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Among low and middle-income countries, especially in Sub-Saharan Africa, the stroke burden is severe, with increasing trends in stroke incidence, prevalence, and mortality. This 6-month, prospective randomized controlled trial (RCT) compared a novel stroke risk reduction approach (TargetEd manAgeMent Intervention (TEAM)) vs. Enhanced Treatment as Usual (ETAU) in 247 Ugandans at risk for stroke. Participants, enrolled across 3 Ugandan sites, were adults with high stroke risk. The primary outcome was a change in systolic blood pressure (SBP) from baseline to 6-month follow-up. Secondary outcomes included changes from baseline to 6 months on diastolic BP (DBP), serum lipids, glycosylated hemoglobin (HbA1c), self-efficacy and stress. The mean sample age was 55.4 (±SD = 12.0) with majority being women (n = 168, 68%). In addition to hypertension, the most common risk factors were hyperlipidemia (n = 199, 80.6%) and obesity (n = 98, 39.7%). Overall mean SBP and DBP at baseline were 143.0 (SD = 19.8, range 94.5-206) and 89.3 (SD = 14.0, range 61-136) respectively. In TEAM, SBP significantly improved from 145.7 (±21.5) at baseline to137.4 (±18.1) at 6-months vs. change from 141.9 (±18.4) to 141.1 (±21.9) for ETAU (p = 0.031). There were similar reductions in DBP favoring TEAM (p = .012). Compared to ETAU, TEAM showed improved physical activity (p = .017), self-efficacy (p < .001) and stress (p = .014). There is a need for effective and practical approaches to reduce stroke burden in Sub-Saharan Africa. Inclusion of the TEAM approach in primary care seems to be a pragmatic and effective way to potentially reduce stroke burden in Uganda. ClinicalTrials.gov identifier: NCT04685408, registered on 28 December 2020.

As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women. We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1-2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. Of the 50 mother-infant pairs enrolled, 48% were ≤12 wk and 52% were 13-24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22-28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the ≤12 weeks, and 14 (12 to 17) for the 13-24 wk infant age groups. Overall, median (IQR) time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 μg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up. The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk. In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure. ClinicalTrials.gov, Identifier: NCT02776748.

Background Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates. Methods This was an analytical observational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes. Results Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01–1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06–0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03–3.05) decreased the likelihood of having low Apgar scores at five minutes. Conclusions Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5 min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery.

Stroke burden is rapidly increasing globally. Modifiable risk factors offer an opportunity to intervene, and targeting hypertension is a key actionable target for stroke risk reduction in sub-Saharan Africa. This 3-site planned randomized controlled trial builds on promising preliminary data. A total of 246 Ugandan adults will be recruited randomized to experimental intervention vs. enhanced treatment control. Intervention participants will receive six weekly group-format stroke risk reduction self-management training sessions, and the controls will receive information on cardiovascular risk. The primary study outcome is systolic B.P. measured at baseline, 13-week, 24 weeks (6 months). Secondary outcomes include other biological and behavioral stroke risk factors. The curriculum-guided self-management TargetEd MAnageMent Intervention (TEAM) program is anticipated to reduce the stroke burden in Uganda. ClinicalTrials.gov identifier: NCT04685408, registered on 28 December 2020.

Aims Dyslipidemia is a major modifiable risk factor for stroke; however, it is poorly understood among patients at risk of stroke in Uganda. This study is aimed at determining the prevalence of dyslipidemia and identifying associated factors among a Ugandan sample at risk for stroke. Methods This was a hospital based cross-sectional study conducted across three Ugandan sites. The serum lipid levels were determined following the National Cholesterol Education Program guidelines. Data were analyzed with STATA employing univariable and multivariable logistic regression. Statistical significance was set at p<0.05. Results We enrolled 247 study participants with a mean age (SD) of 55.4 (12.0) years. Majority of the participants were female, n=168 (68%). About 81% (N=199) had elevated serum lipid levels. Sixty-one (24.7%) had elevated levels of total serum cholesterol, whereas half of female participants had abnormally low levels of HDL cholesterol. About a third (N=82 and 84, respectively) had elevated serum LDL and triglycerides. Nearly 40% (N=98) were obese and 23.5% had a sedentary lifestyle (N==58). Only 20.2% (N=50) were receiving lipid lowering drugs. Prior family stroke history and personal history of stroke had lower odds of 58% (AOR=0.42, 95% CI: 0.20-0.88, p=0.022); and 64% (AOR=0.36, 95% CI: 0.17-0.76, p=0.008), respectively, of having dyslipidemia. Conclusions Approximately four in five Ugandans at risk of stroke have dyslipidemia. The majority also have low HDL-c levels. Implementation of systematic screening and provision of statin therapy among those at high risk for stroke is urgently needed to reduce stroke burden in Uganda. Trial Registration ClinicalTrials.gov identifier: NCT04685408

Background A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda. Methods We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013–2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics. Results In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% ( n  = 72). Severe disease was present in 82% ( n  = 85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% ( n  = 44) of participants, with the highest mortality among those with extradural lesions (60%). Conclusion The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis.

