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Saudi Arabia has made significant progress toward malaria elimination; however, imported cases continue to occur, particularly in the southwestern regions. This study aimed to describe the clinical characteristics and outcomes of patients with malaria in the Aseer Region, Saudi Arabia. A retrospective observational study was conducted at Khamis Mushait General Hospital, Aseer Region, Saudi Arabia, including all patients with malaria from January 2022 to December 2025. Demographic, clinical, laboratory, and outcome data were extracted from the electronic medical records. Severe malaria was defined according to the World Health Organization criteria. Multivariate logistic regression using Firth's penalized maximum likelihood estimation was performed to identify independent predictors of severe malaria (&#x2265;1 WHO criterion). Statistical analysis was performed using R software (version 4.2.1). A total of 311 patients were included, predominantly male (90.0%), with a mean age of 28.8 &#xb1; 11.3 years. Ethiopian nationals comprised nearly half the cases (48.2%), followed by Saudi (16.4%) and Yemeni (15.1%) nationals. Plasmodium vivax was the most common species (51.1%), followed by Plasmodium. falciparum (40.2%). Fever was the most frequent symptom (89.4%), followed by fatigue (50.8%), chills (46.9%), and vomiting (39.5%). Low parasitemia (<1%) was the most frequent finding (33.8%), followed by moderate (27.3%) and mild (18.3%) levels, while high (4.2%) and very high parasitemia (1.9%) were uncommon. Severe malaria (&#x2265;1 criterion) was diagnosed at 43.7%, with severe anemia (26.0%) and jaundice (23.2%) being the most frequent WHO severity criteria. Notably, 84% of the cases occurred during 2024-2025, indicating a recent outbreak, with a sharp peak of 43 cases in October 2024. Multivariate logistic regression identified two independent predictors of having at least one WHO severity criterion: higher parasitemia level (adjusted OR = 1.70 per 1% increase, 95% CI: 1.40-2.11, p < 0.001) and non-Saudi nationality (adjusted OR = 2.40, 95% CI: 1.10-5.62, p = 0.027). Malaria in the Aseer Region predominantly affects young adult male expatriates, suggesting its imported nature. The predominance of P. vivax represents a shift from historical patterns. Parasitemia level and being of non-Saudi nationality independently predict severe malaria and may therefore support risk stratification and clinical decision-making. The dramatic case surge in 2024-2025 highlights regional vulnerability to outbreaks despite control progress. These findings support enhanced screening for at-risk populations, maintenance of clinical capacity for severe malaria management, and robust surveillance systems for early outbreak detection.

Malaria constitutes a major public health burden in Sudan, accounting for most outpatient visits and hospital admissions across approximately 80% of the states. The armed conflict beginning in April 2023 severely disrupted an already fragile health system, affecting the surveillance system infrastructure. No prior studies have assessed the impact of conflict on routine malaria surveillance data reported through District Health Information Software 2 (DHIS2). This study evaluated the effects of conflict on completeness and reporting of malaria impact indicators data across Sudanese states. A mixed-methods design combined quantitative analysis of quarterly DHIS2 data (January 2020-March 2025) from 17 states with qualitative exploration of surveillance system functionality. Quantitative analysis included descriptive analyses and interrupted time series analysis (ITSA) of three malaria impact indicators: quarterly reported malaria cases (presumed and confirmed) per 100,000 state population, test positivity rate (RDT&#x2009;+&#x2009;microscopy), and quarterly inpatient malaria deaths per 100,000 state population. Data completeness was quantified as the proportion of missing quarterly reports per state. Descriptive analysis graphs illustrate pre- and post-conflict trends and missing data patterns. ITSA was conducted for 11 states with complete post-conflict time series; six states with incomplete data were excluded. Three key informant interviews with national- and state-level malaria programme managers, selected from severe and less severe conflict-affected states, provided contextual insights. Qualitative data were analyzed using a deductive framework approach. Missing DHIS2 reporting increased substantially after April 2023. Inter-state variation was observed: western and southern states (except North Kordofan) experienced persistent data gaps, whereas northern and eastern states maintained relatively continuous reporting despite declining trends. Qualitative findings indicated stronger surveillance functionality in less-affected states by conflict. ITSA showed a statistically significant decline in quarterly reported malaria case rates per 100,000 state population at conflict quarter (p&#x2009;=&#x2009;0.02), with no significant post-conflict trend change. Key informants identified health facility destruction, workforce shortages, unpaid salaries, and communication breakdowns as major barriers. The conflict coincided with widening disparities in malaria surveillance across states, reflecting underlying inequalities in health system capacity. Strengthening states' surveillance systems is critical in conflict-affected settings. Future research should examine locality-level impacts to better capture subnational variation.

