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Sample records for newly infected individuals

  1. Genetic diversity of HIV-1 and transmitted drug resistance among newly diagnosed individuals with HIV infection in Hangzhou, China.

    PubMed

    Zhang, Jiafeng; Guo, Zhihong; Yang, Jiezhe; Pan, Xiaohong; Jiang, Jun; Ding, Xiaobei; Zhang, Wenjun; Xia, Yan; Xu, Yun; Huang, Jingjing

    2015-10-01

    HIV transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) in resource-limited countries like China where ART has been scaled up and thus leads to an important public health concern. The aim of the study was to elucidate the HIV-1 genetic characteristics and TDR in Hangzhou, China. Two-hundred eleven ART-naive, newly diagnosed individuals were enrolled during January and August 2013. Specimens were classified as recent or chronic infections using the BED capture enzyme immunoassay (BED-CEIA). The pol fragment covering the entire protease and the first 300 codons of the reverse transcriptase gene was amplified by RT-PCR and nested PCR. Genotypic drug resistance (DR) and phylogenetic analysis were performed on the 200 obtained sequences. Multiple genotypes were identified, including CRF01_AE (62.0%), CRF07_BC (31.0%), subtype B (2.0%), CRF08_BC (1.5%), CRF55_01B (1.0%), CRF18_cpx (0.5%), and unique recombinant forms (URFs, 2.0%). All the four URFs were found in men who have sex with men, consisting of a recombination of CRF01_AE with subtype B or CRF07_BC. The prevalence of primary DR in newly diagnosed individuals in Hangzhou was low (4.0%). The proportion of DR mutation to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 1.5%, 1.5%, and 1.0%, respectively. BED-CEIA revealed that 21.8% (45/211) of the specimens were associated with recent infections. The prevalence of TDR in recent infections was moderate (6.5%). High HIV diversity and relatively high prevalence of TDR in new infections has been found in Hangzhou, indicating an increasing challenge for future HIV prevention and treatment. PMID:25899877

  2. Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009

    PubMed Central

    Hanna, David B.; Buchacz, Kate; Gebo, Kelly A.; Hessol, Nancy A.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, P. Todd; Moore, Richard D.; Napravnik, Sonia; Patel, Pragna; Silverberg, Michael J.; Sterling, Timothy R.; Willig, James H.; Lau, Bryan; Althoff, Keri N.; Crane, Heidi M.; Collier, Ann C.; Samji, Hasina; Thorne, Jennifer E.; Gill, M. John; Klein, Marina B.; Martin, Jeffrey N.; Rodriguez, Benigno; Rourke, Sean B.; Gange, Stephen J.; Benson, A.; Bosch, Ronald J.; Collier, Ann C.; Boswell, Stephen; Grasso, Chris; Mayer, Ken; Hogg, Robert S.; Harrigan, Richard; Montaner, Julio; Cescon, Angela; Brooks, John T.; Buchacz, Kate; Gebo, Kelly A.; Moore, Richard D.; Rodriguez, Benigno; Horberg, Michael A.; Silverberg, Michael J.; Thorne, Jennifer E.; Goedert, James J.; Jacobson, Lisa P.; Klein, Marina B.; Rourke, Sean B.; Burchell, Ann; Rachlis, Anita R.; Hunter-Mellado, Robert F.; Mayor, Angel M.; Gill, M. John; Deeks, Steven G.; Martin, Jeffrey N.; Saag, Michael S.; Mugavero, Michael J.; Willig, James; Eron, Joseph J.; Napravnik, Sonia; Kitahata, Mari M.; Crane, Heidi M.; Justice, Amy C.; Dubrow, Robert; Fiellin, David; Sterling, Timothy R.; Haas, David; Bebawy, Sally; Turner, Megan; Gange, Stephen J.; Anastos, Kathryn; Moore, Richard D.; Saag, Michael S.; Gange, Stephen J.; Kitahata, Mari M.; McKaig, Rosemary G.; Justice, Amy C.; Freeman, Aimee M.; Moore, Richard D.; Freeman, Aimee M.; Lent, Carol; Platt, Aaron; Kitahata, Mari M.; Van Rompaey, Stephen E.; Crane, Heidi M.; Webster, Eric; Morton, Liz; Simon, Brenda; Gange, Stephen J.; Abraham, Alison G.; Lau, Bryan; Althoff, Keri N.; Zhang, Jinbing; Jing, Jerry; Golub, Elizabeth; Modur, Shari; Hanna, David B.; Rebeiro, Peter; Wong, Cherise; Mendes, Adell

    2013-01-01

    Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes. Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness. Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001). Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide. PMID:23315317

  3. Individual-Level and Partner-Level Predictors of Newly Diagnosed HIV Infection Among Black and White Men Who Have Sex with Men in Baltimore, MD.

    PubMed

    Maulsby, Cathy; Jain, Kriti; Sifakis, Frangiscos; German, Danielle; Flynn, Colin P; Holtgrave, David

    2015-05-01

    Black MSM continue to be the group most disproportionately impacted by HIV in the United States. This study assesses the relationship between partner-level and respondent-level characteristics and newly diagnosed HIV infection among a sample of MSM. Ego-centric data were gathered using venue-based time-space sampling on 335 men who reported on a total of 831 male anal sex partners. In multivariate analyses, age of partner, HIV status of partner, and respondent having had an STD in the past twelve months were associated with a newly diagnosed HIV infection among black MSM. Efforts for black MSM are needed that aim to increase HIV and STD testing, foster open communication between partners about HIV status, and address social determinants of health. PMID:25092514

  4. Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China

    PubMed Central

    2012-01-01

    Background The emergence of an HIV-1 epidemic in China was first recognized in Dehong, western Yunnan. Due to its geographic location, Dehong contributed greatly in bridging HIV-1 epidemics in Southeast Asia and China through drug trafficking and injection drug use; and also extensively to the HIV genetic diversity in Yunnan and China. We attempt to monitor HIV-1 in this area by studying the HIV-1 genetic distribution and transmitted drug resistance (TDR) in various at-risk populations. Methods Blood samples from a total of 320 newly HIV-1 diagnosed individuals, who were antiretroviral therapy (ART)-naive, were collected from January 2009 to December 2010 in 2 counties in Dehong. HIV-1 subtypes and pol gene drug resistance (DR) mutations were genotyped. Results Among 299 pol sequences successfully genotyped (93.4%), subtype C accounted for 43.1% (n=129), unique recombinant forms (URFs) for 18.4% (n=55), CRF01_AE for 17.7% (n=54), B for 10.7% (n=32), CRF08_BC for 8.4% (n=25) and CRF07_BC for 1.7% (n=5). Subtype distribution in patients infected by different transmission routes varied. In contract to the previous finding of CRF01_AE predominance in 2002-2006, subtype C predominated in both injecting drug users (IDUs) and heterosexually transmitted populations in this study. Furthermore, we found a high level of BC, CRF01_AE/C and CRF01_AE/B/C recombinants suggesting the presence of active viral recombination in the area. TDR associated mutations were identified in 4.3% (n=13) individuals. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A. Conclusion Our work revealed diverse HIV-1 subtype distributions and intersubtype recombinations. We also identified a low but significant TDR mutation rate among ART-naive patients. These findings

  5. 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…

  6. 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.

  7. The prevalence of transmitted drug resistance in newly diagnosed HIV-infected individuals in Croatia: the role of transmission clusters of men who have sex with men carrying the T215S surveillance drug resistance mutation.

    PubMed

    Grgic, Ivana; Lepej, Snjezana Zidovec; Lunar, Maja M; Poljak, Mario; Vince, Adriana; Vrakela, Ivana Baca; Planinic, Ana; Seme, Katja; Begovac, Josip

    2013-02-01

    The aim of this study was to determine the prevalence of transmitted drug resistance (TDR) in newly diagnosed and treatment-naive HIV-infected patients from Croatia and evaluate a possible contribution of transmission clusters to the spread of resistant virus. The study enrolled treatment-naive HIV-infected patients that entered clinical care at the Croatian Reference Center for HIV/AIDS between 2006 and 2008. The protease gene and a part of the reverse transcriptase gene of the HIV-1 genome were sequenced by using the Trugene HIV-1 Genotyping System. The prevalence of transmitted drug resistance was analyzed by using the surveillance drug resistance mutations (SDRM) list recommended by the WHO in 2009. We report findings for 118 of 180 eligible patients (65.6% coverage). SDRM were detected in 26 of 118 patients (22.0%) who were infected with subtype B and belonged mostly to the men having sex with men (MSM). The majority of patients with primary resistance carried SDRM associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs, 23 of 118 patients, 19.5%). The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). SDRM associated with resistance to nonnucleoside reverse transcriptase inhibitors were detected in three (2.5%) patients and primary resistance to protease inhibitors was not detected. Non-B subtypes were detected in 13/118 patients (11%). A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. This study showed a high prevalence of TDR in newly diagnosed MSM from Croatia and is an important contribution concerning the relationship between local transmission clusters and the spread of resistant virus. PMID:22906365

  8. 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

  9. 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

  10. Limited cross-border infections in patients newly diagnosed with HIV in Europe

    PubMed Central

    2013-01-01

    Background International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. Results Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002–2007 were included. We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045). Conclusions Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics. PMID:23551870

  11. Ocular Syphilis among HIV-Infected Individuals

    PubMed Central

    Li, Jonathan Z.; Tucker, Joseph D.; Lobo, Ann-Marie; Marra, Christina M.; Davis, Benjamin T.; Papaliodis, George N.; Felsenstein, Donna; Durand, Marlene L.; Yawetz, Sigal; Robbins, Gregory K.

    2010-01-01

    We describe a human immunodeficiency virus (HIV)–infected individual with ocular manifestations of secondary syphilis. Twelve other cases of HIV-associated ocular syphilis are also presented. Six of 12 individuals had normal cerebrospinal fluid study results, and 3 patients required retreatment within 1.5 years. In patients with HIV infection, clinicians should be vigilant for ocular syphilis despite normal cerebrospinal fluid measures and for syphilis reinfection. PMID:20604717

  12. Bluetongue virus surveillance in a newly infected area.

    PubMed

    Giovannini, A; Calistri, P; Conte, A; Savini, L; Nannini, D; Patta, C; Santucci, U; Caporale, V

    2004-01-01

    The occurrence of bluetongue virus (BTV) in areas in which intensive animal production is practised and where there is extensive movement of animals may have a substantial impact on both animal trade and husbandry. This situation occurred in Italy after the detection of bluetongue (BT) in August 2000. In such situations, surveillance can be used to delineate with precision those areas in which the virus is circulating and, consequently, to enforce the appropriate animal movement restrictions. Furthermore, surveillance can provide the data required to assess the risk associated with animal movement and trade. A structured surveillance system for the detection of BTV has been in place in Italy since August 2001. The system is based on the periodical testing of unvaccinated sentinel cattle that are uniformly scattered throughout Italy in a grid of 400 km(2) cells. The initial number of sentinel sites and sentinel animals, together with the width of the restricted area generated by the finding of a single seroconversion in a sentinel animal, were based on conservative criteria. Animal movement was restricted in a 20 km radius buffer zone around any positive serological result. This buffer area extends about 1,257 km(2), equivalent to the area of three grid cells. After the commencement of the BT vaccination campaign in Italy, the sentinel surveillance system was the only way in which the effectiveness of vaccination and the incidence of infection in the non-immunised strata of ruminant animals could be estimated. Data collected over two years was used to assess the risks posed by the adoption of less conservative criteria for the delineation of infected areas and by the progressive relaxation of movement restrictions of vaccinated animals. In regard to the delineation of restricted areas, a new approach was tested and validated in the field, based on a Bayesian analysis of the positive and negative results obtained by the testing of sentinel animals from defined

  13. 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

  14. 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

  15. 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

  16. 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. PMID:26732896

  17. Uncultivated Phylotypes and Newly Named Species Associated with Primary and Persistent Endodontic Infections

    PubMed Central

    Siqueira, J. F.; Rôças, I. N.

    2005-01-01

    Endodontic infections have been traditionally studied by culture methods, but recent reports showing that over 50% of the oral microbiota is still uncultivable (B. J. Paster et al., J. Bacteriol. 183:3770-3783, 2001) raise the possibility that many endodontic pathogens remain unknown. This study intended to investigate the prevalence of several uncultivated oral phylotypes, as well as newly named species in primary or persistent endodontic infections associated with chronic periradicular diseases. Samples were taken from the root canals of 21 untreated teeth and 22 root-filled teeth, all of them with radiographic evidence of periradicular bone destruction. Genomic DNA was isolated directly from each sample, and 16S rRNA gene-based nested or heminested PCR assays were used to determine the presence of 13 species or phylotypes of bacteria. Species-specific primers had already been validated in the literature or were developed by aligning closely related 16S rRNA gene sequences. Species specificity for each primer pair was confirmed by running PCRs against a panel of several oral bacteria and by sequencing DNA from representative positive samples. All species or phylotypes were detected in at least one case of primary infections. The most prevalent species or phylotypes found in primary infections were Dialister invisus (81%), Synergistes oral clone BA121 (33%), and Olsenella uli (33%). Of the target bacteria, only these three species were detected in persistent infections. Detection of uncultivated phylotypes and newly named species in infected root canals suggests that there are previously unrecognized bacteria that may play a role in the pathogenesis of periradicular diseases. PMID:16000454

  18. 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

  19. Intellectual Impairment in Patients with Newly Diagnosed HIV Infection in Southwestern Nigeria

    PubMed Central

    Sunmonu, Taofiki A.; Sellner, Johann; Ogunrin, Olubunmi A.; Imarhiagbe, Frank A.; Komolafe, Morenikeji A.; Afolabi, Olusegun T.; Ilesanmi, Olayinka S.; Olanrewaju, Fatai; Oladimeji, Benedicta Y.

    2015-01-01

    Neurocognitive impairment is a detrimental complication of HIV infection. Here, we characterized the intellectual performance of patients with newly diagnosed HIV infection in southwestern Nigeria. We conducted a prospective study at Owo Federal Medical Center by using the adapted Wechsler Adult Intelligence Scale (WAIS). The raw scores were converted to standardized scores (z-scores) and correlated with clinical and laboratory findings. Fifty-eight HIV positive patients were recruited; 72% were in WHO stages 3 and 4. We detected a high rate of intellectual impairment in HIV positive patients and controls (63.8% and 10%, resp.; P < 0.001). HIV positive patients performed worse throughout the subtests of both verbal and performance intelligence quotients. Presence of opportunistic infections was associated with worse performance in the similarities and digit symbol tests and performance and full scale scores. Lower body weight correlated with poor performance in different WAIS subtests. The high rate of advanced disease stage warrants measures aimed at earlier diagnosis and treatment. Assessment of neurocognitive performance at diagnosis may offer the opportunity to improve functioning in daily life and counteract disease progression. PMID:26295033

  20. Intellectual Impairment in Patients with Newly Diagnosed HIV Infection in Southwestern Nigeria.

    PubMed

    Sunmonu, Taofiki A; Sellner, Johann; Ogunrin, Olubunmi A; Imarhiagbe, Frank A; Komolafe, Morenikeji A; Afolabi, Olusegun T; Ilesanmi, Olayinka S; Olanrewaju, Fatai; Oladimeji, Benedicta Y

    2015-01-01

    Neurocognitive impairment is a detrimental complication of HIV infection. Here, we characterized the intellectual performance of patients with newly diagnosed HIV infection in southwestern Nigeria. We conducted a prospective study at Owo Federal Medical Center by using the adapted Wechsler Adult Intelligence Scale (WAIS). The raw scores were converted to standardized scores (z-scores) and correlated with clinical and laboratory findings. Fifty-eight HIV positive patients were recruited; 72% were in WHO stages 3 and 4. We detected a high rate of intellectual impairment in HIV positive patients and controls (63.8% and 10%, resp.; P < 0.001). HIV positive patients performed worse throughout the subtests of both verbal and performance intelligence quotients. Presence of opportunistic infections was associated with worse performance in the similarities and digit symbol tests and performance and full scale scores. Lower body weight correlated with poor performance in different WAIS subtests. The high rate of advanced disease stage warrants measures aimed at earlier diagnosis and treatment. Assessment of neurocognitive performance at diagnosis may offer the opportunity to improve functioning in daily life and counteract disease progression. PMID:26295033

  1. Reduction of bacterial infections in newly hatched chicks by the use of antimicrobial dips: preliminary approaches.

    PubMed

    Barbour, E K; Nabbut, N H; Hinners, S W; Al-Nakhli, H M

    1985-01-01

    Bacteriological examination of hatchery waste eggs, identification of the isolated bacteria, and susceptibility testing against seven antimicrobial agents were used in an attempt to establish a rational basis for reducing bacterial infections in newly hatched chicks. Chloramphenicol at 1000 ppm was selected as the antibiotic for preliminary dipping trials and 0.45% iodophore (Wescodyne) was added for later trials. The control treatment consisted of formaldehyde fumigation. The following conclusions can be drawn: Hatchery waste eggs are highly contaminated (69.1%) and enterobacteriaceae predominate (26.6%). Chloramphenicol is the most effective antimicrobial tested. Dip treatments with either chloramphenicol alone or chloramphenicol plus Wescodyne result in a reduced percentage of abnormal navels (8.4% and 10.4%), as compared with 21.9% for the control treatment. Hatchability of either group of dipped eggs is reduced in comparison with fumigated eggs. Dip treatment with chloramphenicol plus Wescodyne significantly reduces the anal carrier rates for Escherichia coli, Pseudomonas aeruginosa, Salmonella spp., and Staphylococcus aureus. This treatment reduces the incidence of bacterial infection in abnormal navels to zero. PMID:3919494

  2. Laboratory markers slightly overestimate retention in HIV care among newly diagnosed individuals.

    PubMed

    Halperin, Jason; Bean, Madelyne C; Richey, Lauren E

    2016-09-01

    Patients who are retained in HIV care have a higher likelihood of viral suppression and increased survival. Lab markers have been used as surrogate markers for clinical visits to estimate retention, but the accuracy of these markers at predicting retention in care has not been validated. A retrospective cohort study was conducted using patients newly diagnosed with HIV in the Emergency Department of Interim Louisiana Public Hospital (ILPH). Retention in care was defined as two clinical visits to an HIV provider separated by at least three months within a one-year period as per the Health Resources and Services Administration (HRSA) definition. Retention by lab markers was defined as two documented labs, either a CD4 count or an HIV viral load, separated by at least three months within the same one-year period. Ninety-nine patients were newly diagnosed with HIV; 36 patients (36%) were retained at 1 year using the HRSA definition and 40 patients (40%) using lab markers. The sensitivity and specificity of using lab markers among the newly diagnosed were 100% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 90% and 100%, respectively. Among the 99 patients, 56 were linked to the HIV clinic associated with our hospital, of which 63% (36) were retained at year 1 using the HRSA definition and 70% (39) using lab markers. The sensitivity and specificity of using lab markers among linked patients were 100% and 85%, respectively. The PPV and NPV were 92% and 100%, respectively. Lab markers slightly overestimate currently accepted definitions of retention. While lab markers may be the easiest way to estimate retention at the population level, further study should be done before lab markers are accepted as the gold standard surrogate measure for retention. PMID:27010972

  3. 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

  4. Individual Variability of Nosema ceranae Infections in Apis mellifera Colonies.

    PubMed

    Mulholland, Grace E; Traver, Brenna E; Johnson, Nels G; Fell, Richard D

    2012-01-01

    Since 2006, beekeepers have reported increased losses of Apis mellifera colonies, and one factor that has been potentially implicated in these losses is the microsporidian Nosema ceranae. Since N. ceranae is a fairly recently discovered parasite, there is little knowledge of the variation in infection levels among individual workers within a colony. In this study we examined the levels of infection in individual bees from five colonies over three seasons using both spore counting and quantitative real-time PCR. The results show considerable intra-colony variation in infection intensity among individual workers with a higher percentage of low-level infections detected by PCR than by spore counting. Colonies generally had the highest percentage of infected bees in early summer (June) and the lowest levels in the fall (September). Nosema apis was detected in only 16/705 bees (2.3%) and always as a low-level co-infection with N. ceranae. The results also indicate that intra-colony variation in infection levels could influence the accuracy of Nosema diagnosis. PMID:26466731

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. [Sexually transmitted infections among transgender individuals and other sexual identities].

    PubMed

    Toibaro, Javier J; Ebensrtejin, Juan E; Parlante, Angel; Burgoa, Patricia; Freyre, Alejandro; Romero, Marcela; Losso, Marcelo H

    2009-01-01

    Few data are available regarding the prevalence of sexually transmitted infections (STI), including HIV-1 infection, and risk behaviors of transgender individuals. Previous reports indicate that this community has a high prevalence of HIV and STIs. Our objective was to compare the prevalence of HIV-1 infection, STI and risk behaviors of transgender people versus non transgender people. We used a cross sectional design study. Patients who received services at our testing site between November 2002 and April 2006, and provided written informed consent, were included in the analysis. Socio-demographic data, sexual behaviour, recreational drug use, condom use, concurrent or previous STI and HIV-1 infection diagnosis and partner serologic status, were collected. We used descriptive statistics and chi 2 for comparisons of proportions. In the period of the study, 105 transgender individuals were identified in a population of 4118 patients tested. The prevalence of HIV infection in the transgender group was 27.6% (29/105), while in the non transgender group was 6.2% (247/4013) p:0.0000. Low level of formal instruction, alcohol consumption, drug abuse, previous history of STI and sex work (100% transgenders and 2.3% of non-transgenders) were significantly more frequent in the transgender. The referred correct use of condom was similar in both groups. The prevalence of syphilis was 42.3% in transgender group and 18.1% in non-transgender individuals. These data show that this population has a very high prevalence of HIV-1 and STI. This information could be instrumental to design targets for intensive HIV prevention strategies in this particular high risk population. PMID:19622481

  15. Sports behaviour among HIV-infected versus non-infected individuals in a Berlin cohort.

    PubMed

    Stein, L; Hechler, D; Jessen, A B; Neumann, K; Jessen, H; Beneke, R

    2012-01-01

    Physical activity has been recommended based on beneficial effects described in HIV-infected patients. However, such guidelines do not take into account actual sport behaviours and general attitudes towards physical activity. To evaluate actual sport activity and attitudes towards sport in HIV-infected versus non-infected individuals we conducted an anonymous questionnaire investigating the prevalence, as well as possible changes, in sports engagement and the overall attitude to physical activity. A total of 283 patients of a general care facility specialized in the treatment of HIV/AIDS in Berlin, Germany, participated; 124 were HIV infected and 159 were non-infected, mostly men who have sex with men (MSM) (88%), with a median age of 35 years. The HIV-infected participants had a median CD4+ count of 554 cells/µL and 48.8% of them were using antiretroviral therapy (ART) at the time of survey. The proportion of patients actually performing physical activity was significantly lower (P = 0.028) within the HIV-infected group (61.3%) than within the non-infected group (74.2%). This difference remained significant after accounting for possible confounders such as age, gender, injecting drug use and sexual preferences. Previously reported sport activity prevalence was similar in both groups on leaving school. From our data we could not identify an association between the time of HIV diagnosis and changes in sports activity. In conclusion, fewer HIV-infected individuals report physical activity than non-infected individuals. Sociodemographic studies to evaluate potential differences in sports behaviour are required in order to inform exercise guidelines for HIV-infected patients. PMID:22362683

  16. Development and validation of an algorithm to identify patients newly diagnosed with HIV infection from electronic health records.

    PubMed

    Goetz, Matthew Bidwell; Hoang, Tuyen; Kan, Virginia L; Rimland, David; Rodriguez-Barradas, Maria

    2014-07-01

    An algorithm was developed that identifies patients with new diagnoses of HIV infection by the use of electronic health records. It was based on the sequence of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at four large urban Veterans Health Administration (VHA) facilities. Source data were obtained from the VHA National Corporate Data Warehouse. Chart review was done by a single trained abstractor to validate site-level data regarding new diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test within the VHA. Of these, 57% were determined to have prior knowledge of their HIV status from testing at non-VHA facilities. An algorithm based on the sequence and results of available laboratory tests and ICD-9-CM entries identified new HIV diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90%. There were no meaningful demographic or clinical differences between newly diagnosed patients who were correctly or incorrectly classified by the algorithm. We have validated a method to identify cases of new diagnosis of HIV infection in large administrative datasets. This method, which has a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90% can be used in analyses of the epidemiology of newly diagnosed HIV infection. PMID:24564256

  17. Serology and cytokine profiles in patients infected with the newly discovered Bundibugyo ebolavirus.

    PubMed

    Gupta, Manisha; MacNeil, Adam; Reed, Zachary D; Rollin, Pierre E; Spiropoulou, Christina F

    2012-02-20

    A new species of Ebolavirus, Bundibugyo ebolavirus, was discovered in an outbreak in western Uganda in November 2007. To study the correlation between fatal infection and immune response in Bundibugyo ebolavirus infection, viral antigen, antibodies, and 17 soluble factors important for innate immunity were examined in 44 patient samples. Using Luminex assays, we found that fatal infection was associated with high levels of viral antigen, low levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, TNF-α, and high levels of immunosuppressor cytokines like IL-10. Also, acute infected patients died in spite of generating high levels of antibodies against the virus. Thus, our results imply that disease severity in these patients is not due to the multi-organ failure and septic shock caused by a flood of inflammatory cytokines, as seen in infections with other Ebolavirus species. PMID:22197674

  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. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings

    PubMed Central

    Walson, Judd L; John-Stewart, Grace

    2012-01-01

    Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings. These areas often also have high prevalence of other infectious diseases, such as helminth infections. It is important to determine if helminth infection affects the progression of HIV-1 in these co-infected individuals. There are biologically plausible reasons for possible effects of helminth infection in HIV-1 infected individuals and findings from some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate the available evidence from published and unpublished studies to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives Our objective was to determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression (including mortality). Search strategy We searched online for published and unpublished studies in The Cochrane Library (Issue 3, 2006), MEDLINE (November 2006), EMBASE (November 2006), CENTRAL (July 2006), AIDSEARCH (August 2006). We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for randomized and quasi-randomized controlled trials that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminth therapy. Observational studies with relevant data were also included. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, clinical staging and/or mortality after treatment of helminth co-infection were extracted from the reports of the studies. Main results Of 6,384 abstracts identified, 15 met criteria for potential inclusion, of which five were eligible for inclusion. 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. Comparison of intestinal parasitic infection in newly arrived and resident workers in Qatar

    PubMed Central

    2011-01-01

    Background The rapid growth of Qatar in the last two decades has been associated with an enormous expansion of building programs in its cities and in the provision of new service industries. This in turn has attracted a large influx of immigrant workers seeking employment in jobs associated with food handling, domestic service and the building industry. Many of these immigrants come from countries in the tropics and subtropics where intestinal parasitic infections are common. Methods We analyzed intestinal parasitic infections recorded in 2008 among immigrant and long-term resident workers in Doha city, Qatar (n = 1538). Stool examinations were carried out at the Hamad Medical Corporation and at the Medical Commission in Doha using standard procedures. Results Overall, 21.5% of subjects were infected with at least one of the species recorded (8 helminth and 4 protozoan species; the highest prevalence was for hookworms = 8.3%) and there were strong regional effects on prevalence of helminths, with subjects from North East Africa and Nepal showing particularly high prevalence. Most helminths declined in prevalence in subjects that acquired residency status in Qatar, especially among female subjects, but there was a marked exception among male Nepalese workers, who continued to harbour helminth infections (notably hookworms) after they became residents. Contrary to all other regional groups the prevalence of Giardia duodenalis was higher among Nepalese residents compared with new arrivals, while Blastocystis hominis infections were more common among residents of all regions, and especially among North East Africans. Conclusions Our analysis has identified male Nepalese workers as a particular risk group continuing to harbour hookworm infection and G. duodenalis as residents, and subjects from North East Africa are as particularly likely to acquire B. hominis infection after settling in the country. These conclusions have important implications for the health

  3. Experimental infection of cows with newly isolated Akabane virus strain (AKAV-7) causing encephalomyelitis.

    PubMed

    Lee, Hyeyeoun; Jeong, Hansol; Park, Surim; Yang, Myeon-Sik; Kim, Jongwon; Bae, Jaehyun; Kwon, Yonghwan; Kim, Min-Su; Oem, Jae-Ku; Lee, Myoung-Heon; Lim, Chae-Woong; Kim, Bumseok

    2016-01-01

    Akabane virus (AKAV), an arthropod-transmitted bunyavirus, is a major cause of congenital abnormalities and encephalomyelitis in ruminants. In 2010, there was a major outbreak of encephalomyelitis in Korea and fifteen AKAV strains, including AKAV-7, were isolated from cows. To identify the neuropathogenicity of AKAV-7, we performed experimental infection of cows. Six-month-old female Korean Holstein dairy cattle were inoculated with AKAV-7 by various routes, including intracerebral (IC), intrasubarachnoid space (IS), subcutaneous (SC) and intravenous (IV); a separate group was vaccinated before intravenous infection. Five of the six cows in the IC group and two of the six cows in the IS group showed clinical signs such as locomotor ataxia and paralysis of the hind limbs. Three of six cows died after IC infection 9-12 days post infection (dpi). Histopathologic changes such as nonsuppurative encephalomyelitis were confirmed in various parts of the central nervous system in the IC, IS and SC groups. Early onset of neutralizing antibodies in the serum and lower viral mRNA levels in the peripheral blood mononuclear cells (PBMCs) and various tissues in the vaccinated group was noticeable compared to the unvaccinated group (IV group). We suggest that the AKAV vaccine currently used in Korea may be partially effective for protection against AKAV-7 in cows. PMID:27287214

  4. 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…

  5. 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

  6. Differential gene expression in HIV-infected individuals following ART.

    PubMed

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

    2013-11-01

    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 4157 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

  7. Unreported Male Sex Partners Among Men with Newly Diagnosed HIV Infection - North Carolina, 2011-2013.

    PubMed

    Wu, Hsiu; Hightow-Weidman, Lisa B; Gay, Cynthia L; Zhang, Xinjian; Beagle, Steve; Hall, Laura; Jackson, Tonyka; Marmorino, Jenni; Do, Ann N; Peters, Philip J

    2015-09-25

    Human immunodeficiency virus (HIV) prevention interventions, such as preexposure prophylaxis (PrEP), are often targeted to men who have sex with men (MSM) who self-report high-risk behaviors. Data from a prospective study evaluating methods to detect acute HIV infection among a primarily young (aged <25 years) and black or African American (African American) population from North Carolina were analyzed. In the study, participants were asked about risk behaviors during pretest counseling (at the time of testing) and then during a partner services interview (at HIV diagnosis). Participants whose disclosure of sexual risk behaviors during pretest counseling was different from their disclosure of sexual risk behaviors during their partner services interview were identified, and factors associated with these discordant responses were examined. Among 113 HIV-infected men, 26 (23.0%) did not disclose male sex partners at pretest counseling, but subsequently did disclose this information during their partner services interview. When compared with men who disclosed having male partners at pretest counseling, these 26 MSM who did not disclose male partners during pretest counseling were found to have a similar number of male partners during contact tracing, but were more likely to have a female partner (30.8% versus 6.9%). In addition, the proportions of MSM found to have at least one HIV-infected partner were similar for both groups (MSM who disclosed having male partners during pretest counseling and those who did not). To better customize HIV prevention interventions for MSM, HIV prevention programs might consider using novel strategies to accurately assess risk in this population. PMID:26401589

  8. 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

  9. Immunodetection of Fasciola gigantica Circulating Antigen in Sera of Infected Individuals for Laboratory Diagnosis of Human Fascioliasis

    PubMed Central

    Attallah, Abdelfattah M.; Bughdadi, Faisal A.; El-Shazly, Atef M.

