving Antiretroviral Therapy and Procedure-Matched, Uninfected Comparators

    PubMed Central

    King, Joseph T.; Perkal, Melissa F.; Rosenthal, Ronnie A.; Gordon, Adam J.; Crystal, Stephen; Rodriguez-Barradas, Maria C.; Butt, Adeel A.; Gibert, Cynthia L.; Rimland, David; Simberkoff, Michael S.; Justice, Amy C.

    2016-01-01

    IMPORTANCE Antiretroviral therapy (ART) has converted human immunodeficiency virus (HIV) infection into a chronic condition, and patients now undergo a variety of surgical procedures, but current surgical outcomes are inadequately characterized. OBJECTIVE To compare 30-day postoperative mortality in patients with HIV infection receiving ART with the rates in uninfected individuals. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of nationwide electronic medical record data from the US Veterans Health Administration Healthcare System, October 1, 1996, to September 30, 2010. Common inpatient surgical procedures were grouped using the Healthcare Cost and Utilization Project Clinical Classification System to match HIV-infected and uninfected patients in a 1:2 ratio. Data on 1641 patients with HIV infection receiving combination ART who were undergoing inpatient surgery were compared with data on 3282 procedure-matched, uninfected comparators. Poisson regression models of 30-day postoperative mortality were adjusted for procedure year, age, Charlson Comorbidity Index score, hemoglobin level, albumin level, HIV infection, CD4 cell count, and HIV-1 RNA level. MAIN OUTCOMES AND MEASURES All-cause 30-day postoperative mortality. RESULTS The most common procedures in both groups were cholecystectomy (10.5%), hip arthroplasty (10.5%), spine surgery (9.8%), herniorrhaphy (7.4%), and coronary artery bypass grafting (7.0%). In patients with HIV infection, CD4 cell distributions were 80.0% with 200/µL or more, 16.3% with 50/µL to 199/µL, and 3.7% with less than 50/µL; 74.1% of patients with HIV infection had undetectable HIV-1 RNA. Human immunodeficiency virus infection was associated with higher 30-day postoperative mortality compared with the mortality in uninfected patients (3.4% [56 patients]) vs 1.6% [53]); incidence rate ratio [IRR], 2.11; 95% CI, 1.41–3.17; P < .001). CD4 cell count was inversely associated with mortality, but HIV-1 RNA provided no

  1. Assessment of PCR in the detection of Leishmania spp in experimentally infected individual phlebotomine sandflies (Diptera: Psychodidae: Phlebotominae).

    PubMed

    Michalsky, Erika M; Fortes-Dias, Consuelo L; Pimenta, Paulo F P; Secundino, Nágila F C; Dias, Edelberto S

    2002-01-01

    DNA amplification by the polymerase chain reaction (PCR) was applied in the investigation of the presence of Leishmania (Kinetoplastida: Trypanosomatidae) parasites in single phlebotomine sandflies. Three phlebotomine/parasite pairs were used: Lutzomyia longipalpis/Leishmania chagasi, Lutzomyia migonei/Leishmania amazonensis and Lutzomyia migonei/Leishmania braziliensis, all of them incriminated in the transmission of visceral or cutaneous leishmaniasis. DNA extraction was performed with whole insects, with no need of previous digestive tract dissection or pooling specimens. The presence of either mouse blood in the digestive tract of the sandflies or the digestive tract itself did not interfere in the PCR. Infection by as few as 10 Leishmania sp. per individual were sufficient for DNA amplification with genus-specific primers. Using primers for L. braziliensis and L. mexicana complexes, respectively, it was possible to discriminate between L. braziliensis and L. amazonensis in experimentally infected vectors (L. migonei).

  2. Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial.

    PubMed

    Barnabas, Ruanne V; Baeten, Jared M; Lingappa, Jairam R; Thomas, Katherine K; Hughes, James P; Mugo, Nelly R; Delany-Moretlwe, Sinead; Gray, Glenda; Rees, Helen; Mujugira, Andrew; Ronald, Allan; Stevens, Wendy; Kapiga, Saidi; Wald, Anna; Celum, Connie

    2016-02-15

    Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.00 and 2.68/100 person-years, respectively), a relative decrease of 62% (hazard ratio, 0.38; 95% confidence interval, .24-.67; P < .001). Daily acyclovir prophylaxis significantly reduced herpes zoster incidence among HIV-infected persons.

  3. Longitudinal evaluation of regulatory T-cell dynamics on HIV-infected individuals during the first 2 years of therapy

    PubMed Central

    Nobrega, Claudia; Horta, Ana; Coutinho-Teixeira, Vítor; Martins-Ribeiro, Ana; Baldaia, Ana; Rb-Silva, Rita; Santos, Catarina L.; Sarmento-Castro, Rui; Correia-Neves, Margarida

    2016-01-01

    Objectives: A sizeable percentage of individuals infected by HIV and on antiretroviral therapy (ART) fail to increase their CD4+ T-cells to satisfactory levels. The percentage of regulatory T-cells (Tregs) has been suggested to contribute to this impairment. This study aimed to address this question and to expand the analysis of Tregs subpopulations during ART. Design: Longitudinal follow-up of 81 HIV-infected individuals during the first 24 months on ART. Methods: CD4+ T-cell counts, Tregs percentages, and specific Tregs subpopulations were evaluated at ART onset, 2, 6, 9, 12, 16, 20, and 24 months of ART (five individuals had no Tregs information at baseline). Results: The slope of CD4+ T-cell recovery was similar for individuals with moderate and with severe lymphopenia at ART onset. No evidence was found for a contribution of the baseline Tregs percentages on the CD4+ T-cell counts recovery throughout ART. In comparison to uninfected individuals, Tregs percentages were higher at ART onset only for patients with less than 200 cells/μl at baseline and decreased afterwards reaching normal values. Within Tregs, the percentage of naive cells remained low in these patients. Reduced thymic export and increased proliferation of Tregs vs. conventional CD4+ T cells might explain these persistent alterations. Conclusion: No effect of Tregs percentages at baseline was detected on CD4+ T-cell recovery. However, profound alterations on Tregs subpopulations were consistently observed throughout ART for patients with severe lymphopenia at ART onset. PMID:26919738

  4. Causes of liver disease and its outcome in HIV-infected individuals.

    PubMed

    Shamanna, Suryanarayana Bettadpura; Naik, Ramavath Raghu Ramulu; Hamide, Abdoul

    2016-07-01

    Liver disease in HIV-infected patients has remained unaddressed in India. This study describes the causes of liver disease in HIV-infected patients and short-term outcome in them. Designed as a prospective observational study, it was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research between September 2011 and March 2013. All consecutive HIV patients (>13 years) attending the antiretroviral therapy clinic or admitted in the Medicine Department were screened, and patients with liver disease or with either HBsAg or anti-HCV antibody positivity were included in the study. Of the 198 patients screened, 51 (26 %) had either abnormal liver function test or had HBsAg or anti-HCV positivity. The median age of the patients was 40 years and 82 % were males. The median CD4 count was 123 cells/mm(3). Eighteen (35 %) of them had alcoholic liver disease. Six patients had probable hepatic involvement due to tuberculosis. Ten patients had antituberculosis drug-induced hepatotoxicity. One patient had acute hepatitis B and seven patients had chronic hepatitis B. The cause could not be established in 10 patients (20 %). After a median period of 8 months of follow up, 23 patients had improved, 19 patients (37 %) had died, and six patients had been lost to follow up. Of the patients who had died, 11 patients (58 %) had tuberculosis, and 6 patients (30 %) had decompensated alcoholic liver disease. In conclusion, liver disease in HIV-infected patients was associated with high mortality. Alcohol abuse, tuberculosis, and antituberculosis drugs were the major causes.

  5. Causes of liver disease and its outcome in HIV-infected individuals.

    PubMed

    Shamanna, Suryanarayana Bettadpura; Naik, Ramavath Raghu Ramulu; Hamide, Abdoul

    2016-07-01

    Liver disease in HIV-infected patients has remained unaddressed in India. This study describes the causes of liver disease in HIV-infected patients and short-term outcome in them. Designed as a prospective observational study, it was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research between September 2011 and March 2013. All consecutive HIV patients (>13 years) attending the antiretroviral therapy clinic or admitted in the Medicine Department were screened, and patients with liver disease or with either HBsAg or anti-HCV antibody positivity were included in the study. Of the 198 patients screened, 51 (26 %) had either abnormal liver function test or had HBsAg or anti-HCV positivity. The median age of the patients was 40 years and 82 % were males. The median CD4 count was 123 cells/mm(3). Eighteen (35 %) of them had alcoholic liver disease. Six patients had probable hepatic involvement due to tuberculosis. Ten patients had antituberculosis drug-induced hepatotoxicity. One patient had acute hepatitis B and seven patients had chronic hepatitis B. The cause could not be established in 10 patients (20 %). After a median period of 8 months of follow up, 23 patients had improved, 19 patients (37 %) had died, and six patients had been lost to follow up. Of the patients who had died, 11 patients (58 %) had tuberculosis, and 6 patients (30 %) had decompensated alcoholic liver disease. In conclusion, liver disease in HIV-infected patients was associated with high mortality. Alcohol abuse, tuberculosis, and antituberculosis drugs were the major causes. PMID:27435618

  6. Something fishy: an unusual Erysipelothrix rhusiopathiae infection in an immunocompromised individual.

    PubMed

    Sinclair, Marie; Hawkins, Angela; Testro, Adam

    2013-04-03

    A 39-year-old man with a history of Crohn's disease presented to the emergency department with a 12-h history of worsening febrile illness. He deteriorated rapidly with progression to sepsis and was admitted to the intensive care unit. Initial treatment comprised broad spectrum antibiotics and inotropic support resulting in rapid improvement. With the immunocompromised state of the patient, and multiple blood cultures revealing Erysipelothrix rhusiopathiae, a detailed history disclosed a recent injury sustained from a fishing wire as the probable source of an infection. Treatment was narrowed to target the identified pathogen, the patient made a full recovery, and was counselled to be more cautious in future fishing activities.

  7. The Healthy Living Project: An Individually Tailored, Multidimensional Intervention for HIV-Infected Persons

    ERIC Educational Resources Information Center

    Gore-Felton, Cheryl; Rotheram-Borus, Mary Jane; Weinhardt, Lance S.; Kelly, Jeffrey A.; Lightfoot, Marguerita; Kirshenbaum, Sheri B.; Johnson, Mallory O.; Chesney, Margaret A.; Catz, Sheryl L.; Ehrhardt, Anke A.; Remien, Robert H.; Morin, Stephen F.

    2005-01-01

    The NIMH Healthy Living Project (HLP), a randomized behavioral intervention trial for people living with HIV, enrolled 943 individuals, including women, heterosexual men, injection drug users, and men who have sex with men from Los Angeles, Milwaukee, New York, and San Francisco. The intervention, which is based on qualitative formative research…

  8. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections

    PubMed Central

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J.

    2016-01-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1–3 distinct haplotypes per infestation. PMID:26872064

  9. Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals.

    PubMed Central

    Moog, C; Fleury, H J; Pellegrin, I; Kirn, A; Aubertin, A M

    1997-01-01

    In the course of human immunodeficiency virus type 1 (HIV-1) infection, patients develop a strong and persistent immune response characterized by the production of HIV-specific antibodies. The aim of our study was to analyze the appearance of autologous and heterologous neutralizing antibodies in the sera of HIV-infected individuals. For this purpose, primary strains have been isolated from 18 HIV-1-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after seroconversion. Sera, collected at the same time as the virus was isolated and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early after infection, heterologous primary isolates, and cell-line adapted strains. Our neutralization assay, which combines serial dilutions of virus and serial dilutions of sera, is based on the determination of the serum dilution at which a fixed reduction in virus titer (90%) occurs. We have shown that (i) we could not detect autologous neutralizing antibodies in sera collected at the same time as we isolated viruses; (ii) we detected neutralizing antibodies against the autologous strains about 1 year after seroconversion, occasionally after 8 months, but sera were not always available to exclude the presence of neutralizing antibodies at earlier times; (iii) after 1 year, the neutralization response was highly specific to virus present during the early phase of HIV infection; and (iv) heterologous neutralization of primary isolates was detected later (after about 2 years). These results reveal the enormous diversity of neutralization determinants on primary isolates as well as a temporal evolution of the humoral response generating cross-reactive neutralizing antibodies. PMID:9094648

  10. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections.

    PubMed

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J; Fischer, Katja; Papenfuss, Anthony T

    2016-02-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1-3 distinct haplotypes per infestation. PMID:26872064

  11. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections.

    PubMed

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J; Fischer, Katja; Papenfuss, Anthony T

    2016-02-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1-3 distinct haplotypes per infestation.

  12. Is impaired kidney function an independent predictor of the risk of myocardial infarction in HIV-infected individuals?

    PubMed

    Lang, Sylvie; Mary-Krause, Murielle; Partisani, Marialuisa; Gilquin, Jacques; Simon, Anne; Cotte, Laurent; Boccara, Franck; Costagliola, Dominique

    2014-08-24

    We examined whether impaired kidney function is an independent risk factor for myocardial infarction in HIV-infected individuals without pre-existing coronary artery disease. The odds ratio for impaired kidney function fell from 1.22 (95% confidence interval 0.90-1.66) to 0.99 (95% confidence interval 0.69-1.41) after adjustment for cardiovascular risk factors and HIV-related parameters, with hypertension, high-density lipoprotein cholesterol, smoking and the CD4 T-cell nadir as most influential confounders. In this setting, no association was found between impaired kidney function and the risk of myocardial infarction.

  13. Macrophages and CD4+ T lymphocytes from two multiply exposed, uninfected individuals resist infection with primary non-syncytium-inducing isolates of human immunodeficiency virus type 1.

    PubMed Central

    Connor, R I; Paxton, W A; Sheridan, K E; Koup, R A

    1996-01-01

    Despite multiple, high-risk sexual exposures, some individuals remain uninfected with human immunodeficiency virus type 1 (HIV-1). CD4+ lymphocytes from these individuals are less susceptible to infection in vitro with some strains of HIV-1, suggesting that the phenotype of the virus may influence its ability to interact with certain CD4+ cells. In the present study, we examined the susceptibility of CD4+ T lymphocytes and macrophages from two exposed uninfected individuals (EU2 and EU3) to infection with a panel of biologically cloned isolates of HIV-1 having either a non-syncytium-inducing (NSI) or a syncytium-inducing (SI) phenotype. Our results indicate that CD4+ T lymphocytes from EU2 and EU3 are resistant to infection with NSI isolates of HIV-1 but are susceptible to infection with primary SI isolates. In addition, we found that macrophages from EU2 and EU3 are resistant to infection with both NSI and SI isolates. The latter finding was confirmed by using several uncloned NSI and SI isolates obtained from patients during acute HIV-1 infection. In further experiments, env clones encoding glycoproteins characteristic of NSI or SI viruses were used in single-cycle infectivity assays to evaluate infection of CD4+ lymphocytes and macrophages from EU2 and EU3. Consistent with our previous results, we found that macrophages from these individuals are resistant to infection with NSI and SI env-pseudotyped viruses, while CD4+ T lymphocytes are resistant to NSI, but not SI, pseudotyped viruses. Overall, our results demonstrate that CD4+ cells from two exposed uninfected individuals resist infection in vitro with primary, macrophage-tropic, NSI isolates of HIV-1, which is the predominant viral phenotype found following HIV-1 transmission. Furthermore, infection with NSI isolates was blocked in both CD4+ T lymphocytes and macrophages from these individuals, suggesting that there may be a common mechanism for resistance in both cell types. PMID:8971004

  14. Context of risk for HIV and sexually transmitted infections among incarcerated women in the south: individual, interpersonal, and societal factors.

    PubMed

    Fogel, Catherine I; Gelaude, Deborah J; Carry, Monique; Herbst, Jeffrey H; Parker, Sharon; Scheyette, Anna; Neevel, A

    2014-01-01

    Incarcerated women are disproportionately affected by HIV and sexually transmitted infections (STIs) due to risk factors before, during, and after imprisonment. This study assessed the behavioral, social, and contextual conditions that contribute to continuing sexual risk behaviors among incarcerated women to inform the adaptation of an evidenced-based behavioral intervention for this population. Individual, in-depth interviews were conducted with 25 current and 28 former women prisoners to assess HIV/STI knowledge, perceptions of risk, intimate relationships, and life circumstances. Interviews were independently coded using an iterative process and analyzed using established qualitative analytic methods. Major themes identified in the interviews involved three focal points: individual risk (substance abuse, emotional need, self-worth, perceptions of risk, and safer sex practices); interpersonal risk (partner pressure, betrayal, and violence); and risk environment (economic self-sufficiency and preparation for reentry). These findings highlight the critical components of HIV/STI prevention interventions for incarcerated women. PMID:25204565

  15. A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals

    PubMed Central

    Procopio, Francesco Andrea; Fromentin, Rémi; Kulpa, Deanna A.; Brehm, Jessica H.; Bebin, Anne-Gaelle; Strain, Matthew C.; Richman, Douglas D.; O'Doherty, Una; Palmer, Sarah; Hecht, Frederick M.; Hoh, Rebecca; Barnard, Richard J.O.; Miller, Michael D.; Hazuda, Daria J.; Deeks, Steven G.; Sékaly, Rafick-Pierre; Chomont, Nicolas

    2015-01-01

    Background Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the long-lived viral reservoir, but the low frequency of these cells makes this very challenging. Methods We developed TILDA (Tat/rev Induced Limiting Dilution Assay) to measure the frequency of cells with inducible multiply-spliced HIV RNA, as these transcripts are usually absent in latently infected cells but induced upon viral reactivation. TILDA requires less than a million cells, does not require RNA extraction and can be completed in two days. Findings In suppressed individuals on ART, we found the median frequency of latently infected CD4 + T cells as estimated by TILDA to be 24 cells/million, which was 48 times more than the frequency measured by the quantitative viral outgrowth assay, and 6–27 times less than the frequencies of cells harbouring viral DNA measured by PCR-based assays. TILDA measurements strongly correlated with most HIV DNA assays. The size of the latent reservoir measured by TILDA was lower in subjects who initiated ART during the early compared to late stage of infection (p = 0.011). In untreated HIV disease, the frequency of CD4 + cells carrying latent but inducible HIV largely exceeded the frequency of actively producing cells, demonstrating that the majority of infected cells are transcriptionally silent even in the absence of ART. Interpretations Our results suggest that TILDA is a reproducible and sensitive approach to measure the frequency of productively and latently infected cells in clinical settings. We demonstrate that the latent reservoir represents a substantial fraction of all infected cells prior to ART initiation. Research in context In this manuscript, we describe the development of a novel assay that measures the magnitude of the latent HIV reservoir, the main barrier to HIV eradication. This novel assay, termed TILDA for Tat/rev Induced Limiting Dilution Assay, requires only

  16. Cumulative Incidence of Cancer among HIV-infected Individuals in North America

    PubMed Central

    Silverberg, Michael J.; Lau, Bryan; Achenbach, Chad J.; Jing, Yuezhou; Althoff, Keri N.; D’Souza, Gypsyamber; Engels, Eric A.; Hessol, Nancy; Brooks, John T.; Burchell, Ann N.; Gill, M. John; Goedert, James J.; Hogg, Robert; Horberg, Michael A.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, Phillip T.; Mathews, William C.; Mayor, Angel; Modur, Sharada P.; Napravnik, Sonia; Novak, Richard M.; Patel, Pragna; Rachlis, Anita R.; Sterling, Timothy R.; Willig, James H.; Justice, Amy C.; Moore, Richard D.; Dubrow, Robert

    2016-01-01

    Background Cancer is increasingly common among HIV patients given improved survival. Objective To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Design Cohort study Setting North American AIDS Cohort Collaboration on Research and Design during 1996–2009 Patients 86,620 HIV-infected and 196,987 uninfected adults Measurements We estimated cancer-type-specific cumulative incidence by age 75 years by HIV status and calendar era, and examined calendar trends in cumulative incidence and hazard rates. Results Cumulative incidences (%) of cancer by age 75 (HIV+/HIV−) were: Kaposi sarcoma (KS), 4.4/0.01; non-Hodgkin’s lymphoma (NHL), 4.5/0.7; lung, 3.4/2.8; anal, 1.5/0.1; colorectal, 1.0/1.5; liver, 1.1/0.4; Hodgkin lymphoma (HL), 0.9/0.1; melanoma, 0.5/0.6; and oral cavity/pharyngeal, 0.8/0.8. Among HIV-infected subjects, we observed decreasing calendar trends in cumulative incidence and hazard rate for KS and NHL. For anal, colorectal and liver cancers, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed with these cancer types. Despite decreasing hazard rate trends for lung, HL, and melanoma, we did not observe cumulative incidence trends due to the compensating effect of the declining mortality rate on cumulative incidence. Limitations Secular trends in screening, smoking, and viral co-infections were not evaluated. Conclusions Our analytic approach helped disentangle the effects of improved survival and changing cancer-specific hazard rates on cumulative incidence trends among HIV patients. Cumulative cancer incidence by age 75, approximating lifetime risk in HIV patients, may have clinical utility in this population. The high cumulative incidences by age 75 for KS, NHL, and lung cancer supports early and sustained ART and smoking cessation. Primary Funding Source National Institutes of Health PMID:26436616

  17. Factors associated with tobacco smoking and cessation among HIV-infected individuals under care in Rio de Janeiro, Brazil.

    PubMed

    Torres, Thiago S; Luz, Paula M; Derrico, Monica; Velasque, Luciane; Grinsztejn, Eduarda; Veloso, Valdiléa G; Cardoso, Sandra W; Santini-Oliveira, Marília; Grinsztejn, Beatriz; De Boni, Raquel Brandini

    2014-01-01

    Worldwide the prevalence of smoking among people living with HIV/AIDS is elevated compared to the general population. This probably reflects the cluster of individual characteristics that have shared risk factors for HIV infection and smoking. A cross-sectional study, enrolling a convenience sample from a Brazilian HIV clinical cohort was conducted to evaluate the prevalence of tobacco smoking and the factors associated with current smoking and abstinence. A total of 2,775 HIV-infected individuals were interviewed: 46.2% have never smoked, 29.9% were current smokers and 23.9% were former smokers. Current smokers had a higher prevalence of alcohol and illicit drug use when compared to the other two groups. A higher proportion of heterosexual individuals were former smokers or never smokers while among men who have sex with men (MSM) a higher proportion were current smokers. Former smokers had been more frequently diagnosed with high blood pressure, diabetes mellitus, cardiovascular diseases and depression, while for current smokers lung diseases were more frequent. Former smokers and current smokers were more likely to have had any hospital admission (42.0% and 41.2%, respectively) than participants who never smoked (33.5%) (p<0.001). Multivariate model results showed that current smokers (versus never smokers) were more likely to be less educated, to report the use of alcohol, crack and cocaine and to present clinical comorbidities. Former smokers (versus current smokers) were more likely to be older, to have smoked for a shorter amount of time and to have smoked >31 cigarettes/day. MSM (compared to heterosexuals) and cocaine users (versus non-users) had lower odds of being former smokers. Considering our results, smoking cessation interventions should be tailored to younger individuals, MSM and substance users. PMID:25536064

  18. A multi-stage compartmental model for HIV-infected individuals: I--waiting time approach.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Traditionally, epidemic processes have focused on establishing systems of differential-difference equations governing the number of individuals at each stage of the epidemic. Except for simple situations such as when transition rates are linear, these equations are notoriously intractable mathematically. In this work, the process is described as a compartmental model. The model also allows for individuals to go directly from any prior compartment directly to a final stage corresponding to death. This allows for the possibility that individuals can die earlier due to some non-disease related cause. Then, the model is based on waiting times in each compartment. Survival probabilities of moving from a given compartment to another compartment are established. While our approach can be used for general epidemic processes, our framework is for the HIV/AIDS process. It is then possible to establish the impact of the HIV/AIDS epidemic process on, e.g., insurance premiums and payouts and health-care costs. The effect of changing model parameter values on these entities is investigated.

  19. Prevalence and antifungal susceptibility of Candida parapsilosis complex isolates collected from oral cavities of HIV-infected individuals.

    PubMed

    Moris, D V; Melhem, M S C; Martins, M A; Souza, L R; Kacew, S; Szeszs, M W; Carvalho, L R; Pimenta-Rodrigues, M V; Berghs, H A M; Mendes, R P

    2012-12-01

    At present, few data are available on the prevalence and antifungal susceptibility of Candida parapsilosis complex isolates from HIV-infected individuals. The C. parapsilosis complex comprises three species, C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. Fifteen of 318 Candida isolates were identified as members of the C. parapsilosis complex by PCR and restriction fragment length polymorphism (RFLP). The prevalence of C. parapsilosis complex isolates was 4.7 %, 2.2 % being identified as C. parapsilosis sensu stricto and 2.5 % as C. metapsilosis, while no C. orthopsilosis was isolated. This is believed to be the first study that has identified isolates of C. metapsilosis obtained from the oral cavity of HIV-infected individuals. Antifungal susceptibility tests indicated that all the isolates were susceptible to amphotericin B (AMB), fluconazole (FLC), ketoconazole (KTC), itraconazole (ITC), voriconazole (VRC) and caspofungin (CASPO). Although isolates of C. parapsilosis sensu stricto and C. metapsilosis were susceptible to FLC, isolates of C. metapsilosis showed a tendency for higher MICs (≥1.0 µg ml(-1)). Based upon the frequency of candidiasis and the fact that certain isolates of the C. parapsilosis complex respond differently to FLC therapy, our data may be of therapeutic relevance with respect to susceptibility and potential resistance to specific antifungal agents. Our data suggest that C. metapsilosis can be a human commensal; its importance as a pathogen has yet to be confirmed. PMID:22956748

  20. Characterization of Host and Microbial Determinants in Individuals with Latent Tuberculosis Infection Using a Human Granuloma Model

    PubMed Central

    Guirado, Evelyn; Mbawuike, Uchenna; Keiser, Tracy L.; Arcos, Jesus; Azad, Abul K.; Wang, Shu-Hua

    2015-01-01

    ABSTRACT Granulomas sit at the center of tuberculosis (TB) immunopathogenesis. Progress in biomarkers and treatment specific to the human granuloma environment is hindered by the lack of a relevant and tractable infection model that better accounts for the complexity of the host immune response as well as pathogen counterresponses that subvert host immunity in granulomas. Here we developed and characterized an in vitro granuloma model derived from human peripheral blood mononuclear cells (PBMCs) and autologous serum. Importantly, we interrogated this model for its ability to discriminate between host and bacterial determinants in individuals with and without latent TB infection (LTBI). By the use of this model, we provide the first evidence that granuloma formation, bacterial survival, lymphocyte proliferation, pro- and anti-inflammatory cytokines, and lipid body accumulation are significantly altered in LTBI individuals. Moreover, we show a specific transcriptional signature of Mycobacterium tuberculosis associated with survival within human granuloma structures depending on the host immune status. Our report provides fundamentally new information on how the human host immune status and bacterial transcriptional signature may dictate early granuloma formation and outcome and provides evidence for the validity of the granuloma model and its potential applications. PMID:25691598

  1. Patient Navigation Facilitates Medical and Social Services Engagement Among HIV-Infected Individuals Leaving Jail and Returning to the Community

    PubMed Central

    Morewitz, Mark; Pearson, Charles; Weeks, John; Packard, Rebecca; Estes, Milton; Tulsky, Jacqueline; Kang-Dufour, Mi_Suk; Myers, Janet J.

    2014-01-01

    Abstract HIV-infected individuals leaving jails, facilities typically used to confine accused persons awaiting trial or to incarcerate persons for minor offenses, often face barriers to engagement with medical and social-support services. Patient navigation is a model that may ease these barriers by supporting individuals in negotiating fragmented and highly bureaucratic systems for services and care. While there is evidence linking navigation to a reduction in health disparities, little is known about the mechanisms by which the model works. We present findings of an ethnographic study of interactions between navigators and their clients: HIV-infected men and women recently released from jails in San Francisco, California. We conducted 29 field observations of navigators as they accompanied their clients to appointments, and 40 in-depth interviews with clients and navigators. Navigators worked on strengthening clients' abilities to engage with social-services and care systems. Building this strength required navigators to gain clients' trust by leveraging their own similar life experiences or expressing social concordance. After establishing meaningful connections, navigators spent time with clients in their day-to-day environments serving as mentors while escorting clients to and through their appointments. Intensive time spent together, in combination with a shared background of incarceration, HIV, and drug use, was a critical mechanism of this model. This study illustrates that socially concordant navigators are well positioned to facilitate successful transition to care and social-services engagement among a vulnerable population. PMID:24517539

  2. Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals

    PubMed Central

    Keegan, Michael R.; Chittiprol, Seetharamaiah; Letendre, Scott L.; Winston, Alan; Fuchs, Dietmar; Boasso, Adriano; Iudicello, Jennifer; Ellis, Ronald J.

    2016-01-01

    OBJECTIVE Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals. METHODS In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+ (n = 91) and HIV-negative (HIV−) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score ≥0.5 was defined as CI. Nonparametric statistical analyses included Kruskal–Wallis and Mann–Whitney U tests, and multivariate logistic regression. RESULTS Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV− individuals, including a subgroup of aviremic (defined as HIV-1 RNA <50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031). CONCLUSIONS We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD. PMID:27812290

  3. Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine.

    PubMed Central

    Chien, S C; Chow, A T; Rogge, M C; Williams, R R; Hendrix, C W

    1997-01-01

    This phase I, double-blind, randomized, placebo-controlled, parallel-design study was conducted to evaluate the safety and pharmacokinetics of levofloxacin in human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell counts ranging from 100 to 550 and not experiencing significant AZT intolerance were enrolled. Subjects received levofloxacin (350 mg of levofloxacin hemihydrate) or a placebo (eight subjects per treatment group) as a single oral dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with the study drug. In between these doses, AZT was administered according to the regimen used by the subject prior to entering the study up to a maximum of 500 mg/day. Plasma levofloxacin concentrations were monitored for 36 h after levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to 9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma concentration, approximately 1.0 h) and extensively distributed in the body with an apparent volume of distribution of approximately 104 liters (approximately 1.34 liters/kg). Steady-state conditions on day 10 were confirmed. Pharmacokinetic profiles of levofloxacin from single doses and multiple (three-times-daily) doses were similar, with a moderate accumulation (observed day 10-to-day 1 ratio of the maximum plasma concentration, approximately 185% versus expected 169%; for the corresponding ratio of the area under the concentration-time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus expected 169%) at steady state. Mean average steady-state peak plasma concentration, plasma levofloxacin concentration at the

  4. Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease.

    PubMed

    Bishop, Matthew T; Diack, Abigail B; Ritchie, Diane L; Ironside, James W; Will, Robert G; Manson, Jean C

    2013-04-01

    Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt-Jakob disease. Three cases of variant Creutzfeldt-Jakob disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt-Jakob disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt-Jakob disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt-Jakob disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt-Jakob disease agent. Mice were assessed for clinical and pathological signs of disease and transmission data were compared with other transmission studies in variant Creutzfeldt-Jakob disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt-Jakob disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and recipient spleen

  5. Can repeated plasma donation by asymptomatic HIV-infected individuals delay the onset of AIDS?

    PubMed Central

    Bainbridge, D R; Lowdell, M W; Hannet, I M; Strauss, K W; Karpas, A

    1997-01-01

    Healthy HIV-positive regular donors of plasma in a programme of passive immunotherapy for AIDS patients were studied over a period of about two years. None developed symptoms of clinical progression; most seemed to make substantial gains of CD4 cells by comparison with asymptomatic individuals who were not donating. The effects of donation did not seem to diminish with repetition, and donor CD4 counts tended towards stabilizing within normal limits. Asymptomatic HIV-positive individuals were compared immunologically with 'normals' and people with AIDS, using a battery of 25 measurements on peripheral blood. The immunological profiles of donor and non-donor asymptomatics, indistinguishable at the start, became dissimilar: donors' profiles resembled AIDS less, non-donors became less like 'normal' and a few non-donor results could not be distinguished from AIDS. Improvement in the CD4 counts and amelioration of the immunological profile in donors provide prima facie evidence that plasmapheresis may be therapeutic for asymptomatic HIV-positive people. Further studies are justified. PMID:9279896

  6. Pain Self-Management in HIV-infected Individuals with Chronic Pain: A Qualitative Study

    PubMed Central

    Merlin, Jessica S.; Walcott, Melonie; Kerns, Robert; Bair, Matthew J.; Burgio, Kathryn L.; Turan, Janet M.

    2015-01-01

    Objective Chronic pain in individuals with HIV is a common, impairing condition. Behavioral interventions for chronic pain specifically tailored to this population have yet to be developed. We assert that understanding self-management strategies already used by persons living with these conditions is an essential first step, and is the objective of this investigation. Design We conducted a thematic analysis of qualitative data from 25 in-depth interviews with individuals with HIV and chronic pain. Results The primary pain self-management strategies articulated by participants were: physical activity; cognitive and spiritual strategies; spending time with family and friends and social support; avoidance of physical/social activity; medication-centric pain management; and substance use. Conclusions Some of these strategies may be viewed as beneficial and overlap with known HIV self-management strategies (cognitive strategies), whereas others may have negative health consequences (substance use). Interventions that incorporate healthy self-management strategies may be particularly effective in improving both HIV and pain outcomes. PMID:25645646

  7. Relationship between psychiatric status and frontal–subcortical systems in HIV-infected individuals

    PubMed Central

    COLE, MICHAEL A.; CASTELLON, STEVEN A.; PERKINS, ADAM C.; URENO, OSCAR S.; ROBINET, MARTA B.; REINHARD, MATTHEW J.; BARCLAY, TERRY R.; HINKIN, CHARLES H.

    2010-01-01

    Human immunodeficiency virus (HIV)-infected adults frequently evidence both neurocognitive and psychiatric dysfunction. It was hypothesized that apathy and irritability, but not anxiety and depression, are related to HIV effects on frontal–subcortical systems. This hypothesis was evaluated by determining the degree to which these psychiatric features are associated with neurocognitive functioning that is dependent upon frontal–subcortical circuitry and, therefore, thought to be sensitive to the central nervous system effects of HIV. Rating scales assessing irritability, apathy, depression, and anxiety and a dual-task paradigm were administered to 189 HIV-seropositive (HIV+) and 53 HIV-seronegative participants. Deficits in dual-task performance and greater anxiety, depression, apathy, and irritability were observed in HIV+ participants. Simultaneous multivariate regression and communality analyses revealed that only apathy and irritability were associated with dual-task performance in HIV+ participants. Thus, these findings suggest that apathy and irritability, but not depression and anxiety, are likely associated with the effects of HIV on frontal–subcortical circuitry. PMID:17445305

  8. Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study

    PubMed Central

    Milani, Christian; Ticinesi, Andrea; Gerritsen, Jacoline; Nouvenne, Antonio; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Duranti, Sabrina; Mangifesta, Marta; Viappiani, Alice; Ferrario, Chiara; Maggio, Marcello; Lauretani, Fulvio; De Vos, Willem; van Sinderen, Douwe; Meschi, Tiziana; Ventura, Marco

    2016-01-01

    The gut microbiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three groups of hospitalized elderly patients (age ≥ 65) under standard diet including 25 CDI-positive (CDI group), 29 CDI-negative exposed to antibiotic treatment (AB+ group) and 30 CDI-negative subjects not on antibiotic treatment (AB− group). The functional properties of the gut microbiomes of CDI-positive vs CDI-negative subjects were also assessed by shotgun metagenomics. A significantly lower microbial diversity was detected in CDI samples, whose microbiomes clustered separately from CDI-negative specimens. CDI was associated with a significant under-representation of gut commensals with putative protective functionalities, including Bacteroides, Alistipes, Lachnospira and Barnesiella, and over-representation of opportunistic pathogens. These findings were confirmed by functional shotgun metagenomics analyses, including an in-depth profiling of the Peptostreptococcaceae family. In CDI-negative patients, antibiotic treatment was associated with significant depletion of few commensals like Alistipes, but not with a reduction in species richness. A better understanding of the correlations between CDI and the microbiota in high-risk elderly subjects may contribute to identify therapeutic targets for CDI. PMID:27166072

  9. Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals

    PubMed Central

    Chun, Tae-Wook; Justement, J. Shawn; Lempicki, Richard A.; Yang, Jun; Dennis, Glynn; Hallahan, Claire W.; Sanford, Christina; Pandya, Punita; Liu, Shuying; McLaughlin, Mary; Ehler, Linda A.; Moir, Susan; Fauci, Anthony S.

    2003-01-01

    The presence of HIV-1 in latently infected, resting CD4+ T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD4+ T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously ex vivo. The levels of HIV-1 released by resting CD4+ T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD4+ T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD4+ T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD4+ T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD4+ T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy. PMID:12552096

  10. High prevalence of the UGT1A1*28 variant in HIV-infected individuals in Greece.

    PubMed

    Panagopoulos, P; Paraskevis, D; Katsarolis, I; Sypsa, V; Detsika, M; Protopapas, K; Antoniadou, A; Papadopoulos, A; Petrikkos, G; Hatzakis, A

    2014-10-01

    Hyperbilirubinaemia with or without jaundice is one of the side effects of atazanavir boosted with low-dose ritonavir (ATV/rit) related to the drug plasma levels, as a result of its metabolism by UGT1A1 - uridine diphosphate-glucuronosyl transferase. Genotyping for UGT1A1*28 before initiation of antiretroviral therapy containing atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Our objective was to estimate the prevalence of the UGTA1A1*28 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinaemia in patients receiving ATV/rit. The prevalence of the UGTA1A1*28 variant was estimated in 79 HIV-infected patients prior to the administration of the first-line treatment. The UGTA1A1*28 variant was detected in 46 out of 79 individuals (58.2%). Antiretroviral therapy was administered to 64/79 patients (81%). Among them, 26/64 (40.6%) received ATV/rit. Of the ATV/rit-treated patients, 14 were found to be carriers of the UGT1A1*28 variant (54%), and maximum serum bilirubin levels were significantly higher in the carrier population (4.71 vs. 2.69 mg/dL, p = 0.026). In 50% of the population, maximum levels were recorded in the first month of follow-up. Although carriage of UGT1A1 is linked with the development of hyperbilirubinaemia, the implementation of a pharmacogenomic approach in clinical practice cannot yet be recommended as a standard of care. PMID:24516079

  11. Alarming attrition rates among HIV-infected individuals in pre-antiretroviral therapy care in Myanmar, 2011–2014

    PubMed Central

    Oo, Myo Minn; Gupta, Vivek; Aung, Thet Ko; Kyaw, Nang Thu Thu; Oo, Htun Nyunt; Kumar, Ajay MV

    2016-01-01

    Background High retention rates have been documented among patients receiving antiretroviral therapy (ART) in Myanmar. However, there is no information on human immunodeficiency virus (HIV)-infected individuals in care before initiation of ART (pre-ART care). We assessed attrition (loss-to-follow-up [LTFU] and death) rates among HIV-infected individuals in pre-ART care and their associated factors over a 4-year period. Design In this retrospective cohort study, we extracted routinely collected data of HIV-infected adults (>15 years old) entering pre-ART care (June 2011–June 2014) as part of an Integrated HIV Care (IHC) programme, Myanmar. Attrition rates per 100 person-years and cumulative incidence of attrition were calculated. Factors associated with attrition were examined by calculating hazard ratios (HRs). Results Of 18,037 HIV-infected adults enrolled in the IHC programme, 11,464 (63%) entered pre-ART care (60% men, mean age 37 years, median cluster of differentiation 4 (CD4) cell count 160 cells/µL). Of the 11,464 eligible participants, 3,712 (32%) underwent attrition of which 43% were due to deaths and 57% were due to LTFU. The attrition rate was 78 per 100 person-years (95% CI, 75–80). The cumulative incidence of attrition was 70% at the end of a 4-year follow-up, of which nearly 90% occurred in the first 6 months. Male sex (HR 1.5, 95% CI 1.4–1.6), WHO clinical Stage 3 and 4, CD4 count <200 cells/µL, abnormal BMI, and anaemia were statistically significant predictors of attrition. Conclusions Pre-ART care attrition among persons living with HIV in Myanmar was alarmingly high – with most attrition occurring within the first 6 months. Strategies aimed at improving early HIV diagnosis and initiation of ART are needed. Suggestions include comprehensive nutrition support and intensified monitoring to prevent pre-ART care attrition by tracking patients who do not return for pre-ART care appointments. It is high time that Myanmar moves towards a

  12. Exploring the Contribution of Host Susceptibility to Epidemiological Patterns of Schistosoma japonicum Infection Using an Individual-Based Model

    PubMed Central

    Wang, Shuo; Spear, Robert C.

    2015-01-01

    We recently reported the analysis of epidemiological data suggesting variability in individual susceptibility to infection by Schistosoma japonicum among rural villagers who reside in Sichuan Province of southwestern China. By supplementing the data used in the earlier analysis from other studies we have reported from this region, we presented improved estimates of cercarial exposure, which in turn, result in stronger evidence of susceptibility. This analysis was conducted using an individual-based mathematical model (IBM) whose use was motivated by the nature and extent of field data from the low-transmission environments exemplified by one of our datasets and typical of the current situation in most endemic areas of China. In addition to individual susceptibility and water contact, the model includes stochastic aspects of cercarial exposure as well as of diagnostic procedures, the latter being particularly relevant to the low-transmission environment. The simulation studies show that, to produce key aspects of the epidemiological findings, the distribution of susceptibility ranges over several orders of magnitude and is highly right skewed. We found no compelling evidence that the distribution of susceptibility differed between the two populations that underlie both the epidemiological and simulation results. PMID:25870427

  13. Characterization of the mutant spectra of a fish RNA virus within individual hosts during natural infections

    USGS Publications Warehouse

    Emmenegger, Eveline J.; Troyer, Ryan M.; Kurath, Gael

    2003-01-01

    Infectious hematopoietic necrosis virus (IHNV) is an RNA virus that causes significant mortalities of salmonids in the Pacific Northwest of North America. RNA virus populations typically contain genetic variants that form a heterogeneous virus pool, referred to as a quasispecies or mutant spectrum. This study characterized the mutant spectra of IHNV populations within individual fish reared in different environmental settings by RT–PCR of genomic viral RNA and determination of partial glycoprotein gene sequences of molecular clones. The diversity of the mutant spectra from ten in vivo populations was low and the average mutation frequencies of duplicate populations did not significantly exceed the background mutation level expected from the methodology. In contrast, two in vitro populations contained variants with an identical mutational hot spot. These results indicated that the mutant spectra of natural IHNV populations is very homogeneous, and does not explain the different magnitudes of genetic diversity observed between the different IHNV genogroups. Overall the mutant frequency of IHNV within its host is one of the lowest reported for RNA viruses.

  14. RELATED FACTORS FOR COLONIZATION BY Candida SPECIES IN THE ORAL CAVITY OF HIV-INFECTED INDIVIDUALS

    PubMed Central

    MENEZES, Ralciane de Paula; BORGES, Aércio Sebastião; de ARAUJO, Lúcio Borges; PEDROSO, Reginaldo dos Santos; RÖDER, Denise Von Dolinger de Brito

    2015-01-01

    The colonization of the oral cavity is a prerequisite to the development of oropharyngeal candidiasis. Aims: The aims of this study were: to evaluate colonization and quantify Candida spp. in the oral cavity; to determine the predisposing factors for colonization; and to correlate the levels of CD4+ cells and viral load with the yeast count of colony forming units per milliliter (CFU/mL) in HIV-positive individuals treated at a University Hospital. Saliva samples were collected from 147 HIV patients and were plated on Sabouraud Dextrose Agar (SDA) and chromogenic agar, and incubated at 30 ºC for 72 h. Colonies with similar morphology in both media were counted and the result expressed in CFU/mL. Results: Of the 147 HIV patients, 89 had positive cultures for Candida spp., with a total of 111 isolates, of which C. albicans was the most frequent species (67.6%), and the mean of colonies counted was 8.8 × 10³ CFU/mL. The main predisposing factors for oral colonization by Candida spp. were the use of antibiotics and oral prostheses. The use of reverse transcriptase inhibitors appears to have a greater protective effect for colonization. A low CD4+ T lymphocyte count is associated with a higher density of yeast in the saliva of HIV patients. PMID:26603229

  15. Genotyping and Molecular Characterization of Hepatitis B Virus from Human Immunodeficiency Virus-Infected Individuals in Southern Africa

    PubMed Central

    Makondo, Euphodia; Bell, Trevor G.; Kramvis, Anna

    2012-01-01

    Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are hyperendemic in sub-Saharan Africa. The HBV genotypes prevailing in HIV-infected Africans are unknown. Our aim was to determine the HBV genotypes in HIV-infected participants and to identify clinically significant HBV mutations. From 71 HBV DNA+ve HIV-infected participants, 49 basic core promoter/precore (BCP/PC) and 29 complete S regions were successfully sequenced. Following phylogenetic analysis of 29 specimens in the complete S region, 28 belonged to subgenotype A1 and one to D3. Mutations affecting HBeAg expression at the transcriptional (1762T1764A), translational (Kozak 1809–1812, initiation 1814–1816, G1896A with C1858T), or post translational levels (G1862T), were responsible for the high HBeAg-negativity observed. The G1862T mutation occurred only in subgenotype A1 isolates, which were found in one third (7/21) of HBsAg−ve participants, but in none of the 18 HBsAg+ve participants (p<0.05). Pre-S deletion mutants were detected in four HBsAg+ve and one HBsAg−ve participant/s. The following mutations occurred significantly more frequently in HBV isolated in this study than in strains of the same cluster of the phylogenetic tree: ps1F25L, ps1V88L/A; ps2Q10R, ps2 R48K/T, ps2A53V and sQ129R/H, sQ164A/V/G/D, sV168A and sS174N (p<0.05). ps1I48V/T occurred more frequently in females than males (p<0.05). Isolates with sV168A occurred more frequently in participants with viral loads >200 IU per ml (p<0.05) and only sS174N occurred more frequently in HBsAg−ve than in HBsAg+ve individuals (p<0.05). Prior to initiation of ART, ten percent, 3 of 29 isolates sequenced, had drug resistance mutations rtV173L, rtL180M+rtM204V and rtV214A, respectively. This study has provided important information on the molecular characteristics of HBV in HIV-infected southern Africans prior to ART initiation, which has important clinical relevance in the management of HBV/HIV co-infection in our unique setting

  16. High Oral Human Papillomavirus Type 16 Load Predicts Long-term Persistence in Individuals With or at Risk for HIV Infection.

    PubMed

    Beachler, Daniel C; Guo, Yingshi; Xiao, Wiehong; Burk, Robert D; Minkoff, Howard; Strickler, Howard D; Cranston, Ross D; Wiley, Dorothy J; Jacobson, Lisa P; Weber, Kathleen M; Margolick, Joseph B; Sugar, Elizabeth A; Reddy, Susheel; Gillison, Maura L; D'Souza, Gypsyamber

    2015-11-15

    The association between oral human papillomavirus 16 (HPV16) DNA load and infection clearance was evaluated among 88 individuals with oral HPV16 infection who were identified within a prospective cohort of 1470 HIV-infected and uninfected individuals. Oral rinse specimens were collected semiannually for up to 5 years. The oral HPV16 load at the time of the first positive test result was significantly associated with the time to clearance of infection (continuous P trends <.01). Notably, clearance rates by 24 months were 41% and 94% in the highest and lowest HPV16 load tertiles (P = .03), respectively. High oral HPV16 load warrants consideration as a biomarker for infection persistence, the presumed precursor of HPV16-associated oropharyngeal cancer.

  17. Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals.

    PubMed

    Carrillo, Jorge; Molinos-Albert, Luis Manuel; Rodríguez de la Concepción, Maria Luisa; Marfil, Silvia; García, Elisabet; Derking, Ronald; Sanders, Rogier W; Clotet, Bonaventura; Blanco, Julià

    2015-01-01

    Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine. PMID:25803681

  18. Suppression of HIV Replication by Lymphoid Tissue CD8+ Cells Correlates with the Clinical State of HIV-Infected Individuals

    NASA Astrophysics Data System (ADS)

    Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.

    1996-11-01

    Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

  19. Gp120/CD4 Blocking Antibodies Are Frequently Elicited in ART-Naïve Chronically HIV-1 Infected Individuals

    PubMed Central

    Carrillo, Jorge; Molinos-Albert, Luis Manuel; de la Concepción, Maria Luisa Rodríguez; Marfil, Silvia; García, Elisabet; Derking, Ronald; Sanders, Rogier W.; Clotet, Bonaventura; Blanco, Julià

    2015-01-01

    Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine. PMID:25803681

  20. Platelet leukocyte aggregates and markers of platelet aggregation, immune activation and disease progression in HIV infected treatment naive asymptomatic individuals.

    PubMed

    Nkambule, Bongani B; Davison, Glenda; Ipp, Hayley

    2015-11-01

    Platelet aggregates play a crucial role in the immune defence mechanism against viruses. Increased levels of lipopolysaccharide have been reported in human immunodeficiency virus (HIV) infected individuals. Platelets are capable of interacting with bacterial LPS and subsequently forming platelet leukocyte aggregates (PLAs). This study aimed at determining the levels of circulating PLAs in treatment naïve HIV infected individuals and correlating them, with markers of immune activation, disease progression and platelet aggregation. Thirty-two HIV negative and 35 HIV positive individuals were recruited from a clinic in the Western Cape. Platelet monocyte and platelet neutrophil aggregates were measured using flow cytometry at baseline and were correlated with markers of platelet activation (CD62P); aggregation (CD36); monocyte and neutrophil activation (CD69); monocyte tissue factor expression (CD142); immune activation (CD38 on T+ cells); D-dimers (a marker of active coagulation); CD4 count and viral load. Platelet monocyte aggregates were also measured post stimulation with lipopolysaccharide. PMA levels were higher in HIV 25.26 (16.16-32.28) versus control 14.12 (8.36-18.83), p = 0.0001. PMAs correlated with %CD38/8 expression (r = 0.54624, p = 0.0155); CD4 count (r = -0.6964, p = 0.0039) viral load (r = 0.633, p < 0.009) and monocyte %CD69 expression (r = 0.757, p = 0.030). In addition the %PMAs correlated with platelet %CD36 (r = 0.606, p = 0.017). The HIV group showed increased levels of %CD62P 5.44 (2.72-11.87) versus control 1.15 (0.19-3.59), p < 0.0001; %CD36 22.53 (10.59-55.15) versus 11.01 (3.69-26.98), p = 0.0312 and tissue factor (CD142) MFI 4.84 (4.01-8.17) versus 1.74 (1.07-9.3), p = 0.0240. We describe increased levels of circulating PMAs which directly correlates with markers of immune activation, disease progression and platelet aggregation in HIV treatment naïve individuals.

  1. Detection of SENV Virus in Healthy, Hepatitis B- and Hepatitis C-Infected Individuals in Yazd Province, Iran

    PubMed Central

    Hosseini, Sayedeh Azimeh; Bouzari, Majid

    2016-01-01

    Background: SEN virus (SENV) is the latest virus proposed as a cause of unknown hepatitis cases. Among nine detected genotypes of the virus, genotypes D and H are more frequent in hepatitis cases of unknown origin. The aim of this study was to determine the frequency of SENV-D and SENV-H genotypes in the sera of healthy individuals and hepatitis B and C patients. Methods: Totally, 200 serum samples from healthy individuals as well as 50 hepatitis B and 50 hepatitis C patients were collected. Anti-HCV (hepatitis C virus), anti-human immunodeficiency virus, hepatitis B surface antigen and anti-HBV (hepatitis B virus) core antigen were detected, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Viral DNA was subjected to nested PCR. Fisher's exact and unpaired ANOVA tests were used for statistical analyses. Results: SENV was detected in 90%, 66%, and 46% of the healthy individuals HBV and HCV-positive individuals, respectively. The frequency of SENV and its two genotypes were significantly lower in hepatitis B and hepatitis C patients (P<0.01). Also, the frequency of SENV-H was higher than SENV-D in all studied groups. In SENV-positive HBV patients, the level of ALT and AST enzymes were significantly less than SENV-negative patients (P<0.05). It was the same for SENV-H-negative and -positive cases. Conclusions: The levels of liver enzymes were significantly lower in HBV patients co-infected with SENV compared to HBV patients (P<0.05), indicating a positive impact of the virus in liver pathology by decreasing liver damage and thus decreasing the liver enzymes. PMID:26948255

  2. Association of the HLA-B*52 allele with non-progression to AIDS in Brazilian HIV-1-infected individuals.

    PubMed

    Teixeira, S L M; de Sá, N B R; Campos, D P; Coelho, A B; Guimarães, M L; Leite, T C N F; Veloso, V G; Morgado, M G

    2014-04-01

    Several human leukocyte antigen (HLA) class I alleles are associated with the susceptibility to human immunodeficiency virus-1 (HIV-1) infection and/or AIDS progression. Of these, the HLA-B alleles are considered the strongest genetic determinant of disease outcome. We evaluated the influence of the HLA-B alleles on AIDS progression among HIV-1-positive individuals from Rio de Janeiro, Brazil, who were categorized as rapid progressors (RPs), typical progressors (TPs) or long-term non-progressors (LTNPs). In this study, significant differences in HLA-B allele frequencies were observed among the three progression groups for the B*48, B*49 and B*52 alleles. After controlling for other factors associated with AIDS progression, the presence of the B*52 allele was shown to be a significant protective factor (hazard ratio (HR) 0.49 (95% confidence interval (CI) 0.27-0.90) P<0.03). Although no direct association was observed between the presence of the B*27 or B*57 allele and the LTNP profile compared with the TP or RP groups, the adjusted model confirmed that these alleles are protective factors against AIDS progression (HR 0.62 (95% CI 0.38-0.99) P<0.05), as previously described. These data corroborate the existence of significant differences in HLA-B allele frequencies among the distinct AIDS progression profiles and further elucidate the role of HLA alleles in the outcome of HIV infections in diverse populations.

  3. Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals

    SciTech Connect

    Gorny, Miroslaw K.; Pan, Ruimin; Williams, Constance; Wang, Xiao-Hong; Volsky, Barbara; O; Neal, Timothy; Spurrier, Brett; Sampson, Jared M.; Li, Liuzhe; Seaman, Michael S.; Kong, Xiang-Peng; Zolla-Pazner, Susan

    2012-05-18

    The recent analysis of the first successful RV144 vaccine trial revealed that a high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of HIV-1 infection in vaccine recipients. To understand the mechanism of immune correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1 infected individuals. The V2 mAbs target conserved epitopes, including the binding site for {alpha}4{beta}7 integrin, and are broadly cross-reactive with various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly neutralized four to eight of the 41 pseudoviruses tested and resistance to neutralization was correlated with longer V2 domains. The data suggest the presence of shared, conserved structural elements in the V2 loop, and these can be used in the design of vaccine immunogens inducing broadly reactive Abs with anti-viral activities.

  4. Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

    PubMed Central

    Périssé, André R. S.; Smeaton, Laura; Chen, Yun; La Rosa, Alberto; Walawander, Ann; Nair, Apsara; Grinsztejn, Beatriz; Santos, Breno; Kanyama, Cecilia; Hakim, James; Nyirenda, Mulinda; Kumarasamy, Nagalingeswaran; Lalloo, Umesh G.; Flanigan, Timothy; Campbell, Thomas B.; Hughes, Michael D.

    2013-01-01

    Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients. PMID:24391801

  5. Infection.

    PubMed

    Miclau, Theodore; Schmidt, Andrew H; Wenke, Joseph C; Webb, Lawrence X; Harro, Janette M; Prabhakara, Ranjani; Shirtliff, Mark E

    2010-09-01

    Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections.

  6. Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014

    PubMed Central

    Tanuma, Junko; Lee, Kyu Ha; Haneuse, Sebastien; Matsumoto, Shoko; Nguyen, Dung Thi; Nguyen, Dung Thi Hoai; Do, Cuong Duy; Pham, Thuy Thanh; Nguyen, Kinh Van; Oka, Shinichi

    2016-01-01

    Background Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings. Methods HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014. Results Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03–75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8–54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months. Conclusion ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up. PMID:26939050

  7. HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence.

    PubMed

    Moore, David J; Posada, Carolina; Parikh, Mili; Arce, Miguel; Vaida, Florin; Riggs, Patricia K; Gouaux, Ben; Ellis, Ronald J; Letendre, Scott L; Grant, Igor; Atkinson, J Hampton

    2012-11-01

    The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD- persons. Classification of adherent (≥ 90%) or non-adherent (<90%) based on proportion of correctly taken doses over 30 days was determined using electronic medication monitoring devices. HIV+/BD+ persons were significantly less likely to be ART adherent (47.7%) as compared to HIV+/BD- (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed.

  8. Interventions to improve psychological functioning and health outcomes of HIV-infected individuals with a history of trauma or PTSD.

    PubMed

    Seedat, Soraya

    2012-12-01

    The experience of early or later life trauma in HIV-positive adults can have devastating mental and physical health consequences. Women bear the brunt of this double burden. Depression, posttraumatic stress disorder, and alcohol and drug use disorders are among the most common psychiatric disorders documented, both in infected women and men, in high-, middle-, and low-income countries. Traumatized individuals, particularly those with childhood sexual abuse characterized by repeated traumatization, are at high risk of engaging in risky behaviors, including substance abuse and sexual promiscuity. These issues are further compounded by stigma, discrimination, poverty, and low social support. While there is a significant need to pay more attention to psychiatric and psychological outcomes in the context of HIV-trauma and improve screening for traumatic stress in HIV care settings, there are currently few treatment and secondary prevention studies. Group cognitive-behavioral strategies, including prolonged exposure, coping skills training, and stress management have, to date, shown some evidence for efficacy in HIV-positive individuals with childhood trauma and in those with PTSD.

  9. Temporal variation in individual factors associated with hantavirus infection in bank voles during an epizootic: implications for Puumala virus transmission dynamics.

    PubMed

    Tersago, Katrien; Verhagen, Ron; Leirs, Herwig

    2011-06-01

    Puumala virus (PUUV), the causal agent of nephropathia epidemica in humans, is one of the many hantaviruses included in the list of emerging pathogens. Hantavirus infection is not distributed evenly among PUUV reservoir hosts (i.e., bank voles [Myodes glareolus]). Besides environmental factors and local population features, individual characteristics play an important role in vole PUUV infection risk. Identifying the relative importance of these individual characteristics can provide crucial information on PUUV transmission processes. In the present study, bank voles were monitored during the nephropathia epidemica outbreak of 2005 in Belgium. Vole sera were tested for presence of immunoglobulin G against PUUV, and a logistic mixed model was built to investigate the temporal variation in individual characteristics and their relative importance to PUUV infection risk in bank voles. Relative risk calculations for individual vole characteristics related to PUUV infection in the reservoir host show that reproductive activity dominates infection risk. The gender effect is only found in reproductively active voles, where reproductively active males have the highest infection risk. Results also revealed a clear seasonal variation in the importance of reproductive activity linked to PUUV infection. In contrast to the main effect found in other trapping sessions, no difference in infection risk ratio was found between reproductively active and nonactive voles in the spring period. Combined with increased infection risk for the reproductively nonactive group at that time, these results indicate a shift in the transmission process due to changes in bank vole behavior, physiology, or climate conditions. Hence, our results suggest that mathematical models should take into account seasonal shifts in transmission mechanisms. When these results are combined with the seasonal changes in population structure during the epizootic period, we identify vole reproductive activity and

  10. Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy.

    PubMed

    Focà, Emanuele; Magro, Paola; Motta, Davide; Compostella, Silvia; Casari, Salvatore; Bonito, Andrea; Brianese, Nigritella; Ferraresi, Alice; Rodari, Paola; Pezzoli, Maria Chiara; Quiros-Roldan, Eugenia; Castelli, Francesco

    2016-01-01

    Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis. PMID:27023519

  11. Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy

    PubMed Central

    Focà, Emanuele; Magro, Paola; Motta, Davide; Compostella, Silvia; Casari, Salvatore; Bonito, Andrea; Brianese, Nigritella; Ferraresi, Alice; Rodari, Paola; Pezzoli, Maria Chiara; Quiros-Roldan, Eugenia; Castelli, Francesco

    2016-01-01

    Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD—standard deviation—3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis. PMID:27023519

  12. Coreceptor Usage, Diversity, and Divergence in Drug-Naive and Drug-Exposed Individuals from Malawi, Infected with HIV-1 Subtype C for More Than 20 Years

    PubMed Central

    Seager, Ishla; Travers, Simon A.; Leeson, Michael D.; Crampin, Amelia C.; French, Neil; Glynn, Judith R.

    2014-01-01

    Abstract There are few cohorts of individuals who have survived infection with HIV-1 for more than 20 years, reported and followed in the literature, and even fewer from Africa. Here we present data on a cohort of subtype C-infected individuals from rural northern Malawi. By sequencing multiple clones from long-term survivors at different time points, and using multiple genotyping approaches, we show that 5 of the 11 individuals are predicted as CXCR4 using (by ≥3/5 predictors) but only one individual is predicted as CXCR4 using by all five algorithms. Using any one genotyping approach overestimates the number of predicted CXCR4 sequences. Patterns of diversity and divergence were variable between the HIV-1 long-term survivors with some individuals showing very small amounts of variation and change, and others showing a greater amount; both patterns are consistent with what has been described in the literature. PMID:24925099

  13. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    PubMed Central

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  14. Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

    PubMed Central

    Pickering, Suzanne; Hué, Stephane; Kim, Eun-Young; Reddy, Susheel; Wolinsky, Steven M.; Neil, Stuart J. D.

