U.S. President's Malaria Initiative

BackgroundRecent epidemiological data indicate that 30–50% of all malaria infections are asymptomatic, with parasite densities below the limit of detection of standard diagnostic tests. A highly sensitive rapid diagnostic test (hsRDT) was developed to detect these low-density Plasmodium falciparum infections. This study evaluated the diagnostic performance of both hsRDTs and conventional RDTs (cRDT) in reactive case detection (RACD) activities among individuals (contacts) living and/or working in proximity to an “index case” in Ann Township in Rakhine State, Myanmar.MethodsThis prospective community-based RACD study was conducted in 2017–2018 among residents aged at least five years old in 50 villages of Ann Township. We assessed the sensitivity, specificity, and positive and negative predictive values of both a hsRDT (NxTek™ Eliminate Malaria Ag P.f) and a cRDT (SD Malaria Ag P.f/P.v) using an ultra-sensitive polymerase chain reaction (usPCR) diagnostic assay as the gold standard.ResultsA total of 1,990 participants, all contacts of 51 index P. falciparum cases, were recruited. Among them, 28 (1.4%) tested positive by cRDT, 78 (3.9%) by hsRDT, and 171 (8.6%) by usPCR for P. falciparum mono-infection. The sensitivity and specificity of the hsRDT were 27.9% (95% CI 18.2–39.6%) and 98.8% (95% CI 98.2–99.4%), respectively, while the sensitivity and specificity of the cRDT were 13.7% (95% CI 7.6–20.7%) and 100% (95% CI 100–100%), respectively. The differences in sensitivity and specificity between hsRDT and cRDT were statistically significant (p < 0.01 for both).ConclusionsAlthough hsRDTs identified more infected contacts than cRDTs during reactive case detection, they have low overall sensitivity compared to usPCR. In resource-limited settings, such as Myanmar, the use of hsRDTs in RACD should be guided by careful consideration of their field feasibility and cost-effectiveness to support malaria elimination efforts.(285 words).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12936-025-05699-7.

IntroductionSeasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) has been delivered in sub-Saharan Africa since 2014, reaching over 40 million children in 2022. New questions are emerging related to SMC’s sustainability, integration with other interventions and introduction to new regions. Meanwhile, new WHO malaria guidelines have substantially increased flexibility for tailoring malaria strategies to local contexts. The SMC Alliance, bringing together researchers and implementers, commissioned a consultation to identify medium-term SMC research priorities.MethodsThe consultation was conducted online from September 2022 to September 2023 using the eDelphi methodology. An initial list of 46 research priorities was compiled during a workshop with SMC implementers. The wider expert consultation comprised three waves of online surveys available in English, French and Portuguese. Respondents rated research priorities on their importance, feasibility and degree to which they had already been addressed; responses determined elimination or retention of research priorities after each survey wave. Respondents suggested their own research priorities for rating. We also collected anonymised data on respondents’ characteristics. A final ranking exercise was conducted to reach consensus on a top 10 list of research priorities.ResultsA total of 67 unique respondents residing in 20 countries provided 96 survey responses. The surveys achieved balanced representation of respondents by gender, country of residence and professional background. Of the 25 research priorities retained for ranking, the highest-ranked included ‘evaluate duration of prophylactic protection offered by SPAQ and other SMC medicines’ and ‘evaluate the effect of integrating SMC with other malaria prevention interventions on development of antimalarial resistance’.ConclusionsResearch priorities related to sustainability, antimalarial resistance, integration with other interventions and improving quality of SMC delivery featured prominently among the highest-ranked research priorities. It is hoped the results of this consultation can encourage research uptake, guide new research and inform programme adaptation.