    2013-01-01

    Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P < 0.0001) for discriminating Fasciola-infected and noninfected individuals. The developed assay showed high degrees of sensitivity, specificity, and efficiency (>93%), and a significant correlation (r = 0.715, P < 0.0001) between antigen level and parasite egg count was shown. In conclusion, a 27-kDa Fasciola antigen was identified in sera of F. gigantica-infected individuals. A highly sensitive and specific Fasciola antigen detection assay, FgCA-27 ELISA, was developed for laboratory diagnosis of human fascioliasis. PMID:23945158

  10. 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.

  11. 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

  12. 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

  13. The slippery slope: Lubricant Use and Rectal Sexually Transmitted Infections: a newly identified risk

    PubMed Central

    Gorbach, Pamina M.; Weiss, Robert E.; Fuchs, Edward; Jeffries, Robin A.; Hezerah, Marjan; Brown, Stephen; Voskanian, Alen; Robbie, Edward; Anton, Peter; Cranston, Ross D.

    2011-01-01

    Background Use of lubricant products is extremely common during receptive anal intercourse (RAI) yet has not been assessed as a risk for acquisition of sexually transmitted infections (STIs). Methods From 2006–2008 a rectal health and behavior study was conducted in Baltimore and Los Angeles as part of the UCLA Microbicide Development Program (NIAID IPCP# #0606414). Participants completed questionnaires and rectal swabs were tested for Neisseria gonorrhoeae and Chlamydia trachomatis with the Aptima Combo 2 assay and blood was tested for syphilis (for RPR and TPHA with titer) and HIV. Of those reporting lubricant use and RAI, STI results were available for 380 participants. Univariate and multivariate regressions assessed associations of lubricant use in the past month during RAI with prevalent STIs. Results Consistent lubricant use during RAI in the past month was reported by 36% (137/380) of participants. Consistent past month lubricant users had a higher prevalence of STI than inconsistent users (9.5% vs. 2.9%; p=0.006). In a multivariable logistic regression model testing positive for STI was associated with consistent use of lubricant during RAI in the past month (adjusted Odds Ratio (AOR) 2.98 (95%CI 1.09, 8.15) after controlling for age, gender, study location, HIV status, and numbers of RAI partners in the past month. Conclusions Findings suggest some lubricant products may increase vulnerability to STIs. Because of wide use of lubricants and their potential as carrier vehicles for microbicides, further research is essential to clarify if lubricant use poses a public health risk. PMID:22183849

  14. Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks

    PubMed Central

    Paraskevis, Dimitrios; Zavitsanou, Assimina; Magiorkinis, Emmanouil; Gargalianos, Panagiotis; Xylomenos, Georgios; Lazanas, Marios; Chini, Maria; Skoutelis, Athanasios; Papastamopoulos, Vasileios; Antoniadou, Anastasia; Papadopoulos, Antonios; Psichogiou, Mina; Daikos, Georgios; Vassilakis, Alexis; Chrysos, Georgios; Paparizos, Vasilis; Kourkounti, Sofia; Sambatakou, Helen; Kordossis, Theodoros; Koratzanis, Georgios; Panagopoulos, Periklis; Maltezos, Evangelos; Drimis, Stylianos; Hatzakis, Angelos

    2014-01-01

    Introduction The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains. Materials and Methods Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003–2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method. Results We estimated drug resistance levels among naïve patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%–1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003–2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1

  15. Older individuals with HIV infection have greater memory deficits than younger individuals

    PubMed Central

    Tan, IL; Smith, BR; Hammond, E; Vronbrock-Roosa, H; Creighton, JA; Selnes, OA; McArthur, JC; Sacktor, N

    2013-01-01

    Objectives The prevalence of HIV-associated neurocognitive disorder (HAND) remains persistently high in the era of combination anti-retroviral therapy (cART). We aimed to characterize the pattern of neurocognitive dysfunction in older subjects with HAND, in particular amnestic versus non-amnestic impairment. Methods 106 subjects from the Johns Hopkins University NIMH Clinical Outcomes cohort underwent standardized neuropsychological (NP) testing between November 2006 and June 2010. We examined performance in seven cognitive domains (memory, attention, speed of processing, visuospatial, language, motor and executive). Older subjects were defined as age > 50 years at the time of NP testing. Subjects were diagnosed with HAND according to established criteria, and dichotomized into amnestic cognitive impairment or non-amnestic cognitive impairment, with deficit defined as z-scores < −1.5 for the verbal and non-verbal memory domains. Results There were 32 older subjects with a mean age (SD) of 54.2 (2.8) years, and 74 younger subjects, 43.7 (4.3) years. Older age was associated with a 4.8 fold higher odds of memory deficits, adjusted for potential confounders (p=0.035) identified a priori. With age modeled as a continuous covariate, every 1-year increase in age was associated with a 1.11 fold higher odds of memory deficit (p=0.05). Conclusion There was a higher proportion of amnestic cognitive impairment among older subjects than younger subjects with HIV infection. Neurodegenerative processes other than those directly due to HIV may be increasingly important as individuals with chronic HIV infection and HAND survive into older age. PMID:24078559

  16. Invasive lung infection by Scedosporium apiospermum in an immunocompetent individual.

    PubMed

    Agatha, David; Krishnan, Krishnan Usha; Dillirani, Ved-achalam; Selvi, Rangam

    2014-01-01

    Scedosporium apiospermum previously known as Monospermum apiospermum is a ubiquitous fungus found in soil, polluted water and sewage. It causes broad spectrum of diseases, including soft tissue infections, septic arthritis, osteomyelitis, ophthalmic infections, sinusitis, pneumonia, meningitis, brain abscesses, endocarditis and disseminated infection. In recent years, it has been shown to be pathogenic for both immunocompetent and immunosuppressed patients. It is a significant opportunist with very high levels of antifungal resistance. We report here a case of invasive lung infection due to S. apiospermum in an immunocompetent patient who responded to antifungal therapy and surgical treatment. PMID:25308027

  17. 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

  18. 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

  19. 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. PMID:25427101

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

    PubMed

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

    2015-09-01

    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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Determinants of Smoking and Quitting in HIV-Infected Individuals

    PubMed Central

    Regan, Susan; Meigs, James B.; Grinspoon, Steven K.; Triant, Virginia A.

    2016-01-01

    Background Cigarette smoking is widespread among HIV-infected patients, who confront increased risk of smoking-related co-morbidities. The effects of HIV infection and HIV-related variables on smoking and smoking cessation are incompletely understood. We investigated the correlates of smoking and quitting in an HIV-infected cohort using a validated natural language processor to determine smoking status. Method We developed and validated an algorithm using natural language processing (NLP) to ascertain smoking status from electronic health record data. The algorithm was applied to records for a cohort of 3487 HIV-infected from a large health care system in Boston, USA, and 9446 uninfected control patients matched 3:1 on age, gender, race and clinical encounters. NLP was used to identify and classify smoking-related portions of free-text notes. These classifications were combined into patient-year smoking status and used to classify patients as ever versus never smokers and current smokers versus non-smokers. Generalized linear models were used to assess associations of HIV with 3 outcomes, ever smoking, current smoking, and current smoking in analyses limited to ever smokers (persistent smoking), while adjusting for demographics, cardiovascular risk factors, and psychiatric illness. Analyses were repeated within the HIV cohort, with the addition of CD4 cell count and HIV viral load to assess associations of these HIV-related factors with the smoking outcomes. Results Using the natural language processing algorithm to assign annual smoking status yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88–0.91). Ever and current smoking were more common in HIV-infected patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both P<0.001). In multivariate models HIV was independently associated with ever smoking (adjusted rate ratio [ARR] 1.18, 95% CI 1.13–1.24, P <0.001), current smoking (ARR 1.33, 95% CI 1.25

  6. 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

  7. Screening for asymptomatic lymphogranuloma venereum co-infection in men who have sex with men newly diagnosed with HIV, hepatitis C or syphilis.

    PubMed

    Pallawela, Sns; Bradshaw, D; Hodson, L; Rehill, K; Wong, F; Rockwood, N; Gedela, K; Hardie, J; Price, H; Alexander, S; McLean, K; Dean, G; Smith, A; Sullivan, A K

    2016-07-01

    Patients diagnosed with lymphogranuloma venereum have high rates of co-infection with HIV, syphilis and hepatitis C. The aim of this enhanced surveillance was to screen all men who have sex with men (MSM) newly diagnosed with HIV, syphilis or hepatitis C for co-infection with asymptomatic lymphogranuloma venereum as part of the recommended sexual health screen. Of the 145 patients screened, 21 patients were diagnosed with rectal Chlamydia trachomatis, one with both rectal and urethral chlamydia and six with urethral chlamydia. One rectal chlamydia-positive sample, when tested, was equivocal for lymphogranuloma venereum. Our data suggested that there was not a pool of asymptomatic lymphogranuloma venereum infection in MSM recently diagnosed with HIV, hepatitis C and syphilis. However, there have been recent reports of an increased incidence of asymptomatic lymphogranuloma venereum, raising the question whether lymphogranuloma venereum should be screened for in high risk asymptomatic MSM. The prevalence of asymptomatic rectal chlamydia infections was 19%. PMID:26158451

  8. 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

  9. 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

  10. Distribution of individual members of the mosquito Anopheles maculipennis complex in Germany identified by newly developed real-time PCR assays.

    PubMed

    Lühken, R; Czajka, C; Steinke, S; Jöst, H; Schmidt-Chanasit, J; Pfitzner, W; Becker, N; Kiel, E; Krüger, A; Tannich, E

    2016-06-01

    Owing to their role as vectors of malaria parasites, species of the Anopheles maculipennis complex (Diptera: Culicidae) Meigen were intensively studied in the past, but with the disappearance of malaria in Germany in the middle of the last century, the interest in this field of research declined. A comprehensive ecological analysis of the current species distribution for Germany is lacking. Between 2010 and 2013, a total of 1445 mosquitoes of the An. maculipennis complex were collected at 72 different sites in Germany. The samples comprise 722 single individuals as well as 723 individuals in 90 pools of up to 25 mosquitoes. All samples were analysed with newly developed species-specific qPCR assays for the identification of the four German species using nucleotide differences within the internal transcribed spacer 2 (ITS2) ribosomal DNA. All gathered data were used for species distribution modelling. The overall prevalence of An. messeae s.l. was highest with 98.89% of all pools; An. daciae with 6.93% of all individuals and An. messeae s.s. with 69.53%. The prevalence of the other two species was relatively low: An. maculipennis s.s. with 13.30% of all individuals (6.67% of all pools) and An. atroparvus with 1.80% of all individuals (1.11% of all pools). PMID:26787387

  11. Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection

    PubMed Central

    Ananworanich, Jintanat; Sacdalan, Carlo P.; Pinyakorn, Suteeraporn; Chomont, Nicolas; de Souza, Mark; Luekasemsuk, Tassanee; Schuetz, Alexandra; Krebs, Shelly J; Dewar, Robin; Jagodzinski, Linda; Ubolyam, Sasiwimol; Trichavaroj, Rapee; Tovanabutra, Sodsai; Spudich, Serena; Valcour, Victor; Sereti, Irini; Michael, Nelson; Robb, Merlin; Phanuphak, Praphan; Kim, Jerome H.; Phanuphak, Nittaya

    2016-01-01

    Background The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host. Methods AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag−, HIV IgM−) and Fiebig II–IV (HIV-RNA+, p24 Ag + or −, HIV IgM− or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART. Results Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 vs. 190 copies/106 cells) and gut (0 vs. 898 copies/106 cells), and lower HIV-RNA in blood (4.2 vs. 6.2 log10 copies/mL), gut (1.7 vs. 3.1 log10 copies/mg) and cerebrospinal fluid (2.0 vs. 3.8 log10 copies/mL), when compared to Fiebig II–IV individuals (all P<0.01). Median plasma sCD14 level was lower (1.1 vs. 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 vs. 14.9%, both P<0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I vs. 0.5 pg/mL in Fiebig II–IV, P>0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 vs. 2.6%, P>0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 vs. 340 cells/mm3 and 1.1 vs. 0.7, respectively (both P<0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II–IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (P=0.02). Conclusions Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood

  12. Necator americanus Infection: A Possible Cause of Altered Dendritic Cell Differentiation and Eosinophil Profile in Chronically Infected Individuals

    PubMed Central

    Fujiwara, Ricardo T.; Cançado, Guilherme G. L.; Freitas, Paula A.; Santiago, Helton C.; Massara, Cristiano Lara; dos Santos Carvalho, Omar; Corrêa-Oliveira, Rodrigo; Geiger, Stefan M.; Bethony, Jeffrey

    2009-01-01

    Background Hookworms survive for several years (5 to 7 years) in the host lumen, inducing a robust but largely ineffective immune response. Among the most striking aspects of the immune response to hookworm (as with many other helminths) is the ablation of parasite-specific T cell proliferative response (hyporesponsiveness). While the role of the adaptive immune response in human helminth infection has been well investigated, the role of the innate immune responses (e.g., dendritic cells and eosinophils) has received less attention and remains to be clearly elucidated. Methodology/Principal Findings We report on the differentiation/maturation of host dendritic cells in vitro and the eosinophil activation/function associated with human hookworm infection. Mature DCs (mDCs) from Necator americanus (Necator)–infected individuals showed an impaired differentiation process compared to the mDCs of non-infected individuals, as evidenced by the differential expression of CD11c and CD14. These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR. The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected–derived mDCs was further evidenced by their reduced ability to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Antigen-pulsed eosinophils from N. americanus–infected individuals induced significant cell proliferation of autologous PBMCs, when compared to non-infected individuals. Conclusion Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the

  13. Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study

    PubMed Central

    2011-01-01

    Background Hospitals are often the epicentres of newly circulating infections. Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections. This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections. Methods A qualitative study with thematic analysis was conducted using focus group methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece. Results HCWs perceived risk factors for occupationally acquired infectious diseases to be 1.) exposure to patients with undiagnosed infections 2.) break-down in infection control procedures 3.) immuno-naïvety and 4.) symptomatic colleagues. They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health. Staffing demands and loss of income were noted as pressures to attend work when unwell. In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable. In Germany, legislation, privacy and confidentiality were identified as barriers. All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections. These included increased suspicion and awareness among staff and standardised, homogenous absence reporting systems. Conclusions Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings. A pre-requisite will be tackling the drivers for symptomatic HCWs to attend work. PMID:21740552

  14. Cancer "causation" by infections--individual contributions and synergistic networks.

    PubMed

    zur Hausen, Harald; de Villiers, Ethel-Michele

    2014-12-01

    The search for infectious agents playing a role in human carcinogenesis and their identification remain important issues. This could provide clues for a broader spectrum of cancers preventable by vaccination and accessible to specific therapeutic regimens. Yet, the various ways of interacting among different factors functioning synergistically and their different modes of affecting individual cells should bring to question the validity of the term "causation". It also should put a word of caution into all attempts to summarize criteria for "causality" of infectious agents in cancer development. At least in the opinion of these authors, we would be much better off avoiding these terms, replacing "causal factor" by "risk factor" and grading them according to their contribution to an individual's cancer risk. PMID:25499643

  15. 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…

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed

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

    2016-05-01

    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

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

    PubMed Central

    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

  2. Correlated infections: quantifying individual heterogeneity in the spread of infectious diseases.

    PubMed

    Farrington, C Paddy; Whitaker, Heather J; Unkel, Steffen; Pebody, Richard

    2013-03-01

    In this paper, we propose new methods for investigating the extent of heterogeneity in effective contact rates relevant to the transmission of infections. These methods exploit the correlations between ages at infection for different infections within individuals. The methods are developed for serological surveys, which provide accessible individual data on several infections, and are applied to a wide range of infections. We find that childhood infections are often highly correlated within individuals in early childhood, with the correlations persisting into adulthood only for infections sharing a transmission route. We discuss 2 applications of the methods: 1) to making inferences about routes of transmission when these are unknown or uncertain and 2) to estimating epidemiologic parameters such as the basic reproduction number and the critical immunization threshold. Two examples of such applications are presented: elucidating the transmission route of polyomaviruses BK and JC and estimating the basic reproduction number and critical immunization coverage of varicella-zoster infection in Belgium, Italy, Poland, and England and Wales. We speculate that childhood correlations stem from confounding of different transmission routes and represent heterogeneity in childhood circumstances, notably nursery-school attendance. In contrast, it is suggested that correlations in adulthood are route-specific. PMID:23403987

  3. An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas

    PubMed Central

    Gaze, Soraya; Driguez, Patrick; Pearson, Mark S.; Mendes, Tiago; Doolan, Denise L.; Trieu, Angela; McManus, Donald P.; Gobert, Geoffrey N.; Periago, Maria Victoria; Correa Oliveira, Rodrigo; Cardoso, Fernanda C.; Oliveira, Guilherme; Nakajima, Rie; Jasinskas, Al; Hung, Chris; Liang, Li; Pablo, Jozelyn; Bethony, Jeffrey M.; Felgner, Philip L.; Loukas, Alex

    2014-01-01

    Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens. PMID:24675823

  4. Deworming helminth co-infected individuals for delaying HIV disease progression

    PubMed Central

    Walson, Judd L; Herrin, Bradley R; John-Stewart, Grace

    2009-01-01

    Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings where other infectious diseases, such as helminth infections, also are highly prevalent. There are biologically plausible reasons for possible effects of helminth infection in HIV-1-infected individuals, and findings from multiple studies suggest that helminth infection may adversely affect HIV-1 progression. Since initial publication of this review (Walson 2007), additional data from randomized controlled trials (RCTs) has become available. We sought to evaluate all currently available evidence to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives To determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression. Search strategy In this 2008 update, we searched online for published and unpublished studies in The Cochrane Library, MEDLINE, EMBASE, CENTRAL, and AIDSEARCH. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for RCTs and quasi-RCTs that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminthic therapy. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, and/or clinical staging after treatment of helminth co-infection were extracted from identified studies. Main results Of 7,019 abstracts identified (6,384 from original searches plus 635 from updated searches), 17 abstracts were identified as meeting criteria for potential inclusion (15 from previous review plus an additional two RCTs). After restricting inclusion to RCTs, a total of three studies were eligible for inclusion in this updated review. All three

  5. The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia

    PubMed Central

    Abate, Ebba; Belayneh, Meseret; Gelaw, Aschalew; Idh, Jonna; Getachew, Assefa; Alemu, Shitaye; Diro, Ermias; Fikre, Nigussu; Britton, Sven; Elias, Daniel; Aseffa, Abraham; Stendahl, Olle; Schön, Thomas

    2012-01-01

    Background Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. Methodology Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. Results Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. Conclusion One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group. PMID:22952620

  6. Eating and drinking activity of newly weaned piglets: effects of individual characteristics, social mixing, and addition of extra zinc to the feed.

    PubMed

    Dybkjaer, L; Jacobsen, A P; Tøgersen, F A; Poulsen, H D

    2006-03-01

    In production systems, piglets usually fast for a period after weaning, thereby increasing the risk of diarrhea and a reduction in growth. The low level of eating may relate to insufficient drinking activity, as solid feed intake must be accompanied by water intake. Mixing of newly weaned piglets is a well-known stressor and a common procedure in pig production. The effect of mixing on the temporal development of eating and drinking activity in newly weaned piglets has not been elucidated. High concentrations of zinc (Zn) in the feed improve the health and performance of piglets after weaning, but the underlying mechanisms are still obscure. One possibility is that Zn affects eating and drinking behavior. The effects of mixing 4 littermates from each of 2 litters and adding zinc oxide (ZnO; 2,500 ppm of Zn) to the feed were studied in a 2 x 2 factorial experiment using 123 piglets weaned at 27 d of age. Individual eating and drinking times during the initial 48 h after weaning were analyzed on 2 levels of aggregation, day and hour. The piglets spent less time eating on the first day after weaning compared with the second day (20 +/- 5 vs. 98 +/- 10 min, respectively; P < 0.001), whereas they spent more time drinking on the first day compared with the second day (13 +/- 1 vs. 9 +/- 0.5 min, respectively; P < 0.001). Eating and drinking times were positively associated (P < 0.001). Females ate for longer than males (61 +/- 8 vs. 44 +/- 7 min/24 h, respectively, P = 0.002), whereas sex did not affect drinking time. Drinking time increased (P = 0.003) and eating time decreased (P = 0.001) with increasing preweaning growth rate and weaning weight. Neither mixing nor addition of ZnO affected the daily eating time. However, nonmixed piglets given 2,500 ppm of Zn as ZnO in the feed spent more time drinking per day (12 +/- 1 min) than did nonmixed piglets offered 100 ppm of Zn as ZnO (10 +/- 1 min; P = 0.002). Mixing also affected the hourly distribution of the drinking

  7. 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

  8. 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

  9. Exogenous Interleukin-2 Administration Corrects the Cell Cycle Perturbation of Lymphocytes from Human Immunodeficiency Virus-Infected Individuals

    PubMed Central

    Paiardini, Mirko; Galati, Domenico; Cervasi, Barbara; Cannavo, Giuseppe; Galluzzi, Luca; Montroni, Maria; Guetard, Denise; Magnani, Mauro; Piedimonte, Giuseppe; Silvestri, Guido

    2001-01-01

    Human immunodeficiency virus (HIV)-induced immunodeficiency is characterized by progressive loss of CD4+ T cells associated with functional abnormalities of the surviving lymphocytes. Increased susceptibility to apoptosis and loss of proper cell cycle control can be observed in lymphocytes from HIV-infected individuals and may contribute to the lymphocyte dysfunction of AIDS patients. To better understand the relation between T-cell activation, apoptosis, and cell cycle perturbation, we studied the effect of exogenous interleukin-2 (IL-2) administration on the intracellular turnover of phase-dependent proteins. Circulating T cells from HIV-infected patients display a marked discrepancy between a metabolic profile typical of G0 and a pattern of expression of phase-dependent proteins that indicates a more-advanced position within the cell cycle. This discrepancy is enhanced by in vitro activation with ConA and ultimately results in a marked increase of apoptotic events. Conversely, treatment of lymphocytes with IL-2 alone restores the phase-specific pattern of expression of cell cycle-dependent proteins and is associated with low levels of apoptosis. Interestingly, exogenous IL-2 administration normalizes the overall intracellular protein turnover, as measured by protein synthesis, half-life of newly synthesised proteins, and total protein ubiquitination, thus providing a possible explanation for the effect of IL-2 on the intracellular kinetics of cell cycle-dependent proteins. The beneficial effect of IL-2 administration is consistent with the possibility of defective IL-2 function in vivo, which is confirmed by the observation that lymphocytes from HIV-infected patients show abnormal endogenous IL-2 paracrine/autocrine function upon in vitro mitogen stimulation. Overall these results confirm that perturbation of cell cycle control contributes to HIV-related lymphocyte dysfunction and, by showing that IL-2 administration can revert this perturbation, suggest a new

  10. 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

  11. 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

  12. 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 ...

  13. 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.

  14. Individual Predisposition, Household Clustering and Risk Factors for Human Infection with Ascaris lumbricoides: New Epidemiological Insights

    PubMed Central

    Walker, Martin; Hall, Andrew; Basáñez, María-Gloria

    2011-01-01

    Background Much of our current understanding of the epidemiology of Ascaris lumbricoides infections in humans has been acquired by analyzing worm count data. These data are collected by treating infected individuals with anthelmintics so that worms are expelled intact from the gastrointestinal tract. Analysis of such data established that individuals are predisposed to infection with few or many worms and members of the same household tend to harbor similar numbers of worms. These effects, known respectively as individual predisposition and household clustering, are considered characteristic of the epidemiology of ascariasis. The mechanisms behind these phenomena, however, remain unclear. In particular, the impact of heterogeneous individual exposures to infectious stages has not been thoroughly explored. Methodology/Principal Findings Bayesian methods were used to fit a three-level hierarchical statistical model to A. lumbricoides worm counts derived from a three-round chemo-expulsion study carried out in Dhaka, Bangladesh. The effects of individual predisposition, household clustering and household covariates of the numbers of worms per host (worm burden) were considered simultaneously. Individual predisposition was found to be of limited epidemiological significance once household clustering had been accounted for. The degree of intra-household variability among worm burdens was found to be reduced by approximately 58% when household covariates were included in the model. Covariates relating to decreased affluence and quality of housing construction were associated with a statistically significant increase in worm burden. Conclusions/Significance Heterogeneities in the exposure of individuals to infectious eggs have an important role in the epidemiology of A. lumbricoides infection. The household covariates identified as being associated with worm burden provide valuable insights into the source of these heterogeneities although above all emphasize and reiterate

  15. 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

  16. 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

  17. Seroprevalence and risk factors for Toxoplasmosis in HIV infected and non-infected individuals in Bahir Dar, Northwest Ethiopia

    PubMed Central

    2013-01-01

    Background Toxoplasmosis, a zoonotic disease distributed worldwide, is an infection caused by the ubiquitous obligatory intracellular coccidian protozoan organism, Toxoplasma gondii. It is a major public health concern because the disease is serious in terms of mortality or physical and /or psychological sequellae in patients with HIV disease. The aim of the study was to assess the seroprevalence of Toxoplasma gondii IgG and IgM antibodies and associated risk factors in HIV infected and non-infected individuals attending Felege Hiwot referral hospital, Bahir Dar, Northwest Ethiopia. Methods A cross sectional study was conducted at Felege Hiwot referral hospital, Bahir Dar, Amhara National Regional State. Venous blood samples were collected from 103 HIV infected pre anti-retroviral therapy patients at Felege Hiwot referral hospital and 101 HIV negative apparently healthy voluntary blood donors at the blood bank. Serum samples were analyzed for anti-Toxoplasma gondii IgG and IgM antibodies using a commercially available ELISA kit. Socio-demographic and associated risk factors for Toxoplasmosis from each individual were also obtained and the data was analyzed using SPSS version 18. Results Of the examined HIV seropositive individuals, 87.4% (90/103) and 10.7% (11/103) were positive for anti-T. gondii IgG and IgM antibodies, respectively. Multivariate analysis using logistic regression showed that anti-T. gondii seropositivity was independently significantly associated with undercooked or raw meat consumption (adjusted OR=5.73, 95% CI=1.35-24.39; P=0.02) and having contact with cat (adjusted OR= 4.29, 95% CI=1.08-16.94; P=0.04) in HIV positive individuals. In HIV negative apparently healthy blood donors, prevalence of anti-T. gondii antibodies were 70.29% and 2.97% for IgG and IgM, respectively. Multivariate analysis showed that undercooked or raw meat consumption (adjusted OR=6.45, 95% CI=2.16-19.28; p=0.001) and sex (OR=6.79, 95% CI=2.14-21.60; p=0.001) were

  18. 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

  19. Selective decrease of CD26 expression in T cells from HIV-1-infected individuals.

    PubMed

    Blazquez, M V; Madueño, J A; Gonzalez, R; Jurado, R; Bachovchin, W W; Peña, J; Muñoz, E

    1992-11-01

    The decrease of CD4+ cells in AIDS patients is widely documented, although the selective loss within different subsets of CD4+ cells and the mechanisms involved in this phenomenon are controversial. In the present report we have analyzed the proliferative response to Ag and mitogen of peripheral blood T lymphocytes from HIV-infected individuals, the phenotype profile of CD26+ and CD26- subset of cells and their infectivity by the HIV. The expression of CD26 Ag, either in CD4+ or CD8+ cells, was clearly diminished in all the patients tested. On the other hand, the expression of CD29 seems not to be affected, nevertheless T cells from these patients were unable to generate a proliferative response against soluble Ag. In 11 out of 13 patients, polymerase chain reaction studies demonstrated that the CD26- subset of CD4+ cells was the main reservoir for HIV-1 in infected individuals and HIV-1 virus preferentially infected in vitro CD4+/CD26- subpopulation. This capacity for preferential infectivity, together with the selective loss of cells expressing CD26 Ag, helps to explain the progressive impairment in the immune system of these patients and sheds new light on our understanding of the AIDS pathophysiology. PMID:1357035

  20. 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

  1. 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

  2. Recent trends in the spectrum of opportunistic infections in human immunodeficiency virus infected individuals on antiretroviral therapy in South India

    PubMed Central

    Shahapur, Praveen R.; Bidri, Rajendra C.

    2014-01-01

    Background: Opportunistic infections (OI) are the major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. The pattern of OIs differs widely, hence it is necessary to correlate spectrum of OIs and CD4 counts among HIV infected individuals in specific localities. Materials and Methods: The present study describes the clinical and laboratory profiles of different OIs among 55 HIV seropositive patients. CD4 count was estimated and antiretroviral therapy (ART) was started in 27 patients as per National Acquired Immunodeficiency Syndrome Control Organization guidelines. These 27 patients were classified into stage 1, stage 2 and stage 3 based on CD4 counts of >500 cells/μl, 200-499 cells/μl and <200 cells/μl respectively. The OIs presented by respective groups were documented. Results: Pulmonary tuberculosis was found to be the most common OI constituting 43.6% of all cases followed by candidiasis (30.9%), cryptosporidial diarrhea (21.8%), herpes zoster (16.3%), cryptococcal meningitis (3.63%), Pneumocystis jirovecii pneumonia (1.81%), and other miscellaneous infections (23.6%). Only 1 patient was found in stage I while 13 patients each were grouped in stage II or stage III. The mean CD4 count in our study population who were on ART was 230 ± 150 cells/µl. Conclusion: The pattern of OIs among our study group did not differ significantly from patients not receiving ART. The effect of ART on CD4 count differs from patient to patient based on the degree of depletion of CD4 count before the initiation of ART, drug adherence, concomitant OIs and their treatment. PMID:25097422

  3. 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

  4. 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

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

    PubMed Central

    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

  6. Prevalence and Treatment of Latent Tuberculosis Infection Among Newly Arrived Refugees in San Diego County, January 2010–October 2012

    PubMed Central

    Bennett, Rachel J.; Brodine, Stephanie; Waalen, Jill; Moser, Kathleen; Rodwell, Timothy C.

