Search Results (65)

Malaria remains one of the most significant infectious diseases worldwide, requiring rapid, sensitive, and accessible diagnostic tools to improve disease management and control. Conventional diagnostic methods, including microscopy, rapid diagnostic tests, and nucleic acid amplification techniques, present limitations in sensitivity, specificity, cost, or field applicability. This review examines the emerging role of aptamer-based biosensors (aptasensors) as innovative alternatives for malaria detection. Aptamers are synthetic nucleic acid ligands that offer high affinity and specificity toward malaria biomarkers while providing advantages over antibodies, including improved stability, lower production costs, and ease of chemical modification. The review discusses aptamer selection methodologies, major Plasmodium biomarkers targeted for detection, and the integration of aptamers into electrochemical, optical, magnetic, and microfluidic biosensing platforms. Current advances demonstrate the potential of aptasensors to enable highly sensitive, selective, and portable point-of-care diagnostics for malaria surveillance and management. Full article

Malaria pathogenesis involves complex immunopathological mechanisms that hinder early diagnosis and effective treatment. This study integrates multi-omics data and experimental models to identify host-derived biomarkers and elucidate their functional roles. By combining human transcriptomic datasets, weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO, SVM, RF), we identified C1QB as a key hub gene. In human data, C1QB was significantly upregulated in both training and validation cohorts (AUC 0.983 and 0.970). Single-gene GSEA and immune infiltration analyses linked C1QB to apoptosis, inflammation, and altered immune cell composition, including increased activated dendritic cells and neutrophils, and decreased naïve B cells and CD8⁺ T cells. In a murine malaria model (Plasmodium berghei ANKA), C1QB expression rose as early as day one post-infection, preceding detectable parasitemia. Immunohistochemistry revealed C1QB accumulation in the liver and spleen. Single-cell RNA sequencing in the murine model confirmed monocyte-predominant expression, and scTenifoldKnk analysis suggested its role in immune regulation. Crucially, inhibiting C1q in mice via antibody intervention alleviated malaria-induced inflammation, tissue damage, and apoptosis, indicating that C1QB/C1q actively contributes to immunopathology. AI-based drug prediction and molecular docking further supported its therapeutic potential. Collectively, our findings establish C1QB as a dual biomarker and pathogenic driver in malaria, with diagnostic and therapeutic implications. Further studies are required to validate direct target engagement and clarify upstream regulatory mechanisms. Full article

Background: Severe malaria remains a major cause of morbidity and mortality, yet the conserved molecular signatures underlying complicated infections across Plasmodium vivax (P. vivax) and Plasmodium falciparum (P. falciparum) are not well characterized. Identifying shared transcriptional biomarkers and host–parasite interaction networks is crucial for improving diagnosis and discovering new therapeutic targets. Methods: Public transcriptomic datasets (GSE55644, GSE59844, GSE34404) were analyzed using GEO2R to identify differentially expressed genes (DEGs). Volcano plots, Venn diagrams, and KEGG mapping were used to identify conserved DEGs. Principal Component Analysis (PCA) and Support Vector Machine (SVM) models were used to assess predictive performance. Host–parasite cross-species correlation analysis integrated parasite DEGs with host hub-genes. Functional enrichment and network module analysis were performed using Cytoscape v3.10.2 and GO/KEGG annotation tools. Results: A total of 3363 DEGs were identified in P. vivax (GSE55644) and only one DEG in P. falciparum (GSE59844) using adjusted p-values, though 772 DEGs emerged with unadjusted p-values. Cross-dataset comparison revealed 18 common DEGs, with eight upregulated genes—TIM9, NUF2, SRP68, HDAC1, GRP94, DHHC8, PPM9, and RPL27—showing robust predictive performance (AUC = 1.000; CA = 1.000) for distinguishing complicated from uncomplicated malaria in both species. Host analysis identified 1719 DEGs and six hub-genes (TNF, IL6, TLR4, CR1, CD40LG, ICAM1) linked to apoptosis, Toll-like receptor signaling, complement cascades, and cell adhesion. SVM validation predicted parasitemia levels with 75.5–84.0% accuracy. Cross-species correlation revealed strong positive interactions between parasite HDAC1/GRP94 and host IL6/TNF and negative correlations involving NUF2, TIM9, ICAM1, and CR1. Functional enrichment analysis highlighted ER stress, immune activation, and erythrocyte adhesion pathways, which together form three major host–parasite modules. Conclusion: These findings highlight conserved biomarkers and potential therapeutic candidates for future validation, demonstrating that combined DEG profiling and machine-learning approaches can provide a powerful framework for improving diagnostics and intervention strategies for severe malaria. Full article

