Search Results (455)

Malaria continues to affect millions of people around the world. Current control strategies have not been sufficient, and additional tools are required for malaria elimination. A promising approach is the use of bacteria from the mosquito microbiota, such as the Su_YN1 Serratia ureilytica bacterium, which is shown to strongly impair the development of P. falciparum and P. berghei in Anopheles mosquitoes. To evaluate the potential of using S. ureilytica Su_YN1 to block the Plasmodium parasite in South American vectors, we investigated its effects on mosquito fitness and survival. We found that this bacterium does not affect the longevity, blood feeding, fecundity and fertility of Anopheles aquasalis, an important South American vector. Overall, our results provide baseline support for the potential implementation of Su_YN1 for the control of malaria transmission in South America. Full article

Climate change is increasingly recognized as a major driver of emerging infectious diseases, particularly vector-borne diseases (VBDs), which are expanding in range and intensity worldwide. Europe, traditionally considered low-risk for many arboviral infections, is now experiencing autochthonous transmission of pathogens such as dengue, chikungunya, Zika virus, West Nile virus, malaria, and leishmaniasis. Rising temperatures, altered precipitation patterns, and milder winters have facilitated the establishment and spread of competent vectors, including Aedes, Anopheles, Phlebotomus, and Culex species, in previously non-endemic areas. These climatic shifts not only impact vector survival and distribution but also influence vector competence and pathogen development, ultimately increasing transmission potential. This narrative review explores the complex relationship between climate change and VBDs, with a particular focus on pediatric populations. It highlights how children may experience distinct clinical manifestations and complications, and how current data on pediatric burden remain limited for several emerging infections. Through an analysis of existing literature and reported outbreaks in Europe, this review underscores the urgent need for enhanced surveillance, integrated vector control strategies, and climate-adapted public health policies. Finally, it outlines research priorities to better anticipate and mitigate future disease emergence in the context of global warming. Understanding and addressing this evolving risk is essential to safeguard public health and to protect vulnerable populations, particularly children, in a rapidly changing climate. Full article

Artemisinin and its derivatives are widely recognized for their exceptional antimalarial efficacy. Recently, accumulating evidence indicates therapeutic potential beyond malaria. Despite these advances, detailed mechanisms and pharmacological limitations remain incompletely defined. This review summarizes their pharmacological activities and molecular mechanisms associated with oncology, immunoregulation, and metabolic disorders. Mechanistically, these compounds exert potent antitumor effects by inducing oxidative stress, arresting the cell cycle, triggering apoptosis, and inhibiting angiogenesis. They likewise modulate immune responses, re-establishing immune homeostasis and enhancing the effectiveness of immunotherapeutic strategies. Preliminary evidence also suggests involvement in metabolic regulation, pointing to promising avenues for treating metabolic disorders. Given alternative mechanisms of artemisinin and its derivatives, we also discuss the trinity modulation network among antitumor activity, immunoregulation, and metabolic homeostasis. We anticipate that future research will address these knowledge gaps, thereby enhancing the clinical utility of artemisinin and its derivatives and improving patient outcomes across diverse pathologies. Full article

Red blood cell (RBC), accounting for approximately 45% of total blood volume, are essential for oxygen delivery and carbon dioxide removal. Their unique biconcave morphology, high surface area-to-volume ratio, and remarkable deformability enable them to navigate microvessels narrower than their resting diameter, ensuring efficient microcirculation. RBC deformability is primarily determined by membrane viscoelasticity, cytoplasmic viscosity, and cell geometry, all of which can be altered under various physiological and pathological conditions. Reduced deformability is a hallmark of numerous diseases, including sickle cell disease, malaria, diabetes mellitus, sepsis, ischemia–reperfusion injury, and storage lesions in transfused blood. As these mechanical changes often precede overt clinical symptoms, RBC deformability is increasingly recognized as a sensitive biomarker for disease diagnosis, prognosis, and treatment monitoring. Over the past decades, diverse techniques have been developed to measure RBC deformability. These include single-cell methods such as micropipette aspiration, optical tweezers, atomic force microscopy, magnetic twisting cytometry, and quantitative phase imaging; bulk approaches like blood viscometry, ektacytometry, filtration assays, and erythrocyte sedimentation rate; and emerging microfluidic platforms capable of high-throughput, physiologically relevant measurements. Each method captures distinct aspects of RBC mechanics, offering unique advantages and limitations. This review synthesizes current knowledge on the pathophysiological significance of RBC deformability and the methods for its measurement. We discuss disease contexts in which deformability is altered, outline mechanical models describing RBC viscoelasticity, and provide a comparative analysis of measurement techniques. Our aim is to guide the selection of appropriate approaches for research and clinical applications, and to highlight opportunities for developing robust, clinically translatable diagnostic tools. Full article

Children in sub-Saharan Africa remain vulnerable to contracting malaria. While chemoprophylaxis is effective in preventing disease, its impact on social well-being is less understood. In this cross-sectional follow-up study conducted in 2001, we examined the role of chemoprophylaxis on social well-being in rural Gambia. Participants were 141 adolescents (age: 14.8–19.5; 40% male) from five villages, drawn from a longitudinal cohort in which one group received chemoprophylaxis in infancy, while the other received a placebo and began prophylaxis 1–2 years post-trial. Using a walking interview methodology, participants guided researchers through five village locations. Their narrations were coded for emotional content and social themes, followed by network analyses examining the relationships between these themes across treatment groups and gender. Emotional response analysis revealed significant gender differences in valence, with females exhibiting higher positive emotional tone than males (X² = 5.85, p = 0.016). Treatment effects showed gender-specific patterns: among males, the placebo group exhibited higher positive valence compared to the chemoprophylaxis group (X² = 8.34, p = 0.004), while females showed no treatment differences (X² = 1.11, p = 0.291). Affect analysis revealed high positive responses across all groups with no significant differences. Network analysis revealed significant gender differences in how adolescents organize social themes within their communities. Females demonstrated higher centrality in eigenvector (global influence; p = 0.039) and degree centrality (number of direct edges; p < 0.001), indicating greater interconnectedness and influence within the networks. No significant treatment group differences were observed in the network structure across any centrality indicators (all p > 0.05). This study provides an example of how the social–ecological framework and ecologically valid assessment methods, such as the walking interview, can be applied to investigate the interplay between early childhood health interventions, social dynamics, and individual development in a rural African context. The findings revealed that gender exerts a stronger influence than early treatment on adolescent social–emotional development. Full article

Aim: In sub-Saharan Africa, approximately 40 million pregnant women are exposed to parasitic diseases such as malaria caused by Plasmodium falciparum, Schistosome parasites, and soil-transmitted helminths (STHs). When parasitic diseases share the same habitat and overlap in distribution, then high co-infection rates occur. The co-infection can lead to consequences for the child, such as intrauterine growth retardation, low birth weight, pre-term delivery, and neonatal mortality. Methods: The objective of the study was to determine the nature and extent of coinfection from 100 samples collected from the Battor (50) and Adidome (50) towns of Ghana in collaboration with the Noguchi Memorial Institute for Medical Research, University of Ghana. Results: Out of 50 for the Adidome towns determined for P. falciparum by Rapid Diagnostic Test (RDT), Malaria Pan-specific Antigen (PAN), and Malaria Pf kit, 39 were true positive (TP), 8 were true negative (TN), and 30 were false negative (FN). For Battor, 19 were TP, 12 TN, and 20 FN. For S. mansoni in Adidome via polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), 21 tested positive, and 29 were negative, with 52.5% sensitivity and 100% specificity. For S. haematobium, 28 were positive and 22 negative using PCR with 70% sensitivity and 100% specificity. In LAMP, 28 were positive, and 22 negatives, with 70% sensitivity and 100% specificity. In Battor PCR for S. mansoni, 28 positives and 22 negatives with 68.3% sensitivity and 100% specificity. In LAMP, 32 were positive, and 18 were negative, with 80% sensitivity and 100% specificity. For S. haematobium, PCR showed 30 positive and 20 negative, with 73.2% sensitivity and 100% specificity. With LAMP, 21 were positive, and 29 negatives, with 51% sensitivity and 100% specificity. In both towns, 20–30 years had the highest infection prevalence for P. falciparum, S. mansoni, S. haematobium, and Strongyloides stercoralis. Conclusion: The results will be utilized as a part of the continuous surveillance for future research aiming at gathering nationally representative data in Ghana on the prevalence of coinfection and proposing interventions based on that for the vulnerable pregnant women population. Full article

