Contraceptive Preference Among Women at Risk of HIV Acquisition in a Preparatory Screening Study for a Phase III Microbicide Trial in South Western Uganda.

Contraceptive preferences of women at risk for HIV acquisition are not well documented. We report on contraceptive choices among women residing in small townships in southwestern Uganda. This was part of preparatory efforts for recruitment into the Ring Study, a phase 3 microbicide trial, between July 2013 and October 2014. Clinicians provided contraceptives per a woman's choice. HIV testing and screening for other sexually transmitted infections were done at first contact and at screening for the trial. Contraceptive choice was summarized by demographics and regression analysis to show factors associated with use of the injectable method. Of 6725 women contacted, 489 were prescreened. Of these 489 women, most (306, 63%) were already using contraception. Injectables were most preferred (58.7%), followed by implants (23.9%). Women living with a regular sexual partner preferred the injectable method (61.0%, P = 0.06), compared with other methods. Women at risk for HIV infection are willing to initiate use of modern contraceptives, which may reduce study dropout during intervention trials due to unintended pregnancy. Registration no: NCT01539226

Effect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni co-infected patients: a randomised controlled trial

Background: It has been hypothesised that Schistosoma co-infection exacerbates HIV progression, and hence anthelminthic intervention in co-infected individuals will delay it. We evaluated effects of high-intensity versus low-intensity praziquantel treatment of schistosomiasis on HIV disease progression among co-infected patients from fishing populations around Lake Victoria, Uganda. Methods: Between August 2012 and September 2015, we conducted an open-label randomised, controlled trial. Adults, antiretroviral therapy-naïve, CD4 counts ≥350 cells/μl, HIV and S. mansoni co-infected, were randomised 1:1 to praziquantel (40mg/kg) given quarterly (starting at enrolment) or annually (starting 12 weeks after enrolment; such that low-intensity participants were still untreated when sampled at 12 weeks). A non-randomised HIV-positive S. mansoni-negative comparison group was recruited. The primary outcome was mean change in plasma viral load at 12 and 60 weeks. Results: In total 363 participants (high-intensity 113, low-intensity 113, comparison group 137) were recruited; 96 (85.0%), 97 (85.8%) and 107 (78.1%) completed 60 weeks of follow up, respectively. Adjusting for baseline age and viral load, the geometric mean ratio (aGMR [95%CI]) viral load for high-intensity vs low-intensity groups at 12 weeks was 0.90 [0.65, 1.25] p=0.55 and at 60 weeks 1.88 [0.78, 4.53] p=0.16. Results in the comparison group were similar to trial arms. High-intensity, compared to low-intensity, treatment resulted in substantially lower S. mansoni prevalence at all follow up visits (p&lt;0.05). Conclusions: In communities with a high burden of both S. mansoni and HIV infection, high-intensity treatment of S. mansoni does not delay HIV progression despite relevant benefit for parasite clearance. Trial registration: ISRCTN15371662 (17/11/2016)</ns4:p

Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk.

In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and β-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals

Effect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni co-infected patients: a randomised controlled trial

Background: It has been hypothesised that Schistosoma co-infection exacerbates HIV progression, and hence anthelminthic intervention in co-infected individuals will delay it. We evaluated effects of high-intensity versus low-intensity praziquantel treatment of schistosomiasis on HIV disease progression among co-infected patients from fishing populations around Lake Victoria, Uganda. Methods: Between August 2012 and September 2015, we conducted an open-label randomised, controlled trial. Adults, antiretroviral therapy-naïve, CD4 counts ≥350 cells/μl, HIV and S. mansoni co-infected, were randomised 1:1 to praziquantel (40mg/kg) given quarterly (starting at enrolment) or annually (starting 12 weeks after enrolment; such that low-intensity participants were still untreated when sampled at 12 weeks). A non-randomised HIV-positive S. mansoni-negative comparison group was recruited. The primary outcome was mean change in plasma viral load at 12 and 60 weeks. Results: In total 363 participants (high-intensity 113, low-intensity 113, comparison group 137) were recruited; 96 (85.0%), 97 (85.8%) and 107 (78.1%) completed 60 weeks of follow up, respectively. Adjusting for baseline age and viral load, the geometric mean ratio (aGMR [95%CI]) viral load for high-intensity vs low-intensity groups at 12 weeks was 0.90 [0.65, 1.25] p=0.55 and at 60 weeks 1.88 [0.78, 4.53] p=0.16. Results in the comparison group were similar to trial arms. High-intensity, compared to low-intensity, treatment resulted in substantially lower S. mansoni prevalence at all follow up visits (p&lt;0.05). Conclusions: In communities with a high burden of both S. mansoni and HIV infection, high-intensity treatment of S. mansoni does not delay HIV progression despite relevant benefit for parasite clearance. Trial registration: ISRCTN15371662 (17/11/2016)</ns4:p