Abstract Background : In Kenya, limited clinical data on hospitalized malaria patients restricts insights into disease severity and care quality. Using data from the Integrated Facility-based Surveillance (IFBS) system—a sentinel surveillance platform for febrile illnesses across twelve facilities—we assessed risk factors for severe illness and mortality, diagnostic accuracy of microscopy, and adherence to severe malaria treatment guidelines. Methods : We analyzed IFBS data obtained from June 2017 to July 2024 using bivariable logistic regression to identify factors linked to severe illness and deaths. Microscopy results were compared with PCR results to assess diagnostic concordance. We also evaluated whether patients received parasitological confirmation before treatment and if severe cases received IV artesunate followed by artemether-lumefantrine (AL), per standard guidelines. Results : Among 8,487 inpatients, 2,197 (25.9%) tested positive for malaria; among malaria cases, 713 (32.5%) had severe disease and 16 (0.7%) died. Severe illness and deaths were associated with age under one year and delayed care-seeking. Positive routine microscopy was PCR negative in 21% of patients. Only 15% of severe cases were documented to have received both IV artesunate and AL, while 17% received IV quinine. Discussion : Risk factors associated with severe illness and mortality included young age &lt; 1 as well as modifiable risk factors that suggested delayed care seeking. Despite IFBS data reliance on chart reviews, findings reveal critical gaps in diagnostic accuracy and adherence to treatment protocols for severe malaria. Trial registration: N/A

Malaria vector control tools currently focus on insecticide treated nets (ITNs) and indoor residual spraying in malaria-endemic locations, but additional preventative strategies are needed to address protection gaps. Larval source management (LSM) includes larvicide application to aquatic habitat and an array of alternative forms of environmental efforts. An individual-based transmission model for falciparum malaria is used to demonstrate the theoretical benefit of suppressing malaria adult mosquito vector densities through LSM. The model simulates results of epidemiological trials from Western Kenya (a hilly area with papyrus swamps adjacent to human settlements and moderate to high perennial malaria transmission) and Côte d'Ivoire (an area with Sudanese climate, reducing vegetation cover and high transmission) that applied larvicide alongside ITNs, and investigates whether estimated changes in adult density can be used to project changes in human malaria. In the Western Kenya setting generalised linear models estimate 82% (90% credible intervals: 64% - 92%) and 88% (79% - 94%) reductions in the proportion of adult Anopheles funestus and Anopheles gambiae complex mosquitoes respectively as measured by CDC light traps. In Côte d'Ivoire, an 82% (56% - 93%) reduction of the dominant An. gambiae vector was estimated using standard window trap and pyrethrum spray catch. Both studies had variable village-level impacts. The transmission dynamics model predicted that these entomological impacts would result in a reduction in malaria prevalence in children of 6-months to 10-years of age of 48 - 72% in Kenya, and a 11 - 78% reduction in all-age clinical incidence across villages in Côte d'Ivoire, which are broadly consistent with the empirically observed outcomes. High heterogeneity between villages within the same study indicate that the relative or absolute reductions in mosquito adult density observed in these trials cannot be simply extrapolated to other regions. The LSM strategy adopted, unit area covered, and multiple environmental covariates all contribute to differences in indicators that could be used to assess entomological impacts and the corresponding epidemiological outcomes. This important malaria control tool was impactful across all sites examined, though further work is needed to understand how best to use this tool in the fight against malaria.

BackgroundIn 2023, an estimated 36 million pregnancies occurred in malaria endemic sub-Saharan Africa, but only 44% received the WHO recommended ≥ 3 doses of intermittent preventive treatment (IPTp3). Group Antenatal Care (G-ANC) is a service delivery model associated with higher quality of and greater retention in ANC, in which pregnant women are enrolled into groups at their first ANC visit and subsequent care is provided in groups. A cluster-randomized controlled trial was conducted in Atlantique Department, Benin, to assess whether G-ANC improved ANC retention and IPTp3 uptake at community level.MethodsForty purposively selected health facilities (HF) were randomized 1:1 to control (individual ANC) or G-ANC. Cross-sectional household surveys to measure uptake of ANC and IPTp were conducted in each HF catchment area before and after implementation among randomly selected women who had given birth in the previous 12 months. Changes in coverage were assessed using a difference-in-difference approach, adjusting for HF clustering.ResultsAt baseline (N = 1259), coverage of at least 4 ANC visits (ANC4) and IPTp3 was 52.8% and 48.0%, respectively, in the intervention catchment, and 44.9% and 49.4% in the control catchment. Coverage of ANC4 improved in both arms by endline (N = 1280), to 56.7% in the intervention and 46.1% in the control, but the difference in the increase was not significant between arms (p = 0.51). Coverage of IPTp3 increased non-significantly (p = 0.26), to 53.2% (intervention) and 49.7% (control). Overall, only 140 (10.6%) surveyed women reported participating in G-ANC. Participation improved coverage of both ANC4 (65.0% vs 50.5%, p = 0.002; odds ratio (OR) 1.9, 95% CI 1.4–2.5) and IPTp3 (64.0 vs 50.6%, p = 0.004; OR = 1.8, 95% CI 1.2–2.6).ConclusionsG-ANC increased ANC attendance and IPTp3 uptake among women who participated, but participation was limited. Understanding and addressing the barriers to participation is critical if G-ANC is to be used more widely to increase IPTp coverage.Trial Registration: PACTR202405487752509

Abstract Background Rapid diagnostic tests (RDTs) have improved malaria case management by enabling point-of-care confirmation of infection, particularly in low-resource settings. In addition to clinical use, RDT results recorded in health facility registers are a critical component of national malaria surveillance systems. Recently, national programs have explored using stored RDT cassettes to validate register data. However, manufacturers caution that results should be read within 15 - 30 minutes, raising concerns about result validity after this period. This study evaluated the stability of RDT results over a one-month period to assess whether stored cassettes can reliably reflect initial test outcomes. Methods We conducted a prospective, observational study in 48 health facilities across Benin, Nigeria, and Uganda from June to September 2023. A digital artificial intelligence (AI)-powered RDT reader (HealthPulse, Audere, Seattle WA USA) was used to photograph RDTs immediately after interpretation by health workers and again at one week and one month. Images were independently interpreted by a trained panel, with results categorized as positive, negative, invalid, or indeterminate. Only RDTs with valid interpretations at all three time points were included in the final analysis. Positive and negative predictive values (PPV and NPV) were calculated to measure the accuracy of results from stored RDTs relative to the initial interpretation. Results Out of 54,251 RDTs captured, 45,155 (83.2%) met inclusion criteria. At one month, 95.1% of initially positive RDTs remained positive, and 95.3% of initially negative RDTs remained negative. The PPV of a positive result at one month was 96.3% (95% CI 96.1, 96.5), while the NPV of a negative result was 93.8% (95% CI 93.4, 94.1). Most result changes occurred within the first week. Faint lines were associated with higher rates of change in both directions; 26.8% changing from positive to negative and 48.1% changing from negative to positive. Stability of results also varied across RDT products and specific test lines. Conclusions Stored RDT cassettes maintain high result stability over one month and can serve as a reliable reference to verify health facility records. Result changes were linked to premature interpretation, faint lines or product- or line-specific characteristics. Adherence to manufacturer-recommended read times may reduce the proportion of RDTs that change from negative to positive. These findings support the utility of stored RDTs in improving data quality and rational antimalarial use in malaria-affected settings.

