Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. METHODS: This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18-35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7-24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov, NCT03060629, and is complete. FINDINGS: Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20-25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7-24 after the first vaccination was 3·38 (95% CI 2·54-4·41) in the vaccine group and 3·94 (3·04-5·03) in the placebo group, with an estimated VE(7-24) of 14·10% (95% CI -22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. INTERPRETATION: The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute.

Comparing the effect of a multisectoral agricultural intervention on HIV-related health outcomes between widowed and married women.

INTRODUCTION: Widowed women make up 18-40% of the 12 million women living with HIV in eastern and southern Africa. Widowhood has also been associated with greater HIV morbidity and mortality. We compared the effectiveness of a multisectoral climate adaptive agricultural livelihood intervention (called Shamba Maisha) on food insecurity, and HIV related health outcomes among widowed and married women living with HIV in western Kenya. METHODS: We implemented Shamba Maisha (NCT02815579) using a cluster-randomized control trial design. The intervention arm received an US$175 in-kind loan to purchase a micro-irrigation pump, seeds, and fertilizer, and received eight training sessions on sustainable agriculture and financial management. Study outcomes were measured every 6 months over a 24-month follow-up period and trends in outcomes assessed using multilevel mixed-effects models. RESULTS: The trial enrolled 232 (61.5%) married and 145 (38.5%) widowed women. Widowed women (mean age 42.8 ± 8.4 years) were older than married women (35.8 ± 9.0 years) (p < 0.01). Almost all widowed women (97.2%) self-identified as household heads compared to 10.8% of married women. Comparing widowed vs married women, reduction in food insecurity (-3.13, 95%CI -4.42, -1.84 vs. -3.08, 95%CI -4.15, -2.02), depressive symptoms (-0.21, 95%CI -0.36, -0.07 vs. -0.19, 95%CI -0.29, -0.08), internalized stigma (-0.33, 95%CI -0.55, -0.11 vs. -0.38, 95%CI -0.57, -0.19), and anticipated stigma (-0.46 95%CI -0.65, -0.28 vs. -0.35, 95%CI -0.50, -0.21) was similar for both groups. In contrast, improvements in social support (-2.22, 95%CI -3.85, -0.59 vs. -4.00, 95%CI -5.16, -2.84; p = 0.08) and reduction in enacted stigma (0.01, 95%CI -0.06, 0.08 vs. -0.14, 95%CI -0.20, -0.09; p < 0.01) were weaker for widowed than married women. CONCLUSIONS: Our study is among the first comparing the effect of a livelihood intervention on HIV health outcomes among widowed and married women. Widowed women experienced similar benefits as married women on individual-level outcomes, but weaker benefit on outcomes dependent on their external environment like enacted stigma and social support. Future trials and programs targeting widowed women should bolster stigma reduction and social support.

Risk Factors Associated with HIV Acquisition in Males Participating in HIV Vaccine Efficacy Trials in South Africa.

In South Africa, HIV acquisition risk has been studied less in people assigned male at birth. We studied the associations between risk behaviors, clinical features and HIV incidence amongst males in two South African HIV preventive vaccine efficacy trials. We used Cox proportional hazards models to test for associations between demographics, sexual behaviors, clinical variables and HIV acquisition among males followed in the HVTN 503 (n = 219) and HVTN 702 (n = 1611) trials. Most males reported no male sexual partners (99.09% in HVTN 503) or identified as heterosexual (88.08% in HVTN 702). Annual HIV incidence was 1.39% in HVTN 503 (95% CI 0.76-2.32%) and 1.33% in HVTN 702 (95% CI 0.80-2.07%). Increased HIV acquisition was significantly associated with anal sex (HR 6.32, 95% CI 3.44-11.62), transactional sex (HR 3.42, 95% CI 1.80-6.50), and non-heterosexual identity (HR 16.23, 95%CI 8.13-32.41) in univariate analyses and non-heterosexual identity (HR 14.99, 95% CI 4.99-45.04; p < 0.01) in multivariate analysis. It is appropriate that prevention efforts in South Africa, although focused on the severe epidemic in young women, also encompass key male populations, including men who have sex with men, but also men who engage in anal or transactional sex.

