Relationship between maternal and/or newborn cholesterol levels and neonatal septicemia: protocol for a Ugandan cohort of mother-newborn pairs.

BACKGROUND: Many aspects of microbial dissemination appear to vary with host cholesterol levels. Since neonatal septicemia remains a leading cause of newborn admissions and mortality in resource-limited settings, the contribution of abnormal cholesterol levels in maternal and/or newborn blood to the risk of neonatal septicemia and outcome requires elucidation. We aim to determine a relationship between maternal serum and neonatal cord blood cholesterol levels and neonatal septicemia. METHODS: This will be a mother-newborn pair cohort study. Approximately 353 pregnant women who are eligible and consent to participate in the study will have blood drawn for a lipid profile. Upon delivery, we will analyse the cord blood cholesterol of their newborns and follow them for 28 days to determine whether the infants develop clinical signs and symptoms suggestive of neonatal septicemia. Relative risk will be used to determine the association between cholesterol and newborn septicemia. Poisson regression will be used to estimate the relative risk (with 95% confidence intervals) of developing septicemia. DISCUSSION: Findings from our study will contribute evidence to support the inclusion of lipid profile screening for pregnant women and newborns. Our study will determine whether newborns with abnormal cholesterol or those born to mothers with abnormal cholesterol will require rigorous follow-up in neonatal clinics.

A pragmatic approach to identifying implementation barriers and facilitators for a novel pre-exposure prophylaxis (PrEP) delivery model at public facilities in urban Uganda.

BACKGROUND: Scalable HIV pre-exposure prophylaxis (PrEP) delivery models for resource-limited settings are critical for improving PrEP coverage and interrupting HIV transmission. This research uses technical assistance (TA) reports to evaluate implementation barriers and facilitators for a novel delivery model integrating PrEP and antiretroviral therapy (ART) delivery for HIV sero-different couples in public health facilities in Kampala, Uganda. METHODS: We used data from the Partners PrEP Program (PPP)-a stepped-wedge cluster randomized trial that is launching PrEP delivery through an integrated model of oral PrEP and antiretroviral therapy (ART) delivery for HIV sero-different couples at public health facilities in Kampala and Wakiso, Uganda (NCT03586128). Technical assistance teams, comprised of PPP program staff, conducted monthly TA visits to implementing facilities where they identified and addressed implementation challenges in collaboration with health facility staff. Findings were recorded in TA reports, a standardized form structured using the Consolidated Framework for Implementation Research (CFIR). We used a conceptual content analysis approach to evaluate TA reports completed from January to December 2019 and identify implementation barriers and facilitators. RESULTS: Among 39 reports from the 8 implementing facilities (~ 5 per facility), we identified 11 CFIR constructs. Key implementation facilitators included sensitizing and educating facility staff about PrEP (knowledge and beliefs about the innovation); establishing formal and informal feedback and accountability mechanisms (reflecting and evaluating); and empowering facility staff to address implementation challenges (self-efficacy). Key implementation barriers were related to ineffective recruitment and referral of sero-different couples to and from nearby facilities (cosmopolitanism) as well as stockouts of laboratory resources and testing supplies (available resources). CONCLUSIONS: This analysis featured a robust implementation science framework to assess the relationship between early implementation determinants and outcomes of this innovative PrEP delivery model. Further, we have provided important descriptions of early implementation barriers and facilitators that will inform scale-up efforts for PrEP delivery within and beyond Uganda. Future work will refine the analysis of pragmatic program data, qualitatively investigate the identified key themes, and explore strategies for addressing implementation barriers.

Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial.

Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800 mg for 2 weeks, then 400 mg for 10 weeks, then 200 mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100 mg/day doses up to 400 mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n = 4 sertraline group; n = 3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200 mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia.