Early Effects of Scaling Up Dolutegravir-Based ARV Regimens Among Children Living with HIV in Malawi.

Viral suppression (VS) in children has remained suboptimal compared to that in adults. We evaluated the impact of transitioning children weighing < 20 kg to a pediatric formulation of dolutegravir (pDTG) on VS in Malawi. We analyzed routine retrospective program data from electronic medical record systems pooled across 169 healthcare facilities in Malawi supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). We included children who weighed < 20 kg and received antiretroviral therapy (ART) between July 2021-June 2022. Using descriptive statistics, we summarized demographic and clinical characteristics, ART regimens, ART adherence, and VS. We used logistic regression to identify factors associated with post-transition VS. A total of 2468 Children Living with HIV (CLHIV) were included, 55.3% of whom were < 60 months old. Most (83.8%) had initiated on non-DTG-based ART; 71.0% of these had a viral load (VL) test result before transitioning to pDTG, and 62.5% had VS. Nearly all (99.9%) CLHIV transitioned to pDTG-based regimens. Six months after the transition, 52.7% had good ART adherence, and 38.6% had routine VL testing results; 81.7% achieved VS. Post-transition VS was associated with good adherence and pre-transition VS: adjusted odds ratios of 2.79 (95% CI 1.65-4.71), p < 0.001 and 5.32 (95% CI 3.23-9.48), p < 0.001, respectively. After transitioning to pDTG, VS was achieved in most children tested within the first 6 months. However, adherence remained suboptimal post-transition and VL testing at 6 months was limited. Interventions to improve VL testing and enhance ART adherence are still needed in CLHIV on pDTG-based regimens.

Improving TB detection among children in routine clinical care through intensified case finding in facility-based child health entry points and decentralized management: A before-and-after study in Nine Sub-Saharan African Countries.

In 2022, an estimated 1.25 million children <15 years of age developed tuberculosis (TB) worldwide, but >50% remained undiagnosed or unreported. WHO recently recommended integrated and decentralized models of care as an approach to improve access to TB services for children, but evidence remains limited. The Catalyzing Paediatric TB Innovation project (CaP-TB) implemented a multi-pronged intervention to improve TB case finding in children in nine sub-Saharan African countries. The intervention introduced systematic TB screening in different facility-based child-health entry-points, decentralisation of TB diagnosis and management, improved sample collection with access to Xpert® MTB/RIF or MTB/RIF Ultra testing, and implementation of contact investigation. Pre-intervention records were compared with those during intervention to assess effect on paediatric TB cascade of care. The intervention screened 1 991 401 children <15 years of age for TB across 144 health care facilities. The monthly paediatric TB case detection rate increased significantly during intervention versus pre-intervention (+46.0%, 95% CI 36.2-55.8%; p<0.0001), with variability across countries. The increase was greater in the <5 years old compared to the 5-14 years old (+53.4%, 95% CI 35.2-71.9%; p<0.0001 versus +39.9%, 95% CI 27.6-52.2%; p<0.0001). Relative contribution of lower-tier facilities to total case detection rate increased from 37% (71.8/191.8) pre-intervention to 50% (139.9/280.2) during intervention. The majority (89.5%) of children with TB were identified through facility-based intensified case-finding and primarily accessed care through outpatient and inpatient departments. In this multi-country study implemented under real-life conditions, the implementation of integrated and decentralized interventions increased paediatric TB case detection. The increase was driven by lower-tier facilities that serve as the primary point of healthcare contact for most patients. The effect was greater in children < 5 years compared to 5-14 years old, representing an important achievement as the TB detection gap is higher in this subpopulation. (Study number NCT03948698).

Factors associated with COVID-19 vaccine receipt among mobile phone users in Malawi: Findings from a national mobile-based syndromic surveillance survey, July 2021-April 2022.

