To determine the prevalence of malaria parasite carriage and anaemia among senior high school students and to identify the demographic, behavioural and residential factors associated with these outcomes. Cross-sectional study. Participants were enrolled from Tempane Senior High School students in the Tempane District of the Upper East Region of Ghana. 290 senior high school students aged 15-22 years. Demographic characteristics, residential status and insecticide-treated bed net (ITN) use were collected using a structured questionnaire. Venous blood samples were obtained for malaria parasite detection by microscopy and haemoglobin measurement. Association analysis was performed using logistic regression models. The prevalence of malaria parasite carriage was 23.1%, while 49.0% of participants were anaemic. Day students had a significantly higher prevalence of malaria (59.2%) than boarding students (15.8%) (p<0.001). Malaria parasite infection was also more common among students who did not use ITNs (39.7%) compared with users (5.0%) (p<0.001). In multivariate analysis, not using ITN (adjusted OR (aOR)=15.97; 95% CI 6.33 to 40.32; p<0.001) and being a day student (aOR=5.65; 95% CI 2.58 to 12.36; p<0.001) were significant predictors of malaria parasite infection. Students infected with malaria parasites had significantly lower mean haemoglobin (11.50±1.43 g/dL) than uninfected students (12.56±1.35 g/dL) (p<0.001). Malaria parasite infection (aOR=9.36; 95% CI 3.91 to 22.42; p<0.001) and male students (aOR=2.26; 95% CI 1.09 to 4.65; p=0.028) were associated with higher odds of anaemia. Whereas age groups 18-20 years (aOR=0.41; 95% CI 0.17 to 0.97; p=0.043) and those above 20 years (aOR=0.07; 95% CI 0.02 to 0.27; p<0.001) were associated with lower odds of anaemia. Malaria and anaemia remain prevalent among senior high school students in the Upper East Region of Ghana, with asymptomatic malaria strongly linked to anaemia. Not using ITN and being a day student significantly increased the odds of malaria parasite infection. These findings underscore the need to extend malaria prevention interventions to adolescents through school-based programmes, including routine screening, treatment and promotion of consistent ITN use, especially among day students.
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 + 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 = 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'.
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.
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.
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become less effective at preventing malaria due to rising parasite resistance. IPTp with dihydroartemisinin-piperaquine (DP) alone or in combination with SP (DP+SP) dramatically lowers the risk of malaria in pregnancy compared to SP but is associated with lower birthweight and early life wasting. We estimated the effect of IPTp-DP, DP+SP, and SP on infant growth outcomes and assessed possible treatment mechanisms through a causal mediation analysis. We used infant follow-up data (N=761) from a trial ( NCT04336189 ) that randomized pregnant women to receive monthly IPTp-DP, SP, or DP+SP. We compared weight-for-length (WLZ) and length-for-age (LAZ) z-scores between treatment arms. We assessed possible mediation through pregnancy, birth, and infancy factors using interventional indirect effect models. Compared to IPTp-SP, IPTp-DP+SP decreased mean WLZ by 0.18 [95% confidence interval (CI) -0.03, 0.39] between 1-3 months and 0.28 (95% CI 0.07, 0.49) between 4-6 months, with the largest differences among primigravidae. Lower risk of active placental malaria in IPTp-DP+SP helped reduce differences in mean WLZ vs IPTp-SP (+0.06, 95% CI 0.02, 0.10). The IPTp-DP+SP arm had up to 0.28 lower mean LAZ between 7-13 months compared to IPTp-DP, particularly among children who were wasted between 0-6 months; low birthweight had a persistent, mediating effect on linear growth. Adverse birth outcomes contributed to early growth faltering among children born to mothers receiving IPTp-DP+SP vs IPTp-SP, but the prevention of placental malaria partially counteracted the negative effects of IPTp-DP+SP on ponderal growth. Intermittent preventive treatment of malaria in pregnancy (IPTp) with a combination of dihydroartemisinin-piperaquine (DP) and sulfadoxine-pyrimethamine (SP) leads to lower birth weight compared to SP alone, but it is unclear whether effects persist through infancy and what mechanisms drive these differences.DP+SP provided some improvements to ponderal growth over SP by preventing active placental malaria, but these benefits were not large enough to offset negative effects associated with other prenatal factors.Infants born to mothers who received IPTp with DP+SP were at higher risk of growth faltering in the first year of life compared to DP or SP alone; while differences in weight-for-length subsided over time, some children developed chronic forms of malnutrition that may be difficult to recover from.
Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpose the anticancer kinase inhibitor berzosertib for the treatment of malaria, by assessing whether a predicted efficacious human dose for malaria is within the clinically established safety and tolerability profile. First, an oral dose fractionation study was performed in a Plasmodium falciparum-infected humanized mouse model to evaluate the antimalarial pharmacokinetic-pharmacodynamic properties of berzosertib. The activity of berzosertib was shown to be strongly dependent on the time in which the concentrations remain above the minimum parasiticidal concentration (MPC). A human physiologically based pharmacokinetic model was then developed and used to simulate the exposure-response relationships and determine the effective human dose which fulfilled the target pharmacokinetic profile of sustained concentrations above the MPC. Our prediction indicates that six daily intravenous doses of 75 mg of berzosertib will be required for the treatment of an uncomplicated blood stage malaria infection, which is comparatively lower than the clinical maximum tolerated dose for cancer therapy, which was identified as 440 mg administered intravenously twice weekly over a 21-day cycle for up to 18 weeks. Despite berzosertib's potential for repurposing, further preclinical development is necessary to ensure it meets the standard of current and emerging antimalarials.
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 × 103/µL (range 40-171 × 103/µL), 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.
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 = 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; ≥ 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 (≥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 = 0.041). In multivariable analysis, higher fidelity was associated with higher participant responsiveness (β = 3.4, p < 0.001), stronger facilitation strategies (β = 2.8, p < 0.001), and lower perceived intervention complexity (reverse-coded; β = 2.1, p < 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.
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 µM; K1 EC50=31.21 µM) and P. knowlesi (EC50=4.51 µM). Molecular docking studies explored curcumin's interaction with the ATP-binding pocket of P. falciparum glycogen synthase kinase-3 (PfGSK3) with favourable binding affinity (-8.72 kcal/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-α, IFN-γ), 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.
γδ T cells play a key role in modulating immune responses to pregnancy-associated malaria and can enhance vaccine efficacy through their activation and cytotoxic functions. However, the mechanisms guiding γδT cell differentiation in placental malaria (PM) remain poorly understood. We examined ex vivo associations between cytokines, metabolic profiles and γδ T-cell differentiation in women with PM. A case-control study including 50 women at delivery (21 PM+, 29 PM-) was carried out. Peripheral, placental intervillous space, and cord blood mononuclear cells were isolated, and multiparametric flow cytometry was performed to characterize γδT-cells and memory phenotypes, its subsets (Vδ1+, Vδ2+, Vδ3+), and the expression of exhaustion (TIM-3, PD1) and activation (HLA-DR) markers. Ex vivo plasma levels of IL-8, IL-33, and IL-35 were quantified by Luminex assay or ELISA. Immunometabolic profiles were assessed in a subset of 15 samples from uninfected women following cell stimulation with phytohemagglutinin (PHA) by SCENITH assay. In general, the frequency of γδ T cells and their subsets varied depending on the different blood compartments, with naïve and central memory (CM) phenotypes observed mainly in CBMC, while effector memory (EM) and terminally differentiated effector memory (TEMRA) phenotypes were found mainly in PBMC and IVBMC. Ex vivo analyses showed that γδ T cell-modulating cytokine IL-8 were associated, in a compartment-dependent manner, with down-regulation of immunoregulatory markers TIM-3 and PD-1. Interestingly, IL-8 and IL-33 were associated with increased frequency of the TEMRA cell phenotype in peripheral blood, consistent with enhanced differentiation of naïve γδT cells during PM. Metabolic profiling of the different cell types further established an enhanced mitochondrial metabolic activity in predominantly terminally differentiated γδ T cells in PBMC, compared to the mainly glycolytic activities of non-terminally differentiated cells in CBMC and IVBMC. Placental malaria is associated with a compartment-specific memory γδ T cell differentiation, with cytokines and metabolic reprogramming regulating exhaustion. These findings reveal key regulatory processes that determine the function of γδ T cells during placental malaria, which constitute potential targets for new therapeutic intervention against PM.
Despite significant progress, malaria remains a major challenge in Mali, due to heterogeneous transmission. The WHO 'High Burden to High Impact' strategy advocates targeting of high-transmission areas. This study aimed to identify clinical malaria hotspots in two health areas within the Kolondieba district with differing transmission levels. A retrospective cross-sectional study analysed 35,934 confirmed malaria cases extracted from consultation registers between 2019 and 2021 in the health areas of Kadiana (high risk) and Kolondieba Central (moderate risk). Transmission periods were determined in each zone by analysing variations in mean incidence trends, and high-risk clusters (hotspots) were identified using Kulldorff's method according to these periods. Transmission periods and hotspot identification (2019-2021) revealed distinct dynamics between the two health areas. In Kadiana, the majority of clusters remained stable, with persistent hotspots across all eight periods (Kadiana and Tienkourani; RR: 1.8-6.3). In Kolondieba Central, hotspot dynamics evolved from a localised configuration (1 to 2 villages) towards spatial expansion, with more extensive clusters appearing during the final periods (RR: 1.7-2.2). Kolondieba town remained a persistent hotspot. This study confirms the heterogeneity of transmission at a fine scale, with stable hotspots even in both moderate and high-risk areas. It is essential to focus on human mobility to guide malaria control interventions.
