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Major features of parasite adaptation revealed by genomes of Plasmodium falciparum population samples archived for over 50 years.
No full textUnderstanding evolution of human pathogens requires looking beyond the effects of recent interventions. To study malaria parasites prior to widespread drug selection, Plasmodium falciparum genomes were sequenced from the oldest population-based set of archived research samples yet identified, placental blood collected in the Gambia between 1966 and 1971. High-quality data were obtained from 54 infected samples, showing that genomic complexity within infections was high, most infections were genetically unrelated, and no drug resistance alleles were detected. Strong signatures of positive selection are clearly seen at multiple loci throughout the genome, most of which encode surface proteins that bind erythrocytes and are targets of acquired antibody responses. Comparison of population samples obtained over a following period of almost 50 years revealed major directional allele frequency changes at several loci apart from drug resistance genes. Exceptional changes over this time are seen at gdv1 that regulates the rate of parasite sexual conversion required for transmission, and at the unlinked Pfsa1 and Pfsa3 loci previously associated with infection of individuals with sickle-cell trait. Other affected loci encode surface and transporter proteins warranting targeted functional analyses. This identification of key long-term adaptations is important for understanding and managing future evolution of malaria parasites
Ending Preventable Stillbirths and Improving Bereavement Care: A Global Scorecard.
Get PDFBACKGROUND: The Lancet Ending Preventable Stillbirths series issued a global Call to Action to reduce stillbirths and improve bereavement care. To monitor progress, we developed a global scorecard to track performance on key indicators.
OBJECTIVES: To introduce the scorecard and demonstrate its utility with a worked example by comparing global and regional performance in 2022 versus 2018.
METHODS: Descriptive analysis of performance across 20 nominated indicators spanning mortality targets, universal health coverage targets and milestones for ending preventable stillbirths. Data were extracted from global tracking processes undertaken by United Nations agencies and foundations. Data were summarised globally and by region, with performance against indicators coded as below expectation, in progress, on track, or fully achieved.
RESULTS: Seven of the 20 indicators had no available data to assess performance, including those related to stillbirth rate equity, subnational stillbirth rates, national reproductive health plans, the quality of antenatal and intrapartum care, and national processes for stigma reduction. As yet, there is no global consensus on respectful care after a perinatal death. Data were sparse for all indicators in Oceania, Europe and North America, and Latin America and the Caribbean. For most regions and most of the 13 other indicators with available data or estimates, progress was often modest or lacking. Central and South Asia and East and South-East Asia were 'on track' for more indicators than other regions, and there was substantial progress on three indicators in Sub-Saharan Africa. However, for the 10 highest-burden countries, progress remained below expectations. Progress was highest for indicators assessing the existence of plans, and worst for indicators assessing implementation.
CONCLUSIONS: The Global Scorecard for Ending Preventable Stillbirths can be used to provide advocates, policymakers, and practitioners with a detailed status check on data availability and progress in ending preventable stillbirths and improving care after stillbirth
Prevalence, predictors and consequences of reported discrimination against children with disabilities in Lao PDR: a cross-sectional analysis in Xiengkhouang Province.