Malawi recommended COVID-19 vaccines for adults aged ≥18 years in March 2021. We assessed factors associated with receiving COVID-19 vaccines in Malawi as part of a telephone-based syndromic surveillance survey. We conducted telephone-based syndromic surveillance surveys with questions on COVID-19 vaccine receipt among adults (≥18 years old) upon verbal consent from July 2021 to April 2022. We used random digit dialing to select mobile phone numbers and employed electronic data collection forms on secure tablets. Survey questions included whether the respondent had received at least one dose of a COVID-19 vaccine. We used multivariable analysis to identify factors associated with COVID-19 vaccine receipt. Of the 51,577 participants enrolled; 65.7% were male. Males were less likely to receive the COVID-19 vaccine than females (AOR 0.83, 95% CI 0.80-0.86). Compared to those aged 18-24 years, older age had increased odds of vaccine receipt: 25-34 years (AOR 1.32, 95% CI 1.24-1.40), 35-44 years (AOR 2.00, 95% CI 1.88-2.13), 45-54 years (AOR 3.02, 95% CI 2.82-3.24), 55-64 years (AOR 3.24, 95% CI 2.93-3.57) and 65 years+ (AOR 3.98, 95% CI 3.52-4.49). Respondents without formal education were less likely to receive vaccination compared to those with primary (AOR 1.30, 95% CI 1.14-1.48), secondary (AOR 1.76, 95% CI 1.55-2.01), and tertiary (AOR 3.37, 95% CI 2.95-3.86) education. Respondents who thought COVID-19 vaccines were unsafe were less likely to receive vaccination than those who thought it was very safe (AOR 0.26, 95% CI 0.25-0.28). Residents of the Central and Southern regions had reduced odds of vaccine receipt compared to those in the North (AORs 0.79, (95% CI 0.74-0.84) and 0.55, (95% CI 0.52-0.58) respectively). Radio (72.6%), health facilities (52.1%), and social media (16.0%) were the more common self-reported sources of COVID-19 vaccine information. COVID-19 vaccine receipt is associated with gender, age, education, and residence. It is important to consider these factors when implementing COVID-19 vaccination programs.

Safety of Janssen Ad26.COV.S and Astra Zeneca AZD1222 COVID-19 Vaccines among Mobile Phone Users in Malawi: Findings from a National Mobile-Based Syndromic Surveillance Survey, July 2021 to December 2021.

The safety profiles of the Ad26.COV2.S and AZD1222 COVID-19 vaccines have not been described in the general population in Malawi. We present self-reported adverse events (AE) following the receipt of these vaccines in Malawi as part of a national syndromic surveillance survey. We conducted phone-based syndromic surveillance surveys among adults (≥18 years) with verbal consent. We used secure tablets through random digit dialing to select mobile phone numbers and collected data electronically. Survey questions included whether the respondent had received the COVID-19 vaccines, whether they had experienced any AE following vaccination, and the severity of the AE. We used multivariable analysis to identify factors associated with self-reported AE post-COVID-19 vaccination. A total of 11,924 (36.0%) out of 33,150 respondents reported receiving at least one dose of either Ad26.COV2.S or AZD1222 between July-December 2021; of those, 65.1% were female. About 49.2% of the vaccine recipients reported at least one AE, 90.6% of which were mild, and 2.6% were severe. Higher education level and concern about the safety of COVID-19 vaccines were associated with AE self-report (Adjusted Odds Ratio [AOR] 2.63 [95% CI 1.96-3.53] and 1.44, [95% CI 1.30-1.61], respectively), while male gender and older age were associated with reduced likelihood of AE self-report (AORs 0.81, [95% CI 0.75-0.88], 0.62 [95% CI 0.50-0.77], respectively). Ad26.COV2.S and AZD1222 vaccines are well-tolerated, with primarily mild and few severe AE among adults living in Malawi. Self-reporting of AE following COVID-19 vaccination is associated with gender, age, education, and concern about the safety of the vaccines. Recognizing these associations is key when designing and implementing COVID-19 vaccination communication messages to increase vaccination coverage.

Uptake of and intention to use oral pre-exposure prophylaxis for HIV among pregnant and post-natal women in Eswatini: a cross-sectional survey.