Quantifying therapeutic responses in clinical malaria is easier than for most other infections as the intraerythrocytic parasites can be counted by microscopy or estimated using quantitative PCR. In treating the blood-stage of malaria, between 107 and 1013 parasites undergo a first-order decline in densities at a rate determined by the concentrations and potency of the antimalarial drug. A simple conceptual framework based on total intravascular parasite biomass and standard sigmoid concentration-effect relationships for parasite killing explains most, but not all, aspects of antimalarial therapeutic responses, and it has proved very useful in designing chemoprevention and treatment regimens and in understanding the selection and spread of resistance. Drugs acting on younger circulating ring-stage asexual parasites (artemisinins, cipargamin, ganaplacide) provide rapid parasite clearance, which translates into faster clinical recoveries and a life-saving benefit in severe malaria. Artemisinin-sensitive Plasmodium falciparum densities decline with a half-life (PC1/2) of usually less than 5 h. Many antimalarial drugs are eliminated slowly and provide protracted exposures, which allows full treatment to be administered in 3 days, and also provides chemosuppression of newly acquired infections for 1 month. Greater availability of drug measurement in malaria-endemic areas would facilitate the field assessment of antimalarial drugs. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.

Chemoprophylaxis (in travellers) and seasonal chemoprophylaxis and preventive treatment (in endemic areas) are important but not exclusive elements of malaria prevention, which hinges on vector repelling in travellers and more comprehensive vector control measures in endemic areas. In malaria-endemic countries, a comprehensive strategy combining drug-based prevention, vaccines and vector control is essential to reduce disease burden. Chemoprophylaxis in endemic settings primarily involves intermittent preventive treatment in vulnerable groups and mass drug administration in communities, rather than continuous daily chemoprophylaxis (as recommended for non-immune travellers). Vaccination has become a groundbreaking addition to the malaria control portfolio in endemic countries. The World Health Organization-endorsed RTS,S/AS01 (Mosquirix&#xae;) and R21/Matrix-M vaccines rolled out in many highly malaria-endemic sub-Saharan African countries, in addition to other malaria control tools, provide overall moderate protection in young children but significantly reduce severe disease and death, and are considered safe. For travellers, malaria vaccines are not available to date. Effort is being put into the development of monoclonal antibodies against malaria as a preventive treatment strategy both to provide protection for the immunocompromised or unvaccinated high-risk individuals before exposure and to disrupt seasonal malaria transmission with a single application. The evolution of malaria preventive tools is a dynamic process, with numerous novel developments on the horizon. For travel medicine indications, further harmonisation of recommendations on the one hand, but also&#xa0;more sophisticated personalisation of recommendations, is envisaged.

Malaria is one of the most prevalent infectious diseases worldwide, posing a significant threat in the malaria-endemic areas. The rapid emergence of Plasmodium strains resistant to the existing antimalarial drugs underscores the necessity for discovering the next generation of antimalarial drugs with reduced resistance and enhanced potency. Quinoline-based compounds have been long recognized for their remarkable antimalarial efficacy due to their ability to interfere with heme detoxification within the parasites and have been extensively modified to generate molecules with improved pharmacological potential and overcome the resistance. Among the various strategies employed, the incorporation of piperazine moiety has gained considerable attention, as it can improve pharmacokinetic properties, molecular flexibility, and target interactions. Consequently, quinoline-piperazine hybrids have emerged as promising candidates with enhanced antimalarial potential. This review underscores recent advances in the development of quinoline-piperazine hybrids as antimalarial agents, emphasizing their activity against chloroquine-sensitive and resistant Plasmodium falciparum strains. In addition, structure-activity relationship (SAR) trends influencing potency, selectivity, and resistance profiles are discussed. These insights will facilitate the rational design and development of novel chemical entities as next-generation antimalarials.

Many regions in Africa continue to experience a high malaria burden, highlighting the need for improved intervention tools adapted to local eco-epidemiological contexts. The aims of this study were to develop and evaluate adaptive intervention strategies for malaria vector control tailored to these local conditions. This two-stage, cluster, sequential, multiple-assignment, randomised, open-label trial comprised 84 clusters in Muhoroni and Nyakach, subcounties of Kisumu County, western Kenya. Each cluster included 500-600 residents in an area of approximately 2 km2 and all residents in the clusters were invited to participate in the study. In stage 1, clusters were randomly assigned, in a 1:1:1 ratio, to standard pyrethroid-based long-lasting insecticidal nets (LLINs; henceforth standard LLINs) alone, piperonyl butoxide-treated LLINs (henceforth PBO nets), or standard LLINs plus annual indoor residual spraying (IRS), stratified by subcounty. Due to the nature of the interventions, masking to intervention was not feasible. Clusters with an adjusted incidence rate ratio (aIRR) of 0&#xb7;8 or more were classified as non-responders. Non-responding clusters were re-randomised in stage 2. The non-responding clusters from the stage 1 PBO nets group were re-randomised, in a 1:1 ratio, to receive either supplemental microbial larviciding or annual IRS. The non-responding clusters from the stage 1 standard LLINs plus annual IRS group were re-randomised, in a 1:1 ratio, to either IRS twice per year (henceforth biannual IRS), or enhanced IRS annually, which included spraying both indoor residential structures and peridomestic resting structures not covered by routine IRS. The coprimary outcomes were clinical malaria incidence at 1-6 months, 7-12 months, and 13-18 months post-intervention, assessed through active surveillance of cohort populations once every 2 weeks and analysed in all participants with available data. Although the study procedures posed minimal risk to participants, adverse event data were regularly reviewed. The trial was registered with ClinicalTrials.gov (NCT04182126) and is complete. Between March 8, 2021, and Aug 31, 2024, the study enrolled 47&#x2009;614 participants (51&#xb7;8% male, 48&#xb7;2% female) from 14&#x2009;246 households in 84 clusters. In stage 1, PBO nets significantly reduced malaria incidence at 1-6 months post-intervention (aIRR 0&#xb7;75, 95% CI 0&#xb7;69-0&#xb7;81; p<0&#xb7;0001) and at 7-12 months post-intervention compared with standard LLINs (aIRR 0&#xb7;87, 95% CI 0&#xb7;80-0&#xb7;95; p=0&#xb7;0012), and standard LLINs plus annual IRS was more effective than standard LLINs alone at 1-6 months (aIRR 0&#xb7;74, 95% CI 0&#xb7;68-0&#xb7;81; p<0&#xb7;0001). In stage 2, among stage 1 non-responding clusters, adding annual IRS to PBO nets was more effective than supplementing with larviciding at 13-18 months (aIRR 0&#xb7;89, 95% CI 0&#xb7;81-0&#xb7;97; p=0&#xb7;0081). When added to standard LLINs, enhanced IRS was more effective than biannual IRS 13-18 months post-intervention (aIRR 0&#xb7;67, 95% CI 0&#xb7;56-0&#xb7;80; p<0&#xb7;0001). Overall, the four adaptive intervention strategies significantly reduced clinical malaria incidence compared with standard LLINs (all p<0&#xb7;01). Adaptive strategies starting with PBO nets had greater and more sustained incidence reductions than strategies beginning with standard LLINs plus annual IRS. No adverse events or serious adverse events were recorded. This trial supports replacing conventional pyrethroid-only LLINs with PBO nets as the first-line malaria control strategy. In moderate-to-high-risk settings, additional annual IRS or microbial larviciding could be implemented to further reduce malaria burden. US National Institutes of Health. For the Swahili translation of the abstract see Supplementary Materials section.

Malaria remains a critical public health challenge in southeastern Bangladesh, particularly in Cox's Bazar, where the mass displacement of over one million Rohingya refugees since 2017 has heightened transmission risks. The interplay of ecological fragility, overcrowded living conditions, and climatic variability underscores the need for a deeper understanding of malaria epidemiology in this high-risk setting. A 4-year repeated cross-sectional study was conducted (2021-2024) in Camp No. 26, Teknaf, Cox's Bazar. A total of 582 participants were enrolled, comprising 486 individuals from the malaria-endemic refugee camp and 96 healthy controls from a nonendemic region. All were screened for Plasmodium falciparum and Plasmodium vivax using rapid diagnostic tests (RDTs), with microscopy performed to confirm all RDT-positive cases and a subset of RDT-negative samples. Meteorological data (temperature, rainfall, and humidity) were obtained from regional weather stations. Serological profiling assessed total anti-Plasmodium antibodies, while hematological parameters including hemoglobin concentration, RBC and platelet counts, and ESR were measured. Correlation and regression analyses were employed to identify climatic predictors of malaria incidence and their associations with immunohematological changes. Out of 582 individuals, 345 malaria cases were confirmed. Peak transmission occurred during the monsoon season (June-September), particularly in August. P. falciparum infections showed earlier and sharper peaks compared to P. vivax. Relative humidity demonstrated the strongest correlation with incidence (r = 0.724-0.77), followed by rainfall and temperature. Antibody titers were significantly higher in P. falciparum-positive individuals. Infected participants exhibited anemia, thrombocytopenia, and elevated ESR, with more pronounced alterations in P. falciparum cases. This study highlights the seasonal and species-specific nature of malaria transmission in Rohingya refugee camps, driven predominantly by climatic variables, particularly humidity. The observed serological and hematological alterations underscore their potential as biomarkers for surveillance. These findings advocate for climate-sensitive, species-specific malaria control strategies tailored to displaced populations.

Plasmodium vivax malaria is a threat to armed forces operating in the Korean Peninsula. Surges in malaria cases in the Republic of Korea entail increased risk. We report 6 cases from a cluster of P. vivax malaria cases in a non-endemic setting in active duty personnel who had redeployed from the Korean Peninsula. Demographics, disease course, and laboratory data were collected on 6 patients diagnosed with Plasmodium vivax malaria at Fort Bliss in 2022. All patients were males, with a mean age of 23 years (range 20-27 years), exposed in the Dagmar North training area in the Gyeonggi province in 2021, with an average time from symptom onset to diagnosis of 57 days (8-121 days). All had uncomplicated malaria. Laboratory findings included hemoglobin of 12.1g/dL (range 8.1-14.2 g/dL), platelets of 123&#x2009;&#xd7;&#x2009;103/&#xb5;L (range 40-171&#x2009;&#xd7;&#x2009;103/&#xb5;L), and parasitemia <1% (0.1%-0.9%) with diagnosis on peripheral smear and/or rapid antigen testing. No cases received chemoprophylaxis. Patients were treated with artemether/lumefantrine and primaquine. Clearance of parasitemia on peripheral smear was seen after an average of 2.8 days (range 2-4 days). Changing vector ecology and increased tempo of training exercises in the Dagmar North Region near the Demilitarized Zone are hypothesized to contribute to this cluster of cases. Malaria diagnosis post-deployment in non-endemic regions is challenging due to the long latency of illness onset and requires clinician vigilance. Preventive measures of pre-deployment should also be emphasized.

Curcumin, a polyphenolic compound exhibits various bioactivities, including antimalarial and anti-inflammatory effects. This study investigated the long-term antimalarial effects of curcumin through in vivo experiments using Plasmodium berghei NK65-infected mice, complemented by in vitro and in silico analyses targeting the plasmodial GSK3 protein. Through in vitro, the antimalarial activity of curcumin was assessed on P. falciparum K1 (multi-drug resistant strain) and 3D7 (sensitive strain) as well as P. knowlesi A1H1 of Plasmodium lactate dehydrogenase (pLDH) assay, alongside cytotoxic effects on Vero cells using the MTT assay. Curcumin demonstrated its bioactivity to disrupt the parasite's growth and replication based on the effective inhibition on both P. falciparum (3D7 EC50=8.11&#xb5;M; K1 EC50=31.21&#xb5;M) and P. knowlesi (EC50=4.51&#xb5;M). Molecular docking studies explored curcumin's interaction with the ATP-binding pocket of P. falciparum glycogen synthase kinase-3 (PfGSK3) with favourable binding affinity (-8.72kcal/mol), revealing it potential as a selective inhibitor. Further, in vivo experiments validated curcumin's immunomodulatory activities and therapeutic effects in P. berghei-infected mice. Prolonged curcumin treatment has shown to significantly reduce the parasitaemia compared to the controls. Cytokine profiling via ELISA showed enhanced levels of anti-inflammatory cytokines (IL-10, IL-4) and decreased pro-inflammatory markers (TNF-&#x3b1;, IFN-&#x3b3;), mitigating systemic inflammation associated with malaria. Histopathological analysis revealed reduction of tissue damage in the curcumin-treated mice, including decreasing parasite sequestration, inflammatory cell infiltration, hepatocyte necrosis and hemorrhages. This study highlights curcumin's potentials in inhibiting PfGSK3, regulating immune responses, and attenuating tissue damage which support its therapeutic role against malarial infection.