Get PDFBACKGROUND: Children with disabilities are at increased risk of discrimination, contributing to exclusion from services and community life. OBJECTIVE: This study investigates the prevalence, predictors and consequences of reported discrimination against children with disabilities in Lao People's Democratic Republic (Lao PDR). METHODS: Data were collected in the baseline assessment for a non-randomised controlled trial of a cash-plus programme for children with disabilities in Xiengkhouang Province, Lao PDR. Assessment was conducted May to October 2023. Data on reported discrimination was collected using a tool based on a validated measure. Experience of discrimination in the past 30 days was classified into "any" and "frequent". Children aged ≥8 years reported directly on their experiences of discrimination. Caregivers provided proxy response for children <8 years or for children ≥8 years who had severe difficulties communicating. RESULTS: 405 children with disabilities aged ≤18 years were recruited. Prevalence of any reported discrimination in the past 30 days was 72.3%, and of frequent discrimination 28.4%. Reported discrimination was more common against children with cognitive disabilities (aRR: 1.55, 95% CI: 1.03-2.33), Hmong/Lu Mien children (aRR: 1.25, 95% CI: 1.10-1.41), and children without friends (aRR: 1.61, 95% CI: 1.16-2.23). Children experiencing frequent discrimination were substantially more likely to avoid others (aRR: 5.19, 95% CI: 3.48-7.74) and worry about how others act towards them (aRR: 4.05, 95% CI: 2.79-5.88). CONCLUSIONS: Children with disabilities in Lao PDR experience high levels of discrimination. Action is needed to reduce disability-related stigma and discrimination in line with the United Nations Convention on the Rights of Persons with Disabilities
Towards cleaner air: PM2.5 exposure and disparities around childcare providers in England
Get PDFAir pollution poses a significant health risk for young children, particularly in urban and deprived areas. Exposure to fine particulate matter (PM2.5) during early life may contribute to long-term adverse health out-comes. This study examined changes in PM2.5 concentrations around Early Years Providers (EYPs; childcare providers) in England from 2018 to 2022. We assessed associations between small-area socio-demographic
characteristics and exposure levels exceeding the World Health Organisation (WHO) 2021 annual air quality guideline (>5 μg/m3). We integrated data on EYPs locations from Ordnance Survey with annual PM2.5 estimates from DEFRA using Geographic Information Systems and socio-demographic indicators — deprivation, urbanicity, and ethnic composition. A Bayesian spatial regression model with random effects was used to estimate adjusted associations between PM2.5 levels and local population characteristics. The number of EYPs ranged from 15,780 in 2018 to 18,427 in 2019. Mean PM2.5 levels around EYPs changed by 17.8 % over the study period (from 9.4 μg/m3 [SD = 1.8] in 2018 to 7.8 μg/m3 [SD = 1.5] in 2022). However, PM2.5 levels at over 96 % of EYPs remained above the WHO, 2021 annual guideline throughout. Higher PM2.5 concentrations were observed in EYPs located in more deprived, urban, and predominantly non-white communities. Despite recent improvements, PM2.5 levels around most EYPs in England remain above recommended thresholds. Targeted interventions in deprived urban areas are needed to reduce young children’s exposure and address environmental health
inequalities
Migrating longitudinal African mental health data from staging to the OMOP common data model within the INSPIRE network datahub
Get PDFBackground
The standardization and integration of longitudinal mental health data from African cohort studies are critical in advancing research and informing policy. There are several challenges posed by diverse sources, instruments adapted for locals, and the absence of an interoperable framework to allow for meaningful analysis and cross-study comparisons.
Methods
We designed and executed a metadata-driven pipeline using the OMOP Common Data Model within the INSPIRE Network Datahub to harmonise multi-country African mental health datasets. Data extracted previously from longitudinal studies, standardised via a snowflake schema staging database, is now mapped to OMOP vocabularies with local extensions, and validated through quality assurance protocols using OHDSI tools.
Results
A total of 202,013 person records and over 7 million observations across fourteen cohort studies were successfully migrated. Mapping completeness exceeded 99.9%, with high conformance, completeness, and plausibility across all OMOP domains. Custom vocabularies ensured the coverage of context-specific exposures and outcomes, thereby supporting robust cohort construction, event characterization, and longitudinal analyses.
Conclusion
This framework demonstrates scalable harmonisation and integration of African mental health data, bridging the gap between local datasets with global standards. This then enables the performance of federated analysis and reproducible research, increasing the utility and impact of mental health data in informing evidence-based policies and future collaborative studies across Africa
Control of pyrethroid-resistant Anopheles gambiae s.l. with Sovrenta® 15WP, a new isoxazoline insecticide for indoor residual spraying.
