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Malaria remains a major global health burden, with an estimated 282 million cases and 610,000 deaths reported in 2024, disproportionately affecting children under five years of age and pregnant women in sub-Saharan Africa. Although antimalarial drugs are highly effective at clearing infections, their reliance on timely diagnosis and treatment limits their scalability as a population-wide control strategy. Vaccines therefore represent a critical tool for reducing malaria-associated morbidity and mortality, as well as interrupting parasite transmission, by inducing durable protective immunity. However, the complex lifecycle of Plasmodium parasites poses significant challenges for vaccine development, including the identification of protective antigens and optimal vaccine formulations. In this review, we summarize current vaccine strategies and discuss their key limitations. We also highlight emerging opportunities for possible avenues for future research and development. Full article

Background/Objectives: Malaria remains a major cause of hospitalization in rural Madagascar, yet data on in-hospital clinical presentation, management, and patient outcomes remain limited. Methods: We conducted a three-year retrospective study (2023–2025) at a rural district hospital in Ambatoboeny, Madagascar, including patients of all ages hospitalized with malaria confirmed by rapid diagnostic testing and microscopy. Sociodemographic, clinical, laboratory, and treatment data were extracted from routine records. Length of hospital stay (LOS) was analyzed continuously and categorized as ≤2, 3–4, or ≥5 days. Seasonal admission patterns and factors associated with LOS were assessed using chi-square or Fisher’s exact tests, and associations with rainfall seasonality were explored using Spearman’s correlation. Results: Among 134 hospitalized patients, median age was 15 years (interquartile range (IQR) 7–25) and 52.2% were female. Plasmodium falciparum predominated (94.0%), while mixed-species infections were identified in 6.0% of cases; 20.1% of cases were classified as severe malaria, including 10.4% with cerebral malaria. Co-infections were frequent (52.2%), most commonly Schistosoma haematobium infection (14.2%) and typhoid fever (12.7%). Intravenous artesunate was initiated in 97.8% of patients; all received paracetamol and 94.8% received intravenous fluids. Median LOS was 2 days (IQR 2–3); 12.7% had prolonged hospitalization (≥5 days). Prolonged LOS was significantly associated with cerebral malaria, high parasitemia (≥5%), blood transfusion, and age < 15 years (all p ≤ 0.034), while co-infection and nutritional status were not. Conclusions: Hospitalized malaria in rural Madagascar presents with heterogeneous clinical phenotypes and a high burden of co-infections. Prolonged LOS is primarily driven by markers of severe disease and supportive care requirements, underscoring the need for early severity recognition and resource planning in low-resource hospitals. Full article

Prior molecular docking and dynamics studies indicated a pyrazolopyridine–sulfonamide derivative (L87/PPS2, or simply PPS2) as a potential interactant with SARS-CoV-2 protein targets. The in vitro anti-SARS-CoV-2 activity and cytotoxicity profile of PPS2 were screened alongside a series of pyrazolopyrimidine (PZP) and triazolopyrimidine (TZP) derivatives. PPS2 demonstrated only partial inhibition of SARS-CoV-2 growth in Vero E6 cells at 100 µM. Crucially, however, four out of five PZPs and eight out of fourteen TZPs exhibited potent in vitro inhibitory activity against SARS-CoV-2 at 100 µM, with none of the tested compounds displaying cytotoxicity against Vero E6 cells at this concentration. Further characterization of one compound, PZP25, revealed an inhibitory concentration (IC50) of 8.2 µM, combined with low cytotoxicity (CC50 > 800 µM), yielding a selectivity index greater than 100. Time of addition assays indicated that PZP25’s antiviral effects were most pronounced when administered post-infection. While cellular pre-treatment provided a partial reduction in virus growth, modest virucidal activity was also observed at warmer temperatures (20 °C and 37 °C). Collectively, our findings demonstrate that PZP and TZP derivatives possess potent inhibitory activity of SARS-CoV-2 replication in vitro and highlight such compounds as promising chemical scaffolds for the development of novel antiviral agents targeting coronaviruses. Full article