Ethiopia has experienced a marked malaria resurgence in recent years, with the Amhara Region disproportionately affected. Although Ethiopia's national strategy emphasizes test-before-treat and a public-private mix, implementation fidelity of the malaria test-and-treat guideline during resurgence has not been well characterized. This study assessed fidelity to malaria diagnosis and treatment guidelines in public and private health facilities in the Amhara Region within this resurgence context. We conducted a convergent parallel mixed-methods study from February to March 2025 in 53 health facilities (38 public, 15 private) in Amhara Region. The facility was the unit of analysis; one provider primarily responsible for malaria case management was interviewed per facility (n&#x2009;=&#x2009;53). Implementation fidelity was operationalized using Carroll's framework across three domains: content (adherence to key diagnostic/treatment steps), coverage (proportion of suspected cases tested before treatment, extracted from facility registers), and frequency (self-reported consistency of testing for febrile patients in the preceding month). Domain scores were standardized to 0-100 and averaged with equal weights to form a composite fidelity score;&#x2009;&#x2265;&#x2009;75% indicated high fidelity. To explain quantitative patterns, we conducted 32 in-depth interviews and analyzed data using inductive thematic analysis with CFIR-informed interpretation. Quantitative analysis used nonparametric tests and parsimonious multivariable linear regression, with prespecified sensitivity analyses excluding the self-reported frequency domain. Overall mean implementation fidelity was 64.3% (SD 12.1); 40% of facilities had high fidelity (&#x2265;75%), and 13% scored <50%. Public facilities had higher fidelity than private facilities (median 67% [IQR 60-77] vs 63% [IQR 56-70]; Wilcoxon rank-sum p&#x2009;=&#x2009;0.041). In multivariable analysis, higher fidelity was associated with higher participant responsiveness (&#x3b2;&#x2009;=&#x2009;3.4, p&#x2009;<&#x2009;0.001), stronger facilitation strategies (&#x3b2;&#x2009;=&#x2009;2.8, p&#x2009;<&#x2009;0.001), and lower perceived intervention complexity (reverse-coded; &#x3b2;&#x2009;=&#x2009;2.1, p&#x2009;<&#x2009;0.001). Interviews indicated that fidelity gaps were driven by diagnostic and treatment deviations (including non-species-specific prescribing), inconsistent counseling and follow-up mechanisms, supply constraints, and patient pressure, with challenges more frequently emphasized in private facilities. Implementation fidelity to Ethiopia's malaria test-and-treat guideline in Amhara during resurgence was moderate, with lower fidelity in private facilities. Provider responsiveness, facilitation strategies, and lower intervention complexity were identified as factors associated with implementation fidelity. Strengthening supportive supervision and mentorship with explicit inclusion of private facilities, improving supply reliability, and simplifying decision supports may improve adherence during resurgence.