    2014-01-01

    Objectives. We determined the prevalence and treatment rates of latent tuberculosis infection (LTBI) in newly arrived refugees in San Diego County, California, and assessed demographic and clinical characteristics associated with these outcomes. Methods. We analyzed data from LTBI screening results of 4280 refugees resettled in San Diego County between January 2010 and October 2012. Using multivariate logistic regression, we calculated the associations between demographic and clinical risk factors and the outcomes of LTBI diagnosis and LTBI treatment initiation. Results. The prevalence of LTBI was highest among refugees from sub-Saharan Africa (43%) and was associated with current smoking and having a clinical comorbidity that increases the risk for active tuberculosis. Although refugees from sub-Saharan Africa had the highest prevalence of infection, they were significantly less likely to initiate treatment than refugees from the Middle East. Refugees with postsecondary education were significantly more likely to initiate LTBI treatment. Conclusions. Public health strategies are needed to increase treatment rates among high-risk refugees with LTBI. Particular attention is required among refugees from sub-Saharan Africa and those with less education. PMID:24524534

  7. Individual genetic diversity and probability of infection by avian malaria parasites in blue tits (Cyanistes caeruleus).

    PubMed

    Ferrer, E S; García-Navas, V; Sanz, J J; Ortego, J

    2014-11-01

    Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations. PMID:25264126

  8. Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.

    PubMed

    Zhang, Jing; Shen, Zhi-Yong; Li, Zheng; Liang, Shu-Jia; He, Cui; Liang, Fu-Xiong; Feng, Yi; Li, Jian-Jun; Ruan, Yu-Hua; Zhou, Yue-Jiao; Shao, Yi-Ming; Xing, Hui; Liao, Ling-Jie

    2015-05-01

    The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However

  9. Alteration of select gene expression patterns in individuals infected with HIV-1.

    PubMed

    Serrao, Erik; Wang, Chia-Hao; Frederick, Toinette; Lee, Chi-Lin; Anthony, Patricia; Arribas-Layton, David; Baker, Kerry; Millstein, Joshua; Kovacs, Andrea; Neamati, Nouri

    2014-04-01

    Multiple human proteins have been shown to both support and restrict viral replication, and confirmation of virus-associated changes in the expression of these genes is relevant for future therapeutic efforts. In this study a well-characterized panel of 49 individuals either infected with HIV-1 or uninfected was compiled and analyzed for the effect of HIV infection status, viral load, and antiretroviral treatment on specific gene expression. mRNA was extracted and reverse transcribed from purified CD4+ cells, and quantitative real-time PCR was utilized to scrutinize differences in the expression of four host genes that have been demonstrated to either stimulate (HSP90 and LEDGF/p75) or restrict (p21/WAF1 and APOBEC3G) proviral integration. HIV infection status was associated with slight to moderate alterations in the expression of all four genes. After adjusting for age, mRNA expression levels of HSP90, LEDGF/p75 and APOBEC3G were found to all be decreased in infected patients compared to healthy controls by 1.43-, 1.26-, and 4.71-fold, respectively, while p21/WAF1 expression was increased 2.35-fold. Furthermore, individuals receiving raltegravir exhibited a 1.28-fold reduction in LEDGF/p75 compared to those on non-raltegravir antiretroviral treatment. Identification of these and similar HIV-induced changes in gene expression may be valuable for delineating the extent of host cell molecular mechanisms stimulating viral replication. PMID:24482297

  10. 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

  11. 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

  12. Quantification of mitochondrial toxicity in HIV-infected individuals by quantitative PCR compared to flow cytometry

    PubMed Central

    Wagner, Thor A.; Lin, Chen-Han; Tobin, Nicole H.; Côté, Hélène C.F.; Sloan, Derek D.; Jerome, Keith R.; Frenkel, Lisa M.

    2014-01-01

    Background Non-invasive diagnostic assays to evaluate mitochondrial toxicity could have significant clinical utility for HIV-infected individuals on antiretroviral therapy (ART). Methods This study compared the ratio of mitochondrial to nuclear DNA determined by quantitative PCR to the ratio of mitochondrial to nuclear-encoded proteins by flow cytometry, in peripheral blood mononuclear cells from 73 HIV-infected individuals with and without risk factors for mitochondrial toxicity. Results PCR detected similar mitochondrial/nuclear DNA in HIV-infected individuals without a history of ART, and those receiving ART with lipodystrophy, lipoatrophy or a history of suspected lactic acidosis. However, the ratio was significantly greater in ART-untreated compared to those receiving either stavudine or didanosine. In contrast, flow cytometry did not detect any differences in mitochondrial/nuclear protein (1). There was no correlation between the assays (rho = −0.05, p = 0.65). Conclusions Assessment of the mitochondrial/nuclear DNA ratio by quantitative PCR performed better than the mitochondrial/nuclear-encoded protein ratio by flow cytometry to detect adverse effects of nucleoside analogues on mitochondria. PMID:23044657

  13. 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

  14. 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.

  15. Human papillomavirus, anal cancer, and screening considerations among HIV-infected individuals.

    PubMed

    Cachay, Edward R; Mathews, William Christopher

    2013-01-01

    Invasive anal cancer has become an important cause of non AIDS-related cancer among HIV-infected individuals. Human papillomavirus is the main etiological agent. This review explains the pathophysiologic role of human papillomavirus in the development of invasive anal cancer, summarizes recent epidemiological trends of invasive anal cancer, and reviews the evidence to address common clinical questions posed when screening for anal cancer in HIV-infected patients. The effect of highly active antiretroviral therapy on human papillomavirus oncogenesis is still unclear, but given the increased clinical burden of invasive anal cancer among HIV-infected patients, many clinics have implemented screening programs for anal cancer and its precursors. Despite the availability of several modalities for treatment of precursors of anal cancer, evidence that current treatment modalities favorably alter the natural history of human papillomavirus oncogenesis in the anal and perianal regions is still inconclusive. However, there is sufficient evidence to state that the accuracy of anal cancer screening procedures (cytology and high-resolution anoscopy directed biopsy) is comparable to the accuracy of those used in screening for cervical cancer precursors. Studies that systematically assess the efficacy of these anal cancer screening programs in reducing the incidence of and morbidity and mortality from invasive anal cancer among HIV-infected patients are needed. PMID:23681437

  16. 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

  17. Nutritional strategies to boost immunity and prevent infection in elderly individuals.

    PubMed

    High, K P

    2001-12-01

    Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity. PMID:11692301

  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

    Lucas, Gregory M

    2011-05-23

    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. 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

  1. 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

  2. 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

  3. Expression of human immunodeficiency virus (HIV) in naturally infected peripheral blood mononuclear cells: comparison of a standard co-culture technique with a newly developed microculture method.

    PubMed

    Eberlein, B; Baur, A; Neundorfer, M; Jahn, G

    1991-05-01

    Peripheral blood mononuclear cells (PBMCs) from 29 patients infected with human immunodeficiency virus (HIV) were cultured by two different methods. One was the standard co-culture technique, the other a newly developed microculture method. In this assay 10(6) PBMCs were cultivated in 250 microliters medium, no activating agents or allogeneic cells were present. P24 antigen production measured by this method was found in 7 out of 11 PBMC cultures of patients in the Walter Reed (WR) stage 1 or 2, whereas only 4 samples were positive by the co-culture procedure. Cultures from patients in the later stages of the disease (WR 5/6) showed a higher p24 production by the co-culture method than by the microculture assay. It is assumed that rapidly growing HIV strains can be better assessed by the co-culture method which may select for these strains. P24 expression can be more easily obtained by the microculture technique even in cases where slowly replicating strains may be present. In conclusion, results from the microculture procedure described may be a useful supplementation to findings observed by the co-culture method. PMID:1909827

  4. 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

  5. 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.

  6. Regulatory T Cells Expanded from HIV-1-Infected Individuals Maintain Phenotype, TCR Repertoire and Suppressive Capacity

    PubMed Central

    Angin, Mathieu; Klarenbeek, Paul L.; King, Melanie; Sharma, Siddhartha M.; Moodley, Eshia S.; Rezai, Ashley; Piechocka-Trocha, Alicja; Toth, Ildiko; Chan, Andrew T.; Goulder, Philip J.; Ndung'u, Thumbi; Kwon, Douglas S.; Addo, Marylyn M.

    2014-01-01

    While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection. PMID:24498287

  7. Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

    PubMed

    Angin, Mathieu; Klarenbeek, Paul L; King, Melanie; Sharma, Siddhartha M; Moodley, Eshia S; Rezai, Ashley; Piechocka-Trocha, Alicja; Toth, Ildiko; Chan, Andrew T; Goulder, Philip J; Ndung'u, Thumbi; Kwon, Douglas S; Addo, Marylyn M

    2014-01-01

    While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection. PMID:24498287

  8. 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

  9. 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. PMID:24874725

  10. MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection.

    PubMed

    Kubinak, Jason L; Stephens, W Zac; Soto, Ray; Petersen, Charisse; Chiaro, Tyson; Gogokhia, Lasha; Bell, Rickesha; Ajami, Nadim J; Petrosino, Joseph F; Morrison, Linda; Potts, Wayne K; Jensen, Peter E; O'Connell, Ryan M; Round, June L

    2015-01-01

    The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health. PMID:26494419

  11. MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection

    PubMed Central

    Kubinak, Jason L.; Stephens, W. Zac; Soto, Ray; Petersen, Charisse; Chiaro, Tyson; Gogokhia, Lasha; Bell, Rickesha; Ajami, Nadim J.; Petrosino, Joseph F.; Morrison, Linda; Potts, Wayne K.; Jensen, Peter E.; O'Connell, Ryan M.; Round, June L.

    2015-01-01

    The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health. PMID:26494419

  12. 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

  13. Chest Computed Tomography Findings in HIV-Infected Individuals in the Era of Antiretroviral Therapy

    PubMed Central

    Clausen, Emily; Wittman, Catherine; Gingo, Matthew; Fernainy, Khaled; Fuhrman, Carl; Kessinger, Cathy; Weinman, Renee; McMahon, Deborah; Leader, Joseph; Morris, Alison

    2014-01-01

    Background Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications. Methods Cross-sectional study of radiographic abnormalities in an HIV-infected outpatient population during the antiretroviral therapy era. Demographics, chest computed tomography, and pulmonary function tests were obtained in HIV-infected volunteers without acute respiratory illness from the University of Pittsburgh HIV/AIDS clinic. Overall prevalence of radiographic abnormalities and potential risk factors for having any abnormality, nodules, or emphysema were evaluated using univariate and multivariable analyses. Results A majority of the 121 participants (55.4%) had a radiographic abnormality with the most common being emphysema (26.4%), nodules (17.4%), and bronchiectasis (10.7%). In multivariate models, age (odds ratio [OR] per year  = 1.07, 95% confidence interval [CI] 1.04–1.14, p<0.001), pneumonia history (OR  = 3.60, 95% CI  = 1.27–10.20, p = 0.016), and having ever smoked (OR  = 3.66, p = 0.013, 95% CI  = 1.31–10.12) were significant predictors of having any radiographic abnormality. Use of antiretroviral therapy, CD4 cell count, and HIV viral load were not associated with presence of abnormalities. Individuals with radiographic emphysema were more likely to have airway obstruction on pulmonary function tests. Only 85.8% participants with nodules had follow-up imaging resulting in 52.4% having stable nodules, 23.8% resolution of their nodules, 4.8% development of a new nodule, and 4.8% primary lung cancer. Conclusions Radiographic abnormalities remain common in HIV-infected individuals with emphysema, nodules, and bronchiectasis being the most common. Age, smoking, and pneumonia were associated with radiographic abnormalities, but HIV-associated factors did not seem to predict risk. PMID:25409510

  14. High Prevalence of Plasmodium falciparum Infection in Asymptomatic Individuals from the Democratic Republic of the Congo

    PubMed Central

    Mvumbi, Dieudonné Makaba; Bobanga, Thierry Lengu; Melin, Pierrette; De Mol, Patrick; Kayembe, Jean-Marie Ntumba; Situakibanza, Hippolyte Nani-Tuma; Mvumbi, Georges Lelo; Nsibu, Célestin Ndosimao; Umesumbu, Solange Efundu; Hayette, Marie-Pierre

    2016-01-01

    Malaria remains a major public health problem in the Democratic Republic of Congo (DRC) with 14 million cases reported by the WHO Malaria Report in 2014. Asymptomatic malaria cases are known to be prevalent in endemic areas and are generally untreated, resulting in a significant source of gametocytes that may serve as reservoir of disease transmission. Considering that microscopy certainly underestimates the prevalence of Plasmodium infections within asymptomatic carriers and that PCR assays are currently recognized as the most sensitive methods for Plasmodium identification, this study was conducted to weigh the asymptomatic carriage in DRC by a molecular method. Six provinces were randomly selected for blood collection in which 80 to 100 individuals were included in the study. Five hundred and eighty blood samples were collected and molecular diagnosis was performed. Globally, almost half of the samples collected from asymptomatic individuals (280/580; 48.2%) had Plasmodium infections and the most species identified was P. falciparum alone in combination with P. malariae. The high prevalence reported here should interpellate the bodies involved in malaria control in DR Congo to take into account asymptomatic carriers in actions taken and consider asymptomatic malaria as a major hurdle for malaria elimination. PMID:26942036

  15. 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

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

    PubMed

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

    2015-07-22

    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

  17. 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

  18. Plasma Cytokine Levels Are Related to Brain Volumes in HIV-infected Individuals

    PubMed Central

    Gongvatana, Assawin; Correia, Stephen; Dunsiger, Shira; Gauthier, Lynne; Devlin, Kathryn N.; Ross, Skye; Navia, Bradford; Tashima, Karen T.; DeLaMonte, Suzanne; Cohen, A.

    2015-01-01

    Background HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. Methods We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Results Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1β, IL-6, IL-16, IL-18, IP-10, MIP-1β, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. Conclusion The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities. PMID:25273619

  19. Emerging Variability in HIV-1 Genetics among Recently Infected Individuals in Yunnan, China

    PubMed Central

    Chen, Min; Yang, Li; Ma, Yanling; Su, Yingzhen; Yang, Chaojun; Luo, Hongbing; Chen, Huichao; Chen, Ling; Yan, Wenyun; Shi, Yuhua; Jia, Manhong; Lu, Lin

    2013-01-01

    Background Yunnan has the longest endured Human Immunodeficiency Virus-1 (HIV-1) epidemic in China, and the genetic diversity of HIV-1 constitutes an essential characteristic of molecular epidemiology in this region. To obtain a more comprehensive picture of the dynamic changes in Yunnan’s HIV-1 epidemic, a cross-sectional molecular epidemiological investigation was carried out among recently infected individuals. Methodology/Principal Findings We sequenced partial gag (HXB2∶781–1861) and env (HXB2∶7002–7541) genes from 308 plasma samples of recently infected patients. With phylogenetic analysis, 130 specimens generated interpretable genotyping data. We found that the circulating genotypes included: CRF08_BC (40.8%), unique recombinant forms (URFs, 27.7%), CRF01_AE (18.5%), CRF07_BC (9.2%), subtype B (2.3%) and C (1.5%). CRF08_BC was the most common genotype, and was predominant in both intravenous drug users (IDUs) and heterosexually transmitted populations. CRF08_BC and CRF07_BC still predominated in eastern Yunnan, but CRF08_BC showed increasing prevalence in western Yunnan. Strikingly, the URFs raised dramatically in most regions of Yunnan. Seven different types of URFs were detected from 12 prefectures, suggesting that complicated and frequent recombination is a salient feature of Yunnan’s HIV-1 epidemic. Among URFs, two BC clusters with distinctive recombination patterns might be potential new CRF_BCs. CRF01_AE was no longer confined to the prefectures bordering Myanmar, and had spread to the eastern part of Yunnan, especially the capital city of Kunming, with a large number of infections in the transient population. The ratios of the main genotypes showed no statistical differences between infected IDUs and heterosexually transmitted infections. Conclusions/Significance The changing patterns of the dominant HIV-1 genotypes in Yunnan indicate the complex evolving dynamic nature of the epidemic. Understanding new trends in molecular epidemiology of

  20. 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

  1. Autonomic Function is Associated with Fitness Level in HIV-Infected Individuals

    PubMed Central

    Kocher, Morgan H; Hetzler, Ronald K; Shikuma, Cecilia M; Kimura, Iris F; Stickley, Cris D; Lindsey, Rachel A; Nakamoto, Beau K; Chow, Dominic C

    2015-01-01

    Background Cardiovascular fitness can improve autonomic function (AF) in human immunodeficiency virus (HIV)-infected individuals. Methods Cross-sectional study investigating relationship between AF and cardiovascular fitness in HIV+ individuals on antiretroviral therapy. Participants’ (n=29) maximal oxygen consumption (VO2MAX) were assessed by graded exercise test and scaled allometrically, then divided into tertiles by fitness level (Unfit, Low-fit, and Moderately-fit). Heart rate variability (HRV) and the Autonomic Reflex Screen were used to assess AF. Results Median VO2MAX were 104.9, 130.5, and 150.2 mL•kg−.67•min−1 for Unfit (n=10), Low-fit (n=10), and Moderately-fit (n= 9) groups respectively (p<0.05). Positive correlations were found between VO2MAX and HRV (Spearman’s rho range 0.383 to 0.553) were found. Quantitative Sudomotor Axon Reflex Test (QSART) Distal Leg volumes was lower in Unfit compared to Low-fit (p=0.007) and Moderately-fit groups (p=0.018). Unfit QSART total volumes was lower than Moderately-fit (p=0.014). Conclusion A positive relationship existed between AF and fitness levels. HIV+ individuals could benefit from improved fitness. PMID:26213714

  2. 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. PMID:26774333

  3. The quality of interactive computer use among HIV-infected individuals.

    PubMed

    Smaglik, P; Hawkins, R P; Pingree, S; Gustafson, D H; Boberg, E; Bricker, E

    1998-01-01

    This study examined how HIV-infected individuals used an interactive health software package called CHESS (Comprehensive Health Enhancement Support System). CHESS packages information and support in a variety of ways; the research examined how a subset of users whose posttest scores in a larger randomized trial showed significant improvement in quality of life compared on use patterns of CHESS with those who did not improve. The evidence presented here points to the nature of CHESS use more than it does to the amount of CHESS use. Those whose quality of life improved were among the most involved in their use of CHESS information tools. That is, even though Discussion Group accounted for the majority of all CHESS uses and time spent with the system, total use and Discussion Group use appeared less important than use of the information tools, especially if that use was at least somewhat sustained and involved. PMID:10947374

  4. Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals.

    PubMed Central

    Sullivan, D; Haynes, K; Bille, J; Boerlin, P; Rodero, L; Lloyd, S; Henman, M; Coleman, D

    1997-01-01

    Candida dubliniensis is a recently identified chlamydospore-positive yeast species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected (HIV+) patients and is closely related to Candida albicans. Several recent reports have described atypical oral Candida isolates with phenotypic and genetic properties similar to those of C. dubliniensis. In this study 10 atypical chlamydospore-positive oral isolates from HIV+ patients in Switzerland, the United Kingdom, and Argentina and 1 isolate from an HIV-negative Irish subject were compared to reference strains of C. albicans and Candida stellatoidea and reference strains of C. dubliniensis recovered from Irish and Australian HIV+ individuals. All 11 isolates were phenotypically and genetically similar to and phylogenetically identical to C. dubliniensis. These findings demonstrate that the geographical distribution of C. dubliniensis is widespread, and it is likely that it is a significant constituent of the normal oral flora with the potential to cause oral candidiasis, particularly in immunocompromised patients. PMID:9157162

  5. 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

  6. Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals.

    PubMed

    Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan; Jensen, Jørgen Skov; Benfield, Thomas; Gerstoft, Jan; Katzenstein, Terese Lea

    2016-08-23

    Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0.006). In conclusion, this study provides evidence for the use of doxycycline as a treatment option when treating a HIV-infected population for syphilis. PMID:26568359

  7. Individual and Contextual Factors of Sexual Risk Behavior in Youth Perinatally Infected with HIV

    PubMed Central

    Bauermeister, José A.; Robbins, Reuben N.; Gromadzka, Olga; Abrams, Elaine J.; Wiznia, Andrew; Bamji, Mahrukh; Mellins, Claude A.

    2012-01-01

    Abstract This study prospectively examines the effects of maternal and child HIV infection on youth penetrative and unprotected penetrative sex, as well as the role of internal contextual, external contextual, social and self-regulatory factors in influencing the sexual behaviors of HIV−infected (PHIV+), HIV−affected (uninfected with an HIV+ caregiver), and HIV unaffected (uninfected with an HIV− caregiver) youth over time. Data (N=420) were drawn from two longitudinal studies focused on the effects of pediatric or maternal HIV on youth (51% female; 39% PHIV+) and their caregivers (92% female; 46% HIV+). PHIV+ youth were significantly less likely to engage in penetrative sex than HIV− youth at follow-up, after adjusting for contextual, social, and self-regulatory factors. Other individual- and contextual-level factors such as youth alcohol and marijuana use, residing with a biological parent, caregiver employment, caregiver marijuana use, and youth self-concept were also associated with penetrative sex. Youth who used alcohol were significantly more likely to engage in unprotected penetrative sex. Data suggest that, despite contextual, social, and self-regulatory risk factors, PHIV+ youth are less likely to engage in sexual behavior compared to HIV− youth from similar environments. Further research is required to understand delays in sexual activity in PHIV+ youth and also to understand potential factors that promote resiliency, particularly as they age into older adolescence and young adulthood. PMID:22694193

  8. Prescription medication misuse among HIV-infected individuals taking antiretroviral therapy

    PubMed Central

    Newville, Howard; Roley, Jason; Sorensen, James L.

    2014-01-01

    HIV has become a highly treatable disease due to advances in antiretroviral therapy (ART). Additionally, HIV-infected individuals often take opiates, barbiturates, and benzodiazepines to treat co-occurring conditions, including pain and symptoms of HIV. We sought to examine prescription medication misuse by surveying 295 HIV-infected patients receiving ART. Participants answered questions about their demographics, alcohol and other drug use, psychiatric diagnoses, ART adherence and side effects, and quality of life. 11% of our sample acknowledged prescription medication misuse. In regression analysis, prescription medication misusers were more likely to report any drinking to intoxication (OR=4.31, 95% CI: 1.35-13.76, p=0.013), reported greater severity of ART side effects (OR=1.05, 95% CI: 1.01-1.10, p=0.041), and demonstrated poorer cognitive functioning (OR=0.97, 95% CI: 0.94-0.99, p=0.048) compared to those who did not misuse prescription medications. Special care should be taken by medical providers before prescribing medications that may be abused or diverted. Patients should also be screened for aberrant use, even if not prescribed. ART side effects, cognitive deficits, and alcohol abuse may serve as risk factors or indicators of prescription medication misuse, and should be monitored. PMID:25245428

  9. Food insecurity, depression, and social support in HIV-infected Hispanic individuals.

    PubMed

    Kapulsky, Leonid; Tang, Alice M; Forrester, Janet E

    2015-04-01

    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. 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. 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. 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

  10. 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

  11. Quantitative Evaluation of an Instrument to Identify Chronic Pain in HIV-Infected Individuals.

    PubMed

    Merlin, Jessica S; Westfall, Andrew O; Chamot, Eric; Saag, Michael; Walcott, Melonie; Ritchie, Christine; Kertesz, Stefan

    2015-06-01

    A method to rapidly identify the presence of chronic pain would enhance the care of HIV-infected individuals, but such an instrument has not been assessed in this population to date. We assessed the construct validity of the two-question Brief Chronic Pain Questionnaire (BCPQ) in HIV-infected patients by assessing the association between BCPQ responses and known correlates of chronic pain. Participants in the University of Alabama Center for AIDS Research Network of Integrated Clinical Systems cohort completed the BCPQ, along with the EuroQOL to assess physical function, the PHQ-9 to assess depression, and the PHQ-anxiety module to assess anxiety. Among 100 participants, 25% were female, the mean age was 45 (SD 12), 63% were African American, 27% were publicly insured, the median CD4(+) T cell count was 572 cells/mm(3) (IQR 307-788), and 82% had an undetectable viral load. Participants with chronic pain were more likely to have impaired mobility (43% vs. 12%, p=0.001), difficulty with usual activities (47% vs. 12%, p<0.001), lower overall health state (70 vs. 84, p=0.002), pain today (80% vs. 27%, p<0.001), depression (30% vs. 15%, p=0.10), and anxiety (43% vs. 10%, p<0.001) than those without chronic pain. This study provides preliminary evidence for the BCPQ as a brief questionnaire to identify the presence of chronic pain in HIV care settings. PMID:25693683

  12. SCREENING GUIDELINES FOR NON-AIDS DEFINING CANCERS IN HIV-INFECTED INDIVIDUALS

    PubMed Central

    Mani, Deepthi; Aboulafia, David M

    2015-01-01

    Purpose of the Review The growing burden of non-AIDS-defining malignancies (non-ADM) among people living with HIV/AIDS (PLWHA) highlights the need for cancer prevention and early detection. In this article we propose screening guidelines for non-ADM in PLWHA. Recent findings Screening for lung cancer with low-dose helical chest computerized tomography (LDCT) in the National Lung Screening Trial data demonstrated a decrease in lung cancer and all-cause mortality. Recent studies have demonstrated a favorable experience among PLWHA with liver transplantation. Over-diagnosis is common with breast and prostate cancer screening. Anal cancer rates were substantially higher for HIV-infected men who have sex with men (MSM), other men, and women compared with HIV-uninfected individuals. Summary Screening recommendations for the general population can be applied to PLWHA patients for breast, colon and prostate cancer. Screening for lung cancer with LDCT could be considered in PLWHA at risk. American Association for the Study of Liver Diseases screening recommendations with biennial ultrasonography may be applied to at-risk PLWHA for hepatocellular carcinoma. All HIV-infected adults should be offered anal cancer screening as part of clinical care at specialized centers. PMID:23942295

  13. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

    PubMed

    Pérez-Fuentes, Ricardo; Guégan, Jean-François; Barnabé, Christian; López-Colombo, Aurelio; Salgado-Rosas, Hilda; Torres-Rasgado, Enrique; Briones, Bernardo; Romero-Díaz, Mónica; Ramos-Jiménez, Judith; Sánchez-Guillén, María del Carmen

    2003-03-01

    Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease. PMID:12670514

  14. Osteopontin enhances HIV replication and is increased in the brain and cerebrospinal fluid of HIV-infected individuals

    PubMed Central

    Islam, Tanzeem; Adams, Robert; Nerle, Sujata; Kamara, Masiray; Eger, Caitlin; Marder, Karen; Cohen, Bruce; Schifitto, Giovanni; McArthur, Justin C.; Sacktor, Ned; Pardo, Carlos A.