Gender equity in health research publishing in Africa.

INTRODUCTION: Women researchers find it more difficult to publish in academic journals than men, an inequity that affects women's careers and was exacerbated during the pandemic, particularly for women in low-income and middle-income countries. We measured publishing by sub-Saharan African (SSA) women in prestigious authorship positions (first or last author, or single author) during the time frame 2014-2016. We also examined policies and practices at journals publishing high rates of women scientists from sub-Saharan Africa, to identify potential structural enablers affecting these women in publishing. METHODS: The study used Namsor V.2, an application programming interface, to conduct a secondary analysis of a bibliometric database. We also analysed policies and practices of ten journals with the highest number of SSA women publishing in first authorship positions. RESULTS: Based on regional analyses, the greatest magnitude of authorship inequity is in papers from sub-Saharan Africa, where men comprised 61% of first authors, 65% of last authors and 66% of single authors. Women from South Africa and Nigeria had greater success in publishing than those from other SSA countries, though women represented at least 20% of last authors in 25 SSA countries. The journals that published the most SSA women as prominent authors are journals based in SSA. Journals with overwhelmingly male leadership are also among those publishing the highest number of SSA women. CONCLUSION: Women scholars in SSA face substantial gender inequities in publishing in prestigious authorship positions in academic journals, though there is a cadre of women research leaders across the region. Journals in SSA are important for local women scholars and the inequities SSA women researchers face are not necessarily attributable to gender discrepancy in journals' editorial leadership.

Epidemiological and clinical characteristics of patients hospitalised with COVID-19 in Kenya: a multicentre cohort study.

OBJECTIVES: To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality. SETTING: This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya. PARTICIPANTS: We enrolled 787 reverse transcriptase-PCR-confirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. RESULTS: Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30-53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons >60 years compared with those <60 years old; having comorbidities (HR 2.34 (1.68 to 3.25)) and among men (HR 1.76 (1.27 to 2.44)) compared with women. Elevated white cell count and aspartate aminotransferase were associated with higher risk of death. CONCLUSIONS: The risk of death from COVID-19 is high among older patients, those with comorbidities and among men. Clinical parameters including patient clinical signs, haematology and liver function tests were associated with risk of death and may guide stratification of high-risk patients.

Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study.

BACKGROUND: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic. METHODS: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 1010 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual. FINDINGS: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]). INTERPRETATION: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally. FUNDING: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.

Barriers and Facilitators to Integrating Clinical Breast Examinations With Cervical Cancer Screening Programs in Outpatient Clinics in Western Kenya.

PURPOSE: Nearly half of Kenyan women with breast cancer present with advanced disease-owing partially to limited patient education and screening limitations in low- and middle-income countries. With increasing access to nurse-led cervical cancer screening (CCS) in government clinics in Kenya, we investigated provider-perceived barriers and facilitators to integrating clinical breast examinations (CBEs) with ongoing CCS programs in Kisumu County, Kenya. METHODS: CCS providers within the Ministry of Health Clinics in Kisumu County, Kenya, were recruited to participate in a two-phase, sequential, mixed methods study. Knowledge of CBE guidelines was assessed with a questionnaire. Providers with significant CCS and CBE experience then completed a one-on-one interview discussing barriers and facilitators to integration. RESULTS: Sixty-nine providers from 20 randomly selected facilities participated in the survey. Providers all agreed that breast cancer screening was very important. Although 93% said that they routinely offered CBEs, only 22% of these providers screened at least eight of their last 10 patients. Forty-four percent identified four or more of five signs and symptoms of breast cancer, and 33% identified four to five risk factors. Although providers showed enthusiasm for integration of CBEs into their practices, barriers were identified and grouped into four themes: (1) fragmentation of services, (2) staffing shortage and inadequate on-the-job training, (3) limited space and referral system challenges, and (4) limited patient awareness on need for cancer screening. CONCLUSION: Addressing providers' concerns by providing routine on-the-job clinical training, improving staffing shortages, strengthening the diagnostic and treatment referral pathway, and increasing patient education are some of the first steps in facilitating integration of CBEs with CCS services in primary care clinics in Kenya.