South Africa is one of 25 countries identified by the World Health Organization as having the potential to eliminate malaria in the near future. In response to the emerging threat of antimalarial resistance, South Africa enhanced its surveillance programs to enable the mapping of resistance markers prevalence down to the facility level. A total of 4 471 samples, collected between January 2022 and August 2024 from healthcare facilities, and during active surveillance in malaria-eliminating districts in KwaZulu-Natal and Mpumalanga provinces, were assessed for drug (mutations in the kelch13, crt, mdr1, dhfr, and dhps genes) and diagnostic (hrp2/3 gene deletions) resistance markers using PCR and sequencing (Sanger and/or targeted amplicon) protocols. Validated markers of artemisinin partial resistance were rare, with the P574L mutation detected as a minor allele in two samples and the P553L mutation present in one sample. Of the 60 additional non-synonymous mutations detected, the A578S (30/999) and the I494V (13/951) mutations were most prevalent. Almost all parasites assessed carried the crtK76 (99.8%) and mdr1N86 (99.0%) alleles, suggesting susceptibility to chloroquine. The dhfr triple (99.9%) and dhps double (98.2%) mutations associated with pyrimethamine and sulfadoxine resistance, respectively, were close to fixation. No double hrp2/3 gene deletions were detected. These findings suggest that the recommended treatments and diagnostics in South Africa are effective. However, the strong selection for antimalarial drug resistance markers across southern Africa combined with high regional interconnectedness, emphasizes the need for sustained malaria molecular surveillance to support South and southern Africa achieve their elimination goals.

BackgroundIndoor residual spraying (IRS) is a cornerstone malaria control intervention in Burkina Faso. From 2018 to 2021, non-pyrethroid IRS was implemented annually in two regions of Burkina Faso with distinct malaria transmission patterns, concurrently with annual seasonal malaria chemoprevention (SMC), and a mass insecticide-treated net (ITN) distribution in 2019.MethodsA retrospective quasi-experimental approach was used to evaluate the impact of the 2018, 2020, and 2021 IRS campaigns on routinely reported confirmed malaria case incidence at health facilities. The 2019 campaign was excluded due to lack of data reporting during a health sector strike. Controlled interrupted time series models were fit to detect changes in level and trend in malaria case incidence rates following each IRS campaign when compared to the baseline period 24-months before IRS. IRS districts Solenzo (Sudano-Sahelien climate), and Kampti (tropical climate) were compared with neighbouring control districts and the analyses were stratified by region. Modelled health facility catchment population estimates based on travel time to health facilities and weighted by non-malaria outpatient visits were used as an offset. The study period encompassed July 2016 through June 2022, excluding July 2018 to June 2019.ResultsDistrict-level population and structure coverage achieved by IRS campaigns was greater than 85% in 2018, 2020, and 2021 in Solenzo and Kampti. In Solenzo a significant difference in malaria case incidence rates was detected after the 2018 campaign (IRR = 0.683; 95% CI 0.564–0.827) when compared to the control district. The effect was not detected following the 2020 or 2021 IRS campaigns. In Kampti, estimated malaria incidence rates were between 36 and 38% lower than in the control district following all three IRS campaigns compared to the baseline period.ConclusionsImplementation of IRS in Kampti, a tropical region of Burkina Faso, appeared to have a consistent significant beneficial impact on malaria case rates. An initial positive impact in Solenzo after the first IRS campaign was not sustained in the successive evaluated IRS campaigns. This study points to a differential effect of IRS in different malaria transmission settings and in combination with ITN and SMC implementation.

Article summaryThis study suggests that: 1) patients given AL infected with parasites carrying N86 were statistically more likely to experience a recurrent infection; 2) patients given ASAQ infected with parasites carrying 86Y were statistically more likely to experience a recurrent infection.BackgroundPlasmodium falciparum multidrug resistance transporter 1(Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapies (ACTs), particularly those containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies ofPfmdr1single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ.MethodsTo determine whether infection with parasites carrying specificPfmdr1SNPs leads to increased risk of recurrent parasitemia (recrudescent or new infection), data from 4,129 samples from 16 therapeutic efficacy studies from 13 African countries between 2013–2019 were analyzed.ResultsPatients treated with AL and infected with parasites carryingPfmdr1N86 were at greater risk of treatment failure than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carriedPfmdr186Y were more likely to experience a recurrent infection.ConclusionsOur results support prior studies that suggested: 1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; 2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience recurrent infection. These findings suggest that ACT andPfmdr1genotype may influence outcome afterP. falciparuminfection.