One of the strategies for the control and elimination of schistosomiasis is the control of its snail vectors in an endemic area, as is done in other tropical diseases like malaria. However, the strategy currently practiced for the control of the disease in Nigeria is the annual mass administration of preventive chemotherapy (Praziquantel) among school-age children while neglecting the control of its snail intermediate host and other control components. The neglect of malacology and vector control will slow the elimination targets and timeline of 2030 set by the WHO. In this study, we investigated the abundance and seasonal variations in the snail vectors of schistosomiasis and the relationship between the disease among humans and infected snail vectors. A total of 21,282 snails were collected from 13 sites across the six area councils of the Federal Capital Territory (FCT). Of the collected snails, 1451 (6.8%) belong to three species: Biomphelaria pfeifferi (0.5%), Bulinus truncatus (2.1%) and Bulinus globosus (4.2%), which are known to be vectors of Schistosoma mansoni, Schistosoma haematobium and Schistosoma bovis, respectively. These three species were all shedding cercariae both at the time of collection and afterwards, when they were induced to shed cercariae. The association between the reported prevalence of the disease and the percentage of snails shedding cercaria were heterogenous across different communities. While Takushara, with a disease prevalence of 46%, had 60% of the cercaria shedding snails, Kwaita sabo pukafa and Guduji, with disease prevalences of 56% and 26% respectively, had no cercaria shedding snails. Similarly, Dagiri rafin shahu and Gwako 1, with disease prevalences of 60% and 38%, had cercaria shedding snails of less than 1%. Nonetheless, the presence of Bulinus and Biomphelaria species in these communities indicates a potential risk of infection for humans and other animals who may come in contact with the water. Consequently, integrated multisectoral control and elimination measures that combine malacological monitoring with behavioral, environmental, and historical epidemiological assessments with a deliberate health orientation of the people through sensitization and health education is advocated to reduce exposure to the disease risk factors and contribute towards elimination of the disease. Full article

The Democratic Republic of the Congo faces a high tuberculosis (TB) burden. In 2022, 61% of an estimated 402,000 TB cases were reported (World Health Organization Global tuberculosis report). To enhance case detection, the national TB program (NTP) introduced a program quality and efficiency approach (PQE), integrating systematic TB screening into outpatient departments (OPDs). Observational data of the PQE on the TB care cascade (from screening to treatment) across 70 sites in Kinshasa that initiated PQE during the first quarter of 2023 are presented. Data were collected monthly and validated during supervision visits, and disaggregated by sex, healthcare facility type (public, private, or faith-based), facility level (primary or secondary), and OPD within each facility. In 2024, 639,464 individuals were consulted in various OPDs in the participating facilities, 57% of which were female. The median number needed to screen (NNS) was 22.1, with an interquartile range of [9.5–104.3]. There was a significantly lower NNS observed in general practice and human immunodeficiency virus departments. Throughout the TB care cascade, women were less likely than men to be screened, tested, or treated. These findings, to be interpreted within the context of Kinshasa pilot facilities, provide insights to the NTP for developing PQE implementation research aimed at understanding the reasons for these discrepancies and informing NTP scale-up at the national level. Full article

Manual microscopy for malaria diagnosis is labor-intensive and prone to inter-observer variability. This study presents an automated binary classification approach for detecting malaria ring-form infections in thin blood smear single-cell images using a parallel neural network framework. Utilizing a balanced Kaggle dataset of 27,558 erythrocyte crops, images were standardized to 128 × 128 pixels and subjected to on-the-fly augmentation. The proposed architecture employs a dual-branch fusion strategy, integrating a convolutional neural network for local morphological feature extraction with a multi-head self-attention branch to capture global spatial relationships. Performance was rigorously evaluated using 10-fold stratified cross-validation and an independent 10% hold-out test set. Results demonstrated high-level discrimination, with all models achieving an ROC–AUC of approximately 0.99. The primary model (Model#1) attained a peak mean accuracy of 0.9567 during cross-validation and 0.97 accuracy (macro F1-score: 0.97) on the independent test set. In contrast, increasing architectural complexity in Model#3 led to a performance decline (0.95 accuracy) due to higher false-positive rates. These findings suggest that moderate-capacity feature fusion, combining convolutional descriptors with attention-based aggregation, provides a robust and generalizable solution for automated malaria screening without the risks associated with over-parameterization. Despite a strong performance, immediate clinical use remains limited because the model was developed on pre-segmented single-cell images, and external validation is still required before routine implementation. Full article