Decentralized, primary-care delivered epilepsy services in Burera District, Rwanda: Service use, feasibility, and treatment.

BACKGROUND: Integrating epilepsy care into primary care settings could reduce the global burden of illness attributable to epilepsy. Since 2012, the Rwandan Ministry of Health and the international nonprofit Partners In Health have collaboratively used a multi-faceted implementation program- MESH MH-to integrate and scale-up care for epilepsy and mental disorders within rural primary care settings in Burera district, Rwanda. We here describe demographics, service use and treatment patterns for patients with epilepsy seeking care at MESH-MH supported primary care health centers. METHODS AND FINDINGS: This was a retrospective cohort study using routinely collected data from fifteen health centers in Burera district, from January 2015 to December 2016. 286 patients with epilepsy completed 3307 visits at MESH-MH participating health centers over a two year period (Jan 1st 2015 to Dec 31st 2016). Men were over twice as likely to be diagnosed with epilepsy than women (OR 2.38, CI [1.77-3.19]), and children under 10 were thirteen times as likely to be diagnosed with epilepsy as those 10 and older (OR 13.27, CI [7.18-24.51]). Carbamazepine monotherapy was prescribed most frequently (34% of patients). CONCLUSION: Task-sharing of epilepsy care to primary care via implementation programs such as MESH-MH has the potential to reduce the global burden of illness attributable to epilepsy.

Implementation, Outputs, and Cost of a National Operational Research Training in Rwanda.

Background: Training and mentorship in research skills are essential to developing a critical mass of researchers in low- and middle-income countries (LMICs). However, reporting on the details of such training programs, especially regarding the cost of the training, is limited. Objectives: This paper describes a year-long operational research training and mentorship course in Rwanda, implemented between 2013 and 2017. Approach: We describe motivations for the design of the Intermediate Operational Research Training Course (IORT) across four iterations. We also report outputs, evaluate trainee experiences, and estimate training and mentorship costs. Findings: Of the 132 applicants to the course, 55 (41.7%) were selected, and 53 (96.4%) completed the training. The ratio of female-to-male trainees in the course increased from 1:8 in 2013 to 1:3 in 2017. Trainees developed and co-first-authored 28 research manuscripts, 96.4% (n = 27) of which are published in peer-reviewed journals. For the 15 trainees who completed the post-course evaluation, 93.3% and 86.7% reported improvement in their research and analytical skills, respectively. The median cost per trainee to complete the course was US$908 (Range: US$739-US$1,253) and per research project was US$2,708 (US$1,748-US$6,741). The median annual training delivery and mentorship cost was US$47,170 (US$30,563-US$63,849) for a course with a Rwanda-based senior mentor, junior mentor, and training coordinator. The total essential cost for a year-long IORT course with 16 trainees co-leading eight research projects and mentored by two senior and four junior mentors was US$101,254 (US$73,486-US$157,569). Conclusion: We attribute the high course completion rates, publication rates, and skills acquisition to the learning-by-doing approach and intensive hands-on mentorship provided in the course. IORT was costly and funded through institutional resources and international partnerships. We encourage funders to prioritize comprehensive research capacity-building initiatives that provide intensive mentorship as these are likely to improve the pool of skilled researchers in LMICs.

Is development aid to strengthen health systems during protracted conflict a useful investment? The case of South Sudan, 2011-2015.

