Stages Of Parasite Life Cycle Research Articles

Tambjamines as Fast-Acting Multistage Antimalarials.

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages. Notably, our lead candidate 1 (KAR425) displays excellent oral efficacy with complete clearance of parasites within 72 h of treatment in the humanized Plasmodium falciparum (NOD-scid) mouse model at 50 mg/kg × 4 days. Profiling of compound 1 demonstrated a fast in vitro killing profile. In addition, several other tambjamine analogues cured erythrocytic Plasmodium yoelii infections after oral doses of 30 and 50 mg/kg × 4 days in a murine model while exhibiting good safety and metabolic profiles. This study presents the first account of multiple-stage antiplasmodial activities with rapid killing profile in the tambjamine family.

Harnessing cholesterol uptake of malaria parasites for therapeutic applications

Parasites, such as the malaria parasite P. falciparum, are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be ‘hijacked’ for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance.

Vaccine Designing Technology against Leishmaniasis: Current Challenges and Implication.

Leishmaniasis, a debilitating disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of a female sandfly, continues to present significant challenges despite ongoing research and collaboration in vaccine development. The intricate interaction between the parasite's life cycle stages and the host's immunological response, namely the promastigote and amastigote forms, adds complexity to vaccine design. The quest for a potent vaccine against Leishmaniasis demands a comprehensive understanding of the immune mechanisms that confer long-lasting protection, which necessitates extensive research efforts. In this pursuit, innovative approaches such as reverse vaccinology and computer-aided design offer promising avenues for unraveling the intricacies of host-pathogen interactions and identifying effective vaccine candidates. However, numerous obstacles, including limited treatment options, the need for sustained antigenic presence, and the prevalence of co-infections, particularly with HIV, impede progress. Nevertheless, through persistent research endeavours and collaborative initiatives, the goal of developing a highly efficacious vaccine against Leishmaniasis can be achieved, offering hope through the latest Omics data development with immunoinformatics approaches for effective vaccine design for the prevention of this disease.

Endoplasmic reticulum localized TMEM33 domain-containing protein is crucial for all life cycle stages of the malaria parasite.

Endoplasmic reticulum (ER) plays a pivotal role in the regulation of stress responses in multiple eukaryotic cells. However, little is known about the effector mechanisms that regulate stress responses in ER of the malaria parasite. Herein, we aimed to identify the importance of a transmembrane protein 33 (TMEM33)-domain-containing protein in life cycle of the rodent malaria parasite Plasmodium berghei. TMEM33 is an ER membrane-resident protein that is involved in regulating stress responses in various eukaryotic cells. A C-terminal tagged TMEM33 was localized in the ER throughout the blood and mosquito stages of development. Targeted deletion of TMEM33 confirmed its importance for asexual blood stages and ookinete development,in addition to its essential role for sporozoite infectivity in the mammalian host. Pilot scale analysis shows that the loss of TMEM33 results in the initiation of ER stress response and induction of autophagy. Our findings conclude an important role of TMEM33 in the development of all life cycle stages of the malaria parasite, which indicates its potential as an antimalarial target.

Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in Plasmodium falciparum.

The emergence of Plasmodium parasite resistance to current front-line antimalarial treatments poses a serious threat to global malaria control and highlights the necessity for the development of therapeutics with novel targets and mechanisms of action. Plasmepsins IX and X (PMIX/PMX) have been recognised as highly promising targets in Plasmodium due to their contribution to parasite's pathogenicity. Recent research has demonstrated that dual PMIX/PMX inhibition results in the impairment of multiple parasite's life cycle stages, which is an important feature in drug resistance prevention. Herein we report novel hydroxyethylamine photoaffinity labelling (PAL) probes, designed for PMIX/PMX target engagement and proteomics experiments in Plasmodium parasites. The prepared probes have both a photoreactive group (diazirine or benzophenone) for covalent attachment to target proteins, and a terminal alkyne handle allowing their use in bioorthogonal ligation. One of the synthesised benzophenone probes was shown to be highly promising as demonstrated by its outstanding antimalarial potency (IC50 = 15 nM versus D10 P. falciparum) and its inhibitory effect against PfPMX in an enzymatic assay. Molecular docking and molecular dynamics studies show that the inclusion of the benzophenone and alkyne handle does not alter the binding mode compared to the parent compound. The photoaffinity probe can be used in future chemical proteomics studies to allow hydroxyethylamine drug scaffold target identification and validation in Plasmodium. We expect our findings to act as a tool for future investigations on PMIX/PMX inhibition in antimalarial drug discovery.