    2012-01-01

    Despite effective and widely available suppressive anti-HIV therapy, the prevalence of mild neurocognitive dysfunction continues to increase. HIV-associated neurocognitive disorder (HAND) is a multifactorial disease with sustained central nervous system inflammation and immune activation as prominent features. Inflammatory macrophages, HIV-infected and uninfected, play a central role in the development of HIV dementia. There is a critical need to identify biomarkers and to better understand the molecular mechanisms leading to cognitive dysfunction in HAND. In this regard, we identified through a subtractive hybridization strategy osteopontin (OPN, SPP1, gene) an inflammatory marker, as an upregulated gene in HIV-infected primary human monocyte-derived macrophages. Knockdown of OPN in primary macrophages resulted in a threefold decrease in HIV-1 replication. Ectopic expression of OPN in the TZM-bl cell line significantly enhanced HIV infectivity and replication. A significant increase in the degradation of the NF-κB inhibitor, IκBα and an increase in the nuclear-to-cytoplasmic ratio of NF-κB were found in HIV-infected cells expressing OPN compared to controls. Moreover, mutation of the NF-κB binding domain in the HIV-LTR abrogated enhanced promoter activity stimulated by OPN. Interestingly, compared to cerebrospinal fluid from normal and multiple sclerosis controls, OPN levels were significantly higher in HIV-infected individuals both with and without neurocognitive disorder. OPN levels were highest in HIV-infected individuals with moderate to severe cognitive impairment. Moreover, OPN was significantly elevated in brain tissue from HIV-infected individuals with cognitive disorder versus those without impairment. Collectively, these data suggest that OPN stimulates HIV-1 replication and that high levels of OPN are present in the CNS compartment of HIV-infected individuals, reflecting ongoing inflammatory processes at this site despite anti-HIV therapy. PMID

  15. Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study

    PubMed Central

    2012-01-01

    Background The delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay. Methods A nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values. Results From a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 – 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative. Conclusion The present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV. PMID:22958583

  16. Coregulation mapping based on individual phenotypic variation in response to virus infection

    PubMed Central

    2010-01-01

    Background Gene coregulation across a population is an important aspect of the considerable variability of the human immune response to virus infection. Methodology to investigate it must rely on a number of ingredients ranging from gene clustering to transcription factor enrichment analysis. Results We have developed a methodology to investigate the gene to gene correlations for the expression of 34 genes linked to the immune response of Newcastle Disease Virus (NDV) infected conventional dendritic cells (DCs) from 145 human donors. The levels of gene expression showed a large variation across individuals. We generated a map of gene co-expression using pairwise correlation and multidimensional scaling (MDS). The analysis of these data showed that among the 13 genes left after filtering for statistically significant variations, two clusters are formed. We investigated to what extent the observed correlation patterns can be explained by the sharing of transcription factors (TFs) controlling these genes. Our analysis showed that there was a significant positive correlation between MDS distances and TF sharing across all pairs of genes. We applied enrichment analysis to the TFs having binding sites in the promoter regions of those genes. This analysis, after Gene Ontology filtering, indicated the existence of two clusters of genes (CCL5, IFNA1, IFNA2, IFNB1) and (IKBKE, IL6, IRF7, MX1) that were transcriptionally co-regulated. In order to facilitate the use of our methodology by other researchers, we have also developed an interactive coregulation explorer web-based tool called CorEx. It permits the study of MDS and hierarchical clustering of data combined with TF enrichment analysis. We also offer web services that provide programmatic access to MDS, hierarchical clustering and TF enrichment analysis. Conclusions MDS mapping based on correlation in conjunction with TF enrichment analysis represents a useful computational method to generate predictions underlying gene

  17. HIV-1 diversity in infected individuals in Suzhou and Suqian, China.

    PubMed

    Qin, Chenhao; Zhang, Ping; Zhu, Weiguang; Hao, Fangyuan; Gu, Aiping; Fen, Ping; Zhu, Xueming; Du, Hong

    2016-01-01

    Jiangsu is one province with severe HIV-1 epidemic in China. However, the molecular epidemiological characterizations of HIV-1 in many cities of Jiangsu remain unclear. A molecular epidemiological investigation was performed based on 38 HIV-positive samples collected from Suzhou and Suqian during 2011-2013. Five HIV-1 genomic fragments, p17, pol, vif-vpr, vpr-env, and C2V3 were amplified and sequenced from these samples. HIV-1 group M subtype of each sample was determined by phylogenetic analyses with the standard reference sequences. Among these infected individuals, 81.6 % (31/38) self-reported to be infected via sexual contacts, including 50.0 % (19/38) via heterosexual contact and 31.6 % (12/38) via homosexual contact. Among 34 samples with available pol or vif-env sequence, 19 (55.9 %) CRF01_AE, 7 (20.6 %) CRF07_BC, 3 (8.8 %) CRF08_BC, and 5 (14.7 %) inter-subtype recombinants were identified. No pure B, B' and C subtypes were found in this cohort. The five recombinants contain one B/C, three CRF01/B and one CRF01/B/C recombinants. These results suggest that CRF01_AE was the most predominant HIV-1 group M subtype and CRF01_AE-involved recombinants were the major recombinant forms. Comparison showed that there was no obvious difference in HIV-1 group M subtype distribution between Jiangsu (including Suzhou and Suqian) and the surrounding provinces (e.g., Shanghai, Anhui, and Shandong). CRF01_AE and CRF07_BC were the top two predominant HIV-1 genotypes in Jiangsu, and less and/or no pure subtype B and C was currently circulating here. We predicted that more CRF01/CRF07 recombinants, but fewer B/C recombinants will be generated in Jiangsu in future. PMID:27386334

  18. A CONCISE PANEL OF BIOMARKERS IDENTIFIES NEUROCOGNITIVE FUNCTIONING CHANGES IN HIV-INFECTED INDIVIDUALS

    PubMed Central

    Marcotte, Thomas D.; Deutsch, Reena; Michael, Benedict Daniel; Franklin, Donald; Cookson, Debra Rosario; Bharti, Ajay R.; Grant, Igor; Letendre, Scott L.

    2013-01-01

    Background Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Methods Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. Results At the first visit, subjects were mostly middle-aged (median 45) white (58%) men (84%) who had AIDS (70%). Of the 73% who took antiretroviral therapy (ART), 54% had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82% of Wo and SN subjects, including 88% of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81% of Im and SI subjects, including 100% of SI subjects. Conclusions This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on

  19. 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

  20. 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

  1. 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

  2. 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. PMID:25639813

  3. 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

  4. 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

  5. Treatment considerations for HIV-infected individuals with severe mental illness.

    PubMed

    Blank, Michael B; Himelhoch, Seth; Walkup, James; Eisenberg, Marlene M

    2013-12-01

    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

  6. 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. PMID:26851588

  7. 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

  8. [Prevalence of subclinical udder infections and individual somatic cell counts in three dairy goat herds during a full lactation].

    PubMed

    Schaeren, W; Maurer, J

    2006-12-01

    For dairy goats, both the determination of the somatic cell counts (SCC) and the interpretation of these values may be a problem. Several investigations have shown that SCC for goat's milk, even from not infected mammary halves, are often higher than for cows milk. In the three herds examined about 40% of mammary halves and 30% of the goats were infected. However large differences between the three herds could be observed. In most cases, infections were caused by coagulase negative staphylococci (CNS) or corynebacteria. The SCC of individual milk samples from goats without any udder infection hardly differed from those of goats with at least one udder half infected with CNS. In 20% and 30% of the cases the SCC was higher than 750'000 cells/ml, respectively. The relation between California Mastitis Test (CMT) reactions and udder infections was not very close. Over 20% of mammary halves infected with CNS showed negative CMT reactions. On the other hand, 25% of samples from mammary halves without a proven infection reacted positively. The large differences in individual cell counts on herd and animal level indicate that production and breeding systems might be important reasons for the higher SCC. As a consequence, the most common methods for or the control of udder health and udder infections (SCC, California Mastitis Test) are of limited value for goats. Since there was only a weak relation between milk quality properties and SCC, any arguments for the introduction of legal limits below 1 million cells per ml can hardly be found. PMID:17263081

  9. Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+ T-Cell Responses to Mycobacteria

    PubMed Central

    Banda, Dominic H.; Afran, Louise; Kankwatira, Anstead M.; Malamba, Rose D.; Allain, Theresa J.; Gordon, Stephen B.; Heyderman, Robert S.; Russell, David G.

    2014-01-01

    Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4+ T-cell responses observed in HIV-infected ART-naive adults. Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4+ T-cell responses to Mycobacterium in HIV-infected individuals. Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4+ T-cell responses were measured by intracellular cytokine staining. Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4+ T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4+ T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4+ T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4+ T-cell responses were impaired in adults on ART irrespective of duration. Conclusions: AM and mycobacteria-specific alveolar CD4+ T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated. PMID:25225948

  10. Evaluation of effects of novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid on the formation of an infection bladder stone using a newly designed urolithiasis model in rats.

    PubMed

    Satoh, M; Munakata, K; Takeuchi, H; Yoshida, O; Takebe, S; Kobashi, K

    1991-04-01

    By using our new infection stone model of a rat, we evaluated the effect of a novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid (P-GHA), on the formation of an infection bladder stone. The oral dosing of P-GHA significantly inhibited the elevation of the urinary ammonia level of rats having the urinary tract infection with Proteus mirabilis. A short term regimen (7 d, 730 +/- 38 mg/kg) with P-GHA significantly inhibited the development of the infection bladder stone. Furthermore, a long term combination regimen (11 d) of P-GHA and aminobenzylpenicillin markedly inhibited the development of the infection bladder stone, and also caused a very slight renal impairment to the rats tested in contrast with the method of Vermeulen et al. Our infection stone model in rats, therefore, seems to be useful for the evaluation of therapeutic agents in long term examinations. PMID:1893494

  11. Non-tuberculous mycobacterium skin infections after tattooing in healthy individuals: A systematic review of case reports.

    PubMed

    Mudedla, Sreenuvasu; Avendano, Esther E; Raman, Gowri

    2015-06-01

    In recent years, several case reports and outbreaks reported occurrence of non-tuberculous mycobacteria (NTM) infections within 6 months after receiving a tattoo in healthy individuals. NTM species (e.g., Chelonae, Fortuitum, Hemophillum, and Abscessus) are widespread in the environment and it is often suspected that contamination may occur through unsterile instrumentation or unsterile water used for diluting tattoo ink to dilute color. In reported cases, lesions were mainly restricted to a single color 'gray' part of the tattoo. Mycobacterium Chelonae was the most common cause of tattoo associated NTM infections. Less than 50% of the case reports tested tattoo ink for acid fast bacilli stains and cultures. Subjects required treatment with either clarithromycin alone or in combination with quinolones for 6 to 9 months. An increase in NTM skin infections in healthy individuals after tattooing indicates the need for sterile standards during tattooing and improved local and regional regulatory oversight. PMID:26158355

  12. 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

  13. 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

  14. A concise panel of biomarkers identifies neurocognitive functioning changes in HIV-infected individuals.

    PubMed

    Marcotte, Thomas D; Deutsch, Reena; Michael, Benedict Daniel; Franklin, Donald; Cookson, Debra Rosario; Bharti, Ajay R; Grant, Igor; Letendre, Scott L

    2013-12-01

    Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. At the first visit, subjects were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %). Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81 % of Im and SI subjects, including 100 % of SI subjects. This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the

  15. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia

    PubMed Central

    Peligero, Cristina; Argilaguet, Jordi; Güerri-Fernandez, Roberto; Torres, Berta; Ligero, Carmen; Colomer, Pilar; Plana, Montserrat; Knobel, Hernando; García, Felipe; Meyerhans, Andreas

    2015-01-01

    Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject’s plasma viremia. PMID:26633181

  16. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.

    PubMed

    Peligero, Cristina; Argilaguet, Jordi; Güerri-Fernandez, Roberto; Torres, Berta; Ligero, Carmen; Colomer, Pilar; Plana, Montserrat; Knobel, Hernando; García, Felipe; Meyerhans, Andreas

    2015-12-01

    Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia. PMID:26633181

  17. 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.

  18. 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

  19. High Seroprevalence of Human Herpesviruses in HIV-Infected Individuals Attending Primary Healthcare Facilities in Rural South Africa

    PubMed Central

    Schaftenaar, Erik; Verjans, Georges M. G. M.; Getu, Sarah; McIntyre, James A.; Struthers, Helen E.; Osterhaus, Albert D. M. E.; Peters, Remco P. H.

    2014-01-01

    Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa. PMID:24914671

  20. Quality of life among human immunodeficiency virus-1 infected and human immunodeficiency virus-1/hepatitis C virus co-infected individuals in Iranian patients

    PubMed Central

    Sabouri, Sarah; Delavar, Ali; Jabbari, Hossain

    2016-01-01

    Background: The aim of this study was to compare the quality of life (QOL) of people infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The study design was a cross sectional descriptive survey, using self administered questionnaires. Materials and Methods: A convenience sample of 242 patients (131 of them HIV/HCV), Iranian adults (aged 18–57) living with HIV/AIDS, was recruited from outpatient referring to Imam Khomeini Hospital behavioral counseling center in Tehran city, Iran. The instruments included the Multidimensional QOL HIV (MQoL HIV) and a demographic section. Results: The majority of the samples were male and single. The mean age was 36.52 years (standard deviation = 8.5). HIV mono infected patients reported higher scores in social support and physical functioning, but lower scores in physical health compared with HIV/HCV co infected individuals. There was no significant difference in overall MQOL HIV score between HIV and HIV/HCV patients. Conclusion: Future studies will need to explore the impact of HCV on HIV infected individuals' QOL.

  1. Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

    PubMed Central

    Walson, Judd L.; John-Stewart, Grace

    2007-01-01

    Background and Objectives The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings. It is important to determine if other prevalent infections affect the progression of HIV-1 in co-infected individuals in these settings. Some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate existing evidence on whether treatment of helminth infection impacts HIV-1 progression. Review Methods This review was conducted using the HIV/AIDS Cochrane Review Group (CRG) search strategy and guidelines. Published and unpublished studies were obtained from The Cochrane Library (Issue 3, 2006), MEDLINE (November 2006), EMBASE (November 2006), CENTRAL (July 2006), and AIDSEARCH (August 2006). Databases listing conference abstracts and scanned reference lists were searched, and authors of included studies were contacted. Data regarding changes in CD4 count, HIV-1 RNA levels, clinical staging and/or mortality were extracted and compared between helminth-treated and helminth-untreated or helminth-uninfected individuals. Results Of 6,384 abstracts identified, 15 met criteria for potential inclusion, of which 5 were eligible for inclusion. In the single randomized controlled trial (RCT) identified, HIV-1 and schistosomiasis co-infected individuals receiving treatment for schistosomiasis had a significantly lower change in plasma HIV-1 RNA over three months (−0.001 log10 copies/mL) compared to those receiving no treatment (+0.21 log10 copies/mL), (p = 0.03). Four observational studies met inclusion criteria, and all of these suggested a possible beneficial effect of helminth eradication on plasma HIV-1 RNA levels when compared to plasma HIV-1 RNA changes prior to helminth treatment or to helminth-uninfected or persistently helminth-infected individuals. The follow-up duration in these studies ranged from three to six months. The reported magnitude of effect on HIV-1 RNA was variable

  2. 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

  3. 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

  4. Distinctive western blot antibody patterns induced by infection of mice with individual strains of the Mycobacterium avium complex.

    PubMed Central

    Elsaghier, A; Nolan, A; Allen, B; Ivanyi, J

    1992-01-01

    Systemic infection of mice with organisms of the Mycobacterium avium complex (MAC) induced antibody responses, characteristic for each of the three tested individual strains. The influence of host genetic factors was reflected up to 3 months after infection by the finding of generally oligobanded and multibanded Western blot patterns in C57B1/6 and BALB/c mice, respectively. Nevertheless, more bands developed at 6 months in C57BL/6 mice. The response to three antigens of 18,000, 38,000 and 24,000 MW was analysed in greater detail. Antibodies to a protease-resistant 18,000 MW band produced only by BALB/c mice were either strain specific, following infection with M. avium, strain Maa-B2, or cross-reactive within MAC, following infection with M. avium strain Maa-A6 and M. paratuberculosis, strain Map-203. Another protease-resistant antigen of 38,000 MW was immunogenic only in Maa-B2 infected mice. This constituent was found to be related to the protease-sensitive antigen of corresponding molecular weight from M. tuberculosis. Two 24,000 MW proteins of M. paratuberculosis were separated by two-dimensional gel electrophoresis: antibodies to the anodic band were induced by Map-203 infection, whilst the cathodic band was revealed by heteroclitic antibodies from Maa-B2-infected mice. The latter antigen is apparently expressed during in vivo replication, but not during in vitro culture of Maa-B2 bacteria. We generally conclude, that the selective antibody patterns after live infection, could be attributed to differences in the release of native antigens within mycobacterial lesions. In view of a high degree of species specificity, some of the immunogenic constituents identified may also be useful for serodiagnostic application. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1526646

  5. Interventions to Address Chronic Disease and HIV: Strategies to Promote Exercise and Nutrition Among HIV-Infected Individuals

    PubMed Central

    Botros, Diana; Somarriba, Gabriel; Neri, Daniela; Miller, Tracie L.

    2012-01-01

    Food insecurity, micronutrient deficits, dyslipidemia, insulin resistance, obesity, cardiovascular disease, and bone disorders complicate the treatment of HIV infection. Nutrition and exercise interventions can be effective in ameliorating these symptoms that are associated with HIV and antiretroviral therapy (ART). In this literature review, we examine the most recent nutrition and exercise interventions for HIV-infected patients. Macronutrient supplementation can be useful in treating malnutrition and wasting. Multivitamin (vitamin B complex, vitamin C, and vitamin E) supplements and vitamin D may improve quality of life and decrease morbidity and mortality. Nutritional counseling and exercise interventions are effective for treating obesity, fat redistribution, and metabolic abnormalities. Physical activity interventions improve body composition, strength, and fitness in HIV-infected individuals. Taken collectively, the evidence suggests that a proactive approach to nutrition and physical activity guidance and interventions can improve outcomes and help abrogate the adverse metabolic, cardiovascular, and psychological consequences of HIV and its treatments. PMID:22933247

  6. 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

  7. Anti-HIV Designer T Cells Progressively Eradicate a Latently Infected Cell Line by Sequentially Inducing HIV Reactivation then Killing the Newly Gp120-Positive Cells

    PubMed Central

    Sahu, Gautam K; Sango, Kaori; Selliah, Nithianandan; Ma, Qiangzhong; Skowron, Gail; Junghans, Richard P

    2013-01-01

    The current antiretroviral therapy (ART) can effectively reduce plasma HIV loads to undetectable levels, but cannot eliminate latently infected resting memory CD4 T cells that persist for the lifetime of infected patients. Therefore, designing new therapeutic approaches to eliminate these latently infected cells or the cells that produce HIV upon reactivation from latency is a priority in the ART era in order to progress to a cure of HIV. Here, we show that “designer” T cells expressing chimeric antigen receptor (CAR), CD4-CD28-CD3ζ, can target and kill HIV Env-expressing cells. Further, they secrete effector cytokines upon contact with HIV Env+ target cells that can reactivate latent HIV in a cell line model, thereby exposing those cells to recognition and killing by anti-HIV CAR+ T cells. Taken to the limit, this process could form the basis for an eventual functional or sterilizing cure for HIV in patients. PMID:24074590

  8. 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

  9. 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. PMID:26997870

  10. 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

  11. 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

  12. Association of Blood Biomarkers of Bone Turnover in HIV-1 Infected Individuals Receiving Anti-Retroviral Therapy (ART)

    PubMed Central

    Aziz, Najib; Butch, Anthony W; Quint, Joshua J; Detels, Roger

    2015-01-01

    Objective To evaluate the association of bone turnover biomarkers with blood levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and other blood markers in HIV-1 infected men receiving anti-retroviral therapy (ART). Advances in the treatment of HIV-1 infection have extended the life span of HIV-1 infected individuals. However, these advances may come at the price of metabolic side effects and bone disorders, including premature osteopenia, osteoporosis and osteonecrosis. Methods Analyses of Ostase BAP, osteocalcin, and TRAP in blood were measured in three groups of MACS participants: 35 HIV-1 infected men on ART (A); 35 HIV-1- infected men not on ART (B); and 34 HIV-1 uninfected men (C). Results The mean and standard deviation results for groups A, B, and C were 19.7 ± 6.56, 17.2 ± 3.96, and 16.9 ± 5.78 for ostase BAP; 7.9 ± 9.53, 8.5 ± 8.30, and 5.5 ± 1.65 for osteocalcin; and 3.9 ± 1.04, 3.1 ± 0.81, and 2.5 ± 0.59 for TRAP, respectively. Simple and multivariate analyses showed significant differences in mean TRAP and BAP concentrations between the three groups. In addition strong correlations between blood levels of Ostase BAP and TRAP (r=0.570, p=0.0004), and between blood levels of Ostase BAP and PTH (r=0.436, P=0.0098) for HIV-1 infected men on ART were observed. Conclusion New strategies for measurement of blood and urine biochemical markers of bone formation and resorption during bone turnover can be useful for clinical monitoring of treatment of HIV-1 infected patients. Recently developed methods for measuring serum levels of TRAP and Ostase BAP represent superior laboratory tools for assessing the hyperactivity of osteoclasts, osteoblasts and bone loss in HIV-1 infected individuals receiving ART. Measurements of TRAP and BAP as bone turnover biomarkers are economical and are important for monitoring bone metabolism during ART and

  13. 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

  14. Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in individuals infected with HIV.

    PubMed

    Coughlin, Jennifer M; Wang, Yuchuan; Ma, Shuangchao; Yue, Chen; Kim, Pearl K; Adams, Ashley V; Roosa, Heidi V; Gage, Kenneth L; Stathis, Marigo; Rais, Rana; Rojas, Camilo; McGlothan, Jennifer L; Watkins, Crystal C; Sacktor, Ned; Guilarte, Tomas R; Zhou, Yun; Sawa, Akira; Slusher, Barbara S; Caffo, Brian; Kassiou, Michael; Endres, Christopher J; Pomper, Martin G

    2014-06-01

    Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test-retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings. PMID:24567030

  15. 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

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

    PubMed

    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

    2015-08-01

    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

  17. HPV and anal cancer in HIV-infected individuals: a review.

    PubMed

    Schim van der Loeff, Maarten F; Mooij, Sofie H; Richel, Oliver; de Vries, Henry J C; Prins, Jan M

    2014-09-01

    HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long run. PMID:24990810

  18. Test Positivity for Chlamydia, Gonorrhea and Syphilis Infection Among a Cohort of Individuals Released from Jail in Marion County, Indiana

    PubMed Central

    Wiehe, Sarah E.; Barai, Nikita; Rosenman, Marc B.; Aalsma, Matthew C.; Scanlon, Michael L.; Fortenberry, J. Dennis

    2014-01-01

    Background Individuals entering jails have high rates of sexually transmitted infections (STI) but there are few data on STI in the post-incarceration period. This study aimed to describe rates of chlamydia, gonorrhea and syphilis infection among individuals released from Marion County (Indianapolis), Indiana jails. Methods We conducted a retrospective cohort study of individuals incarcerated in Marion County, Indiana jails from 2003–2008 (N=118,670). We linked county jail and public health data to identify individuals with positive STI test results in the one-year following release from jail. Rates per 100,000 individuals and cox proportional hazard analyses were performed for each STI, stratified by demographic, STI and jail characteristics. Results We found significantly higher rates of STI in this cohort than in the general population, with rates in the one-year following release being 2 to 7 times higher for chlamydia, 5 to 24 times higher for gonorrhea, and 19 to 32 times higher for syphilis compared to rates in the general population. Characteristics most associated with increased risk of a positive STI test among this cohort were younger age for chlamydia and gonorrhea, older age for syphilis, black race for men, being jailed for prostitution for women, history of STI, and history of prior incarceration. Conclusions This study found high rates of STIs among a cohort of individuals recently released from jail and identified a number of risk factors. Further study is needed to improve targeted STI testing and treatment among this high-risk population. PMID:25504298

  19. Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

    PubMed

    Georgitsi, M D; Vitoros, V; Panou, C; Tsangaris, I; Aimoniotou, E; Gatselis, N K; Chasou, E; Kouliatsis, G; Leventogiannis, K; Velissaris, D; Belesiotou, E; Dioritou-Aggaliadou, O; Giannitsioti, E; Netea, M G; Giamarellos-Bourboulis, E J; Giannikopoulos, G; Alexiou, Z; Voloudakis, N; Koutsoukou, A

    2016-04-01

    Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8. PMID:26768584

  20. Synthetic Consensus HIV-1 DNA Induces Potent Cellular Immune Responses and Synthesis of Granzyme B, Perforin in HIV Infected Individuals

    PubMed Central

    Morrow, Matthew P; Tebas, Pablo; Yan, Jian; Ramirez, Lorenzo; Slager, Anna; Kraynyak, Kim; Diehl, Malissa; Shah, Divya; Khan, Amir; Lee, Jessica; Boyer, Jean; Kim, J Joseph; Sardesai, Niranjan Y; Weiner, David B; Bagarazzi, Mark L

    2015-01-01

    This study evaluated the safety and immunogenicity of PENNVAX-B in 12 HIV infected individuals. PENNVAX-B is a combination of three optimized synthetic plasmids encoding for multiclade HIV Gag and Pol and a consensus CladeB Env delivered by electroporation. HIV infected individuals whose virus was effectively suppressed using highly active antiretroviral therapy (HAART) received PENNVAX-B DNA followed by electroporation with CELLECTRA-5P at study weeks 0, 4, 8, and 16. Local administration site and systemic reactions to PENNVAX-B were recorded after each treatment along with any adverse events. Pain of the treatment procedure was assessed using a Visual Analog Scale. Whole PBMCs were isolated for use in IFN ELISpot and Flow Cytometric assays. PENNVAX-B was generally safe and well tolerated. Overall, the four dose regimen was not associated with any serious adverse events or severe local or systemic reactions. A rise in antigen-specific SFU was detected in the INFγ ELISpot assay in all 12 participants. T cells from 8/12 participants loaded with both granzyme B and perforin in response to HIV antigen, an immune finding characteristic of long-term nonprogressors (LTNPs) and elite controllers (ECs). Thus administration of PENNVAX-B may prove useful adjunctive therapy to ART for treatment and control of HIV infection. PMID:25531694

  1. Synthetic consensus HIV-1 DNA induces potent cellular immune responses and synthesis of granzyme B, perforin in HIV infected individuals.

    PubMed

    Morrow, Matthew P; Tebas, Pablo; Yan, Jian; Ramirez, Lorenzo; Slager, Anna; Kraynyak, Kim; Diehl, Malissa; Shah, Divya; Khan, Amir; Lee, Jessica; Boyer, Jean; Kim, J Joseph; Sardesai, Niranjan Y; Weiner, David B; Bagarazzi, Mark L

    2015-03-01

    This study evaluated the safety and immunogenicity of PENNVAX-B in 12 HIV infected individuals. PENNVAX-B is a combination of three optimized synthetic plasmids encoding for multiclade HIV Gag and Pol and a consensus CladeB Env delivered by electroporation. HIV infected individuals whose virus was effectively suppressed using highly active antiretroviral therapy (HAART) received PENNVAX-B DNA followed by electroporation with CELLECTRA-5P at study weeks 0, 4, 8, and 16. Local administration site and systemic reactions to PENNVAX-B were recorded after each treatment along with any adverse events. Pain of the treatment procedure was assessed using a Visual Analog Scale. Whole PBMCs were isolated for use in IFN ELISpot and Flow Cytometric assays. PENNVAX-B was generally safe and well tolerated. Overall, the four dose regimen was not associated with any serious adverse events or severe local or systemic reactions. A rise in antigen-specific SFU was detected in the INFγ ELISpot assay in all 12 participants. T cells from 8/12 participants loaded with both granzyme B and perforin in response to HIV antigen, an immune finding characteristic of long-term nonprogressors (LTNPs) and elite controllers (ECs). Thus administration of PENNVAX-B may prove useful adjunctive therapy to ART for treatment and control of HIV infection. PMID:25531694

  2. Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

    PubMed Central

    Been-Tiktak, A M; Williams, I; Vrehen, H M; Richens, J; Aldam, D; van Loon, A M; Loveday, C; Boucher, C A; Ward, P; Weller, I V; Borleffs, J C

    1996-01-01

    Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients. PMID:8913487

  3. 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

  4. B cells pulsed with Helicobacter pylori antigen efficiently activate memory CD8+ T cells from H. pylori-infected individuals.

    PubMed

    Azem, Josef; Svennerholm, Ann-Mari; Lundin, B Samuel

    2006-01-01

    Helicobacter pylori infection causes chronic gastritis that may progress to peptic ulcers or gastric adenocarcinoma and thereby cause major world-wide health problems. Previous studies have shown that CD4+ T cells are important in the immune response to H. pylori in humans, but the role of CD8+ T cells is less clear. In order to study the CD8+ T cell response to H. pylori in greater detail, we have evaluated efficient conditions for activation of CD8+ T cells in vitro. We show that H. pylori-reactive CD8+ T cells can be activated most efficiently by B cells or dendritic cells pulsed with H. pylori antigens. We further show that the majority of CD8+ T cells in H. pylori-infected gastric mucosa are memory cells, and that memory CD8+ T cells sorted from peripheral blood of H. pylori-infected individuals respond 15-fold more to H. pylori urease compared to memory cells from uninfected subjects. We conclude that CD8+ T cells do participate in the immune response to H. pylori, and this may have implications for the development of more severe disease outcomes in H. pylori-infected subjects. PMID:16324887

  5. Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals.

    PubMed

    Koch, Kristina; Koch, Nora; Sandaradura de Silva, Ute; Jung, Norma; Schulze zur Wiesch, Julian; Fätkenheuer, Gerd; Hartmann, Pia; Romerio, Fabio; Lehmann, Clara

    2015-12-01

    In HIV-1 infection elevated serum levels of interferon-α (IFN-α) and interleukin-10 (IL-10) are associated with immune hyperactivation and disease progression. Recently, coexpression of CD49b and LAG-3 was shown to identify Type 1 regulatory T (Tr1) cells, which secrete large amounts of the immunosuppressive cytokine IL-10. We analyzed the frequency of CD49b/LAG-3(+) Tr1 cells in the peripheral blood of HIV-infected individuals at different stages of the disease. We found increased levels of CD49b/LAG-3(+) Tr1 cells as well as IL-10 in HIV patients. With disease progression, Tr1 cells negatively correlate with frequency of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. However, elevated IL-10 levels could not be ascribed to the CD49b/LAG-3(+)Tr1 cell population. Moreover, we showed in vitro that IFN-α leads to an upregulation of IL-10 as well as CD49b/LAG-3(+) Tr1 cell counts in healthy controls, recapitulating effects observed in vivo during HIV infection. Our results suggest that overexpression of IFN-α during HIV infection drives the generation of CD49b/LAG-3(+) Tr1 cells and the immunosuppressive cytokine IL-10. Furthermore, it remains unclear whether elevated IL-10 levels are beneficial or detrimental in regard to disease progression. PMID:26192268

  6. 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

  7. ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 5, A NEWLY RECOGNIZED ELEPHANT HERPESVIRUS ASSOCIATED WITH CLINICAL AND SUBCLINICAL INFECTIONS IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS)

    PubMed Central

    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.

    2013-01-01

    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. PMID:23505714

  8. 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. PMID:26142452

  9. Antibody Responses After Analytic Treatment Interruption in Human Immunodeficiency Virus-1-Infected Individuals on Early Initiated Antiretroviral Therapy

    PubMed Central

    Stephenson, Kathryn E.; Neubauer, George H.; Bricault, Christine A.; Shields, Jennifer; Bayne, Madeleine; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Seaman, Michael S.; Rosenberg, Eric S.; Barouch, Dan H.