Introduction: Is achievement of Sustainable Development Goal (SDG) 16 (building peaceful societies) a precondition for achieving SDG 3 (health and well-being in all societies, including conflict-affected countries)? Do health system investments in conflict-affected countries waste resources or benefit the public's health? To answer these questions, we examine the maternal, newborn, child and reproductive health (MNCRH) service provision during protracted conflicts and economic shocks in the Republic of South Sudan between 2011 (at independence) and 2015. Methods: We conducted two national cross-sectional probability surveys in 10 states (2011) and nine states (2015). Trained state-level health workers collected data from households randomly selected using probability proportional to size sampling of villages in each county. County data were weighted by their population sizes to measure state and national MNCRH services coverage. A two-sample, two-sided Z-test of proportions tested for changes in national health service coverage between 2011 (n=11 800) and 2015 (n=10 792). Results: Twenty-two of 27 national indicator estimates (81.5%) of MNCRH service coverage improved significantly. Examples: malaria prophylaxis in pregnancy increased by 8.6% (p<0.001) to 33.1% (397/1199 mothers, 95% CI ±2.9%), institutional deliveries by 10.5% (p<0.001) to 20% (230/1199 mothers, ±2.6%) and measles vaccination coverage in children aged 12-23 months by 11.2% (p<0.001) to 49.7% (529/1064 children, ±2.3%). The largest increase (17.7%, p<0.001) occurred for mothers treating diarrhoea in children aged 0-59 months with oral rehydration salts to 51.4% (635/1235 children, ±2.9%). Antenatal and postnatal care, and contraceptive prevalence did not change significantly. Child vitamin A supplementation decreased. Despite significant increases, coverage remained low (median of all indicators = 31.3%, SD = 19.7). Coverage varied considerably by state (mean SD for all indicators and states=11.1%). Conclusion: Health system strengthening is not a uniform process and not necessarily deterred by conflict. Despite the conflict, health system investments were not wasted; health service coverage increased.

Measuring health system resilience in a highly fragile nation during protracted conflict: South Sudan 2011-15.

Health systems resilience (HSR) is defined as the ability of a health system to continue providing normal services in response to a crisis, making it a critical concept for analysis of health systems in fragile and conflict-affected settings (FCAS). However, no consensus for this definition exists and even less about how to measure HSR. We examine three current HSR definitions (maintaining function, improving function and achieving health system targets) using real-time data from South Sudan to develop a data-driven understanding of resilience. We used 14 maternal, newborn and child health (MNCH) coverage indicators from household surveys in South Sudan collected at independence (2011) and following 2 years of protracted conflict (2015), to construct a resilience index (RI) for 9 of the former 10 states and nationally. We also assessed health system stress using conflict-related indicators and developed a stress index. We cross tabulated the two indices to assess the relationship of resilience and stress. For maintaining function for 80% of MNCH indicators, seven state health systems were resilient, compared with improving function for 50% of the indicators (two states were resilient). Achieving the health system national target of 50% coverage in half of the MNCH indicators displayed no resilience. MNCH coverage levels were low, with state averages ranging between 15% and 44%. Central Equatoria State displayed high resilience and high system stress. Lakes and Northern Bahr el Ghazal displayed high resilience and low stress. Jonglei and Upper Nile States had low resilience and high stress. This study is the first to investigate HSR definitions using a resilience metric and to simultaneously measure health system stress in FCAS. Improving function is the HSR definition detecting the greatest variation in the RI. HSR and health system stress are not consistently negatively associated. HSR is highly complex warranting more in-depth analyses in FCAS.

Stuck in the middle: a systematic review of authorship in collaborative health research in Africa, 2014-2016.