    2014-01-01

    The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-κB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-κB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy. PMID:24465210

  15. Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific

    PubMed Central

    Tanuma, Junko; Jiamsakul, Awachana; Makane, Abhimanyu; Avihingsanon, Anchalee; Ng, Oon Tek; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Kumarasamy, Nagalingeswaran; Nguyen, Kinh Van; Pham, Thuy Thanh; Lee, Man Po; Ditangco, Rossana; Merati, Tuti Parwati; Choi, Jun Yong; Wong, Wing Wai; Kamarulzaman, Adeeba; Yunihastuti, Evy; Sim, Benedict LH; Ratanasuwan, Winai; Kantipong, Pacharee; Zhang, Fujie; Mustafa, Mahiran; Saphonn, Vonthanak; Pujari, Sanjay; Sohn, Annette H.

    2016-01-01

    Background In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use. Methods We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression. Results Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62–1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52–11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22–3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17–0.85, p = 0.018). Conclusions Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region. PMID:27560968

  16. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2.

    PubMed

    Demissie, Abebech; Abebe, Markos; Aseffa, Abraham; Rook, Graham; Fletcher, Helen; Zumla, Alimuddin; Weldingh, Karin; Brock, Inger; Andersen, Peter; Doherty, T Mark

    2004-06-01

    The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.

  17. Increased Escherichia coli-Induced Interleukin-23 Production by CD16+ Monocytes Correlates with Systemic Immune Activation in Untreated HIV-1-Infected Individuals

    PubMed Central

    Manuzak, Jennifer A.; Dillon, Stephanie M.; Lee, Eric J.; Dong, Zachary M.; Hecht, Daniel K.

    2013-01-01

    The level of microbial translocation from the intestine is increased in HIV-1 infection. Proinflammatory cytokine production by peripheral antigen-presenting cells in response to translocated microbes or microbial products may contribute to systemic immune activation, a hallmark of HIV-1 infection. We investigated the cytokine responses of peripheral blood myeloid dendritic cells (mDCs) and monocytes to in vitro stimulation with commensal enteric Escherichia coli in peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected subjects and from uninfected controls. Levels of interleukin 23 (IL-23) produced by PBMC from HIV-1-infected subjects in response to E. coli stimulation were significantly higher than those produced by PBMC from uninfected subjects. IL-23 was produced primarily by CD16+ monocytes. This subset of monocytes was increased in frequency and expressed higher levels of Toll-like receptor 4 (TLR4) in HIV-1-infected individuals than in controls. Blocking TLR4 on total CD14+ monocytes reduced IL-23 production in response to E. coli stimulation. Levels of soluble CD27, an indicator of systemic immune activation, were elevated in HIV-1-infected subjects and were associated with the percentage of CD16+ monocytes and the induction of IL-23 by E. coli, providing a link between these parameters and systemic inflammation. Taken together, these results suggest that IL-23 produced by CD16+ monocytes in response to microbial stimulation may contribute to systemic immune activation in HIV-1-infected individuals. PMID:24067979

  18. Explaining variance of avian malaria infection in the wild: the importance of host density, habitat, individual life-history and oxidative stress

    PubMed Central

    2013-01-01

    Background Avian malaria (Plasmodium sp.) is globally widespread, but considerable variation exists in infection (presence/absence) patterns at small spatial scales. This variation can be driven by variation in ecology, demography, and phenotypic characters, in particular those that influence the host’s resistance. Generation of reactive oxygen species (ROS) is one of the host’s initial immune responses to combat parasitic invasion. However, long-term ROS exposure can harm the host and the redox response therefore needs to be adjusted according to infection stage and host phenotype. Here we use experimental and correlational approaches to assess the relative importance of host density, habitat composition, individual level variation and redox physiology for Plasmodium infection in a wild population of great tits, Parus major. Results We found that 36% of the great tit population was infected with Plasmodium (22% P. relictum and 15% P. circumflexum prevalence) and that patterns of infection were Plasmodium species-specific. First, the infection of P. circumflexum was significantly higher in areas with experimental increased host density, whereas variation in P. relictum infection was mainly attributed to age, sex and reproduction. Second, great tit antioxidant responses – total and oxidizied glutathione - showed age- , sex- and Plasmodium species-specific patterns between infected and uninfected individuals, but reactive oxygen metabolites (ROM) showed only a weak explanatory power for patterns of P. relictum infection. Instead ROM significantly increased with Plasmodium parasitaemia. Conclusions These results identify some key factors that influence Plasmodium infection in wild birds, and provide a potential explanation for the underlying physiological basis of recently documented negative effects of chronic avian malaria on survival and reproductive success. PMID:23565726

  19. Predictors of New Onset Distal Neuropathic Pain in HIV-infected Individuals in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Malvar, Jemily; Vaida, Florin; Sanders, Chelsea Fitzsimons; Atkinson, J. Hampton; Bohannon, William; Keltner, John; Robinson-Papp, Jessica; Simpson, David M.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin; Fan, Juanjuan; Grant, Igor; Ellis, Ronald J.

    2015-01-01

    Despite modern combination antiretroviral therapy (CART), distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semi-annual clinical evaluations were administered at six U.S. sites. DNP was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New onset DNP was recorded at the first follow-up visit at which it was reported. Mixed effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2,306 visits during a median follow-up of 24 months [interquartile range (IQR) 12-42]. In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a prior history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood. PMID:25659067

  20. Chronic Burkholderia multivorans bronchial infection in a non-cystic fibrosis individual with mannose binding lectin deficiency

    PubMed Central

    Whitehouse, J; Exley, A; Foweraker, J; Bilton, D

    2005-01-01

    The case history is presented of a woman with multiple respiratory infections and mannose binding lectin (MBL) deficiency but no evidence of bronchiectasis who developed a chronic Burkholderia multivorans infection. Careful microbiological assessment is needed in patients with recurrent respiratory infection and the presence of B multivorans should trigger further immunological investigation including assessment of MBL status. PMID:15681508

  1. Incidence of Pancreatitis in HIV-1–Infected Individuals Enrolled in 20 Adult AIDS Clinical Trials Group Studies

    PubMed Central

    Reisler, Ronald B.; Murphy, Robert L.; Redfield, Robert R.; Parker, Robert A.

    2005-01-01

    Objective To report on the incidence of clinical- and laboratory-defined pancreatitis in HIV-1–infected individuals treated with antiretrovirals (ARVs). Methods Pancreatitis incidence rates were calculated based on a Poisson distribution for subjects enrolled in 1 or more of 20 Adult AIDS Clinical Trials Group studies from October 1989 through July 1999. Results A total of 8451 subjects were enrolled. The overall pancreatitis rates were 0.61 per 100 person-years (PYs) clinical and 2.23 per 100 PYs clinical/laboratory. Pancreatitis rates for single, dual, and triple nucleoside reverse transcriptase inhibitors (NRTIs) were similar. Rates of pancreatitis in didanosine (ddI) arms seemed to be dose dependent. Pancreatitis rates in ddI/hydroxyurea (HU) arms were not significantly different from the rates for ddI alone. Overall pancreatitis rates for ddI/stavudine (d4T) trials were high at 4.16 per 100 PYs clinical and 6.25 per 100 PYs clinical/laboratory. The highest rates were seen with the combination of indinavir (IDV)/ddI/d4Twith or without HU. Conclusions The combination of NRTIs and definition has an impact on the incidence of pancreatitis. Standardization of definition and more comprehensive evaluations are needed to determine how much of this pancreatitis is directly caused by ARVs and how much is attributable to preexisting comorbidities and other known risk factors. PMID:15905731

  2. Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid.

    PubMed

    Souza, Anselmo; Santos, Silvane; Carvalho, Lucas P; Grassi, Maria Fernanda R; Carvalho, Edgar M

    2016-08-01

    T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination. PMID:27282836

  3. Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid.

    PubMed

    Souza, Anselmo; Santos, Silvane; Carvalho, Lucas P; Grassi, Maria Fernanda R; Carvalho, Edgar M

    2016-08-01

    T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination.

  4. Association of inflammatory cytokines and endothelial adhesion molecules with immunological, virological, and cardiometabolic disease in HIV-infected individuals.

    PubMed

    Lacerda, Heloísa Ramos; Falcão, Maria da Conceição Correia; de Albuquerque, Valéria Maria Gonçalves; Zírpoli, Josefina Claudia; Miranda-Filho, Demócrito de Barros; de Albuquerque, Maria de Fátima Pessoa Militão; Montarroyos, Ulisses; Ximenes, Ricardo Arraes de Alencar

    2014-05-01

    Elevated levels of inflammatory and endothelial biomarkers are related to chronic diseases, cancers, and cardiovascular disease. This study aimed at evaluating the association of inflammatory cytokines and endothelial adhesion molecules with immunological, virological, and cardiometabolic disease in HIV-infected individuals. A cross-sectional study was initiated to evaluate the association of CD4 lymphocyte count, viral load, antiretroviral therapy, and metabolic and cardiovascular disease with inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α)], adhesion molecules [soluble intercellular Adhesion Molecule 1 (sICAM) and soluble Vascular Adhesion Molecule 1 (sVCAM)], and highsensitive C-reactive protein (hs-CRP) levels in 125 HIV-infected patients. The associations between independent variables and biomarkers were analyzed by means of multivariate logistic regression. A viral load ≥100,000 copies/mL had a stronger association with high levels of sVCAM-1 (P=0.026; OR=2.54; CI=1.12-5.78) and TNF-α (P=0.048; OR=2.42; CI=1.01-5.85) than the current viral load using a multivariate analysis. Antiretroviral treatment was associated with lower levels of sVCAM-1 (P=0.20; OR=0.20; CI=0.05-0.78), TNF-α (P=0.060; OR=0.22; CI=0.05-1.07), and hs-CRP (P=0.093; OR=0.44; CI=0.17-1.15). CD4 counts <200 cells/mm(3) were associated with high IL-6 levels (P=0.013; OR=3.17; CI=1.27-7.91); however, antiretroviral treatment was not associated with IL-6 levels. Metabolic syndrome was associated with high hs-CRP levels, systolic hypertension was associated with IL-6 levels, and family history of coronary disease was associated with TNF-α levels. High biomarker levels were associated not only with viral and immunological characteristics but also with cardiometabolic factors. The maximum viral load attained was an important risk factor for high levels of TNF-α and sVCAM-1. Treatment protected patients from high biomarker levels, except IL-6.

  5. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  6. Central nervous system penetration-effectiveness rank does not reliably predict neurocognitive impairment in HIV-infected individuals

    PubMed Central

    Libertone, Raffaella; Lorenzini, Patrizia; Balestra, Pietro; Pinnetti, Carmela; Ricottini, Martina; Maddalena Plazzi, Maria; Menichetti, Samanta; Zaccarelli, Mauro; Nicastri, Emanuele; Bellagamba, Rita; Ammassari, Adriana; Antinori, Andrea

    2014-01-01

    Introduction Central nervous system (CNS) penetration-effectiveness (CPE) rank was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS, and validated as predictor of CSF HIV-1 replication. Results on predictive role of CPE on neurocognitive and clinical outcome were conflicting. Materials and Methods Retrospective, cross-sectional analysis of neurocognitive profile in HIV-infected cART-treated patients. All patients underwent neuropsychological (NP) assessment by standardized battery of 14 tests on 5 different domains. People were classified as having NCI if they scored >1 standard deviation (SD) below the normal mean in at least two tests, or >2 SD below in one test. Linear and logistic regression analyses were fitted using as outcome Npz8 and impaired/not impaired respectively. Results A total of 660 HIV-infected cART-treated individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49 (IQR 43–56), male 82%; median current CD4 586/mm3; 18% HCV infected; HIV-RNA <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in 32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5–6.7). As per test multivariable analysis, higher CPE values were associated to poor NP tasks (Beta=−0,09; 95% CI −0,14 −0,03; p=0.002 at multivariable linear regression). The association between higher CPE and increased NCI risk was confirmed at multivariable logistic regression, with a 1.24-fold risk of NCI occurrence for each point increase of CPE of current regimen at the time of NP testing (see Table 1). In a sensitivity analysis performed only on patients at the first NP test, the association between higher CPE and poor NP tasks and enhanced NCI risk was only marginally confirmed (Beta=−0,05; [−0,12–0,02]; p=0,19; OR 1,13 [0,95–1,34]; p=0.17). Older age, longer time from HIV diagnosis, current CD4 count <350 cell/mm3 and lower education level were all associated to an increased risk of

  7. Intra-individual variability across neurocognitive domains in chronic hepatitis C infection: elevated dispersion is associated with serostatus and unemployment risk.

    PubMed

    Morgan, Erin E; Woods, Steven Paul; Rooney, Alexandra; Perry, William; Grant, Igor; Letendre, Scott L

    2012-01-01

    Approximately one-third of persons infected with the hepatitis C virus (HCV) evidence mild cognitive impairment that is consistent with frontostriatal systems dysfunction, including cognitive dyscontrol, and impacts everyday functioning. The present study examined the effects of HCV on neurocognitive dispersion, or within-person variability in neurocognitive performance across domains, which may be a function of poor sustained cognitive control. High dispersion was also hypothesized to increase risk for unemployment. The study sample included 37 individuals with HCV infection (HCV+) and 45 demographically comparable uninfected comparison participants (HCV-). Dispersion was operationalized as an intra-individual standard deviation (ISD) calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests. Multiple linear regression and logistic regression approaches were used to evaluate associations between dispersion and HCV serostatus and employment status, respectively. HCV serostatus was significantly associated with higher dispersion, independent of mean level of neurocognitive ability, psychiatric factors, and liver disease severity. Within the HCV+ group, higher dispersion was associated with an increased risk of unemployment among individuals with higher overall mean neurocognitive ability. Increased neurocognitive dispersion among HCV+ individuals may indicate vulnerability to cognitive dyscontrol expressed as poor regulation of performance across tasks. Higher dispersion may manifest as functional difficulties in daily life, particularly among neurocognitively normal HCV-infected persons, which speaks to the potential clinical value of considering intra-individual variability when evaluating risk for everyday function problems in this population.

  8. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  9. High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did not develop symptoms

    PubMed Central

    2013-01-01

    Background Plasmodium vivax has the potential to infect 2.85 billion individuals worldwide. Nevertheless, the limited number of studies investigating the immune status of individuals living in malaria-endemic areas, as well as the lack of reports investigating serological markers associated with clinical protection, has hampered development of vaccines for P. vivax. It was previously demonstrated that naturally total IgG against the N-terminus of P. vivax merozoite surface protein 1 (Pv-MSP1) was associated with reduced risk of malarial infection. Methods Immune response against Pv-MSP1 (N-terminus) of 313 residents of the Rio Pardo rural settlement (Amazonas State, Brazil) was evaluated in a cross-sectional and longitudinal follow up over two months (on site) wherein gold standard diagnosis by thick blood smear and rRNA gene-based nested real-time PCR were used to discriminate symptomless Plasmodium vivax-infected individuals who did not develop clinical symptoms during a 2-months from those uninfected ones or who have had acute malaria. The acquisition of antibodies against Pv-MSP1 was also evaluated as survival analysis by prospective study over a year collecting information of new malaria infections in surveillance database. Results The majority of P. vivax-infected individuals (52-67%) showed immune recognition of the N-terminus of Pv-MSP1. Interesting data on infected individuals who have not developed symptoms, total IgG levels against the N-terminus Pv-MSP1 were age-dependent and the IgG3 levels were significantly higher than levels of subjects had acute malaria or those uninfected ones. The total IgG anti ICB2-5 was detected to be an important factor of protection against new malaria vivax attacks in survival analysis in a prospective survey (p = 0.029). Conclusions The study findings illustrate the importance of IgG3 associated to 2-months of symptomless in P. vivax infected individuals and open perspectives for the rationale of malaria vaccine

  10. CMV Latent Infection Improves CD8+ T Response to SEB Due to Expansion of Polyfunctional CD57+ Cells in Young Individuals

    PubMed Central

    Pera, Alejandra; Campos, Carmen; Corona, Alonso; Sanchez-Correa, Beatriz; Tarazona, Raquel; Larbi, Anis; Solana, Rafael

    2014-01-01

    Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality ―degranulation (CD107a), IFN-gamma and TNF-alpha production―, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB). Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57− cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing

  11. CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals.

    PubMed

    Pera, Alejandra; Campos, Carmen; Corona, Alonso; Sanchez-Correa, Beatriz; Tarazona, Raquel; Larbi, Anis; Solana, Rafael

    2014-01-01

    Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a), IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB). Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing pro

  12. Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite.

    PubMed

    Stanisic, Danielle I; Gerrard, John; Fink, James; Griffin, Paul M; Liu, Xue Q; Sundac, Lana; Sekuloski, Silvana; Rodriguez, Ingrid B; Pingnet, Jolien; Yang, Yuedong; Zhou, Yaoqi; Trenholme, Katharine R; Wang, Claire Y T; Hackett, Hazel; Chan, Jo-Anne A; Langer, Christine; Hanssen, Eric; Hoffman, Stephen L; Beeson, James G; McCarthy, James S; Good, Michael F

    2016-09-01

    Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.

  13. Effect of cytokine level variations in individuals on the progression and outcome of bacterial urogenital infections--a meta-analysis.

    PubMed

    Singer, Martin; Ouburg, Sander

    2016-03-01

    Bacterial urogenital infections such as chlamydia, gonorrhoea and syphilis are widespread inflammatory diseases, which may be accompanied by severe complications. These complications can range from basic inflammation to tubal pathology, infertility and neurological dysfunction, though infections go unnoticed in the majority of cases. Cytokines in the host play a vital role in both the initial and long-term immune response and inflammation. However, levels of cytokine expression vary between individuals. A meta-analysis was performed to evaluate the effect of cytokine expression differences on severity of infections with these pathogens. Studies comparing expression of cytokines in humans with inflammation or inflammation-based complications were identified using NCBI, Google Scholar and Cochrane databases. Only studies into human cytokine expressions were included, and three articles per subject were required to be suitably analysed during meta-analysis. A total of 52 articles were included for meta-analysis. It was shown that differences in IL-1, IL-6, IL-8, IL-10, TNFα and IFNγ affect the clinical outcome of Chlamydia trachomatis infection significantly. Similarly, IL-1 and IL-8 expression during Neisseria gonorrhoeae infection significantly affects the outcome of the disease. For Treponema pallidum infection, it was shown that IFNγ variation in hosts could be linked to severity of disease. However, a lack of studies to use in the meta-analysis and fluctuation in the resulting data depending on the adjustments makes adequate evaluation difficult. PMID:26733496

  14. West Nile alternative open reading frame (N-NS4B/WARF4) is produced in infected West Nile Virus (WNV) cells and induces humoral response in WNV infected individuals

    PubMed Central

    2012-01-01

    Background West Nile Virus (WNV) is a flavivirus that requires an efficient humoral and cellular host response for the control of neuroinvasive infection. We previously reported the existence of six alternative open reading frame proteins in WNV genome, one of which entitled WARF4 is exclusively restricted to the lineage I of the virus. WARF4 is able to elicit antibodies in WNV infected horses; however, there was no direct experimental proof of the existence of this novel protein. The purpose of this study was to demonstrate the in vitro production of WARF4 protein following WNV infection of cultured VERO cells and its immunity in WNV infected individuals. Results We produced a monoclonal antibody against WARF4 protein (MAb 3A12) which detected the novel protein in WNV lineage I-infected, cultured VERO cells while it did not react with WNV lineage II infected cells. MAb 3A12 specificity to WARF4 protein was confirmed by its reactivity to only one peptide among four analyzed that cover the full WARF4 amino acids sequence. In addition, WARF4 protein was expressed in the late phase of WNV lineage I infection. Western blotting and bioinformatics analyses strongly suggest that the protein could be translated by programmed −1 ribosomal frameshifting process. Since WARF4 is embedded in the NS4B gene, we rename this novel protein N-NS4B/WARF4. Furthermore, serological analysis shows that N-NS4B/WARF4 is able to elicit antibodies in WNV infected individuals. Conclusions N-NS4B/WARF4 is the second Alternative Reading Frame (ARF) protein that has been demonstrated to be produced following WNV infection and might represent a novel tool for a better characterization of immune response in WNV infected individuals. Further serological as well as functional studies are required to characterize the function of the N-NS4B/WARF4 protein. Since the virus might actually make an extensive use of ARFs, it appears important to investigate the novel six ARF putative proteins of WNV. PMID

  15. Newly Deployed Sojourner Rover

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This 8-image mosaic was acquired during the late afternoon (near 5pm LST, note the long shadows) on Sol 2 as part of the predeploy 'insurance panorama' and shows the newly deployed rover sitting on the Martian surface. This color image was generated from images acquired at 530,600, and 750 nm. The insurance panorama was designed as 'insurance' against camera failure upon deployment. Had the camera failed, the losslessly-compressed, multispectral insurance panorama would have been the main source of image data from the IMP.

    However, the camera deployment was successful, leaving the insurance panorama to be downlinked to Earth several weeks later. Ironically enough, the insurance panorama contains some of the best quality image data because of the lossless data compression and relatively dust-free state of the camera and associated lander/rover hardware on Sol 2.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal investigator.

  16. Absence of Pneumocystis jirovecii Colonization in Human Immunodeficiency Virus-Infected Individuals With and Without Airway Obstruction and With Undetectable Viral Load.

    PubMed

    Ronit, Andreas; Klitbo, Ditte Marie; Kildemoes, Anna Overgaard; Benfield, Thomas; Gerstoft, Jan; Vestbo, Jørgen; Jensen, Jørgen Skov; Kurtzhals, Jørgen; Nielsen, Susanne Dam

    2016-01-01

    Pneumocystis jirovecii colonization has been associated with non-acquired immune deficiency syndrome (AIDS) pulmonary comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (PCR), targeting the large mitochondrial ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein. Pneumocystis jirovecii deoxyribonucleic acid (DNA) was detected in 1 of 156 (95% confidence interval, .1%-3.5%) virologically suppressed human immunodeficiency virus (HIV)-infected individuals confirmed by all PCR methods. Thus, prevalence of P jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group of well treated HIV-infected individuals. PMID:27006967

  17. Differences in Antibody Responses of Individuals with Natural Infection and Those Vaccinated against Pandemic H1N1 2009 Influenza▿

    PubMed Central

    Chan, Kwok-Hung; To, Kelvin K. W.; Hung, Ivan F. N.; Zhang, Anna J. X.; Chan, Jasper F. W.; Cheng, Vincent C. C.; Tse, Herman; Che, Xiao-Yan; Chen, Honglin; Yuen, Kwok-Yung

    2011-01-01

    The differential antibody response measured by the commonly used hemagglutination inhibition (HI) and microneutralization (MN) assays in patients with natural infection and vaccination has not been fully assessed. HI and conventional MN (CMN) assays were performed on sera from 651 patients with natural infection by pandemic H1N1 2009 influenza virus and on sera from 567 recipients of the corresponding vaccine. Surprisingly, the overall seroprotection rates determined by CMN and HI assays in vaccine recipients were only 44.8 and 35.1%, respectively. Antibody titers measured by the CMN assay was significantly higher than that obtained by HI assay in vaccine recipients aged ≥50 years, but these titers were not significantly different among younger vaccine recipients. In contrast, the HI titer was greater than the CMN titer for the age group from 16 to 29 years but was not significantly different in other age groups for natural infection. Lower antibody levels were found in both naturally infected patients and immunized recipients in the older than in the younger age groups, but naturally infected patients exhibited higher HI and CMN titers than did the corresponding vaccine recipients. In addition, we developed a rapid fluorescent focus microneutralization (FFMN) assay to test sera from naturally infected patients. The FFMN assay has a better correlation with CMN than with HI (ρ = 0.810 versus 0.684), which is expected of neutralizing antibody mainly targeted toward the inhibition of viral entry into cells. The higher antibody level elicited by natural infection than by vaccination may be related to differences between antigen presentation by the intramuscular route of vaccination and mucosal viral replication in mucosal cells of the respiratory tract. PMID:21411604

  18. Individual Factors of Social Acceptance in Patients Infected With Human Immunodeficiency Virus (HIV) at the Yazd Behavioral Consultation Center in Iran

    PubMed Central

    Bidaki, Reza; Mousavi, Seyed Mahdi; Bashardoust, Nasrollah; Sabouri Ghannad, Masoud; Dashti, Naser

    2016-01-01

    Background: A considerable number of patients infected with HIV also have mental health problems. Individual psychotherapy is an effective way to treat these issues. Lack of social acceptance is a barrier to patients receiving proper medication and emotional/psychological support. Objectives: The purpose of this study was to examine the individual factors of social acceptance in patients infected with human immunodeficiency virus. Patients and Methods: Fifty HIV-infected patients who were registered in the Behavioral Consultation Center entered the study. Each of them filled out a questionnaire based on the Crown-Marlow social acceptance scale. Their answers were evaluated according to the questionnaire key. Results: Forty-five patients (90%) were male and five (10%) were female. Their ages ranged between 28 and 52 years old. Other variables researched in this study include patients’ age, sex, education, occupation, place of living, marital status, family history of HIV, and family history of psychological disorders. Employed patients experienced more social acceptance than housewives and people who were unemployed or retired. Conclusions: This study showed that HIV-infected patients with jobs enjoy a great deal of acceptance from the people around them and a higher quality of life in general. It also led to suggestions for further study with the purpose of finding more effective solutions for HIV prevention and better strategies for dealing with psychological disorders. Such research could also help in providing an enhanced understanding of the potential psychological impact that AIDS has on patients in Iran. PMID:27218064

  19. How Many HIV infections may be averted by targeting primary infection in men who have sex with men? Quantification of changes in transmission-risk behavior, using an individual-based model.

    PubMed

    White, Peter J; Fox, Julie; Weber, Jonathan; Fidler, Sarah; Ward, Helen

    2014-12-01

    In the United Kingdom, human immunodeficiency virus (HIV) transmission among men who have sex with men (MSM) is not under control, despite readily available treatment, highlighting the need to design a cost-effective combination prevention package. MSM report significantly reduced transmission risk behavior following HIV diagnosis. To assess the effectiveness of HIV diagnosis in averting transmission during highly infectious primary HIV infection (PHI), we developed a stochastic individual-based model to calculate the number of HIV-transmission events expected to occur from a cohort of recently infected MSM with and those without the behavior changes reported after diagnosis. The model incorporates different types of sex acts, incorporates condom use, and distinguishes between regular and casual sex partners. The impact on transmission in the 3 months after infection depends on PHI duration and testing frequency. If PHI lasts for 3 months and testing is performed monthly, then behavior changes after diagnosis would have reduced estimated transmission events by 49%-52%, from 31-45 to 15-23 events; a shorter duration of PHI and/or a lower testing frequency reduces the number of infections averted. Diagnosing HIV during PHI can markedly reduce transmission by changing transmission-risk behavior. Because of the high infectivity but short duration of PHI, even short-term behavior change can significantly reduce transmission. Our quantification of the number of infections averted is an essential component of assessment of the cost-effectiveness of strategies to increase detection and diagnoses of PHI. PMID:25381380

  20. Depression longitudinally mediates the association of appearance concerns to ART non-adherence in HIV-infected individuals with a history of injection drug use.

    PubMed

    Blashill, Aaron J; Gordon, Janna R; Safren, Steven A

    2014-02-01

    Appearance concerns are common among HIV-infected individuals, and previous cross-sectional and longitudinal data indicate that these concerns are associated with antiretroviral therapy (ART) non-adherence. However, to date, no known prospective data have explored the mechanism behind this relationship. Thus, the aim of the current study was to test depression severity as a prospective mediator of the relationship between appearance concerns and ART non-adherence in HIV-infected individuals with a history of injection drug use (IDU). Participants were 89 HIV-infected individuals with a history of IDU who participated in a prospective, randomized controlled trial of cognitive behavioral therapy for depression and medication adherence. Clinician-administered measures of depression severity and appearance concerns, along with electronic monitoring of ART non-adherence were included. Data were analyzed using longitudinal linear mixed-level modeling, and mediation was tested via the Monte Carlo Method of Assessing Mediation. Appearance concerns were predictive of depression severity, γ = .31, SE = .076, 95 % CI [.16, .46], t = 4.1, p = .0001, and depression severity was predictive of ART non-adherence, γ = 3.3, SE = 1.3, 95 % CI [.8, 5.8], t = 2.6, p = .01. The effect of appearance concerns on ART non-adherence, however, was significantly mediated by depression severity, γ = 1.02, 95 % CI [.21, 2.1]. Appearance concerns are associated with depression severity, which in turn is associated with ART non-adherence. Integrative interventions addressing appearance concerns, depression and ART adherence are needed, as this is one potential pathway towards worse health outcomes in HIV-infected individuals.

  1. Valproic Acid Inhibits the Release of Soluble CD40L Induced by Non-Nucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus Infected Individuals

    PubMed Central

    Davidson, Donna C.; Schifitto, Giovanni; Maggirwar, Sanjay B.

    2013-01-01

    Despite the use of highly active antiretroviral therapies (HAART), a majority of Human Immunodeficiency Virus Type 1 (HIV) infected individuals continually develop HIV – Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistent with this notion, we have previously shown that levels of the inflammatory mediator soluble CD40 ligand (sCD40L) are elevated in the plasma and cerebrospinal fluid (CSF) of HIV infected, cognitively impaired individuals, and that excess sCD40L can contribute to blood brain barrier (BBB) permeability in vivo, thereby signifying the importance of this inflammatory mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) induces the release of circulating sCD40L in both HIV infected individuals and in an in vitro suspension of washed human platelets, which are the main source of circulating sCD40L. Additionally, EFV was found to activate glycogen synthase kinase 3 beta (GSK3β) in platelets, and we now show that valproic acid (VPA), a known GSK3β inhibitor, was able to attenuate the release of sCD40L in HIV infected individuals receiving EFV, and in isolated human platelets. Collectively these results have important implications in determining the pro-inflammatory role that some antiretroviral regimens may have. The use of antiretrovirals remains the best strategy to prevent HIV-associated illnesses, including HAND, however these drugs have clear limitations to this end, and thus, these results underscore the need to develop adjunctive therapies for HAND that can also minimize the undesired negative effects of the antiretrovirals. PMID:23555843

  2. High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

    PubMed Central

    Bedell, Richard A.; Anderson, Suzanne T. B.; van Lettow, Monique; Åkesson, Ann; Corbett, Elizabeth L.; Kumwenda, Moses; Chan, Adrienne K.; Heyderman, Robert S.; Zachariah, Rony; Harries, Anthony D.; Ramsay, Andrew R.

    2012-01-01

    Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations. PMID:22761767

  3. A Systematic Review of Individual and Contextual Factors Affecting ART Initiation, Adherence, and Retention for HIV-Infected Pregnant and Postpartum Women

    PubMed Central

    Hodgson, Ian; Plummer, Mary L.; Konopka, Sarah N.; Colvin, Christopher J.; Jonas, Edna; Albertini, Jennifer; Amzel, Anouk; Fogg, Karen P.