A recent study conducted in West Khasi Hills (WKH) and West Jaintia Hills (WJH) districts of Meghalaya has documented a low occurrence of the primary malaria vectors, Anopheles baimaii and An. minimus, alongside a relatively higher abundance of other anophelines, particularly members of the Maculatus Group. Plasmodium infection in the An. maculatus sensu lato (s.l.) was last reported in 1941, with no subsequent implication of An. maculatus s.l. in malaria transmission from Meghalaya or Northeast (NE) India for over eight decades. Given this apparent gap between species abundance and its recognised vector status, the present study was undertaken to examine the species composition and vector potential of predominant species using molecular tools in the Khasi Hills and Garo Hills regions of Meghalaya. In this study, we employed molecular techniques for precise species identification and detection of parasites. Our findings confirm natural infections of Plasmodium falciparum in An. maculatus sensu stricto (s.s.) and An. pseudowillmori-two member species of the Maculatus Group in Meghalaya. Resting adult Anopheles mosquitoes were collected between 2019 and 2023 (excluding 2021 due to the COVID-19 pandemic) in the Khasi Hills and Garo Hills regions using a mouth aspirator and torchlight, both indoors and outdoors. Out of 215 specimens analysed, 177 (82.32%) were identified as An. maculatus s.s., 33 (15.34%) as An. pseudowillmori, and 5 (2.32%) as An. willmori. Notably, Plasmodium infection was detected in 49 (27.68%) of 177 An. maculatus s.s. specimens and 16 (48.48%) of 33 An. pseudowillmori specimens, reinforcing their potential vectorial role in malaria transmission. FST analysis revealed significant genetic differentiation between An. maculatus s.s. populations from the Khasi Hills Region (KHR) and Garo Hills Region (GHR), further supported by haplotype network analysis. Additionally, blood meal analysis of specimens collected from cattle sheds during evening resting hours indicated diverse host feeding patterns: 15% had fed on humans, 16% on cattle, and 17% on both. The presence of mixed blood meals suggests that An. maculatus s.s. exhibits opportunistic and flexible feeding behaviour. These results provide molecular evidence of malaria transmission by specific members of the Maculatus Group in Meghalaya, underscoring their epidemiological importance. The genetic divergence and feeding plasticity highlight the need for targeted vector control in the region.

Malaria is endemic in Burkina Faso, with seasonal transmission during the rainy season. Environmental changes such as dam construction may influence mosquito ecology and malaria transmission; however, entomological data from this area remain limited. This study aimed to characterize malaria vector dynamics, including species composition, blood meal sources, and sporozoite infection rates, in five villages at varying distances from the Soum dam located in the Nanoro Health District catchment area in Burkina Faso. From March 2022 to February 2023, mosquitoes were collected monthly via pyrethrum spray catches (PSCs) targeting indoor resting vectors. Mosquitoes were identified morphologically via taxonomic keys. PCR analyses were performed to identify species within the Anopheles gambiae complex, determine blood meal sources, and assess Plasmodium falciparum infection. A total of 11,378 Anopheles mosquitoes were collected, including 3,432 males (30.1%) and 7,948 females (69.9%). An. gambiae s.l. was the most abundant species (86.5%), followed by An. funestus (10.6%). Within the An. gambiae complex, 91.5% were An. coluzzii, 8.3% An. arabiensis, and 0.2% An. gambiae sensu stricto. The vector density was highest in Soum (49.7%) and decreased with distance from the dam. The overall sporozoite rate was 6.2%, with higher rates in Seguedin (9.5%) and Soala (8.7%). Among the tested mosquitoes, 34.7% fed on humans, 14.2% on animals, and 23.6% on both. Anopheles coluzzii was the predominant vector and showed moderate anthropophilic behavior. Despite higher vector density near the dam, infection rates were greater in distant villages, highlighting the complexity of vector dynamics in dam-associated areas and the need for localized control strategies.

Due to the emergence of resistance to both artemisinin derivatives, and their partner drugs, new antimalarials are urgently needed. Ideally, new orally active antimalarials would not only engage new targets but also demonstrate a high barrier to resistance selection, and the ability to kill both proliferating rings and growth-arrested rings resulting from artemisinin exposure. In this report we disclose a novel antimalarial chemotype, the imidazo[4,5-c]pyridine-6-carboxamides, and a representative compound 10b that possesses all these qualities. Orally dosed 10b (4 &#xd7; 60 mg/kg/day or 1 &#xd7; 160 mg/kg) cures Plasmodium yoelii-infected mice out to 28 days. This compound is unaffected by over 40 distinct target- and efflux-based resistance mutations in the AReBaR resistome screen, suggesting a novel mode of action. Furthermore, at a minimum inoculum of resistance of 109 parasites, 10b proved refractory to resistance selection. Lastly, with a 6 h exposure, 250 nM 10b kills both proliferating rings and dihydroartemisinin-induced dormant parasites.

