Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.

Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.

Immune cells in bronchoalveolar lavage fluid of Ugandan adults who resist versus those who develop latent Mycobacterium tuberculosis infection.

BACKGROUND: The search for immune correlates of protection against Mycobacterium tuberculosis (MTB) infection in humans is limited by the focus on peripheral blood measures. Bronchoalveolar lavage (BAL) can safely be done and provides insight into cellular function in the lung where infection is first established. In this study, blood and lung samples were assayed to determine if heavily MTB exposed persons who resist development of latent MTB infection (RSTR) vs those who develop latent MTB infection (LTBI), differ in the make-up of resident BAL innate and adaptive immune cells. METHODS: Bronchoscopy was performed on 21 healthy long-term Ugandan RSTR and 25 LTBI participants. Immune cell distributions in BAL and peripheral blood were compared by differential cell counting and flow cytometry. RESULTS: The bronchoscopy procedure was well tolerated with few adverse reactions. Differential macrophage and lymphocyte frequencies in BAL differed between RSTR and LTBI. When corrected for age, this difference lost statistical significance. BAL CD4+ and CD8+ T cells were almost entirely composed of effector memory T cells in contrast to PBMC, and did not differ between RSTR and LTBI. BAL NKT, γδ T cells and NK cells also did not differ between RTSR and LTBI participants. There was a marginally significant increase (p = 0.034) in CD8 T effector memory cells re-expressing CD45RA (TEMRA) in PBMC of LTBI vs RSTR participants. CONCLUSION: This observational case-control study comparing unstimulated BAL from RSTR vs LTBI, did not find evidence of large differences in the distribution of baseline BAL immune cells. PBMC TEMRA cell percentage was higher in LTBI relative to RSTR suggesting a role in the maintenance of latent MTB infection. Functional immune studies are required to determine if and how RSTR and LTBI BAL immune cells differ in response to MTB.

Knowledge and use of family planning among men in rural Uganda.

BACKGROUND: Unmet need for family planning exceeds 33% in Uganda. One approach to decreasing unmet need is promoting male involvement in family planning. Male disapproval of use of family planning by their female partners and misconceptions about side effects are barriers to family planning globally and in Uganda in particular. Researchers have conducted a number of qualitative studies in recent years to examine different aspects of family planning among Ugandan men. The present study aimed to quantify men's knowledge of family planning in rural Uganda to understand how better to involve men in couples' contraceptive decision-making, particularly in low-resource settings. METHODS: Data were derived from in-person, researcher-administered surveys of men in a rural agrarian district in Uganda (N = 178). Participant demographics and knowledge of family planning methods, side effects, and use were queried. Descriptive statistics were used for analysis. RESULTS: Men were 34 years of age on average (range 18-71) and about half (56%) had a primary school education or less. Ninety-eight percent reported any knowledge of family planning, with 73% of men reporting obtaining information via radio and only 43% from health workers. The most common method known by men was the male condom (72%), but more than half also knew of injections (54%) and pills (52%). Relatively few men reported knowing about the most effective reversible contraceptive methods, intrauterine devices and implants (both 16%). Men identified many common contraceptive side-effects, such as vaginal bleeding (31%), and misconceptions about side effects, such as increased risk of infertility and birth defects, were relatively uncommon (both < 10%). About half of all men reported ever using a family planning method (53%), and 40% reported current use. CONCLUSIONS: This study's quantitative results build on those of recent qualitative studies and provide information about the types of family planning information men are lacking and avenues for getting this information to them.