    2014-01-01

    Background Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women. Methods Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women), intervention (ART), and outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories. Results Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman’s awareness and control (e.g., commitment to child’s health or age). Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes. Conclusions To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in

  4. Plasmodium vivax infection in Anajás, State of Pará: no differential resistance profile among Duffy-negative and Duffy-positive individuals

    PubMed Central

    2012-01-01

    Background There is large body of evidence that states that invasion of Plasmodium vivax requires the Duffy antigen, but the universality of this specificity is certainly now under question with recent reports showing that in some parts of the world P. vivax infects and causes disease in Duffy-negative people. These findings reinforce the idea that this parasite is rapidly evolving, being able to use other receptors than Duffy to invade the erythrocytes, which may have an enormous impact in P. vivax current distribution. The presence of P. vivax infection in Duffy-negative individuals was investigated in a cross-sectional study conducted in Anajás, Archipelago of Marajó, State of Pará, which is an area of malaria transmission in the Brazilian Amazonia. Methods Duffy genotyping and Plasmodium species diagnostic assays were performed successfully in 678 individuals. An allele-specific primer polymerase chain reaction (PCR) technique was used for Duffy blood group genotyping. Identification of Plasmodium species was achieved by conventional blood smear light microscopy and a TaqMan-based real-time PCR method to detect mitochondrial genome of Plasmodium falciparum and P. vivax. Results Plasmodium spp. infection was detected in 137 samples (20.2%). Prevalence of each Plasmodium species was 13.9% P. vivax, 5.8% P. falciparum, and 0.6% P. vivax plus P. falciparum. Overall, 4.3% (29/678) were genotyped as Duffy-negative (FY*BES/*BES). Among Duffy-negative individuals 6.9% were P. vivax PCR positive and among Duffy-positive 14.2% were P. vivax PCR positive. Although lower, the risk of Duffy-negatives to experience a P. vivax blood stage infection was not significantly different to that of Duffy-positives. Furthermore, the genotypic and allelic frequencies of the Duffy blood group among P. vivax-infected patients and in the control group did not differ significantly, also suggesting no reduction in infection rates among the carriers of FY*BES allele. Conclusions The data

  5. Prevalence of Lymphatic Filariasis and Treatment Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-Tanzania

    PubMed Central

    Maganga, Lucas; Clowes, Petra; Maboko, Leonard; Hoerauf, Achim; Makunde, Williams H.; Haule, Antelmo; Mviombo, Prisca; Pitter, Bettina; Mgeni, Neema; Mabuye, Joseph; Kowuor, Dickens; Mwingira, Upendo; Malecela, Mwelecele N.; Löscher, Thomas; Hoelscher, Michael

    2016-01-01

    Background Annual mass treatment with ivermectin and albendazole is used to treat lymphatic filariasis in many African countries, including Tanzania. In areas where both diseases occur, it is unclear whether HIV co-infection reduces treatment success. Methodology In a general population study in Southwest Tanzania, individuals were tested for HIV and circulating filarial antigen, an indicator of Wuchereria bancrofti adult worm burden, before the first and after 2 consecutive rounds of anti-filarial mass drug administration. Principle Findings Testing of 2104 individuals aged 0–94 years before anti-filarial treatment revealed a prevalence of 24.8% for lymphatic filariasis and an HIV-prevalence of 8.9%. Lymphatic filariasis was rare in children, but prevalence increased in individuals above 10 years, whereas a strong increase in HIV was only seen above 18 years of age. The prevalence of lymphatic filariasis in adults above 18 years was 42.6% and 41.7% (p = 0.834) in HIV-negatives and–positives, respectively. Similarly, the HIV prevalence in the lymphatic filariasis infected (16.6%) and uninfected adult population (17.1%) was nearly the same. Of the above 2104 individuals 798 were re-tested after 2 rounds of antifilarial treatment. A significant reduction in the prevalence of circulating filarial antigen from 21.6% to 19.7% was found after treatment (relative drop of 8.8%, McNemar´s exact p = 0.036). Furthermore, the post-treatment reduction of CFA positivity was (non-significantly) larger in HIV-positives than in HIV-negatives (univariable linear regression p = 0.154). Conclusion/Significance In an area with a high prevalence for both diseases, no difference was found between HIV-infected and uninfected individuals regarding the initial prevalence of lymphatic filariasis. A moderate but significant reduction in lymphatic filariasis prevalence and worm burden was demonstrated after two rounds of treatment with albendazole and ivermectin. Treatment effects were

  6. National Trend and Characteristics of Acute Hepatitis C among HIV-Infected Individuals: A Matched Case-Control Study—Taiwan, 2001–2014

    PubMed Central

    Lo, Yi-Chun; Tsai, Mao-Song; Sun, Hsin-Yun; Hung, Chien-Ching; Chuang, Jen-Hsiang

    2015-01-01

    Background Hepatitis C virus (HCV) infection has been increasingly recognized among HIV-infected men who have sex with men (MSM) worldwide. We investigated the trend of and factors associated with acute hepatitis C (AHC) among HIV-infected individuals in Taiwan. Methods The National Disease Surveillance System collects characteristics of AHC, HIV, syphilis, and gonorrhea cases through mandatory reports and patient interviews. Reported AHC patients in 2014 were interviewed additionally on sexual and parenteral exposures. Information on HCV genotypes were collected from the largest medical center serving HIV-infected Taiwanese. We defined an HIV/AHC case as a documented negative HCV antibody test result followed within 12 months by a positive test in a previously reported HIV-infected individual. Each case was matched to two HIV-infected, non-AHC controls for age, age of HIV diagnosis, sex, transmission route, HIV diagnosis date, and county/city. Conditional logistic regression was used to identify associated characteristics. Results During 2001–2014, 93 of 6,624 AHC reports were HIV/AHC cases; the annual case count increased from one in 2009 to 34 in 2014. All were males (81 [87%] MSM) aged 21–49 years with AHC diagnosed 2–5,923 days after HIV diagnoses. Sixty-eight (73%) lived in the Taipei metropolitan area. Detected HCV genotypes were 2a (n = 6), 1b (n = 5), 1b + 2a (n = 1) and 2b (n = 1). Among 28 HIV/AHC patients interviewed in 2014, 13 (46%) reported engaging in unprotected sex ≤3 months before AHC diagnosis. Seventy-nine HIV/AHC cases were matched to 158 controls. HIV/AHC was associated with recent syphilis (adjusted odds ratio [aOR], 10.9; 95% confidence interval [CI], 4.2–28.6) and last syphilis >6 months (aOR, 2.9; 95% CI, 1.2–6.9). Conclusions HIV/AHC cases continued to increase particularly among sexually active HIV-infected MSM with a syphilis diagnosis in northern Taiwan. We recommend surveillance of associated behavioral and virologic

  7. Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.

    PubMed

    Riou, Catherine; Tanko, Ramla F; Soares, Andreia P; Masson, Lindi; Werner, Lise; Garrett, Nigel J; Samsunder, Natasha; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Burgers, Wendy A

    2015-09-01

    Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation. After ART initiation, the frequency of M. tuberculosis-specific CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were significantly lower (p = 0.003). There was no difference in the polyfunctional or memory profile of Ag-specific CD4(+) T cells before and after ART. The replenishment of Ag-specific CD4(+) T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion, restoration of copathogen-specific memory CD4(+) T cells during treated HIV infection is related to their memory phenotype, in which early differentiated cells (such as most M. tuberculosis-specific cells) have a higher replenishment capacity compared with late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of copathogen immunity in HIV-infected individuals on ART.

  8. Relationship between community-level alcohol outlet accessibility and individual-level HSV-2 infection among young women in South Africa

    PubMed Central

    Rosenberg, Molly; Pettifor, Audrey; Lippman, Sheri A.; Thirumurthy, Harsha; Emch, Michael; Miller, William C.; Selin, Amanda; Gómez-Olivé, F. Xavier; Hughes, James P.; Laeyendecker, Oliver; Tollman, Stephen; Kahn, Kathleen

    2015-01-01

    Background Exposure to alcohol outlets may influence sexual health outcomes at the individual- and community-level. Visiting alcohol outlets facilitates alcohol consumption and exposes patrons to a risky environment and network of potential partners, while presence of alcohol outlets in the community may shift social acceptance of riskier behavior. We hypothesize that living in communities with more alcohol outlets is associated with increased sexual risk. Methods We performed a cross-sectional analysis in a sample of 2,174 South African schoolgirls (ages 13–21) living across 24 villages in the rural Agincourt sub-district, underpinned by long-term health and socio-demographic surveillance. To examine the association between number of alcohol outlets in village of residence and individual-level prevalent HSV-2 infection, we used generalized estimating equations with logit links, adjusting for individual- and village-level covariates. Results The median number of alcohol outlets per village was three (range zero to seven). HSV-2 prevalence increased from villages with no outlets [1.4%, (95% CI: 0.2, 12.1)], to villages with one to four outlets [4.5% (3.7, 5.5)], to villages with more than four outlets [6.3% (5.6, 7.1)]. An increase of one alcohol outlet per village was associated with an 11% increase in odds of HSV-2 infection [adjusted odds ratio (95% CI): 1.11 (0.98, 1.25)]. Conclusions Living in villages with more alcohol outlets was associated with increased prevalence of HSV-2 infection in young women. Structural interventions and sexual health screenings targeting villages with extensive alcohol outlet environments could help prevent the spread of sexually transmitted infections. PMID:25868138

  9. Twenty-Five-Year Outbreak of Pseudomonas aeruginosa Infecting Individuals with Cystic Fibrosis: Identification of the Prairie Epidemic Strain

    PubMed Central

    Glezerson, Bryan A.; Sibley, Christopher D.; Sibley, Kristen A.; Duong, Jessica; Purighalla, Swathi; Mody, Christopher H.; Workentine, Matthew L.; Storey, Douglas G.; Surette, Michael G.; Rabin, Harvey R.

    2014-01-01

    Transmissible strains of Pseudomonas aeruginosa have been described for cystic fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive strain biobank spanning 3 decades, we sought to determine the prevalence and stability of chronic P. aeruginosa infection in an adult population. P. aeruginosa isolates from sputum samples collected at initial enrollment in our adult clinic and at the most recent clinic visit were examined by a combination of pulsed-field gel electrophoresis and multilocus sequence typing and compared against a collection of established transmissible and local non-CF bronchiectasis (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient-years, including 66 patients with matched isolates from initial and final encounters, were screened. A novel clone with increased antibacterial resistance, termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of chronically infected patients referred from multiple prairie-based CF centers. This isolate was not found in those diagnosed with CF as adults or in a control population with nCFB. While 90% (60/66 patients) of patients had stable infection over a mean of 10.8 years, five patients experienced strain displacement of unique isolates, with PES occurring within 2 years of transitioning to adult care. PES has been present in our cohort since at least 1987, is unique to CF, generally establishes chronic infection during childhood, and has been found in patients at the time of transition of patients from multiple prairie-based CF clinics, suggesting broad endemicity. Studies are under way to evaluate the clinical implications of PES infection. PMID:24452167

  10. Gastrointestinal viral load and enteroendocrine cell number are associated with altered survival in HIV-1 infected individuals.

    PubMed

    van Marle, Guido; Sharkey, Keith A; Gill, M John; Church, Deirdre L

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis. PMID:24146801

  11. Gastrointestinal Viral Load and Enteroendocrine Cell Number Are Associated with Altered Survival in HIV-1 Infected Individuals

    PubMed Central

    van Marle, Guido; Sharkey, Keith A.; Gill, M. John; Church, Deirdre L.

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis. PMID:24146801

  12. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

    PubMed Central

    Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T

    2009-01-01

    Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these

  13. Diagnostic performance of a cytokine and IFN-γ-induced chemokine mRNA assay after Mycobacterium tuberculosis-specific antigen stimulation in whole blood from infected individuals.

    PubMed

    Kim, Sunghyun; Lee, Hyejon; Kim, Hyunjung; Kim, Yeun; Cho, Jang-Eun; Jin, Hyunwoo; Kim, Dae Yeon; Ha, Sang-Jun; Kang, Young Ae; Cho, Sang-Nae; Lee, Hyeyoung

    2015-01-01

    Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and evaluated the assay with three different study groups. Results showed that the sensitivity of TNF-α, IL-2R, and CXCL10 in the active pulmonary tuberculosis (PTB) group was 96.43%, 96.43%, and 100%, respectively. The sensitivity of IL-2R and CXCL10 in the latent tuberculosis infection group was 86.36% and 81.82%, respectively. Statistical results showed that TNF-α and CXCL9 were the best individual markers for differentiating between the PTB, LTBI, and non-TB groups. For optimal sensitivity and differentiation of M. tuberculosis infection status, the simultaneous detection of multiple targets was attempted. The combination of IFN-γ, TNF-α, and IL-2R, and the combination of TNF-α, IL-2R, CXCL9, and CXCL10 showed the best performance for detecting active PTB (both 100% positivity) and LTBI (86.36% and 81.82% positivity, respectively). These results imply that the combination of suitable markers is useful in efficiently diagnosing TB and differentiating M. tuberculosis infection status.

  14. MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression

    PubMed Central

    Bargalló, Manel E.; Planet, Evarist; Vilaplana, Elisenda; Escribà, Tuixent; Pérez, Iñaki; Gatell, Josep Maria; García, Felipe; Arnedo, Mireia; Plana M, Montserrat

    2016-01-01

    Background The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. Methods miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms. Results A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response. Conclusions Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected

  15. Normal immune function and inability to isolate virus in culture in an individual with long-term human immunodeficiency virus type 1 infection.

    PubMed

    Greenough, T C; Somasundaran, M; Brettler, D B; Hesselton, R M; Alimenti, A; Kirchhoff, F; Panicali, D; Sullivan, J L

    1994-04-01

    A detailed, longitudinal study was undertaken to investigate the immunological and virological features of an individual with hemophilia infected with human immunodeficiency virus type-1 (HIV-1) for 10 years without disease. Methods applied to serial samples of peripheral blood included Western blot analysis, neutralizing antibody assays, antibody-dependent cell-mediated cytotoxicity (ADCC) titration, HIV-1 specific cytotoxic T lymphocyte (CTL) assays, viral cultures, and PCR with sequence analysis of viral regulatory genes. Strong antibody responses against HIV-1 antigens as measured by Western blot and ADCC assays have persisted throughout infection. Repeated attempts to isolate HIV-1 using sensitive culture techniques and to demonstrate viremia with standard PCR methods have failed. Using the "booster" PCR technique, a period of viremia in peripheral blood mononuclear cells was demonstrated. Concurrent with detection of circulating virus, titers of neutralizing antibodies and circulating HIV-1-specific CTLs became measurable. Sequencing studies of a portion of the viral genome showed no significant abnormalities of the regulatory genes. In this individual, the combination of low viral load in the peripheral blood and a strong, responsive immune system is associated with long-term, disease-free coexistence with HIV-1 infection.

  16. CCR5Δ32 Genotypes in a German HIV-1 Seroconverter Cohort and Report of HIV-1 Infection in a CCR5Δ32 Homozygous Individual

    PubMed Central

    Oh, Djin-Ye; Jessen, Heiko; Kücherer, Claudia; Neumann, Konrad; Oh, Nari; Poggensee, Gabriele; Bartmeyer, Barbara; Jessen, Arne; Pruss, Axel

    2008-01-01

    Background Homozygosity (Δ32/Δ32) for the 32 bp deletion in the chemokine receptor 5 (CCR5) gene is associated with strong resistance against HIV infection. Heterozygosity is associated with protection of HIV-1 disease progression. Methodology/Principal Findings We genotyped a population of 737 HIV-positive adults and 463 healthy controls for the CCR5Δ32 deletion and found heterozygous frequencies of 16.2% (HIV-negative) and 17.5% (HIV-positive) among Caucasian individuals. Analysis of CCR5Δ32 influence on disease progression showed notably lower viral setpoints and a longer time to a CD4 count of <200 µl−1 in seroconverters heterozygous for the deletion. Furthermore, we identified one HIV-positive man homozygous for the Δ32 deletion. Conclusions/Significance The protective effect of CCR5 Δ32 heterozygosity is confimed in a large cohort of German seroconverters. The HIV-infected CCR5 Δ32 homozygous individual, however, displays extremely rapid disease progression. This is the 12th case of HIV-infection in this genotype described worldwide. PMID:18648518

  17. The effect of HIV on filarial-specific antibody response before and after treatment with diethylcarbamazine in Wuchereria bancrofti infected individuals.

    PubMed

    Petersen, Heidi H; Nielsen, Nina O; Monrad, Jesper; Magesa, Stephen M; Simonsen, Paul E

    2009-06-01

    The effect of HIV on filarial-specific antibody response before and after treatment with diethylcarbamazine (DEC) was analysed by comparing two groups of Wuchereria bancrofti-infected adult individuals (positive for circulating filarial antigen) who were positive (n=15) or negative (n=21) for HIV co-infection. Prior to DEC treatment there was no significant difference in filarial-specific IgG1, IgG2, IgG4 and IgE antibody response between the HIV negative and the HIV positive group, while a five times (statistically significant) higher filarial-specific IgG3 response was observed in the HIV positive than in the HIV negative group. At 12 weeks after treatment with DEC, a significant decrease in filarial-specific IgG4 was observed in the HIV positive but not in the HIV negative group, indicating that DEC treatment had a stronger antifilarial effect in individuals co-infected with HIV. DEC treatment had no significant effect on the other classes of filarial specific antibodies, neither in the HIV negative or the HIV positive group. PMID:19567236

  18. The pharmacokinetics of lopinavir/ritonavir when given with isoniazid in South African HIV-infected individuals.

    PubMed

    Decloedt, E H; van der Walt, J S; McIlleron, H; Wiesner, L; Maartens, G

    2015-10-01

    Isoniazid preventive therapy is recommended in patients on antiretroviral treatment (ART) with latent tuberculous infection to prevent progression to active tuberculosis disease. Isoniazid (INH) inhibits cytochrome (CY) P3A4, which metabolises lopinavir (LPV). The administration of INH may cause higher LPV concentrations, which may increase LPV toxicity. LPV bioavailability is increased by co-formulated ritonavir (r), which may enhance the interaction of INH on LPV. We studied the effect of INH on LPV concentrations by administering INH for 7 days and performing intensive pharmacokinetic sampling in 16 human immunodeficiency virus infected patients established on LPV/r-based ART. INH did not significantly increase steady-state LPV area under the plasma concentration-time curve calculated for the 12 h-dosing interval.

  19. Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals.

    PubMed

    Hu, Haitao; Eller, Michael A; Zafar, Shah; Zhou, Yu; Gu, Mengnan; Wei, Zhi; Currier, Jeffrey R; Marovich, Mary A; Kibuuka, Hannah N; Bailer, Robert T; Koup, Richard A; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Ratto-Kim, Silvia

    2014-09-16

    Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3α and α4β7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies. PMID:25197078

  20. 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

  1. Prevalence of antibodies to Brucella spp. and individual risk factors of infection in traditional cattle, goats and sheep reared in livestock-wildlife interface areas of Zambia.

    PubMed

    Muma, J B; Samui, K L; Siamudaala, V M; Oloya, J; Matop, G; Omer, M K; Munyeme, M; Mubita, C; Skjerve, E

    2006-04-01

    A cross-sectional study was performed in the livestock-wildlife interface areas of Lochinvar and Blue Lagoon National Parks and the non-interface area of Kazungula to determine the prevalence of antibodies to Brucella spp. in domestic ruminants and identify individual animal risk factors of infection. A total of 1245 cattle from 124 herds and 280 goats and sheep from 29 flocks were tested sequentially for Brucella antibodies using the Rose Bengal test (RBT) and competitive ELISA. In cattle, individual seroprevalence ranged from 14.1% to 28.1%, while herd sero-prevalence ranged from 46.2% to 74.0% in the three study areas. No goat or sheep tested positive for Brucella antibodies. Three types of cattle grazing strategies were encountered: locally grazed herds (LGH), transhumantly grazed herds (TGH) and river flood plain grazed herds (FGH). Brucella seroprevalence was seen to vary according to area and grazing strategy: Lochinvar and transhumant grazed herds recorded the highest figures, respectively. Age, sex and history of abortion were found to have independent effects on individual seroprevalence. This study establishes that brucellosis is endemic in domestic animals in the livestock-wildlife interface areas of Blue Lagoon and Lochinvar national parks and the disease is also present in Kazungula. We observed that type of grazing strategy had significant impact on cattle Brucella seroprevalence and that transhumant herds were at high risk of being infected.

  2. Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

    PubMed Central

    2011-01-01

    Background Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. Methods We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. Results From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. Conclusion The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB. PMID:22176628

  3. The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals.

    PubMed

    Saito, Masaaki; Suzuki, Koichi; Maeda, Takafumi; Kato, Takaharu; Kamiyama, Hidenori; Koizumi, Kei; Miyaki, Yuichiro; Okada, Shinichiro; Kiyozaki, Hirokazu; Konishi, Fumio

    2012-06-01

    Helicobacter pylori (HP) infection is widely recognized as a risk factor for gastric cancer, but only a minority of infected individuals develop gastric cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer. A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals, as well as 83 patients with single and 18 with synchronous double gastric cancer (GC) were enrolled in this study. The relative demethylation levels (RDLs) of repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any differences within each respective group, whereas LINE-1 RDL was significantly elevated in cancer tissues compared with the NGM in the other groups (P<0.001). Our results indicated that a gradual increase in Sat α RDL correlated with HP infection and cancer development. Sat α RDL was significantly elevated in the NGM in HP-positive compared with HP-negative (P<0.001), and significantly elevated in cancer tissues (P<0.001). Although the Sat α RDL of the NGM in the total population increased in an age-dependent manner, it was significantly increased in a fraction of younger GC patients (<45 years) compared with all of the others (45 years or older, P=0.0391). In addition, double GC exhibited a significantly higher Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions, Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion, the present study demonstrated that the accumulation of DNA demethylation in Sat α RDL in the NGM with HP infection potentially renders susceptibility to gastric cancer in a fraction of GC patients younger than 45 years or in patients with multiple cancers. PMID:22426602

  4. Plasma and cerebrospinal fluid biomarkers predict cerebral injury in HIV-infected individuals on stable combination antiretroviral therapy

    PubMed Central

    Anderson, Albert M.; Harezlak, Jaroslaw; Bharti, Ajay; Mi, Deming; Taylor, Michael J.; Daar, Eric S.; Schifitto, Giovanni; Zhong, Jianhui; Alger, Jeffry R.; Brown, Mark S.; Singer, Elyse J.; Campbell, Thomas B.; McMahon, Deborah D.; Buchthal, Steven; Cohen, Ronald; Yiannoutsos, Constantin; Letendre, Scott L.; Navia, Bradford A.

    2015-01-01

    Objectives HIV-associated brain injury persists despite antiretroviral therapy (cART), but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy (MRS) in chronically HIV-infected subjects. Methods Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate+Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Predictive models were built via linear regression and the best models were chosen using the Akaike Information Criterion. Results Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG while metabolite changes in the FWM for NAA/Cr, GlxCr and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the three models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and MRS metabolites. Conclusions Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region dependent manner in chronically HIV-infected patients on stable cART. PMID:25622053

  5. Intravenous immunoglobulin (IVIG) treatment for modulation of immune activation in human immunodeficiency virus type 1 infected therapy-naive individuals.

    PubMed

    Vermeulen, Joost N; Prins, Jan M; Bunnik, Evelien; Hack, C Erik; Jurriaans, Suzanne; Miedema, Frank; Lange, Joep M A; Schuitemaker, Hanneke

    2007-11-01

    We evaluated the ability of intravenous immunoglobulin (IVIG) to diminish immune hyperactivation, which is considered a major cause of CD4+ T cell loss during chronic HIV-1 infection and whether this affected CD4+ T cell counts and plasma HIV-1 RNA (pVL). Therefore, we treated six chronically HIV-1-infected, antiretroviral-therapy-naive patients with IVIG (0.4 g/kg) at weeks 0 and 4, with a follow-up of 12 weeks after the second dosage during which pVL, T cell numbers, and T cell activation were measured. At baseline median CD4+ T cell counts were 300 (range 200-460) x 10(6)/liter and median pVL was 5.0 (range 3.2-5.2) log10 copies/ml. IgG plasma levels peaked during the first days after administration. We observed a decrease in the percentage of activated (CD38+ HLA-DR+) CD4+ and CD8+ T cells [3.5% (range 1-7%) and 5% (1-10%), respectively (p = 0.027)], but no effect on the fraction of proliferating CD4+ or CD8+ T cells as measured by Ki67 expression. CD4+ T cell counts were significantly increased on day 4 (median +55 cells, range 0-150, p = 0.043). pVL was significantly increased on day 1 after IVIG infusion (median +0.13 log10, range 0.01-0.55, p = 0.028). All these parameters returned to baseline levels within 1 week after infusion. In conclusion, administration of IVIG caused a temporary decrease in T cell activation and an increase in CD4+ T cell counts, despite an increase in pVL. Our results support the hypothesis that T cell activation, rather than direct HIV-1 infection, mediates the loss of CD4+ T cells and suggest that immunomodulating therapy in HIV-1 infection could indeed be effective.

  6. Eradication strategy for persistent methicillin-resistant Staphylococcus aureus infection in individuals with cystic fibrosis—the PMEP trial: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) respiratory infection in cystic fibrosis (CF) has increased dramatically over the last decade, and is now affecting approximately 25% of patients. Epidemiologic evidence suggests that persistent infection with MRSA results in an increased rate of decline in FEV1 and shortened survival. Currently, there are no conclusive studies demonstrating an effective and safe treatment protocol for persistent MRSA respiratory infection in CF. Methods/Design The primary objective of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation in combination with oral antibiotics in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. This is a two-center, randomized, double-blind, comparator-controlled, parallel-group study with 1:1 assignment to either vancomycin for inhalation (250 mg twice a day) or taste-matched placebo for 28 days in individuals with cystic fibrosis. In addition, both groups will receive oral rifampin, a second oral antibiotic – trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol determined – mupirocin intranasal cream, and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled: 20 will be randomized to vancomycin for inhalation and 20 to a taste-matched placebo. The primary outcome will be the presence of MRSA in sputum respiratory tract cultures 1 month after the conclusion of treatment. Secondary outcomes include the efficacy of the intervention on: FEV1% predicted, patient reported outcomes, pulmonary exacerbations, and MRSA colony-forming units found in respiratory tract sample culture. Discussion Results of this study will provide guidance to clinicians regarding the safety and effectiveness of a targeted eradication strategy for persistent MRSA infection in CF. Trial registration This trial is registered at Clinical

  7. Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark.

    PubMed

    Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Palm, Angelica A; Gerstoft, Jan; Kronborg, Gitte; Hønge, Bo Langhoff; Jespersen, Sanne; da Silva, Zacarias José; Karlsson, Ingrid; Fomsgaard, Anders

    2016-05-01

    The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine. PMID:26621287

  8. Hypertension, Cardiovascular Risk Factors and Anti-Hypertensive Medication Utilization among HIV-infected Individuals in Rakai, Uganda

    PubMed Central

    Sander, Laura D.; Newell, Kevin; Ssebbowa, Paschal; Serwadda, David; Quinn, Thomas C.; Gray, Ronald H.; Wawer, Maria J.; Mondo, George; Reynolds, Steven

    2014-01-01

    Objectives To assess the prevalence of hypertension, elevated blood pressure and cardiovascular risk factors among HIV-positive individuals in rural Rakai District, Uganda. Methods We assessed 426 HIV-positive individuals in Rakai, Uganda from 2007 to 2010. Prevalence of hypertension and elevated blood pressure assessed by clinical measurement was compared to clinician-recorded hypertension in case report forms. Multiple logistic regression and z-tests were used to examine the association of hypertension and elevated blood pressure with age, sex, body mass index, CD4 cell count, and anti-retroviral treatment (ART) use. For individuals on anti-hypertensives, medication utilization was reviewed. Results The prevalence of hypertension (two elevated blood pressure readings at different time points) was 8.0% (95% CI: 5.4–10.6%), and that of elevated blood pressure (one elevated blood pressure reading) was 26.3% (95% CI: 22.1–30.5%). Age ≥50 years and higher body mass index were positively associated with elevated blood pressure. ART use, time on ART, and CD4 cell count were not associated with hypertension. 83% of subjects diagnosed with hypertension were on anti-hypertensive medications, most commonly beta-blockers and calcium channel blockers. Conclusions Hypertension is common among HIV-positive individuals in rural Uganda. PMID:25430847

  9. Food Insecurity, Dietary Diversity, and Body Mass Index of HIV-Infected Individuals on Antiretroviral Therapy in Rural Haiti.

    PubMed

    Rebick, Gabriel W; Franke, Molly F; Teng, Jessica E; Gregory Jerome, J; Ivers, Louise C

    2016-05-01

    Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p < 0.001). Compared with those with little to no food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.

  10. Molecular Detection and Clinical Implications of HTLV-1 Infections among Antiretroviral Therapy-Naïve HIV-1-Infected Individuals in Abuja, Nigeria

    PubMed Central

    Nasir, Idris Abdullahi; Ahmad, Abdurrahman Elfulaty; Emeribe, Anthony Uchenna; Shehu, Muhammad Sagir; Medugu, Jessy Thomas; Babayo, Adamu

    2015-01-01

    BACKGROUND Individuals with human T-cell lymphotrophic virus type-1 (HTLV-1)/HIV-1 coinfection have been demonstrated to undergo CD4+ lymphocytosis even in the face of immunodeficiency and increased vulnerability to opportunistic pathogens that can lead to poor prognosis. OBJECTIVE This study investigated the prevalence as well as the effects of HIV-1/HTLV-1 coinfection on CD4+ cell counts, routine hematology, and biochemical parameters of study participants. MATERIALS AND METHODS This prospective cross-sectional study involved 184 blood samples collected from HIV-1-seropositive individuals attending HIV-special clinic of the University of Abuja Teaching Hospital, Gwagwalada, Nigeria. These samples were analyzed for anti-HTLV-1/2 IgM antibodies using enzyme-linked immunosorbent assay, CD4+ cell counts, and some routine hematological and biochemical parameters. All samples were also tested for HTLV-1 provirus DNA using real-time polymerase chain reaction (PCR) assay. RESULTS Of the 184 subjects studied, 9 (4.9%) were anti-HTLV-1/2 IgM seropositive; however, upon real-time PCR testing, 12 (6.5%) had detectable HTLV-1 provirus DNA. The CD4+ cell count was significantly high in HTLV-1-positive (742 ± 40.2) subjects compared to their HTLV-1-negative (380 ± 28.5) counterpart (P-value = 0.025). However, there was no significant association between HTLV-1 positivity with other hematology and biochemical parameters studied (P > 0.05). CONCLUSION All subjects (100%) who were HTLV-1/HIV-1-coinfected had normal CD4+ counts. This gives contrasting finding on the true extent of immunodeficiency of subjects. So it is suggested to be very careful in using only CD4+ counts to monitor disease progression and as indicators for antiretroviral therapy (ART) in resource-limited settings. In such conditions, there may be a need to test for HTLV-1 alongside HIV viral loads in order to begin appropriate ART regimens that contain both pathogens. PMID:26688662

  11. A one-year study of campylobacter carriage by individual Danish broiler chickens as the basis for selection of Campylobacter spp. strains for a chicken infection model.