Introduction: In Eswatini, HIV incidence among women of childbearing age is 1.45%. Eswatini introduced oral pre-exposure prophylaxis (PrEP) for HIV prevention in 2016 and requires that all HIV-negative pregnant and post-natal women (PPW) visiting health care facilities be offered PrEP. Methods: Between September-November 2021, we conducted a survey among HIV-negative PPW from 16 purposively selected healthcare facilities in the Hhohho and Shiselweni regions in Eswatini. We interviewed consenting HIV-negative PPW using a structured questionnaire to collect data on PrEP knowledge, attitudes, intentions, and practices, as well as information on partner HIV status and stigma. Multivariate logistic regression was used to determine predictors of PrEP use and intention, adjusted for significant covariates. Results: Of 1,484 PPW women approached, 1,149 consented and were interviewed, of whom 704 (61.3%) were post-partum and 445 (38.7%) pregnant. The median age was 25 years [Interquartile Range (IQR) = 21-30 years], with 533 (46.4%) 18-24 years old. Among the 1,149 women, 930 (80.7%) had ever heard about PrEP; 635 (55.3%) had knowledge about PrEP; 183 (15.9%) were currently using PrEP; and 285 (24.8%) had ever used PrEP. Increased odds of PrEP use were associated having HIV-positive male partner (aOR:7.76, 95%CI 3.53- 17.04); positive attitudes to PrEP (aOR:1.56, 95%CI: 1.02-2.40); and high self-efficacy (aOR:1.49, 95%CI:1.13-1.98). Among 864 women who never used PrEP, 569 (65.3%) intended to use PrEP in the future. Odds of intention to use PrEP were higher among women with low levels of education (aOR:2.23, 95% CI: 1.32-3.77); who ever heard about PrEP (aOR:1.69, 95%CI: 1.12-2.56); and had high self-efficacy (aOR:1.57, 95%CI: 1.31-1.87). Regarding stigma, among all women, 759 (66%) either agreed or strongly agreed that people would think they have HIV if they were to use PrEP; 658 (57.3%) reported they would be labelled as having multiple sex partners; 468 (40.7%) reported that their partner would think they are having risky sex with other people. Of 102 women who had discontinued PrEP, a majority stopped due to side effects 32 (35.2%). Conclusion: Only about 50% of women had knowledge of PrEP, and PrEP uptake among PPW was low, though intention to use appeared high. More efforts to reduce stigma and promote PrEP use, including adequate information on side effects, are needed.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe: A randomized controlled trial.

BACKGROUND: In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. METHODS: The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. RESULTS: Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance. CONCLUSION: In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH.

Protocol to implement a syndromic surveillance survey of COVID-19 in Malawi.

Introduction: Malawi experienced two waves of COVID-19 between April 2020 and February 2021. A High negative impact of COVID-19 was experienced in the second wave, with increased hospital admissions that overwhelmed the healthcare system. This paper describes a protocol to implement a telephone-based syndromic surveillance system to assist public health leaders in the guidance, implementation, and evaluation of programs and policies for COVID-19 prevention and control in Malawi. Study design: This is a serial cross-sectional telephonic-based national survey focusing on the general population and People living with HIV and AIDS. Methods: We will conduct a serial cross-sectional telephone survey to assess self-reported recent and current experience of influenza-like illness (ILI)/COVID-19-like-illness (CLI), household deaths, access to routine health services, and knowledge related to COVID-19. Structured questionnaires will be administered to two populations: 1) the general population and 2) people living with HIV (PLHIV) on antiretroviral therapy (ART) at EGPAF-supported health facilities. Electronic data collection forms using secure tablets will be used based on randomly selected mobile numbers from electronic medical records (EMR) for PLHIV. We will use random digit dialing (RDD) for the general population to generate phone numbers to dial respondents. The technique uses computer-generated random numbers, using the 10-digit basic structure of mobile phone numbers for the two existing mobile phone companies in Malawi. Interviews will be conducted only with respondents that will verbally consent. A near real-time online dashboard will be developed to help visualize the data and share results with key policymakers. Conclusion: The designed syndromic surveillance system is low-cost and feasible to implement under COVID-19 restrictions, with no physical contact with respondents and limited movement of the study teams and communities. The system will allow estimation proportions of those reporting ILI/CLI among the general population and PLHIV on ART and monitor trends over time to detect locations with possible COVID-19 transmission. Reported household deaths in Malawi, access to health services, and COVID-19 knowledge will be monitored to assess the burden and impact on communities in Malawi.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Pregnancy in Sub-Saharan Africa: A 6-Country Retrospective Cohort Analysis.