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

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

Accurate malaria diagnosis is essential for effective case management and transmission control; however, the sensitivity, operational requirements, and field applicability of current conventional methods are limited. Hemozoin, an optically and magnetically active crystalline biomarker produced by Plasmodium species, offers a reagent-free target for next-generation diagnostics. This scoping review, following PRISMA-ScR and Joanna Briggs Institute guidance, synthesizes recent advances in hemozoin-based detection technologies and maps the current landscape. Twenty-four studies were reviewed, spanning eight major technology classes: magneto-optical platforms, magnetophoretic microdevices, photoacoustic detection, Raman/SERS spectroscopy, optical and hyperspectral imaging, NMR relaxometry, smartphone-based microscopy, and flow cytometry. Magneto-optical systems—including Hz-MOD, Gazelle™, and RMOD—demonstrated the highest operational readiness, with robust specificity but reduced sensitivity at low parasitemia. Photoacoustic Cytophone studies demonstrated promising sensitivity and noninvasive in vivo detection. Raman/SERS platforms achieved sub-100 infected cell/mL analytical sensitivity but remain laboratory-bound. Microfluidic and smartphone-based tools offer emerging, potentially low-cost alternatives. Across modalities, performance varied by parasite stage, with reduced detection of early ring forms. In conclusion, hemozoin-targeted diagnostics represent a rapidly evolving field with multiple viable translational pathways. While magneto-optical devices are closest to field deployment, further clinical validation, improved low-density detection, and standardized comparison across platforms are needed to support future adoption in malaria-endemic settings. Full article

Falciparum malaria is a life-threatening vector-borne disease prevalent in tropical and subtropical regions. The complexity of severe malaria demands a thorough investigation of host–parasite interactions. Twenty male Sprague Dawley rats were divided into two groups: uninfected controls and Plasmodium berghei-infected rats, infected via intraperitoneal injection of parasitized red blood cells. Serum samples were analysed using high-resolution untargeted Gas Chromatography–Time-of-Flight Mass Spectrometry. Metabolomic analyses revealed altered metabolites and enriched metabolic pathways. Distinct metabolite profiles were observed between infected and control groups. Infected rats showed elevated urea levels and reduced concentrations of 1,5-anhydroglucitol, D-(+)-Talose, and arachidonic acid. Pathway analysis revealed significant enrichment of the glucose-alanine cycle, alpha-linolenic acid metabolism, and linoleic acid metabolism in infected rats. Minimal enrichment was observed in arachidonic acid metabolism and lactose biosynthesis. The upregulation of the glucose-alanine cycle suggests increased gluconeogenesis in response to parasite-induced glucose depletion and energy demand. Elevated urea indicates enhanced amino acid catabolism. These findings highlight the potential of metabolomics as a diagnostic tool for malaria detection and prognosis. Full article

Plasmodium parasites are the causative agents of malaria and can infect humans and other vertebrates, impacting socioeconomic development and causing significant health issues globally. Plasmodium falciparum causes the most severe type of infection, which can lead to chronic morbidity and other severe complications like anemia and cerebral malaria. The onset of infection is marked by the injection of sporozoites into the skin through the bite of a female Anopheles mosquito. This triggers a cascade of reactions elicited both by the host immune system in response to infection and by the parasite in a bid to evade the host immune system, survive, and replicate. The dynamics of this host–parasite relationship have prompted extensive research in an attempt to understand and exploit it in the fight against malaria. Thus, understanding the temporal and spatial dimensions of adaptation in host–parasite relationships is critical for forecasting parasite evolution and spread within and between host populations. One such relationship is the complex interplay between malaria and cellular aging processes. Understanding this dynamic will provide novel insights into the pathophysiology of the disease. This comprehensive review takes us on that journey by providing an overview of the interaction between the Plasmodium parasite and its host and the interplay between infection mechanisms, host immune response, and parasite evasion strategies, narrowing it down to how it affects cellular aging biomarkers and how this can be explored as a platform in the fight against the disease. Full article

Cerebral malaria is a life-threatening neurological complication of Plasmodium falciparum infection and a leading cause of pediatric mortality in endemic regions of sub-Saharan Africa. It is defined clinically by coma accompanied by peripheral parasitemia, without alternative causes. Pathogenetically, cytoadherence of parasitized erythrocytes in the cerebral microvasculature, together with a widespread inflammatory response and endothelial activation, causes profound microvascular injury. This injury includes disruption of the blood–brain barrier and the development of multifactorial cerebral oedema (both vasogenic and cytotoxic), resulting in elevated intracranial pressure and often diffuse brain swelling as seen on imaging in fatal cases. Recent high-resolution MRI studies in pediatric cohorts from these endemic regions have identified characteristic neuroimaging findings such as basal ganglia infarcts, brainstem lesions, and corpus callosum abnormalities that strongly predict poor outcomes. Notably, circulating extracellular vesicles—released by parasitized erythrocytes and activated endothelial cells have emerged as potent mediators of microvascular inflammation. Extracellular vesicles contain parasite-derived antigens and host inflammatory signals, implicating them in disease mechanisms. These vesicles are under investigation as novel diagnostic and prognostic biomarkers for severe malaria. Importantly, survivors of cerebral malaria often endure persistent neurocognitive impairments, behavioral problems, and epilepsy, underscoring the need to prevent secondary neuronal injury during the acute phase to reduce long-term disability. Taken together, these insights highlight the interplay between cerebral microvascular pathology and neurological outcome in cerebral malaria. This review synthesizes recent advances in the pathophysiology of cerebral malaria and cutting-edge diagnostic modalities. It highlights novel therapeutic targets and neuroprotective strategies that may enable precision medicine approaches aimed at preventing lasting neurological disability in survivors. 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