This study aimed to determine the prevalence and associated factors of anemia among HIV-positive children receiving antiretroviral therapy (ART) at two urban clinics in Mbarara City, Southwestern Uganda. We conducted a cross-sectional study among 293 HIV-positive children (<18 years) attending ART clinics at Mbarara Municipal Health Center IV and Holy Innocent Children's Hospital between July and September 2025. A structured questionnaire captured sociodemographic and clinical data. Venous blood were collected for complete blood count (CBC) analysis, and stool samples were examined for intestinal parasites. Data on CD4 count and viral load were abstracted from medical records. Anemia was defined using age-specific WHO criteria. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with anemia, with statistical significance set at p ≤ 0.05. The overall prevalence of anemia was 6.14% (95% CI: 3.4% - 8.9%). Normocytic normochromic anemia was the predominant morphological type (72.2%). In the multivariate analysis, a recent episode of malaria (AOR = 9.61; 95% CI: 3.26-28.34), the presence of an opportunistic infection (AOR = 6.78; 95% CI: 1.28-35.83), and poor adherence to ART (AOR = 14.75; 95% CI: 1.31-165.65) were independently and significantly correlated with anaemia. While the prevalence of anemia in this cohort of HIV-infected children on ART was lower than global averages, it remains a significant clinical concern. The strong associations with malaria, opportunistic infections, and suboptimal ART adherence highlight critical areas for intervention. Targeted strategies, including integrated malaria control, enhanced prevention and management of OIs, and reinforced adherence support, are required to decrease the anaemia burden and optimize health outcomes in this at-risk population.
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.
The emergence of artemisinin resistance in Plasmodium falciparum threatens the sustainability of malaria control programs and underscores the need for new therapeutic strategies. Recently, two proteins, RAD5 (PfRAD5) and WD40-repeat protein 11 (PfWD11), have been implicated in parasite survival and drug resistance. Their druggability, however, remains underexplored. We integrated computational and experimental approaches to assess PfRAD5 and PfWD11 as antimalarial targets. Structural models were retrieved from AlphaFold and aligned with orthologues across Plasmodium species. A library of 216 antibiotics was screened by molecular docking, and molecular dynamics simulations. Top-ranked compounds were tested against P. falciparum 3D7 cultures in vitro, alone and in combination, and gene expression changes in PfRAD5 and PfWD11 were quantified by qPCR. Docking identified strong binders to PfRAD5 (talampicillin, dicloxacillin, raltegravir) and PfWD11 (cervinomycin A2 monoacetate, eAmSPC 2593, puromycin). Molecular dynamics confirmed the stability of protein-ligand complexes. In vitro, puromycin exhibited the highest inhibition (85% at 100 μg/mL), while combinations enhanced activity. The triple combination (puromycin + raltegravir + dicloxacillin) achieved complete inhibition, and puromycin + chloroquine exhibited synergistic effects at in a concentration-dependent manner. qPCR showed consistent downregulation of PfRAD5 and PfWD11 following puromycin-based treatments, whereas chloroquine alone upregulated PfRAD5 expression. PfRAD5 and PfWD11 represent novel antimalarial targets. Repurposed antibiotics, particularly puromycin in synergistic regimens, offer a cost-effective strategy to counteract emerging resistance and accelerate therapeutic development.
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, ≥100 µg/g, >250 µg/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 ≥100 µg/g, and 7% had fCal >250 µg/g. Schistosoma mansoni prevalence was 49.1%. Infection intensity was positively associated with all fCal outcomes (detectable: OR 1.20, ≥100 µg/g: OR 1.11, >250 µg/g: OR 1.26; continuous: β .06) while infection status was positively related to all but the continuous fCal outcome. HIV was associated with fCal ≥100 µg/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.
Context: In numerous low- and middle-income nations, malaria remains a significant issue due to the challenges associated with diagnosing it through thin blood smears. The appearance of images can vary significantly depending on the microscope type, magnification, lighting conditions, slide preparation methods, and staining techniques. Due to the delicate morphology of parasites, false negatives might adversely affect patient care. Objective: To achieve optimal outcomes from validation, it is essential to construct a robust and easily replicable process. This pipeline should integrate the optimal elements of classical machine learning and end-to-end deep learning, enhance reliability by pairwise ensembling, and select ensemble weights in a logical, data-driven manner. Method: To achieve our objective, we propose two tracks. The initial track encompasses real-time augmentation, convolution-based feature extraction, and the training of calibrated classical classifiers. The second module focuses on training many convolutional networks from inception to completion. Subsequently, we construct paired ensembles and employ a hybrid methodology to select convex weights for combining the findings. This method initially evaluates a set of candidate weights and then refines them to maximise validation accuracy. Results: The precision of the two-track architecture consistently improves, transitioning from conventional baselines to end-to-end models. Optimal and consistent enhancements are achieved through weighted ensembling. Utilising optimised fusion reduces the incidence of false negatives for subtle parasites and false positives caused by staining artefacts. This yields an accuracy of 96.35% on the reserved data and reduced variance across folds. Conclusions: The integration of augmentation, multiple modelling tracks, and optimal pairwise ensembling yields the highest accuracy in categorising malaria smears. It facilitates further enhancements by incorporating supplementary models, multi-class extensions, and operating-point calibration.