Background: Fixed-dose combination drugs (FDCs) are combinations of two or more active ingredients in a single dosage form. These formulations have proven effective in combating the development of resistance in diseases such as tuberculosis and malaria. Despite the benefits observed in the aforementioned cases, fixed-dose antibiotics combinations (FDACs) are increasingly raising questions about their rationality. This is the case for several FDACs listed in the AWaRe classification as not recommended, which unfortunately remain available on the pharmaceutical market, particularly in low- and middle-income countries like the Democratic Republic of Congo (DRC). Objectives: To identify the essential medicines available in pharmacies open to the public in the city of Kinshasa and to assess their inclusion in the DRC’s National List of Essential Medicines (NLEM) and in the World Health Organization’s (WHO) List of Essential Medicines (LEM). The rationality of the FDACs circulating in the city of Kinshasa were also evaluated based on the 2023 AWaRe classification. Methods: A cross-sectional and descriptive study was conducted between February and October 2025 in Kinshasa. For this purpose, fifty registered pharmacies open to the public were selected by systematic random sampling as the research sample. Data collection consisted of completing a data collection form after we had provided the pharmacies’ owners with the necessary explanations regarding the importance of the study and guaranteed their anonymity. Results: The controlled FDACs encountered comprised 27 specialties across 15 different formulations. Out of 15 formulations, 12 (80%) were included on the WHO list of non-recommended antibiotics and were not included in the DRC’s NLEM nor in the WHO’s LEM. Some had been withdrawn from the market in their countries of manufacture. Of the 15 FDACs evaluated for their rationality and compliance, the injectable FDACs presented problems related to the relevance and completeness of information contained on their packaging. On their primary packaging, there was a significant difference in the expiration dates of the powder and sterile water for injection contained in the combination pack, ranging from 6 to 36 months. Furthermore, the secondary packaging lacked data related to the sterile water for injection contained in the combination pack. In addition, several medications contained the same therapeutic combination. For injectable FDAC, for example, the combination Ceftriaxone-Sulbactam was represented by eight medications. For oral FDACs, the combination Sulfamethoxazole-Trimethoprim was represented by seven medications. Globally, 100% of these drug combinations originated from India. Conclusions: Fifteen varieties of FDACs were available in Kinshasa, most of which (80%) were unsuitable. It is important that public health authorities address this situation and develop stricter guidelines for granting marketing authorizations, particularly for FDACs. Full article

In malaria-endemic regions, women remain vulnerable to Plasmodium falciparum infection at the time of delivery. However, the immunological mechanisms underlying infection-associated inflammation in primigravid women remain poorly characterized. This exploratory study investigated cytokine-based immune profiles reflecting malaria infection status at delivery. We assessed 33 primigravid women from Nanoro, Burkina Faso (mean age 19 years; range 18–20.5) at childbirth. Antibody responses to P. falciparum antigens (PfCSP, PfAMA-1, and EBA-175) and plasma levels of cytokines (IL-4, IL-10, IL-6, TNF-α, and IFN-γ) were quantified using enzyme immunoassays. Multivariate analyses, including principal component analysis (PCA) and hierarchical clustering, identified three distinct immune profiles: (1) a low-inflammatory cluster with reduced IL-6 and TNF-α, (2) a TNF-α–dominant cluster, and (3) a highly pro-inflammatory cluster with elevated IL-6 and TNF-α. Cluster stability was supported by bootstrap analysis (AU ≥ 92%). All women in the most inflammatory cluster were P. falciparum–positive at delivery (Fisher’s exact test, p = 0.04; exploratory association). These cytokine-driven profiles reflect biologically distinct inflammatory states associated with concurrent infection at delivery rather than predictive immune predispositions. The findings underscore the potential of cytokine profiling as a hypothesis-generating tool to guide future longitudinal studies on immune regulation and the postpartum period. Full article

Kaposi’s Sarcoma-associated herpesvirus (KSHV) has been etiologically linked to several human cancers, including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). However, recent studies suggest that KSHV infection may also be associated with the development of other diseases or increased risks, such as KSHV inflammatory cytokine syndrome (KICS), diabetes, malaria, heart disease, and other cancers. In this review, we summarize these findings from clinical observations, epidemiological studies or laboratory research, though more studies are needed in these emerging areas. We believe that this work will enhance our understanding of the molecular mechanisms underlying KSHV pathogenesis and contribute to improving treatments for related human diseases. Full article

