Search Results (1,041)

Background/Objectives: Severe Plasmodium falciparum malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa. The clinical outcome is largely driven by the balance between pro-inflammatory and anti-inflammatory cytokines. However, immunological data from Sudanese children remain limited and the diagnostic utility of cytokine biomarkers has not been formally evaluated in this population. Therefore, this study aims to compare plasma levels of IFN-γ and IL-10 among Sudanese children with severe malaria (SM), uncomplicated malaria (UM) and healthy controls (HC) and to evaluate their diagnostic accuracy using in differentiating SM from UM cases. Methods: A hospital-based case–control study was conducted at Mohamed Elamin Hamid Pediatric Hospital, Omdurman, Sudan. The study enrolled 105 children (aged 3 months to 16 years) divided into three age- and sex-matched groups (n = 35 per group): SM, UM and HC. Plasma cytokines IFN-γ and IL-10 were measured by ELISA. Results: The anthropometric measurements did not differ significantly across the groups. SM was significantly associated with lower hemoglobin and markedly reduced platelet counts. Both IFN-γ and IL-10 were significantly elevated in SM versus UM and HC (p < 0.001). A strong positive correlation was observed between IFN-γ and IL-10 (rho = 0.688, p < 0.001) in malaria patients. Additionally, a significant correlation was observed between IL-10 and platelet count (rho = −0.338, p = 0.009). Both IL-10 (AUC = 0.0.720) and IFN-γ (AUC = 0.687) demonstrated moderate diagnostic performance in discriminating between SM vs. UM. Conclusions: Elevated levels of IFN-γ and IL-10 strongly associated with severe P. falciparum malaria in Sudanese children. Measuring IL-10 and IFN-γ at the time of presentation may differentiate between SM and UM cases. Further studies are needed. Full article

Malaria remains a leading cause of morbidity and mortality among children in sub-Saharan Africa. Acute kidney injury (AKI) is increasingly recognized as a frequent and severe complication of pediatric severe malaria, yet it remains largely underdiagnosed. This under-recognition is driven by important limitations in current diagnostic approaches. The World Health Organization (WHO) criteria rely on fixed serum creatinine (SCr) thresholds that are poorly adapted to children, whereas Kidney Disease Improving Global Outcomes (KDIGO) criteria require baseline SCr (bSCr) values that are rarely available in low-resource settings. The estimation of bSCr using back-calculation methods is further complicated by population-specific factors, particularly malnutrition, which reduces creatinine generation and may mask kidney injury. In addition, urine output (UO) monitoring is often underutilized despite its diagnostic value, and access to laboratory testing remains limited. Emerging biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and kidney injury molecule-1 (KIM-1) show promise for early detection and risk stratification but remain insufficiently validated in African pediatric populations. In this narrative review, we highlight key challenges in diagnosing malaria-associated AKI (MAKI) in children and discuss potential strategies to improve early detection in resource-limited settings, with the aim of reducing morbidity and mortality. Full article

Different protozoan parasites are the causative agents of tropical diseases, including malaria, toxoplasmosis, leishmaniasis, and Chagas disease (CD), which, altogether, affect over 300 million people throughout the world. Except for two recently approved malaria vaccines, individuals affected by or at risk of contracting any of these four diseases still experience a lack of effective treatments and vaccines. Many vaccine studies, including those that have reached clinical trials, are based on inactivated parasites, adjuvanted recombinant proteins, or viral vector vaccines. Here, we review the current advances towards the development of vaccines based on genetically modified live-attenuated parasites (GMLAP) as well as RNA formulations encoding parasite antigens. Because these are diseases caused by intracellular pathogens that depend on efficient T-cell responses for parasite control, these two new vaccine platforms have generated great expectations, since they are known to induce a robust cellular immune response. Although preclinical studies aimed at developing new malaria, toxoplasmosis, and leishmaniasis vaccines have led to significant progress that may soon result in clinical trials, advances in next-generation vaccines against CD are lagging behind. Increased collaborative efforts between research groups, governments, and the pharmaceutical industry, particularly in Africa, Asia, and Latin American countries, are urgently needed to accelerate the development of vaccines for all neglected and less-studied diseases. Full article