Background Malaria remains a critical global health challenge, with over 68% of Ethiopia's population living in at-risk areas. While Long-Lasting Insecticidal Nets (LLINs) are a cornerstone of prevention, their effectiveness depends on consistent use. This study aimed to assess LLIN ownership and utilization patterns and identify socio-behavioral and physical determinants of their effectiveness in endemic communities. Methods A community-based, cross-sectional survey was conducted from October 2024 to January 2025 across 11 administrative regions in Ethiopia. Using a two-stage stratified cluster sampling technique, data were collected from 9,222 households (34,427 individuals) through face-to-face interviews and direct physical observations. Data analysis was performed using the SPSS Complex Samples module and hierarchical multivariable logistic regression. Results The survey found a household LLIN ownership rate of 71.5%, while the proportion of sufficient LLINs for every two people was 58.3%. Among those who owned nets, the overall utilization rate was 59.9%, with significantly higher rates in rural areas (72.7%) than in urban areas. Vulnerable groups achieved higher usage levels, specifically pregnant women (78.5%) and children under five (67.2%). Multivariable analysis indicated that age and pregnancy status were the strongest predictors of LLIN use, with ORs of 0.258 (p < 0.001) and 0.662 (p < 0.001), respectively. Major barriers identified included a 60.5% lack of confidence in hanging nets (p < 0.001) and a widespread misconception (64.1%) that malaria risk is restricted to the rainy season. Conclusion Although Ethiopia has made strides in LLIN ownership and prioritized protection for vulnerable demographics, overall utilization remains below the 80% threshold required for community-wide protection. To bridge the gap between ownership and consistent use, national strategies should transition toward skill-based interventions and targeted communication to address practical barriers and seasonal misconceptions.
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 particulièrement élevée en Afrique subsaharienne. Pour les voyageurs se rendant dans des zones endémiques, la connaissance du risque d’infection et l’application rigoureuse de mesures de prévention appropriées sont essentielles. En Suisse, une méthodologie transparente a été élaborée en collaboration avec d’autres pays européens, permettant de classer les zones à risque de paludisme sur la base de données épidémiologiques récentes et de représenter les mesures de prévention harmonisées dans des cartes détaillées. Ces cartes aident les médecins de premier recours et de médecine des voyages à donner des conseils uniformes, fondés sur des preuves et adaptés à la pratique, et sont disponibles sur le site de référence suisse de médecine des voyages : www.healthytravel.ch.
The extent to which inflammation from overweight or obesity influences interpretation of commonly used vitamin A status biomarkers is uncertain. We examined relationships among weight status, inflammation, and retinol or retinol-binding protein (RBP) among women (15-49 y) and children (6-59 mo) with normal weight to overweight or obesity. Cross-sectional data were separately analyzed from 24 surveys representing 24 countries (n = 16,771 women in 13 surveys and n = 24,707 children in 22 surveys) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (women) or BMI-for-age z-score (BAZ, children), inflammatory biomarkers C-reactive protein (CRP) and/or α1-acid glycoprotein (AGP), and retinol or RBP by linear regression. We also examined potential mediation by CRP and/or AGP in relationships between BMI/BAZ and retinol/RBP with structural equation modeling. Regression and mediation models accounted for complex survey designs and were adjusted for potential confounders. Among women, BMI was positively associated with retinol/RBP in 5 of 13 surveys and positively associated with CRP and/or AGP in 10 of 13 surveys; associations between biomarkers of inflammation and retinol/RBP varied in direction and magnitude. Among children, BAZ was positively associated with retinol/RBP in 3 of 22 surveys and positively associated with CRP in 1 survey (none with AGP); inflammation biomarkers were consistently negatively associated with retinol/RBP. In 3 of 13 women's surveys and 1 of 22 children's surveys, inflammation partially mediated the relationship between BMI/BAZ and retinol/RBP; however, the direction of associations varied. In these surveys limited to individuals without undernutrition or malaria, inflammation associated with overweight or obesity does not appear to impact vitamin A assessment when measured with retinol/RBP. However, findings support measurement of biomarkers reflecting inflammation (of any source) to interpret vitamin A status, particularly among children.