Leslie Nielsen

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa

The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.

HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda.

Objectives Recent publications suggest that fishing populations may be highly affected by the HIV epidemic. However, accurate data are scarce. The authors determined HIV and syphilis prevalence and associated risk factors in a fishing population of Lake Victoria in Uganda. Methods 10 188 volunteers aged ≥13 years from a census carried out in five fishing communities between February and August 2009 were invited to attend central study clinics established in each community. After informed consent, 2005 randomly selected volunteers responded to socio-demographic and risk assessment questions, provided blood for HIV testing and 1618 volunteers were also tested for syphilis. Risk factors were analysed using logistic regression. Results HIV and active syphilis (rapid plasma reagin titre ≥1:8) prevalences were 28.8% (95% CI 26.8 to 30.8) and 4.3% (95% CI 3.3 to 5.4), respectively, and high risk sexual behaviour was frequently reported. HIV prevalence was independently associated with female sex, increasing age, occupation (highest in fishermen), relationship to household head, self-reported genital sores and knowledge of an HIV infected partner. Alcohol consumption, syphilis and sexually transmitted infections (STIs) reported by health workers were associated with HIV in women, and genital discharge and inconsistent condom use in men. Syphilis prevalence was independently associated with age and alcohol consumption in women, and recent genital sores and sex under the influence of drugs in men. Conclusion This fishing population characterised by a very high HIV prevalence, high syphilis prevalence and frequently reported sexual risk behaviours, urgently needs improved STI services and targeted behavioural interventions.

High HIV incidence and socio-behavioral risk patterns in fishing communities on the shores of Lake Victoria, Uganda.

Background: We report on HIV acquisition and its associated risk factors in 5 fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000 HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and followed up for 18 months. Methods: At enrollment and semiannual visits, socio-demographic and risk behavior data were collected through a structured questionnaire and blood samples tested for HIV and syphilis. Detailed life histories were collected from 78 volunteers using in-depth interviews. Results: Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%) reaching the study end points (either seroconverted or completed 4 visits). There were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV incidence rates were among those working in bars (9.8/100 PYAR [4.7–20.6]), protestants (8.6/100 PYAR [5.8–12.7]), those aged 13 to 24 years (7.5/100 PYAR [5.2–11.0]), and new immigrants (6.6/100 PYAR [4.9–8.9]). HIV infection was independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95% CI = 1.3–4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6–5.0]), regular alcohol consumption (aHR = 3.3 [1.6–6.1]), use of marijuana (aHR = 2.9 [1.0–8.0]), cigarette smoking (aHR = 3.6 [1.4–9.3]), and religion (compared with Catholics, Protestants had aHR = 2.7 [1.4–5.3] and Muslims had aHR = 2.3 [1.1–4.8]). Conclusions: These fishing communities experienced high HIV infection, which was mainly explained by high-risk behavior. There is an urgent need to target HIV prevention and research efforts to this vulnerable and neglected group.

High Incidence of HIV-1 Infection in a General Population of Fishing Communities around Lake Victoria, Uganda

Background High HIV-1 incidence rates were reported among persons in fisherfolk communities (FFC) in Uganda who were selected for high risk behaviour. We assessed the incidence of HIV-1 and associated risk factors in a general population FFC to determine population-wide HIV rates. Methods A community-based cohort study was conducted among a random sample of 2191 participants aged 18–49 years. At baseline and 12 months post-baseline, data were collected on socio-demographic characteristics and risky behaviors (including number of partners, new partners, condom use, use of alcohol and illicit drug use). Venous blood was collected for HIV serological testing. HIV incidence was calculated per 100 person years at-risk (pyar) and adjusted incidence rate ratios (Adj.IRR) were estimated by multivariable Poisson regression. Results Overall follow up at 12 months was 76.9% (1685/2191) and was significantly higher among HIV uninfected persons and those with at least 1 year duration of stay in community. Overall HIV-1 incidence was 3.39/100 pyar (95% CI: 2.55–4.49). Among the 25–29 years who drank alcohol, HIV incidence was 7.67/100pyar (95% CI;4.62–12.7) while it was 5.67/100pyar (95% CI;3.14–10.2) for 18–24 year olds who drank alcohol. The risk of HIV infection was higher among 25–29 years (adj.IRR = 3.36; 95% CI: 1.48–7.65) and 18–24 years (adj.IRR = 2.65; 95% CI: 1.05–6.70) relative to 30+ years. Compared to non-drinkers, HIV incidence increased by frequency of alcohol drinking - occasional drinkers (adj.IRR = 3.18; 95% CI: 1.18–8.57) and regular drinkers (adj.IRR = 4.93; 95% CI: 1.91–12.8). Conclusion HIV-1 incidence in general fisherfolk population along L.Victoria, Uganda, is high and is mainly associated with young age and alcohol drinking. HIV prevention and control strategies are urgently needed in this population.

High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria, Uganda

HIV epidemics in sub‐Saharan Africa are generalized, but high‐risk subgroups exist within these epidemics. A recent study among fisher‐folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person‐years). However, those findings may not reflect population‐wide HIV rates in FFC since the study population was selected for high‐risk behaviour.