Repetitive display of the major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S/AS01 and R21/Matrix-M. Recently, however, the CIS43 monoclonal antibody that preferentially targets the junctional region of PfCSP has been shown to be highly protective in humans, highlighting its junctional epitope as a key vaccine target. Here, we develop a vaccine based on tandem repeats of the junctional epitope displayed on a self-assembling nanoparticle and compare this CIS43-based junctional vaccine alone or in combination with the benchmark R21 vaccine, using both B cell analysis and monoclonal antibody isolation to define targeting of the immune response. Comparable reduction in liver burden was observed following vaccination with the best junctional vaccine and R21 at a dose of 1&#x2009;&#x3bc;g. At a dose of 0.25&#x2009;&#x3bc;g, a modest reduction of malaria liver burden with the junctional vaccine was observed compared to R21. Further, combining the junctional and R21 vaccines did not yield substantial improvement, although a modest trend was observed. While the R21 vaccine elicited antibodies primarily against the major repeats, the junctional vaccine elicited antibodies against both junctional and major repeat regions. In vivo B cell analysis and isolation of monoclonal antibodies confirmed differences in vaccine-induced antibody specificities. Altogether, these data suggest the nanoparticle-formatted tandem-repeated CIS43-junctional vaccine to be a promising approach to broaden immunity against malaria, either as a standalone intervention or in combination with R21.

The role of gut inflammation for intestinal schistosomiasis remains poorly understood in chronically infected and repeatedly treated populations. We conducted a cross-sectional study nested in the SchistoTrack cohort within Pakwach district, Uganda. In 2024, 640 participants aged 6-85 years were examined for Schistosoma mansoni by Kato-Katz. Fecal calprotectin (fCal) concentration was measured by enzyme-linked immunosorbent assays. Fecal calprotectin was analyzed as binary outcomes (detectable, &#x2265;100&#x2005;&#xb5;g/g, >250&#x2005;&#xb5;g/g) and natural log-transformed continuous values. Co-endemic infections (malaria, HIV, hepatitis B [HBV]) and sociodemographic covariates were investigated in logistic regressions with covariate selection. 74.4% of participants had detectable fCal, 22.3% had fCal &#x2265;100&#x2005;&#xb5;g/g, and 7% had fCal >250&#x2005;&#xb5;g/g. Schistosoma mansoni prevalence was 49.1%. Infection intensity was positively associated with all fCal outcomes (detectable: OR 1.20, &#x2265;100&#x2005;&#xb5;g/g: OR 1.11, >250&#x2005;&#xb5;g/g: OR 1.26; continuous: &#x3b2; .06) while infection status was positively related to all but the continuous fCal outcome. HIV was associated with fCal &#x2265;100&#x2005;&#xb5;g/g (OR 2.52), while malaria and HBV were uninformative. Schistosoma mansoni infections are characterized by persistent, clinically concerning levels of gut inflammation in chronically infected populations with repeated praziquantel treatment. Integration of fCal thresholds into clinical guidelines may improve management of schistosomiasis-related morbidity.

Cis-regulatory elements (CREs) drive tissue- and cell-specific gene expression and are essential for safe, sustainable genetic control strategies in pest and vector insects, including the engineering of gene drives in the primary human-malaria vector Anopheles gambiae. Yet CREs remain poorly defined in mosquitoes due to limited computational tools and practical methods for identification and validation. We present a systematic in silico approach for CRE discovery, correlating targeted DNA-motif searches with gene expression, followed by frequency and distribution analysis within putative promoter regions. Applied to the A. gambiae germline, this approach identified hundreds of putative CREs significantly correlated with germline expression in one or both sexes, often linked to distinct sperm developmental stages and chromosomal locations, suggesting roles in broader regulatory mechanisms such as dosage compensation and meiotic silencing. When mapped onto pre-characterised germline promoters, CRE distribution aligned with regions associated with experimental expression patterns. Finally, we validated a top-ranked testis-enriched CRE using an in vivo dual-reporter assay, showing that mutation of conserved nucleotides drastically altered male germline expression. To the best of our knowledge this work provides the first nucleotide-resolution regulatory genome annotation of the A. gambiae germline, offering a transferable framework to aid promoter design for genetic control strategies against malaria mosquitoes and other insect pests.