BACKGROUND: Collaborations are often a cornerstone of global health research. Power dynamics can shape if and how local researchers are included in manuscripts. This article investigates how international collaborations affect the representation of local authors, overall and in first and last author positions, in African health research. METHODS: We extracted papers on 'health' in sub-Saharan Africa indexed in PubMed and published between 2014 and 2016. The author's affiliation was used to classify the individual as from the country of the paper's focus, from another African country, from Europe, from the USA/Canada or from another locale. Authors classified as from the USA/Canada were further subclassified if the author was from a top US university. In primary analyses, individuals with multiple affiliations were presumed to be from a high-income country if they contained any affiliation from a high-income country. In sensitivity analyses, these individuals were presumed to be from an African country if they contained any affiliation an African country. Differences in paper characteristics and representation of local coauthors are compared by collaborative type using χ² tests. RESULTS: Of the 7100 articles identified, 68.3% included collaborators from the USA, Canada, Europe and/or another African country. 54.0% of all 43 429 authors and 52.9% of 7100 first authors were from the country of the paper's focus. Representation dropped if any collaborators were from USA, Canada or Europe with the lowest representation for collaborators from top US universities-for these papers, 41.3% of all authors and 23.0% of first authors were from country of paper's focus. Local representation was highest with collaborators from another African country. 13.5% of all papers had no local coauthors. DISCUSSION: Individuals, institutions and funders from high-income countries should challenge persistent power differentials in global health research. South-South collaborations can help African researchers expand technical expertise while maintaining presence on the resulting research.

Health Facility Cost of Cesarean Delivery at a Rural District Hospital in Rwanda Using Time-Driven Activity-Based Costing.

Objective To determine the health facility cost of cesarean section at a rural district hospital in Rwanda. Methods Using time-driven activity-based costing, this study calculated capacity cost rates (cost per minute) for personnel, infrastructure and hospital indirect costs, and estimated the costs of medical consumables and medicines based on purchase prices, all for the pre-, intra- and post-operative periods. We estimated copay (10% of total cost) for women with community-based health insurance and conducted sensitivity analysis to estimate total cost range. Results The total cost of a cesarean delivery was US$339 including US$118 (35%) for intra-operative costs and US$221 (65%) for pre- and post-operative costs. Costs per category included US$46 (14%) for personnel, US$37 (11%) for infrastructure, US$109 (32%) for medicines, US$122 (36%) for medical consumables, and US$25 (7%) for hospital indirect costs. The estimated copay for women with community-based health insurance was US$34 and the total cost ranged from US$320 to US$380. Duration of hospital stay was the main marginal cost variable increasing overall cost by US$27 (8%). Conclusions for Practice The cost of cesarean delivery and the cost drivers (medicines and medical consumables) in our setting were similar to previous estimates in sub-Saharan Africa but higher than earlier average estimate in Rwanda. The estimated copay is potentially catastrophic for poor rural women. Investigation on the impact of true out of pocket costs on women's health outcomes, and strategies for reducing duration of hospital stay while maintaining high quality care are recommended.

Emergency general surgery in Rwandan district hospitals: a cross-sectional study of spectrum, management, and patient outcomes.

BACKGROUND: Management of emergency general surgical conditions remains a challenge in rural sub-Saharan Africa due to issues such as insufficient human capacity and infrastructure. This study describes the burden of emergency general surgical conditions and the ability to provide care for these conditions at three rural district hospitals in Rwanda. METHODS: This retrospective cross-sectional study included all patients presenting to Butaro, Kirehe and Rwinkwavu District Hospitals between January 1st 2015 and December 31st 2015 with emergency general surgical conditions, defined as non-traumatic, non-obstetric acute care surgical conditions. We describe patient demographics, clinical characteristics, management and outcomes. RESULTS: In 2015, 356 patients presented with emergency general surgical conditions. The majority were male (57.2%) and adults aged 15-60 years (54.5%). The most common diagnostic group was soft tissue infections (71.6%), followed by acute abdominal conditions (14.3%). The median length of symptoms prior to diagnosis differed significantly by diagnosis type (p < 0.001), with the shortest being urological emergencies at 1.5 days (interquartile range (IQR):1, 6) and the longest being complicated hernia at 17.5 days (IQR: 1, 208). Of all patients, 54% were operated on at the district hospital, either by a general surgeon or general practitioner. Patients were more likely to receive surgery if they presented to a hospital with a general surgeon compared to a hospital with only general practitioners (75% vs 43%, p < 0.001). In addition, the general surgeon was more likely to treat patients with complex diagnoses such as acute abdominal conditions (33.3% vs 4.1%, p < 0.001) compared to general practitioners. For patients who received surgery, 73.3% had no postoperative complications and 3.2% died. CONCLUSION: While acute abdominal conditions are often considered the most common emergency general surgical condition in sub-Saharan Africa, soft tissue infections were the most common in our setting. This could represent a true difference in epidemiology in rural settings compared to referral facilities in urban settings. Patients were more likely to receive an operation in a hospital with a general surgeon as opposed to a general practitioner. This provides evidence to support increasing the surgical workforce in district hospitals in order to increase surgical availability for patients.