BACKGROUND: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. RESULTS: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13). CONCLUSIONS: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.

Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale.

Tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy program in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care simplified amplification-based assays (Diagnostics for the Real World, Sunnyvale, CA, USA) at Chidamoyo Christian Hospital and rate of virological suppression (VS) on TLD (VL <1,000 copies/mL) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median [interquartile range (IQR)] age was 15 (11-19) years, above half of the participants were female (57%). Before switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ≥1,000 copies/mL on TLD, 90% (9/10) were failing on their previous regimens, 6 of 9 (67%) having been on boosted protease inhibitor-based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virological failure and emergence of resistance in Africa. However, longer follow-up might be needed to ascertain sustained VS in this vulnerable population. Randomized Control Trial NCT03986099.

Maternal mortality decline in Zimbabwe, 2007/2008 to 2018/2019: findings from mortality surveys using civil registration, vital statistics and health system data.

BACKGROUND: Sustainable Development Goal (SDG) 3.1 target is to reduce the global maternal mortality ratio (MMR) to less than 70 maternal deaths per 100 000 live births by 2030. In the Ending Preventable Maternal Mortality strategy, a supplementary target was added, that no country has an MMR above 140 by 2030. We conducted two cross-sectional reproductive age mortality surveys to analyse changes in Zimbabwe's MMR between 2007-2008 and 2018-2019 towards the SDG target. METHODS: We collected data from civil registration, vital statistics and medical records on deaths of women of reproductive ages (WRAs), including maternal deaths from 11 districts, randomly selected from each province (n=10) using cluster sampling. We calculated weighted mortality rates and MMRs using negative binomial models, with 95% CIs, performed a one-way analysis of variance of the MMRs and calculated the annual average reduction rate (ARR) for the MMR. RESULTS: In 2007-2008 we identified 6188 deaths of WRAs, 325 pregnancy-related deaths and 296 maternal deaths, and in 2018-2019, 1856, 137 and 130, respectively. The reproductive age mortality rate, weighted by district, declined from 11 to 3 deaths per 1000 women. The MMR (95% CI) declined from 657 (485 to 829) to 217 (164 to 269) deaths per 100 000 live births at an annual ARR of 10.1%. CONCLUSIONS: Zimbabwe's MMR declined by an annual ARR of 10.1%, against a target of 10.2%, alongside declining reproductive age mortality. Zimbabwe should continue scaling up interventions against direct maternal mortality causes to achieve the SDG 3.1 target by 2030.

Changes in causes of pregnancy-related and maternal mortality in Zimbabwe 2007-08 to 2018-19: findings from two reproductive age mortality surveys.

BACKGROUND: Reducing maternal mortality is a priority of Sustainable Development Goal 3.1 which requires frequent epidemiological analysis of trends and patterns of the causes of maternal deaths. We conducted two reproductive age mortality surveys to analyse the epidemiology of maternal mortality in Zimbabwe and analysed the changes in the causes of deaths between 2007-08 and 2018-19. METHODS: We performed a before and after analysis of the causes of death among women of reproductive ages (WRAs) (12-49 years), and pregnant women from the two surveys implemented in 11 districts, selected using multi-stage cluster sampling from each province of Zimbabwe (n=10); an additional district selected from Harare. We calculated mortality incidence rates and incidence rate ratios per 10000 WRAs and pregnant women (with 95% confidence intervals), in international classification of disease groups, using negative binomial models, and compared them between the two surveys. We also calculated maternal mortality ratios, per 100 000 live births, for selected causes of pregnancy-related deaths. RESULTS: We identified 6188 deaths among WRAs and 325 PRDs in 2007-08, and 1856 and 137 respectively in 2018-19. Mortality in the WRAs decreased by 82% in diseases of the respiratory system and 81% in certain infectious or parasitic diseases' groups, which include HIV/AIDS and malaria. Pregnancy-related deaths decreased by 84% in the indirect causes group and by 61% in the direct causes group, and HIV/AIDS-related deaths decreased by 91% in pregnant women. Direct causes of death still had a three-fold MMR than indirect causes (151 vs. 51 deaths per 100 000) in 2018-19. CONCLUSION: Zimbabwe experienced a decline in both direct and indirect causes of pregnancy-related deaths. Deaths from indirect causes declined mainly due to a reduction in HIV/AIDS-related and malaria mortality, while deaths from direct causes declined because of a reduction in obstetric haemorrhage and pregnancy-related infections. Ongoing interventions ought to improve the coverage and quality of maternal care in Zimbabwe, to further reduce deaths from direct causes.

Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries.

IMPORTANCE: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. OBJECTIVE: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. EXPOSURES: Age, sex, preexisting comorbidities, and region of residence. MAIN OUTCOMES AND MEASURES: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. RESULTS: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. CONCLUSIONS AND RELEVANCE: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

Methods used to measure maternal mortality in Sub-Saharan Africa from 1980 to 2020: A systematic literature review.

BACKGROUND: Gobally, Sub-Saharan Africa (SSA) has the largest maternal mortality burden, but the region lacks accurate data. OBJECTIVE: To review methods historically used to measure maternal mortality in SSA to inform future study methods. SEARCH STRATEGY: We searched databases: PubMed, Medline, WorldCat and CINHAL, using keywords "maternal mortality," "pregnancy-related death," "reproductive age mortality," "ratio," "rate," and "risk," using Boolean operators "OR" and "AND" to combine the search terms. SELECTION CRITERIA: We searched for empirical and analytical studies that: (1) measured maternal mortality levels, (2) were in SSA, (3) reported original results, and (4) were not duplicate studies. We included studies published in English since 1980. DATA COLLECTION AND ANALYSIS: We screened the studies using titles and abstracts, reading the full text of selected studies. We analyzed the estimates and strengths, and limitations of the methods. MAIN RESULTS: We identified 96 studies that used nine methods: demographic surveillance (n = 4), health record reviews (n = 18), confidential enquiries and maternal death surveillance and response (n = 7), prospective cohort (n = 9), reproductive age mortality survey (RAMOS) (n = 6), sisterhood method (n = 35), mixed methods (n = 4), and mathematical modeling (n = 13). CONCLUSION: Sisterhood method studies and RAMOS studies that combined institutional records and community data produced maternal mortality ratios more comparable with WHO estimates.

Causes of maternal mortality in Sub-Saharan Africa: A systematic review of studies published from 2015 to 2020.