Disruption of a Plasmodium falciparum patatin-like phospholipase delays male gametocyte exflagellation.

An essential process in transmission of the malaria parasite to the Anopheles vector is the conversion of mature gametocytes into gametes within the mosquito gut, where they egress from the red blood cell (RBC). During egress, male gametocytes undergo exflagellation, leading to the formation of eight haploid motile microgametes, while female gametes retain their spherical shape. Gametocyte egress depends on sequential disruption of the parasitophorous vacuole membrane and the host cell membrane. In other life cycle stages of the malaria parasite, phospholipases have been implicated in membrane disruption processes during egress, however their importance for gametocyte egress is relatively unknown. Here, we performed comprehensive functional analyses of six putative phospholipases for their role during development and egress of Plasmodium falciparum gametocytes. We localize two of them, the prodrug activation and resistance esterase (PF3D7_0709700) and the lysophospholipase 1 (PF3D7_1476700), to the parasite plasma membrane. Subsequently, we show that disruption of most of the studied phospholipase genes does neither affect gametocyte development nor egress. The exception is the putative patatin-like phospholipase 3 (PF3D7_0924000), whose gene deletion leads to a delay in male gametocyte exflagellation, indicating an important, albeit not essential, role of this enzyme in male gametogenesis.

Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action.

Over the last two decades, global malaria cases caused by Plasmodium falciparum have declined due to the implementation of effective treatments and the use of insecticides. However, the COVID-19 pandemic caused major disruption in the timely delivery of medical goods and diverted public health resources, impairing malaria control. The emergence of resistance to all existing frontline antimalarials underpins an urgent need for new antimalarials with novel mechanisms of action. Furthermore, the need to reduce malaria transmission and/or prevent malaria infection has shifted the focus of antimalarial research towards the discovery of compounds that act beyond the symptomatic blood stage and also impact other parasite life cycle stages. Phenotypic screening has been responsible for the majority of new antimalarial lead compounds discovered over the past 10 years. This review describes recently reported novel antimalarial hits that target multiple parasite stages and were discovered by phenotypic screening during the COVID-19 pandemic. Their modes of action and targets in blood stage parasites are also discussed.

Covalent Macrocyclic Proteasome Inhibitors Mitigate Resistance in Plasmodium falciparum.

The Plasmodium proteasome is a promising antimalarial drug target due to its essential role in all parasite lifecycle stages. Furthermore, proteasome inhibitors have synergistic effects when combined with current first-line artemisinin and related analogues. Linear peptides that covalently inhibit the proteasome are effective at killing parasites and have a low propensity for inducing resistance. However, these scaffolds generally suffer from poor pharmacokinetics and bioavailability. Here we describe the development of covalent, irreversible, macrocyclic inhibitors of the Plasmodium falciparum proteasome. We identified compounds with excellent potency and low cytotoxicity; however, the first generation suffered from poor microsomal stability. Further optimization of an existing macrocyclic scaffold resulted in an irreversible covalent inhibitor carrying a vinyl sulfone electrophile that retained high potency and low cytotoxicity and had acceptable metabolic stability. Importantly, unlike the parent reversible inhibitor that selected for multiple mutations in the proteasome, with one resulting in a 5,000-fold loss of potency, the irreversible analogue only showed a 5-fold loss in potency for any single point mutation. Furthermore, an epoxyketone analogue of the same scaffold retained potency against a panel of known proteasome mutants. These results confirm that macrocycles are optimal scaffolds to target the malarial proteasome and that the use of a covalent electrophile can greatly reduce the ability of the parasite to generate drug resistance mutations.

Malaria Vaccines: From the Past towards the mRNA Vaccine Era.

Plasmodium spp. is the etiological agent of malaria, a life-threatening parasitic disease transmitted by infected mosquitoes. Malaria remains a major global health challenge, particularly in endemic regions. Over the years, various vaccine candidates targeting different stages of Plasmodium parasite life-cycle have been explored, including subunit vaccines, vectored vaccines, and whole organism vaccines with Mosquirix, a vaccine based on a recombinant protein, as the only currently approved vaccine for Plasmodium falciparum malaria. Despite the aforementioned notable progress, challenges such as antigenic diversity, limited efficacy, resistant parasites escaping protective immunity and the need for multiple doses have hindered the development of a highly efficacious malaria vaccine. The recent success of mRNA-based vaccines against SARS-CoV-2 has sparked renewed interest in mRNA vaccine platforms. The unique mRNA vaccine features, including their potential for rapid development, scalability, and flexibility in antigen design, make them a promising avenue for malaria vaccine development. This review provides an overview of the malaria vaccines' evolution from the past towards the mRNA vaccine era and highlights their advantages in overcoming the limitations of previous malaria vaccine candidates.