Adapting operational research training to the Rwandan context: the Intermediate Operational Research Training programme.

BACKGROUND: Promoting national health research agendas in low- and middle-income countries (LMICs) requires adequate numbers of individuals with skills to initiate and conduct research. Recently, non-governmental organizations (NGOs) have joined research capacity building efforts to increase research leadership by LMIC nationals. Partners In Health, an international NGO operating in Rwanda, implemented its first Intermediate Operational Research Training (IORT) course to cultivate Rwandan research talent and generate evidence to improve health care delivery. OBJECTIVE: This paper describes the implementation of IORT to share experiences with other organizations interested in developing similar training programmes. METHODS: The Intermediate Operational Research Training utilized a deliverable-driven training model, using learning-by-doing pedagogy with intensive hands-on mentorship to build research skills from protocol development to scientific publication. The course had short (two-day) but frequent training sessions (seven sessions over eight months). Trainees were clinical and programme staff working at the district level who were paired to jointly lead a research project. RESULTS: Of 10 trainees admitted to the course from a pool of 24 applicants, nine trainees completed the course with five research projects published in peer-reviewed journals. Strengths of the course included supportive national and institutional research capacity guidelines, building from a successful training model, and trainee commitment. Challenges included delays in ethical review, high mentorship workload of up to 250 hours of practicum mentorship, lack of access to literature in subscription journals and high costs of open access publication. CONCLUSIONS: The IORT course was an effective way to support the district-based government and NGO staff in gaining research skills, as well as answering research questions relevant to health service delivery at district hospitals. Other NGOs should build on successful programmes while adapting course elements to address context-specific challenges. Mentorship for LMIC trainees is critical for effectiveness of research capacity building initiatives.

Health worker attrition at a rural district hospital in Rwanda: a need for improved placement and retention strategies.

INTRODUCTION: The shortage and maldistribution of health care workers in sub-Saharan Africa is a major concern for rural health facilities. Rural areas have 63% of sub-Saharan Africa population but only 37% of its doctors. Although attrition of health care workers is implicated in the human resources for health crisis in the rural settings, few studies report attrition rates and risk factors for attrition in rural district hospitals in sub-Saharan Africa. METHODS: We assessed attrition of health care workers at a Kirehe District Hospital in rural Rwanda. We included all hospital staff employed as of January 1, 2013 in this retrospective cohort study. We report the proportion of staff that left employment during 2013, and used a logistic regression to assess individual characteristics associated with attrition. RESULTS: Of the 142 staff employed at Kirehe District Hospital at the start of 2013, 31.7% (n=45) of all staff and 81.8% (n=9) of doctors left employment in 2013. Being a doctor (OR=10.0, 95% CI: 1.9-52.1, p=0.006) and having up to two years of experience at the hospital (OR=5.3, 95% CI: 1.3-21.7, p=0.022) were associated with attrition. CONCLUSION: Kirehe District Hospital experienced high attrition rates in 2013, particularly among doctors. Opportunities for further training through Rwanda's Human Resources for Health program in 2013 and a two-year compulsory service program for doctors that is not linked to interventions for rural retention may have driven these patterns. Efforts to link these programs with rural placement and retention strategies are recommended.