Neglected parasitic diseases such as Chagas disease and malaria continue to pose major public health challenges, particularly in low-resource settings. Current therapies are often limited by high toxicity, poor efficacy, drug resistance, and limited accessibility. Phytochemicals, naturally occurring compounds in plants, have played a crucial role in medicine since ancient times and have gained renewed attention for their demonstrated antiparasitic activity. However, many products of natural origin (PNOs) face significant barriers to clinical use, including poor solubility, low bioavailability, and chemical instability. These limitations have driven researchers to explore alternative and innovative approaches based on the use of PNOs to tackle these parasitic infections more effectively. This review provides a comprehensive overview of key PNOs with proven activity against Trypanosoma cruzi and Plasmodium spp., the causative agents of Chagas disease and malaria, respectively. Recent advances in the design of phytonanoformulations are analyzed and discussed, emphasizing the potential of nanocarrier-based systems incorporating PNOs as a strategy to improve the pharmacokinetic and therapeutic properties of these natural products. By critically examining the integration of phytochemicals into nanotechnology-based drug delivery platforms, this review highlights the promise of phytonanotechnology to overcome current limitations in antiparasitic therapy and support the development of more effective and accessible treatments for neglected parasitic diseases. Full article

Climate change has magnified health disparities across the Southern African Development Community (SADC) region by destabilizing the critical natural systems, which include water security, food production, and disease ecology. The IPCC (2007) underscores the disproportionate impact on low-income populations characterized by limited adaptive capacity, exacerbating existing vulnerabilities. Rising temperatures, erratic precipitation patterns, and increased frequency of extreme weather events ranging from prolonged droughts to catastrophic floods have created favourable conditions for the spread of waterborne diseases such as cholera, dysentery, and typhoid, as well as the expansion of vector-borne diseases zone also characterized by warmer and wetter conditions where diseases like malaria thrives. This study employed a comparative analysis of climate and health data across Malawi, Zimbabwe, Mozambique, and South Africa examining the interplay between climatic shifts and disease patterns. Through reviews of national surveillance reports, adaptation policies, and outbreak records, the analysis reveals the existence of critical gaps in preparedness and response. Zimbabwe’s Matabeleland region experienced a doubling of diarrheal diseases in 2019 due to drought-driven water shortages, forcing communities to rely on unsafe alternatives. Mozambique faced a similar crisis following Cyclone Idai in 2019, where floodwaters precipitated a threefold surge in cholera cases, predominantly affecting children under five. In Malawi, Cyclone Ana’s catastrophic flooding in 2022 contaminated water sources, leading to a devastating cholera outbreak that claimed over 1200 lives. Meanwhile, in South Africa, inadequate sanitation in KwaZulu-Natal’s informal settlements amplified cholera transmission during the 2023 rainy season. Malaria incidence has also risen in these regions, with warmer temperatures extending the geographic range of Anopheles mosquitoes and lengthening the transmission seasons. The findings underscore an urgent need for integrated, multisectoral interventions. Strengthening disease surveillance systems to incorporate climate data could enhance early warning capabilities, while national adaptation plans must prioritize health resilience by bridging gaps between water, agriculture, and infrastructure policies. Community-level interventions, such as water purification programs and targeted vector control, are essential to reduce outbreaks in high-risk areas. Beyond these findings, there is a critical need to invest in longitudinal research so as to elucidate the causal pathways between climate change and disease burden, particularly for understudied linkages like malaria expansion and urbanization. Without coordinated action, climate-related health inequalities will continue to widen, leaving marginalized populations increasingly vulnerable to preventable diseases. The SADC region must adopt evidence-based, equity-centred strategies to mitigate these growing threats and safeguard public health in a warming world. Full article

The regulation of angiotensin-converting enzyme 2 (ACE2) expression by medications such as ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has raised critical questions regarding their potential benefits and risks during COVID-19. ACE2, a regulator of blood pressure through the renin–angiotensin system (RAS), is the primary receptor for SARS-CoV-2. ACEis and ARBs can modulate ACE2 expression, potentially exacerbating viral load. However, the risks of higher viral load could be mitigated by favorable anti-inflammatory responses associated with ACEi and ARB use, highlighting the complexity of their impact on viral replication and disease outcomes. This study investigates the effects of sustained Losartan monotherapy (ARB) and combination Losartan + Lisinopril (ARB + ACEi) on viral replication, inflammation, lung function, and clinical measures of disease severity in a murine model of severe COVID-19 involving humanized ACE2 transgenic mice infected with SARS-CoV-2 Wuhan strain. Both ARB and ARB + ACEi treatments led to increased ACE2 expression in the lungs and higher viral load post-infection. Despite this, the ARB + ACEi combination improved clinical scores, reduced weight loss and inflammatory cytokine levels, and preserved lung function, though it did not improve survival. Overall, the results of these controlled experiments provide insight into the complex dynamics of ACEi and ARB use in COVID-19; while these drugs induce expression of the ACE2 receptor and increase viral load, they provide compensatory modulation of the inflammatory response that appears to diminish severity of the infection. Full article

Malaria is still one of the biggest global health problems, especially in parts of the world, such as sub-Saharan Africa, which remains most heavily affected. Despite significant advancements in testing, treatment, and prevention, malaria continues to seriously impact millions, primarily young children and populations in rural and impoverished areas. This paper looks at how the malaria parasite works inside the body, how it avoids the immune system, and how it becomes resistant to current drugs. Thanks to new advances in genetic and biochemical research, scientists are discovering new weak points in the parasite that could lead to better treatments. New vaccines, like RTS, S and R21, along with antibody-based therapies, offer renewed hope; however, extending the duration of the immunity they induce and ensuring effectiveness across diverse parasite strains remain significant challenges. Solving the malaria crisis will require more than science—it also necessitates equitable and timely access to treatments, robust health systems, and international collaboration. Continued research and global cooperation bring the world closer to ending malaria for good. Full article

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, along with its derived fractions, demonstrated potent in vitro activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 (Pf3D7), with the ethyl acetate-soluble (IC₅₀ = 11.35 µg/mL) and alkaloid-rich (IC₅₀ = 4.75 µg/mL) fractions showing particularly strong inhibition. UHPLC-DAD-ESI-QTOF-MS/MS-based molecular networking enabled the identification of thirty-two secondary metabolites (1–32), comprising twenty-five cyclopeptide alkaloids (CPAs), five of which had not yet been described (11, 20, 22, 23, 25), and seven known triterpenoids. Bioactivity-guided isolation yielded thirteen purified compounds (5, 6, 14, 26–30, 32–36), with betulinic acid (30; IC₅₀ = 19.0 µM) and zizyberenalic acid (32; IC₅₀ = 20.45 µM) exhibiting the most potent antiplasmodial effects. Computational ADMET analysis identified mauritine F (4), hemisine A (10), and nummularine R (21) as particularly promising lead compounds, demonstrating favourable pharmacokinetic properties, low toxicity profiles, and predicted activity against both family A G protein-coupled receptors and evolutionarily distinct Plasmodium protein kinases. Quantitative analysis revealed exceptionally high concentrations of key bioactive constituents, notably zizyberenalic acid (24.3 mg/g) in the root extracts. These findings provide robust scientific validation for the traditional use of Z. mauritiana in malaria treatment while identifying specific cyclopeptide alkaloids and triterpenoids as valuable scaffolds for antimalarial drug development. The study highlights the effectiveness of combining advanced metabolomics, bioassay-guided fractionation, and computational pharmacology in natural product-based drug discovery against resistant malaria strains. Full article

Plasmodium falciparum is the causative agent of malaria, a parasitic disease that affects millions of people in terms of prevalence and is associated with hundreds of thousands of deaths. Current antimalarial medications, in addition to exhibiting moderate to serious adverse reactions, are not efficacious enough due to factors such as drug resistance. In silico approaches can speed up the discovery and design of new molecules with wide-spectrum antimalarial activity. Here, we report a unified computational methodology combining a perturbation theory machine learning model based on multilayer perceptron networks (PTML-MLP) and the fragment-based topological design (FBTD) approach for the prediction and design of novel molecules virtually exhibiting versatile antiplasmodial activity against diverse P. falciparum strains. Our PTML-MLP achieved an accuracy higher than 85%. We applied the FBTD approach to physicochemically and structurally interpret the PTML-MLP, subsequently extracting several suitable molecular fragments and designing new drug-like molecules. These designed molecules were predicted as multi-strain antiplasmodial inhibitors, thus representing promising chemical entities for future synthesis and biological experimentation. The present work confirms the potential of combining PTML modeling and FBTD for early antimalarial drug discovery while opening new horizons for extended computational applications for antimicrobial research and beyond. Full article

Lippia multiflora Moldenke is widely used in Angola, on the African continent, and beyond for the treatment of many health conditions such as hypertension, enteritis, colds, gastrointestinal disturbances, stomachaches, jaundice, coughs, fevers, nausea, bronchial inflammation, conjunctivitis, malaria, and venereal diseases. However, there is limited literature about the active compounds linked with the reported biological activities. This study aims to assess the chemical profiles, antioxidant properties, and the cytotoxicity effects of the roots, stem bark, and leaves of L. multiflora. Chemical characterization of the crude extracts was assessed through quantification of total phenolic and flavonoid contents followed by Q exactive plus orbitrap™ ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) screening. The correlation between the extracts and the correlation between the compounds were studied using the multivariate analysis. Principal component analysis (PCA) loading scores and principal component analysis (PCA) biplots and correlation plots were used to connect specific compounds with observed biological activities. The antioxidant activities of the crude extracts were carried out in vitro using DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and reducing power assays, while the in vitro toxicology of the crude extracts was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A total of twenty constituents were characterized and identified using the UHPLC–Q/Orbitrap/MS. The methanol leaf extract showed the highest antioxidant activity in the DPPH free radical scavenging activity (IC₅₀ = 0.559 ± 0.269 μg/mL); however, the stem bark extract had the highest reducing power (IC_0.5 = 0.029 ± 0.026 μg/mL). High phenolic and flavonoid content was found in the dichloromethane leaf extract (32.100 ± 1.780 mg GAE/g) and stem bark extract (624.153 ± 29.442 mg QE/g), respectively. The results show the stem bark, methanol leaf, and dichloromethane leaf extracts were well-tolerated by the Vero cell line at concentrations up to 50 µg/mL. However, at 100 µg/mL onward, some toxicity was observed in the root, methanol leaf, and dichloromethane leaf extracts. The UHPLC–Q/Orbitrap/MS profiles showed the presence of terpenoids (n = 5), flavonoids (n = 5), phenols (n = 4), alkaloids (n = 3), coumarins (n = 1), fatty acids (n = 1), and organic acids (n = 1). According to several studies, these secondary metabolites have been reported and proven to be the most abundant for antioxidant potential. The identified flavonoids (catechin, quercitrin, and (−)-epigallocatechin) and phenolic compound (6-gingerol) can significantly contribute to the antioxidant properties of different plant parts of L. multiflora. The research findings obtained in this study provide a complete phytochemical profile of various parts of L. multiflora that are responsible for the antioxidant activity using UHPLC–Q/Orbitrap/MS analysis. Furthermore, the results obtained in this study contribute to the scientific information or data on the therapeutic properties of Lippia multiflora and provide a basis for further assessment of its potential as a natural remedy. Full article

The risk of non-human primate (NHP) malaria transmission to humans is increasing, with Plasmodium knowlesi and Plasmodium cynomolgi emerging as significant zoonotic threats, particularly in Malaysia. While P. knowlesi is well-documented, P. cynomolgi infections in humans remain underreported, largely due to diagnostic challenges. Routine microscopy and standard molecular diagnostic tools often misdiagnose P. cynomolgi infections as P. vivax due to morphological similarities and genetic homology. We report a new case of a human P. cynomolgi infection misdiagnosed as Plasmodium vivax in a 32-year-old male with no prior malaria history or travel to endemic countries. The initial diagnoses made by the microscopy and qPCR conducted by the Kota Bharu Public Health Laboratory in Kelantan identified the infection as P. vivax. However, cross-examination by the Institute for Medical Research (IMR) revealed the presence of mixed-species infection, prompting further analysis. The real-time PCR and sequencing performed at MAPELAB, Spain, confirmed the co-infection of P. vivax and P. cynomolgi. This case highlights the diagnostic limitations in detecting P. cynomolgi, which shares high genetic similarity with P. vivax, leading to potential cross-reactivity and diagnostic inaccuracies. As P. cynomolgi emerges as the second zoonotic malaria species after P. knowlesi capable of infecting humans in Southeast Asia, improved diagnostic methods are urgently needed. Enhanced molecular diagnostics and comprehensive epidemiological studies are essential to elucidate transmission dynamics, assess public health implications, and inform effective malaria control strategies. Full article

Climate change threatens health and social development gains in Kenya, necessitating health policy planning for risk reduction and mitigation. To understand the state of knowledge on climate-related health impacts in Kenya, a scoping review of 25 years of environmental health research was conducted. In compliance with a pre-registered protocol, nine bibliographic databases and grey literature sources were searched for articles published from 2000 to 2024. Of 19,234 articles screened, 816 full texts were reviewed in duplicate, and a final 348 articles underwent data extraction for topic categorisation, trend analysis, and narrative summary. Most of the studies (97%, n = 336) were journal articles, with 64% published after 2014 (n = 224). The health topics centred on vector-borne diseases (45%, n = 165), primarily vector abundance (n = 111) and malaria (n = 67), while mental health (n = 12) and heat exposure (n = 9) studies were less frequent. The research was geographically concentrated on the Lake Victoria Basin, Rift Valley, and Coastal regions, with fewer studies from the northern arid and semi-arid regions. The findings show a shift from a focus on infectious diseases towards broader non-communicable outcomes, as well as regional disparities in research coverage. This review highlights the development of baseline associations between environmental exposures and health outcomes in Kenya, providing a necessary foundation for evidence-informed climate change and health policy. However, challenges in data and study designs limit some of the evidentiary value. Full article