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The impact of the PEPFAR funding freeze on HIV deaths and infections: a mathematical modelling study of seven countries in sub-Saharan Africa
Get PDFBackground: On January 24, 2025, the United States government issued an executive order to freeze all foreign aid programs, including The President's Emergency Plan for AIDS Relief (PEPFAR), for 90 days. A limited waiver option became available, but its implementation remains incomplete. We estimated the impact of these policy changes on HIV deaths and new infections in seven sub-Saharan African (SSA) countries—Ethiopia, Kenya, Malawi, South Africa, Tanzania, Zambia, and Zimbabwe –, which together account for about half of all people living with HIV in SSA. Methods: We used STDSIM, an established individual-based simulation model, and previously published quantifications for the seven countries. We predicted changes in HIV deaths and new infections over the period 2025–2030 for four scenarios: (1) Executive order—proportional, where treatment disruption was proportional to the country-specific PEPFAR's share of total HIV funding; (2) Executive order—realistic, assuming near-total system collapse due to program dependencies; and (3–4) Waiver scenarios where treatment was resumed after 4 or after 8 weeks. Resumptions of programs accounted for delays due to organizational and logistical challenges. Findings: A 90-day funding freeze would result in 60 thousand [95% UI: 49–71 thousand] excess HIV deaths for the Executive order—proportional scenario. This number would increase to 74 thousand excess HIV deaths [95% UI: 63–89 thousand] for the Executive order—realistic scenario. Under a 4-week and 8-week waiver scenario, projected excess HIV deaths ranged between 21 thousand [95% UI: 15–28 thousand] and 28 thousand [95% UI: 22–36 thousand] respectively. Excess new infections ranged between 35 and 103 thousand for the different scenarios. Interpretation: The sudden cessation of PEPFAR funding likely results in tens of thousands of HIV deaths and new infections. These losses of life and health should compel the United States government to rapidly and fully re-instate one of the most successful health programs in history. Funding: None.</p
Three annual cross-sectional community-based Knowledge, Attitudes and Practices (KAP) and prevalence surveys for urogenital schistosomiasis infection in two rural communities within Mangochi and Nsanje Districts, southern Malawi
Get PDFIn 2022 the World Health Organization (WHO) issued guidelines with key interventions to control and eliminate schistosomiasis in endemic countries. In Malawi, whilst praziquantel Mass Drug Administration (MDA) campaigns have been ongoing for over a decade, implementation of other interventions have not been formally assessed. To help formulation of an integrated country-specific control strategy, we assessed the Knowledge, Attitudes and Practices (KAP) and infection prevalences in two representative rural communities in Mangochi and Nsanje Districts. Longitudinal cross-sectional community-based questionnaire surveys were undertaken with participants aged from 6 to 45 years in 2022 and later repeated in 2023 and in 2024. Participants (including children aged 2 to 5 years) provided urine samples for parasitological tests. Comparative analysis involved calculation of percentages, tabulations, frequencies, and a logistic regression (logit) model to assess the effect of education level, gender, age, and study area on general and correct knowledge of schistosomiasis. A total of 1964 participants took part in the KAP surveys in 2022, and 1789 and 1908 participants were followed up in 2023 and 2024 respectively, while for the parasitological surveys, 2,319 participants took part in 2022, and 2,006 and 2,014 participants were followed up in 2023 and 2024 surveys respectively. In total, 53.2 % were from Mangochi, 55.5 % were females, 62.1 % were School-Aged Children (SAC) and 37.9 % were adults with their mean ages at 11 and 28 years, respectively. Overall, 65.5 % of respondents demonstrated satisfactory (≥50.0 % – ≤70.0 %) knowledge of schistosomiasis while only 5.1 % correctly mentioned freshwater snails as intermediate hosts. In 2022, prevalence of urogenital schistosomiasis by urine microscopy was 43.6 %, which despite annual MDA increased to 44.1 % in 2023, then after biannual MDA decreased to 27.0 % in 2024. In 2022, 10.5 % of all participants had heavy-intensity infections which increased to 11.4 % in 2023 before decreasing to 7.7 % in 2024. The majority (91.3 %) used a borehole or piped source of drinking water and used a latrine to urinate or defecate (93.8 %) although many (59.6 %) reported to have visited a freshwater body more than once in a day. Since MDA has taken place over several years in these areas and only had insufficient local impact, we strongly encourage addition of complementary methods to bolster its impact. It is therefore essential to engage individuals and communities, improving their understanding of disease and behaviour change to more effectively control and potentially eliminate schistosomiasis.</p