Malaria parasites are obligately sexual hermaphrodite protozoans, with gamete fusion occurring in the mosquito midgut, followed by meiosis and recombination. Parasite populations display a range of mating structures, from predominantly selfing to highly outcrossed; yet, the fitness consequences of selfing versus outcrossing remain poorly understood. This project investigated gamete fusion dynamics within mosquitoes and compared the fitness of selfed and outcrossed zygotes. We generated fluorescently labelled clones of NF54 (mCherry; African) and NHP4026 (GFP; Thai), crossed these parasites and genotyped 8540 oocysts from 435 mosquitoes collected 7-14 days post-infection. In two independent crosses, we observed decreasing proportions of outcrossed oocysts and increasing selfing over time. This pattern is consistent with the faster maturation of outcrossed oocysts compared with selfed oocysts. Our results suggest a substantial fitness advantage of outcrossing, potentially due to the removal of deleterious mutations accumulated during asexual replication in the vertebrate host. We also found that selfed NF54 oocysts were larger than either outcrossed or selfed NHP4026 oocysts, which may influence sporozoite production and transmission potential. Fluorescently labelled parasites provide clear resolution of mating patterns, temporal dynamics and transmission potential in mosquitoes. Importantly, faster maturation of outcrossed parasites may maximize levels of recombination in transmitted malaria parasite populations.

Background: The Democratic Republic of the Congo accounts for approximately 12-13% of the global malaria burden. While international guidelines oppose the use of Artemisia annua infusions due to risks of sub-therapeutic dosing and resistance selection, the plant remains widely used in resource-limited regions. This study evaluates the clinical acceptability and perceptions of healthcare providers regarding the integration of Artemisia annua tea into formal malaria control in the Maniema province. Methods: A cross-sectional survey was conducted among 337 healthcare professionals in the Kalima health district using the KoboCollect digital platform. Multivariate logistic regression was employed to identify the primary socio-professional determinants of clinical acceptability. Results: The overall clinical acceptability of Artemisia annua integration was 81.0%, with 82.8% of providers perceiving the preparation as effective. Rural residency was the strongest predictor of adherence (AOR = 6.847; p = 0.003), reflecting a pragmatic response to frequent ACT stockouts and high treatment costs. Despite high acceptability, 49.0% of providers identified the lack of clinical evidence as a major barrier, and 91.4% demanded formal training on standardized dosage and biological mechanisms. Conclusions: A significant "policy-practice gap" exists between international guidelines and field realities in the DRC. Healthcare providers demonstrate high readiness for integration but emphasize the absolute necessity of galenic standardization to mitigate resistance risks. To address these concerns, a complementary genomic investigation is currently underway in the same study area, comparing PfKelch13 mutation prevalence among Artemisia tea users versus ACT-treated patients. This molecular surveillance will provide essential evidence to define safety parameters for future phytopharmaceutical integration.

Malaria remains a major infectious disease worldwide, with a particularly high incidence in sub-Saharan Africa. For travelers visiting endemic areas, awareness of the risk of infection and the rigorous application of appropriate preventive measures are essential to prevent this life-threatening disease. In Switzerland, a transparent methodology was developed in collaboration with other European countries classifying malaria risk areas based on current epidemiological data and presenting harmonized preventive measures in detailed maps. These maps support travel medicine experts as well as primary care physicians in providing consistent, evidence-based, and practice-oriented travel medicine advice. They are available on the Swiss reference website for travel medicine: www.healthytravel.ch. Le paludisme reste une maladie infectieuse majeure dans le monde, avec une incidence particuli&#xe8;rement &#xe9;lev&#xe9;e en Afrique subsaharienne. Pour les voyageurs se rendant dans des zones end&#xe9;miques, la connaissance du risque d&#x2019;infection et l&#x2019;application rigoureuse de mesures de pr&#xe9;vention appropri&#xe9;es sont essentielles. En Suisse, une m&#xe9;thodologie transparente a &#xe9;t&#xe9; &#xe9;labor&#xe9;e en collaboration avec d&#x2019;autres pays europ&#xe9;ens, permettant de classer les zones &#xe0; risque de paludisme sur la base de donn&#xe9;es &#xe9;pid&#xe9;miologiques r&#xe9;centes et de repr&#xe9;senter les mesures de pr&#xe9;vention harmonis&#xe9;es dans des cartes d&#xe9;taill&#xe9;es. Ces cartes aident les m&#xe9;decins de premier recours et de m&#xe9;decine des voyages &#xe0; donner des conseils uniformes, fond&#xe9;s sur des preuves et adapt&#xe9;s &#xe0; la pratique, et sont disponibles sur le site de r&#xe9;f&#xe9;rence suisse de m&#xe9;decine des voyages : www.healthytravel.ch.