An Overview of Rift Valley Fever Vaccine Development Strategies.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality in ruminants and a mild to fatal hemorrhagic fever in humans. There are no licensed RVF vaccines for human use while for livestock, commercially available vaccines are all either live attenuated or inactivated and have undesirable characteristics. The live attenuated RVF vaccines are associated with teratogenicity and residual virulence in ruminants while the inactivated ones require multiple immunisations to induce and maintain protective immunity. Additionally, nearly all licensed RVF vaccines lack the differentiating infected from vaccinated animals (DIVA) property making them inappropriate for use in RVF nonendemic countries. To address these limitations, novel DIVA-compatible RVF vaccines with better safety and efficacy than the licensed ones are being developed, aided fundamentally by a better understanding of the molecular biology of the RVF virus and advancements in recombinant DNA technology. For some of these candidate RVF vaccines, sterilizing immunity has been demonstrated in the discovery/feasibility phase with minimal adverse effects. This review highlights the progress made to date in RVF vaccine research and development and discusses the outstanding research gaps

Hepatitis B prevalence and incidence in the fishing communities of Lake Victoria, Uganda: a retrospective cohort study.

INTRODUCTION: Hepatitis B is a serious potentially fatal hepatocellular disease caused by the hepatitis B virus. In the fishing communities of Lake Victoria Uganda, the hepatitis B virus infection burden is largely unknown. This study assessed the prevalence and incidence of hepatitis B in these communities. METHODS: This was a retrospective cohort study that tested serum samples collected from 13 to 49-year-old study participants that were residing in two Ugandan Lake Victoria fishing communities of Kasenyi (a mainland) and Jaana (an island). The samples were collected between 2013 and 2015 during the conduct of an HIV epidemiological cohort study in these communities. A total of 467 twelve-month follow-up and 50 baseline visit samples of participants lost to follow-up were tested for hepatitis B serological markers to determine prevalence. To determine hepatitis B virus incidence, samples that were hepatitis B positive at the follow-up visit had their baseline samples tested to identify hepatitis B negative samples whose corresponding follow-up samples were thus incident cases. RESULTS: The baseline mean age of the 517 study participants was 31.1 (SD ± 8.4) years, 278 (53.8%) of whom were females. A total of 36 (7%) study participants had hepatitis B virus infection, 22 (61.1%) of whom were male. Jaana had a higher hepatitis B virus prevalence compared to Kasenyi (10.2% vs 4.0%). In total, 210 (40.6%) study participants had evidence of prior hepatitis B virus infection while 48.6% had never been infected or vaccinated against this disease. A total of 20 (3.9%) participants had results suggestive of prior hepatitis B vaccination. Hepatitis B incidence was 10.5 cases/100PY (95% CI: 7.09-15.53). Being above 25 years of age and staying in Jaana were significant risk factors for hepatitis B virus acquisition (AOR 1.6, 95% CI: 1.1-2.2; p < 0.01 and 1.4, 95% CI: 1.1-1.8; p < 0.01 respectively). CONCLUSION: Hepatitis B virus incidence in Lake Victoria fishing communities of Uganda is very high, particularly in the islands. Interventions to lower hepatitis B virus transmission in these communities are urgently needed

Evaluation of HIV-1 rapid tests and identification of alternative testing algorithms for use in Uganda.

INTRODUCTION: The World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated. METHODS: In total 11 blood based and 3 oral transudate kits were evaluated. All together 2746 participants from seven sites, covering the four different regions of Uganda participated. Two enzyme immunoassays (EIAs) run in parallel were used as the gold standard. The performance and cost of the different algorithms was calculated, with a pre-determined price cut-off of either cheaper or within 20% price of the current algorithm of Determine + Statpak + Unigold. In the second phase, the three best algorithms selected in phase I were used at the point of care for purposes of quality control using finger stick whole blood. RESULTS: We identified three algorithms; Determine + SD Bioline + Statpak; Determine + Statpak + SD Bioline, both with the same sensitivity and specificity of 99.2% and 99.1% respectively and Determine + Statpak + Insti, with sensitivity and specificity of 99.1% and 99% respectively as having performed better and met the cost requirements. There were 15 other algorithms that performed better than the current one but rated more than the 20% price. None of the 3 oral mucosal transudate kits were suitable for inclusion in an algorithm because of their low sensitivities. Band intensity affected the performance of individual RTs but not the final algorithms. CONCLUSION: We have come up with three algorithms we recommend for public or Government procurement based on accuracy and cost. In case one algorithm is preferred, we recommend to replace Unigold, the current tie breaker with SD Bioline. We further recommend that all the 18 algorithms that have shown better performance than the current one are made available to the private sector where cost may not be a limiting factor

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 7.67/100 pyar (95% CI;4.62-12.7) while it was 5.67/100 pyar (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

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

Population attributable fraction of incident HIV infections associated with alcohol consumption in fishing communities around Lake Victoria, Uganda.