Genetic diversity within Strongyloides fuelleborni: Mitochondrial genome analysis reveals a clear African and Asian division
Get PDFFollowing the recent report of strongyloidiasis caused by Strongyloides fuelleborni within a semi-captive colony of baboons in a UK safari park, we investigated the genetic relationships of this isolate with other Strongyloides isolates across the world. Whole genome sequence (WGS) data were generated with later phylogenetic analysis of mitochondrial (mt) cytochrome oxidase subunit 1 (cox1) and nuclear ribosomal 18S sequences against 300 published Strongyloides reference genotypes. The putative African origin of the UK S. fuelleborni was confirmed and full length mt genome sequences were assembled to facilitate a more detailed phylogenetic analysis of 14 mt coding regions against all available Strongyloides species. Our analyses demonstrated that the UK isolate represented a novel African lineage not previously described. Additional complete mt genomes were assembled for several individual UK safari park worms to reveal a slightly altered mt genome gene arrangement, allowing clear separation from Asian S. fuelleborni. Furthermore, these UK worms possessed expanded intergenic regions of unknown function that increase their mt genome size to approximately 24 kilobases (kb) as compared with some 16 kb for Asian S. fuelleborni; this may have arisen from unique populational founder and genetic drift effects set within the peculiar mixed species baboon and drill ancestry of this semi- captive primate colony. A maximum likelihood phylogeny constructed from 14 mitochondrial coding regions supported an evolutionary distinction between Asian and African S. fuelleborni, most likely supporting paraphyly.</p
Small for gestational age subgroups have differential morbidity, growth, and neurodevelopment at age 2: the INTERBIO-21st Newborn Study
Get PDFBackground: Small for gestational age is a complex perinatal syndrome associated with increased neonatal morbidity, mortality, and impaired childhood growth and neurodevelopment. Current classifications rely primarily on birthweight, which does not capture the heterogeneity of the condition nor predict long-term health outcomes. Here we aim to identify and characterize distinct small for gestational age subgroups and assess their neonatal and early childhood health trajectories. Objective: To refine the classification of small for gestational age by identifying subgroups based on maternal, fetal, and environmental factors and evaluating their associations with neonatal morbidity, growth, and neurodevelopment at age 2. Study Design: Prospective cohort study. In six countries worldwide, between 2012 and 2018, the INTERBIO-21st Study enrolled small for gestational age and non-small for gestational age newborns defined by the <10th centile of international standards with moderate (≥third–<10th centile) and severe (<third centile) small for gestational age subgroups; we assessed their growth, health, nutrition, motor development, and neurodevelopment up to age 2. We used 2-step cluster analysis to identify small for gestational age subgroups, and a probabilistic approach to choose the optimal subgroup model based on a statistical measure of fit. We performed logistic regression analysis (odds ratio; 95% confidence interval) to assess health and development outcomes among subgroups using the non-small for gestational age as reference group, adjusting for key confounders. Results: We enrolled 5153 non-small for gestational age and 1549 small for gestational age newborns: moderate (≥third–<10th centile) small for gestational age=947 and severe (<third centile) small for gestational age=602. We identified 9 small for gestational age subgroups: “no main condition detected” (29.0%); “previous low birthweight or preterm birth” (14.6%); “severe maternal disease” (12.0%); “maternal short stature” (11.6%); “hypertensive disorders” (9.6%); “extrauterine infection” (6.8%); “previous miscarriage(s)” (6.5%); “smoking” (5.2%); and “maternal undernutrition” (4.7%). Severe small for gestational age newborns in the “severe maternal disease” (odds ratio, 3.2; 95% confidence interval, 1.8–6.0), “previous low birthweight or preterm birth” (odds ratio, 2.8; 95% confidence interval, 1.6–4.8), and “smoking” (odds ratio, 5.4; 95% confidence interval, 1.3–21.8) subgroups had increased risk of neonatal and long-term morbidity and low anthropometric measures at age 2 as compared to the non-small for gestational age group. Moderate small for gestational age newborns in the “hypertensive disorders” subgroup had increased risk of neonatal morbidity (odds ratio, 2.6; 95% confidence interval, 1.5–4.6) and higher odds of scoring <10th centile of normative values in language (odds ratio, 3.5; 95% confidence interval, 1.0–12.0) and positive behavior (odds ratio, 2.2; 95% confidence interval, 1.1–4.5). The “severe maternal disease” subgroup had also higher risk of deficit (<10th centile of normative values) in language (odds ratio, 5.7; 95% confidence interval, 1.3–24.8) and positive behavior (odds ratio, 3.4; 95% confidence interval, 1.5–7.6). Conclusion: Small for gestational age comprises heterogeneous subgroups with distinct patterns of neonatal morbidity, postnatal growth, and neurodevelopmental outcomes up to age 2.</p