A Novel Combined Mother-Infant Clinic to Optimize Post-Partum Maternal Retention, Service Utilization, and Linkage to Services in HIV Care in Rural Rwanda.

BACKGROUND AND OBJECTIVES: Despite recent improvements in accessibility of services to prevent mother-to-child transmission of HIV, maternal retention in HIV care remains a challenge in the post-partum period. This study assessed service utilization, program retention, and linkage to routine services, as well as clinical outcomes for mothers and infants, following implementation of an integrated mother-infant clinic in rural Rwanda. METHODS: We conducted a retrospective cohort study of all HIV-positive mothers and their infants enrolled in the integrated clinics in two rural districts between July 1, 2012, and June 30, 2013. At 18 months post-partum, data on mother-infant service utilization and program outcomes were reported. RESULTS: Of the 185 mother-infant pairs in the clinics, 98.4% of mothers were on antiretroviral therapy (ART) and 30.3% used modern contraception at enrollment. At 18 months post-partum, 98.4% of mothers were retained and linked back to adult HIV program. All mothers were on ART and 72.0% on modern contraception. For infants, 93.0% completed follow-up. Two (1.1%) infants tested HIV positive. CONCLUSION AND GLOBAL HEALTH IMPLICATION: An integrated clinic was successfully implemented in rural Rwanda with high mother retention in care and low mother to child HIV transmission rates. This model of integration of services may contribute to improved mother-infant retention in care during post-partum period and should be considered as one approach to addressing this challenge in similar settings.

Longer travel time to district hospital worsens neonatal outcomes: a retrospective cross-sectional study of the effect of delays in receiving emergency cesarean section in Rwanda.

BACKGROUND: In low-resource settings, access to emergency cesarean section is associated with various delays leading to poor neonatal outcomes. In this study, we described the delays a mother faces when needing emergency cesarean delivery and assessed the effect of these delays on neonatal outcomes in Rwanda. METHODS: This retrospective study included 441 neonates and their mothers who underwent emergency cesarean section in 2015 at three district hospitals in Rwanda. Four delays were measured: duration of labor prior to hospital admission, travel time from health center to district hospital, time from admission to surgical incision, and time from decision for emergency cesarean section to surgical incision. Neonatal outcomes were categorized as unfavorable (APGAR <7 at 5 min or death) and favorable (alive and APGAR ≥7 at 5 min). We assessed the relationship between each type of delay and neonatal outcomes using multivariate logistic regression. RESULTS: In our study, 9.1% (40 out of 401) of neonates had an unfavorable outcome, 38.7% (108 out of 279) of neonates' mothers labored for 12-24 h before hospital admission, and 44.7% (159 of 356) of mothers were transferred from health centers that required 30-60 min of travel time to reach the district hospital. Furthermore, 48.1% (178 of 370) of cesarean sections started within 5 h after hospital admission and 85.2% (288 of 338) started more than 30 min after the decision for cesarean section was made. Neonatal outcomes were significantly worse among mothers with more than 90 min of travel time from the health center to the district hospital compared to mothers referred from health centers located on the same compound as the hospital (aOR = 5.12, p = 0.02). Neonates with cesarean deliveries starting more than 30 min after decision for cesarean section had better outcomes than those starting immediately (aOR = 0.32, p = 0.04). CONCLUSIONS: Longer travel time between health center and district hospital was associated with poor neonatal outcomes, highlighting a need to decrease barriers to accessing emergency maternal services. However, longer decision to incision interval posed less risk for adverse neonatal outcome. While this could indicate thorough pre-operative interventions including triage and resuscitation, this relationship should be studied prospectively in the future.

Maternal predictors of neonatal outcomes after emergency cesarean section: a retrospective study in three rural district hospitals in Rwanda.