Get PDFINTRODUCTION: An expanded portfolio of more effective WHO-prequalified insecticides for indoor residual sparing (IRS) is needed to provide additional options to disease control programmes and enhance their capacity to efficiently apply IRS rotations for managing vector resistance to insecticides. We investigated the efficacy and residual activity of Sovrenta® 15WP, a wettable powder formulation of the newly discovered isoxazoline insecticide isocycloseram, (active ingredient trademarked as PLINAZOLIN® technology) for IRS in laboratory bioassays and experimental hut studies. METHODS: Sovrenta® 15WP, was evaluated under laboratory conditions for 12 months at the dose of 120 mg a.i./m2 on cement, mud and wood block substrates against insecticide-susceptible Anopheles gambiae sensu stricto Kisumu and pyrethroid-resistant An. gambiae sensu lato (s.l.) Covè strains. An experimental hut trial was also performed to investigate its efficacy and residual activity on cement and mud-plastered walls at the target dose of 120 mg a.i./m2 over 12 months against wild free-flying pyrethroid-resistant An. gambiae sl at the Covè experimental hut station in Benin. Mosquito mortality was recorded every 24 h for up to 168 h post-exposure. Sovrenta® 15 WP was compared to Actellic® 300CS, a WHO/PQ-listed pirimiphos-methyl IRS insecticide applied at 1000 mg a.i./m2 RESULTS: In laboratory cone bioassays, Sovrenta® 15WP induced > 80% mortality of susceptible and pyrethroid-resistant An. gambiae sl for 11-12 months on cement, mud and wood block substrates. A total of 12,850 wild pyrethroid-resistant An. gambiae s.l. were collected in the experimental hut trial. Sovrenta® 15WP induced significantly higher mosquito mortality in the experimental huts over 12 months compared to Actellic® 300CS (68-72% vs 44-46%, p 80% for 12 months with Sovrenta® 15WP and 9 months with Actellic® 300CS. CONCLUSION: Sovrenta® 15WP provided extended control of pyrethroid-resistant malaria vectors when applied for IRS on local wall substrates. The insecticide presents a new effective IRS option for achieving improved malaria control and managing insecticide resistance through the rotation of IRS insecticides
Reframing TB Care: A Perspective on Multimorbidity-Centered Care for People with TB.
Get PDFTuberculosis (TB) rarely occurs in isolation; most people with TB experience multiple coexisting conditions, including HIV, diabetes, undernutrition, depression, and substance use disorders, which worsen disease severity and compromise treatment outcomes. Although the World Health Organization has issued disease-specific guidance for managing key comorbidities, TB care remains largely siloed and poorly equipped to address the growing burden of multimorbidity, particularly in African health systems. In this perspective article, we propose a phased framework for multimorbidity-centered TB care. The first phase emphasizes systematic screening for common comorbidities and establishment of basic referral pathways. The second phase focuses on strengthening coordination between TB programs and existing health and social services, including task sharing and longitudinal follow-up. The third phase advances toward fully integrated, co-located, multidisciplinary models of care that embed TB services within broader multimorbidity platforms. Together, this framework offers a pragmatic roadmap for TB programs to deliver more person-centered, equitable, and efficient care, strengthen primary care systems, and accelerate progress toward ending TB as a public health threat in Africa
Exploring measures of sustainability in the WHO Joint External Evaluation and the WOAH performance of veterinary services tools-A qualitative assessment of perceived usefulness and acceptability to one health and global health security experts.
Get PDFINTRODUCTION: Amidst global policy reforms including the 2024 amendments to the International Health Regulations (IHR) and the ongoing Pandemic Agreement negotiations, there is a renewed emphasis on sustainability, equity, and multisectoral coordination in global health security. However, the operationalization of sustainability in core assessment tools-such as the WHO Joint External Evaluation (JEE) and the WOAH Performance of Veterinary Services (PVS)-remains poorly defined and underdeveloped, particularly as they relate to low- and middle-income countries (LMICs). METHODS: We conducted a qualitative study involving semi-structured interviews with 29 global experts across human, animal and environment health from both high and low/middle income countries affiliated with the One Health High-Level Expert Panel, the World Bank Pandemic Fund Technical Advisory Panel, and technical focal points from Quadripartite institutions. Using thematic analysis grounded in the Social Construction Framework and an adapted Schell et al. sustainability model, we explored how sustainability is conceptualized and measured across human, animal, and environmental health domains. RESULTS: Participants critiqued existing tools for framing sustainability narrowly, including their focus on short-term processes and compliance, rather than long-term outcomes, equity, or resilience. Sectoral and contextual differences emerged: human health experts emphasized workforce and financing; animal health experts stressed economic and institutional continuity; environmental health experts highlighted ecosystem resilience and intergenerational equity. LMIC respondents underscored the impact of donor dependency, weak local ownership, and limited transition planning. Several determinants of sustainability-such as financing, governance, workforce retention, and community engagement-are already measured in existing reporting tools but are not explicitly or coherently framed as sustainability indicators. DISCUSSION: We recommend that future iterations of JEE and PVS incorporate a clear definition of sustainability and explicitly integrate sustainability metrics, aligned with the revised IHR, the One Health Joint Plan of Action, relevant SDG targets and national planning cycles. Tools must also reflect sectoral and contextual nuances and integrate long-term monitoring frameworks that promote domestic accountability. In the field of One Health and GHS, strengthening the sustainability components of these tools is essential to build equitable and resilient health systems globally
Cost-effectiveness of cancer interventions in Rwanda: literature review and expert elicitation for health benefits package design.