BACKGROUND: Maternal deaths remain high in Sub-Saharan Africa (SSA) and their causes of maternal death must be analysed frequently in this region to guide interventions. METHODS: We conducted a systematic review of studies published from 2015 to 2020 that reported the causes of maternal deaths in 57 SSA countries. The objective was to identify the leading causes of maternal deaths using the international classification of disease - 10th revision, for maternal mortality (ICD-MM). We searched PubMed, WorldCat Discovery Libraries Worldwide (including Medline, Web of Science, LISTA and CNHAL databases), and Google Scholar databases and citations, using the search words "maternal mortality", "maternal death", "pregnancy-related death", "reproductive age mortality" and "causes" as MeSH terms or keywords. The last date of search from all databases was 21 May 2021. We included original research articles published in English and excluded articles that mentioned SSA country names without study results for those countries, studies that reported death from a single cause or assigned causes of death using computer models or incompletely broke down the causes of death. We exported, de-duplicated and screened the searches electronically in EndNote version 20. We selected the final articles by reading the titles, abstracts and full texts. Two authors searched the articles and assessed the risk of bias using a tool adapted from Montoya and others. Data from the articles were extracted onto an Excel worksheet and the deaths classified into ICD-MM groups. Proportions were calculated with 95% confidence intervals and compared for deaths attributed to each cause and ICD-MM group. We compared the results with WHO and Global Burden of Disease (GDB) estimates. RESULTS: We identified 38 studies that reported 11 427 maternal and four incidental deaths. Twenty-one of the third-eight studies were retrospective record reviews. The leading causes of death (proportions and 95% confidence intervals (CI)) were obstetric hemorrhage: 28.8% (95% CI = 26.5%-31.2%), hypertensive disorders in pregnancy: 22.1% (95% CI = 19.9%-24.2%), non-obstetric complications: 18.8% (95% CI = 16.4%-21.2%) and pregnancy-related infections: 11.5% (95% CI = 9.8%-13.2%). The studies reported few deaths of unknown/undetermined and incidental causes. CONCLUSIONS: Limitations of this review were the failure to access more data from government reports, but the study results compared well with WHO and GDB estimates. Obstetric hemorrhage, hypertensive disorders in pregnancy, non-obstetric complications, and pregnancy-related infections are the leading causes of maternal deaths in SSA. However, deaths from incidental causes are likely under-reported in this region. SSA countries must continue to invest in health information systems that collect and publishes comprehensive, quality, maternal death causes data. A publicly accessible repository of data sets and government reports for causes of maternal death will be helpful in future reviews. This review received no specific funding and was not registered.

Developing and Validating an Effective Pediatric and Adolescent HIV Testing Eligibility Screening Tool for High-Volume Entry Points in Uganda.

INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents.

A randomized controlled trial evaluating the effects of a family-centered HIV care model on viral suppression and retention in care of HIV-positive children in Eswatini.

INTRODUCTION: A family-centered care model (FCCM) providing family-based HIV services, rather than separate adult/pediatric services, has been proposed to increase pediatric retention and treatment adherence. MATERIALS AND METHODS: Eight health-care facilities in the Hhohho region of Eswatini were randomized to implement FCCM (n = 4) or continue standard-of-care (SOC) separate adult/pediatric clinics (n = 4). HIV-positive children and caregivers were enrolled; caregiver interview and child/caregiver chart abstraction were done at enrollment and every three months; pediatric viral load was evaluated at enrollment and every six months through 12 months. Because of study group differences in 12-month viral load data availability (89.4% FCCM and 72.0% SOC children had 12-month viral load), we used three separate analyses to evaluate the effects of FCCM on children's viral suppression (<1,000 copies/mL) and undetectable virus (<400 copies/mL) at 12 months. In the first analysis, all children with missing viral outcome data were excluded from the analysis (modified intent to treat, mITT). The second analysis used inverse probability of missingness weighted logistic regression to estimate the effect of FCCM on 12-month viral outcomes compared to SOC (weighted mITT). For the third approach, missing virologic outcome data were imputed as virologic failure (imputed ITT). We also examined factors associated with viral suppression at 12 months using multivariable logistic regression. RESULTS: We enrolled 379 HIV-positive children and 363 caregivers. Among all children at enrollment, viral suppression and undetectability was 78.4% and 73.9%, respectively, improving to 90.2% and 87.3% at 12 months. In mITT and weighted mITT analyses, there was no significant difference in children's 12-month viral suppression between FCCM and SOC groups (89.2% and 91.6%, respectively). Using imputed ITT, there was a modest increase in 12-month viral suppression in FCCM versus SOC children (79.7% and 69.8%, respectively, p = 0.051) and 12-month undetectability (78.7% and 65.7%, respectively, p = 0.015). Among the 255 children suppressed at enrollment, more FCCM versus SOC children (98.0% versus 95.3%) were suppressed at 12-months, but this was not statistically significant in mITT or weighted mITT analyses, with a marginally significant difference using imputed mITT analysis (p = 0.042). A higher proportion of children suppressed at enrollment had undetectable viral load at 12 months in FCCM versus SOC children (98.0% versus 92.5%), a statistically significant difference across analytical methods. Among the 61 children unsuppressed at enrollment, achieving suppression was higher among SOC versus FCCM children, but this difference was not statistically significant and included only 38 children; and there were no significant differences in detectable viral load at 12 months. There were no significant differences between study groups in retention or ART adherence at 12 months for children or caregivers. Factors associated with lack of viral suppression/detectability at 12 months included lack of viral suppression at enrollment and having a younger caregiver (age <25 years). CONCLUSIONS: FCCM in Eswatini was associated with a modest increase in viral suppression/undetectability at 12-months; 12-month retention and adherence did not differ by study group for children or caregivers. High levels of suppression and retention in both groups may have limited our ability to detect a difference. TRIAL REGISTRATION: NCT03397420; ClinicalTrials.gov.