BACKGROUND: In sub-Saharan Africa, neonatal mortality post-cesarean delivery is higher than the global average. In this region, most emergency cesarean sections are performed at district hospitals. This study assesses maternal predictors for poor neonatal outcomes post-emergency cesarean delivery in three rural district hospitals in Rwanda. METHODS: This retrospective study includes a random sample of 441 neonates from Butaro, Kirehe and Rwinkwavu District Hospitals, born between 01 January and 31 December 2015. We described the demographic and clinical characteristics of the mothers of these neonates using frequencies and proportions. We assessed the association between maternal characteristics with poor neonatal outcomes, defined as death within 24 h or APGAR < 7 at 5 min after birth, using Fisher's exact test. Factors significant at α = 0.20 significance level were considered for the multivariate logistic regression model, built using a backwards stepwise process. We stopped when all the factors were significant at the α = 0.05 level. RESULTS: For all 441 neonates included in this study, 40 (9.0%) had poor outcomes. In the final model, three factors were significantly associated with poor neonatal outcomes. Neonates born to mothers who had four or more prior pregnancies were more likely to have poor outcomes (OR = 3.01, 95%CI:1.23,7.35, p = 0.015). Neonates whose mothers came from health centers with ambulance travel times of more than 30 min to the district hospital had greater odds of having poor outcomes (for 30-60 min: OR = 3.80, 95%CI:1.07,13.40, p = 0.012; for 60+ minutes: OR = 5.82, 95%CI:1.47,23.05, p = 0.012). Neonates whose mothers presented with very severe indications for cesarean section had twice odds of having a poor outcome (95% CI: 1.11,4.52, p = 0.023). CONCLUSIONS: Longer travel time to the district hospital was a leading predictor of poor neonatal outcomes post cesarean delivery. Improving referral systems, ambulance availability, number of equipped hospitals per district, and road networks may lessen travel delays for women in labor. Boosting the diagnostic capacity of labor conditions at the health center level through facilities and staff training can improve early identification of very severe indications for cesarean delivery for early referral and intervention.

Research capacity building integrated into PHIT projects: leveraging research and research funding to build national capacity.

BACKGROUND: Inadequate research capacity impedes the development of evidence-based health programming in sub-Saharan Africa. However, funding for research capacity building (RCB) is often insufficient and restricted, limiting institutions' ability to address current RCB needs. The Doris Duke Charitable Foundation's African Health Initiative (AHI) funded Population Health Implementation and Training (PHIT) partnership projects in five African countries (Ghana, Mozambique, Rwanda, Tanzania and Zambia) to implement health systems strengthening initiatives inclusive of RCB. METHODS: Using Cooke's framework for RCB, RCB activity leaders from each country reported on RCB priorities, activities, program metrics, ongoing challenges and solutions. These were synthesized by the authorship team, identifying common challenges and lessons learned. RESULTS: For most countries, each of the RCB domains from Cooke's framework was a high priority. In about half of the countries, domain specific activities happened prior to PHIT. During PHIT, specific RCB activities varied across countries. However, all five countries used AHI funding to improve research administrative support and infrastructure, implement research trainings and support mentorship activities and research dissemination. While outcomes data were not systematically collected, countries reported holding 54 research trainings, forming 56 mentor-mentee relationships, training 201 individuals and awarding 22 PhD and Masters-level scholarships. Over the 5 years, 116 manuscripts were developed. Of the 59 manuscripts published in peer-reviewed journals, 29 had national first authors and 18 had national senior authors. Trainees participated in 99 conferences and projects held 37 forums with policy makers to facilitate research translation into policy. CONCLUSION: All five PHIT projects strongly reported an increase in RCB activities and commended the Doris Duke Charitable Foundation for prioritizing RCB, funding RCB at adequate levels and time frames and for allowing flexibility in funding so that each project could implement activities according to their trainees' needs. As a result, many common challenges for RCB, such as adequate resources and local and international institutional support, were not identified as major challenges for these projects. Overall recommendations are for funders to provide adequate and flexible funding for RCB activities and for institutions to offer a spectrum of RCB activities to enable continued growth, provide adequate mentorship for trainees and systematically monitor RCB activities.