BackgroundAlthough the association between alcohol consumption and HIV risk is well documented, few studies have examined the magnitude of new HIV infections that could be prevented by controlling alcohol use. We report the population attributable fraction (PAF) of incident HIV infections due to alcohol consumption among the HIV high-risk population of fishing communities along Lake Victoria, Uganda.MethodsIn a community-based cohort study, 1607 HIV sero-negative participants aged 18-49 years were enrolled from eight fishing communities along Lake Victoria, Uganda. At follow up 12 months later, 1288 (80.1%) were seen and interviewed. At baseline and follow-up visits, participants completed interviewer-administered questionnaires on alcohol consumption, demographics, and sexual risk behavior, and were tested for HIV infection. HIV incidence and adjusted incident rate ratios (adjusted IRRs) were estimated using Poisson regression models; the crude and adjusted PAFs of incident HIV infections associated with alcohol consumption were calculated using the Greenland and Drescher method for cohort studies.ResultsAmong the 1288 participants seen at follow up, 53.5% reported drinking alcohol of whom 24.4% drank occasionally (2 days a week or less) and 29.1% drank regularly (3-7 days a week). Forty eight incident HIV infections occurred giving an incidence rate of 3.39/100 person years at-risk (pyar) (95% CI, 2.55-4.49). Compared to non-drinkers, the adjusted IRR of HIV was 3.09 (1.13-8.46) among occasional drinkers and 5.34 (2.04-13.97) among regular drinkers. The overall adjusted PAF of incident HIV infections due alcohol was 64.1 (95% CI; 23.5-83.1); ranging from 52.3 (11.9-74.2) among Muslims to 71.2 (32.6-87.7) for participants who reported ≥ 2 sexual partners in the past 12 months.ConclusionIn fishing communities along Lake Victoria, Uganda, 64% of new HIV infections can be attributed to drinking alcohol. Interventions to reduce alcohol consumption should be integrated in HIV/AIDS prevention activities for populations in whom both HIV and alcohol consumption are highly prevalent

Population attributable fraction of incident HIV infections associated with alcohol consumption in fishing communities around Lake Victoria, Uganda.

BACKGROUND:Although the association between alcohol consumption and HIV risk is well documented, few studies have examined the magnitude of new HIV infections that could be prevented by controlling alcohol use. We report the population attributable fraction (PAF) of incident HIV infections due to alcohol consumption among the HIV high-risk population of fishing communities along Lake Victoria, Uganda. METHODS:In a community-based cohort study, 1607 HIV sero-negative participants aged 18-49 years were enrolled from eight fishing communities along Lake Victoria, Uganda. At follow up 12 months later, 1288 (80.1%) were seen and interviewed. At baseline and follow-up visits, participants completed interviewer-administered questionnaires on alcohol consumption, demographics, and sexual risk behavior, and were tested for HIV infection. HIV incidence and adjusted incident rate ratios (adjusted IRRs) were estimated using Poisson regression models; the crude and adjusted PAFs of incident HIV infections associated with alcohol consumption were calculated using the Greenland and Drescher method for cohort studies. RESULTS:Among the 1288 participants seen at follow up, 53.5% reported drinking alcohol of whom 24.4% drank occasionally (2 days a week or less) and 29.1% drank regularly (3-7 days a week). Forty eight incident HIV infections occurred giving an incidence rate of 3.39/100 person years at-risk (pyar) (95% CI, 2.55-4.49). Compared to non-drinkers, the adjusted IRR of HIV was 3.09 (1.13-8.46) among occasional drinkers and 5.34 (2.04-13.97) among regular drinkers. The overall adjusted PAF of incident HIV infections due alcohol was 64.1 (95% CI; 23.5-83.1); ranging from 52.3 (11.9-74.2) among Muslims to 71.2 (32.6-87.7) for participants who reported ≥ 2 sexual partners in the past 12 months. CONCLUSION:In fishing communities along Lake Victoria, Uganda, 64% of new HIV infections can be attributed to drinking alcohol. Interventions to reduce alcohol consumption should be integrated in HIV/AIDS prevention activities for populations in whom both HIV and alcohol consumption are highly prevalent