Updated fine-scale location data for Blantyre district collected using a low-cost approach
Get PDFKnowing up-to-date geographical location of residential areas is crucial for understanding health-related factors and formulating targeted interventions. However, such data are often unavailable or resource-intensive to collect. This study employed low-cost approaches to map residential areas in Blantyre district, Malawi, which was severely affected by a cholera outbreak that lasted over a year (March 2022 to August 2023). We trained five data collectors using KoBo Toolbox and engaged Health Surveillance Assistants (HSAs) and motorcycle operators for precise location identification. We validated the data by involving key stakeholders from Blantyre District Health Office (DHO) and Malawi-Liverpool-Wellcome Research Programme (MLW). We successfully mapped 764 locations, demonstrating the effectiveness in rapidly mapping both residential and hard-to-reach areas. Associated costs were calculated based on MLW standard rates. This process highlighted the critical importance of accurate geolocation for public health research and interventions. Our study provides valuable spatial data and showcases the feasibility of cost-effective methods for gathering crucial public health information in resource-limited settings, potentially serving as a model for similar efforts globally.</p
Data for Clinical Trial Antimalarial Dose Justification and Tolerability (ADJusT) Study of DHA-Piperaquine in the 5–24 kg Weight Band in Malawi
No full textEvolution of Mycobacterium tuberculosis transcription regulation is associated with increased transmission and drug resistance
Get PDFMycobacterium tuberculosis (Mtb) has co-evolved with humans for thousands of years and is characterized by variation in virulence, transmissibility, and disease phenotypes. To identify bacterial contributors to phenotypic diversity, we developed new RNA sequencing (RNA-seq) and phylogenomic tools to capture hundreds of Mtb isolate transcriptomes, link transcriptional and genetic variation, and find associations between variants and epidemiologic traits. Across 274 Mtb clinical isolates, we uncovered unexpected diversity in virulence gene expression, which we linked to known and unknown regulators. Surprisingly, we found that many isolates harbor variants associated with decreased expression of EsxA (Esat6) and EsxB (Cfp10), which are virulence effectors, dominant T cell antigens, and immunodiagnostic targets. Across >55,000 isolates, these variants associate with increased transmissibility, especially in drug-resistant Mtb strains. Our data suggest expression of Mtb virulence genes is evolving in response to drug-linked pressure, raising concerns about use of these targets in immunodiagnostics and next-generation vaccines.</p
Understanding Resilience in UNRWA Health Response to the Syrian Crisis: Lessons from Causal Loop Analysis
Get PDFBetter methods, better data: landscaping the priorities for improving methodologies in vector control
Get PDFThis article addresses the evolving challenges in evaluating insecticide-based tools for vector control. In response to the emergence of insecticide resistance in major malaria vectors, novel chemistries and products are coming to market, and there is a need to review the available testing methodologies. Commonly used methods for evaluating insecticides, such as the World Health Organization (WHO) cone bioassay, are inadequate for the diverse range of tools now available. Innovation to Impact (I2I) has studied the variability in laboratory methods, with the aim of identifying key factors that contribute to variation and providing recommendations to tighten up protocols. The I2I Methods Landscape is a living document which presents a review of existing methods for evaluating vector control tools, with the scope currently extending to insecticide-treated nets (ITNs) and indoor residual sprays (IRS). The review reveals a lack of validation for many commonly used vector control methods, highlighting the need for improved protocols to enhance reliability and robustness of the data that is generated to make decisions in product development, evaluation, and implementation. A critical aspect highlighted by this work is the need for tailored methods to measure endpoints relevant to the diverse modes of action of novel insecticides. I2I envisage that the Methods Landscape will serve as a decision-making tool for researchers and product manufacturers in selecting appropriate methods, and a means to prioritise research and development. We call for collective efforts in the pro-active development, validation, and consistent implementation of suitable methods in vector control to produce the data needed to make robust decisions.</p