    2016-01-01

    The examination of antibody responses in human immunodeficiency virus (HIV)-1-infected individuals in the setting of antiretroviral treatment (ART) interruption can provide insight into the evolution of antibody responses during viral rebound. In this study, we assessed antibody responses in 20 subjects in AIDS Clinical Trials Group A5187, wherein subjects were treated with antiretroviral therapy during acute/early HIV-1 infection, underwent analytic treatment interruption, and subsequently demonstrated viral rebound. Our data suggest that early initiation of ART arrests the maturation of HIV-1-specific antibody responses, preventing epitope diversification of antibody binding and the development of functional neutralizing capacity. Antibody responses do not appear permanently blunted, however, because viral rebound triggered the resumption of antibody maturation in our study. We also found that antibody responses measured by these assays did not predict imminent viral rebound. These data have important implications for the HIV-1 vaccine and eradication fields. PMID:27419172

  10. 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

  11. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the “Probio-HIV” Clinical Trial

    PubMed Central

    d’Ettorre, Gabriella; Ceccarelli, Giancarlo; Giustini, Noemi; Serafino, Sara; Calantone, Nina; De Girolamo, Gabriella; Bianchi, Luigi; Bellelli, Valeria; Ascoli-Bartoli, Tommaso; Marcellini, Sonia; Turriziani, Ombretta; Brenchley, Jason M.; Vullo, Vincenzo

    2015-01-01

    Background HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. Methods In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. Results We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. Conclusions Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis. Trial Registration ClinicalTrials.gov NCT02164344 PMID:26376436

  12. Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

    PubMed

    Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

    2015-01-01

    OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI. PMID:25627761

  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. Molecular characterization and infectivity of a Tomato leaf curl New Delhi virus variant associated with newly emerging yellow mosaic disease of eggplant in India

    PubMed Central

    2011-01-01

    Background Begomoviruses have emerged as serious problem for vegetable and fiber crops in the recent past, frequently in tropical and subtropical region of the world. The association of begomovirus with eggplant yellow mosaic disease is hitherto unknown apart from one report from Thailand. A survey in Nagpur, Central India, in 2009-2010 showed severe incidence of eggplant yellow mosaic disease. Here, we have identified and characterized a begomovirus responsible for the newly emerging yellow mosaic disease of eggplant in India. Results The complete DNA-A and DNA-B genomic components of the causative virus were cloned and sequenced. Nucleotide sequence analysis of DNA-A showed that it shared highest 97.6% identity with Tomato leaf curl New Delhi virus-India[India:Udaipur:Okra:2007] and lowest 87.9% identity with Tomato leaf curl New Delhi virus-India[India:NewDelhi:Papaya:2005], while DNA-B showed highest 94.1% identity with ToLCNDV-IN[IN:UD:Ok:07] and lowest 76.2% identity with ToLCNDV-India[India:Lucknow]. Thus, it appears that this begomovirus is a variant of ubiquitous ToLCNDV and hence, we suggest the name ToLCNDV-India[India:Nagpur:Eggplant:2009] for this variant. The pathogenicity of ToLCNDV-IN[IN:Nag:Egg:09] isolate was confirmed by agroinfiltraion and dimeric clones of DNA-A and DNA-B induced characteristic yellow mosaic symptoms in eggplants and leaf curling in tomato plants. Conclusion This is the first report of a ToLCNDV variant moving to a new agriculturally important host, eggplant and causing yellow mosaic disease. This is also a first experimental demonstration of Koch's postulate for a begomovirus associated with eggplant yellow mosaic disease. PMID:21676270

  15. 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

  16. 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

  17. 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

  18. 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…

  19. Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study

    PubMed Central

    Falasca, Katia; Vecchiet, Jacopo; Ucciferri, Claudio; Di Nicola, Marta; D’Angelo, Chiara; Reale, Marcella

    2015-01-01

    Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients. PMID:26426044

  20. 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

  1. 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

  2. Factors Associated with Tobacco Smoking and Cessation among HIV-Infected Individuals under Care in Rio de Janeiro, Brazil

    PubMed Central

    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

  3. 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

  4. Reprint of: cancer "causation" by infections--individual contributions and synergistic networks.

    PubMed

    Zur Hausen, Harald; de Villiers, Ethel-Michele

    2015-04-01

    The search for infectious agents playing a role in human carcinogenesis and their identification remain important issues. This could provide clues for a broader spectrum of cancers preventable by vaccination and accessible to specific therapeutic regimens. Yet, the various ways of interacting among different factors functioning synergistically and their different modes of affecting individual cells should bring to question the validity of the term "causation". It also should put a word of caution into all attempts to summarize criteria for "causality" of infectious agents in cancer development. At least in the opinion of these authors, we would be much better off avoiding these terms, replacing "causal factor" by "risk factor" and grading them according to their contribution to an individual's cancer risk. PMID:25843727

  5. The shifting locus of risk-reduction: the critical role of HIV infected individuals.

    PubMed

    Indyk, Debbie; Golub, Sarit A

    2006-01-01

    This article discusses the shifting locus of control over risk-reduction and examines its implications for the care and support of HIV-positive individuals. We begin by presenting a brief history of the continuum of HIV related risk, illustrating the ways in which advances in risk-assessment and intervention have led to this important shift. Second, we discuss the current state of risk assessment and intervention as it relates to three factors: (a) the point along the continuum of risk at which risk assessment and intervention occurs; (b) the locus of control over risk reduction; and (c) the distinction between primary and secondary risk reduction efforts. Finally, we discuss the meaning of HIV risk and the role of HIV-positive individuals in the new geometry of care that integrates treatment and prevention. How is HIV-risk defined and understood? Who is of risk to whom? Who is responsible for reducing risk?. PMID:16687378

  6. Individual and Social Network Sexual Behavior Norms of Homeless Youth at High Risk for HIV Infection

    PubMed Central

    Tyler, Kimberly A.; Melander, Lisa A.

    2012-01-01

    Although previous research shows that homeless youth engage in numerous risky sexual behaviors, little is known about whether or not specific rules govern this conduct within their social networks and how group norms influence subsequent sexual actions. The current study utilizes 19 in-depth interviews with homeless youth to investigate different elements of their sexual behavior. Findings reveal that their decision to have sex generally depends on chemistry and physical appearance whereas a potential partner’s risky sexual history and heavy substance use discourages youth from engaging in sex. Both males and females discuss condom usage as it relates to unknown sexual history, availability, pregnancy, and the prevention of sexually transmitted infections (STIs). Sixteen homeless youth indicate that they do not discuss safe sex practices with their partners or social network members. PMID:23162182

  7. Seroprevalence of Herpes Simplex Virus Infection in HIV Coinfected Individuals in Eastern India with Risk Factor Analysis

    PubMed Central

    Nag, Soumyabrata; Sarkar, Soma; Chattopadhyay, Debprasad; Bhattacharya, Sanjoy; Biswas, Rahul; SenGupta, Manideepa

    2015-01-01

    Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes while HSV-1 is responsible for orolabial and facial lesions. In immunocompromised individuals, like HIV patients, impaired immunity leads to more frequent symptomatic and asymptomatic HSV infection. Fifty-two blood samples from HIV patients with clinically diagnosed HSV infection were taken as cases, while 45 blood samples each from HIV-infected (HIV control) and noninfected patients without any herpetic lesion (non-HIV control) were taken as control. Serum was tested for IgM and IgG antibodies of both HSV-1 and HSV-2 by ELISA. The seroprevalence was compared among the three groups of study population, considering the demographic and socioeconomic parameters. The HSV-2 IgM was significantly higher (p < 0.005) in the HIV patient group (34.6%) than the HIV control (2.2%) and non-HIV control (2.2%) groups, whereas HSV-2 IgG seroprevalence was higher in both HIV patient (61.5%) and HIV control (57.8%) groups than the non-HIV control group (17.8%). The prevalence of HSV-2 was significantly higher in persons with multiple partners and in the reproductive age group. The overall seroprevalence of HSV-1 IgM was too low (<5%), whereas it was too high (about 90%) with HSV-1 IgG in all three study groups. PMID:26557849

  8. 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

  9. 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

  10. Patient navigation facilitates medical and social services engagement among HIV-infected individuals leaving jail and returning to the community.

    PubMed

    Koester, Kimberly A; Morewitz, Mark; Pearson, Charles; Weeks, John; Packard, Rebecca; Estes, Milton; Tulsky, Jacqueline; Kang-Dufour, Mi Suk; Myers, Janet J

    2014-02-01

    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

  11. A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

    PubMed Central

    Lane, Jérôme; McLaren, Paul J.; Dorrell, Lucy; Shianna, Kevin V.; Stemke, Amanda; Pelak, Kimberly; Moore, Stephen; Oldenburg, Johannes; Alvarez-Roman, Maria Teresa; Angelillo-Scherrer, Anne; Boehlen, Francoise; Bolton-Maggs, Paula H.B.; Brand, Brigit; Brown, Deborah; Chiang, Elaine; Cid-Haro, Ana Rosa; Clotet, Bonaventura; Collins, Peter; Colombo, Sara; Dalmau, Judith; Fogarty, Patrick; Giangrande, Paul; Gringeri, Alessandro; Iyer, Rathi; Katsarou, Olga; Kempton, Christine; Kuriakose, Philip; Lin, Judith; Makris, Mike; Manco-Johnson, Marilyn; Tsakiris, Dimitrios A.; Martinez-Picado, Javier; Mauser-Bunschoten, Evelien; Neff, Anne; Oka, Shinichi; Oyesiku, Lara; Parra, Rafael; Peter-Salonen, Kristiina; Powell, Jerry; Recht, Michael; Shapiro, Amy; Stine, Kimo; Talks, Katherine; Telenti, Amalio; Wilde, Jonathan; Yee, Thynn Thynn; Wolinsky, Steven M.; Martinson, Jeremy; Hussain, Shehnaz K.; Bream, Jay H.; Jacobson, Lisa P.; Carrington, Mary; Goedert, James J.; Haynes, Barton F.; McMichael, Andrew J.; Goldstein, David B.; Fellay, Jacques

    2013-01-01

    Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979–1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population. PMID:23372042

  12. Characterization of Platelet-Monocyte Complexes in HIV-1 Infected Individuals: Possible Role in HIV-associated Neuroinflammation1

    PubMed Central

    Singh, Meera V.; Davidson, Donna C.; Jackson, Joseph W.; Singh, Vir B.; Silva, Jharon; Ramirez, Servio H.; Maggirwar, Sanjay B.

    2014-01-01

    HIV-1-associated neuroinflammation persists even with effective combined anti-retroviral therapy (cART), and is associated with the presence of activated monocytes/macrophages within the CNS. In order to infiltrate the CNS, monocytes transmigrate across the selectively permeable blood brain barrier (BBB), which is compromised during HIV infection. Interestingly, platelet-derived excess soluble CD40L (sCD40L) found in the plasma and cerebrospinal fluid (CSF) of HIV-1 infected individuals with cognitive impairment has previously been implicated in increased BBB permeability. Here we show that sCD40L also promotes the formation of complexes between inflammatory monocytes and activated platelets (PMCs), which are detected by flow cytometry as monocytes that express excess of CD61, a platelet marker and that these complexes are increased in individuals with HIV infection. PMCs exhibit an enhanced ability to adhere to human brain microvascular endothelial cells as compared to monocytes alone and migrate across transendothelial barrier. These complexes can be found marginalized in the lumen of post-capillary venules in post-mortem brain tissue derived from cases of HIV-1-associated encephalitis (HIV-E). The extravasation of monocytes across the brain endothelium may exacerbate neuroinflammation, indicating that enhancing this event via platelet interaction may be a contributing factor in the development of cognitive impairment. Thus, dampening platelet activation, and in turn PMC formation, with anti-platelet agents may prove beneficial in developing adjunctive therapies for use in combination with cART in an effort to reduce HIV-1-associated neurological deficit PMID:24729609

  13. 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

  14. Fungal infection of the feet in soccer players and non-athlete individuals.

    PubMed

    Purim, Kátia Sheylla Malta; Bordignon, Gisele Pesquero Fernandes; Queiroz-Telles, Flávio de

    2005-03-01

    This study was conducted to evaluate the occurrence of mycoses affecting the feet of soccer players and to compare this results with those in non-athlete individuals of the same age and sex. Initial evaluation consisted of a dermatological examination of the foot in 22 Chinese athletes, 83 Brazilian athletes and 24 Brazilian non-athletes. Scales of plantar skin, interdigital and subungual areas of the foot were collected for mycological examination (direct and culture). Nail clippings were obtained for histopathologic analysis. Tinea pedis was diagnosed more frequently among the non-athlete individuals. None of the Chinese athletes had tinea pedis alone. However, in this group onychomycosis was frequently higher when compared to the other groups. The fungal microbiota comprised Trichophyton rubrum (40%), Trichophyton mentagrophytes (36.4%) and Candida spp (20%). Candida spp was isolated only from Brazilian athletes. Results obtained with KOH wet mounts agreed with the results obtained in culture and with histopathologic examinations (50.5% vs 40.9%). The frequency of tinea pedis among soccer players was lower than the other groups in this study, possibly due to health education and professional feet care. PMID:15813681

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

    PubMed

    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

  16. 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

  17. Identification of inflections in T-cell counts among HIV-1-infected individuals and relationship with progression to clinical AIDS

    PubMed Central

    Gange, Stephen J.; Muñoz, Alvaro; Chmiel, Joan S.; Donnenberg, Albert D.; Kirstein, Lynn M.; Detels, Roger; Margolick, Joseph B.

    1998-01-01

    Studies of circulating T (CD3+) lymphocytes have shown that on a population basis T-cell numbers remain stable for many years after HIV-1 infection (blind T-cell homeostasis), but decline rapidly beginning approximately 1.5–2.5 years before the onset of clinical AIDS. We derived a general method for defining the loss of homeostasis on the individual level and for determining the prevalence of homeostasis loss according to HIV status and the occurrence of AIDS in more than 5,000 men enrolled in the Multicenter AIDS Cohort Study. We used a segmented regression model for log10 CD3+ cell counts that included separate T-cell trajectories before and after a time (the T-cell inflection point) where the loss of T-cell homeostasis was most likely to have occurred. The average slope of CD3+ lymphocyte counts before the inflection point was close to zero for HIV− and HIV+ men, consistent with blind T-cell homeostasis. After the inflection point, the HIV+ individuals who developed AIDS generally showed a dramatic decline in CD3+ cell counts relative to HIV− men and HIV+ men not developing AIDS. A CD3+ cell decline of greater than 10 percent per year was present in 77% of HIV+ men developing AIDS but in only 23% of HIV+ men with no onset of AIDS. Our findings at the individual level support the blind T-cell homeostasis hypothesis and provide strong evidence that the loss of homeostasis is an important mechanism in the pathogenesis of the severe immunodeficiency that characterizes the late stages of HIV infection. PMID:9724793

  18. Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

    PubMed Central

    Mulanovich, Victor E.; Jiang, Y.; Lewis, Russell E.

    2014-01-01

    Although primary antifungal prophylaxis (PAP) is routinely administered in patients with acute myeloid leukemia (AML) during remission-induction and consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal infections (IFIs) is not well described. We retrospectively analyzed the incidence of IFIs in 152 patients with AML who had been admitted to a tertiary cancer center between August 2009 and March 2011 and received PAP within 120 days after first remission-induction chemotherapy. We excluded patients who had undergone stem cell transplantation. Patients received a PAP drug with anti-Aspergillus activity during 72% (7,660/10,572) of prophylaxis-days. The incidence of documented IFIs (definite or probable according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000 prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus 0.4/1,000 prophylaxis-days; P = 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000 prophylaxis-days, respectively) was associated with higher rates of documented IFIs than anti-Aspergillus azoles (voriconazole or posaconazole) (2.4 and 1.1/1,000 prophylaxis-days, respectively) at both 42 days (P = 0.03) and 120 days (P < 0.0001) after first remission-induction chemotherapy. The incidence of overall (documented and presumed) IFIs (P < 0.001), documented IFIs (P < 0.01), and empirical antifungal therapies (P < 0.0001) was higher during the first 42 days than after day 42. Despite the broad use of PAP with anti-Aspergillus activity, IFIs, especially molds, remain a significant cause of morbidity and mortality in AML patients, predominantly during the remission-induction phase. Patients receiving echinocandin-based PAP experienced higher rates of IFIs than did those receiving anti-Aspergillus azoles. PMID:24277033

  19. Genetic variation and dynamics of infections of equid herpesvirus 5 in individual horses.

    PubMed

    Back, Helena; Ullman, Karin; Leijon, Mikael; Söderlund, Robert; Penell, Johanna; Ståhl, Karl; Pringle, John; Valarcher, Jean-François

    2016-01-01

    Equid herpesvirus 5 (EHV-5) is related to the human Epstein-Barr virus (human herpesvirus 4) and has frequently been observed in equine populations worldwide. EHV-5 was previously assumed to be low to non-pathogenic; however, studies have also related the virus to the severe lung disease equine multinodular pulmonary fibrosis (EMPF). Genetic information of EHV-5 is scanty: the whole genome was recently described and only limited nucleotide sequences are available. In this study, samples were taken twice 1 year apart from eight healthy horses at the same professional training yard and samples from a ninth horse that was diagnosed with EMPF with samples taken pre- and post-mortem to analyse partial glycoprotein B (gB) gene of EHV-5 by using next-generation sequencing. The analysis resulted in 27 partial gB gene sequences, 11 unique sequence types and five amino acid sequences. These sequences could be classified within four genotypes (I-IV) of the EHV-5 gB gene based on the degree of similarity of the nucleotide and amino acid sequences, and in this work horses were shown to be identified with up to three different genotypes simultaneously. The observations showed a range of interactions between EHV-5 and the host over time, where the same virus persists in some horses, whereas others have a more dynamic infection pattern including strains from different genotypes. This study provides insight into the genetic variation and dynamics of EHV-5, and highlights that further work is needed to understand the EHV-5 interaction with its host. PMID:26518010

  20. 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

  1. Temporal analysis of HIV envelope sequence evolution and antibody escape in a subtype A-infected individual with a broad neutralizing antibody response

    PubMed Central

    Bosch, Katherine A.; Rainwater, Stephanie; Jaoko, Walter; Overbaugh, Julie

    2010-01-01

    The origin of broadly neutralizing HIV-specific antibodies and their relation to HIV evolution are not well defined. Here we examined virus evolution and neutralizing antibody escape in a subtype A infected individual with a broad, cross subtype, antibody response. The majority of envelope variants isolated over the first ~ 5 years post-infection were poorly neutralized by contemporaneous plasma that neutralized variants from earlier in infection, consistent with a dynamic process of escape. The majority of variants could be neutralized by later plasma, suggesting these evolving variants may have contributed to the elicitation of new antibody responses. However, some variants from later in infection were recognized by plasma from earlier in infection, including one notably neutralization-sensitive variant that was sensitive due to a proline at position 199 in V2. These studies suggest a complex pattern of virus evolution in this individual with a broad NAb response, including persistence of neutralization-sensitive viruses. PMID:20034648

  2. 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.

  3. Altered production of tumour necrosis factors alpha and beta and interferon gamma by HIV-infected individuals.

    PubMed Central

    Vyakarnam, A; Matear, P; Meager, A; Kelly, G; Stanley, B; Weller, I; Beverley, P

    1991-01-01

    In vitro studies shows that recombinant tumour necrosis factor (TNF) alpha and beta, and interferon-gamma (IFN-gamma) can enhance HIV replication, and peripheral blood mononuclear cells (PBMC) infected with HIV in vitro secrete high levels of the same cytokines. As T cells secrete all three mediators, the capacity of T cell activation signals to trigger cytokine production in PBMC from HIV-infected individuals was investigated as such patients may be immunocompromised. We demonstrate that asymptomatic seropositives in CDC group II/III as well as patients who have progressed to CDC group IV of the disease proliferate efficiently to anti-CD3 antibody, recombinant interleukin-2 (rIL-2), phytohaemagglutinin (PHA), PHA plus phorbol 12,13 dibutyrate (PMA) but secrete significantly (P less than 0.05) higher amounts of TNF-alpha, TNF-beta and IFN-gamma compared with controls in response to the same stimulants. We also show a difference between group II/III and group IV patients with the latter secreting more TNF-alpha and IFN-gamma. The kinetics of TNF-alpha and -beta, and IFN-gamma production was stimulus dependent with overall levels varying in time for each stimulus. Furthermore, the kinetics of the response to all three stimulants were altered in seropositives; CDC group II/III and group IV patients secreted higher levels of cytokines over several time points compared to controls. The altered production of these mediators by HIV-infected patients may contribute to disease progression and to the pathogenesis of AIDS. PMID:1901776

  4. 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.

  5. 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

  6. Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Mycobacterium tuberculosis–infected Individuals

    PubMed Central

    Sander, Clare R.; Pathan, Ansar A.; Beveridge, Natalie E. R.; Poulton, Ian; Minassian, Angela; Alder, Nicola; Van Wijgerden, Johan; Hill, Adrian V. S.; Gleeson, Fergus V.; Davies, Robert J. O.; Pasvol, Geoffrey; McShane, Helen

    2009-01-01

    Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas. Clinical trial registered with www.clinicaltrials.gov (NCT00456183). PMID:19151191

  7. 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.

  8. Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals.

    PubMed

    Euler, Zelda; van Gils, Marit J; Boeser-Nunnink, Brigitte D; Schuitemaker, Hanneke; van Manen, Daniëlle

    2013-01-01

    Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10-30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68 × 10(-7)), HLA-B (P = 6.96 × 10(-6)) and in the coding region of HCP5 (P = 1.34 × 10(-5)). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA. PMID:23372753

  9. Computational deconvolution of gene expression by individual host cellular subsets from microarray analyses of complex, parasite-infected whole tissues.

    PubMed

    Banskota, Nirad; Odegaard, Justin I; Rinaldi, Gabriel; Hsieh, Michael H

    2016-06-01

    Analyses of whole organs from parasite-infected animals can reveal the entirety of the host tissue transcriptome, but conventional approaches make it difficult to dissect out the contributions of individual cellular subsets to observed gene expression. Computational deconvolution of gene expression data may be one solution to this problem. We tested this potential solution by deconvoluting whole bladder gene expression microarray data derived from a model of experimental urogenital schistosomiasis. A supervised technique was used to group B-cell and T-cell related genes based on their cell types, with a semi-supervised technique to calculate the proportions of urothelial cells. We demonstrate that the deconvolution technique was able to group genes into their correct cell types with good accuracy. A clustering-based methodology was also used to improve prediction. However, incorrectly predicted genes could not be discriminated using this methodology. The incorrect predictions were primarily IgH- and IgK-related genes. To our knowledge, this is the first application of computational deconvolution to complex, parasite-infected whole tissues. Other computational techniques such as neural networks may need to be used to improve prediction. PMID:27025770

  10. Risk of latent TB infection in individuals employed in the healthcare sector in Germany: a multicentre prevalence study

    PubMed Central

    2010-01-01

    Background Healthcare workers are still recognised as a high-risk group for latent TB infection (LTBI). Therefore, the screening of people employed in the healthcare sector for active and LTBI is fundamental to infection control programmes in German hospitals. It was the aim of the study to determine the prevalence and putative risk factors of LTBI. Methods We tested 2028 employees in the healthcare sector with the QuantiFERON-Gold In-tube (QFT-IT) test between December 2005 and May 2009, either in the course of contact tracing or in serial testing of TB high-risk groups following German OSH legislation. Results A positive IGRA was found in 9.9% of the healthcare workers (HCWs). Nurses and physicians showed similar prevalence rates (9.7% to 9.6%). Analysed by occupational group, the highest prevalence was found in administration staff and ancillary nursing staff (17.4% and 16.7%). None of the individuals in the trainee group showed a positive IGRA result. In the different workplaces the observed prevalence was 14.7% in administration, 12.0% in geriatric care, 14.2% in technicians (radiology, laboratory and pathology), 6.5% in admission ward staff and 8.3% in the staff of pulmonary/infectious disease wards. Putative risk factors for LTBI were age (>55 years: OR14.7, 95% CI 5.1-42.1), being foreign-born (OR 1.99, 95% CI 1.4-2.8), TB in the individual's own history (OR 4.96, 95% CI 1.99-12.3) and previous positive TST results (OR 3.5, 95% CI 2.4-4.98). We observed no statistically significant association with gender, BCG vaccination, workplace or profession. Conclusion The prevalence of LTBI in low-incidence countries depends on age. We found no positive IGRA results among trainees in the healthcare sector. Incidence studies are needed to assess the infection risk. Pre-employment screening might be helpful in this endeavour. PMID:20429957

  11. THERAPEUTIC DRUG MONITORING OF PROTEASE INHIBITORS AND EFAVIRENZ IN HIV-INFECTED INDIVIDUALS WITH ACTIVE SUBSTANCE RELATED DISORDERS

    PubMed Central

    Ma, Qing; Zingman, Barry S.; Luque, Amneris; Fischl, Margaret A.; Gripshover, Barbara; Venuto, Charles; DiFrancesco, Robin; Forrest, Alan; Morse, Gene D.

    2011-01-01

    (3.75 vs. 5.30 µg/mL). Conclusions The pharmacokinetic data indicate differences between HIV-infected patients with and without SRD that may influence viral load suppression during long-term ARV treatment. These findings require additional investigation in a randomized design with more intensive pharmacokinetic assessment to identify individual factors that are contributing to suboptimal ARV exposure in patients with SRDs. PMID:21544014

  12. 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

  13. Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

    PubMed

    McNurlan, M A; Garlick, P J; Steigbigel, R T; DeCristofaro, K A; Frost, R A; Lang, C H; Johnson, R W; Santasier, A M; Cabahug, C J; Fuhrer, J; Gelato, M C

    1997-10-15

    This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease. PMID:9329979

  14. Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

    PubMed Central

    McNurlan, M A; Garlick, P J; Steigbigel, R T; DeCristofaro, K A; Frost, R A; Lang, C H; Johnson, R W; Santasier, A M; Cabahug, C J; Fuhrer, J; Gelato, M C

    1997-01-01

    This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease. PMID:9329979

  15. Predictors of new-onset distal neuropathic pain in HIV-infected individuals in the era of combination antiretroviral therapy.

    PubMed

    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

    2015-04-01

    Despite modern combination antiretroviral therapy, 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, semiannual clinical evaluations were administered at 6 US sites. Distal neuropathic pain 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 2306 visits during a median follow-up of 24 months (interquartile range 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 history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood. PMID:25659067

  16. Binding of Excreted and/or Secreted Products of Adult Hookworms to Human NK Cells in Necator americanus-Infected Individuals from Brazil▿

    PubMed Central

    Teixeira-Carvalho, Andréa; Fujiwara, Ricardo T.; Stemmy, Erik J.; Olive, Denise; Damsker, Jesse M.; Loukas, Alex; Corrêa-Oliveira, Rodrigo; Constant, Stephanie L.; Bethony, Jeffrey M.

    2008-01-01

    The impact of the interaction between excreted and/or secreted (ES) Necator americanus products and NK cells from Necator-infected individuals was analyzed. We investigated the binding of ES products to NK cells, the expression of NK cell receptors (CD56, CD159a/NKG2A, CD314/NKG2D, CD335/NKp46, and KLRF1/NKp80), the frequency of gamma interferon (IFN-γ)-producing NK cells after whole-blood in vitro stimulation, and the capacity of N. americanus ES products to induce NK cell chemotaxis. In contrast to those from noninfected individuals, NK cells from Necator-infected individuals demonstrated no binding with N. americanus ES products. This phenomenon was not due to alterations in NK cell receptor expression in infected subjects and could not be reproduced with NK cells from uninfected individuals by incubation with immunoregulatory cytokines (interleukin-10/transforming growth factor β). Further, we found that a significantly greater percentage of NK cells from infected subjects than NK cells from uninfected individuals spontaneously produced IFN-γ upon ex vivo culture. Our findings support a model whereby NK cells from Necator-infected individuals may interact with ES products, making these cells refractory to binding with exogenous ES products. During N. americanus infection, human NK cells are attracted to the site of infection by chemotactic ES products produced by adult Necator worms in the gut mucosa. Binding of ES products causes the NK cells to become activated and secrete IFN-γ locally, thereby contributing to the adult hookworm's ability to evade host immune responses. PMID:18838519

  17. Detection of immunogenic parasite and host-specific proteins in the sera of active and chronic individuals infected with Toxoplasma gondii.

    PubMed

    Yeng, Chen; Osman, Emelia; Mohamed, Zeehaida; Noordin, Rahmah

    2010-12-01

    Toxoplasma gondii infection in pregnant women may result in abortion and foetal abnormalities, and may be life-threatening in immunocompromised hosts. To identify the potential infection markers of this disease, 2-DE and Western blot methods were employed to study the parasite circulating antigens and host-specific proteins in the sera of T. gondii-infected individuals. The comparisons were made between serum protein profiles of infected (n=31) and normal (n=10) subjects. Antigenic proteins were identified by immunoblotting using pooled sera and monoclonal anti-human IgM-HRP. Selected protein spots were characterised using mass spectrometry. Prominent differences were observed when serum samples of T. gondii-infected individuals and normal controls were compared. A significant up-regulation of host-specific proteins, α(2)-HS glycoprotein and α(1)-B glycoprotein, was also observed in the silver-stained gels of both active and chronic infections. However, only α(2)-HS glycoprotein and α(1)-B glycoprotein in the active infection showed immunoreactivity in Western blots. In addition, three spots of T. gondii proteins were detected, namely (i) hypothetical protein chrXII: 3984434-3 TGME 49, (ii) dual specificity protein phosphatase, catalytic domain TGME 49 and (iii) NADPH-cytochrome p450 reductase TGME 49. Thus, 2-DE approach followed by Western blotting has enabled the identification of five potential infection markers for the diagnosis of toxoplasmosis: three are parasite-specific proteins and two are host-specific proteins. PMID:21080484

  18. CD4+ T Cell Depletion, Immune Activation and Increased Production of Regulatory T Cells in the Thymus of HIV-Infected Individuals

    PubMed Central

    Bandera, Alessandra; Ferrario, Giulio; Saresella, Marina; Marventano, Ivana; Soria, Alessandro; Zanini, Fabio; Sabbatini, Francesca; Airoldi, Monica; Marchetti, Giulia; Franzetti, Fabio; Trabattoni, Daria; Clerici, Mario; Gori, Andrea

    2010-01-01

    Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation. PMID:20520721

  19. 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

  20. 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

  1. 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

  2. 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

  3. Absolute Lymphocyte Count as a Surrogate Marker of CD4 Count in Monitoring HIV Infected Individuals: A Prospective Study

    PubMed Central

    Rane, Sharda Raju; Jadhav, Meenal Vitthal

    2016-01-01

    Introduction CD4 cell count has been proposed to be substituted by Absolute lymphocyte count in monitoring HIV infected individuals as methods of CD4 cell count and plasma viral estimation require expensive, specialized equipments and highly trained personnel. Aim To assess the clinical utility of the Absolute Lymphocyte Count (ALC) to serve as a surrogate marker for predicting a CD4 count < 200 cells/μl in patients with HIV infection in resource poor countries. Materials and Methods A prospective study of 61 patients with HIV/AIDS was conducted. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) of various ALC cut-offs were computed for CD4 cell count < 200 cells/μl for age < 30 or age ≥ 30 years. Pearson correlation, Linear regression and Receiver Operating Characteristics (ROC), were used. Results For patients aged ≥ 30 years, sensitivity, specificity, positive and negative predictive value of ALC <1200 cells/μl to predict CD4 cell count < 200 cells/μl were 34.48%, 67.5%, 43.48%, 58.69% respectively. For subjects aged < 30 years, these values were 27.27%, 67.5%, 18.75%, 77.14%, respectively. A ALC < 1643 was found to have maximal sensitivity for predicting a CD4 cell count <200/ μl. Conclusion Our data revealed good correlation between ALC and CD4 cell counts but ALC cut-off of 1200 was not a surrogate marker for CD4 cell count < 200 cells/μl. As we increase the cut-off to <1643/ μl it could be the cost-effective surrogate marker for CD4 cell counts < 200 cells/μl in resource limited settings. PMID:27437225

  4. 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

  5. Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran

    PubMed Central

    Fatholahi, Maryam; Bouzari, Majid

    2015-01-01

    Background: Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. Objectives: The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. Materials and Methods: Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. Results: In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). Conclusions: Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies. PMID:26862377

  6. 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

  7. 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

  8. CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection

    PubMed Central

    Canaday, David H.; Sridaran, Sankar; Van Epps, Puja; Aung, Htin; Burant, Christopher J.; Nsereko, Mary; Mayanja-Kizza, Harriet; Betts, Michael R.; Toossi, Zahra

    2015-01-01

    CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multi-parametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population. PMID:25956974

  9. 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

  10. Carbohydrate assimilation profiles of the first Italian Candida dubliniensis clinical isolates recovered from an HIV-infected individual.