    PubMed Central

    Bang, D. D.; Nielsen, E. M.; Knudsen, K.; Madsen, M.

    2003-01-01

    From February 1999 to February 2000, 1,250 individual broiler chickens representing 125 broiler flocks originating from 62 broiler farms in Denmark were screened for campylobacter carriage. Every month, 10 flocks were tested for campylobacter carriage. The swabs were tested individually and as a pooled sample representing the flocks. Campylobacter spp. carriage was detected from 512 (40.9%) broiler chickens originating from 63 (50.4%) positive flocks. Campylobacter carriage by both individual chickens and flocks showed seasonal variation. Campylobacter jejuni was the dominant species (95.5%). Campylobacter isolates were typed using Penner heat-stable serotyping and flaA-typing methods. Data of campylobacter carriage by individual chickens and data generated by the use of different typing methods contributed to a better understanding of the dynamics of campylobacter infection within the broiler flocks. C. jejuni Penner heat-stable serotype HS2, flaA-type 1 was the most common type found in Danish broiler chickens. PMID:12729201

  12. Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population.

    PubMed

    Hasse, Barbara; Tarr, Philip E; Marques-Vidal, Pedro; Waeber, Gerard; Preisig, Martin; Mooser, Vincent; Valeri, Fabio; Djalali, Sima; Andri, Rauch; Bernasconi, Enos; Calmy, Alexandra; Cavassini, Matthias; Vernazza, Pietro; Battegay, Manuel; Weber, Rainer; Senn, Oliver; Vollenweider, Peter; Ledergerber, Bruno; Aubert, V; Barth, J; Battegay, M; Bernasconi, E; Böni, J; Bucher, H C; Burton-Jeangros, C; Calmy, A; Cavassini, M; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, C A; Gorgievski, M; Günthard, H; Haerry, D; Hasse, B; Hirsch, H H; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, R; Kovari, H; Ledergerber, B; Martinetti, G; Martinez de Tejada, B; Metzner, K; Müller, N; Nadal, D; Pantaleo, G; Rauch, A; Regenass, S; Rickenbach, M; Rudin, C; Schöni-Affolter, F; Schmid, P; Schultze, D; Schüpbach, J; Speck, R; Staehelin, C; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Jean-Michel, Aubry; Murielle, Bochud; Jean Michel, Gaspoz; Christoph, Hock; Thomas, Lüscher; Pedro, Marques Vidal; Vincent, Mooser; Fred, Paccaud; Martin, Preisig; Peter, Vollenweider; Roland, Von Känel; Aidacic, Vladeta; Gerard, Waeber; Jürg, Beriger; Markus, Bertschi; Heinz, Bhend; Martin, Büchi; Hans-Ulrich, Bürke; Ivo, Bugmann; Reto, Cadisch; Isabelle, Charles; Corinne, Chmiel; Sima, Djalali; Peter, Duner; Simone, Erni; Andrea, Forster; Markus, Frei; Claudius, Frey; Jakob, Frey; Ali, Gibreil Musa; Matthias, Günthard; Denis, Haller; Marcel, Hanselmann; Walter, Häuptli; Simon, Heininger; Felix, Huber; Paul, Hufschmid; Eva, Kaiser; Vladimir, Kaplan; Daniel, Klaus; Stephan, Koch; Beat, Köstner; Benedict, Kuster; Heidi, Kuster; Vesna, Ladan; Giovanni, Lauffer; Werner, Leibundgut Hans; Phillippe, Luchsinger; Severin, Lüscher; Christoph, Maier; Jürgen, Martin; Damian, Meli; Werner, Messerli; Titus, Morger; Valentina, Navarro; Jakob, Rizzi; Thomas, Rosemann; Hana, Sajdl; Frank, Schindelek; Georg, Schlatter; Oliver, Senn; Pietro, Somaini; Jacques, Staeger; Alfred, Staehelin; Alois, Steinegger; Claudia, Steurer; Othmar, Suter; Phuoc, Truong The; Marco, Vecellio; Alessandro, Violi; René, Von Allmen; Hans, Waeckerlin; Fritz, Weber; Johanna, Weber-Schär; Joseph, Widler; Marco, Zoller

    2015-09-01

    Background.  Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods.  We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results.  Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions.  Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and

  13. The Effect of Central Nervous System Penetration Effectiveness of Highly Active Antiretroviral Therapy on Neuropsychological Performance and Neuroimaging in HIV Infected Individuals.

    PubMed

    Baker, Laurie M; Paul, Robert H; Heaps-Woodruff, Jodi M; Chang, Jee Yoon; Ortega, Mario; Margolin, Zachary; Usher, Christina; Basco, Brian; Cooley, Sarah; Ances, Beau M

    2015-09-01

    The incidence of HIV-associated dementia has been greatly reduced in the era of highly active antiretroviral therapy (HAART); however milder forms of cognitive impairment persist. It remains uncertain whether HAART regimens with a high degree of central nervous system penetration effectiveness (CPE) exert beneficial neurological outcomes in HIV-infected (HIV+) individuals on stable treatment. Sixty-four HIV-infected adults on HAART were assigned a CPE score using a published ranking system and divided into high (≥7; n = 35) and low (<7; n = 29) CPE groups. All participants completed neuropsychological testing in addition to structural neuroimaging. Neuropsychological tests included measures known to be sensitive to HIV with values converted into standardized scores (NPZ-4) based on published normative scores. A semi-automated methodology was utilized to assess brain volumetrics within cortical (grey and white matter) and subcortical (thalamus, caudate, putamen) regions of interest. Analyses assessed NPZ-4 and brain volumetric differences between HIV+ individuals with high and low CPE scores. No significant differences in brain integrity were observed between the two groups. Long-term HAART regimens with a high degree of CPE were not associated with significantly improved neuropsychological or neuroimaging outcomes in HIV+ adults. Results suggest that alternate mechanisms may potentially contribute to better neurological outcomes in the era of HAART.

  14. T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia.

    PubMed

    Riaño, Felipe; Arroyo, Leonar; París, Sara; Rojas, Mauricio; Friggen, Annemieke H; van Meijgaarden, Krista E; Franken, Kees L M C; Ottenhoff, Tom H M; García, Luis F; Barrera, Luis F

    2012-03-01

    Mycobacterium tuberculosis DosR regulon-encoded proteins elicit strong immune T-cell responses in individuals with latent tuberculosis (LTBI). Also, resuscitation (Rpf) proteins can induce such responses. However, variations in the immunogenicity of the DosR and Rpf proteins have been observed in European and African populations, and no data are published from other geographic areas. In Colombian LTBI and patients with recently diagnosed PTB, we therefore studied the immune response to DosR, Rpf, stress, and nominal antigens from Mtb, in 7-day stimulated cultures. Three DosR (Rv1737c, Rv2029c, Rv2628c) and 2 Rpf (Rv0867 and Rv2389c) antigens were recognized most prominently on the basis of the net IFNγ production (DosR) or the percentage of responding individuals (Rpf). Results show that the selected DosR antigens induced a higher proportion of CD4-T cells producing IFNγ from LTBI, compared to pulmonary TB patients (PTB), while there were no differences in the proportion of CD8-T cells. An increased frequency of CD4, but not CD8 T-cells with a CD45RO(+)CD27(+) phenotype was observed in LTBI in response to Rv2029c, Rv0867c, and Rv2389c, compared to PTB. The levels of cytokines and chemokines in the supernatants of stimulated cells, showed that the DosR and Rpf antigens induced higher levels of IFNγ in cultures from LTBI compared to PTB, although the induced pattern of cytokines and chemokines was also antigen dependent. In summary, our results are consistent with the significant immunogenicity of Mtb DosR and Rpf antigens in LTBI individuals, and confirm and extend previously reported data from other TB affected human populations.

  15. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study.

    PubMed

    Elzi, Luigia; Conen, Anna; Patzen, Annalea; Fehr, Jan; Cavassini, Matthias; Calmy, Alexandra; Schmid, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Battegay, Manuel

    2016-01-01

    Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV. PMID:26955645

  16. A Randomized Controlled Trial of Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in HIV-infected Individuals

    PubMed Central

    Safren, Steven A.; O’Cleirigh, Conall; Tan, Judy; Raminani, Sudha; Reilly, Laura C.; Otto, Michael W.; Mayer, Kenneth H.

    2008-01-01

    Objective To evaluate cognitive behavioral therapy to enhance medication adherence and reduce depression (CBT-AD) in individuals with HIV. Design A two arm, randomized, controlled, cross-over trial comparing CBT-AD, to enhanced treatment as usual only (ETAU). ETAU, which both groups received, included a single-session intervention for adherence and a letter to the patient’s provider documenting her or his continued depression. The intervention group also received 10 to 12 sessions of CBT-AD. Main Outcome Measures Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems (MEMs) and depression as assessed by blinded structured evaluation. Results At the acute outcome assessment (3-months), those who received CBT-AD evidenced significantly greater improvements in medication adherence and depression relative to the comparison group. Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes. Treatment gains for those in the intervention group were generally maintained at 6 and 12-month follow-up assessments. By the end of the follow-up period, those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations, though these differences did not emerge before the cross-over, and hence there were not between-group differences. Conclusions CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence. Replication and extension in larger efficacy trials are needed. PMID:19210012

  17. Weaning management of newly received beef calves with or without exposure to a persistently infected bovine viral diarrhea virus type 1b calf: Effects on health, performance, BVDV type 1a titers, and circulating leukocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a major culprit in the development of bovine respiratory disease (BRD) either directly via acute clinical illness or indirect effects of immunosuppression. Calves born persistently infected (PI) with BVDV are the primary transmission source of the virus; however...

  18. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on health, performance, bovine viral diarrhea virus titers,

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation that may have health and growth consequences; however, effects may differ in low-risk, preconditioned (PC) vs. high-risk, auction market (AM) cattle. Our objective was to compare health...

  19. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on rectal temperature, peripheral blood leukocytes and serum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation in cohorts. It is hypothesized that the extent of modulation differs for preconditioned (PC) vs. auction market (AM) cattle. Our objective was to compare immune responses of PC or AM ca...

  20. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on rectal temperature and serum proinflammatory cytokine and haptog

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation in cohorts. It is hypothesized that the extent of modulation differs for low-risk, preconditioned (PC) vs. high-risk, auction market (AM) beef cattle. Our objective was to compare immun...

  1. CD4+ T cell–dependent and –independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals

    PubMed Central

    Arnold, Kelly B.; Szeto, Gregory L.; Alter, Galit; Irvine, Darrell J.; Lauffenburger, Douglas A.

    2015-01-01

    A vital defect in the immune systems of HIV-infected individuals is the loss of CD4+ T cells, resulting in impaired immune responses. We hypothesized that there were CD4+ T cell–dependent and –independent alterations in the immune responses of HIV-1+ individuals. To test this, we analyzed the secretion of cytokines and chemokines from stimulated peripheral blood mononuclear cell (PBMC) populations from HIV+ donors, healthy donors, and healthy donors with CD4+ T cells experimentally depleted. Multivariate analyses of 16 cytokines and chemokines at 6 and 72 hours after three stimuli (antibody-coated beads to stimulate T cells and R848 or LPS to stimulate innate immune cells) enabled integrative analysis of secreted profiles. Two major effects in HIV+ PBMCs were not reproduced upon depleting CD4+ T cell in healthy PBMCs: (i) HIV+ PBMCs maintained T cell–associated secreted profiles after T cell stimulation; (ii) HIV+ PBMCs showed impaired IFN-γ secretion early after innate stimulation. These changes arose from hyperactive T cells and debilitated natural killer (NK) cell, respectively. Modeling and experiments showed that early IFN-γ secretion predicted later differences in secreted profiles in vitro. This effect was recapitulated in healthy PBMCs by blocking the interferon-γ (IFN-γ) receptor. Thus, we identified a critical deficiency in NK cell responses of HIV-infected individuals, independent of CD4+ T cell depletion, which directs secreted profiles. Our findings illustrate a broad approach for identifying key disease-associated nodes in a multicellular, multivariate signaling network. PMID:26486173

  2. Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy

    PubMed Central

    Massanella, Marta; Gianella, Sara; Schrier, Rachel; Dan, Jennifer M.; Pérez-Santiago, Josué; Oliveira, Michelli F.; Richman, Douglas D.; Little, Susan J.; Benson, Constance A.; Daar, Eric S.; Dube, Michael P.; Haubrich, Richard H.; Smith, Davey M.; Morris, Sheldon R.

    2015-01-01

    We investigated the associations between methamphetamine (meth) use, immune function, and the dynamics of HIV and cytomegalovirus [CMV] in the blood and genital tract of HIV-infected ART-suppressed subjects. Self-reported meth use was associated with increased CD4+ and CD8+ T-cell proliferation (Ki67+, p < 0.005), CD4+ T-cell activation (CD45RA–CD38+, p = 0.005) and exhaustion (PD-1+, p = 0.0004) in blood, compared to non-meth users. Meth use was also associated with a trend towards higher blood HIV DNA levels (p = 0.09) and more frequent shedding of CMV in seminal plasma (p = 0.002). To explore possible mechanisms, we compared ex vivo spontaneous and antigen-specific proliferation in PBMC collected from subjects with and without positive meth detection in urine (Utox+ vs. Utox-). Despite higher levels of spontaneous proliferation, lymphocytes from Utox+ meth users had a significantly lower proliferative capacity after stimulation with a number of pathogens (CMV, candida, mycobacterium, toxoplasma, HIV, p < 0.04 in all cases), compared to Utox- participants. Our findings suggest that meth users have greater proliferation and exhaustion of the immune system. Meth use is also associated with a loss of control of CMV replication, which could be related to loss of immune response to pathogens. Future studies should consider meth use as a potential modulator of T-cell responses. PMID:26299251

  3. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals

    PubMed Central

    Blanco-Heredia, Juan; Lecanda, Aarón; Valenzuela-Ponce, Humberto; Brander, Christian; Ávila-Ríos, Santiago; Reyes-Terán, Gustavo

    2016-01-01

    Background Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART) efficacy and may be an integral part of future cure strategies. Methods We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR) positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations. Results Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64%) corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual) or DR (median 6 pairs/individual) were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001). While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient’s virus (mean 68% of cases), responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002). Conclusions Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides. PMID:26808823

  4. HIV-1 Reverse Transcriptase Drug-Resistance Mutations in Chronically Infected Individuals Receiving or Naïve to HAART in Cameroon

    PubMed Central

    Burda, Sherri T.; Viswanath, Ragupathy; Zhao, Jiangqin; Kinge, Thompson; Anyangwe, Christopher; Tinyami, Erick T.; Haldar, Bijayesh; Powell, Rebecca L.R.; Jarido, Veronica; Hewlett, Indira K.; Nyambi, Phillipe N.

    2010-01-01

    The most common first-line, highly active anti-retroviral therapy (HAART) received by individuals infected with HIV-1 in Cameroon is the combination therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate, the reverse transcriptase (RT) viral sequences in patient plasma were analyzed for the presence of mutations that confer drug resistance. Forty-nine HIV-1-positive individuals were randomly selected from those receiving care in HIV/AIDS outpatient clinics in the South-West and North-West Regions of Cameroon. Among the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46% (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among those with drug-resistance mutations, there was a median of 14 months from the start of HAART, versus 9 months for those without; no difference was observed in the average viral load (10,997 copies/ml vs. 8,056 copies/ml). In contrast, drug-naïve individuals had a significantly higher average viral load (27,929 copies/ml) than those receiving HAART (9,527 copies/ml). Strikingly, among the 21 drug-naïve individuals, 24% harbored viruses with drug-resistance mutations, suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon. Given the high frequency of resistance mutations among those on first-line HAART, coupled with the high prevalence of HIV-1 variants with drug-resistance mutations among drug-naïve individuals, this study emphasizes the need for extensive monitoring of resistance mutations and the introduction of a second-line HAART strategy in Cameroon. PMID:20029816

  5. Detection of Tuberculosis in HIV Co-infected Individuals: Use of Multiple ELISA Responses to 38kDa, Lipoarabinomannan and ESAT– 6 of M. tuberculosis

    PubMed Central

    Gutlapalli, Ravi; Sykam, Aparna; Tenali, Sandeep P; Chandran, Priscilla; Suneetha, Sujai

    2016-01-01

    Introduction There is a constant search for more sensitive and specific laboratory markers for tuberculosis (TB) infection. The early detection of TB in HIV co infected individuals is a diagnostic challenge. This is further compounded in those harbouring extrapulmonary disease. Aim To evaluate the use of multiple Enzyme Linked Immunosorbent Assays (ELISA) quantifying antibody responses to 38kDa, LAM and ESAT-6 M.tb antigens in detection of TB in patients with TB and HIV-TB co-infection. Materials and Methods This is a cross-sectional study carried out in Hyderabad, India. Patient groups included 124 HIV-TB {62 with pulmonary TB (PTB) and 62 with extrapulmonary TB (ETB)}, 39 TB, 56 HIV and 57 healthy subjects (HS). A combination of anti 38kDa and LAM ELISAs measuring IgG, IgM and IgA levels and another ELISA measuring anti ESAT-6 combined antibody levels of IgG, IgM and IgA were evaluated. One-way ANOVA was performed to compare antibody responses among groups. To assess the efficacy of multiple ELISAs in detecting TB, concomitant seropositivity of an individual for all four ELISAs were evaluated for sensitivity and specificity. Results A single ELISA carried out to detect TB in HIV patients showed a sensitivity ranging from 39% to 72%. The sensitivities of concomitant evaluation of multiple ELISAs were 92% for any single, 72% for any two, 44% for any three and 14% for any four. Based on the specificities, a simple algorithm for TB detection can be deduced. When four ELISAs are positive (specificity 100%) in a patient-confirmed TB; when three ELISAs are positive (specificity 98%) – probably TB; when two ELISAs are positive (specificity 95%) – possibly TB; and when one ELISA is positive (specificity 70%) – suspicion of TB. Conclusion The present study establishes the value of combining two or more M.tb antigen based ELISAs to enhance the sensitivity and specificity of TB detection in patients with tuberculosis as well as in those co-infected with HIV. PMID

  6. Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C.

    PubMed

    Fernandes-Cardoso, Juliana; Süffert, Theodoro Armando; Correa, Maria da Gloria; Jobim, Luiz Fernando Job; Jobim, Mariana; Salim, Patricia Hartstein; Arruda, Monica Barcelos; Boullosa, Lidia Theodoro; Tanuri, Amilcar; Porto, Luis Cristóvão; Ferreira, Orlando C

    2016-10-01

    There is a great variety of HIV-1 subtypes circulating in Brazil, including subtype C, whose prevalence is on the rise, particularly in the southern region. Many host and viral genetic factors may be involved in this trend. We evaluated the influence of human leukocyte antigen (HLA) class I alleles and killer-cell immunoglobulin-like receptor (KIR) genotypes on viral set point and T-CD4(+) parameters in 84 treatment-naïve HIV-1-positive individuals. Frequency data in the infected group were compared to data of 548 healthy control subjects. Individuals with the KIR AA genotype had a higher viral load (VL) than individuals with the KIR Bx genotype. The HIV-1 group was subdivided into three subgroups according to HLA-B allele presence: those with protection to disease alleles (HLA-B(+)), accelerated disease progression alleles (HLA-B(-)), or neither (HLA-B(o)) were grouped. We observed a significant effect of the HLA-B allele presence on VL. The HLA-B(+) group had significantly lower VL than the HLA-B(-) group and trended toward a lower VL than the HLA-B(o) group. There were significant differences between groups expressing extreme VL values: KIR-AA+HLA-B(-) vs. KIR Bx+HLA-B(+) and KIR-AA+HLA-B(o)vs. KIR Bx+HLA-B(+). The relationship of KIR/HLA host genetics with slow HIV disease progression in southern Brazil may be useful for vaccine developers, epidemiologists, and clinicians.

  7. Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function

    PubMed Central

    Curriu, Marta; Fausther-Bovendo, Hughes; Pernas, María; Massanella, Marta; Carrillo, Jorge; Cabrera, Cecilia; López-Galíndez, Cecilio; Clotet, Bonaventura; Debré, Patrice; Vieillard, Vincent; Blanco, Julià

    2012-01-01

    Background CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. Methods We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. Results Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. Conclusions Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack

  8. TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

    PubMed

    Aroucha, Dayse Celia; Carmo, Rodrigo Feliciano; Vasconcelos, Luydson Richardson Silva; Lima, Raul Emidio; Mendonça, Taciana Furtado; Arnez, Lucia Elena; Cavalcanti, Maria do Socorro Mendonça; Muniz, Maria Tereza Cartaxo; Aroucha, Marcilio Lins; Siqueira, Erika Rabelo; Pereira, Luciano Beltrão; Moura, Patrícia; Pereira, Leila Maria Moreira Beltrão; Coêlho, Maria Rosangela

    2016-09-01

    Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.

  9. The relationship between adherence to clinic appointments and year-one mortality for newly enrolled HIV infected patients at a regional referral hospital in Western Kenya, January 2011-December 2012.

    PubMed

    Kimeu, Muthusi; Burmen, Barbara; Audi, Beryl; Adega, Anne; Owuor, Karen; Arodi, Susan; Bii, Dennis; Zielinski-Gutiérrez, Emily

    2016-01-01

    This retrospective cohort analysis was conducted to describe the association between adherence to clinic appointments and mortality, one year after enrollment into HIV care. We examined appointment-adherence for newly enrolled patients between January 2011 and December 2012 at a regional referral hospital in western Kenya. The outcomes of interest were patient default, risk factors for repeat default, and year-one risk of death. Of 582 enrolled patients, 258 (44%) were defaulters. GEE revealed that once having been defaulters, patients were significantly more likely to repeatedly default (OR 1.4; 95% CI 1.12-1.77), especially the unemployed (OR 1.43; 95% CI 1.07-1.91), smokers (OR 2.22; 95% CI 1.31-3.76), and those with no known disclosure (OR 2.17; 95% CI 1.42-3.3). Nineteen patients (3%) died during the follow-up period. Cox proportional hazards revealed that the risk of death was significantly higher among defaulters (HR 3.12; 95% CI 1.2-8.0) and increased proportionally to the rate of patient default; HR was 4.05 (95% CI1.38-11.81) and 4.98 (95% CI 1.45-17.09) for a cumulative of 4-60 and ≥60 days elapsed between all scheduled and actual clinic appointment dates, respectively. Risk factors for repeat default suggest a need to deliver targeted adherence programs.

  10. Phage-displayed antibody fragments recognizing dengue 3 and dengue 4 viruses as tools for viral serotyping in sera from infected individuals.

    PubMed

    Cabezas, Sheila; Rojas, Gertrudis; Pavon, Alequis; Bernardo, Lidice; Castellanos, Yinet; Alvarez, Mayling; Pupo, Maritza; Guillen, Gerardo; Guzman, Maria G

    2009-01-01

    The current study shows the usefulness of dengue-3- and dengue-4-specific phage-displayed antibody fragments as tools for viral detection and serotyping in sera from infected individuals. C6/36 HT cells were inoculated with acute-phase sera from patients, and supernatants were collected daily and analyzed by ELISA using phage-displayed antibody fragments as serotype-specific detector reagents. Serotyping of most samples was possible as early as two to three days postinoculation. Results were comparable with those obtained by indirect immunofluorescence assay but were obtained in a shorter period of time (<1 week). Phage-displayed antibody fragments were better tools for diagnosis and serotyping than their soluble counterparts. Our approach combines the advantages of viral isolation and ELISA techniques. These results could be the basis for the development of a high-throughput method for identifying dengue virus serotypes, which is crucial for the management and control of the disease.

  11. Bartonella henselae in eastern Poland: the relationship between tick infection rates and the serological response of individuals occupationally exposed to tick bites.

    PubMed

    Zając, Violetta; Wójcik-Fatla, Angelina; Dutkiewicz, Jacek; Szymańska, Jolanta

    2015-06-01

    To explore the potential role of Ixodes ricinus as the presumed vector of Bartonella henselae in eastern Poland, ticks collected in various geographic locations were examined for the presence of B. henselae, and the results were matched against the prevalence of anti-B. henselae antibodies in individuals occupationally exposed to tick bites. The presence of Bartonella DNA was investigated by PCR in a total of 1,603 unfed Ixodes ricinus ticks. The presence of IgG antibodies against B. henselae was investigated in serum samples from 332 people occupationally exposed to tick bites (94 farmers and 238 forestry workers). The total prevalence of B. henselae in ticks was 1.7%; the infection rates in males (3.1%) and females (2.7%) were nearly ten times greater than in nymphs (0.3%). The prevalence of seropositive results in the risk group (30.4%), farmers (27.7%) and forestry workers (31.5%), was significantly greater compared to the control group (8.9%). The results showed a weak positive correlation between the degree of infection of ticks and humans living in the same geographic region. The lack of a direct relationship indicates that exposure to tick bites is only one of the factors contributing to the significant preponderance of a seropositive response to B. henselae in the forestry workers and farmers over the control group. Other factors must be considered, such as contact with cats, which are popular domestic animals in Polish villages, and exposure to cat fleas.

  12. Molecular Individual-Based Approach on Triatoma brasiliensis: Inferences on Triatomine Foci, Trypanosoma cruzi Natural Infection Prevalence, Parasite Diversity and Feeding Sources

    PubMed Central

    Almeida, Carlos Eduardo; Faucher, Leslie; Lavina, Morgane; Costa, Jane; Harry, Myriam

    2016-01-01

    We used an individual-based molecular multisource approach to assess the epidemiological importance of Triatoma brasiliensis collected in distinct sites and ecotopes in Rio Grande do Norte State, Brazil. In the semi-arid zones of Brazil, this blood sucking bug is the most important vector of Trypanosoma cruzi—the parasite that causes Chagas disease. First, cytochrome b (cytb) and microsatellite markers were used for inferences on the genetic structure of five populations (108 bugs). Second, we determined the natural T. cruzi infection prevalence and parasite diversity in 126 bugs by amplifying a mini-exon gene from triatomine gut contents. Third, we identified the natural feeding sources of 60 T. brasiliensis by using the blood meal content via vertebrate cytb analysis. Demographic inferences based on cytb variation indicated expansion events in some sylvatic and domiciliary populations. Microsatellite results indicated gene flow between sylvatic and anthropic (domiciliary and peridomiciliary) populations, which threatens vector control efforts because sylvatic population are uncontrollable. A high natural T. cruzi infection prevalence (52–71%) and two parasite lineages were found for the sylvatic foci, in which 68% of bugs had fed on Kerodon rupestris (Rodentia: Caviidae), highlighting it as a potential reservoir. For peridomiciliary bugs, Galea spixii (Rodentia: Caviidae) was the main mammal feeding source, which may reinforce previous concerns about the potential of this animal to link the sylvatic and domiciliary T. cruzi cycles. PMID:26891047

  13. Molecular Individual-Based Approach on Triatoma brasiliensis: Inferences on Triatomine Foci, Trypanosoma cruzi Natural Infection Prevalence, Parasite Diversity and Feeding Sources.

    PubMed

    Almeida, Carlos Eduardo; Faucher, Leslie; Lavina, Morgane; Costa, Jane; Harry, Myriam

    2016-02-01

    We used an individual-based molecular multisource approach to assess the epidemiological importance of Triatoma brasiliensis collected in distinct sites and ecotopes in Rio Grande do Norte State, Brazil. In the semi-arid zones of Brazil, this blood sucking bug is the most important vector of Trypanosoma cruzi--the parasite that causes Chagas disease. First, cytochrome b (cytb) and microsatellite markers were used for inferences on the genetic structure of five populations (108 bugs). Second, we determined the natural T. cruzi infection prevalence and parasite diversity in 126 bugs by amplifying a mini-exon gene from triatomine gut contents. Third, we identified the natural feeding sources of 60 T. brasiliensis by using the blood meal content via vertebrate cytb analysis. Demographic inferences based on cytb variation indicated expansion events in some sylvatic and domiciliary populations. Microsatellite results indicated gene flow between sylvatic and anthropic (domiciliary and peridomiciliary) populations, which threatens vector control efforts because sylvatic population are uncontrollable. A high natural T. cruzi infection prevalence (52-71%) and two parasite lineages were found for the sylvatic foci, in which 68% of bugs had fed on Kerodon rupestris (Rodentia: Caviidae), highlighting it as a potential reservoir. For peridomiciliary bugs, Galea spixii (Rodentia: Caviidae) was the main mammal feeding source, which may reinforce previous concerns about the potential of this animal to link the sylvatic and domiciliary T. cruzi cycles.

  14. Body Composition, Soluble Markers of Inflammation, and Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1 Infected Individuals

    PubMed Central

    Brown, Todd T.; Chen, Yun; Currier, Judith S.; Ribaudo, Heather J.; Rothenberg, Jennifer; Dubé, Michael P.; Murphy, Robert; Stein, James H.; McComsey, Grace A.

    2013-01-01

    Objective To determine the association between bone mineral density (BMD), inflammatory markers, and alterations in fat and lean mass in untreated HIV-infected individuals. Design Cross-sectional analysis of antiretroviral therapy (ART)-naïve persons enrolled into a randomized clinical trial Methods Dual energy x-ray absorptiometry (DXA) for BMD, lean and fat mass, and a laboratory assessment were performed. Soluble biomarkers included adipocytokines (leptin, adiponectin), inflammatory markers (hsCRP, IL-6), and markers related to bone metabolism (osteoprotegerin (OPG)), receptor activator of NFκB Ligand (RANKL)). BMD at the lumbar spine, total hip, and femoral neck was expressed as a Z-score (number of standard deviations away from an age-, race-, sex-matched reference population). Results 331 subjects had a median (Q1, Q3) age of 36 (28,45) years, were 89% male, and 44% white. The prevalence of low BMD (Z-score ≤ −2 at any of the 3 sites) was 10%. No associations were detected between Z-scores and hsCRP, IL-6, or RANKL (P≥0.1). In a linear model adjusting for age, gender, race, and total fat mass, lower lumbar spine Z-scores were associated with lower total lean mass, higher serum adiponectin, and lower OPG. Results at the total hip or femoral neck were similar. Conclusions Among ART-naïve HIV-infected individuals, lower BMD was associated with lower lean mass, higher adiponectin, and lower OPG, but not HIV disease variables or any of the inflammatory markers. These findings may have implications for bone metabolism in untreated HIV, in which hypoadiponectinemia and higher OPG may mitigate bone loss. PMID:23591634

  15. Salmonella enterica Infections in the United States and Assessment of Coefficients of Variation: A Novel Approach to Identify Epidemiologic Characteristics of Individual Serotypes, 1996–2011

    PubMed Central

    Boore, Amy L.; Hoekstra, R. Michael; Iwamoto, Martha; Fields, Patricia I.; Bishop, Richard D.; Swerdlow, David L.