High quality PhD training in sub-Saharan Africa is important to strengthen research evidence to advance development and health. Training a critical mass of independent investigators capable of original scientific research requires strong mentorship, research environments, and international networks. We sought to iteratively improve a PhD training model in Uganda through systems capacity building. PhD students were selected through a rigorous competitive application and selection process, which included a written proposal and a face-to-face panel interview. The program provided administrative support, paid tuition fees, tools (space, equipment, research money), skills (short research courses on study design, biostatistics, manuscript and grant writing), and infrastructure (finance, grants management support, and lab infrastructure). Guidance to identify local and international mentorship was also provided in addition to two to three group meetings per year where data was presented and progress assessed by the program leaders in addition to available local mentors. Seventeen PhD students were selected, and fifteen will complete training through the MEPI-MESAU program. To date, 60% have completed, including 2 students who started 2 years into the program. So far, 169 publications have been published in the peer-reviewed literature. Our PhD students have supervised and mentored 65 Master's students, which illustrates the cascade effect of PhD training on the academic medical school environment. The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others.

Among low and middle-income countries, especially in Sub-Saharan Africa, the stroke burden is severe, with increasing trends in stroke incidence, prevalence, and mortality. This 6-month, prospective randomized controlled trial (RCT) compared a novel stroke risk reduction approach (TargetEd manAgeMent Intervention (TEAM)) vs. Enhanced Treatment as Usual (ETAU) in 247 Ugandans at risk for stroke. The mean sample age was 55.4 (±SD = 12.0) with majority being women (n = 168, 68%). In addition to hypertension, the most common risk factors were hyperlipidemia (n = 199, 80.6%) and obesity (n = 98, 39.7%). Overall mean SBP and DBP at baseline were 143.0 (SD = 19.8, range 94.5-206) and 89.3 (SD = 14.0, range 61-136) respectively. In TEAM, SBP significantly improved from 145.7 (±21.5) at baseline to137.4 (±18.1) at 6-months vs. change from 141.9 (±18.4) to 141.1 (±21.9) for ETAU (p = 0.031). There were similar reductions in DBP favoring TEAM (p = .012). Compared to ETAU, TEAM showed improved physical activity (p = .017), self-efficacy (p < .001) and stress (p = .014). There is a need for effective and practical approaches to reduce stroke burden in Sub-Saharan Africa. Inclusion of the TEAM approach in primary care seems to be a pragmatic and effective way to potentially reduce stroke burden in Uganda.

Evidence supporting secondary stroke in sub-Saharan Africa is scarce. This study describes the incidence of stroke recurrence and associated risk factors in sub-Saharan Africa. Scientific databases were systematically searched from January 2000 to December 2022 for population-based observational studies, case-control or cohort studies of recurrent stroke involving adults aged 18 years and above in sub-Saharan Africa (SSA). We assessed the quality of the eligible studies using the Critical Appraisal Skills Program (CASP) checklist for observational studies. Six studies met the inclusion criteria and were included in this study. Stroke recurrence rates in SSA ranged from 9.4% to 25%. Majority of the studies were conducted from Western Africa and showed that stroke recurrence rates are high within sub-Saharan Africa ranging from 2% to 25%. The known stroke risk factors such as hypertension, chronic alcohol consumption, etc., remained the leading causes of stroke recurrence. The studies reported a higher mortality rate ranging from 20.5 -23% among those with recurrent strokes compared to primary strokes. This systematic review is an update and summary of the available literature on stroke recurrence within sub-Saharan Africa. Further studies are warranted to assess the outcomes and burden of stroke recurrence in SSA.

The study set out to perform a systematic literature review of evidence-based interventions that target the reduction of secondary stroke risk in Africa. The review analyzed longitudinal intervention studies conducted in Sub-Saharan Africa, focusing on adult participants who had suffered a prior stroke. It encompassed publications and peer-reviewed papers sourced from reputable databases, including PubMed, Ovid, Cochrane, and Web of Science. Three randomized clinical trial (RCT) studies were included with sample sizes ranging from 16 to 400 participants, mean age ranged between 50 and 66 years, with 64.5% male participants. All studies applied multidisciplinary team interventions of enhanced patient follow-up involving care givers, nurse educators, physicians, and social workers. Interventions ranged from comprehensive patient education, tracking of medication adherence and enforcing healthy lifestyle behaviors (regular exercise, regular BP checks, and dietary changes). We found a decrease in Systolic Blood Pressure over time in 2 of 3 treatment groups, an improvement in medical adherence in all treatment groups, and a decrease in cholesterol levels in 1 treatment group. Evidence-based interventions involving multidisciplinary teams and comprehensive patient education were found to demonstrate promising results in reducing secondary stroke risk in Africa, leading to significant improvements in medical adherence and reductions in systolic blood pressure in the majority of treatment groups. However, more research is required to confirm the influence of these interventions on cholesterol levels and to establish their lasting advantages in preventing strokes among African communities.