    PubMed

    Giammanco, G M; Pignato, S; Salvo, S; Giammanco, G

    2000-12-01

    A total of six Candida dubliniensis isolates were obtained during 1 year of monitoring by monthly swabs from the oral cavity of an asymptomatic human immunodeficiency virus-infected individual in Catania, Italy. To the authors' knowledge, this constitutes the first recovery of C. dubliniensis from a human in Italy. Our identification procedure was based on colony color on CHROMagar Candida and carbohydrate assimilation profiles obtained by two commercial systems: API ID 32C and API 20C AUX. Karyotyping by pulsed-field gel electrophoresis confirmed the phenotypic identification. The biocodes obtained with API 20C AUX and with API ID 32C were 6172134 and 7142140015, respectively, for all six isolates. Both biocodes corresponded to those described in the literature as being produced by most C. dubliniensis isolates with each of the two identification systems. Our results confirm that both API 20C AUX and API ID 32C are able to rapidly and accurately differentiate C. dubliniensis from C. albicans. PMID:11191815

  11. 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

  12. Antiretroviral Medication Adherence and Amplified HIV Transmission Risk Among Sexually Active HIV-Infected Individuals in Three Diverse International Settings.

    PubMed

    Magidson, Jessica F; Li, Xin; Mimiaga, Matthew J; Moore, Ayana T; Srithanaviboonchai, Kriengkrai; Friedman, Ruth Khalili; Limbada, Mohammad; Hughes, James P; Cummings, Vanessa; Gaydos, Charlotte A; Elharrar, Vanessa; Celentano, David; Mayer, Kenneth H; Safren, Steven A

    2016-04-01

    Successful biomedical prevention/treatment-as-prevention (TasP) requires identifying individuals at greatest risk for transmitting HIV, including those with antiretroviral therapy (ART) nonadherence and/or 'amplified HIV transmission risk,' defined as condomless sex with HIV-uninfected/unknown-status partners when infectious (i.e., with detectable viremia or STI diagnosis according to Swiss criteria for infectiousness). This study recruited sexually-active, HIV-infected patients in Brazil, Thailand, and Zambia to examine correlates of ART nonadherence and 'amplified HIV transmission risk'. Lower alcohol use (OR = .71, p < .01) and higher health-related quality of life (OR = 1.10, p < .01) were associated with greater odds of ART adherence over and above region. Of those with viral load data available (in Brazil and Thailand only), 40 % met Swiss criteria for infectiousness, and 29 % had 'amplified HIV transmission risk.' MSM had almost three-fold (OR = 2.89, p < .001) increased odds of 'amplified HIV transmission risk' (vs. heterosexual men) over and above region. TasP efforts should consider psychosocial and contextual needs, particularly among MSM with detectable viremia. PMID:26246068

  13. 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

  14. High Blood Pressure and Related Factors Among Individuals at High Risk for HIV/Sexually Transmitted Infections.

    PubMed

    Nam, Soohyun; Whittemore, Robin; Jeon, Sangchoon; Davey-Rothwell, Melissa A; Latkin, Carl

    2016-06-01

    Data from a social network-based human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention study with a total of 330 men and women at high risk for HIV/STIs were used to examine the relationships between substance use, depressive symptoms, general health, cardiovascular disease risk factors, sociodemographic characteristics, and systolic/diastolic blood pressure (SBP/DBP). Approximately 60% of the participants had prehypertension to stage 2 hypertension. In the base model, older patients (P<.0001), men (P=.003), and patients with poorer self-reported health (P=.029) were significantly associated with high SBP, whereas older age (P<.001) and higher body mass index (P<.001) were significantly associated with higher DBP. After adjusting for the base model, high frequency of alcohol drinking and high frequency of binge drinking remained significant for high SBP and DBP. These data suggest that future cardiovascular disease programs should target moderate alcohol consumption to improve blood pressure among individuals at high risk for HIV/STIs. PMID:26514661

  15. Hepatitis C virus infection in HIV type 1-infected individuals does not accelerate a decrease in the CD4+ cell count but does increase the likelihood of AIDS-defining events.

    PubMed

    Stebbing, Justin; Waters, Laura; Mandalia, Sundhiya; Bower, Mark; Nelson, Mark; Gazzard, Brian

    2005-09-15

    Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection remains a point of controversy. In a multivariate analysis of a cohort of 5832 individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to that for individuals infected with HIV-1 alone. However, coinfection was associated with a statistically significant increased likelihood of onset of an acquired immunodeficiency syndromedefining illness or developing a CD4+ cell count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio, 1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly active antiretroviral therapy were significantly less likely to progress to either end point, because of their higher CD4+ cell counts. In conclusion, there was an increased number of adverse events in coinfected individuals, compared with individuals infected with HIV-1 alone. PMID:16107994

  16. Diminished Systemic and Antigen-Specific Type 1, Type 17, and Other Proinflammatory Cytokines in Diabetic and Prediabetic Individuals With Latent Mycobacterium tuberculosis Infection

    PubMed Central

    Kumar, Nathella Pavan; George, Parakkal Jovvian; Kumaran, Paul; Dolla, Chandra Kumar; Nutman, Thomas B.; Babu, Subash

    2014-01-01

    Background. Diabetes mellitus type 2 (DM) is known to be a major risk factor for the development of active tuberculosis, although its influence on latent Mycobacterium tuberculosis infection (hereafter, “latent infection”) remains poorly characterized. Methods. We examined circulating plasma cytokine levels in individuals with latent infection with DM or pre-DM (ie, intermediate hyperglycemia) and compared them to levels in patients with latent infection and normal glycemic control. Results. In persons with DM or pre-DM, latent infection is characterized by diminished circulating levels of type 1 (interferon γ, interleukin 2, and tumor necrosis factor α) and type 17 (interleukin 17F) cytokines. This was associated with decreased systemic levels of other proinflammatory cytokines (interleukin 1β and interleukin 18) and the antiinflammatory cytokine interleukin 10 but not with decreased systemic levels of type 2 cytokines. Moreover, latently infected individuals with DM had diminished levels of spontaneous and M. tuberculosis antigen–specific levels of type 1 and type 17 cytokines when antigen-stimulated whole blood was examined. Finally, there was no significant correlation between the levels of any of the cytokines measured (with the exception of interleukin 22) with hemoglobin A1c levels. Conclusions. Our data reveal that latent infection in the presence of DM or pre-DM, is characterized by diminished production of cytokines, implicated in the control of M. tuberculosis activation, allowing for a potential immunological mechanism that could account for the increased risk of active tuberculosis in latently infected individuals with DM. PMID:24907382

  17. 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

  18. Use of RT-Defective HIV Virions: New Tool to Evaluate Specific Response in Chronic Asymptomatic HIV-Infected Individuals

    PubMed Central

    Arberas, Hodei; García-Pérez, Javier; García, Felipe; Bargalló, Manuel Enric; Maleno, María José; Gatell, José María; Mothe, Beatriz; Alcami, José; Sánchez-Palomino, Sonsoles; Plana, Montserrat

    2013-01-01

    Background Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy. Methods We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry. Results The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: “full-responders” (positive response against both viral particles), “partial-responders” (positive response only against NL4-3/ΔRT virions) and “non-responders” (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals. Conclusions In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and

  19. The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy

    PubMed Central

    Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

    2012-01-01

    Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

  20. Individual administration of three tanniferous forage plants to lambs artificially infected with Haemonchus contortus and Cooperia curticei.

    PubMed

    Heckendorn, Felix; Häring, Dieter Adrian; Maurer, Veronika; Senn, Markus; Hertzberg, Hubertus

    2007-05-15

    We investigated direct anthelmintic effects associated with the feeding of fresh tanniferous forages against established populations of Haemonchus contortus and Cooperia curticei in lambs. Twenty-four parasite naive lambs were inoculated with a single dose of infective larvae of these two parasites 27 days prior to the start of the feeding experiment. Lambs were individually fed with either chicory (Cichorium intybus), birdsfoot trefoil (Lotus corniculatus), sainfoin (Onobrychis viciifolia) or a ryegrass/lucerne mixture (control) for 17 days. Animals where then united to one flock and subjected to control feeding for another 11 days to test the sustainability of potentially lowered egg excretion generated by tanniferous forage feeding. When compared to the control, administration of all tanniferous forages was associated with significant reductions of total daily faecal egg output specific to H. contortus (chicory: 89%; birdsfoot trefoil: 63%; sainfoin: 63%; all tests P<0.05) and a tendency of reduced H. contortus worm burden (chicory: 15%; birdsfoot trefoil: 49% and sainfoin: 35% reduction). Irrespective of the condensed tannin (CT) containing fodder, no anthelmintic effects were found against C. curticei. Cessation of CT-feeding followed by non-CT control feeding did not result in a re-emergence of faecal egg counts based on faecal dry matter (FECDM) in any group, suggesting that egg output reductions are sustainable. The moderate to high concentrations of CTs in birdsfoot trefoil (15.2 g CTs kg(-1) dry matter (DM)) and sainfoin (26.1 g CTs kg(-1) DM) were compatible with the hypothesis that the antiparasitic effect of these forages is caused by their content of CTs. For chicory (3 g CTs kg(-1) DM), however, other secondary metabolites need to be considered. Overall, birdsfoot trefoil and in particular sainfoin seem promising candidates in contributing to an integrated control strategy against H. contortus not only by mitigating parasite related health

  1. 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

  2. CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals.

    PubMed

    Loiseau, C; Requena, M; Mavigner, M; Cazabat, M; Carrere, N; Suc, B; Barange, K; Alric, L; Marchou, B; Massip, P; Izopet, J; Delobel, P

    2016-09-01

    The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-β (TGF-β) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals. PMID:26883727

  3. 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 ...

  4. 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

  5. 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

  6. Infection of less virulent Helicobacter pylori strains in asymptomatic healthy individuals in Thailand as a potential contributing factor to the Asian enigma.

    PubMed

    Hirai, Itaru; Sasaki, Tadahiro; Kimoto, Ai; Yamamoto, Yoshimasa; Azuma, Takeshi; Mahachai, Varocha; Hansomburana, Piyathida; Lertkupinit, Comsun; Luangjaru, Somchai; Noophan, Phadet; Chanatrirattanapan, Rattikorn; Piyanirandr, Vanich; Sappajit, Theeranan; Suthivarakom, Karun; Sangsuk, Leelaowadee; Wangroongsarb, Piyada

    2010-03-01

    In Thailand, gastric cancer incidence is considerably low despite the high prevalence of Helicobacter pylori infection. We investigated the prevalence of H. pylori infection and the genotypes of cagA by using 179 stool specimens obtained from asymptomatic Thai individuals. In this study, the prevalence of H. pylori infection was 43.6%, and the detection rate of cagA-positive strains was 43.5%. In addition, the proportion of the highly virulent East-Asian type of cagA was 7.2%. These results indicate that the low prevalence of cagA-positive H. pylori strain as well as the low prevalence of East-Asian genotype cagA-positive strains may contribute to the low gastric cancer incidence. PMID:20036753

  7. Absence of Pneumocystis jirovecii Colonization in Human Immunodeficiency Virus-Infected Individuals With and Without Airway Obstruction and With Undetectable Viral Load

    PubMed Central

    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

  8. 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

  9. 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

  10. 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

  11. Antibody but not memory B-cell responses are tuned-down in vertically HIV-1 infected children and young individuals being vaccinated yearly against influenza.

    PubMed

    Rinaldi, Stefano; Zangari, Paola; Cotugno, Nicola; Manno, Emma Concetta; Brolatti, Noemi; Castrucci, Maria Rita; Donatelli, Isabella; Rossi, Paolo; Palma, Paolo; Cagigi, Alberto

    2014-02-01

    Yearly immunization against seasonal influenza is highly recommended for HIV-1 infected individuals but evaluating the success of vaccination by serological markers may not be fully informative in this population. Recently, it has been hypothesized that the generation of long-lasting immune responses may depend on whether similar antigens challenge the immune system frequently and intermittently. In the present study, in order to search for additional correlates of vaccine-induced protective immunity and to further dissect this theory, both humoral and memory B-cell responses to the trivalent 2012-2013 seasonal influenza vaccination has been evaluated by strain-specific (separately for H1N1, H3N2 and B strain) standard hemagglutination inhibition (HI) assay and B-cell enzyme-linked immunosorbent spot (ELISpot) in a cohort of vertically HIV-1 infected children and young individuals as compared to age-matched healthy controls. A high number of HIV-1 infected individuals had protective antibody levels prior to vaccination and showed low seroconversion rates after vaccination as compared to healthy controls. On the contrary, similar frequencies of influenza-specific memory B-cells were detected by B-cell ELISpot in both groups suggesting that an adequate B-cell response has been elicited. Data from the H1N1 strain, which is recurrent in seasonal influenza vaccines since 2009, pointed out decreasing antibody but not memory B-cell responses for HIV-1 infected patients being vaccinated for a greater number of years. Further investigations are required to standardize the influenza-specific B-cell ELISpot and to understand whether it could be used routinely as an additional tool to evaluate response to influenza vaccination in immune-compromised individuals being vaccinated yearly. PMID:24333344

  12. 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. PMID:23180286

  13. 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

  14. Depression longitudinally mediates the association of appearance concerns to ART non-adherence in HIV-infected individuals with a history of injection drug use

    PubMed Central

    Gordon, Janna R.; Safren, Steven A.

    2012-01-01

    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. PMID:23180286

  15. APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression

    PubMed Central

    Vázquez-Pérez, Joel A; Ormsby, Christopher E; Hernández-Juan, Ramón; Torres, Klintsy J; Reyes-Terán, Gustavo

    2009-01-01

    Background APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infected individuals at different disease stages. APOBEC3G mRNA was measured in PBMCs from three groups: healthy controls with no known risk factor to HIV infection (n = 26), exposed uninfected individuals who had unprotected sex with their HIV+ partners for at least 3 months (n = 37), and HIV infected patients at various disease stages (n = 45), including 8 patients with low HIV viral loads < 10,000 copies/mL (LVL) for at least 3 years. Additionally, we obtained sequences from the env, gag, pol, nef, vif and the LTR of the patients' virus. Results Exposed uninfected individuals expressed higher APOBEC3G than healthy controls (3.86 vs. 1.69 relative expression units), and their expression significantly decreased after a year from the HIV diagnosis and subsequent treatment of their partners. Infected individuals showed a positive correlation (Rho = 0.57, p = 0.00006) of APOBEC3G expression with CD4+ T cell count, and a negative correlation with HIV viremia (Rho = -0.54, p = 0.00004). The percentage of G to A mutations had a positive correlation (Rho = 0.43, p = 0.0226) with APOBEC3G expression, and it was higher in LVL individuals than in the other patients (IQR 8.27 to 9.64 vs. 7.06 to 8.1, p = 0.0084). Out of 8 LVLs, 3 had hypermutations, and 4 had premature stop codons only in viral vif. Conclusion The results suggest that exposure to HIV may trigger APOBEC3G expression in PBMCs, in the absence of infection. Additionally, cessation of exposure or advanced disease is associated with decreased APOBEC3G expression. PMID:19254362

  16. Differences in shell shape of naturally infected Lymnaea stagnalis (L.) individuals as the effect of the activity of digenetic trematode larvae.

    PubMed

    Zbikowska, Elzbieta; Zbikowski, Janusz

    2005-10-01

    The shells of Lymnaea stagnalis show great morphological variability. This phenomenon has been described as the result of an environmental influence. The main object of the present study was to compare some biometric data from shells of naturally infected and uninfected snails from 25 different lakes in the central part of Poland. The height of the shell, the height of the spiral, and the width of the shell were measured. Some inter- and intrapopulation differences among individuals were found. Greater variability of shell shape was observed among snails parasitized with digenean larvae than in nonparasitized ones. Snails infected with Echinoparyphium aconiatum, Echinostoma revolutum, Diplostomum pseudospathaceum, and Opisthioglyphe ranae differed in shell shape compared with uninfected individuals. Snails infected with Plagiorchis elegans did not differ from uninfected individuals. The same was true of snails in which the commensal oligochaete, Chaetogaster limnei, was found. The results of the present study support the assumption that the deformation of shells of the snails under study was in some way influenced by the presence of certain species of digenetic trematodes. PMID:16419747

  17. Determinants of benzodiazepine use in a representative population of HIV-infected individuals: the role of HIV status disclosure (ANRS-EN12-VESPA study).

    PubMed

    Roux, Perrine; Fugon, Lionel; Michel, Laurent; Lert, France; Obadia, Yolande; Spire, Bruno; Carrieri, Maria Patrizia

    2011-09-01

    HIV infection may result in stressful situations such as disclosure to others and could be a mediator between seropositivity status and psychiatric illness, depression, or anxiety. Several results have shown that anxiolytic use (mainly benzodiazepines [BDZ]) is highly prevalent in HIV-infected individuals, but few studies have highlighted to what extent this use could be associated with HIV disclosure. A national cross-sectional survey representative of people living with HIV and AIDS in France enrolled 2932 individuals in 102 French HIV hospital departments. Face-to-face interviews and self-administered questions collected information about patients' experience with HIV and HIV care, including use of psychotropic drugs, social support, stigma, and disclosure of HIV status. We identified factors associated with regular BDZ use (i.e., more than once a week) using a weighted logistic regression model. Regular BDZ use and anxiety symptoms were reported by 16% and 29% of the patients, respectively. After multiple adjustment for known correlates of BDZ use and anxiety symptoms, individuals who had disclosed their HIV status to relatives or friends were found to be more likely (OR [95% CI] = 1.78 [1.02-3.09]) to regularly use BDZ. These results show both to what extent disclosure to others continues to be a stressful step in the course of HIV infection and that disclosure is something that could be identified by BDZ use. They also highlight the need for appropriate case management and psychiatric care to help patients manage the consequences of disclosure. PMID:21562996

  18. Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon

    PubMed Central

    Fratus, Alessandra Sampaio Bassi; Cabral, Fernanda Janku; Fotoran, Wesley Luzetti; Medeiros, Márcia Melo; Carlos, Bianca Cechetto; Martha, Rosimeire dalla; da Silva, Luiz Hildebrando Pereira; Lopes, Stefanie Costa Pinto; Costa, Fabio Trindade Maranhão; Wunderlich, Gerhard

    2014-01-01

    In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. PMID:25099336

  19. Soluble Levels of Receptor for Advanced Glycation Endproducts (RAGE) and Progression of Atherosclerosis in Individuals Infected with Human Immunodeficiency Virus: ACTG NWCS 332.

    PubMed

    Danoff, Ann; Kendall, Michelle A; Currier, Judith S; Kelesidis, Theodoros; Schmidt, Ann Marie; Aberg, Judith A

    2016-08-01

    Identification of biomarkers and/or mediators of cardiovascular disease (CVD) associated with HIV infection would be of diagnostic and therapeutic value. As soluble receptor for advanced glycation endproducts (sRAGE) and endogenous secretory (esRAGE) have been implicated in vascular complications in other settings, we investigated whether either soluble form of RAGE was associated with changes in carotid intima-media thickness (CIMT) in HIV-infected patients and HIV-uninfected controls. We found no differences in sRAGE, esRAGE, or CIMT among groups at study entry, or in yearly rates of change in sRAGE, esRAGE, or CIMT by HIV-serostatus (all p > 0.10). However, yearly rates of change in sRAGE (p = 0.07) and esRAGE (p < 0.001) were higher in those taking protease inhibitors, and lower baseline esRAGE levels (p = 0.06) were associated with increased odds of CIMT progression in HIV-infected individuals. Although esRAGE was not altered by HIV-serostatus (p = 0.17), its inverse relationship with CIMT progression in HIV-infected patients suggests a possible role as a mediator of CVD in HIV-infected persons. PMID:27216802

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Sequences of Wolbachia wsp genes reveal multiple infection of individual northern corn rootworms (Diabrotica barberi) by several Wolbachia strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Northern corn rootworm (Diabrotica barberi)(NCR) populations in the USA are infected with at least 4 strains of the endosymbiont, Wolbachia. NCR from eastern Illinois to Pennsylvania appear to harbor at least 4 different strains designated wBar1, wBar3, wBar4, and wBar5. NCR from central Illinois ...

  6. 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

  7. 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

  8. An adapted frailty-related phenotype and the VACS Index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals

    PubMed Central

    Akgün, Kathleen M.; Tate, Janet P.; Crothers, Kristina; Crystal, Stephen; Leaf, David A.; Womack, Julie; Brown, Todd T.; Justice, Amy C.; Oursler, Krisann K.

    2014-01-01

    Background Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted, survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA. Methods Defined from self-reported domains of physical shrinking, exhaustion, slowness and low physical activity in Veterans Aging Cohort Study (VACS) participants, aFRP was considered present with ≥3 domains and pre-frailty with 1-2 domains. Cox survival analysis determined hazard ratios (HR) for 5-year hospitalization and mortality risk adjusting for frailty states, demographics, health behaviors, comorbidities, and a validated risk index incorporating HIV-specific and general organ system biomarkers, the VACS Index. Model discrimination was assessed. Results Participants with complete data were included (6515/7324 (89%)). Of these, 3.9% of HIV-infected with HIV-1 RNA>400copies/ml; 2.0% of HIV-infected with HIV-1 RNA ≤ 400copies/ml; and 2.8% of uninfected individuals met aFRP criteria (p=0.01). After adjustment for other covariates, aFRP was associated with hospitalization (HR=1.78, 95% CI [1.48, 2.13]) and mortality (HR=1.75, 95% CI [1.28, 2.40]). C-statistics for the VACS Index for hospitalization (0.633) and for mortality (0.756) were higher than for aFRP frailty (0.565 and 0.584, respectively). C-statistic for hospitalization improved modestly when VACS Index and aFRP were both included (0.646) and minimally for mortality (0.761). Conclusions aFRP was independently associated with adverse health outcomes among HIV-infected and uninfected individuals. aFRP modestly improved prediction for hospitalization. However, the aFRP is rare among HIV-infected individuals with undetectable HIV-1 RNA. PMID:25202921

  9. 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

  10. HTLV-1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells.

    PubMed

    Zane, Linda; Sibon, David; Capraro, Valérie; Galia, Perrine; Karam, Maroun; Delfau-Larue, Marie-Hélène; Gilson, Eric; Gessain, Antoine; Gout, Olivier; Hermine, Olivier; Mortreux, Franck; Wattel, Eric

    2012-08-15

    Untransformed HTLV-1 positive CD4(+) cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+) cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV-1 positive CD4(+) but not uninfected CD4(+) or CD8(+) clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4(+) cells. In conclusion HTLV-1-dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression. PMID:21717459

  11. 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

  12. Brief Report: L-Selectin (CD62L) Is Downregulated on CD4+ and CD8+ T Lymphocytes of HIV-1-Infected Individuals Naive for ART.

    PubMed

    Vassena, Lia; Giuliani, Erica; Buonomini, Anna R; Malagnino, Vincenzo; Andreoni, Massimo; Doria, Margherita

    2016-08-15

    The expression of L-selectin (CD62L) in HIV-1 infection has not been extensively investigated. Here, we measured CD62L expression on T-cell subsets of HIV-1-infected individuals naive for antiretroviral therapy (ART-naive) or receiving therapy (ART), and seronegative control subjects (HIV-neg). We found reduced frequencies of CD62L cells among CD4 and CD8 T cells from ART-naive as compared with ART and HIV-neg groups, particularly within naive and central memory subsets. CD62L expression on T cells inversely correlated with viral load and rapidly increased after ART initiation. Plasma sCD62L levels did not correlate with CD62L expression, being higher in all HIV-1-infected individuals as compared with HIV-neg subjects. Finally, CD62L downregulation was found associated with the expression of the CD38 activation marker in CD8 T cells, but not in CD4 T cells. We suggest that CD62L downregulation due to unconstrained HIV-1 replication may have important consequences for T-cell circulation and function and for disease progression. PMID:27003497

  13. Delay of Antiretroviral Therapy Initiation is Common in East African HIV-Infected Individuals in Serodiscordant Partnerships

    PubMed Central

    MUJUGIRA, Andrew; CELUM, Connie; THOMAS, Katherine K.; FARQUHAR, Carey; MUGO, Nelly; KATABIRA, Elly; BUKUSI, Elizabeth A.; TUMWESIGYE, Elioda; BAETEN, Jared M.

    2014-01-01

    Objective WHO guidance recommends antiretroviral therapy (ART) initiation for all persons with a known HIV-uninfected partner, as a strategy to prevent HIV transmission. Uptake of ART among HIV-infected partners in serodiscordant partnerships is not known, which we evaluated in African HIV serodiscordant couples. Design Prospective cohort study. Methods Among HIV-infected persons from Kenya and Uganda who had a known heterosexual HIV-uninfected partner, we assessed ART initiation in those who became ART-eligible under national guidelines during follow-up. Participants received quarterly clinical and semi-annual CD4 monitoring, and active referral for ART upon becoming eligible. Results Of 1958 HIV-infected ART-eligible partners, 58% were women and the median age was 34 years. At the first visit when determined to be ART eligible, the median CD4 count was 273 cells/μL (IQR 221, 330), 77% had WHO stage 1 or 2 HIV disease, and 96% were receiving trimethoprim-sulfamethoxazole prophylaxis. The cumulative probabilities of initiating ART at 6, 12, and 24 months after eligibility were 49.9%, 70.0% and 87.6%, respectively. Younger age (<25 years) (adjusted hazard ratio [AHR] 1.39, p=0.001), higher CD4 count (AHR 1.95, p<0.001 for >350 compared with <200 cells/μL), higher education (AHR 1.25, p<0.001), and lack of income (AHR 1.15, p=0.02) were independent predictors for delay in ART initiation. Conclusions In the context of close CD4 monitoring, ART counseling, and active linkage to HIV care, a substantial proportion of HIV-infected persons with a known HIV-uninfected partner delayed ART initiation. Strategies to motivate ART initiation are needed, particularly for younger persons with higher CD4 counts. PMID:24798765

  14. Protective Effects of Higher Cognitive Reserve for Neuropsychological and Daily Functioning Among Individuals Infected with Hepatitis C

    PubMed Central

    Sakamoto, Maiko; Woods, Steven Paul; Kolessar, Michael; Kriz, Daniel; Anderson, J. Renee; Olavarria, Hannah; Sasaki, Anna W.; Chang, Michael; Flora, Kenneth D.; Loftis, Jennifer M.; Huckans, Marilyn

    2013-01-01

    Higher levels of cognitive reserve (CR) can be protective against the neuropsychological manifestation of neural injury across a variety of clinical disorders. However, the role of CR in the expression of neurocognitive deficits among persons infected with the hepatitis C virus (HCV) is not well understood. Thirty-nine HCV-infected participants were classified as having either high (n=19) or low (n=20) CR based on educational attainment, oral word reading, and IQ scores. A sample of 40 demographically comparable healthy adults (HA) was also included. All participants completed the Neuropsychological Assessment Battery (NAB), Delis-Kaplan Executive Function System (D-KEFS), and Behavioral Rating Inventory of Executive Function, Adult Version (BRIEF-A). Linear regression analyses, controlling for gender, depression and lifetime substance use disorders, found significant effects of HCV/CR group on verbal fluency, executive functions, and daily functioning T-scores, but not in learning or the BRIEF-A. Pairwise comparisons revealed that the HCV group with low CR performed significantly below the HCV high CR and HA cohorts, who did not differ from one another. Findings indicate that higher levels of CR may be a protective factor in the neurocognitive and real-world manifestation of neural injury commonly associated with HCV infection. PMID:24018902

  15. Durability and Effectiveness of Maraviroc-Containing Regimens in HIV-1-Infected Individuals with Virological Failure in Routine Clinical Practice

    PubMed Central

    Potard, Valérie; Reynes, Jacques; Ferry, Tristan; Aubin, Céline; Finkielsztejn, Laurent; Yazdanpanah, Yazdan; Costagliola, Dominique

    2015-01-01

    Introduction Limited data are available on the durability and effectiveness of maraviroc in routine clinical practice. We assessed the durability of maraviroc-containing regimens during a 30-month period, as well as their immunovirological and clinical efficacy, according to viral tropism in treatment-experienced individuals with viral load (VL) >50 copies/ml in the French Hospital Database on HIV. Methods Virological success was defined as VL<50 copies/ml, immunological success as a confirmed increase of at least 100 CD4 cells/mm3 measured twice at least one month apart, and clinical failure as hospitalization for a non-AIDS event, an AIDS event, or death. Multivariable Cox regression models adjusted for potential confounders were used to assess the influence of viral tropism on durability, the immunovirological responses, and clinical outcome. Results 356 individuals started maraviroc with VL>50 copies/ml of whom 223 harbored R5 viruses, 44 non-R5 viruses and 89 viruses of unknown tropism. Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 viruses. In multivariable analysis, non-R5 viruses were associated with a lower likelihood of both virological success (hazard ratio (HR): 0.42; 95% confidence interval (CI), 0.25–0.70) and immunological success (HR: 0.37; 95% CI, 0.18–0.77). No difference in clinical outcome was found between individuals with R5 and non-R5 viruses. The effectiveness of maraviroc-containing regimens in individuals with unknown viral tropism was not significantly different from that in individuals with R5 viruses. A limitation of the study is the absence of genotypic susceptibility score. Conclusion In this observational study, maraviroc-containing regimens yielded high rates of viral

  16. Health and social support services to HIV/AIDS infected individuals in Tanzania: employees and employers perceptions

    PubMed Central

    2014-01-01

    Background HIV is a major public health problem in the world, especially in sub-Saharan Africa. It often leads to loss of productive labour and disruption of existing social support system which results in deterioration of population health. This poses a great challenge to infected people in meeting their essential goods and services. This paper examines health and social support services provided by employers to HIV/AIDS infected employees in Tanzania. Methods This was a cross-sectional study, which employed qualitative and quantitative methods in data collection and analysis. Structured questionnaires and in-depth interviews were used to assess the health and social support services provision at employers and employees perspectives. The study participants were employees and employers from public and private organizations. Results A total of 181 employees and 23 employers from 23 workplaces aged between 18–68 years were involved. The results show that 23.8% (i.e., 20.4% males and 27.3% females) of the employees had at least one member of the family or close relatives living with HIV at the time of the study. Fifty six percent of the infected employees reported to have been receiving health or social support from their employers. Employees’ responses were consistent with those reported by their employers. A total of 12(52.2%) and 11(47.8%) employers reported to have been providing health and social supports respectively. Female employees (58.3%) from the private sector (60.0%) were more likely to receive supports than male employees (52.6%) and than those from the public sector (46.2%). The most common health and social support received by the employees were treatment, and nutritional support and reduction of workload, respectively. Conclusions HIV/AIDS infected employees named treatment and nutritional support, and soft loans and reduced workload respectively, as the most important health and social supports they needed from their employers. This study

  17. High rate of missed HIV infections in individuals with indeterminate or negative HIV western blots based on current HIV testing algorithm in China.

    PubMed

    Liu, Man-Qing; Zhu, Ze-Rong; Kong, Wen-Hua; Tang, Li; Peng, Jin-Song; Wang, Xia; Xu, Jun; Schilling, Robert F; Cai, Thomas; Zhou, Wang

    2016-08-01

    It remains unclear if China's current HIV antibody testing algorithm misses a substantial number of HIV infected individuals. Of 196 specimens with indeterminate or negative results on HIV western blot (WB) retrospectively examined by HIV-1 nucleic acid test (NAT), 67.57% (75/111) of indeterminate WB samples, and 16.47% (14/85) of negative WB samples were identified as NAT positive. HIV-1 loads in negative WB samples were significantly higher than those in indeterminate WB samples. Notably, 86.67% (13/15) of samples with negative WB and double positive immunoassay results were NAT positive. The rate of HIV-1 infections missed by China's current HIV testing algorithm is unacceptably high. Thus, China should consider using NAT or integrating fourth generation ELISA into current only antibodies-based HIV confirmation. J. Med. Virol. 88:1462-1466, 2016. © 2016 Wiley Periodicals, Inc. PMID:26856240

  18. 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

  19. 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

  20. Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort.

    PubMed

    Hleyhel, Mira; Belot, Aurélien; Bouvier, Anne-Marie; Tattevin, Pierre; Pacanowski, Jérôme; Genet, Philippe; De Castro, Nathalie; Berger, Jean-Luc; Dupont, Caroline; Lavolé, Armelle; Pradier, Christian; Salmon, Dominique; Simon, Anne; Martinez, Valérie; Spano, Jean-Philippe; Costagliola, Dominique; Grabar, Sophie

    2015-11-15

    Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997-2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001-2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992-1996) and early-cART (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001-2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future. PMID:25976897

  1. Serum (1→3)-β-D-glucan levels in HIV-infected individuals are associated with immunosuppression, inflammation, and cardiopulmonary function

    PubMed Central

    Morris, Alison; Hillenbrand, Maria; Finkelman, Malcolm; George, M. Patricia; Singh, Vikas; Kessinger, Cathy; Lucht, Lorrie; Busch, Michelle; McMahon, Deborah; Weinman, Renee; Steele, Chad; Norris, Karen A.; Gingo, Matthew R.

    2012-01-01

    Background Translocation of gastrointestinal bacteria in HIV-infected individuals is associated with systemic inflammation, HIV progression, mortality, and co-morbidities. HIV-infected individuals are also susceptible to fungal infection and colonization, but whether fungal translocation occurs and influences HIV progression or co-morbidities is unknown. Methods Serum (1→3)-β-D-glucan was measured by a Limulus Amebocyte Lysate assay (Fungitell®) in 132 HIV-infected outpatients. Selected plasma cytokines and markers of peripheral T-cell activation were measured. Pulmonary function testing and Doppler-echocardiography were performed. Relationship of high (≥40pg/ml) and low (<40pg/ml) levels of (1→3)-β-D-glucan with HIV-associated variables, inflammation markers, and pulmonary function and pulmonary hypertension measures were determined. Results Forty-eight percent had detectable (1→3)-β-D-glucan, and 16.7% had high levels. Individuals with high (1→3)-β-D-glucan were more likely to have CD4 counts below 200 cells/μl (31.8% vs. 8.4%, p=0.002), had higher log10 HIV viral levels (2.85 vs. 2.13 log copies/ml, p=0.004), and were less likely to use ART (68.2% vs. 90.0%, p=0.006). Plasma IL-8 (p=0.033), TNF-α (p=0.029), and CD8+CD38+ (p=0.046) andCD8+HLA-DR+ (p=0.029) were also increased with high levels. Abnormalities in diffusing capacity (p=0.041) and in pulmonary artery pressures (p=0.006 for pulmonary artery systolic pressure and 0.013 for tricuspid regurgitant velocity) were more common in those with high (1→3)-β-D-glucan. Conclusions We found evidence of peripheral fungal cell wall polysaccharides in an HIV-infected cohort. We also demonstrated an association between high serum (1→3)-β-D-glucan, HIV-associated immunosuppression, inflammation, and cardiopulmonary co-morbidity. These results implicate a new class of pathogen in HIV-associated microbial translocation and suggest a role in HIV progression and co-morbidities. PMID:22972021

  2. Cocaine Alters Cytokine Profiles in HIV-1-Infected African American Individuals in the DrexelMed HIV/AIDS Genetic Analysis Cohort

    PubMed Central

    Parikh, Nirzari; Dampier, Will; Feng, Rui; Passic, Shendra R.; Zhong, Wen; Frantz, Brian; Blakey, Brandon; Aiamkitsumrit, Benjamas; Pirrone, Vanessa; Nonnemacher, Michael R.; Jacobson, Jeffrey M.; Wigdahl, Brian

    2014-01-01

    Background This study evaluated the relationship between illicit drug use and HIV-1 disease severity in HIV-1-infected patients enrolled in the DrexelMed HIV/AIDS Genetic Analysis Cohort. Since, cocaine is known to have immunomodulatory effects, the cytokine profiles of preferential nonusers, cocaine users, and multidrug users were analyzed to understand the effects of cocaine on cytokine modulation and HIV-1 disease severity. Methods Patients within the cohort were assessed approximately every 6 months for HIV-1 clinical markers and for history of illicit drug, alcohol, and tobacco use. The Luminex human cytokine 30-plex panel was used for cytokine quantitation. Analysis was performed using a newly developed biostatistical model. Results Substance abuse was common within the cohort. Utilizing the drug screens at the time of each visit, the subjects in the cohort were categorized as preferential nonusers, cocaine users, or multidrug users. The overall health of the nonuser population was better than that of the cocaine users, with peak and current viral loads in nonusers substantially lower than those in cocaine and multidrug users. Among the 30 cytokines investigated, differential levels were established within the 3 populations. The T-helper 2 cytokines, interleukin-4 and -10, known to play a critical role during HIV-1 infection, were positively associated with increasing cocaine use. Clinical parameters such as latest viral load, CD4+ T-cell counts, and CD4:CD8 ratio were also significantly associated with cocaine use, depending on the statistical model used. Conclusions Based on these assessments, cocaine use appears to be associated with more severe HIV-1 disease. PMID:24732878

  3. 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

  4. 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

  5. Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses

    PubMed Central

    Mouquet, Hugo; Klein, Florian; Scheid, Johannes F.; Warncke, Malte; Pietzsch, John; Oliveira, Thiago Y. K.; Velinzon, Klara; Seaman, Michael S.; Nussenzweig, Michel C.

    2011-01-01

    Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency. PMID:21931643

  6. Management of Lipid Levels and Cardiovascular Disease in HIV-Infected Individuals: Just Give Them a Statin?

    PubMed

    Stein, James H

    Current guidelines for managing cholesterol to reduce cardiovascular disease (CVD) risk focus on providing the appropriate intensity of statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) level. There is very little evidence supporting the use of treatments aimed at raising high-density lipoprotein cholesterol level or reducing triglyceride levels. HIV-infected persons have excess risk of CVD compared with the general population. Statins are less effective at reducing LDL-C levels in HIV-infected persons who are also at greater risk for adverse effects from statin treatment. When selecting a statin to achieve desired lowering of LDL-C level, the potential for drug interactions with antiretroviral therapy must be considered. Information from ongoing research is expected to help identify optimal strategies for use of statin treatment in this population. This article summarizes a presentation by James H. Stein, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Chicago, Illinois, in May 201. PMID:27398770

  7. 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. PMID:26350637

  8. Phenotypical and functional evaluation of CD8+/S6F1+ T lymphocytes in haemophiliac individuals with HIV-1 infection.

    PubMed Central

    Cavallin, F; Traldi, A; Zambello, R

    1993-01-01

    In this study we investigated the distribution of the S6F1 antigen, an epitope of the lymphocyte function-associated antigen, on CD8+ T lymphocytes in a series of 15 HIV-1+ and 20 HIV-1- haemophiliac patients. MoAbs recognizing the S6F1 antigen have been claimed to distinguish between killer effectors (brightly S6F1+ stained) and suppressor cells (dimly S6F1+ stained) within the CD8+ lymphoid population. In addition, we tried to find a correlation between the spontaneous in vitro immunoglobulin synthesis from patients' peripheral blood lymphocytes and the pattern of S6F1 expression. Although the total number of double-positive CD8+/S6F1+ cells was similar in both HIV-1+ and HIV-1- haemophiliac patients, a significant increase in the CD8+/S6F1+ population bright versus dim was documented in HIV-1-infected with respect to HIV-1- haemophiliacs (bright/dim ratio 3.97 +/- 0.61 versus 0.75 +/- 0.1, respectively, P < 0.005). This finding was correlated to a significant increase in spontaneous in vitro immunoglobulin production in HIV-1+ subjects compared with control haemophiliacs (P < 0.005). Purified CD8+ lymphocytes from HIV-1+ subjects showed a reduced suppressor activity on mitogen-induced immunoglobulin production. Taken together, these data suggest that HIV-1 infection favours the generation of CD8+/S6F1+ bright cells with putative cytotoxic-associated function, leading to a progressive reduction in the number of CD8+/S6F1+ dim suppressor lymphocytes. This phenomenon may contribute to the polyclonal hypergammaglobulinaemia present in HIV-1+ haemophiliac patients. PMID:8324903

  9. [HIV infection and immigration].

    PubMed

    Monge, Susana; Pérez-Molina, José A

    2016-01-01

    Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care. PMID:27016136

  10. 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

  11. Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population

    PubMed Central

    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

    2015-01-01

    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

  12. 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

  13. 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

  14. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study

    PubMed Central

    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

  15. Impact of etravirine use on hospitalization rates among highly pre-treated failing HIV-1 infected individuals between 2005 and 2011

    PubMed Central

    Lacombe, Jean-Marc; Goujard, Cecile; Valantin, Marc-Antoine; Cheret, Arnaud; Lahoulou, Rima; Girard, Pierre-Marie; Costagliola, Dominique

    2014-01-01

    Introduction Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor available in France since 2006, is indicated for the treatment of HIV-1 infection in combination with a ritonavir boosted protease inhibitor (PI) in antiretroviral treatment-experienced adult patients. To assess its impact in routine clinical care, our objective was to compare hospitalization rates in highly pre-treated failing HIV-1 infected individuals between 2005 and 2011 depending on whether or not they received ETR+PI. Methods From the French Hospital Database on HIV (ANRS CO4), we selected highly pre-treated individuals (prior exposure to at least 2NRTI, 2PI and 1 NNRTI) with a viral load (VL)>50 copies/mL initiating a new regimen between 2005 and 2011. Hospitalization rates were calculated for each calendar month and depending on whether patients never received ETR+PI at any time or during months before initiating ETR+PI (no ETR+PI) or during months after initiating ETR+PI (ETR+PI), using an intention to continue treatment approach. Poisson regression models were used to compare incidence between the two groups, after adjustment for potential confounders (age, transmission group, origin, AIDS, PCP prophylaxis, viral load, CD4, nb of previous ARV). Results Overall 3884 patients fulfilled inclusion criteria. Among them 838 (21.6%) received ETR+PI at least once. Among all enrolled patients, 35.8% had CD4 <200/mm3, 17.5% had VL >100,000 copies/ml, 42.8% had had an AIDS event and 47.8% had received more than 10 different antiretroviral drugs. There were 2484 hospitalizations in 808 individuals over 13,986 patient-years. The hospitalization rates for 1000 P-Y were 169.0 for the ETR+PI group and 179.3 for the no ETR+PI group. After adjustment, the corresponding figures were 144.8 for 1000 P-Y and 192.7 for 1000 P-Y respectively, with a relative risk estimated as 0.75 (95% CI 0.67–0.84). Conclusions Access to ETR+PI between 2005 and 2011 was associated with a 25% reduction in the

  16. The effects of antiretroviral treatment initiation on cognition in HIV-infected individuals with advanced disease in Pune, India.

    PubMed

    Ghate, Manisha; Mehendale, Sanjay; Meyer, Rachel; Umlauf, Anya; Deutsch, Reena; Kamat, Rujvi; Thakar, Madhuri; Risbud, Arun; Kulkarni, Smita; Sakamoto, Maiko; Alexander, Terry; Franklin, Donald; Letendre, Scott; Heaton, Robert K; Grant, Igor; Marcotte, Thomas D

    2015-08-01

    There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART). But the prevalence of milder forms of HAND still remains high. Data from systematically conducted studies on the effects of ART on cognition are scanty in India, where HIV-1 clade C is prevalent. The purpose of the present study was to assess the effect of antiretroviral therapy in HIV-seropositive (HIV+) individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and domain-specific levels of cognitive functioning were determined using a locally recruited normative sample, and a change in neurocognitive functioning at the 1-year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6 % of the HIV+ group at baseline. At the 1-year follow-up, the group showed significant improvement in the Learning domain (p < 0.05). HIV+ individuals showing improvement in the global cognitive scores had a significantly lower baseline CD4 cell count compared to others. Overall, the degree of improvement associated with the magnitude of rise in CD4 suggests the possibility that early, mild subclinical deficits may also benefit from treatment. PMID:25750072

  17. CD4+ T cell-dependent and CD4+ T cell-independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals.

    PubMed

    Arnold, Kelly B; Szeto, Gregory L; Alter, Galit; Irvine, Darrell J; Lauffenburger, Douglas A

    2015-10-20

    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 CD4(+) T cell-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 lipopolysaccharide to stimulate innate immune cells) enabled integrative analysis of secreted profiles. Two major effects in HIV(+) PBMCs were not reproduced upon depletion of CD4(+) T cells in healthy PBMCs: (i) HIV(+) PBMCs maintained T cell-associated secreted profiles after T cell stimulation; (ii) HIV(+) PBMCs showed impaired interferon-γ (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 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

  18. The “Buruli Score”: Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon

    PubMed Central

    Mueller, Yolanda K.; Bastard, Mathieu; Nkemenang, Patrick; Comte, Eric; Ehounou, Geneviève; Eyangoh, Sara; Rusch, Barbara; Tabah, Earnest Njih; Trellu, Laurence Toutous; Etard, Jean-Francois

    2016-01-01

    Background Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. Methododology/Principal Findings Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0–98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2–84.7). Patients with intermediate BU probability needed to be tested by PCR. Conclusions/Significance We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use. PMID:27045293

  19. 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

  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. 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...

  2. 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...

  3. 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...

  4. Pre-Arrival Management of Newly Received Beef Calves With or Without Exposure to a Persistently Infected Bovine Viral Diarrhea Virus Type I Calf Affects Health, Performance, BVDV Type I Titers, and Circulating Leukocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a major culprit in the development of BRD either directly via acute clinical disease or through indirect effects of immunosuppression. Calves born persistently infected (PI) with BVDV are the primary vector for introduction of the virus into herds or productio...

  5. Serum Zinc Concentration and C-Reactive Protein in Individuals with Human Immunodeficiency Virus Infection: the Positive Living with HIV (POLH) Study.

    PubMed

    Poudel, Krishna C; Bertone-Johnson, Elizabeth R; Poudel-Tandukar, Kalpana

    2016-05-01

    Low zinc levels and chronic inflammation are common in individuals infected with human immunodeficiency virus (HIV). Zinc deficiency may promote systemic inflammation, but research on the role of zinc in inflammation among HIV-positive individuals taking account of anti-retroviral therapy is lacking. We assessed the association between serum zinc and C-reactive protein (CRP) concentration in a cohort of HIV-positive individuals. A cross-sectional survey was conducted among 311 HIV-positive individuals (177 men and 134 women) aged 18-60 years residing in Kathmandu, Nepal. High-sensitive or regular serum CRP concentrations were measured by the latex agglutination nephelometry or turbidimetric method, and zinc concentrations were measured by the atomic absorption method. Relationships were assessed using multiple linear regression analysis. The geometric means of zinc in men and women were 73.83 and 71.93 ug/dL, respectively, and of CRP were 1.64 and 0.96 mg/L, respectively. Mean serum CRP concentration was significantly decreased with increasing serum zinc concentration across zinc tertiles (P for trend = 0.010), with mean serum CRP concentration in the highest tertile of serum zinc concentration was 44.2 % lower than that in the lowest tertile. The mean serum CRP concentrations in men and women in the highest tertile of serum zinc concentrations were 30 and 35.9 % lower, respectively, than that in the lowest tertile (P for trend = 0.263 and 0.162, respectively). We found a significant inverse relation between log zinc and log CRP concentrations (beta for 1 unit change in log zinc; β = -1.79, p = 0.0003). Serum zinc concentration may be inversely associated with serum CRP concentration in HIV-positive individuals. PMID:26429417

  6. 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

  7. Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.

    PubMed

    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

  8. Polymorphisms of CUL5 are associated with CD4+ T cell loss in HIV-1 infected individuals.

    PubMed

    An, Ping; Duggal, Priya; Wang, Li Hua; O'Brien, Stephen J; Donfield, Sharyne; Goedert, James J; Phair, John; Buchbinder, Susan; Kirk, Gregory D; Winkler, Cheryl A

    2007-01-26

    Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters of evolutionarily related haplotypes. Cox survival analysis and mixed effects models were used to assess time to AIDS outcomes and CD4(+) T cell trajectories, respectively. Relative to cluster I haplotypes, the collective cluster II haplotypes were associated with more rapid CD4(+) T cell loss (relative hazards [RH] = 1.47 and p = 0.009), in a dose-dependent fashion. This effect was mainly attributable to a single cluster II haplotype (Hap10) (RH = 2.49 and p = 0.00001), possibly due to differential nuclear protein-binding efficiencies of a Hap10-specifying SNP as indicated by a gel shift assay. Consistent effects were observed for CD4(+) T cell counts and HIV-1 viral load trajectories over time. The findings of both functional and genetic epidemiologic consequences of CUL5 polymorphism on CD4(+) T cell and HIV-1 levels point to a role for Cullin 5 in HIV-1 pathogenesis and suggest interference with the Vif-Cullin 5 pathway as a possible anti-HIV-1 therapeutic strategy. PMID:17257057

  9. 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

  10. Host Genetic Factors and Dendritic Cell Responses Associated with the Outcome of Interferon/Ribavirin Treatment in HIV-1/HCV Co-Infected Individuals

    PubMed Central

    Sehgal, Mohit; Zeremski, Marija; Talal, Andrew H.; Khan, Zafar K.; Capocasale, Renold; Philip, Ramila; Jain, Pooja

    2015-01-01

    HIV-1/HCV co-infection is a significant health problem. Highly active antiretroviral treatment (HAART) against HIV-1 has proved to be fairly successful. On the other hand, direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns. Therefore PEGylated interferon (PEG-IFN) and ribavirin (RBV) still remain essential components of HCV treatment, and identification of host factors that predict IFN/RBV treatment response is necessary for effective clinical management of HCV infection. Impaired dendritic cell (DC) and T cell responses are associated with HCV persistence. It has been shown that IFN/RBV treatment enhances HCV-specific T cell functions and it is likely that functional restoration of DCs is the underlying cause. To test this hypothesis, we utilized an antibody cocktail (consisting of DC maturation, adhesion and other surface markers) to perform comprehensive phenotypic characterization of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in a cohort of HIV-1/HCV co-infected individuals undergoing IFN/RBV treatment. Our results show that pre-treatment frequencies of mDCs are lower in non-responders (NRs) compared to responders (SVRs) and healthy controls. Although, the treatment was able to restore the frequency of mDCs in NRs, it downregulated the frequency of CCR7+, CD54+ and CD62L+ mDCs. Pre-treatment frequencies of pDCs were lower in NRs and decreased further upon treatment. Compared to SVRs, NRs exhibited higher ratio of PD-L1+/CD86+ pDCs prior to treatment; and this ratio remained high even after treatment. These findings demonstrate that enumeration and phenotypic assessment of DCs before/during therapy can help predict the treatment outcome. We also show that before treatment, PBMCs from SVRs secrete higher amounts of IFN-γ compared to controls and NRs. Upon genotyping IFNL3 polymorphisms rs12979860, rs4803217 and ss469415590, we found rs12979860 to be a better predictor of

  11. 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

  12. Mathematical analysis and modeling of epidemics of rubber tree root diseases: Probability of infection of an individual tree

    SciTech Connect

    Chadoeuf, J.; Joannes, H.; Nandris, D.; Pierrat, J.C.

    1988-12-01

    The spread of root diseases in rubber tree (Hevea brasiliensis) due to Rigidoporus lignosus and Phellinus noxius was investigated epidemiologically using data collected every 6 month during a 6-year survey in a plantation. The aim of the present study is to see what factors could predict whether a given tree would be infested at the following inspection. Using a qualitative regression method we expressed the probability of pathogenic attack on a tree in terms of three factors: the state of health of the surrounding trees, the method used to clear the forest prior to planting, and evolution with time. The effects of each factor were ranked, and the roles of the various classes of neighbors were established and quantified. Variability between successive inspections was small, and the method of forest clearing was important only while primary inocula in the soil were still infectious. The state of health of the immediate neighbors was most significant; more distant neighbors in the same row had some effect; interrow spread was extremely rare. This investigation dealt only with trees as individuals, and further study of the interrelationships of groups of trees is needed.

  13. 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. PMID:26890368

  14. Regulation of Gag- and Env-Specific CD8+ T Cell Responses in ART-Naïve HIV-Infected Patients: Potential Implications for Individualized Immunotherapy

    PubMed Central

    Prebensen, Christian; Lind, Andreas; Dyrhol-Riise, Anne-Ma; Kvale, Dag

    2016-01-01

    Strategies to develop a functional cure for HIV infection will likely require boosting of effector T cell responses to eliminate reactivated, latently infected cells. We have recently explored an assay for assessing antigen-specific regulation of T cell proliferation, which was related to clinical progression in untreated patients and to vaccine efficacy in two trials of therapeutic Gag-based vaccines. We here expand the same assay to further investigate regulation mediated by various inhibitory pathways. Peripheral blood mononuclear cells from 26 asymptomatic HIV-infected, antiretroviral therapy-naïve patients were stimulated with Gag and Env overlapping peptide panels for 5 days. Monoclonal antibodies (mAbs) blocking inhibitory mediators interleukin (IL) 10, transforming growth factor (TGF) β, programmed death ligand (PD–L) 1 and herpes virus entry mediator (HVEM) were added to parallel cultures. Functional T cell regulation (FTR) was defined as the difference in proliferation between stimulated cultures with and without blocking mAbs. FTR was detected in 54% of patients. Blockade of IL-10/PD-L1 and IL10/TGF-β detected all cases with Gag- and Env-associated FTR, respectively. In accordance with previous findings, isolated Env FTR was associated with higher plasma HIV RNA and lower CD4 counts, while patients with both Gag and Env FTR also had higher Gag- and Env-specific proliferative CD8+ T cell responses. There was no association between FTR and frequencies of activated regulatory T cells. In conclusion, we observed substantial heterogeneity in FTR between patients, inhibitory pathways and HIV antigens. FTR may help to individualize immunomodulation and warrants further assessment in clinical immunotherapy trials. PMID:27128502

  15. Boosted Lopinavir– Versus Boosted Atazanavir–Containing Regimens and Immunologic, Virologic, and Clinical Outcomes: A Prospective Study of HIV-Infected Individuals in High-Income Countries

    PubMed Central

    2015-01-01

    Background. Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience. Methods. We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004–2013. Antiretroviral therapy–naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the ‘intention-to-treat’ effect for atazanavir vs lopinavir regimens on each of the outcomes. Results. A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53–.91) for death, 0.67 (95% CI, .55–.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84–.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, −.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone. Conclusions. Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens. PMID:25567330

  16. 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

  17. 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

  18. 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. PMID:26572059

  19. 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

  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. 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.

  2. Depression is not an Inevitable Outcome of Disclosure Avoidance: HIV Stigma and Mental Health in a Cohort of HIV Infected Individuals from Southern India

    PubMed Central

    Steward, Wayne T.; Chandy, Sara; Singh, Girija; Panicker, Siju Thomas; Osmand, Thomas A.; Heylen, Elsa; Ekstrand, Maria L.

    2010-01-01

    Previous research has shown that HIV stigma in India can be characterized by a framework dividing manifestations into enacted (discrimination), vicarious (hearing stories of discrimination), felt normative (perceptions of stigma’s prevalence) and internalized stigma (personal endorsement of stigma beliefs). We examined if this framework could explain associations among stigma, efforts to avoid HIV serostatus disclosure, and depression symptoms in a cohort of 198 HIV-infected individuals from southern India who were followed for one year as part of a study of antiretroviral adherence. Prior studies had suggested that disclosure avoidance was a primary outcome of stigma and that impaired well-being was a primary outcome of disclosure avoidance. Analyses from our longitudinal research revealed that the pattern of associations among stigma, disclosure avoidance, and depression symptoms remained consistent over time. Enacted and vicarious stigmas were correlated with felt normative stigma beliefs. In turn, felt normative stigma was correlated with disclosure avoidance. And enacted stigma, internalized stigma, and disclosure avoidance were all associated with depression symptoms. However, even though the overall framework held together, internalized stigma and depression symptoms dropped significantly over time while other components remained unchanged. These findings suggest that, although HIV stigma may limit disclosure, it does not invariably lead to psychological maladjustment. Amidst ongoing perceptions and experiences of stigma, HIV-positive individuals can achieve significant improvements in their acceptance of the disease and in mental wellbeing. PMID:21218366

  3. Depression is not an inevitable outcome of disclosure avoidance: HIV stigma and mental health in a cohort of HIV-infected individuals from Southern India.

    PubMed

    Steward, Wayne T; Chandy, Sara; Singh, Girija; Panicker, Siju T; Osmand, Thomas A; Heylen, Elsa; Ekstrand, Maria L

    2011-01-01

    Previous research has shown that HIV stigma in India can be characterized by a framework dividing manifestations into enacted (discrimination), vicarious (hearing stories of discrimination), felt normative (perceptions of stigma's prevalence), and internalized stigma (personal endorsement of stigma beliefs). We examined whether this framework could explain associations among stigma, efforts to avoid HIV serostatus disclosure, and depression symptoms in a cohort of 198 HIV-infected individuals from Southern India who were followed up for one year as part of a study of antiretroviral adherence. Prior studies had suggested that disclosure avoidance was a primary outcome of stigma and that impaired well-being was a primary outcome of disclosure avoidance. Analyses from our longitudinal research revealed that the pattern of associations among stigma, disclosure avoidance, and depression symptoms remained consistent over time. Enacted and vicarious stigmas were correlated with felt normative stigma beliefs. In turn, felt normative stigma was correlated with disclosure avoidance. And, enacted stigma, internalized stigma, and disclosure avoidance were all associated with depression symptoms. However, even though the overall framework held together, internalized stigma and depression symptoms dropped significantly over time while other components remained unchanged. These findings suggest that, although HIV stigma may limit disclosure, it does not invariably lead to psychological maladjustment. Amidst ongoing perceptions and experiences of stigma, HIV-positive individuals can achieve significant improvements in their acceptance of the disease and in mental well-being. PMID:21218366

  4. Individual Differences in Self-Regulatory Failure and Menstrual Dysfunction Predict Upper Respiratory Infection Symptoms and Antibody Response to Flu Immunization

    PubMed Central

    Strauman, Timothy J.; Coe, Christopher L.; McCrudden, Megan C.; Vieth, Angela Z.; Kwapil, Lori

    2008-01-01

    Prior research indicates that cognitive priming manipulations that activate personal goals acutely increase or decrease natural killer cell cytotoxicity depending on whether individuals see themselves as making or failing to make progress toward their goals. Those findings in a laboratory setting revealed a psychobiological pathway whereby experiences of failure can influence health, but did not assess the impact of chronic perceived success/failure in goal pursuit on actual health outcomes. Three new studies investigated whether individual differences in perceived failure to attain personal goals influenced the self-reported symptoms of upper respiratory infections (URIs) as well as antibody response to flu immunization. Based on pilot data in young women, it also was hypothesized that the occurrence of menstrual dysfunction might interact with goal pursuit failure to more specifically predict cold and flu symptoms and optimal responses to vaccination. Perceived failure to attain goals did predict the reporting of URI symptoms as well as antibody levels post-immunization, both alone and in combination with menstrual dysfunction. PMID:18294813

  5. 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

  6. Tracking the Extent of Multi-Strain Infection of Individual Northern Corn Rootworms (Diabrotica barberi) Using Specific Primers for Different wsp Hypervariable Regions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The northern corn rootworm (Diabrotica barberi) in eastern and central North America exhibits at least three distinct populations with respect to Wolbachia infection: uninfected; singly-infected; multi-infected. The infected states are associated with different mtDNA haplotypes and reduced mt variab...

  7. Wolbachia wsp gene clones detect the distribution of Wolbachia variants and wsp hypervariable regions among individuals of a multistrain infected population of Diabrotica barberi (Coleoptera: Chrysomelidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The northern corn rootworm (Diabrotica barberi) in eastern and central North America exhibits at least three distinct populations with respect to Wolbachia infection: uninfected; singly-infected; multi-infected. The infected states are associated with different mtDNA haplotypes and reduced mtDNA var...

  8. 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

  9. KLRG1 impairs CD4+ T cell responses via p16ink4a and p27kip1 pathways - Role in hepatitis B vaccine failure in individuals with hepatitis C virus infection

    PubMed Central

    Shi, Lei; Wang, Jia M.; Ren, Jun P.; Cheng, Yong Q.; Ying, Ruo S.; Wu, Xiao Y.; Lin, Shu M.; Griffin, Jeddidiah WD; Li, Guang Y.; Moorman, Jonathan P.; Yao, Zhi Q.

    2014-01-01

    Co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. HBV vaccine responses in HCV-infected individuals, however, are often blunted when compared to uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in regulation of CD4+ T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was over-expressed on CD4+ T cells from HCV-infected, HBV vaccine non-responders (HBV-NR) compared to those responders (HBV-R). The capacity of CD4+ T cell to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement of CD4+ T cell proliferation and IL-2 production in HCV-infected, HBV-NR in response to T cell receptor (TCR) stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser473) and decreased the expression of cell cycle inhibitors p16ink4a and p27kip1, which subsequently enhanced CDK 2 and cyclin E expressions. These results suggest that the KLRG1 pathway impairs CD4+ T cell responses to neo-antigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection. PMID:24337749

  10. 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. PMID:26047187

  11. 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

  12. 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

  13. Creating a Positive School Culture in Newly Opened Schools

    ERIC Educational Resources Information Center

    Holmes, Michael Todd

    2009-01-01

    The purpose of this study was to determine the most effective practices by school administrators when creating school culture in newly opened schools. Using semi-structured interviews, four principals who opened a new school were interviewed individually and in a focus group. The constant comparative method was used to analyze the data. Two themes…

  14. KLRG1 impairs CD4+ T cell responses via p16ink4a and p27kip1 pathways: role in hepatitis B vaccine failure in individuals with hepatitis C virus infection.

    PubMed

    Shi, Lei; Wang, Jia M; Ren, Jun P; Cheng, Yong Q; Ying, Ruo S; Wu, Xiao Y; Lin, Shu M; Griffin, Jeddidiah W D; Li, Guang Y; Moorman, Jonathan P; Yao, Zhi Q

    2014-01-15

    Coinfection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. However, HBV vaccine responses in HCV-infected individuals are often blunted compared with uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in the regulation of CD4(+) T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was overexpressed on CD4(+) T cells from HCV-infected, HBV vaccine nonresponders compared with HBV vaccine responders. The capacity of CD4(+) T cells to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement in CD4(+) T cell proliferation and IL-2 production in HCV-infected, HBV vaccine nonresponders in response to TCR stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser(473)) and decreased the expression of cell cycle inhibitors p16(ink4a) and p27(kip1), which subsequently enhanced the expression of cyclin-dependent kinase 2 and cyclin E. These results suggest that the KLRG1 pathway impairs CD4(+) T cell responses to neoantigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative-signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection. PMID:24337749

  15. Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users

    PubMed Central

    Moore, David J.; Montoya, Jessica L.; Blackstone, Kaitlin; Depp, Colin A.; Atkinson, J. Hampton; TMARC Group, The

    2013-01-01

    The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART) adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB), n = 20) were compared to those in the active comparison condition (n = 9). Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P < 0.05). The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277. PMID:24078868

  16. A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens

    PubMed Central

    Baumann, Ralf; Kaempfer, Susanne; Chegou, Novel N.; Oehlmann, Wulf; Spallek, Ralf; Loxton, André G.; van Helden, Paul D.; Black, Gillian F.; Singh, Mahavir; Walzl, Gerhard

    2015-01-01

    Elevated antibody responses to Mycobacterium tuberculosis antigens in individuals with latent infection (LTBI) have previously been linked to an increased risk for progression to active disease. Studies in the field focussed mainly on IgG antibodies. In the present study, IgA and/or IgG responses to the mycobacterial protein antigens AlaDH, NarL, 19 kDa, PstS3, and MPT83 were determined in a blinded fashion in sera from 53 LTBI controls, 14 healthy controls, and 42 active TB subjects. Among controls, we found that elevated IgA levels against all investigated antigens were not randomly distributed but concentrated on a subgroup of <30%—with particular high levels in a small subgroup of ~5% comprising one progressor to active TB. Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls. In conclusion, the consistently elevated IgA levels in a subgroup of controls suggest higher mycobacterial load, a risk factor for progression to active TB, and together with high IgG levels may have prognostic potential and should be investigated in future large scale studies. The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases. PMID:26347586

  17. 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

  18. Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users.

    PubMed

    Moore, David J; Montoya, Jessica L; Blackstone, Kaitlin; Rooney, Alexandra; Gouaux, Ben; Georges, Shereen; Depp, Colin A; Atkinson, J Hampton; Tmarc Group, The

    2013-01-01

    The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART) adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB), n = 20) were compared to those in the active comparison condition (n = 9). Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P < 0.05). The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277. PMID:24078868

  19. 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

  20. 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

  1. 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, and peripheral blood leukocytes.

    PubMed

    Richeson, J T; Kegley, E B; Powell, J G; Beck, P A; Ley, B L Vander; Ridpath, J F

    2012-06-01

    Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation of cohorts that may have health and growth consequences; however, effects may differ in low-risk, preconditioned (PC) vs. high-risk, auction market (AM) beef cattle. Our objective was to compare health and performance of PC or AM management systems with (PI) or without (CON) presence of a PI-BVDV pen mate using a 2 × 2 factorial arrangement. Four shipment blocks of crossbred PC steers (n = 236) from 3 ranch-origins were weaned, dewormed, vaccinated, tested for PI-BVDV, and kept on the ranch for ≥42 d. Subsequently, PC steers were transported to a stocker receiving unit (RU), weighed (251 ± 2 kg), blood sampled, stratified by d -1 BW, and assigned randomly to treatment (PCPI or PCCON) with no additional processing. Simultaneously, 4 blocks of crossbred AM calves (n = 292) were assembled from regional auction markets and transported to the RU ± 36 h from PC arrival. The AM calves were weighed (245 ± 1.3 kg), stratified by gender and d -1 BW, processed under the same regimen used for PC steers at their origin ranch except bull calves were castrated, and then assigned randomly to treatment (AMPI or AMCON). Treatment pens (0.45 ha) were arranged spatially such that PI did not have fence-line or water source contact with CON. Calves were fed identically and followed the same antibiotic treatment protocol. Daily BW gain for the entire 42-d receiving trial was greater (P < 0.001) for PC (1.2 kg) compared with AM (0.85 kg). There was an exposure effect (P = 0.002) on ADG from d 28 to 42; CON gained 1.12 kg vs. 0.90 kg BW for PI cohort. Morbidity was markedly greater (P < 0.001) in AM (70%) vs. PC (7%), resulting in (P < 0.001) an antibiotic treatment cost of $20.52 and $2.48/animal, respectively. Treatment with a third antibiotic occurred more often (P = 0.04) for PI cohort, and the percentage of chronically ill cattle was greatest (P = 0.06) for AMPI

  2. [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

  3. 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

  4. 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. PMID:26631832

  5. 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

  6. 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

  7. 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

  8. Glomerular filtration rate estimated by creatinine, cystatin C, or both markers and the risk of clinical events in HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.; Cozzi-Lepri, Alessandro; Wyatt, Christina M.; Post, Frank A.; Bormann, Alison M.; Crum-Cianflone, Nancy F.; Ross, Michael J.

    2013-01-01

    Background The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFRcr), cystatin C (GFRcys), and the combination of these markers (GFRcr-cys) has recently been assessed in HIV-infected individuals. Methods We compared the associations of baseline GFRcr, GFRcys, and GFRcr-cys (using the CKD-EPI equations) with mortality, cardiovascular events (CVE), and opportunistic diseases (OD) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR. Results 4,614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFRcys was weakly to moderately correlated with HIV RNA, CD4 cell count, high sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFRcr had little or no correlation with these factors. GFRcys had the strongest associations with the three clinical outcomes, followed closely by GFRcr-cys, with GFRcr having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors, and inflammation markers, a 1-SD lower GFRcys was associated with a 55% (95% confidence interval [CI], 27% -90%) increased risk of mortality, a 21% (95% CI, 0% -47%) increased risk of CVE, and a 22% (95% CI, 0% -48%) increased risk of OD. Conclusions Of the three CKD-EPI GFR equations, GFRcys had the strongest associations with mortality, CVE, and OD. PMID:24024499

  9. 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

  10. 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

  11. Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

    PubMed

    Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

    2013-03-01

    Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA <500 copies/ml) and time to failure (>500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B. PMID:23034083

  12. 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

  13. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  14. A screen-and-treat strategy targeting visceral leishmaniasis in HIV-infected individuals in endemic East African countries: the way forward?

    PubMed

    van Griensven, Johan; Diro, Ermias; Lopez-Velez, Rogelio; Ritmeijer, Koert; Boelaert, Marleen; Zijlstra, Ed E; Hailu, Asrat; Lynen, Lutgarde

    2014-08-01

    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

  15. Newly Diagnosed Acute Promyelocytic Leukemia

    PubMed Central

    Avvisati, Giuseppe

    2011-01-01

    Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA, targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years, rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome. Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up. PMID:22220261

  16. [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. PMID:23541879

  17. Spinach curly top virus: A Newly Described Curtovirus Species from Southwest Texas with Incongruent Gene Phylogenies.

    PubMed

    Baliji, Surendranath; Black, Mark C; French, Roy; Stenger, Drake C; Sunter, Garry

    2004-07-01

    ABSTRACT A curtovirus associated with a disease of spinach was isolated in southwest Texas during 1996. Disease symptoms included severe stunting and chlorosis, with younger leaves curled, distorted, and dwarfed. Viral DNA was purified and an infectious clone obtained. Agroinoculation using a construct bearing full-length tandem repeats of the cloned viral genome resulted in systemic infection of species in six of seven plant families tested, indicating that the virus has a wide host range. Symptoms produced in spinach agroinoculated with cloned viral DNA were similar to those observed in the field. Viral single-stranded and double-stranded DNA forms typical of curtovirus infection were detected in host plants by Southern blot hybridization. The complete sequence of the infectious clone comprised 2,925 nucleotides, with seven open reading frames encoding proteins homologous to those of other curtoviruses. Complete genome comparisons revealed that the spinach curtovirus shared 64.2 to 83.9% nucleotide sequence identity relative to four previously characterized curtovirus species: Beet curly top virus, Beet severe curly top virus, Beet mild curly top virus, and Horseradish curly top virus. Phylogenetic analysis of individual open reading frames indicated that the evolutionary history of the three virion-sense genes was different from that of the four complementary-sense genes, suggesting that recombination among curtoviruses may have occurred. Collectively, these results indicate that the spinach curtovirus characterized here represents a newly described species of the genus Curtovirus, for which we propose the name Spinach curly top virus. PMID:18943911

  18. 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

  19. Pneumocystis jirovecii infection and the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations in HIV-positive individuals from Pune, India.

    PubMed

    Mane, Arati; Gujar, Pankaj; Chandra, Jipsi; Lokhande, Rahul; Dhamgaye, Tilak; Ghorpade, Shivhari; Risbud, Arun

    2015-02-01

    The present study was undertaken to detect Pneumocystis jirovecii infection among HIV-positive patients presenting with symptoms of lower respiratory tract infection and analyze the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations. P. jirovecii infection was detected in 12.6% cases. We did not find DHPS gene mutations at the commonest positions of codon 55 and 57; however, mutation at codon 171 was detected in two cases. No mutations in DHFR gene were detected. The results indicate low prevalence of DHPS and DHFR mutations in Indian P. jirovecii isolates, suggesting that the selective pressure of sulfa drugs on the local strains has probably not reached the levels found in developed nations. PMID:25266324

  20. 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

  1. [Molecular epidemiological characteristics of HIV-1 strains isolated from newly diagnosed MSM subjects (2006-2010) in Beijing, China].

    PubMed

    Ye, Jing-Rong; Zang, Wan-Chun; Su, Xue-Li; Lu, Hong-Yan; Hao, Ming-Qiang; Xin, Ruo-Lei; Chen, Guo-Min; He, Xiong; Zeng, Yi

    2014-03-01

    This study aims to analyze the molecular epidemiological characteristics of HIV-1 strains prevailing among men who have sex with men (MSM) in Beijing, China. The pol gene fragments from 250 newly diagnosed HIV-1-infected MSM individuals during 2006-2010 in Beijing were amplified by RT-nested PCR, sequenced, and phylogenetically analyzed. HIV-1 pol gene from 189 individuals were amplified and analyzed; 81 (42. 9%), 3 (1. 6%), 2 (1.0%), 88 (46. 6%), and 15 (7.9%) individuals were infected with HIV-1 subtypes B, B', C, CRF01_AE, and CRF07_BC, respectively. The subtypes B and CRF01_AE could both be grouped into two clusters, and CRFO7_BC strains shared high homology and were presumed to originate from a common ancestor. The HIV-1 circulating in MSM in Beijing had a lower genetic diversity than in heterosexuals. The HIV-1 epidemic (2006-2010) in MSM in Beijing was actually a rapid spread of HIV-1 CRF01 AE and B, or rather native strains of the two viruses. PMID:24923166

  2. Viral culture and p24 antigenemia of human immunodeficiency virus (HIV)-infected individuals correlated with antibody profiles determined with recombinant polypeptides of all HIV-1 open-reading frames.

    PubMed

    Baur, A; Vornhagen, R; Korn, K; Sonneborn, H H; Eberlein, B; Harrer, T; Brockhaus, W; Jahn, G

    1992-03-01

    The association between viral activity and antibody profiles was investigated in 202 individuals infected by the human immunodeficiency virus (HIV) grouped according to their Walter Reed clinical stage. Each study group was subdivided into subjects positive or negative for markers of active viral replication: presence of serum p24 antigen and viral culture. In Western blots using recombinant antigens, sera of HIV-positive individuals with positive viral markers had a significantly lower antibody reactivity to several viral proteins than did individuals without viral markers. Noticeably, proteins of the gag (p24, p17) and env (gp120, COOH-terminal part of gp41) open-reading frames revealed a decreased reactivity. The antibody response to the regulatory proteins revealed no or poor association with viral activity in the host. The results suggest that seroreactivity is mainly influenced by factors reflecting the viral activity of an HIV-infected individual, while the clinical stage of the patient is less important. Especially, reductions in antibodies against gp120 and p17 were useful markers associated with increased viral activity. PMID:1371534

  3. 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

  4. 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

  5. Identifying the major bacteria causing intramammary infections in individual milk samples of sheep and goats using traditional bacteria culturing and real-time polymerase chain reaction.

    PubMed

    Rovai, M; Caja, G; Salama, A A K; Jubert, A; Lázaro, B; Lázaro, M; Leitner, G

    2014-09-01

    Use of DNA-based methods, such as real-time PCR, has increased the sensitivity and shortened the time for bacterial identification, compared with traditional bacteriology; however, results should be interpreted carefully because a positive PCR result does not necessarily mean that an infection exists. One hundred eight lactating dairy ewes (56 Manchega and 52 Lacaune) and 24 Murciano-Granadina dairy goats were used for identifying the main bacteria causing intramammary infections (IMI) using traditional bacterial culturing and real-time PCR and their effects on milk performance. Udder-half milk samples were taken for bacterial culturing and somatic cell count (SCC) 3 times throughout lactation. Intramammary infections were assessed based on bacteria isolated in ≥2 samplings accompanied by increased SCC. Prevalence of subclinical IMI was 42.9% in Manchega and 50.0% in Lacaune ewes and 41.7% in goats, with the estimated milk yield loss being 13.1, 17.9, and 18.0%, respectively. According to bacteriology results, 87% of the identified single bacteria species (with more than 3 colonies/plate) or culture-negative growth were identical throughout samplings, which agreed 98.9% with the PCR results. Nevertheless, the study emphasized that 1 sampling may not be sufficient to determine IMI and, therefore, other inflammatory responses such as increased SCC should be monitored to identify true infections. Moreover, when PCR methodology is used, aseptic and precise milk sampling procedures are key for avoiding false-positive amplifications. In conclusion, both PCR and bacterial culture methods proved to have similar accuracy for identifying infective bacteria in sheep and goats. The final choice will depend on their response time and cost analysis, according to the requirements and farm management strategy. PMID:24996276

  6. 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. PMID:27508262

  7. 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

  8. 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

  9. Remodeling the Endoplasmic Reticulum by Poliovirus Infection and by Individual Viral Proteins: an Autophagy-Like Origin for Virus-Induced Vesicles

    PubMed Central

    Suhy, David A.; Giddings, Thomas H.; Kirkegaard, Karla

    2000-01-01

    All positive-strand RNA viruses of eukaryotes studied assemble RNA replication complexes on the surfaces of cytoplasmic membranes. Infection of mammalian cells with poliovirus and other picornaviruses results in the accumulation of dramatically rearranged and vesiculated membranes. Poliovirus-induced membranes did not cofractionate with endoplasmic reticulum (ER), lysosomes, mitochondria, or the majority of Golgi-derived or endosomal membranes in buoyant density gradients, although changes in ionic strength affected ER and virus-induced vesicles, but not other cellular organelles, similarly. When expressed in isolation, two viral proteins of the poliovirus RNA replication complex, 3A and 2C, cofractionated with ER membranes. However, in cells that expressed 2BC, a proteolytic precursor of the 2B and 2C proteins, membranes identical in buoyant density to those observed during poliovirus infection were formed. When coexpressed with 2BC, viral protein 3A was quantitatively incorporated into these fractions, and the membranes formed were ultrastructurally similar to those in poliovirus-infected cells. These data argue that poliovirus-induced vesicles derive from the ER by the action of viral proteins 2BC and 3A by a mechanism that excludes resident host proteins. The double-membraned morphology, cytosolic content, and apparent ER origin of poliovirus-induced membranes are all consistent with an autophagic origin for these membranes. PMID:10982339

  10. Human immunodeficiency virus type 1 strains in the lungs of infected individuals evolve independently from those in peripheral blood and are highly conserved in the C-terminal region of the envelope V3 loop.

    PubMed Central

    Itescu, S; Simonelli, P F; Winchester, R J; Ginsberg, H S

    1994-01-01

    To determine whether human immunodeficiency virus type 1 (HIV-1) strains in the lungs of infected individuals are derived from proviral forms contemporaneously present in the peripheral blood or whether they evolve independently as an autonomous pool of viral quasispecies, HIV-1 envelope V3 domain structures at these sites were analyzed and compared. The V3 loop proviral nucleotide and inferred amino acid sequences from lung bronchoalveolar lavage, where HIV-1 is primarily found in macrophages, were more homogeneous within individuals than those from unseparated peripheral blood mononuclear cells, where virus is predominantly in T cells. Comparison between individuals revealed that strains from bronchoalveolar lavage, but not from peripheral blood mononuclear cells, contained V3 domain nucleotide sequences with a great degree of homogeneity in the C-terminal region and a highly conserved, negatively charged amino acid motif. This V3 loop C-terminal structure could be important in the ability of HIV-1 to infect alveolar macrophages. Phylogenetic analyses of V3 domain nucleotide sequences in cells of monocyte/macrophage lineage at both sites revealed the strains in lung macrophages to have evolved further from a presumed ancestral species than those in blood monocytes and to differ considerably in the inferred V3 loop amino acid structures. These results show that, as disease progression occurs, viral strains in monocyte/macrophage lineage cells within the lung and blood microenvironments are not in a state of unrestricted bidirectional traffic but, instead, evolve independently. Images PMID:7972068

  11. Generational differences among newly licensed registered nurses.

    PubMed

    Keepnews, David M; Brewer, Carol S; Kovner, Christine T; Shin, Juh Hyun

    2010-01-01

    Responses of 2369 newly licensed registered nurses from 3 generational cohorts-Baby Boomers, Generation X, and Generation Y-were studied to identify differences in their characteristics, work-related experiences, and attitudes. These responses revealed significant differences among generations in: job satisfaction, organizational commitment, work motivation, work-to-family conflict, family-to-work conflict, distributive justice, promotional opportunities, supervisory support, mentor support, procedural justice, and perceptions of local job opportunities. Health organizations and their leaders need to anticipate intergenerational differences among newly licensed nurses and should provide for supportive working environments that recognize those differences. Orientation and residency programs for newly licensed nurses should be tailored to the varying needs of different generations. Future research should focus on evaluating the effectiveness of orientation and residency programs with regard to different generations so that these programs can be tailored to meet the varying needs of newly licensed nurses at the start of their careers. PMID:20494691

  12. 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

  13. Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

    PubMed Central

    Lang, Sylvie; Lacombe, Jean-Marc; Mary-Krause, Murielle; Partisani, Marialuisa; Bidegain, Frédéric; Cotte, Laurent; Aslangul, Elisabeth; Chéret, Antoine; Boccara, Franck; Meynard, Jean-Luc; Pradier, Christian; Roger, Pierre-Marie; Tattevin, Pierre; Costagliola, Dominique; Molina, Jean-Michel

    2015-01-01

    Background The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals. Methods Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated. Results Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights. Conclusion The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population. PMID:26200661

  14. 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

  15. Opportunistic fungal and bacterial infection in the renal transplant recipient.

    PubMed

    Tolkoff-Rubin, N E; Rubin, R H

    1992-06-01

    The risk of opportunistic infection in the renal transplant recipient is determined by the interaction between two factors: the epidemiologic exposures the individual encounters within the community and the hospital and a complex function termed the net state of immunosuppression. There are two general categories of opportunistic fungal infection in this patient population: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and (2) opportunistic infection with fungal species that rarely cause invasive infection in the normal host (Aspergillus species, Candida species, Cryptococcus neoformans, and the Mucoraceae), with these last usually being acquired within the hospital environment. Newly available azole compounds, fluconazole and itraconazole, are exciting new alternatives to amphotericin in the treatment of at least some of these infections. The three most important forms of opportunistic bacterial infections are those due to Listeria monocytogenes, Nocardia asteroides, and a variety of mycobacterial species. Clinical diseases with these first two are effectively prevented by low-dose trimethoprim-sulfamethoxazole prophylaxis. There are two cardinal therapeutic rules to be followed by clinicians in dealing with these infections: prevention is better than treatment; when treatment is required, however, the major determinant of the success of therapy is the rapidity with which the diagnosis is made and effective therapy is initiated. PMID:1498286

  16. Framework for controlling infection through isolation precautions in Japan.

    PubMed

    Kawakami, Kazumi; Misao, Hanako

    2014-03-01

    In Japan, nurses certified in infection control face organizational and structural challenges to the implementation of the recommended isolation precautions. In this study, we developed a conceptual framework for the problem-solving process of certified nurses in infection control when implementing appropriate isolation-precaution measures. We conducted a qualitative, descriptive study using directed content analysis. Semistructured interviews were conducted with 40 nurses who had over five years' experience in infection control. Factors assessing the risk of infection in patients were identified, including microorganism characteristics, patient characteristics, and risk of infection to the entire unit. The nurses also assessed the risk of infection in institutions from the following perspectives: organizational culture, infection control system, human resources, environment surrounding the facility, ethical issues, and external factors. Individual characteristics, such as attributes, knowledge, expertise, and job function, were identified as major influencing factors in the problem-solving process. These findings could be useful for newly-certified nurses in infection control and provide recommendations on implementing isolation-precaution measures. PMID:24635895

  17. 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

  18. Health status of newly arrived refugees in Toronto, Ont

    PubMed Central

    Redditt, Vanessa J.; Janakiram, Praseedha; Graziano, Daniela; Rashid, Meb

    2015-01-01

    Abstract Objective To determine the prevalence of selected infectious diseases among newly arrived refugee patients and whether there is variation by key demographic factors. Design Retrospective chart review. Setting Primary care clinic for refugee patients in Toronto, Ont. Participants A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. Main outcome measures Demographic information (age, sex, and region of birth); prevalence of HIV, hepatitis B, hepatitis C, Strongyloides, Schistosoma, intestinal parasites, gonorrhea, chlamydia, and syphilis infections; and varicella immune status. Results The median age of patients was 29 years and 56% were female. Refugees were born in 87 different countries. Approximately 33% of patients were from Africa, 28% were from Europe, 14% were from the Eastern Mediterranean Region, 14% were from Asia, and 8% were from the Americas (excluding 4% born in Canada or the United States). The overall rate of HIV infection was 2%. The prevalence of hepatitis B infection was 4%, with a higher rate among refugees from Asia (12%, P < .001). Hepatitis B immunity was 39%, with higher rates among Asian refugees (64%, P < .001) and children younger than 5 years (68%, P < .001). The rate of hepatitis C infection was less than 1%. Strongyloides infection was found in 3% of tested patients, with higher rates among refugees from Africa (6%, P = .003). Schistosoma infection was identified in 15% of patients from Africa. Intestinal parasites were identified in 16% of patients who submitted stool samples. Approximately 8% of patients were varicella nonimmune, with higher rates in patients from the Americas (21%, P < .001). Conclusion This study highlights the importance of screening for infectious diseases among refugee patients to provide timely preventive and curative care. Our data also point to possible policy and clinical implications, such as targeted screening approaches and improved access to vaccinations and

  19. Rapid progression to gummatous syphilitic hepatitis and neurosyphilis in a patient with newly-diagnosed HIV.

    PubMed

    Pilozzi-Edmonds, Laura; Kong, Ling Yuan; Szabo, Jason; Birnbaum, Leora M

    2015-11-01

    We review the literature on hepatic involvement in patients with HIV and syphilis co-infection and describe a case of rapid progression to neurosyphilis and presumed gummatous syphilitic hepatitis in a patient newly diagnosed with HIV. To our knowledge, this is the first case of syphilitic hepatitis with gummas described in the HIV population. PMID:25525055

  20. 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.

  1. Pattern of co-infection by enteric pathogenic parasites among HIV sero-positive individuals in a Tertiary Care Hospital, Mumbai, India

    PubMed Central

    Ahmed, Nishat Hussain; Chowdhary, Abhay

    2015-01-01

    Introduction: One of the major medical concerns in people living with HIV/AIDS (PLHA) is management of diarrhea that can lead to severe morbidity and mortality. Such clinical scenario warrants an analysis of intestinal parasites, which are important opportunistic pathogens in PLHA. Owing to the scarcity of recent pattern of intestinal opportunistic infections from this region, the study was designed to determine the opportunistic parasites causing diarrhea in PLHA; and to find out whether there is any significant difference in the enteric parasitic pathogens in patients with different immunological status and in those on highly active anti retro-viral therapy (HAART). Materials and Methods: Analysis of the spectrum of intestinal parasites was carried out with 192 subjects in two groups (142 HIV sero-positive patients having diarrhea and 50 HIV sero-negative patients having diarrhea). The routine light microscopic examination was carried out to determine the infection and CD4+ T-Lymphocyte count was estimated using flow cytometry. Results: Enteric parasites were detected in 35.9% of HIV sero-positive patients having diarrhea and 18% of HIV sero-negative patients having diarrhea. Most common opportunistic enteric parasite was Isospora belli (11.5%); others were Entamoeba histolytica (4.7%), Cryptosporidium sp. (3.6%), Strongyloides stercoralis (3.1%), Giardia intestinalis (3.1%) and Cyclospora cayatanenesis (1.6%). Opportunistic enteric parasites were detected in significantly low numbers in patients with CD4+ T-Lymphocyte counts >500 cells/ml; and in those taking HAART. PMID:26392653

  2. Contribution of Individual Ebp Pilus Subunits of Enterococcus faecalis OG1RF to Pilus Biogenesis, Biofilm Formation and Urinary Tract Infection

    PubMed Central

    Sillanpää, Jouko; Chang, Chungyu; Singh, Kavindra V.; Montealegre, Maria Camila; Nallapareddy, Sreedhar R.; Harvey, Barrett R.; Ton-That, Hung; Murray, Barbara E.

    2013-01-01

    The endocarditis and biofilm-associated pilus (Ebp) operon is a component of the core genome of Enterococcus faecalis that has been shown to be important for biofilm formation, adherence to host fibrinogen, collagen and platelets, and in experimental endocarditis and urinary tract infection models. Here, we created single and double deletion mutants of the pilus subunits and sortases; next, by combining western blotting, immunoelectron microscopy, and using ebpR in trans to increase pilus production, we identified EbpA as the tip pilin and EbpB as anchor at the pilus base, the latter attached to cell wall by the housekeeping sortase, SrtA. We also confirmed EbpC and Bps as the major pilin and pilin-specific sortase, respectively, both required for pilus polymerization. Interestingly, pilus length was increased and the number of pili decreased by deleting ebpA, while control overexpression of ebpA in trans restored wild-type levels, suggesting a dual role for EbpA in both initiation and termination of pilus polymerization. We next investigated the contribution of each pilin subunit to biofilm formation and UTI. Significant reduction in biofilm formation was observed with deletion of ebpA or ebpC (P<0.001) while ebpB was found to be dispensable; a similar result was seen in kidney CFUs in experimental UTI (ΔebpA, ΔebpC, P≤0.0093; ΔebpB, non-significant, each vs. OG1RF). Hence, our data provide important structural and functional information about these ubiquitous E. faecalis pili and, based on their demonstrated importance in biofilm and infection, suggest EbpA and EbpC as potential targets for antibody-based therapeutic approaches. PMID:23874774

  3. 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…

  4. HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality

    PubMed Central

    Serrano-Villar, Sergio; Sainz, Talia; Lee, Sulggi A.; Hunt, Peter W.; Sinclair, Elizabeth; Shacklett, Barbara L.; Ferre, April L.; Hayes, Timothy L.; Somsouk, Ma; Hsue, Priscilla Y.; Van Natta, Mark L.; Meinert, Curtis L.; Lederman, Michael M.; Hatano, Hiroyu; Jain, Vivek; Huang, Yong; Hecht, Frederick M.; Martin, Jeffrey N.; McCune, Joseph M.; Moreno, Santiago; Deeks, Steven G.

    2014-01-01

    A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28− and CD57+CD28−), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions. PMID:24831517

  5. 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