    2015-01-01

    Background Despite control efforts, salmonellosis continues to cause an estimated 1.2 million infections in the United States (US) annually. We describe the incidence of salmonellosis in the US and introduce a novel approach to examine the epidemiologic similarities and differences of individual serotypes. Methods Cases of salmonellosis in humans reported to the laboratory-based National Salmonella Surveillance System during 1996–2011 from US states were included. Coefficients of variation were used to describe distribution of incidence rates of common Salmonella serotypes by geographic region, age group and sex of patient, and month of sample isolation. Results During 1996–2011, more than 600,000 Salmonella isolates from humans were reported, with an average annual incidence of 13.1 cases/100,000 persons. The annual reported rate of Salmonella infections did not decrease during the study period. The top five most commonly reported serotypes, Typhimurium, Enteritidis, Newport, Heidelberg, and Javiana, accounted for 62% of fully serotyped isolates. Coefficients of variation showed the most geographically concentrated serotypes were often clustered in Gulf Coast states and were also more frequently found to be increasing in incidence. Serotypes clustered in particular months, age groups, and sex were also identified and described. Conclusions Although overall incidence rates of Salmonella did not change over time, trends and epidemiological factors differed remarkably by serotype. A better understanding of Salmonella, facilitated by this comprehensive description of overall trends and unique characteristics of individual serotypes, will assist in responding to this disease and in planning and implementing prevention activities. PMID:26701276

  16. Association of Single Nucleotide Polymorphisms in the Lens Epithelium-Derived Growth Factor (LEDGF/p75) with HIV-1 Infection Outcomes in Brazilian HIV-1+ Individuals

    PubMed Central

    Caetano, Diogo Gama; Teixeira, Sylvia Lopes Maia; Guimarães, Monick Lindenmeyer; Campos, Dayse Pereira; Veloso, Valdilea Gonçalves; Babic, Dunja Z.; Stevenson, Mario; Moraes, Milton Ozório; Morgado, Mariza Gonçalves

    2014-01-01

    The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1 gene, is an important host co-factor that interacts with HIV-1 integrase to target integration of viral cDNA into active genes. The aim of this study was to investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV-1 infected patients. We performed a genetic association study in a cohort of 171 HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n = 69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n = 23). The exonic SNP rs61744944 and 9 tag SNPs were genotyped. A group of 192 healthy subjects was analyzed to determine the frequency of SNPs and haplotypes in the general population. Linkage disequilibrium (LD) analyses indicated that the SNPs analyzed were not in high LD (r2<0.8). Logistic regression models suggested that patients carrying the T allele rs61744944 (472L) were more likely to develop a LTNP phenotype (OR = 4.98; p = 0.05) as compared to TP group. The same trend was observed when LTNPs were compared to the RP group (OR = 3.26). Results of haplotype analyses reinforced this association, since the OR values obtained for the haplotype carrying allele T at rs61744944 also reflected an association with LTNP status (OR = 6.05; p = 0.08 and OR = 3.44; p = 0.12 for comparisons to TP and RP, respectively). The rare missense variations Ile436Ser and Thr473Ile were not identified in the patients enrolled in this study. Gene expression analyses showed lower LEDGF/p75 mRNA levels in peripheral blood mononuclear cells obtained from HIV-1 infected individuals. However, these levels were not influenced by any of the SNPs investigated. In spite of the limited number of LTNPs, these data suggest that the PSIP1 gene could be associated with the outcome of HIV-1 infection. Further analyses of this gene may guide the identification of causative variants to help predict disease course

  17. The relationship between adherence to clinic appointments and year-one mortality for newly enrolled HIV infected patients at a regional referral hospital in Western Kenya, January 2011–December 2012

    PubMed Central

    Kimeu, Muthusi; Burmen, Barbara; Audi, Beryl; Adega, Anne; Owuor, Karen; Arodi, Susan; Bii, Dennis; Zielinski-Gutiérrez, Emily

    2016-01-01

    This retrospective cohort analysis was conducted to describe the association between adherence to clinic appointments and mortality, one year after enrollment into HIV care. We examined appointment-adherence for newly enrolled patients between January 2011 and December 2012 at a regional referral hospital in western Kenya. The outcomes of interest were patient default, risk factors for repeat default, and year-one risk of death. Of 582 enrolled patients, 258 (44%) were defaulters. GEE revealed that once having been defaulters, patients were significantly more likely to repeatedly default (OR 1.4; 95% CI 1.12–1.77), especially the unemployed (OR 1.43; 95% CI 1.07–1.91), smokers (OR 2.22; 95% CI 1.31–3.76), and those with no known disclosure (OR 2.17; 95% CI 1.42–3.3). Nineteen patients (3%) died during the follow-up period. Cox proportional hazards revealed that the risk of death was significantly higher among defaulters (HR 3.12; 95% CI 1.2–8.0) and increased proportionally to the rate of patient default; HR was 4.05 (95% CI1.38–11.81) and 4.98 (95% CI 1.45–17.09) for a cumulative of 4–60 and ≥60 days elapsed between all scheduled and actual clinic appointment dates, respectively. Risk factors for repeat default suggest a need to deliver targeted adherence programs. PMID:26572059

  18. Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals

    PubMed Central

    Okulicz, Jason F.; Le, Tuan D.; Agan, Brian K.; Camargo, Jose F.; Landrum, Michael L.; Wright, Edwina; Dolan, Matthew J.; Ganesan, Anuradha; Ferguson, Tomas M.; Smith, Davey M.; Richman, Douglas D.; Little, Susan J.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.

    2014-01-01

    IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4+ counts in HIV-1–uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4+ counts to 900 cells/μL or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4+ count in HIV-1–uninfected populations was approximately 900 cells/μL. Among 1119 HIV-1–infected participants, CD4+ normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P = .001). Incrementally higher CD4+ recovery (<500,500–899, and ≥900 cells/μL) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1–uninfected persons. Participants with CD4+ counts of 500 cells/μL or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51–2.64; P < .001) or ART initiation (aOR, 4.08; 95% CI, 3.14–5.30; P < .001) had significantly increased CD4+ normalization rates compared with other participants. However, even among individuals with a CD4+ count of 500 cells

  19. Population genetic structure and disease in montane boreal toads: More heterozygous individuals are more likely to be infected with amphibian chytrid

    USGS Publications Warehouse

    Addis, Brett; Lowe, Winsor; Hossack, Blake R.; Allendorf, Fred

    2015-01-01

    Amphibians are more threatened than any other vertebrate group, with 41 % of species classified as threatened. The causes of most declines are not well understood, though many declines have been linked to disease. Additionally, amphibians are physiologically constrained to moist habitats and considered poor dispersers; thus, they may suffer genetic consequences of population isolation. To understand threats to the persistence of boreal toads (Bufo boreas) in Glacier National Park, USA, we genotyped 551 individuals at 11 microsatellite loci and used Bayesian clustering methods to describe population genetic structure and identify barriers to gene flow. We found evidence of two primary genetic groups that differed substantially in elevation and two secondary groups within the high elevation group. There was also evidence of further substructure within the southern high elevation group, suggesting mountain ridges are barriers to gene flow at local scales. Overall, genetic variation was high, but allelic richness declined with increasing elevation, reflecting greater isolation or smaller effective population sizes of high altitude populations. We tested for Batrachochytrium dendrobatidis (Bd), the fungal pathogen which causes chytridiomycosis, and we found that 35 of 199 toads were positive for Bd. Unexpectedly, more heterozygous individuals were more likely to be infected. This suggests that dispersal facilitates the spread of disease because heterozygosity may be highest where dispersal and gene flow are greatest.

  20. Laboratory diagnosis of human chlamydial infections.

    PubMed Central

    Barnes, R C

    1989-01-01

    Chlamydia trachomatis is a human pathogen that causes ocular disease (trachoma and inclusion conjunctivitis), genital disease (cervicitis, urethritis, salpingitis, and lymphogranuloma venereum), and respiratory disease (infant pneumonitis). Respiratory chlamydioses also occur with infection by avian strains of C. psittaci or infection by the newly described TWAR agent. Diagnosis of most acute C. trachomatis infections relies on detection of the infecting agent by cell culture, fluorescent antibody, immunoassay, cytopathologic, or nucleic acid hybridization methods. Individual non-culture tests for C. trachomatis are less sensitive and specific than the best chlamydial cell culture system but offer the advantages of reduced technology and simple transport of clinical specimens. Currently available nonculture tests for C. trachomatis perform adequately as screening tests in populations in which the prevalence of infection is greater than 10%. A negative culture or nonculture test for C. trachomatis does not, however, exclude infection. The predictive value of a positive nonculture test may be unsatisfactory when populations of low infection prevalence are tested. Tests that detect antibody responses to chlamydial infection have limited utility in diagnosis of acute chlamydial infection because of the high prevalence of persistent antibody in healthy adults and the cross-reactivity due to infection by the highly prevalent C. trachomatis and TWAR agents. Assays for changes in antibody titer to the chlamydial genus antigen are used for the diagnosis of respiratory chlamydioses. A single serum sample that is negative for chlamydial antibody excludes the diagnosis of lymphogranuloma venereum. PMID:2650858

  1. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Dao, Dyda; Gysin, Christian Michael; Lytvyn, Lyubov; Loeb, Mark

    2016-01-01

    Objective Vitamin D supplementation may be a simple preventive measure against respiratory tract infections (RTIs) but evidence from randomized controlled trials is inconclusive. We aimed to systematically summarize results from interventions studying the protective effect of vitamin D supplementation on clinical and laboratory confirmed RTIs in healthy adults and children. Methods Medline, EMBASE, CENTRAL, and CINAHL were screened from inception until present (last updated in January 2016) completed by a search of the grey literature, clinical trial registers and conference abstracts. We included randomized trials comparing vitamin D versus placebo or no treatment. Two independent reviewers were responsible for study selection and data extraction. Cochrane’s risk of bias tool and the GRADE approach were used for quality assessment. Estimates were pooled with random-effects models. Heterogeneity was explored by sub-group and meta-regression analyses. Results Of 2627 original hits, 15 trials including 7053 individuals were ultimately eligible. All used oral cholecalciferol. We found a 6% risk reduction with vitamin D3 supplementation on clinical RTIs, but the result was not statistically significant (RR 0.94; 95% CI 0.88 to 1.00). Heterogeneity was large (I-square 57%) and overall study quality was low. There were too few studies to reliably assess a potential risk reduction of laboratory confirmed RTI. Evidence was insufficient to demonstrate an association between vitamin D supplementation and risk of clinical RTI in sub-groups with vitamin D deficiency. Conclusions In previously healthy individuals vitamin D supplementation does not reduce the risk of clinical RTIs. However, this conclusion is based on a meta-analysis where the included studies differed with respect to population, baseline vitamin D levels and study length. This needs to be considered when interpreting the results. Future trials should focus on vitamin D deficient individuals and apply more

  2. Challenges in anti-infective development in the era of bad bugs, no drugs: a regulatory perspective using the example of bloodstream infection as an indication.

    PubMed

    Boucher, Helen W

    2010-01-01

    Bloodstream infections present many challenges to clinicians. The number of hospitalized patients with bloodstream infection continues to increase, and the number of newly available antimicrobial agents to treat these particularly lethal infections and many other serious infections continues to decrease. Drug-development programs for bloodstream infection that have adhered to existing regulatory guidelines have not been significantly successful. This article examines the regulatory history of the bloodstream infection indication as an example of the challenges faced by individuals and sponsors developing drugs for treatment of the current spectrum of antimicrobial-resistant infections, with the goal of providing insight into development pathways for agents targeting drug-resistant bacterial pathogens. Disease-specific and pathogen-specific indications are discussed, and recent regulatory approvals for bloodstream infection caused by vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus are reviewed. PMID:20067391

  3. Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV-1 infected individuals not selected for a certain HLA allele.

    PubMed

    Roider, Julia; Kalteis, Anna-Lena; Vollbrecht, Thomas; Gloning, Lisa; Stirner, Renate; Henrich, Nadja; Bogner, Johannes R; Draenert, Rika

    2013-01-01

    HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8 T cell epitopes. A viral escape mutation can lead to a decline of the respective CD8 T cell response. Our question was what happened after the decline of a CD8 T cell response and - in the case of viral escape - if a new CD8 T cell response towards the mutated antigen could be generated in a population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral escape mutations with one de-novo response (8%). The de-novo response, however, showed less effector functions than the original CD8 T cell response. In addition we identified 4 shifts in immunodominance. For one further shift in immunodominance, the mutations occurred outside the optimal epitope and might represent processing changes. Interestingly, four adaptations to the virus (the de-novo response and 3 shifts in immunodominance) occurred in the group of chronically infected progressors. None of the subjects with adaptation to the changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that CD8 T cell responses adapt to the mutations of HIV. However it was limited to only 20% (5 out of 25) of the epitopes with viral sequence changes in a cohort not expressing protective HLA alleles.

  4. Development of a molecular-beacon assay to detect the G1896A precore mutation in hepatitis B virus-infected individuals.

    PubMed

    Waltz, Therese L; Marras, Salvatore; Rochford, Gemma; Nolan, John; Lee, Eugenia; Melegari, Margherita; Pollack, Henry

    2005-01-01

    The 1896 precore (PC) mutation is the most frequent cause of hepatitis B virus e-antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Detection of the 1896 PC mutation has application in studies monitoring antiviral therapy and the natural history of the disease. Identification of this mutation is usually performed by direct sequencing, which is both costly and laborious. The aim of this study was to develop a rapid, high-throughput assay to detect the 1896 PC mutation using real-time PCR and molecular-beacon technology. The assay was initially standardized on oligonucleotide targets and plasmids containing the wild-type (WT) and PC mutation and then tested on plasma samples from children with HBV DNA of >10(6) copies/ml. Nine individuals were HBeAg negative and suspected to harbor HBeAg mutations, while 12 children were HBeAg positive and selected as controls. Ninety percent (19 of 21) of plasma samples tested with molecular beacons were in complete agreement with sequencing results. The remaining 10% (2 of 21) of samples were identified as heterogeneous mixtures of WT and mutant virus by molecular beacons, though sequencing found only a homogeneous mutant in both cases. Overall, the 1896 PC mutation was detected by this assay in 55.5% of the children with HBeAg-negative infection. In summary, this assay is a rapid, sensitive, and specific technique that effectively discriminates WT from 1896 PC mutant HBV and may be useful in clinical and epidemiological studies.

  5. Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals

    PubMed Central

    Moqueet, Nasheed; Infante-Rivard, Claire; Platt, Robert W.; Young, Jim; Cooper, Curtis; Hull, Mark; Walmsley, Sharon; Klein, Marina B.

    2015-01-01

    Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals. PMID:25803108

  6. Net survival of perinatally and postnatally HIV-infected children: a pooled analysis of individual data from sub-Saharan Africa

    PubMed Central

    Marston, Milly; Becquet, Renaud; Zaba, Basia; Moulton, Lawrence H; Gray, Glenda; Coovadia, Hoosen; Essex, Max; Ekouevi, Didier K; Jackson, Debra; Coutsoudis, Anna; Kilewo, Charles; Leroy, Valériane; Wiktor, Stefan; Nduati, Ruth; Msellati, Philippe; Dabis, François; Newell, Marie-Louise; Ghys, Peter D

    2011-01-01

    Background Previously, HIV epidemic models have used a double Weibull curve to represent high initial and late mortality of HIV-infected children, without distinguishing timing of infection (peri- or post-natally). With more data on timing of infection, which may be associated with disease progression, a separate representation of children infected early and late was proposed. Methods Paediatric survival post-HIV infection without anti-retroviral treatment was calculated using pooled data from 12 studies with known timing of HIV infection. Children were grouped into perinatally or post-natally infected. Net mortality was calculated using cause-deleted life tables to give survival as if HIV was the only competing cause of death. To extend the curve beyond the available data, children surviving beyond 2.5 years post infection were assumed to have the same survival as young adults. Double Weibull curves were fitted to both extended survival curves to represent survival of children infected perinatally or through breastfeeding. Results Those children infected perinatally had a much higher risk of dying than those infected through breastfeeding, even allowing for background mortality. The final-fitted double Weibull curves gave 75% survival at 5 months after infection for perinatally infected, and 1.1 years for post-natally infected children. An estimated 25% of the early infected children would still be alive at 10.6 years compared with 16.9 years for those infected through breastfeeding. Conclusions The increase in available data has enabled separation of child mortality patterns by timing of infection allowing improvement and more flexibility in modelling of paediatric HIV infection and survival. PMID:21247884

  7. CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1–infected individuals

    PubMed Central

    Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J

    2008-01-01

    The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. PMID:18376407

  8. Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection.

    PubMed

    Günaydın, Gökçe; Nordgren, Johan; Sharma, Sumit; Hammarström, Lennart

    2016-01-01

    The histo-blood group antigens (HBGAs) have recently been suggested to serve as attachment factors for rotavirus VP8* (P-genotype) in vitro and associated with susceptibility in vivo. We thus investigated whether rotavirus antibody titers and genotype specific neutralization titers correlate with HBGA status in Swedish individuals. We investigated the effect of inactivating mutations in the secretor FUT2 (rs601338) and Lewis FUT3 genes (rs28362459, rs3894326, rs812936 and rs778986) on serum IgG antibody titers and neutralizing antibody titers to rotavirus strains of the P[8] and P[6] genotypes in Swedish healthy blood donors and patients with IgA deficiency using genotyping, enzyme linked immunosorbent assay and a neutralization assay. Rotavirus-specific serum IgG and neutralizing antibody titers to the Wa strain (G1P[8]), but not to the ST3 (G4P[6]) strain, were significantly higher in secretors (with at least one functional FUT2 gene) than in non-secretors (P<0.001) (with homozygous nonsense mutation in the FUT2 gene). Thus, our results represent that secretors show elevated rotavirus specific serum antibodies, suggesting a higher susceptibility to rotavirus infections, as compared to non-secretors in Sweden.

  9. Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: a systematic review of individual case data.

    PubMed

    Lai, Shengjie; Qin, Ying; Cowling, Benjamin J; Ren, Xiang; Wardrop, Nicola A; Gilbert, Marius; Tsang, Tim K; Wu, Peng; Feng, Luzhao; Jiang, Hui; Peng, Zhibin; Zheng, Jiandong; Liao, Qiaohong; Li, Sa; Horby, Peter W; Farrar, Jeremy J; Gao, George F; Tatem, Andrew J; Yu, Hongjie

    2016-07-01

    Avian influenza A H5N1 viruses have caused many, typically severe, human infections since the first human case was reported in 1997. However, no comprehensive epidemiological analysis of global human cases of H5N1 from 1997 to 2015 exists. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the outbreaks since November, 2014, which have the highest number of cases ever reported worldwide in a similar period. Data on individual patients were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May, 1997, and April, 2015. The number of affected countries rose between 2003 and 2008, with expansion from east and southeast Asia, then to west Asia and Africa. Most cases (67·2%) occurred from December to March, and the overall case-fatality risk was 483 (53·5%) of 903 cases which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November, 2014, compared with the cases beforehand, there were no significant differences in the fatality risk, history of exposure to poultry, history of patient contact, and time from onset to hospital admission in the recent cases. PMID:27211899

  10. Changes Over Time in Risk Factors for Cardiovascular Disease and Use of Lipid-Lowering Drugs in HIV-Infected Individuals and Impact on Myocardial Infarction

    PubMed Central

    2009-01-01

    Background Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)–infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. Methods The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. Results The proportion of patients at high risk of CVD increased from 35.3% during 1999–2000 to 41.3% during 2005–2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29–0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999–2000], 0.73 cases per 100 PY [95% CI, 0.50–1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44–0.94 cases per 100 PY]; in 2005–2006, 0.36 cases per 100 PY [95% CI, 0.24–0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999–2000], 1.06 cases per 100 PY [95% CI, 0.63–1

  11. HPTN 062: A Pilot Randomized Controlled Trial Exploring the Effect of a Motivational-Interviewing Intervention on Sexual Behavior among Individuals with Acute HIV Infection in Lilongwe, Malawi

    PubMed Central

    Pettifor, Audrey; Corneli, Amy; Kamanga, Gift; McKenna, Kevin; Rosenberg, Nora E.; Yu, Xuesong; Ou, San-San; Massa, Cecilia; Wiyo, Patricia; Lynn, Diana; Tharaldson, Jenae; Golin, Carol; Hoffman, Irving

    2015-01-01

    Objective We pilot tested a Motivational Interviewing (MI) –based counseling intervention for individuals with Acute HIV Infection (AHI) to reduce risky sexual behavior in Lilongwe, Malawi. Methods Twenty-eight individuals diagnosed with AHI were randomized to receive either brief education alone, or the brief education plus the MI-based intervention, called Uphungu Wanga. Participants in Uphungu Wanga received four sessions delivered on the day of diagnosis, three days later and at weeks 1 and 2 with a booster session at week 8; participants were followed for 24 weeks from diagnosis. An interviewer administered quantitative questionnaire was conducted at baseline and at weeks 2, 4, 8, 12, 16, 20 and 24. Semi-structured qualitative interviews (SSI) were conducted at weeks 2, 8, 12, and 24. Results The majority of participants in both arms reported rapid and sustained behavior change following diagnosis with AHI. Very few participants reported having sex without a condom after diagnosis. Participants reported a trend towards fewer sex partners and abstaining from sex during study follow-up. Participants in the MI-based arm provided concrete examples of risk reduction strategies in the SSIs while those in the brief education arm primarily described reducing risk behavior, suggesting that the MI-based group may have acquired more risk reduction skills. Conclusions Individuals in both study arms reduced risky sexual behaviors after diagnosis with AHI. We found few major differences between study arms during the 6-month follow up period in self-reported sexual behaviors therefore a MI-based intervention may not be needed to trigger behavior change following AHI. However, comparing the MI-based intervention to repeated brief education sessions made it difficult to assess the potential benefit of an MI-based intervention in a setting where standard counseling often consists of one post-test session. Nevertheless, provision of counseling immediately following diagnosis

  12. Explaining variability in first grazing season heifer growth combining individually measured parasitological and clinical indicators with exposure to gastrointestinal nematode infection based on grazing management practice.

    PubMed

    Merlin, Aurélie; Chauvin, Alain; Madouasse, Aurélien; Froger, Sébastien; Bareille, Nathalie; Chartier, Christophe

    2016-07-30

    The objective of our study was to explain the variability of average daily weight gain (ADWG) due to gastrointestinal nematode (GIN) infection for 291 non treated first grazing season (FGS) heifers, from 12 independent groups in the western part of France, by combining parasitological and clinical indicators at individual level and grazing management indicators at group level. Parasitological indicators were faecal egg count (FEC), anti Ostertagia ostertagi antibody level (Ostertagia ODR), and pepsinogen level. Clinical indicators were diarrhea score (DISCO) and breech soiling score (BSS). At group level, grazing management practice (GMP), based on three variables (supplementation, month of turnout, grazing season duration), was clustered into three categories reflecting low, medium or high exposure (EXP) to GIN. Depending on the groups, turnout was from mid-March to early July and housing was from mid-October to late November, with a FGS duration ranging from 4 to 8.4 months. At turnout, the mean age of heifers was 8 months (range: 6-16 months) and they weighed between 175 and 268kg. In each GMP category, FEC significantly decreased between the mid-season and the housing, while Ostertagia ODR and pepsinogen level increased gradually throughout the grazing season. In contrast, clinical indicators did not show any seasonal variation. In a multivariate linear model, 22% of the ADWG variability was significantly explained by two individual indicators (Ostertagia ODR: 12.6%, DISCO: 4.8%) and by the group indicator (GMP category: 4.8%). ADWG losses due to GIN exposure (Ostertagia ODR) were estimated up to 39kg per heifer for the overall grazing season. For groups within the low EXP category the difference between animals with low (<697g/day) or high (>697g/day) ADWG was explained by the clinical indicator DISCO. In contrast, for groups within the medium and high EXP categories this difference was explained by a parasitological indicator (Ostertagia ODR). This study

  13. The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis

    PubMed Central

    Pho, Mai T.; Swaminathan, Soumya; Kumarasamy, Nagalingeswaran; Losina, Elena; Ponnuraja, C.; Uhler, Lauren M.; Scott, Callie A.; Mayer, Kenneth H.; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2012-01-01

    Background Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. Methods We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm3, and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). Results Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. Conclusions Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care. PMID:22558301

  14. People newly in love are more responsive to positive feedback.

    PubMed

    Brown, Cassandra L; Beninger, Richard J

    2012-06-01

    Passionate love is associated with increased activity in dopamine-rich regions of the brain. Increased dopamine in these regions is associated with a greater tendency to learn from reward in trial-and-error learning tasks. This study examined the prediction that individuals who were newly in love would be better at responding to reward (positive feedback). In test trials, people who were newly in love selected positive outcomes significantly more often than their single (not in love) counterparts but were no better at the task overall. This suggests that people who are newly in love show a bias toward responding to positive feedback, which may reflect a general bias towards reward-seeking.

  15. Resuscitation of the newly born.

    PubMed

    Johannson, A B; Biarent, D

    2002-01-01

    International guidelines developed recommendations in the resuscitation of the new-born: at least one person trained in resuscitation of the newly born should attend every delivery. A minority of the new-borns require active resuscitation to achieve regular respiration, heart rhythm above 100/min, pink colour and adequate tone. Establishment of adequate ventilation should be of primary concern. Most new-borns who require positive-pressure ventilation can be adequately ventilated with a bag and mask. All healthcare providers, who may be asked to deal with an emergency delivery, should master such technique. In case of meconium-stained amniotic fluid, thorough oropharyngeal suctioning should be perform before the delivery of the chest. Tracheal aspiration of mecomium should be perform only in depressed child. Very few infants require chest compressions and much less administration of drugs. Umbilical access remains the most widely recommended access in new-born. Adequate transfer to Neonatal Unit improves outcome. PMID:12503356

  16. Hemiballistic movements in a newly HIV patient.

    PubMed

    Magano, Rita; Jorge, Rita; Prata, Margarida; Ventura, Maria Conceição; Saraiva da Cunha, José Gabriel

    2016-01-01

    Infections of central nervous system (CNS) include a broad group of conditions and pose a particular challenge to physicians, especially in immunocompromised individuals. This case refers to a 26-year-old male patient with a history of smoked hashish and drug abuse admitted to the infectious disease department with hemiballismus of left hemibody and a positive HIV serologic test. A magnetic resonance imaging (MRI) study showed lesions at lower left and right cerebellar hemisphere, one of them thalamus - mesencephalic suggesting an opportunistic infection or an HIV associated encephalopathy. Lumbar puncture, brain biopsy and successive neuroimaging were not conclusive for one disease and despite the use of directed therapy for cerebral toxoplasmosis, meningeal tuberculosis, anti-retrovirals and sedative medication, after over 6 weeks of hospitalization pallidotomy was performed. After 5 months of oral and surgical treatment the patient showed clinical, immunological and radiological recovery. PMID:27583209

  17. [HIV infection : Test and treatment].

    PubMed

    Rockstroh, J K; Wasmuth, J-C

    2016-08-01

    In Europe depending on the country 15-80 % of all individuals infected with human immunodeficiency virus (HIV) are either not aware of the diagnosis or are diagnosed later. An early HIV diagnosis could, however, considerably improve the prognosis of individuals infected with HIV and decrease the risk of new infections; therefore, in the presence of indicator diseases, such as sexually transmitted diseases, oral thrush, herpes zoster and lymphoma, the performance of a HIV test is of utmost importance. A newly diagnosed HIV infection represents an indication for starting antiretroviral combination therapy independent of the clinical stage or CD4 cell count. A decline of the viral burden to below the limit of detection and subsequent continuous suppression of viral replication can prevent transition from HIV to acquired immune deficiency syndrome (AIDS) and if started early enough a normal life expectancy can be achieved. Challenges which remain in HIV therapy are the lifelong daily intake of medication and the complex long-term adverse effects. PMID:27368530

  18. The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

    PubMed

    Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

    2016-01-01

    Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.

  19. External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection: An Individual Patient Data Meta-Analysis

    PubMed Central

    Schierenberg, Alwin; Minnaard, Margaretha C.; Hopstaken, Rogier M.; van de Pol, Alma C.; Broekhuizen, Berna D. L.; de Wit, Niek J.; Reitsma, Johannes B.; van Vugt, Saskia F.; Graffelman, Aleida W.; Melbye, Hasse; Rainer, Timothy H.; Steurer, Johann; Holm, Anette; Gonzales, Ralph; Dinant, Geert-Jan; de Groot, Joris A. H.; Verheij, Theo J. M.

    2016-01-01

    Background Pneumonia remains difficult to diagnose in primary care. Prediction models based on signs and symptoms (S&S) serve to minimize the diagnostic uncertainty. External validation of these models is essential before implementation into routine practice. In this study all published S&S models for prediction of pneumonia in primary care were externally validated in the individual patient data (IPD) of previously performed diagnostic studies. Methods and Findings S&S models for diagnosing pneumonia in adults presenting to primary care with lower respiratory tract infection and IPD for validation were identified through a systematical search. Six prediction models and IPD of eight diagnostic studies (N total = 5308, prevalence pneumonia 12%) were included. Models were assessed on discrimination and calibration. Discrimination was measured using the pooled Area Under the Curve (AUC) and delta AUC, representing the performance of an individual model relative to the average dataset performance. Prediction models by van Vugt et al. and Heckerling et al. demonstrated the highest pooled AUC of 0.79 (95% CI 0.74–0.85) and 0.72 (0.68–0.76), respectively. Other models by Diehr et al., Singal et al., Melbye et al., and Hopstaken et al. demonstrated pooled AUCs of 0.65 (0.61–0.68), 0.64 (0.61–0.67), 0.56 (0.49–0.63) and 0.53 (0.5–0.56), respectively. A similar ranking was present based on the delta AUCs of the models. Calibration demonstrated close agreement of observed and predicted probabilities in the models by van Vugt et al. and Singal et al., other models lacked such correspondence. The absence of predictors in the IPD on dataset level hampered a systematical comparison of model performance and could be a limitation to the study. Conclusions The model by van Vugt et al. demonstrated the highest discriminative accuracy coupled with reasonable to good calibration across the IPD of different study populations. This model is therefore the main candidate for

  20. Sequence conservation in the Ancylostoma secreted protein-2 of Necator americanus (Na-ASP-2) from hookworm infected individuals in Thailand.