Advancing collaborations in health research and clinical trials in Sub-Saharan Africa: development and implementation of a biostatistical collaboration module in the Masters in Biostatistics Program at Stellenbosch University.

BACKGROUND: Sub-Saharan Africa continues to carry a high burden of communicable diseases such as TB and HIV and non-communicable diseases such as hypertension and other cardiovascular conditions. Although investment in research has led to advances in improvements in outcomes, a lot still remains to be done to build research capacity in health. Like many other regions in the world, Sub-Saharan Africa suffers from a critical shortage of biostatisticians and clinical trial methodologists. METHODS: Funded through a Fogarty Global Health Training Program grant, the Faculty of Medicine and Health Sciences at Stellenbosch University in South Africa established a new Masters Program in Biostatistics which was launched in January 2017. In this paper, we describe the development of a biostatistical and clinical trials collaboration Module, adapted from a similar course offered in the Health Research Methodology program at McMaster University. DISCUSSION: Guided by three core principles (experiential learning; multi-/inter-disciplinary approach; and formal mentorship), the Module aims to advance biostatistical collaboration skills of the trainees by facilitating learning in how to systematically apply fundamental statistical and trial methodological knowledge in practice while strengthening some soft skills which are necessary for effective collaborations with other healthcare researchers to solve health problems. We also share some preliminary findings from the first four cohorts that took the Module in January-November 2018 to 2021. We expect that this Module can provide an example of how to improve biostatistical and clinical trial collaborations and accelerate research capacity building in low-resource settings. FUNDING SOURCE: Fogarty International Center of the National Institutes of Health.

Survival following screening and preemptive antifungal therapy for subclinical cryptococcal disease in advanced HIV infection.

OBJECTIVES: Our study's primary objective was to compare 1-year survival rates between serum cryptococcal antigen (sCrAg)-positive and sCrAg-negative HIV-positive individuals with CD4+ cell counts less than 100 cells/µl without symptoms of meningitis in Zimbabwe. DESIGN: This was a prospective cohort study. METHODS: Participants were enrolled as either sCrAg-positive or sCrAg-negative and followed up for 52 weeks or less, with death as the outcome. Lumbar punctures were recommended to all sCrAg-positives and inpatient management with intravenous amphotericin B and high-dose fluconazole was recommended to those with disseminated Cryptococcus. Antiretroviral therapy was initiated immediately in sCrAg-negatives and after at least 4 weeks following initiation of antifungals in sCrAg-positives. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: We enrolled 1320 participants and 130 (9.8%) were sCrAg positive, with a median sCrAg titre of 1 : 20. Sixty-six (50.8%) sCrAg-positives had lumbar punctures and 16.7% (11/66) had central nervous system (CNS) dissemination. Cryptococcal blood cultures were performed in 129 sCrAg-positives, with 10 (7.8%) being positive. One-year (48-52 weeks) survival rates were 83.9 and 76.1% in sCrAg-negatives and sCrAg-positives, respectively, P = 0.011. Factors associated with increased mortality were a positive sCrAg, CD4+ cell count less than 50 cells/µl and having presumptive tuberculosis (TB) symptoms. CONCLUSION: Our study reports a high prevalence of subclinical cryptococcal antigenemia and reiterates the importance of TB and a positive sCrAg as risk factors for mortality in advanced HIV disease (AHD). Therefore, TB and sCrAg screening remains a crucial component of AHD package, hence it should always be part of the comprehensive clinical evaluation in AHD patients.