Characterization of Neutrophil Subsets in Healthy Human Pregnancies

We have previously shown that in successful pregnancies increased arginase activity is a mechanism that contributes to the suppression of the maternal immune system. We identified the main type of arginase-expressing cells as a population of activated low-density granulocytes (LDGs) in peripheral blood mononuclear cells and in term placentae. In the present study, we analyzed the phenotype of LDGs and compared it to the phenotype of normal density granulocytes (NDGs) in maternal peripheral blood, placental biopsies and cord blood. Our data reveal that only LDGs but no NDGs could be detected in placental biopsies. Phenotypically, NDGs and LDGs from both maternal and cord blood expressed different levels of maturation, activation and degranulation markers. NDGs from the maternal and cord blood were phenotypically similar, while maternal, cord and placental LDGs showed different expression levels of CD66b. LDGs present in cord blood expressed higher levels of arginase compared to maternal and placental LDGs. In summary, our results show that in maternal and cord blood, two phenotypically different populations of neutrophils can be identified, whereas in term placentae, only activated neutrophils are present.

Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria, Uganda: a nested case–control study

It has been suggested that Schistosoma mansoni, which is endemic in African fishing communities, might increase susceptibility to human immunodeficiency virus (HIV) acquisition. If confirmed, this would be of great public health importance in these high HIV‐risk communities. This study was undertaken to determine whether S. mansoni infection is a risk factor for HIV infection among the fishing communities of Lake Victoria, Uganda. We conducted a matched case–control study, nested within a prospective HIV incidence cohort, including 50 HIV seroconverters (cases) and 150 controls during 2009‐2011.

Are fishing communities another most-at-risk- population? Results of a community-based study along Lake Victoria, Uganda

Background A recent study reported HIV prevalence of 28.8% among high risk persons in fishing communities (FC) of Uganda, indicating that FC may be another most-at-risk-population (MARP). However, these findings do not reflect the population-based HIV prevalence in FC. We conducted a community-based study to determine the population representative HIV prevalence and incidence among FC along Lake Victoria shores, Uganda. Methods

Use of Modern Family Planning Methods in Fishing Communities of Lake Victoria, Uganda.

Introduction Fishing communities (FCs) in Uganda have high HIV infection rates but poor access to health services including family planning (FP). Although FP is a cost-effective public health intervention, there is a paucity of data on knowledge and use of modern FP in FCs. This study determined knowledge and use of modern FP methods in FCs of Uganda. Methods Data were accrued from a 12-month follow up of 1,688 HIV-uninfected individuals, 18–49 years from 8 FCs along Lake Victoria, between September 2011 and March 2013. Data on knowledge and use of modern FP were collected through a semi-structured questionnaire. Prevalence Risk Ratios with corresponding 95% CIs were used to determine factors associated with Modern FP knowledge and use. Results The mean age was 31.4 years, with nearly half (48.8%) being females while more than half (58.6%) had attained up to primary education level. Knowledge of modern FP was high, 87.5% (1477/1688); significantly higher among females [adj. PRR = 4.84 (95% CI; 3.08, 7.61)], among older respondents (25–29 years) [adj. PRR = 1.83 (95% CI; 1.12, 2.99)] compared to younger ones (18–24 years) and among those conducting business [adj. PRR = 2.42(95% CI; 1.02, 5.74)] relative to those primarily in fishing. Just over a third (35.2%, 595/1688) reported use of at least one modern FP method. Use of modern FP methods was significantly higher among females [adj. PRR = 2.04 (95% CI; 1.56, 2.65, and among those reporting multiple sexual partnerships [adj. PRR = 2.12, 95% CI; 1.63, 2.76)]. Nonuse of modern methods was mostly due to desire for more children (30.6%), fear of side effects (12.2%) and partner refusal (5.2%). Conclusion Despite their high knowledge of FP, FCs have low use of modern FP methods. Key barriers to use of modern FP methods were high fertility desires, fear of perceived side effects and partner refusal of methods.

Schistosoma mansoni Infection in Ugandan Men Is Associated with Increased Abundance and Function of HIV Target Cells in Blood, but Not the Foreskin: A Cross-sectional Study.

Background Schistosoma mansoni infection has been associated with an increased HIV prevalence in humans and SHIV incidence in primate models. We hypothesized that immune activation from this gastrointestinal mucosa infection would increase highly HIV-susceptible CD4 T cell subsets in the blood and the foreskin through common mucosal homing. Methodology/Principal Findings Foreskin tissue and blood were obtained from 34 HIV- and malaria-uninfected Ugandan men who volunteered for elective circumcision, 12 of whom were definitively positive for S. mansoni eggs in stool and 12 definitively negative for both S. mansoni eggs and worm antigen. Tissue and blood T cell subsets were characterized by flow cytometry and immunohistochemistry (IHC). Th17 and Th1 cells from both the blood and foreskin expressed higher levels of CCR5 and were more activated than other CD4 T cell subsets. S. mansoni-infected men had a higher frequency of systemic Th1 cells (22.9 vs. 16.5% of blood CD4 T cells, p<0.05), Th17 cells (2.3 vs. 1.5%, p<0.05), and Th22 cells (0.5 vs. 0.3%, p<0.01) than uninfected men. Additionally, Th17 cells in the blood of S. mansoni-infected men demonstrated enhanced function (28.1 vs. 16.3% producing multiple cytokines, p = 0.046). However, these immune alterations were not observed in foreskin tissue. Conclusions/Significance S. mansoni infection was associated with an increased frequency of highly HIV-susceptible Th1, Th17 and Th22 cell subsets in the blood, but these T cell immune differences did not extend to the foreskin. S. mansoni induced changes in T cell immunology mediated through the common mucosal immune system are not likely to increase HIV susceptibility in the foreskin.