New insecticides for indoor residual spraying (IRS) are being developed to manage resistance. Chlorfenapyr (Sylando^® 240SC), a pro-insecticide, is metabolized by active mosquitoes into the toxic metabolite tralopyril. This mode of action requires adapted “free flying” bioassays (because chlorfenapyr is converted to its toxic metabolite tralopyril when mosquitoes are metabolically active). A miniature-experimental hut (MEH) assay was developed within the Ifakara Ambient Chamber Test (I-ACT) with a rabbit as a host to measure residual efficacy under controlled conditions. Sylando^® 240SC was compared with SumiShield^® 50WG (clothianidin) for 12-month residual efficacy against malaria and arbovirus vectors. Residual activity was assessed on mud, wood and concrete with two huts per substrate treated with Sylando^® 240SC, one with SumiShield^® 50WG, and one with untreated control. Five replicates of 20 mosquitoes per strain (malaria vectors: pyrethroid-susceptible Anopheles gambiae and -resistant An. arabiensis and An. funestus; culicines Aedes aegypti and Culex quinquefasciatus) were exposed overnight at one-week post spraying and monthly thereafter. Multivariable mixed-effect logistic regression with binomial errors and log link function assessed non-inferiority with a 7% margin on mosquito mortality as the primary outcome for malaria vectors. Both products induced delayed mortality, with higher effects on malaria vectors than culicines. Across all substrates and malaria species combined over the full 12 months of observation, Sylando^® 240SC was non-inferior to SumiShield^® 50WG on mortality measured at 72 h (76% vs. 67%, OR = 0.86, 95% CI: 0.77–0.97) and 168 h (89% vs. 82%, OR = 0.74, 95% CI: 0.63–0.87). Sylando^® 240SC performed comparably to SumiShield^® 50WG, supporting its use as an IRS additional option. The new I-ACT mini-experimental-hut assay provides a practical tool for evaluating pro-insecticides. The importance of free-flight evaluation methods for pro-insecticides is discussed. Full article

Background: At the end of each year, stakeholders of the Essential Immunization Programme (EPI) in the DR Congo meet to review progress made and lessons learned from the implementation of the Annual Operational Plan (AOP) and to set priorities for the following year. This paper presents a conference report that summarizes the main outcomes of the 2025 annual review meeting, which took place from 15 to 20 December 2025, and attracted 76 participants. Conference takeaways: While the 2024 WUENIC data show that the DR Congo is off-track for the 2030 Immunization agenda targets for all antigens, the administrative coverages were reported as optimal in 2025. EPI activities are planned based on administrative coverages, likely overestimated. In 2025, 47% of health zones in North-Kivu, South-Kivu and Ituri (49 out of 104) were fully or partially controlled by armed groups, leading to partial disruptions of immunization service delivery. In 2025, the DR Congo successfully launched the measles–rubella vaccine introduction preceded by a catch-up vaccination campaign in children aged from 6 months to 14 years old and continued to roll out malaria vaccines using a phased approach. Conclusions: Learning from the implementation of the 2025 AOP, the EPI stakeholders adopted a set of priority actions for the immunization programme in 2026. Full article

Background/Objectives: Next to malaria, respiratory viruses, particularly respiratory syncytial virus (RSV), are responsible for the hospitalization and death of thousands of young children each year in sub-Saharan Africa. During peak seasons, conducting separate tests is time-consuming and distressing. This underscores the need for efficient, rapid multiplexed diagnostic tools. This study aimed to evaluate the clinical performance of a lateral flow assay (LFA) based antigen combo rapid diagnostic test (ML Ag Combo RDT, manufactured by MobiLab) that detects RSV, influenza viruses A and B (Flu A/B), and SARS-CoV-2. Methods: The Allplex panel 1 rRT-qPCR assay was used as a reference assay to evaluate the clinical performance of the LFA Ag Combo RDT in pediatric hospital settings. It was performed using 470 nasopharyngeal swab (NPS) specimens from hospitalized children under two years of age with respiratory symptoms. Results: Based on the comparative analysis of the testing results for 470 NPS, the ML Ag Combo RDT demonstrated high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90.06%, 98.38%, 93.67, and 97.39% for RSV, and 30%, 100%, 100%, and 95.43 for Flu A/B, respectively. Agreement with the Allplex panle1 1 rRT-qPCR was strong (κ = 0.90 for RSV) and moderate (κ = 0.45 for Flu A/B), with overall accuracies of 96.63% for RSV and 95.5 for Flu A/B. This was further supported by ROC analysis for aggregated data (RSV and, Flu A/B) with an AUC value of 0.925. As expected, in samples with high viral loads (Ct < 20), the Ag Combo RDT achieved 100% sensitivity for RSV and Flu A/B. Sensitivity declined slightly at lower viral loads (Ct > 35). Conclusions: The ML Ag Combo RDT demonstrates high specificity and diagnostic accuracy for the detection of RSV and Flu A/B in pediatric hospital settings where timely diagnosis is critical. Full article