Mosquito-borne diseases are a major global health concern, infecting up to 700 million people annually and causing over one million deaths. Of the several genera of biting mosquitoes, species of Anopheles are mostly studied for their ability (vector competence) to transmit Plasmodium protozoan parasites, some species of which cause malaria. More than 480 species of Anopheles have been described worldwide, and about 70 of these are responsible for Plasmodium spp. transmission. However, the focus on Anopheles as vectors of Plasmodium has led to a relative lack of study about the ability of Anopheles to transmit viruses. Some Anopheles species have been experimentally confirmed as competent for various arboviruses. In most cases, they are secondary vectors, with relatively low competence, contributing to overall transmission while other species of mosquito or other vectors are responsible for sustained transmission. Although secondary vectors may contribute less to transmission, they may play important epidemiological roles by extending transmission seasons and/or providing a means of overwintering viruses. Here, we conducted a review of scientific repositories to build a database of known Anopheles competence for arboviruses. After exclusions, we retained 427 laboratory-confirmed studies from 7343 papers reviewed. Our analysis suggests some Anopheles spp. could contribute to arbovirus overwintering in temperate regions. Full article

Background/Objectives: Malaria affects almost half of the world’s population and causes more than 600,000 deaths annually. Young children in malaria-endemic areas have the highest mortality rate because of their immature immune systems. Global efforts to control the disease have had limited success, with two WHO-recommended pre-erythrocytic malaria vaccines showing suboptimal efficacy; no vaccine has yet been approved against the blood stages of the parasite that causes the clinical symptoms of malaria. Therefore, there is an urgent need to identify new vaccine candidates against the parasite’s blood stages to achieve protection against the disease. Methods: Previous studies in our lab identified a few potential vaccine candidates expressed on the surface of malaria-parasite-infected RBCs using sera from disease-resistant children from malaria-endemic regions and a phage-displayed cDNA library generated from P. falciparum. In an innovative approach, we successfully immunized mice using live Plasmodium falciparum-infected red blood cells {Pf-iRBCs (L)}, the membrane fraction of P. falciparum-infected RBCs {Pf-iRBCs (M)}, and live uninfected human red blood cells (hRBCs) in suitable adjuvants. The polyclonal sera produced against Pf-iRBC immunizations were evaluated for specificity and parasite inhibition in vitro and used in a phage display biopanning assay to identify novel antigens on the surface of Pf-iRBCs. Results: Our data indicate that the polyclonal serum produced in BALB/cJ mice, against live Pf-iRBC (L) and their membrane fraction, specifically interacts with surface antigens of parasitic origin on Pf-iRBCs. Additionally, the anti-Pf-iRBC polyclonal serum exhibits significant parasite-killing activity in the in vitro growth inhibition assay (GIA). We have identified both known and novel antigens associated with the Pf-iRBC membrane using phage display cDNA library screening assays. Conclusions: As a proof of concept, our phage display screening identified antigens known to be associated with the Pf-iRBC membrane. Additionally, we identified several unknown Pf-iRBC antigens predicted to be associated with Pf-iRBC membrane (PlasmoDB), suggesting that our approach has the potential to identify novel antigens yet to be evaluated as vaccine candidates against falciparum malaria. In our follow-on studies, we will evaluate the newly identified antigen using an integrated in vitro and in vivo challenge experiment. These studies form the core supporting data for further evaluation of the vaccine potential of novel Pf-iRBC antigens and for follow-on vaccine trials in non-human primates, with an ultimate goal of a malaria vaccine for humans. Full article

Background: The end of the COVID-19 public health emergency of international concern (PHEIC) in May 2023 marked a transition from disruption to recovery and rebuilding of health systems. The WHO African Region entered this period with declining routine immunization coverage, widening inequities, and fragile surveillance systems. We conducted a critical narrative synthesis of post-PHEIC recovery and the transformation of immunization systems in the region from 2023 to 2025. Methods: We thematically analyzed publicly available data from the WHO and other sources using a systems-oriented framework covering immunization coverage, equity, vaccine introductions, disease control, governance, financing, and data systems. Results: Regional coverage for most antigens was restored to 2019 pre-pandemic levels by 2024, e.g., three doses of diphtheria-tetanus-pertussis-containing vaccines at 76%. However, progress remains insufficient to meet the Immunization Agenda 2030 (IA2030) target of 90% coverage. In addition, there were 6.7 million zero-dose children in the 2024 birth cohort (6.3% higher than the 6.3 million in 2019), concentrated in a few countries. The IA2030 target is a 50% reduction in the number of zero-dose children by 2030, compared to 2019. Recovery initiatives have restored services, while accelerated introductions (e.g., malaria vaccines introduced in 20 new countries in 2024–2025) signal renewed system momentum. Yet, progress has plateaued at pre-pandemic levels, reflecting structural constraints rather than sustained transformation. Concurrently, recurrent outbreaks of measles, yellow fever, and other vaccine-preventable diseases highlight persistent immunity gaps and surveillance limitations. Structural constraints (including financing fragility, subnational inequities, and system fragmentation) continue to limit sustained progress. Conclusion: This study offers important insights that can inform immunization policymaking in the WHO African Region and beyond. Current post-PHEIC trends reflect recovery without transformation. Achieving IA2030 targets will require a shift from broad coverage expansion to precision delivery approaches that prioritize zero-dose and underserved populations. Immunization must be positioned as a central pillar of primary health care and health security systems. Full article

Background/Objectives: Malaria remains a major global health burden, particularly in sub-Saharan Africa, where the recent invasion and urban expansion of Anopheles stephensi are increasing transmission risk in densely populated areas. Conventional vector control strategies, including widespread insecticide application, are progressively losing efficacy due to the rapid spread of resistance. These limitations have accelerated the development of genetic control approaches aimed at either suppressing vector populations or replacing them with genetically modified mosquitoes incapable of transmitting pathogens, with the shared objective of reducing disease transmission. For population suppression strategies, an essential component is a conditional regulatory system that enables precise control of toxic or otherwise deleterious effector proteins. The most widely used platform, the tetracycline-dependent (Tet) system, modulates gene expression in response to tetracycline. However, this system can exhibit leaky expression and variable regulation, which may compromise its reliability and limit its application in certain contexts. The dihydrofolate reductase (DHFR) destabilization domain (DD) system, developed in Drosophila, offers an alternative strategy for post-translational control of protein stability. In this system, proteins fused to a destabilization domain are rapidly degraded unless stabilized by the small molecule trimethoprim (TMP), enabling tight and reversible control. In Drosophila and prior reports, this system has been associated with relatively low fitness costs, although such effects have not been systematically evaluated in mosquitoes. Before adapting this system for mosquito genetic control, it is therefore essential to assess the impact of TMP exposure on key life-history traits. Methods: Here, we assessed the effects of varying TMP concentrations on mosquito development, survival, and reproductive output. Results: Our results demonstrate that low concentrations of TMP exposure had no detectable effects on immature development, adult survival, or reproductive output under the conditions tested, supporting the implementation of the DHFR-DD system in mosquitoes. Importantly, these effects were dose-dependent, with moderate to high TMP concentrations producing measurable impacts on mosquito fitness. Conclusions: These findings provide a foundational step toward the development of more precise and reliable conditional expression systems for genetic vector control, advancing innovative strategies to mitigate malaria transmission in high-risk regions. Full article

Measles remains one of the most contagious infectious diseases globally and continues to pose substantial public health risks despite decades of effective vaccination. This narrative review examines both classical and contemporary computational approaches used for measles monitoring, prediction, and control, with particular attention given to the emerging role of artificial intelligence (AI). We synthesized findings from 46 studies; 31 focused directly on measles and 15 on methodologically relevant studies from related infectious diseases (COVID-19, influenza, malaria), selected through searches of PubMed, Scopus, Web of Science, IEEE Xplore, and preprint servers, conducted between June and December 2025. Traditional compartmental models (SIR, SEIR, MSEIR), statistical tools (ARIMA, SARIMA), and seroepidemiological analysis provide transparent, well-characterized frameworks for estimating transmission dynamics and simulating intervention scenarios. Spatial modeling, network analysis, and Monte Carlo simulations have added geographic granularity to outbreak characterization. More recently, AI and machine learning (ML) methods, including supervised algorithms (Random Forest, XGBoost, SVM), deep learning architectures (CNN, LSTM), and hybrid mechanistic ML models, have shown improved predictive performance by integrating multiple data sources: epidemiological records, demographic profiles, mobility patterns, and behavioral indicators. AI-based approaches appear most valuable for high-dimensional risk prediction and image-based diagnostic tasks, while classical models retain clear advantages for policy-oriented scenario analysis. However, no AI-based or hybrid model identified in this review has been adopted into routine national measles surveillance or used for vaccination policy decisions at scale. Important challenges remain: data quality varies across settings, model generalizability cannot be assumed, and computational infrastructure disparities limit deployment in high-burden regions. Explainable AI, federated learning, workforce training for model interpretation, and integration of vaccination registries with mobility and genomic surveillance data represent concrete future directions for strengthening computational support for measles elimination. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Malaria remains a major public health issue worldwide and a repeated cause of illness and death in tropical and subtropical areas. It is caused by protozoan parasites of the genus Plasmodium and transmitted through bites of infected female Anopheles mosquitoes, but it can also be transmitted via blood transfusions, organ transplants, and congenitally from mother to child. Despite decades of intervention efforts, millions of new cases and hundreds of thousands of deaths still occur each year, primarily in low- and middle-income countries. This review summarizes current epidemiological data on the global burden of malaria, mainly from the World Health Organization’s (WHO) World Malaria Report 2024 and Global Burden of Disease estimates. It brings together the latest evidence on worldwide malaria epidemiology, regional trends, determinants, and control strategies, with a particular focus on socio-economic factors, intervention methods, and emerging challenges such as drug resistance, climate change, and limited funding. Disease prevention and management require global, multifactorial approaches that are tailored to the local environment. Strengthening health education with locally relevant knowledge is important to improving outcomes in primary health prevention, secondary health prevention, and tertiary health prevention. The review concludes with a discussion of policy priorities needed in the future to meet the WHO Global Technical Strategy goals for malaria elimination by 2030. Full article

Malaria remains a major global health challenge. While treatments targeting parasite replication exist, effective interventions for neurological manifestations are scarce, necessitating new strategies for cerebral malaria. In this study, we investigated the effect of a single-chain variable fragment (scFv) against glycosylphosphatidylinositol (GPI) as an intervention tool to mitigate the effects of Plasmodium in a preclinical model. We used C57BL/6J mice infected with Plasmodium berghei-ANKA (PbA) and treated them with anti-GPI scFv or phosphate-buffered saline (PBS) on days 0, 3, and 6 post-infection. Uninfected controls were treated on the same days with scFv or PBS. The animals were evaluated for morbidity and mortality, body weight, parasitemia, blood count, cytokines, and histopathology. Results show that anti-GPI scFv prevented lethality in 71.4% of infected animals and promoted recovery from weight loss. Furthermore, the intervention inhibited neurological and systemic signs, reduced parasitemia, and improved hematological and histopathological parameters in the brain, lungs, and kidneys. In conclusion, anti-GPI scFv exerts a significant systemic effect on experimental cerebral malaria (ECM) pathology, representing a promising tool for severe manifestations of the disease. 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

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

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

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