INTRODUCTION:Progress in reducing the global malaria burden has stalled since 2015, with increases in malaria incidence and mortality reported in many African countries after 2020. In 2021, the WHO issued a conditional recommendation for house screening, including windows, ceilings, doors, and eave spaces, as a complementary intervention. However, evidence gaps remain, particularly regarding its effectiveness in combination with or as an alternative to long-lasting insecticide-treated nets (LLINs). This trial aims to evaluate the piperonyl butoxide-pyrethroid (PBO)-ceiling nets, a novel house screening tool covering ceilings, among high-risk households in Kenya with poor use of LLINs. METHODS:This trial includes both superiority and non-inferiority comparisons. Superiority comparisons will evaluate whether the combination of PBO-ceiling nets and PBO-LLINs provides greater protection than either intervention alone. Non-inferiority comparisons will assess whether PBO-ceiling nets alone are not inferior to PBO-LLINs alone in reducing malaria infection prevalence and entomological indicators. In Homa Bay County, Kenya, 500 households will be randomized into three arms: (1) receiving PBO-ceiling nets, (2) receiving PBO-LLINs at a ratio of one net per two household members, and (3) receiving both PBO-ceiling nets and PBO-LLINs. The primary outcome is the prevalence of Plasmodium infections by PCR among all age groups at 12 months post-intervention. Secondary outcomes include entomological indicators, such as the density of primary malaria vectors sampled using CDC light traps. DISCUSSION:This trial addresses key evidence gaps related to housing modifications for malaria prevention by evaluating the effectiveness of PBO-ceiling nets among high-risk populations with limited access to conventional LLINs. Although household-level randomization may limit the ability to capture potential spillover effects and introduce challenges such as open-label and observer biases, several measures have been incorporated to mitigate these risks, including frequent adherence reminders and blinding of laboratory and data analysis staff. Despite these limitations, the study is expected to generate important epidemiological and entomological data that will contribute to the evidence base for novel vector control strategies in malaria-endemic regions. TRIAL REGISTRATION:PACTR202506499755138. Registered on June 20, 2025.

Neglected tropical diseases (NTDs) impose a substantial global burden, yet diagnostic innovation for these conditions has historically been lower than for other major infectious diseases. Addressing this diagnostic gap is a prerequisite for their elimination, as recognised by the World Health Organization (WHO). This critical review evaluates the current scope of point-of-care nucleic acid amplification tests (POC NAATs) through a systematic analysis of 39 studies. This is achieved via a breakdown of the nucleic acid amplification workflow and associated implementation barriers with a focus on operational feasibility rather than analytical metrics such as sensitivity and specificity. The reviewed publications showed several reoccurring themes such as simplified extraction methods, integrated workflows on platforms or devices, smartphone apps for interpretation, reducing cold-chain dependence, and electricity-independent workflows. However, several technical, analytical, and implementation barriers were also identified which hinder the transition from proof-of-concept prototypes to field-deployable tools that meet the criteria set up by the WHO for POC tests. The review showcases that a majority of current NAAT developments for NTDs do not yet fulfil the WHO criteria for POC application in resource-limited settings. Whilst there are opportunities for improvement as well as for repurposing NAAT platforms for other diseases, careful examination of all steps from sample collection to mature implementation in the field is required to achieve the aim set up by the WHO.

Malaria, caused by Plasmodium parasites, kills 610,000 people annually. The increasing availability of large-scale whole-genome sequencing (WGS) datasets enables investigation of parasite genetic diversity, population structure, and the spread of drug resistance. To investigate Plasmodium falciparum evolution, we analyse 17,565 isolates (17,489 previously published; 76 newly sequenced) from 39 countries, using identity-by-descent (IBD) networks,  population structure inference, and selection scans. Analyses reveal distinct patterns of selection, transmission, and drug resistance. Selection analyses identify genomic regions across multiple metrics, encompassing established and emerging drug-resistance loci. These patterns highlight region-specific adaptive processes within Southeast Asia. IBD analyses reveal recent haplotype sharing that shows strong local selection. New WGS from Brazil show increased IBD around pfcrt, consistent with local drug-selection pressures. Similarly, isolates from Vietnam exhibit high relatedness and elevated IBD around pfKIC3, with all isolates carrying the pfkelch13 C580Y artemisinin resistance mutation. Elevated IBD in pfKIC7 and pfKIC9 in South America and the Horn of Africa suggests alternative pathways for future artemisinin resistance. Together, these findings highlight the genomic basis of P. falciparum adaptation and offer improved resolution for genomic surveillance of evolving parasite populations.

Malaria transmission has been reduced considerably in some Kenyan regions; however, it remains high in the Lake Victoria basin. Ceiling nets fall under house screening as interventions in vector control under the World Health Organization’s Guidelines on Malaria and has a conditional recommendation with low-to moderate-certainty evidence of impact against malaria. This study aimed at assessing the perceptions of health system managers on the health system readiness in integrating ceiling nets into malaria vector control in and implementation pathways.A cross-sectional, qualitative, action research design was used aimed at providing actionable solutions to health systems challenges in the inclusion of ceiling nets as a complementary vector control strategy in the comprehensive approach on malaria prevention in Suba West sub-county, Homa Bay county. Key-informant interviews on perspectives on health system readiness for ceiling net integration into routine programmatic vector control strategies were conducted among health system managers. Qualitative data was captured using audio tapes and field notes, transcribed and analyzed using case-based in-depth inductive and deductive analysis using a thematic framework to classify and organize data into themes.Key emergent themes included perception and experiences in malaria vector control strategies, role of community health in malaria vector control strategies, systemic barriers and facilitators in malaria vector control, perspectives on integration of the ceiling nets in malaria vector control. This study demonstrates that health system managers perceive ceiling nets as a feasible, acceptable, and operationally integrablecomplement to existing malaria vector control strategies, while also identifying concrete system bottlenecks that must be addressed for scale-up. The ceiling nets showed high acceptability, appropriateness of fit in structurally heterogenous housing structures and high feasibility as an addition to a comprehensive complementary vector control strategy.The findings inform decision-ready implementation pathways of complementary ceiling nets in existing vector control strategies. Ceiling nets are perceived by frontline health system managers as a system-ready, acceptable house-modification intervention that can close critical protection gaps left by bed-net–centric malaria control, provided community health platforms and supply chains are deliberately leveraged. Successful scale up implementation hinges on a structured approach of integration that includes community buy-in, task-shifting of community health promoters in ceiling net installation, effective supply chains, and robust monitoring and evaluation systems to track, maintain and assess system level indicators and community level indicators. ### Competing Interest Statement The authors declare that they have no competing interests. ### Funding Statement This work was part of a 5-year project funded under SATREPS by AMED and JICA under the project- Interdisciplinary research for an integrated community-directed strategy for sustainable freedom from research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study obtained ethical clearance from Mount Kenya University’s Institutional Scientific Ethics review committee under the application approval number 1710. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The qualitative data, including the de-identified interview transcript excerpts relevant to this study, are publicly available and deposited in the Open Science Framework repository under the following Link:https://osf.io/wpu7m/overview.

Background Placental malaria (PM) remains a leading driver of maternal and neonatal mortality, largely attributed to the sequestration of Plasmodium falciparum–infected red blood cells in the placenta. For decades, PM vaccine development has singularly focused on VAR2CSA, the immunodominant variant surface antigen. However, extreme polymorphism, limited cross-strain protection, and the structural complexity of VAR2CSA have hindered the development of a highly efficacious PM vaccine, necessitating a paradigm shift. Methods This review examines existing literature to map potential vaccine antigens implicated in placental malaria ,and outlines a comprehensive vaccine development pipeline. It synthesizes emerging data on antigen expression profiles, immunogenicity, and mechanistic roles in placental pathogenesis. In addition, it highlights both key placental and blood-stage antigens expressed during pregnancy and reviews identification and testing strategies to guide rational PM vaccine design. Results This Review maps the expanding antigenic landscape of PM beyond VAR2CSA, identifying non-canonical surface and exported proteins, including SURFINs, PHISTs, PfRON3, and PfCSA-L, as critical targets that may circumvent current bottlenecks. The findings highlight the relevance of these antigens in placental malaria pathogenesis and their potential as alternative or complementary vaccine candidates. Conclusions Furthermore, we propose an integrated framework for rational vaccine design that couples high-throughput antigen discovery and structural immunogen engineering with multivalent formulation strategies. By bridging the gap between molecular parasitology and translational immunology, this roadmap offers a strategic path toward a broadly protective placental malaria (PM) vaccine.

ABSTRACT Maternal health during pregnancy is critical for favorable birth outcomes and long-term wellbeing of both mothers and infants. Women in rural, malaria-endemic regions face unique biological and socioeconomic challenges that may increase the risk of adverse pregnancy outcomes (APOs). This study investigated the incidence and determinants of APOs among pregnant women attending antenatal care at Webuye sub-County Hospital in Western Kenya, a rural malaria-endemic setting. We conducted a retrospective cohort analysis utilizing previously collected data of 300 women enrolled during early pregnancy and followed through delivery. Maternal demographic, clinical, and infection-related factors were assessed, and associations with APOs were evaluated using chi-square tests and multivariable logistic regression. Maternal age and gestational age at enrollment were significantly associated with malaria history (P<0.001). Maternal BMI abnormality (124.5/1000 pregnancies), anemia (99.3/1000), fetal or neonatal death (81.3/1000), and preterm birth (43.8/1000) were observed (all P<0.001), suggesting a substantial burden. Younger mothers (<20 years) and older mothers (>35 years) were significantly more likely to develop anemia (P =0.026), and prior malaria infection further increased anemia risk (P =0.02). Abnormal urinalysis findings indicative of urinary tract infection were significantly associated with low birthweight (P =0.031). No significant associations were found between APOs and infant sex, parity, gravidity, or maternal ABO blood type. These findings highlight a substantial burden of APOs in this rural population, exceeding national and global estimates. Strengthening malaria prevention, nutritional support, urinary infection screening, and encouraging early antenatal care attendance are critical to improving maternal and neonatal outcomes. Targeted interventions for adolescent and older mothers, along with enhanced point-of-care diagnostics, may reduce preventable complications in similar resource-limited, malaria-endemic settings.

Background: Malaria transmission in Kenya is highly variable across ecological zones and seasons, shaped by environmental variability, ecological context, and evolving transmission dynamics. Evidence on how the interaction between climatic variability and land-use change shapes transmission dynamics at national scale remains limited. We aimed to quantify climatic and environmental determinants on county-level malaria incidence and identify emerging hotspots using a decade of routine surveillance data to inform evidence-based adaptive risk stratification. Methods: We conducted a nationwide county-level spatiotemporal analysis of malaria incidence in Kenya from January 2016 to December 2025 using routine surveillance data from the Kenya Health Information System. Monthly case counts were modelled within a Bayesian hierarchical spatiotemporal framework using a negative binomial likelihood and Besag–York–Mollié spatial structure. Climatic, environmental, demographic, and land-cover covariates were incorporated, with lagged effects specified for temperature and rainfall. Model outputs were used to characterise seasonal and spatial patterns, identify environmental determinants, and generate dynamic, model-based malaria risk stratification across all 47 counties. Findings: Over the 10-year period, 41,608,369 malaria cases were reported, averaging 4,160,837 cases per year. Incidence exhibited pronounced seasonality aligned with rainfall and temperature cycles and seasonal amplitudes in historically high-burden counties. Across all counties combined, total monthly malaria incidence was 3.6% during the long rains season (March–May) and 26.8% higher during the short rains season (October–December) relative to the dry season (3287 per 10,000), consistent with Kenya's bimodal rainfall pattern. The Lake Victoria basin and coastal counties remained persistently high-burden zones, but a marked epidemiological shift emerged in northern Kenya, where Turkana County recorded the highest incidence by 2024 and 2025. Temperature (IRR = 1·021, 95% CrI 1·009–1·033), rainfall (IRR = 1·032, 95% CrI 1·015–1·050), cropland rainfed (1·013, 95% CrI 1·004–1·022), wetland (IRR = 1·137, 95% Crl 1·012–1·276), relative humidity (IRR = 1·009, 95% Crl 1·006–1·011), and natural vegetation (IRR = 1·040, 95% CrI 1·013–1·067) were positively associated with malaria incidence. Model-based risk stratification classified six very high-risk counties and reclassified several counties relative to existing frameworks, revealing both persistent hotspots and emerging transmission zones. Interpretation: Malaria risk in Kenya is dynamic and spatially uneven, with routine surveillance data revealing epidemiological transitions not fully captured by static risk maps. The emergence of Turkana as a major malaria focus highlights the need for adaptive, climate-informed surveillance and periodic re-stratification to support geographically targeted control and early detection of emerging hotspots.

Purpose: Organ donations can save or prolong life. Clinicians play a key role in promoting organ donation and transplant; hence, their knowledge may have positive effect on organ donation. The aim of this study was to assess the knowledge, attitude and practices about organ donation among students undertaking training in Clinical Medicine and Community health at Mount Kenya University, Kenya. Methodology: A cross-sectional descriptive survey among students undertaking an undergraduate course in Clinical Medicine at Mount Kenya University using a pre-tested questionnaire conducted between January and April 2017. The study used purposive sampling methodology of the students. Findings: Seventy-six participants, mean (sd) age of 22 (2.1) years and thirty-nine (51%) females were recruited. Only 3 (4.0%, 95% CI 0.8 to 11%) students had ever made a donation, all of them blood donation. Although sixty-seven (88%) of the study participants had heard the term organ donation only 15 (20%) of them knew someone who had donated organ. The most common source of information about organ donation was from internet/online according to thirty-three participants (43%). Seventy-one (93%) of the participants reported that organ donation was for saving life and fifty-eight (84%) were aware that organ donation involved risk and that the most important risk was infection. Only 4% were aware of local legislation guiding organ donation and transplantation in Kenya while 53% unaware. Forty-nine of the participants 64% agreed that they would receive organ for transplantation. Of the participants, thirty-nine (51%) considered `health status of the recipient’ as the main factor of the greatest importance when donating organ. Forty-three (57%) and forty-nine (64%) of the participants reported the donor and family member should consent for living donation and after death respectively. Thirty-one (41%) and twenty-six (34%) of the respondents think medical doctors and judges should make decisions about organ donation for unclaimed dead bodies respectively. Unique Contribution to Theory, Practice and Policy: Clinical medicine students have significant gaps in knowledge regarding the organ donation and transplantation. There is a low rate of donation even for blood despite the awareness of the need to save lives and therefore need to increase awareness on importance and promote laws to govern organ donation. Addressing these gaps would provide valuable insights to guide education, policy, and advocacy strategies aimed at improving organ donation practices in Kenya.

Background:Placental malaria (PM) remains a leading driver of maternal and neonatal mortality, largely attributed to the sequestration of Plasmodium falciparum-infected red blood cells in the placenta. For decades, PM vaccine development has singularly focused on VAR2CSA, the immunodominant variant surface antigen. However, extreme polymorphism, limited cross-strain protection, and the structural complexity of VAR2CSA have hindered the development of a highly efficacious PM vaccine, necessitating a paradigm shift. Methods:This review examines existing literature to map potential vaccine antigens implicated in placental malaria ,and outlines a comprehensive vaccine development pipeline. It synthesizes emerging data on antigen expression profiles, immunogenicity, and mechanistic roles in placental pathogenesis. In addition, it highlights both key placental and blood-stage antigens expressed during pregnancy and reviews identification and testing strategies to guide rational PM vaccine design. Results:This Review maps the expanding antigenic landscape of PM beyond VAR2CSA, identifying non-canonical surface and exported proteins, including SURFINs, PHISTs, PfRON3, and PfCSA-L, as critical targets that may circumvent current bottlenecks. The findings highlight the relevance of these antigens in placental malaria pathogenesis and their potential as alternative or complementary vaccine candidates. Conclusions:Furthermore, we propose an integrated framework for rational vaccine design that couples high-throughput antigen discovery and structural immunogen engineering with multivalent formulation strategies. By bridging the gap between molecular parasitology and translational immunology, this roadmap offers a strategic path toward a broadly protective placental malaria (PM) vaccine.

The percentage of the population sleeping under insecticide-treated nets (ITN) increased in sub-Saharan Africa from 3 to 59

Trichomoniasis and malaria, caused by Trichomonas vaginalis (T. vaginalis) and Plasmodium falciparum (P. falciparum), respectively, remain major public health threats, primarily in resource-limited regions like sub-Saharan Africa. In particular, malaria in pregnancy (MiP) poses serious diagnostic challenges due to the placental sequestration of P. falciparum, often leading to underdetection by conventional tools like microscopy or rapid diagnostic tests (RDTs). Meanwhile, T. vaginalis, the most prevalent nonviral sexually transmitted infection, exacerbates poor maternal and fetal outcomes when co-infections occur. In this study, we present a multiplexed isothermal nucleic acid amplification assay (iso-IMRS) for simultaneous detection of P. falciparum and T. vaginalis. We built on prior work validating iso-IMRS for P. falciparum and PCR-IMRS for T. vaginalis using a modified workflow better suited to near point-of-care (POC) settings. The assay was tested in simulated and human urine matrices, aiming for a low-cost, non-invasive, and field-ready diagnostic solution. The assay detected P. falciparum and T. vaginalis at 100 copies/μL in processed human urine, demonstrating clinically relevant sensitivity for noninvasive, multiplexed detection. However, use with a neat urine sample requires a processing step that may limit POC use. In our clinics in Kenya, we process samples nearby, and a fast molecular test that does not require thermocycling, with a turnaround time within the span of a typical prenatal visit, will positively impact our patients.

Abstract Extended-spectrum beta-lactamase-producing Enterobacterales such as Escherichia coli and Enterobacter hormaechei represent a growing public health challenge in clinical settings, particularly in low-and middle-income countries, due to the escalating threat of antimicrobial resistance (AMR). In this study, we aimed to identify the antibiotic resistance genes present in E. coli (n=4) and E. hormaechei (n=3) clinical isolates. Multidrug-resistant phenotypes were confirmed using disc diffusion assays against 20 antibiotics. Whole-genome sequencing of resistant isolates was performed using Oxford Nanopore Technologies. Genome assembly and analysis revealed high-risk clones, including sequence type (ST) 1193 in E. coli and ST78 in E. hormaechei . All E. coli isolates harbored the bla CTX-M gene in their chromosomes along with point mutations conferring resistance to fluoroquinolones, while E. hormaechei isolates encoded bla ACT in their chromosomes. Additionally, both species carried plasmids with multiple antibiotic resistance genes, including bla OXA and bla TEM , co-located with metal resistance operons, indicating the potential for horizontal gene transfer. BLAST analysis revealed high sequence similarity between the plasmids identified in clinical isolates and those previously recovered from environmental sources, highlighting the role of environmental reservoirs in AMR dissemination. Notably, no carbapenem resistance genes were detected in any isolate. These findings underscore the growing threat posed by multidrug-resistant Enterobacterales in clinical settings and emphasize the urgent need for strengthened infection prevention and control measures to mitigate AMR spread.

Objectives: Long COVID (LC), i.e. the persistence of new or worsening symptoms for 3 months after Severe Acute Respiratory Syndrome of Coronavirus 2 (SARS-CoV-2) infection, is an emerging global health burden. The prevalence of LC remains poorly characterized in low- and middle-income countries (LMICs), where other respiratory diseases, like tuberculosis (TB), are prevalent. We aimed to address this gap in Mycobacterium tuberculosis (Mtb)-exposed populations in Peru. Methods: We recruited people with TB (n = 36) and their asymptomatic household contacts (n = 63) in Peru. We collected clinical data using a questionnaire adapted from a United States-based study of LC. Participants were recruited within 2 years of SARS-CoV-2 diagnosis. Results: In Peru, 41% participants reported LC symptoms. The most common LC symptoms were neurological (e.g., headache) and musculoskeletal (e.g., back pain). We did not detect an association between TB disease or Mtb infection and LC at this sample size. However, the quality-of-life dimensions worsened during the post-COVID period. Conclusions: LC prevalence in Peru aligns with global trends, underscoring significant health burdens. Those with LC reported high levels of musculoskeletal and neurological symptoms, highlighting the need for long-term follow-up and larger studies in different geographic settings to dissect the impact of TB comorbidity on LC.

Background: Mass Drug Administration (MDA) is a WHO-recommended strategy for accelerating malaria elimination. However, its effectiveness in highly mobile populations remains uncertain. Studies show rapid parasitological rebound after cessation of MDA, this suggests that drug-based clearance alone is insufficient in interconnected settings. Although the resurgence is attributed to a combination of waning chemoprophylaxis and parasite importation, the relative contribution of these mechanisms and the quantitative conditions required for sustained elimination remain poorly defined. Methods: We developed a stochastic model of Susceptible-Infected-Recovered-Susceptible (SIRS) compartmentalized to a longitudinal PCR prevalence trial Ngodhe Island (artemisinin-piperaquine + primaquine) in 2016. Based on Bayesian estimation of transmission potential and daily importation rates, we simulated scenarios for a period of 4 years (2016–2019). We compared the epidemiological effects of increasing the MDA schedules (annual versus bimodal, which is two rounds during the two low transmission seasons) and measured the combined effect of integrating enhanced vector control coverage (90% LLIN coverage), port-of-entry screening (80% reduction in importation) and reactive focal MDA. Results: Model simulations have indicated that an intensifying MDA schedule (annual versus bimodal) is not associated with a proportional decrease in mean prevalence, the mean prevalence plateaus at 4.1% as a result of an importation induced equilibrium. This finding implies that, without reducing external seeding, the system will have an equilibrium at the pace of importation faster than the drug pulses can suppress transmission rates. Single-intervention strategies did not meet elimination thresholds but a combination strategy with bimodal MDA combined with improved vector control and importation screening exhibited a non-linear type of intervention combination, as it was able to drive and maintain mean prevalence below the pre-elimination threshold (< 1%). Conclusions: With high mobility like in Ngodhe Island, increasing the frequency of mass treatment is not a viable solution to suppress the reintroduction of parasites. Our results provide mechanistic evidence that elimination requires a shift from the current mono-therapeutic scaling to interventions that are multi-modal. The rollout of importation control and vector control should be made a priority alongside MDA, as chemoprevention alone is not sufficient in interrupting transmission.

Background: Long-lasting insecticidal nets (LLINs) reduce malaria risk through direct protection of users and potential community-level protection that may extend to non-users. The magnitude of these spillover impacts across African settings remains poorly characterised. Methods: We conducted a cross-sectional analysis of the latest Demographic and Health Survey (DHS) and Malaria Indicator Survey (MIS) data from malaria-endemic countries in Africa. Using the g-formula under a partial interference framework, we estimated spillover impacts of increasing community LLIN coverage from 50% to 70% on childhood malaria prevalence. The primary pooled analysis included 19 countries and was restricted to clusters with observed LLIN coverage of at least 50%. Findings: The pooled overall spillover estimate was protective but did not reach statistical significance (overall risk ratio [RR] 0·925, 95% CI 0·840–1·019; users 0·946, 0·853–1·049; non-users 0·934, 0·824–1·059). In a sensitivity analysis restricted to 13 countries with sufficient high-coverage clusters, spillover impacts were stronger and statistically significant (overall RR 0·885, 0·797–0·983; non-users RR 0·839, 0·761–0·926). Significant protection was also observed among socioeconomically vulnerable populations and in high-transmission settings. Interpretation: Community LLIN coverage showed a consistent protective association with childhood malaria prevalence. These findings support efforts to achieve high LLIN coverage and highlight the importance of accounting for spillover benefits in programme evaluation.

IntroductionTimely, protocol-adherent clinical decisions are crucial for reducing neonatal mortality in low-resource settings. Translating extensive national guidelines into bedside practice remains challenging.ObjectiveWe developed and evaluated AIFYA, a human-supervised, large language model (LLM)-based clinical decision support system (CDSS) aligned with Kenya's national newborn care protocols.MethodsThis prospective, mixed-methods, early-stage evaluation, guided by the DECIDE-AI framework, embedded AIFYA into routine workflows at two public health facilities (Level 5 and Level 4) in Bungoma County, Kenya, from September 2024 to June 2025. Primary outcomes were: (1) adoption, measured by cumulative neonatal cases managed; (2) training reach, assessed by credentialed healthcare workers (HCWs); and (3) guideline and citation concordance, evaluated through blinded review of 118 AI-generated recommendations by two neonatologists, with adjudication by a third. Secondary outcomes included protocol adherence and triage-to-decision time.ResultsA total of 50 HCWs were trained, and 550 neonatal cases were managed over 10 months. Among surveyed HCWs (n = 33), 76% were female (mean age 32.1 years). Expert review found 75% of recommendations were correct and 15% partially correct, with strong inter-rater reliability (weighted Cohen's kappa 0.85; 95% CI 0.79–0.91) between reviewers. Citation accuracy was 96%. In 40 complex dosing scenarios, 75% of outputs were rated correct. The median triage-to-decision time was 23 min (IQR 18–31). Implementation was supported by an offline-first architecture and a facility-based coaching model, sustaining engagement despite staff turnover.ConclusionA human-supervised, guideline-aligned AI CDSS can be feasibly implemented in routine neonatal care in low-resource settings, with high adoption and guideline concordance. Citation-linked recommendations enhance transparency and support clinical verification with most clinically appropriate recommendations. However, variability in complex scenarios highlights the need for ongoing refinement and strict clinical oversight. These findings support progression to control trials to evaluate clinical effectiveness and safety.

INTRODUCTION:Annually, approximately 174 million people globally are affected by Trichomonas vaginalis (T. vaginalis) infection. Half of these infections occur in resource-limited regions. Untreated T. vaginalis infections are associated with complications such as pelvic inflammatory disease and adverse pregnancy outcomes mostly seen in women. In resource-limited regions, the World Health Organization (WHO) advocates for syndromic case management. However, this can lead to unnecessary treatment. Accurate diagnosis of T. vaginalis is required for effective and prompt treatment. Molecular tests such as Polymerase Chain Reaction (PCR) have the advantage of having a short turn-around time and allow the use of non-invasive specimens such as urine and vaginal swabs. However, these diagnostic techniques have numerous disadvantages such as high infrastructure costs, false negative and positive results, and interstrain variation among others. This study aimed to evaluate the use of identical multi-repeat sequences (IMRS) as amplification primers for developing ultrasensitive diagnostic for T. vaginalis. METHODS:We used genome-mining approaches based on identical multi-repeat sequences (IMRS) algorithm to identify sequences distributed on the T. vaginalis genome to design a primer pair that targets a total of 69 repeat sequences. Genomic T. vaginalis DNA was diluted from 5.8×102 to 5.8×10-4 genome copies/μl and used as a template in the IMRS-based amplification assay. For performance comparison, 18S rRNA PCR assay was employed. RESULTS:The T. vaginalis -IMRS primers offered a higher test sensitivity of 0.03 fg/μL compared to the 18S rRNA PCR (0.714 pg/μL). The limit of detection for the Isothermal assay was 0.58 genome copies/mL. Using real-time PCR, the analytical sensitivity of the T. vaginalis -IMRS primers was <0.01 pg/μL, equivalent to less than one genome copy/μL. CONCLUSION:De novo genome mining of T. vaginalis IMRS as amplification primers serves as a platform for developing ultrasensitive diagnostics for Trichomoniasis and a wide range of infectious pathogens.

Evaluating the real-world effectiveness of the newly approved malaria vaccines, RTS,S/AS01 and R21/Matrix-M, is critical for informing vaccine policy, especially in areas not represented in the original clinical trials. Observational study designs such as cohort studies using the target trial emulation framework or the test-negative design offer promising approaches for estimating vaccine effectiveness in the real world. However, both designs require accurate, individual-level vaccination data, which remains a major challenge in many African countries. Strengthening electronic immunization registries, alongside continued efforts to improve the quality and completeness of paper-based immunization records, is essential in African countries, not only for the evaluation of current vaccines such as RTS,S/AS01 and R21/Matrix-M, but also in preparation for future malaria vaccines, to support robust vaccine monitoring and decision-making.

Despite significant progress in global malaria reduction since 2000, driven primarily by supply-side interventions including improvements in bed nets and medication availability, recent years have seen a stagnation in this decline. In certain regions, cases have even increased ([World Health Organization], [World Malaria Report], [2023]). This trend is particularly concerning in high-burden areas such as Suba South Sub-county in Homa Bay County, Kenya, where malaria remains a persistent public health challenge. However, demand-side barriers—such as lack of knowledge of the disease and perceived costs of prevention and treatment among residents—have been relatively overlooked in control efforts. To address this gap, we conducted a cluster-randomized controlled trial (cRCT) to investigate the impact of an educational intervention and financial incentives on malaria-related behaviors (Trials 25:165, 2024). This second-round cRCT aims to build upon the first-round findings, with modifications to the experimental design and educational content to further explore the potential of demand-side interventions and inform future malaria control strategies. This second-round cRCT will re-randomize the original 92 clusters to either conditional cash transfer (CCT), lottery incentive scheme (LIS), or control arms. Each intervention arm will include updated malaria education and financial incentives linked to negative malaria test results, with reward amounts adjusted to reflect local inflation. We will re-assess malaria prevalence using RDT, microscopy, and PCR at 3 and 6 months post-intervention. The primary outcomes are changes in malaria prevalence, LLIN usage, and knowledge/perception of malaria. The analysis will combine data from both the first and second rounds to improve statistical power and provide a more comprehensive assessment of the intervention’s impact. This study addresses the limitations of the first-round trial by increasing statistical power and refining the educational component. By evaluating the effectiveness of demand-side interventions, we aim to inform policy and program design for malaria control in high-burden settings. The resulting evidence on the role of demand-side factors will complement traditional supply-side approaches, ultimately refining future malaria control policies and programs. This research, thereby, has the potential to contribute to the development of sustainable, community-based strategies for malaria elimination. Trial registration UMIN000053284. Registered on January 6, 2024.