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Malaria remains a significant public health challenge, particularly in endemic regions. The extensive genetic diversity of Plasmodium falciparum (Pf) complicates outbreak prediction and transmission control. One of its most polymorphic markers, merozoite surface protein 2 (MSP2), presents a potential target for molecular surveillance. This cross-sectional study, conducted at King Faisal Hospital Rwanda (KFHR) from October 2021 to June 2023, assessed MSP2’s utility in malaria prediction. PfMSP2 was sequenced, and selected amplicons were cloned, expressed in bacteria, and purified. These antigens were tested against sera from malaria patients and geographically diverse healthy individuals, with complementary surveys contextualizing serological findings. Of the 75 processed monoallelic clinical isolates, 3D7 strains predominated over FC27. Three MSP2-derived biomarkers were produced, eliciting significantly low IgG responses in malaria patients and Belgian controls, but a complex pattern emerged in healthy individuals, with significant differences between Rwandan and Cameroonian samples. IgG3 was the predominant subclass in individuals with high IgG responses. Notably, Rwandan individuals with weak humoral responses to the tested antigens but also other with high responses experienced malaria episodes in the subsequent year. These findings highlight MSP2 polymorphism as a valuable tool for malaria surveillance and outbreak prediction. Integrating genotyping and serology could enable precise, community-specific malaria risk assessments, strengthening control strategies. Full article

Background: In recent decades, malaria has become a major worldwide public health problem in endemic countries, especially with children below five years. Malaria causes inflammation, and inflammatory biomarkers like α-1-glycoprotein (AGP) and C-reactive protein (CRP) are elevated in serum during malaria. This work aimed at assessing the serum levels of AGP (chronic inflammation) and CRP (acute inflammation) biomarkers and IgG4 and their correlation with malaria in children below five years in the Buea Health District of the South West Region of Cameroon. Methods: This cross-sectional study was carried out between February and April, 2024. AGP and CRP were measured using Q-7plex Human Micronutrient Measurement Kit while IgG4 levels were measured using Enzyme-Linked Immunosorbent Assay with 80 samples. Results: Serum AGP and CRP biomarker levels were significantly higher in malaria-positive children compared to malaria-negative children (p < 0.001 and p < 0.001, respectively). IgG4 levels were high in malaria-negative children (mean OD = 0.51) compared to children infected with the malaria parasite (mean OD = 0.29), in a manner that was statistically significant (p < 0.03). Hemoglobin (Hb) had a strong negative correlation with AGP (−0.62) and CRP (−0.46), meaning that as Hb levels increased, AGP and CRP levels decreased. CRP had a strong positive correlation with both age (0.3) and AGP (0.5), suggesting that as age increased or as AGP levels rose, CRP levels tended to increase as well. Conclusions: This study revealed that malaria causes alterations in the serum levels of AGP, CRP, and IgG4 in children below the age of 5 in the Buea municipality of Cameroon. It impacts immune responses by increasing the level of inflammation biomarkers like AGP and CRP and decreasing IgG4, a marker associated with immune regulation. Thus, this study helps the understanding of the inflammatory nature of malaria and could be expanded to aid in the broader public health efforts to control and prevent malaria, reduce its complications, and improve overall health outcomes in children in the Buea municipality. Full article

Malaria is a tropical disease caused by the Plasmodium parasite, which was responsible for 249 million cases worldwide in 2022. Malaria is currently diagnosed using RDTs, PCR-based methods, or blood smear microscopy. Ideal biomarkers have been identified for malaria, with the potential for improving treatment, diagnosis, and overall clinical outcomes. This review discusses the types of existing biomarkers and the opportunities for new biomarkers to be used as diagnostic components in detecting Plasmodium, including in terms of sensitivity, detection limit, specificity, and the species of Plasmodium that can be detected. Following a comparison, five main ideal malaria biomarkers were identified, namely HRP2, pLDH, hemozoin, aldolase, and pGDH. These biomarkers distinguished themselves markedly from the others in terms of specificity in Plasmodium detection, sensitivity in analysis, and the use of non-invasive samples. Several other biomarkers, such as CRP, Ang-1, Ang-2, and PCT, show potential for malaria detection in terms of their ability to differentiate disease severity, and the levels of these biomarkers can be determined in the body for comparison with malaria parasitemia. Of the five ideal biomarkers, hemozoin and aldolase can still be developed regarding the types of samples used and their sensitivity to different Plasmodium species. Further research on the biomarkers CRP, Ang-1, Ang-2, and PCT is still needed to evaluate their potential. Full article