    PubMed

    Ungcharoensuk, Charoenchai; Putaporntip, Chaturong; Pattanawong, Urassaya; Jongwutiwes, Somchai

    2012-12-01

    The Ancylostoma secreted protein-2 of Necator americanus (Na-ASP-2) was one of the promising vaccine candidates against the most prevalent human hookworm species as adverse vaccine reaction has compromised further human vaccine trials. To elucidate the gene structure and the extent of sequence diversity, we determined the complete nucleotide sequence of the Na-asp-2 gene of individual larvae from 32 infected subjects living in 3 different endemic areas of Thailand. Sequence analysis revealed that the gene encoding Na-ASP-2 comprised 8 exons. Of 3 nucleotide substitutions in these exons, only one causes an amino acid change from leucine to methionine. A consensus conserved GT and AG at the 5' and the 3' boundaries of each intron was observed akin to those found in other eukaryotic genes. Introns of Na-asp-2 contained 23 nucleotide substitutions and 0-18 indels. The mean number of nucleotide substitutions per site (d) in introns was not significantly different from the mean number of synonymous substitutions per synonymous site (d(S)) in exons whereas d in introns was significantly exceeded d(N) (the mean number of nonsynonymous substitutions per nonsynonymous site) in exons (p<0.05), suggesting that introns and synonymous sites in exons may evolve at a similar rate whereas functional constraints at the amino acid could limit amino acid substitutions in Na-ASP-2. A recombination site was identified in an intron near the 3' portion of the gene. The positions of introns and the intron phases in the Na-asp-2 gene comparing with those in other pathogenesis-related-1 proteins of Loa loa, Onchocerca volvulus, Heterodera glycines, Caenorhabditis elegans and human were relatively conserved, suggesting evolutionary conservation of these genes. Sequence conservation in Na-ASP-2 may not compromise further vaccine design if adverse vaccine effects could be resolved whereas microheterogeneity in introns of this locus may be useful for population genetics analysis of N. americanus

  1. Sequence conservation in the Ancylostoma secreted protein-2 of Necator americanus (Na-ASP-2) from hookworm infected individuals in Thailand.

    PubMed

    Ungcharoensuk, Charoenchai; Putaporntip, Chaturong; Pattanawong, Urassaya; Jongwutiwes, Somchai

    2012-12-01

    The Ancylostoma secreted protein-2 of Necator americanus (Na-ASP-2) was one of the promising vaccine candidates against the most prevalent human hookworm species as adverse vaccine reaction has compromised further human vaccine trials. To elucidate the gene structure and the extent of sequence diversity, we determined the complete nucleotide sequence of the Na-asp-2 gene of individual larvae from 32 infected subjects living in 3 different endemic areas of Thailand. Sequence analysis revealed that the gene encoding Na-ASP-2 comprised 8 exons. Of 3 nucleotide substitutions in these exons, only one causes an amino acid change from leucine to methionine. A consensus conserved GT and AG at the 5' and the 3' boundaries of each intron was observed akin to those found in other eukaryotic genes. Introns of Na-asp-2 contained 23 nucleotide substitutions and 0-18 indels. The mean number of nucleotide substitutions per site (d) in introns was not significantly different from the mean number of synonymous substitutions per synonymous site (d(S)) in exons whereas d in introns was significantly exceeded d(N) (the mean number of nonsynonymous substitutions per nonsynonymous site) in exons (p<0.05), suggesting that introns and synonymous sites in exons may evolve at a similar rate whereas functional constraints at the amino acid could limit amino acid substitutions in Na-ASP-2. A recombination site was identified in an intron near the 3' portion of the gene. The positions of introns and the intron phases in the Na-asp-2 gene comparing with those in other pathogenesis-related-1 proteins of Loa loa, Onchocerca volvulus, Heterodera glycines, Caenorhabditis elegans and human were relatively conserved, suggesting evolutionary conservation of these genes. Sequence conservation in Na-ASP-2 may not compromise further vaccine design if adverse vaccine effects could be resolved whereas microheterogeneity in introns of this locus may be useful for population genetics analysis of N. americanus.

  2. Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

    PubMed Central

    2011-01-01

    Background Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction). Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success. PMID:21255386

  3. Selection pressure in CD8⁺ T-cell epitopes in the pol gene of HIV-1 infected individuals in Colombia. A bioinformatic approach.

    PubMed

    Acevedo-Sáenz, Liliana; Ochoa, Rodrigo; Rugeles, Maria Teresa; Olaya-García, Patricia; Velilla-Hernández, Paula Andrea; Diaz, Francisco J

    2015-03-20

    One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells.

  4. Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

    PubMed Central

    Cánepa, Camila; Salido, Jimena; Ruggieri, Matías; Fraile, Sindy; Pataccini, Gabriela; Berini, Carolina; Biglione, Mirna

    2015-01-01

    Background: indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas. Objectives: (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases. Results: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-time PCR (qPCR) was performed to 52 HTLV-1+ samples, classified as Group 1 (G1): 25 WB+ samples from individuals with pathologies; Group 2 (G2): 18 WB+ samples from asymptomatic carriers (AC); and Group 3 (G3): 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03). Conclusions: indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described;  their functional relevance remains to be determined. PMID:26516904

  5. Selection Pressure in CD8+ T-cell Epitopes in the pol Gene of HIV-1 Infected Individuals in Colombia. A Bioinformatic Approach

    PubMed Central

    Acevedo-Sáenz, Liliana; Ochoa, Rodrigo; Rugeles, Maria Teresa; Olaya-García, Patricia; Velilla-Hernández, Paula Andrea; Diaz, Francisco J.

    2015-01-01

    One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells. PMID:25803098

  6. Combining the Estimated Date of HIV Infection with a Phylogenetic Cluster Study to Better Understand HIV Spread: Application in a Paris Neighbourhood

    PubMed Central

    Robineau, Olivier; Frange, Pierre; Barin, Francis; Cazein, Françoise; Girard, Pierre-Marie; Chaix, Marie-Laure; Kreplak, Georges; Boelle, Pierre-Yves; Morand-Joubert, Laurence

    2015-01-01

    Objectives To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV. Methods HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP). Data on socio-demographic, clinical and biological features in clustered and non-clustered patients were compared. Chains of infection structure was also analysed. Results 547 patients were included, 49 chains of infection containing 108 (20%) patients were identified by phylogenetic analysis. analysis. Eighty individuals formed pairs and 28 individuals were belonging to larger clusters. The median time between two successive HIV diagnoses in the same chain of infection was 248 days [CI = 176–320]. 34.7% of individuals were considered as VEP, and 27% of them were included in chains of infection. Multivariable analysis showed that belonging to a cluster was more frequent in VEP and those under 30 years old (OR: 3.65, 95 CI 1.49–8.95, p = 0.005 and OR: 2.42, 95% CI 1.05–5.85, p = 0.04 respectively). The prevalence of drug resistance was not associated with belonging to a pair or a cluster. Within chains, VEP were not grouped together more than chance predicted (p = 0.97). Conclusions Most newly diagnosed patients did not belong to a chain of infection, confirming the importance of undiagnosed or untreated HIV infected individuals in transmission. Furthermore, clusters involving both recently infected individuals and longstanding infected individuals support a substantial role in transmission of the latter before diagnosis. PMID:26267615

  7. Export of newly formed LSW

    NASA Astrophysics Data System (ADS)

    Müller, Katharina; Klein, Birgit; Karstensen, Johannes; Fischer, Jürgen; Baumann, Till; Kanzow, Torsten

    2015-04-01

    The Atlantic meridional overturning circulation represents the strongest mechanism for oceanic northward heat transport. This is accomplished by moving warm water northward in the upper ocean compensated by a deep return flow of cold and dense North Atlantic Deep Water (NADW). Labrador Sea Water (LSW) constitutes the shallowest component of NADW. Since LSW is also supposed to be the most sensitive NADW component to climate change it is of particular interest. LSW is formed by deep convection not only in the centre of the Labrador Sea but also near its western boundary. Recent studies have suggested that LSW formed in the boundary region enters its export route from the Labrador Sea, the Deep Western Boundary Current, faster than LSW originating from the central Labrador Sea. In this study the spatial and temporal evolution of the export of newly formed LSW is investigated. For this purpose hydrographic mooring data from an array located at the western bounndary at 53°N starting in the late 1990s until 2014 and data from the Argo float network is used. The averaged seasonal salinity cycle at the array, particularly at the moorings further onshore, shows a pronounced freshwater signal in May indicating the arrival of newly formed LSW in the boundary current. In order to learn more about its preceding pathway and the corresponding export timescale the mooring data is complemented by data from Argo floats. Besides the annual cycles of LSW formation and export, their interannual variations are important aspects affecting the large-scale circulation. For instance, in years of relatively strong convection, as in 2008 and 2012, LSW is observed to pass the boundary current array at 53°N earlier, i.e. in February and March, respectively, than in years with weak convection, as in 2007 or 2010. Besides seasonal variations in the boundary current, a possible explanation for the earlier freshwater signal in years of enhanced convection might be a shift in convection sites

  8. Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

    PubMed Central

    Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2015-01-01

    Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

  9. Characterization of newly isolated lytic bacteriophages active against Acinetobacter baumannii.

    PubMed

    Merabishvili, Maia; Vandenheuvel, Dieter; Kropinski, Andrew M; Mast, Jan; De Vos, Daniel; Verbeken, Gilbert; Noben, Jean-Paul; Lavigne, Rob; Vaneechoutte, Mario; Pirnay, Jean-Paul

    2014-01-01

    Based on genotyping and host range, two newly isolated lytic bacteriophages, myovirus vB_AbaM_Acibel004 and podovirus vB_AbaP_Acibel007, active against Acinetobacter baumannii clinical strains, were selected from a new phage library for further characterization. The complete genomes of the two phages were analyzed. Both phages are characterized by broad host range and essential features of potential therapeutic phages, such as short latent period (27 and 21 min, respectively), high burst size (125 and 145, respectively), stability of activity in liquid culture and low frequency of occurrence of phage-resistant mutant bacterial cells. Genomic analysis showed that while Acibel004 represents a novel bacteriophage with resemblance to some unclassified Pseudomonas aeruginosa phages, Acibel007 belongs to the well-characterized genus of the Phikmvlikevirus. The newly isolated phages can serve as potential candidates for phage cocktails to control A. baumannii infections.

  10. A Screen-and-Treat Strategy Targeting Visceral Leishmaniasis in HIV-Infected Individuals in Endemic East African Countries: The Way Forward?

    PubMed Central

    van Griensven, Johan; Diro, Ermias; Lopez-Velez, Rogelio; Ritmeijer, Koert; Boelaert, Marleen; Zijlstra, Ed E.; Hailu, Asrat; Lynen, Lutgarde

    2014-01-01

    In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL–HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk–benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection. PMID:25101627

  11. Timing of entry to care by newly diagnosed HIV cases before and after the 2010 New York State HIV testing law.

    PubMed

    Gordon, Daniel E; Bian, Fuqin; Anderson, Bridget J; Smith, Lou C

    2015-01-01

    Prompt entry to care after HIV diagnosis benefits the infected individual and reduces the likelihood of further transmission of the virus. The New York State HIV Testing Law of 2010 requires diagnosing providers to refer persons newly diagnosed with HIV to follow-up medical care. This study used routinely collected HIV-related laboratory data from the New York State HIV surveillance system to assess whether the fraction of newly diagnosed cases entering care within 90 days of diagnosis increased after the implementation of the law. Laboratory data on 23,302 newly diagnosed cases showed that entry to care within 90 days rose steadily from 72.0% in 2007 to 85.4% in 2012. The rise was observed across all race/ethnic groups, ages, transmission risk groups, sexes, and regions of residence. Logistic regression analyses of entry to care pre-law and post-law, controlling for demographic characteristics, transmission risk, and geographic area, indicate that percentage of newly diagnosed cases entering care within 90 days grew more rapidly in the post-law period. This is consistent with a positive effect of the law on entry to care.

  12. Minimization of genetic distances by the consensus, ancestral, and center-of-tree (COT) sequences for HIV-1 variants within an infected individual and the design of reagents to test immune reactivity.

    PubMed

    Kesturu, Girish S; Colleton, Bonnie A; Liu, Yi; Heath, Laura; Shaikh, Obaid Shakil; Rinaldo, Charles R; Shankarappa, Raj

    2006-05-10

    Eliciting maximal immune responses to highly divergent viruses is a challenge and a focus in AIDS vaccine development. Another challenge is to identify the immune correlates of protective immunity. Recent AIDS vaccine design approaches attempt to use reconstructed centralized viral sequences that minimize genetic differences to circulating viruses. Using these approaches, we derive and analyze consensus (CON), ancestral (ANC), and center-of-tree (COT) sequences to represent intra-individual HIV-1 env variants encoding a range of diversities and phylogenetic structures. Each reconstructed sequence significantly minimized genetic distances to extant sequences throughout the first 5 years of infection of an individual. Interestingly, ANC sequences diverged and were not significantly better than extant sequences in minimizing genetic distances at later stages of infection and disease, likely due to the development of a substantially asymmetric phylogeny. COT or CON sequences derived from autologous virus samplings may be useful for increasing the sensitivity of assessments of immune reactivity against HIV.

  13. Newly Identified Pathogens Associated with Periodontitis

    PubMed Central

    Pérez-Chaparro, P.J.; Gonçalves, C.; Figueiredo, L.C.; Faveri, M.; Lobão, E.; Tamashiro, N.; Duarte, P.; Feres, M.

    2014-01-01

    There is substantial evidence supporting the role of certain oral bacteria species in the onset and progression of periodontitis. Nevertheless, results of independent-culture diagnostic methods introduced about a decade ago have pointed to the existence of new periodontal pathogens. However, the data of these studies have not been evaluated together, which may generate some misunderstanding on the actual role of these microorganisms in the etiology of periodontitis. The aim of this systematic review was to determine the current weight of evidence for newly identified periodontal pathogens based on the results of “association” studies. This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE, EMBASE, and Cochrane databases were searched up to September 2013 for studies (1) comparing microbial data of subgingival plaque samples collected from subjects with periodontitis and periodontal health and (2) evaluating at least 1 microorganism other than the already-known periodontal pathogens. From 1,450 papers identified, 41 studies were eligible. The data were extracted and registered in predefined piloted forms. The results suggested that there is moderate evidence in the literature to support the association of 17 species or phylotypes from the phyla Bacteroidetes, Candidatus Saccharibacteria, Firmicutes, Proteobacteria, Spirochaetes, and Synergistetes. The phylum Candidatus Saccharibacteria and the Archaea domain also seem to have an association with disease. These data point out the importance of previously unidentified species in the etiology of periodontitis and might guide future investigations on the actual role of these suspected new pathogens in the onset and progression of this infection. PMID:25074492

  14. [The Spanish AIDS Study Group and Spanish National AIDS Plan (GESIDA/Secretaría del Plan Nacional sobre el Sida) recommendations for the treatment of tuberculosis in HIV-infected individuals (Updated January 2013)].

    PubMed

    Rivero, Antonio; Pulido, Federico; Caylá, Joan; Iribarren, José A; Miró, José M; Moreno, Santiago; Pérez-Camacho, Inés

    2013-12-01

    This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group.

  15. HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A

    PubMed Central

    Vince, Nicolas; Bashirova, Arman A.; Lied, Alexandra; Gao, Xiaojiang; Dorrell, Lucy; McLaren, Paul J.; Fellay, Jacques; Carrington, Mary

    2014-01-01

    A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond homozygosity for CCR5-Δ32. Since variation in HLA class I and KIR genes is not well interrogated by standard GWAS techniques, we tested whether these 2 loci were involved in protection from HIV-1 infection in the same hemophilia cohort, using controls from the general population. Our data indicate that HLA class I alleles, presence or absence of KIR genes, and functionally relevant combinations of the HLA/KIR genotypes are not involved in resistance to parenterally transmitted HIV-1 infection. PMID:24719475

  16. Prevalence of hyperglycemia among adults with newly diagnosed HIV/AIDS in China

    PubMed Central

    2013-01-01

    Background The prevalence of hyperglycemia among HIV-infected persons who are not receiving antiretroviral therapy is unknown. We conducted a cross-sectional survey to estimate the prevalence of hyperglycemia among Chinese adults with newly diagnosed HIV/AIDS. Methods Two thousand and six newly diagnosed HIV/AIDS patients from 10 provinces and municipalities in China were selected during 2009 to 2010. After an overnight fast, serum samples were collected to measure glucose concentrations. Demographics and medical histories were recorded. Factors associated with the presence of diabetes were analysed by logistic regression. Results Among the 2006 patients, 75.67% were male. Median age was 40 years (range: 18–86 years). 19.99% had hyperglycemia, 9.47% had impaired fasting glucose (IFG) and 10.52% had diabetes. The prevalences of hyperglycemia, of IFG and of diabetes were 21.54%, 10.28% and 11.27% among men and 15.16%, 6.97% and 8.20% among women, respectively. The prevalence of diabetes increased with increasing age (7.00%, 13.36% and 21.21% among patients who were 18–40, 40–60, and ≥60 years of age respectively) and with decreasing CD4 count (6.74%, 8.45%, 9.69%, and 12.66% among patients with CD4 count of ≥350, 200–350, 50–200, and < 50/mm3 respectively). The prevalence of diabetes was higher among ethnic minority patients than among the Han patients (14.37% versus 9.24%). The logistic analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of diabetes. Conclusions Hyperglycemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS. Older age, lower CD4 count and minority ethnicity are associated with increased risk of diabetes. All newly diagnosed HIV/AIDS individuals should be routinely evaluated for hyperglycemia. PMID:23394285

  17. Identification of Past and Recent Parvovirus B19 Infection in Immunocompetent Individuals by Quantitative PCR and Enzyme Immunoassays: a Dual-Laboratory Study

    PubMed Central

    Hedman, Lea; Dhanilall, Pravesh; Kantola, Kalle; Nurmi, Visa; Söderlund-Venermo, Maria; Brown, Kevin E.; Hedman, Klaus

    2014-01-01

    Parvovirus B19 (B19V) is a member of the family Parvoviridae, genus Erythrovirus. B19V-specific IgG and IgM react differently against conformational and linear epitopes of VP1 and VP2 antigens, leading to the development of IgG avidity and epitope type specificity (ETS) enzyme immunoassays (EIAs) for distinguishing past from recent infection. Additionally, B19V viral load determination (by quantitative PCR [qPCR]) is increasingly used in the staging of B19V infection. In this study, the utility of these methods is compared. A panel of 78 sera was jointly tested by the Virus Reference Department (VRD), London, United Kingdom, and the Haartman Institute (HI), Helsinki, Finland, using a number of EIAs, e.g., B19V-specific IgG and IgM, IgG avidity, and ETS EIAs. At VRD, the sera were also tested by a B19V viral load PCR (qPCR). By consensus analysis, 43 (55.1%) sera represented past infection, 28 (35.9%) sera represented recent infection, and 7 (9.0%) sera were indeterminate. Both VRD B19V qPCR and HI B19V VP2 IgM EIA gave the highest agreement with consensus interpretation for past or recent infection, with an overall agreement of 99% (95% confidence interval [CI], 92 to 100) and positive predictive value (PPV) of 100% (95% CI, 87 to 100). Nine sera designated as representing past infection by consensus analysis were B19V IgM positive by a commercial VRD B19V IgM EIA and B19V IgM negative by a new HI in-house B19V VP2 IgM EIA. A new VRD B19V IgG avidity EIA showed good (>95%) agreement (excluding equivocal results) with consensus interpretations for past or recent infection. Correct discrimination of past from recent B19V infection was achieved through application of qPCR or by appropriate selection of EIAs. PMID:24403307

  18. Time-Resolved Visualisation of Nearly-Native Influenza A Virus Progeny Ribonucleoproteins and Their Individual Components in Live Infected Cells.

    PubMed

    Avilov, Sergiy; Magnus, Julie; Cusack, Stephen; Naffakh, Nadia

    2016-01-01

    Influenza viruses are a global health concern because of the permanent threat of novel emerging strains potentially capable of causing pandemics. Viral ribonucleoproteins (vRNPs) containing genomic RNA segments, nucleoprotein oligomers, and the viral polymerase, play a central role in the viral replication cycle. Our knowledge about critical events such as vRNP assembly and interactions with other viral and cellular proteins is poor and could be substantially improved by time lapse imaging of the infected cells. However, such studies are limited by the difficulty to achieve live-cell compatible labeling of active vRNPs. Previously we designed the first unimpaired recombinant influenza WSN-PB2-GFP11 virus allowing fluorescent labeling of the PB2 subunit of the viral polymerase (Avilov et al., J.Virol. 2012). Here, we simultaneously labeled the viral PB2 protein using the above-mentioned strategy, and virus-encoded progeny RNPs through spontaneous incorporation of transiently expressed NP-mCherry fusion proteins during RNP assembly in live infected cells. This dual labeling enabled us to visualize progeny vRNPs throughout the infection cycle and to characterize independently the mobility, oligomerization status and interactions of vRNP components in the nuclei of live infected cells. PMID:26978069

  19. Time-Resolved Visualisation of Nearly-Native Influenza A Virus Progeny Ribonucleoproteins and Their Individual Components in Live Infected Cells

    PubMed Central

    Avilov, Sergiy; Magnus, Julie; Cusack, Stephen; Naffakh, Nadia

    2016-01-01

    Influenza viruses are a global health concern because of the permanent threat of novel emerging strains potentially capable of causing pandemics. Viral ribonucleoproteins (vRNPs) containing genomic RNA segments, nucleoprotein oligomers, and the viral polymerase, play a central role in the viral replication cycle. Our knowledge about critical events such as vRNP assembly and interactions with other viral and cellular proteins is poor and could be substantially improved by time lapse imaging of the infected cells. However, such studies are limited by the difficulty to achieve live-cell compatible labeling of active vRNPs. Previously we designed the first unimpaired recombinant influenza WSN-PB2-GFP11 virus allowing fluorescent labeling of the PB2 subunit of the viral polymerase (Avilov et al., J.Virol. 2012). Here, we simultaneously labeled the viral PB2 protein using the above-mentioned strategy, and virus-encoded progeny RNPs through spontaneous incorporation of transiently expressed NP-mCherry fusion proteins during RNP assembly in live infected cells. This dual labeling enabled us to visualize progeny vRNPs throughout the infection cycle and to characterize independently the mobility, oligomerization status and interactions of vRNP components in the nuclei of live infected cells. PMID:26978069

  20. Data on pro-inflammatory cytokines IL-1β, IL-17, and IL-6 in the peripheral blood of HIV-infected individuals.

    PubMed

    Saing, Tommy; Valdivia, Anddre; Hussain, Parveen; Ly, Judy; Gonzalez, Leslie; Guilford, Frederick T; Pearce, Daniel; Venketaraman, Vishwanath

    2016-09-01

    Our most recent data indicate differences in the levels of pro-inflammatory cytokines (IL-1β, IL-17, and IL-6) and malondialdehyde (MDA), a stable end-product of lipid peroxidation in the plasma samples between HIV positive individuals with low CD4 T cell counts <200 mm(3) and HIV positive individuals with CD4 T cell counts between 200 and 300 mm(3) (ee). The data lend support and provide valuable correlation between CD4 T cell counts and the levels of inflammatory cytokines in HIV positive individuals.

  1. Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.

    PubMed

    Hansjee, Natasha; Kaufmann, Gilbert R; Strub, Christoph; Weber, Rainer; Battegay, Manuel; Erb, Peter

    2004-06-01

    CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration. PMID:15167285

  2. Estimation of the Undiagnosed Intervals of HIV-Infected Individuals by a Modified Back-Calculation Method for Reconstructing the Epidemic Curves

    PubMed Central

    Wong, Ka Hing; Lee, Man Po; Tsang, Owen T. Y.; Chan, Denise P. C.; Lee, Shui Shan

    2016-01-01

    Background Undiagnosed infections accounted for the hidden proportion of HIV cases that have escaped from public health surveillance. To assess the population risk of HIV transmission, we estimated the undiagnosed interval of each known infection for constructing the HIV incidence curves. Methods We used modified back-calculation methods to estimate the seroconversion year for each diagnosed patient attending any one of the 3 HIV specialist clinics in Hong Kong. Three approaches were used, depending on the adequacy of CD4 data: (A) estimating one’s pre-treatment CD4 depletion rate in multilevel model;(B) projecting one’s seroconversion year by referencing seroconverters’ CD4 depletion rate; or (C) projecting from the distribution of estimated undiagnosed intervals in (B). Factors associated with long undiagnosed interval (>2 years) were examined in univariate analyses. Epidemic curves constructed from estimated seroconversion data were evaluated by modes of transmission. Results Between 1991 and 2010, a total of 3695 adult HIV patients were diagnosed. The undiagnosed intervals were derived from method (A) (28%), (B) (61%) and (C) (11%) respectively. The intervals ranged from 0 to 10 years, and were shortened from 2001. Heterosexual infection, female, Chinese and age >64 at diagnosis were associated with long undiagnosed interval. Overall, the peaks of the new incidence curves were reached 4–6 years ahead of reported diagnoses, while their contours varied by mode of transmission. Characteristically, the epidemic growth of heterosexual male and female declined after 1998 with slight rebound in 2004–2006, but that of MSM continued to rise after 1998. Conclusions By determining the time of seroconversion, HIV epidemic curves could be reconstructed from clinical data to better illustrate the trends of new infections. With the increasing coverage of antiretroviral therapy, the undiagnosed interval can add to the measures for assessing HIV transmission risk in

  3. Confidence in leadership among the newly qualified.

    PubMed

    Bayliss-Pratt, Lisa; Morley, Mary; Bagley, Liz; Alderson, Steven

    2013-10-23

    The Francis report highlighted the importance of strong leadership from health professionals but it is unclear how prepared those who are newly qualified feel to take on a leadership role. We aimed to assess the confidence of newly qualified health professionals working in the West Midlands in the different competencies of the NHS Leadership Framework. Most respondents felt confident in their abilities to demonstrate personal qualities and work with others, but less so at managing or improving services or setting direction.

  4. HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: advantages of the Cuban population for HLA studies of dengue virus infection.

    PubMed

    Sierra, Beatriz; Alegre, Roberto; Pérez, Ana B; García, Gissel; Sturn-Ramirez, Katharina; Obasanjo, Olugbenga; Aguirre, Eglys; Alvarez, Mayling; Rodriguez-Roche, Rosmari; Valdés, Luis; Kanki, Phyllis; Guzmán, María G

    2007-06-01

    Dengue virus infection has emerged as one of the most important arthropod-borne diseases. In some dengue-infected individual, the disease progresses to its severe, life-threatening form, dengue hemorrhagic fever (DHF). Host genetic factors may be relevant and predispose some individuals to the severe dengue disease. The unique history of dengue outbreaks in Cuba is extremely advantageous for genetic studies of dengue disease resistance or susceptibility. Consequently, samples collected from 120 healthy individuals that developed dengue fever (DF) and DHF during the 1997 dengue 2 outbreak in the Santiago de Cuba municipality were HLA genotyped using polymerase chain reaction-sequence-specific primers. Polymorphism at the human leukocyte antigen (HLA) class I loci was significantly associated with DHF disease susceptibility, but polymorphism in the HLA-DRB1 was associated with protection. Amino acid peptides present in the poly-protein of the dengue 2 Jamaica strain, which are able to bind to the HLA class I and class II allotypes associated with susceptibility to or protection against the dengue clinical disease, respectively, were predicted using the BIMAS and SYFPEITHI predictive algorithms of peptide/MHC interaction.

  5. A multi-stage compartmental model for HIV-infected individuals: II--application to insurance functions and health-care costs.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Stochastic population processes have received a lot of attention over the years. One approach focuses on compartmental modeling. Billard and Dayananda (2012) developed one such multi-stage model for epidemic processes in which the possibility that individuals can die at any stage from non-disease related causes was also included. This extra feature is of particular interest to the insurance and health-care industries among others especially when the epidemic is HIV/AIDS. Rather than working with numbers of individuals in each stage, they obtained distributional results dealing with the waiting time any one individual spent in each stage given the initial stage. In this work, the impact of the HIV/AIDS epidemic on several functions relevant to these industries (such as adjustments to premiums) is investigated. Theoretical results are derived, followed by a numerical study.

  6. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity.

    PubMed

    Cheroni, Cristina; Donnici, Lorena; Aghemo, Alessio; Balistreri, Francesca; Bianco, Annalisa; Zanoni, Valeria; Pagani, Massimiliano; Soffredini, Roberta; D'Ambrosio, Roberta; Rumi, Maria Grazia; Colombo, Massimo; Abrignani, Sergio; Neddermann, Petra; De Francesco, Raffaele

    2015-01-01

    Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment.

  7. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity

    PubMed Central

    Aghemo, Alessio; Balistreri, Francesca; Bianco, Annalisa; Zanoni, Valeria; Pagani, Massimiliano; Soffredini, Roberta; D’Ambrosio, Roberta; Rumi, Maria Grazia; Colombo, Massimo; Abrignani, Sergio; Neddermann, Petra; De Francesco, Raffaele

    2015-01-01

    Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment. PMID:26405760

  8. Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient.