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy in which numerous biomarker candidates have been reported, yet few progress to clinical use. Beyond biological complexity, this low translational yield reflects the lack of systematic criteria for prioritizing biomarkers during the discovery stage. In particular, tumor-derived signals identified in tissue often fail to persist in clinically accessible biofluids, as cross-compartment signal behavior is rarely evaluated explicitly. Methods: We developed an extracellular vesicle (EV)-guided, multi-compartment proof-of-concept framework to assess biomarker robustness and translatability early in discovery. EV proteomes from three biologically distinct CCA cell lines and a normal cholangiocyte were analyzed using multivariate and machine-learning-assisted approaches to identify conserved EV-associated features. These were integrated with public transcriptomic, epigenetic, copy-number, promoter usage, and miRNA regulatory data. Tissue relevance was assessed using TCGA/GTEx RNA-seq datasets, and exploratory signal behavior was examined in pooled serum- and urine-derived EVs from CCA patients and controls. Results: EV proteomics revealed marked molecular heterogeneity across CCA models but identified a small subset of conserved EV-associated proteins. SERPINF2 was used as a representative example, showing consistently reduced EV-associated abundance across all CCA models with coordinated regulation across multiple molecular layers. SERPINF2 expression was independent of patient sex and tumor stage and clearly distinguished tumor from normal bile duct tissue. Exploratory biofluid analyses demonstrated compartment-dependent signal behavior, with SERPINF2 depletion detectable in urine-derived EVs but not in serum-derived EVs. Conclusions: Rather than validating a single biomarker, this study presents an EV-guided, multi-compartment framework for prioritizing biomarker candidates at the discovery stage. By explicitly accounting for tumor heterogeneity and compartment-specific signal preservation, this proof-of-concept approach provides a practical decision-support strategy for identifying biomarkers with greater translational potential in heterogeneous cancers such as CCA. Full article

This study demonstrates the feasibility of using a T7 phage display platform to deliver a library of tick antigens as a vaccine to disrupt tick feeding in cattle. Cattle were vaccinated at three-week intervals via intradermal and intramuscular routes with a cocktail of male and female Amblyomma americanum T7 phage display cDNA libraries, with and without adjuvant. ELISA and Western blot analyses confirmed that vaccinated cattle mounted immune responses directed against phage-displayed tick proteins rather than the T7 phage backbone. Vaccine-induced antibodies recognized both native tick salivary gland proteins and selected recombinant salivary proteins, indicating effective antigen presentation and biologically relevant immunity with binding to native tick saliva proteins. The adjuvanted formulation elicited significantly stronger immune responses than phage-only immunization. Immunized cattle exhibited robust immune memory, evidenced by a pronounced anamnestic response following tick infestation. This immunity translated into measurable anti-tick effects, including reduced tick feeding efficiency and blood ingestion. Tick reproductive success was severely compromised, with larval hatching declining from 54% in ticks fed on control cattle to 4% in ticks fed on immunized cattle. This study establishes a practical and scalable T7 phage-displayed whole-tick antigen platform capable of inducing durable anti-tick immunity in cattle. Full article

The identification of species complexes in freshwater snails remains challenging due to limited diagnostic morphological characters and incomplete taxonomic knowledge in many taxa. Within the family Bithyniidae, species have traditionally been classified using shell morphology and genital anatomy to distinguish intraspecific variation from interspecific differences. However, extensive morphological plasticity has hindered reliable species delimitation, and the presence of cryptic diversity further complicates taxonomy. Recent DNA barcoding studies of Hydrobioides have provided evidence of such cryptic diversity, highlighting the need for taxonomic reassessment within the genus. In the present study, we examined morphological variation in Hydrobioides nassa from Thailand in conjunction with mitochondrial DNA sequence data. Molecular phylogenetic analyses based on cytochrome c oxidase subunit I (cox1) sequences revealed three well-supported genetic lineages within H. nassa, accompanied by high levels of pairwise genetic divergence. Morphological comparisons of shell, operculum, and radular characters further supported differentiation among these lineages, although some characters showed overlap. While Hydrobioides has previously been regarded as comprising a single morphologically defined species, our results demonstrate that H. nassa represents a complex of genetically distinct lineages with subtle but consistent morphological differences. This study highlights the importance of integrating molecular approaches with traditional morphological analyses to improve taxonomic resolution and to better understand biodiversity within freshwater snail groups exhibiting cryptic diversity. Full article