Schistosomiasis transmission at high altitude crater lakes in Western Uganda

<p>Abstract</p> <p>Background</p> <p>Contrary to previous reports which indicated no transmission of schistosomiasis at altitude >1,400 m above sea level in Uganda, in this study it has been established that schistosomiasis transmission can take place at an altitude range of 1487–1682 m above sea level in western Uganda.</p> <p>Methods</p> <p>An epidemiological survey of intestinal schistosomiasis was carried out in school children staying around 13 high altitude crater lakes in Western Uganda. Stool samples were collected and then processed with the Kato-Katz technique using 42 mg templates. Thereafter schistosome eggs were counted under a microscope and eggs per gram (epg) of stool calculated. A semi-structured questionnaire was used to obtain demographic data and information on risk factors.</p> <p>Results</p> <p>36.7% of the pupils studied used crater lakes as the main source of domestic water and the crater lakes studied were at altitude ranging from 1487–1682 m above sea level. 84.6% of the crater lakes studied were infective with over 50% of the users infected.</p> <p>The overall prevalence of <it>Schistosoma mansoni </it>infection was 27.8% (103/370) with stool egg load ranging from 24–6048 per gram of stool. 84.3%( 312) had light infections (<100 eggs/gm of stool), 10.8%( 40) had moderate infections (100–400 eggs/gm of stool) and 4.9% (18) had heavy infections (>400 egg/gm of stool). Prevalence was highest in the age group 12–14 years (49.5%) and geometric mean intensity was highest in the age group 9–11 years (238 epg). The prevalence and geometric mean intensity of infection among girls was lower (26%; 290 epg) compared to that of boys (29.6%; 463 epg) (t = 4.383, p < 0.05). Though 61%(225) of the pupils interviewed were aware of the existence of the disease, 78% (290)didn't know the mode of transmission and only 8% (30) of those found infected were aware of their infection status. In a multivariate logistic regression model, altitude and water source (crater lakes) were significantly associated with infection.</p> <p>Conclusion and recommendations</p> <p>The altitudinal threshold for <it>S. mansoni </it>transmission in Uganda has changed and use of crater water at an altitude higher than 1,400 m above sea level poses a risk of acquiring <it>S. mansoni </it>infection in western Uganda. However, further research is required to establish whether the observed altitudinal threshold change is as a result of climate change or other factors. It is also necessary to establish the impact this could have on the epidemiology of schistosomiasis and other vector-borne diseases in Uganda. In addition, sensitisation and mass treatment of the affected community is urgently required.</p

Reduced susceptibility to pyrethroid insecticide treated nets by the malaria vector Anopheles gambiae s.l. in western Uganda

<p>Abstract</p> <p>Background</p> <p>Pyrethroid insecticide-treated mosquito nets are massively being scaled-up for malaria prevention particularly in children under five years of age and pregnant mothers in sub-Saharan Africa. However, there is serious concern of the likely evolution of widespread pyrethroid resistance in the malaria vector <it>Anopheles gambiae s.l</it>. due to the extensive use of pyrethroid insecticide-treated mosquito nets. The purpose of this study was to ascertain the status of pyrethroid resistance in <it>An. gambiae s.l</it>. in western Uganda.</p> <p>Methods</p> <p>Wild mosquitoes (1–2 days old) were exposed in 10 replicates to new nets impregnated with K-othrine (Deltamethrin 25 mg/m²), Solfac EW50 (Cyfluthrin 50 mg/m²) and Fendona 6SC (Cypermethrin 50 mg/m²) and observed under normal room temperature and humidity (Temperature 24.8°C���27.4°C, Humidity 65.9–45.7). A similar set of mosquitoes collected from the control area 80 km away were exposed to a deltamethrin 25 mg/m²impregnated net at the same time and under the same conditions. The 10-year mean KDT₅₀and mortality rates for each of the three pyrethroid insecticides were compared using the Student <it>t</it>-test.</p> <p>Results</p> <p>A significant increase in the mean knockdown time (KDT₅₀) and mean mortality rate were observed in almost all cases an indication of reduced susceptibility. The overall results showed a four-fold increase in the mean knockdown time (KDT₅₀) and 1.5-fold decrease in mortality rate across the three pyrethroid insecticides. There was a significant difference in the 10-year mean KDT₅₀between deltamethrin and cyfluthrin; deltamethrin and cypermethrin, but no significant difference between cyfluthrin and cypermethrin. The 10-year mean difference in KDT50 for mosquitoes exposed to deltamethrin from the control site was significantly different from that of mosquitoes from the intervention site (p<0.05, t=3.979, 9df). The 10-year mean difference in mortality rate between deltamethrin (84.64%); cyfluthrin (74.18%); cypermethrin (72.19%) and the control (90.45%) showed a significant decline in mortality across all the three insecticides.</p> <p>Conclusion</p> <p>Generally the results showed a trend of increase in mosquito resistance status with cross-resistance against all the three pyrethroid insecticides. This study reveals for the first time the development of pyrethroid resistance in <it>An. gambiae s.l</it>. in Western Uganda. It is therefore strongly recommended that the impact of this development on malaria control efforts be closely monitored and alternative fabric treatments be considered before this problem curtails community wide implementation of this malaria control strategy in Uganda.</p

Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: the experience of The AIDS Support Organization (TASO), Kampala, Uganda

BACKGROUND: Poor adherence to highly active antiretroviral therapy (HAART) may result in treatment failure and death. Most reports of the effect of adherence to HAART on mortality come from studies where special efforts are made to provide HAART under ideal conditions. However, there are few reports of the impact of non-adherence to HAART on mortality from community HIV/AIDS treatment and care programmes in developing countries. We therefore conducted a study to assess the effect of adherence to HAART on survival in The AIDS Support Organization (TASO) community HAART programme in Kampala, Uganda. METHODS: The study was a retrospective cohort of 897 patients who initiated HAART at TASO clinic, Kampala, between May 2004 and December 2006. A total of 7,856 adherence assessments were performed on the data. Adherence was assessed using a combination of self-report and pill count methods. Patients who took 95%. The crude death rate was 12.2 deaths per 100 patient-years, with a rate of 42.5 deaths per 100 patient-years for non-adherent patients and 6.1 deaths per 100 patient-years for adherent patients. Non-adherence to ART was significantly associated with mortality. Patients with a CD4 count of less than 50 cells/mm3 had a higher mortality (HR = 4.3; 95% CI: 2.22-5.56) compared to patients with a CD4 count equal to or greater than 50 cells/mm3 (HR = 2.4; 95% CI: 1.79-2.38). CONCLUSION: Our study showed that good adherence and improved survival are feasible in community HIV/AIDS programmes such as that of TASO, Uganda. However, there is need to support community HAART programmes to overcome the challenges of funding to provide sustainable supplies particularly of antiretroviral drugs; provision of high quality clinical and laboratory support; and achieving a balance between expansion and quality of services. Measures for the early identification and treatment of HIV infected people including home-based VCT and HAART should be strengthened

Uptake of long acting reversible contraception following integrated couples HIV and fertility goal-based family planning counselling in Catholic and non-Catholic, urban and rural government health centers in Kigali, Rwanda.

BACKGROUND: When integrated with couples' voluntary HIV counselling and testing (CVCT), family planning including long acting reversible contraceptives (LARC) addresses prongs one and two of prevention of mother-to-child transmission (PMTCT). METHODS: In this observational study, we enrolled equal numbers of HIV concordant and discordant couples in four rural and four urban clinics, with two Catholic and two non-Catholic clinics in each area. Eligible couples were fertile, not already using a LARC method, and wished to limit or delay fertility for at least 2 years. We provided CVCT and fertility goal-based family planning counselling with the offer of LARC and conducted multivariate analysis of clinic, couple, and individual predictors of LARC uptake. RESULTS: Of 1290 couples enrolled, 960 (74%) selected LARC: Jadelle 5-year implant (37%), Implanon 3-year implant (26%), or copper intrauterine device (IUD) (11%). Uptake was higher in non-Catholic clinics (85% vs. 63% in Catholic clinics, p < 0.0001), in urban clinics (82% vs. 67% in rural clinics, p < 0.0001), and in HIV concordant couples (79% vs. 70% of discordant couples, p = .0005). Religion of the couple was unrelated to clinic religious affiliation, and uptake was highest among Catholics (80%) and lowest among Protestants (70%) who were predominantly Pentecostal. In multivariable analysis, urban location and non-Catholic clinic affiliation, Catholic religion of woman or couple, younger age of men, lower educational level of both partners, non-use of condoms or injectable contraception at enrollment, prior discussion of LARC by the couple, and women not having concerns about negative side effects of implant were associated with LARC uptake. CONCLUSIONS: Fertility goal-based LARC recommendations combined with couples' HIV counselling and testing resulted in a high uptake of LARC methods, even among discordant couples using condoms for HIV prevention, in Catholic clinics, and in rural populations. This model successfully integrates prevention of HIV and unplanned pregnancy

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. METHODS: We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. FINDINGS: Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. INTERPRETATION: KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. FUNDING: Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development