    PubMed

    Kammalac Ngouana, Thierry; Drakulovski, Pascal; Krasteva, Donika; Kouanfack, Charles; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice Fekam; Mallié, Michèle; Bertout, Sebastien

    2016-07-01

    Cryptococcal meningitis is a dreadful opportunistic fungal infection amongst human immunodeficiency virus (HIV)-infected patients. One complication in the management of the disease is the possible infection of a patient by two or more different strains of Cryptococcus neoformans. This study investigated the intra-individual genetic diversity and antifungal susceptibility of C. neoformans isolates from Yaoundé (Cameroon) HIV-infected patients with cryptococcal meningitis. Twenty-five clinical isolates were obtained during a prospective study. Five colonies were randomly collected from each initial sample. The 150 isolates obtained (125 colonies and 25 initial samples) were submitted to serotyping by multiplex PCR. Genotyping analyses were achieved using RFLP, and minisatellite- and microsatellite-length polymorphism. The antifungal susceptibility testing was carried out using a Sensititre YeastOne kit. Seven antifungals were tested: itraconazole, fluconazole, amphotericin B, ketoconazole, 5-fluorocytosine, posaconazole and voriconazole. The 150 isolates were identified as C. neoformans serotype A and genotype VNI. The microsatellite and minisatellite sequence analyses generated 15 genotypes. Six out of 25 (24 %) patients were found to be infected by two different genotypes. Antifungal susceptibility showed several profiles: posaconazole (0.015-0.25 µg ml-1), amphotericin B (0.06-1 µg ml-1), fluconazole (0.5-16 µg ml-1), itraconazole (0.008-0.12 µg ml-1), ketoconazole (0.008-0.12 µg ml-1), 5-fluorocytosine (0.25-16 µg ml-1) and voriconazole (0.008-0.12 µg ml-1). It was noted that isolates from the same patient might present different susceptibility profiles to an antifungal drug with differences of more than four dilutions. The results achieved highlighted the possible presence of isolates with different genotypes in a patient with dissimilar antifungal susceptibility profiles during a single episode of cryptococcal meningitis. PMID:27100672

  9. Detection and Isolation of Swine Influenza A Virus in Spiked Oral Fluid and Samples from Individually Housed, Experimentally Infected Pigs: Potential Role of Porcine Oral Fluid in Active Influenza A Virus Surveillance in Swine

    PubMed Central

    Decorte, Inge; Steensels, Mieke; Lambrecht, Bénédicte

    2015-01-01

    Background The lack of seasonality of swine influenza A virus (swIAV) in combination with the capacity of swine to harbor a large number of co-circulating IAV lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swIAV surveillance. To date, active surveillance of swIAV worldwide is barely done because of the short detection period in nasal swab samples. Therefore, more sensitive diagnostic methods to monitor circulating virus strains are requisite. Methods qRT-PCR and virus isolations were performed on oral fluid and nasal swabs collected from individually housed pigs that were infected sequentially with H1N1 and H3N2 swIAV strains. The same methods were also applied to oral fluid samples spiked with H1N1 to study the influence of conservation time and temperature on swIAV infectivity and detectability in porcine oral fluid. Results All swIAV infected animals were found qRT-PCR positive in both nasal swabs and oral fluid. However, swIAV could be detected for a longer period in oral fluid than in nasal swabs. Despite the high detectability of swIAV in oral fluid, virus isolation from oral fluid collected from infected pigs was rare. These results are supported by laboratory studies showing that the PCR detectability of swIAV remains unaltered during a 24 h incubation period in oral fluid, while swIAV infectivity drops dramatically immediately upon contact with oral fluid (3 log titer reduction) and gets lost after 24 h conservation in oral fluid at ambient temperature. Conclusions Our data indicate that porcine oral fluid has the potential to replace nasal swabs for molecular diagnostic purposes. The difficulty to isolate swIAV from oral fluid could pose a drawback for its use in active surveillance programs. PMID:26431039

  10. Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

    PubMed Central

    Murray, Daniel D.; Suzuki, Kazuo; Law, Matthew; Trebicka, Jonel; Neuhaus, Jacquie; Wentworth, Deborah; Johnson, Margaret; Vjecha, Michael J.; Kelleher, Anthony D.; Emery, Sean

    2015-01-01

    Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection. PMID:26465293

  11. HIV-1 Genetic Diversity and Transmitted Drug Resistance Among Recently Infected Individuals at Men Who Have Sex with Men Sentinel Surveillance Points in Hebei Province, China.

    PubMed

    Lu, Xinli; Kang, Xianjiang; Chen, Suliang; Zhao, Hongru; Liu, Yongjian; Zhao, Cuiying; Zhang, Yuqi; Li, Jingyun; Cui, Ze; Wang, Xianfeng

    2015-10-01

    For this study, 50 HIV-1 plasma samples of recently infected men who have sex with men (MSM) were amplified and sequenced. Multiple subtypes were identified by phylogenetic analyses of HIV-1 gag, env, and pol gene regions, including CRF01_AE (56.0%), CRF07_BC (30.0%), subtype B (12.0%), and unique recombinant forms (URFs, 6.0%). CRF01_AE was the most frequent genotype in the epidemic. Three recombination patterns of URFs were identified: 01BC, 01B, and 01C. The rate of HIV-1 transmitted drug resistance (TDR) mutation (M46L) was 2.08% (1/48). URFs and TDR first identified in this study suggest that HIV-1 prevalence is more and more complicated, and HIV-1 drug-resistant strains have begun to spread among at risk populations in Hebei. Our findings can provide vital information for an efficient surveillance system and strategic HIV prevention and control measures in China by revealing the evolutionary status and HIV-1 TDR of HIV-1 strains among recently infected MSM in Hebei Province.

  12. HIV-1 Genetic Diversity and Transmitted Drug Resistance Among Recently Infected Individuals at Men Who Have Sex with Men Sentinel Surveillance Points in Hebei Province, China.

    PubMed

    Lu, Xinli; Kang, Xianjiang; Chen, Suliang; Zhao, Hongru; Liu, Yongjian; Zhao, Cuiying; Zhang, Yuqi; Li, Jingyun; Cui, Ze; Wang, Xianfeng

    2015-10-01

    For this study, 50 HIV-1 plasma samples of recently infected men who have sex with men (MSM) were amplified and sequenced. Multiple subtypes were identified by phylogenetic analyses of HIV-1 gag, env, and pol gene regions, including CRF01_AE (56.0%), CRF07_BC (30.0%), subtype B (12.0%), and unique recombinant forms (URFs, 6.0%). CRF01_AE was the most frequent genotype in the epidemic. Three recombination patterns of URFs were identified: 01BC, 01B, and 01C. The rate of HIV-1 transmitted drug resistance (TDR) mutation (M46L) was 2.08% (1/48). URFs and TDR first identified in this study suggest that HIV-1 prevalence is more and more complicated, and HIV-1 drug-resistant strains have begun to spread among at risk populations in Hebei. Our findings can provide vital information for an efficient surveillance system and strategic HIV prevention and control measures in China by revealing the evolutionary status and HIV-1 TDR of HIV-1 strains among recently infected MSM in Hebei Province. PMID:26200883

  13. Interleukin-35 is upregulated in response to influenza virus infection and secondary bacterial pneumonia.

    PubMed

    Chen, Yi; Wang, Chuan-jiang; Lin, Shi-hui; Zhang, Mu; Li, Sheng-yuan; Xu, Fang

    2016-05-01

    Postinfluenza pneumococcal pneumonia is an important cause of global morbidity and mortality. What causes this increased susceptibility is not well elucidated. IL-35 is a newly described cytokine in infectious tolerance. A murine model was established to study postinfluenza pneumococcal pneumonia and evaluate the role of IL-35 in host defense against postinfluenza pneumococcal pneumonia. Pulmonary IL-35 was rapidly up-regulated during murine influenza infection, which was partially mediated by type I IFN-α/β receptor signaling pathway. Secondary pneumococcal infection led to a synergistic IL-35 response in influenza-infected mice. Clinical analysis showed that IL-35 levels were significantly elevated in the patients with influenza infection compared with healthy individuals and influenza infection could induce IL-35 production from human peripheral blood mononuclear cells. These data suggest that IL-35 contributes to the increased susceptibility to secondary pneumococcal pneumonia at least in part by inhibiting the early immune response.

  14. Social Individualism.

    ERIC Educational Resources Information Center

    Cornille, Thomas A.; Harrigan, John

    Relationships between individuals and society have often been presented from the perspective of the social institution. Social psychology has addressed the variables that affect the individual in relationships with larger groups. Social individualism is a conceptual framework that explores the relationship of the individual and society from the…

  15. Regulatory T cells generated during cytomegalovirus in vitro stimulation of mononuclear cells from HIV-infected individuals on HAART correlate with decreased lymphocyte proliferation

    SciTech Connect

    Jesser, Renee D.; Li, Shaobing; Weinberg, Adriana . E-mail: Adriana.Weinberg@uchsc.edu

    2006-09-01

    HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, we studied the phenotype and function of in vitro cytomegalovirus (CMV)-stimulated T cells from HAART recipients. CFSE-measured proliferation showed CD4{sup +} and CD8{sup +} cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from HAART recipients had lower {sup 3}H-thymidine incorporation; lower IFN{gamma} and TNF{alpha} production; higher CD4{sup +}CD27{sup -}CD28{sup -} and CD8{sup +}CD27{sup -}CD28{sup -} frequencies; lower CD4{sup +}CD25{sup hi}; and higher FoxP3 expression in CD8{sup +}CD25{sup hi} cells. CMV-specific proliferation correlated with higher IFN{gamma}, TNF{alpha} and IL10 levels and higher CD4{sup +}perforin{sup +} and CD8{sup +}perforin{sup +} frequencies. Decreased proliferation correlated with higher CD4{sup +}CD27{sup -}CD28{sup -} frequencies and TGF{beta}1 production, which also correlated with each other. Anti-TGF{beta}1 neutralizing antibodies restored CMV-specific proliferation in a dose-dependent fashion. In HIV-infected subjects, decreased proliferation correlated with higher CMV-stimulated CD8{sup +}CD25{sup hi} frequencies and their FoxP3 expression. These data indicate that FoxP3- and TGF{beta}1-expressing regulatory T cells contribute to decreased immunity in HAART recipients.

  16. Discovery of a Novel Mutation (X8Del) Resulting in an 8-bp Deletion in the Hepatitis B Virus X Gene Associated with Occult Infection in Korean Vaccinated Individuals.

    PubMed

    Kim, Hong; Gong, Jeong-Ryeol; Lee, Seoung-Ae; Kim, Bum-Joon

    2015-01-01

    Universal infantile hepatitis B virus (HBV) vaccination may lead to an increase in vaccine escape variants, which may pose a threat to the long-term success of massive vaccination. To determine the prevalence of occult infections in Korean vaccinated individuals, 87 vaccinated subjects were screened for the presence of HBV DNA using both the nested PCR protocol and the VERSANT HBV DNA 3.0 assay. The mutation patterns of variants were analyzed in full-length HBV genome sequences. Their HBsAg secretion and replication capacities were investigated using both in vitro transient transfection and in vivo hydrodynamic injection. The presence of HBV DNA was confirmed in 6 subjects (6.9%). All six variants had a common mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of the HBV X gene (HBxAg). Our in vitro and in vivo analyses using the full-length HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg and HBV virions compared to the wild type. In conclusion, our data suggest that a novel mutation (X8Del) may contribute to occult HBV infection in Korean vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by compromising HBxAg's transacting capacity. PMID:26437447

  17. The efficacy of oxytetracycline treatment at batch, pen and individual level on Lawsonia intracellularis infection in nursery pigs in a randomised clinical trial.

    PubMed

    Larsen, Inge; Nielsen, Søren Saxmose; Olsen, John Elmerdahl; Nielsen, Jens Peter

    2016-02-01

    Antimicrobial consumption in animal husbandry is of great scientific and political concern due to the risk of selection of resistant bacteria. Whilst a reduction in the use of antimicrobials is therefore preferable, the efficacy of treatment must be maintained in order to ensure animal welfare and profitability of pig production. The objective of this study was to evaluate the efficacy of three treatment strategies under field conditions against Lawsonia intracellularis (LI)-related diarrhoea. A randomised clinical trial was carried out in four Danish pig herds, including a total of 520 pigs from 36 nursery batches. A high prevalence of LI was demonstrated in all herds prior to the initiation of the study. Treatment efficacy was assessed by faecal shedding of LI, the occurrence of diarrhoea and average daily weight gain (ADG) after treatment. All strategies were implemented at batch level at presence of LI-related diarrhoea and included daily treatment with 10mg oxytetracycline (OTC) per kilogram of bodyweight for 5 days, though the OTC was administered differently: either by oral treatment of all pigs in a batch, by oral treatment of pigs in diarrhoeic pens only, or by intramuscular treatment of individual diarrhoeic pigs only. The treatment strategies were randomly allocated to batches and were initiated at the presence of diarrhoea. From the included batches, 100% of the trial pigs were medicated in the batch treatment strategy, 87% in the pen treatment strategy and 55% in the individual treatment strategy. All strategies reduced the occurrence of diarrhoea and faecal shedding of LI after treatment. However, batch treatment was found to be most efficient in reducing both high-level LI shedding and diarrhoea when compared to the treatment of diarrhoeic pens or individual diarrhoeic pigs. There was no significant difference identified in ADG between the treatment strategies. In conclusion, batch treatment of all pigs in a section resulted in the highest efficacy

  18. Fusarium Solani: a causative agent of skin and nail infections.

    PubMed

    Kuruvilla, Thomas S; Dias, Meena

    2012-07-01

    Fusarium spp are non-dermatophytic hyaline moulds found as saprophytes and plant pathogens. Human infections are probably a result of various precipitating predisposing factors of impaired immune status. Immunocompetent individuals of late are also vulnerable to various unassuming saprophytic and plant pathogens. To stress the need to identify correctly and institute appropriate antifungal therapy in newly emerging human fungal infectious agents. Repeated mycological sampling of the skin and nails of the suspected fungal infection were processed as per the standard format including direct microscopy and fungal culture on Sabouraud's dextrose agar. The fungus was isolated as Fusarium solani. Fusarium is an important plant pathogen and soil saprophyte. Infection is acquired by direct inoculation or inhalation of spores. It is associated with a variety of diseases like keratitis, onychomycosis, eumycetoma, skin lesions and disseminated diseases.

  19. [Influence of Opiate Abuse on Expression of Toll-like Receptor 9 in Peripheral Blood Mononuclear Cells of HIV-1-Infected Individuals].

    PubMed

    Pan, Peijiang; Wei, Fumei; Jiang, Junjun; Liang, Bingyu; Huang, Jiegang; Liao, Yanyan; Su, Jinming; Li, Yu; Yang, Xiaoyi; Chen, Hui; Ye, Li; Liang, Hao

    2015-03-01

    The aim of this study was to investigate the influence of opiate abuse on the expression of Toll-like receptor 9 (TLR9) in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients and to elucidate possible mechanisms involved in the enhancement of HIV-1 replication by opiate abuse. A total of 200 participants were enrolled in the study by random selection from methadone treatment centers and voluntary HIV counseling and testing centers in the cities of Nanning, Liuzhou, and Qinzhou. These participants included 50 HIV-positive opiate abusers (Opiates HIV(+) group), 50 HIV-negative opiate abusers (Opiates HIV(-) group), 50 HIV-positive subjects who were not opiate abusers (Non-opiates HIV (+) group), and 50 HIV-negative subjects who were not opiate abusers (Control group). PBMCs were isolated from the peripheral blood samples from the subjects and the expression levels of TLR9 mRNA and protein were determined by q-PCR and western blot respectively. There was no significant difference among the four groups in age, gender, nationality, domicile, marital status, educational background or duration of drug abuse (P > 0.05). The median viral loads of the Opiates HIV(+) were significantly higher than those of the Non-Opiates HIV(+) groups (4.450 x 10(3) and 3.977 x 10(3) copies/mL respectively, P < 0.05). The relative expression levels of TLR9 mRNA in the Opiates HIV(+), Non-Opiates HIV(+), Opiates HIV(-) and Control groups were (2.13 +/- 1.59) x 10(-3), (3.66 +/- 2.22) x 10(-3), (1.96 +/- 1.42) x 10(-3) and (7.66 +/- 4.87) x 10(-3), respectively. The expression of TLR9 mRNA was significantly lower in both HIV-1-infected and -uninfected groups of opiate abusers compared with groups of non-abusers (P < 0.05). There was no significant difference in TLR9 mRNA expression levels between the Opiates HIV(+) group and the Opiates HIV(-) group (P > 0.05). However, in the non-opiate groups, the expression levels of TLR9 mRNA in the HIV(+) group were significantly

  20. Patterns and predictors of multiple sexual partnerships among newly arrived Latino migrant men

    PubMed Central

    Althoff, Meghan D; Anderson-Smits, Colin; Kovacs, Stephanie; Salinas, Oscar; Hembling, John; Schmidt, Norine; Kissinger, Patricia

    2012-01-01

    Multiple sexual partnerships (MSP), both concurrent and serial short gap, are thought to increase the risk of HIV and sexually transmitted infection (STI) acquisition and transmission. In this study we evaluate potential individual and environmental risk factors for engaging in MSP in a cohort of newly arrived Latino migrant men (LMM) in New Orleans, LA, USA. Participants were surveyed at three time points over a nine-month period to examine factors associated with MSP. Of the 113 men, 32.5% reported ever MSP. In 290 observations, 19.5% of men had concurrent, and 15.0% had serial short gap partnerships in at least one interviews. Substance was associated with MSP, OR (95% CI) 2.00 (1.16, 3.45) whereas belonging to a community organization was found to be protective, OR 0.32 (0.17, 0.59). Interventions to reduce substance use and promote social connection are needed to prevent a potential HIV/STI epidemic in this population. PMID:22996353

  1. Use of the Alcohol Use Disorders Identification Test (AUDIT) to determine the prevalence of alcohol misuse among HIV-infected individuals.

    PubMed

    Surah, S; Kieran, J; O'Dea, S; Shiel, C; Raffee, S; Mulcahy, F; Keenan, E; Lyons, F

    2013-07-01

    The aim of the paper is to evaluate alcohol misuse among an inner city adult HIV clinic population with AUDIT (Alcohol Use Disorders Identification Test). A cross-sectional HIV outpatient clinic analysis between 28 February 2011 and 11 March 2011 was carried out. AUDIT, demographic and clinical data were collected. Univariate analysis was performed to look for the associations between variables. Backward stepwise multivariate analyses were performed on significant variables from the univariate analysis to assess for predictors of alcohol dependence. In total, 111 patients were included (60% uptake of clinic attendees); 66% were men and 26% were hepatitis C virus (HCV) co-infected. The median AUDIT score was 5 (within normal range). Thirty-four 'AUDIT positive' cases were identified: five (4.5%) indicated consumption of hazardous levels of alcohol; 21 (19%) indicated harmful levels of alcohol; and eight (7%) were likely alcohol dependent. Younger age (<40 years old) was significantly associated with AUDIT positivity (P = 0.006). On multivariate analysis younger age (P = 0.045, odds ratio 13.8) and lower level of education (P = 0.006, odds ratio 6.7) were predictive of scores indicative of alcohol dependence (AUDIT ≥20). In conclusion, younger age and lower educational levels were associated with scores consistent with alcohol dependence. AUDIT was well tolerated and easy to administer in this outpatient HIV clinic population.

  2. Diagnostic tests in HIV management: a review of clinical and laboratory strategies to monitor HIV-infected individuals in developing countries.

    PubMed Central

    Kimmel, April D.; Losina, Elena; Freedberg, Kenneth A.; Goldie, Sue J.

    2006-01-01

    We conducted a systematic review on the performance of diagnostic tests for clinical and laboratory monitoring of HIV-infected adults in developing countries. Diagnostic test information collected from computerized databases, bibliographies and the Internet were categorized as clinical (non-laboratory patient information), immunologic (information from immunologic laboratory tests), or virologic (information from virologic laboratory tests). Of the 51 studies selected for the review 28 assessed immunologic tests, 12 virologic tests and seven clinical and immunologic tests. Methods of performance evaluation were primarily sensitivity and specificity for the clinical category and correlation coefficients for immunologic and virologic categories. In the clinical category, the majority of test performance measures was reported as >70% sensitive and >65% specific. In the immunologic category, correlation coefficients ranged from r=0.54 to r=0.99 for different CD4 count enumeration techniques, while correlation for CD4 and total lymphocyte counts was between r=0.23 and r=0.74. In the virologic category, correlation coefficients for different human immunodeficiency virus (HIV) ribonucleic acid (RNA) quantification techniques ranged from r=0.54 to r=0.90. Future research requires consensus on designing studies, and collecting and reporting data useful for decision-makers. We recommend classifying information into clinically relevant categories, using a consistent definition of disease across studies and providing measures of both association and accuracy. PMID:16878233

  3. Identifying the Needs of Newly Unemployed Workers.

    ERIC Educational Resources Information Center

    Parsons, Margaret A.; And Others

    1983-01-01

    Surveyed newly unemployed workers (N=171) regarding their needs for information and community services. Workers rated items relating directly to employment and financial concerns (i.e., information on job search methods, food, family budgeting) as most important, and rated pamphlets as the preferred method for obtaining information on most items.…

  4. The Florida Survey of Newly Legalized Persons.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; Nimnicht, Glen

    This study was conducted to gather more definitive information about aliens who were newly legalized under the Immigration Reform and Control Act of 1986. Two groups of eligible legal aliens were interviewed in Florida: those residing in the United States before 1982 (PRE-82s) and special agricultural workers (SAWs). The 1,300 subjects were asked…

  5. Anxiety and the Newly Returned Adult Student

    ERIC Educational Resources Information Center

    Cleary, Michelle Navarre

    2012-01-01

    Based on interviews with students who had recently returned to school, this essay demonstrates the need for, challenges of, and ways to respond to the writing anxiety many adults bring with them back to school. Jessica and Sam were two of twenty-five newly returned adult students whom the author spent over sixty hours interviewing in the fall of…

  6. Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder.

    PubMed

    Cockerell, C J; LeBoit, P E

    1990-03-01

    Bacillary angiomatosis (also called epithelioid angiomatosis) is a newly recognized disease most often characterized by a cutaneous infection with reddish papules of vascular origin. It is caused by a weakly reactive gram-negative bacillus, which can be easily demonstrated in tissue sections with the Warthin-Starry stain. Bacillary angiomatosis usually responds readily to treatment with oral erythromycin, 250 to 500 mg, taken four times a day for 2 weeks to 1 month. Because the skin is the most common site of involvement, it is important that the dermatologist recognize this unusual condition. It is essential that treatment be started as soon as possible because deaths may result from visceral and mucosal involvement. The clinical, histologic, and microbiologic aspects of bacillary angiomatosis are discussed and depicted in detail and speculations regarding the pathogenesis are rendered.

  7. Magnitude of Virologic Blips Is Associated With a Higher Risk for Virologic Rebound in HIV-Infected Individuals: A Recurrent Events Analysis

    PubMed Central

    Grennan, J. Troy; Loutfy, Mona R.; Su, DeSheng; Harrigan, P. Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S. G.; Rourke, Sean; Tsoukas, Christos; Hogg, Bob

    2012-01-01

    (See the editorial commentary by Taiwo and Bosch, on pages 1189–91.) Background. The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Methods. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. Results. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500–999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50–499 were not. Conclusions. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk. PMID:22438396

  8. What Triggers a Diagnosis of HIV Infection in the Tokyo Metropolitan Area? Implications for Preventing the Spread of HIV Infection in Japan

    PubMed Central

    Nishijima, Takeshi; Takano, Misao; Matsumoto, Shoko; Koyama, Miki; Sugino, Yuko; Ogane, Miwa; Ikeda, Kazuko; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

    2015-01-01

    Background Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%). Methods A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed. Results The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/μL) was significantly higher than that of patients who had never been tested (203/μL, p<0.001). Conclusions Only 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000–2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area. PMID:26606382

  9. Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension

    PubMed Central

    Yang, Bo; Ding, Fang; Wang, Feng-Lei; Yu, Wei; Li, Duo

    2016-01-01

    Abstract Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension. We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (±2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis. After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n-6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n-3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45–0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46–3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified

  10. Antibodies of symptomatic human immunodeficiency virus type 1-infected individuals are directed to the V3 domain of noninfectious and not of infectious virions present in autologous serum.

    PubMed Central

    Schreiber, M; Petersen, H; Wachsmuth, C; Müller, H; Hufert, F T; Schmitz, H

    1994-01-01

    The present study was designed to determine the antibody specificity for the human immunodeficiency virus type 1 (HIV-1) V3 domains of infectious and noninfectious virions present in the serum of AIDS patients. To accomplish this, HIV-1 was isolated in the presence of autologous antibodies from the serum samples of six AIDS patients in HIV-1-negative donor peripheral blood mononuclear cells by short-term cultivation. The isolated virus, defined as the infectious cell-free virus (iCFV), was characterized by sequence analysis of the proviral DNA coding for the third hypervariable (V3) region of the external glycoprotein gp120. This was carried out by amplifying and cloning the V3 region. In all six cases studied, 20 randomly selected V3 clones derived from the proviral DNA of the iCFV, 20 clones from patient cell-free virus, and 20 clones from cell-integrated virus were sequenced to study the distribution and frequency of the intrapatient virus population. The number of major virus variants in the six patients ranged from three to nine. The various V3 sequences found in the AIDS patients showed the typical amino acid pattern of the syncytium-inducing and non-syncytium-inducing viral phenotypes characteristic for the late stage of infection. However, only one patient-specific iCFV variant was detected within the 20 V3 clones analyzed per virus isolation. For the six patients a total of 34 V3-loop variants, either iCFV or non-iCFV, was observed. All 34 V3-loop sequences were expressed as glutathione-S-transferase fusion proteins (V3-GST). The autologous antibody response to the V3-GST fusion proteins was studied by Western immunoblot analysis. A strong antibody response to almost all non-iCFV V3-GST proteins was found in the sera of the six patients. In contrast, the autologous antibody response to the six iCFV V3 loops was undetectable (in four patients) or very faint (in two patients) compared with that to the non-iCFV V3 loops. Five of the six iCFV loops showed

  11. A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India.

    PubMed

    Kumarasamy, N; Flanigan, T P; Vallabhaneni, S; Cecelia, A J; Christybai, P; Balakrishnan, P; Yepthomi, T; Solomon, S; Carpenter, C C J; Mayer, K H

    2007-04-01

    This randomised control trial, conducted in Chennai, India, compared structured interrupted therapy (SIT) and continuous therapy (CT) in relation to immunologic and virologic outcomes, adverse events (AEs) and cost of therapy. ART-naïve adult HIV1-infected participants with CD4 counts 50-350 cells/mm(3), and plasma viral load (PVL)>5000 copies/mL were enrolled and placed on Indian-manufactured generic ART: zidovudine(AZT)/stavudine(d4T)+lamivudine(3TC)+efavirenz(EFV). After at least six months of continuous therapy, subjects were randomised to SIT (one-week-on/one-week-off cycles) or CT. The primary end-point was the proportion of subjects maintaining CD4>200 cells/mm(3) at six and 12 months after randomisation. Secondary end-points were effective viral suppression (PVL<400 copies/mL), AEs and cost. All analyses used intention-to-treat methodology. Of 40 participants (69% male; mean age 36+/-7; median baseline CD4 and PVL: 162 cell/mm(3)and 259,000 copies/mL), 17 were randomised to SIT and 18 to CT. At randomisation, median CD4s for SIT and CT were 378 cells/mm(3) and 357 cells/mm(3), respectively. All participants had PVL<400 copies/mL at time of randomisation. Median CD4 six months after randomisation was 498 cells/mm(3) and 417 cells/mm(3) for SIT and CT respectively. All participants had CD4>200 cells/mm(3). One participant on CT and two on SIT had sustained PVL>400 copies/mL. There were no serious AEs or deaths. Structured interrupted therapy cost was half of CT. Structured interrupted therapy was effective at maintaining CD4 above 200 cells/mm(3). Adverse events were comparable in both groups, with 50% reduction in cost for SIT. Further research on such strategies may benefit resource-constrained settings.

  12. Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals.

    PubMed

    Khoshgoo, Naghmeh; Zahedifard, Farnaz; Azizi, Hiva; Taslimi, Yasaman; Alonso, Maribel Jiménez; Rafati, Sima

    2008-10-29

    Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is the best approach to control it. One of the major groups of virulence factors in Leishmania belongs to cysteine proteinase family. In this study, for the first time, the protective potential of Leishmania infantum cysteine proteinase type III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The experiment was carried out in three groups of mice. Vaccinated group was primed with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in vaccinated group is significantly higher than controls. Furthermore, the parasite load of vaccinated group is significantly lower than controls. In addition, sera reactivity of visceral leishmaniasis individuals was examined and showed considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis. The achieved result is highly encouraging the use of cysteine proteinases types I, II and III as vaccine candidate against visceral leishmaniasis.

  13. Diagnosis of subclinical amniotic fluid infection prior to rescue cerclage using gram stain and glucose tests: an individual patient meta-analysis.

    PubMed

    Lisonkova, Sarka; Sabr, Yasser; Joseph, K S

    2014-02-01

    Objectifs : L’invasion microbienne de la cavité amniotique (IMCA) peut affecter les issues à la suite d’un cerclage d’urgence. Nous avons mené une étude visant à comparer le rendement diagnostique de la coloration de Gram à celui de la concentration en glucose pour ce qui est du dépistage d’une IMCA subclinique. Méthodes : Nous avons utilisé des données personnelles issues d’études publiées ayant porté sur l’utilisation de la coloration de Gram, de la concentration en glucose et de la mise en culture du liquide amniotique chez des femmes connaissant un travail préterme. Nous avons calculé la sensibilité, la spécificité, la surface sous la courbe (SSC) et d’autres indices, les résultats de la mise en culture du liquide amniotique étant utilisés à titre de test de référence. La probabilité de constater une infection à la suite de l’utilisation des deux tests à titre de facteurs prédictifs a également été estimée au moyen d’une régression logistique. Résultats : Le taux d’IMCA confirmée par mise en culture était de 11,8 % (34 femmes sur 288). Le test par coloration de Gram a présenté une sensibilité de 65 % (IC à 95 %, 46 % - 78 %) et une spécificité de 99 % (IC à 95 %, 98 % - 100 %). L’obtention d’un résultat positif à la suite d’une coloration de Gram ou de la mesure de la concentration en glucose présentait une sensibilité de 88 % (IC à 95 %, 72 % - 96 %) et une spécificité de 87 % (IC à 95 %, 82 % - 90 %), tandis que l’obtention d’un résultat positif à la suite d’une coloration de Gram et de la mesure de la concentration en glucose présentait une sensibilité de 62 % (IC à 95 %, 44 % - 77 %) et une spécificité de 100 % (IC à 95 %, 98 % - 100 %). Les SSC étaient de 0,82 (IC à 95 %, 0,74 - 0,90) pour la coloration de Gram, de 0,86 (IC à 95 %, 0,80 - 0,93) pour la concentration en glucose et de 0,92 (IC à 95 %, 0,86 - 0,98) pour la combinaison

  14. Magnetospheric substorms - A newly emerging model

    NASA Astrophysics Data System (ADS)

    Akasofu, S.-I.

    1981-10-01

    A surge of progress in magnetospheric substorm studies is expected by the following three recent developments: (1) the finding of the solar wind-magnetosphere energy coupling function epsilon, (2) the determination of the Pedersen current distribution over the entire polar region, and (3) a new understanding of the auroral potential structure. In this paper, the significance of the three developments and the newly emerging model of magnetospheric substorms is described.

  15. Sensitivity of individual-donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections

    PubMed Central

    Vermeulen, Marion; Coleman, Charl; Mitchel, Josephine; Reddy, Ravi; van Drimmelen, Harry; Ficket, Tracy; Lelie, Nico

    2016-01-01

    BACKGROUND Several comparison studies showed that the Ultrio assay (Novartis Diagnostics) used in individual-donation nucleic acid amplification testing (ID-NAT) format was as sensitive as the TaqScreen assay (Roche) on minipools of six donations (MP6), but the sensitivity of HBV DNA detection has been improved in the new Ultrio Plus version of the assay. A head-to-head comparison study was designed to compare the clinical sensitivity of the Ultrio and Ultrio Plus assay in ID, MP4, and MP8 formats using TaqScreen MP6 as a reference assay. STUDY DESIGN AND METHODS Plasma samples of 107 hepatitis B surface antigen (HBsAg)-negative, HBV ID-NAT (Ultrio) positive-yield samples and 29 HBV DNA–negative, HBsAg-positive samples were used for comparison of NAT options in replicate testing of di