Get PDFINTRODUCTION: Prioritising health benefits packages (HBPs) that specify which health services are covered under insurance is sometimes done in disease-specific clusters. Cancer is a good candidate for this, given its high cost and rising disease burden, particularly in low- and middle-income countries.The Government of Rwanda assessed 49 cancers against nine criteria to inform the design of its HBP. Each cancer had a basic, core and enhanced package of services, and one preventive intervention was assessed, totalling 148 interventions. This paper focuses on the results of one criterion: cost-effectiveness. The objectives were to specify which cost-effectiveness methods were selected and why; to assess the cost-effectiveness of 148 cancer interventions; and to recommend how to strengthen the global cost-effectiveness evidence base. METHODS: Methods were selected using an adaptive health technology assessment approach, by considering the trade-offs between available time, data and capacity. The assessment undertook a review of the Tufts cost-effectiveness assessment (CEA) registry and filled evidence gaps with structured expert elicitation. Analysts summarised lessons learnt to recommend improvements to the global cost-effectiveness evidence base. RESULTS: Of the 148 cost-effectiveness ratios (CERs) sought, 39 were from the Tufts registry and 83 were expert elicited. Limited availability of CERs from the literature resulted in a disproportionate number of CERs being elicited from experts. Analysts recommend better reporting and improved consistency in the extraction of CEAs to support HBP design. CONCLUSION: This is the first study to assess the cost-effectiveness of many cancers simultaneously for HBP design. It highlights the strengths and limitations of existing evidence and demonstrates the feasibility of combining rapid review with expert elicitation to obtain replicable CER estimates. These cost-effectiveness findings were used to prioritise a package of cancer services for Rwanda alongside several other criteria (reported separately)
Retinoblastoma outcomes in Europe: a prospective analysis of 483 patients from 40 countries.
Get PDFPURPOSE: To describe presentation, treatment and outcomes for a cohort of children presenting with retinoblastoma (Rb) throughout Europe during 2017.
METHODS: A prospective analysis of 483 patients diagnosed in Europe between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years.
RESULTS: Unilateral cases 339/483 (70%) predominated, presenting older (mean age 26 months) than the 144 (30%) bilateral cases (mean age 12 months p < 0.0005). Only 4/477 (0.8%) children had extra-ocular Rb at presentation (mean age 53 months vs 21 months for those without p = 0.002). Children from middle income countries did not present older, but were more likely (p < 0.001) to present with late-stage disease (3-4) than high-income children (74/151 (49%) vs 108/332 (33%), RR 1.25 95%CI 1.09-1.44). For unilaterals, primary treatment was intravenous chemotherapy (IVC) in 29% and intra-arterial chemotherapy (IAC) in 20%. For bilaterals, primary treatment was IVC in 113/144 (78%) and IAC in 14/144 (10%). Overall, 58% of children underwent enucleation, 36% of which as primary treatment. Risk of enucleation was determined by stage and laterality, but not economic status. Twelve (2.5%) children died from Rb. More children (OR = 146-7 13.9-1549.4, p < 0.0005) presenting with extra-ocular tumour died (3 of 4 (75%)) than with intra-ocular tumour (9/449 (2%)) More children (OR = 29.8 3.8-232.0, p < 0.0005), from middle income countries died from Rb (11/132 (8%)) than from high income countries (1/327 (0.3%)).
CONCLUSION: Even within a wealthy continent such as Europe, economic factors may influence survival, but not global salvage rates. The majority of children still lose an eye