Plasmodium falciparum Eukaryotic Translation Initiation Factor 3 is Stabilized by Quinazoline-Quinoline Bisubstrate Inhibitors.

Malaria drug resistance is hampering the fight against the deadliest parasitic disease affecting over 200 million people worldwide. We recently developed quinoline-quinazoline-based inhibitors (as compound 70) as promising new antimalarials. Here, we aimed to investigate their mode of action by using thermal proteome profiling (TPP). The eukaryotic translation initiation factor 3 (EIF3i) subunit I was identified as the main target protein stabilized by compound 70 in Plasmodium falciparum. This protein has never been characterized in malaria parasites. P. falciparum parasite lines were generated expressing either a HA tag or an inducible knockdown of the PfEIF3i gene to further characterize the target protein. PfEIF3i was stabilized in the presence of compound 70 in a cellular thermal shift Western blot assay, pointing that PfEIF3i indeed interacts with quinoline-quinazoline-based inhibitors. In addition, PfEIF3i-inducible knockdown blocks intra-erythrocytic development in the trophozoite stage, indicating that it has a vital function. We show that PfEIF3i is mostly expressed in late intra-erythrocytic stages and localizes in the cytoplasm. Previous mass spectrometry reports show that PfEIF3i is expressed in all parasite life cycle stages. Further studies will explore the potential of PfEIF3i as a target for the design of new antimalarial drugs active all along the life cycle of the parasite.

Chemical modulation of Schistosoma mansoni lysine specific demethylase 1 (SmLSD1) induces wide-scale biological and epigenomic changes.

Background: Schistosoma mansoni, a parasitic worm species responsible for the neglected tropical disease schistosomiasis, undergoes strict developmental regulation of gene expression that is carefully controlled by both genetic and epigenetic processes. As inhibition of S. mansoni epigenetic machinery components impairs key transitions throughout the parasite's digenetic lifecycle, a greater understanding of how epi-drugs affect molecular processes in schistosomes could lead to the development of new anthelmintics. Methods: In vitro whole organism assays were used to assess the anti-schistosomal activity of 39 Homo sapiens Lysine Specific Demethylase 1 (HsLSD1) inhibitors on different parasite life cycle stages. Moreover, tissue-specific stains and genomic analysis shed light on the effect of these small molecules on the parasite biology. Results: Amongst this collection of small molecules, compound 33 was the most potent in reducing ex vivo viabilities of schistosomula, juveniles, miracidia and adults. At its sub-lethal concentration to adults (3.13 µM), compound 33 also significantly impacted oviposition, ovarian as well as vitellarian architecture and gonadal/neoblast stem cell proliferation. ATAC-seq analysis of adults demonstrated that compound 33 significantly affected chromatin structure (intragenic regions > intergenic regions), especially in genes differentially expressed in cell populations (e.g., germinal stem cells, hes2 + stem cell progeny, S1 cells and late female germinal cells) associated with these ex vivo phenotypes. KEGG analyses further highlighted that chromatin structure of genes associated with sugar metabolism as well as TGF-beta and Wnt signalling were also significantly perturbed by compound 33 treatment. Conclusions: This work confirms the importance of histone methylation in S. mansoni lifecycle transitions, suggesting that evaluation of LSD1 - targeting epi-drugs may facilitate the search for next-generation anti-schistosomal drugs. The ability of compound 33 to modulate chromatin structure as well as inhibit parasite survival, oviposition and stem cell proliferation warrants further investigations of this compound and its epigenetic target SmLSD1.

Antimalarial Assessment of Certain 1,2,4-Triazoles and Benzoquinolones against Plasmodium knowlesi A1H1

Previous studies have reported the use of nitrogen-heterocyclic compounds to treat malaria. Interestingly, quinolone and 1,2,4-triazole scaffolds demonstrated an outstanding capacity to target at least two stages of the malaria parasite life cycle, especially when they are hybrid with other nitrogen heterocycles. Thus, the objective of this study is to assess the drug susceptibility of Plasmodium knowlesi A1H1 parasites to certain 1,2,4-triazoles and benzoquinones that bear pyrrolidinones using a plasmodium lactate dehydrogenase assay. All synthesized compounds showed moderate activity against P. knowlesi A1H1 with EC50 values in the range of 13.39-28.85 μM. Both 1,2,4-triazoles and quinolone derivatives were synthesized using commercially available pyrrolidinones.

Toxoplasma gondii AP2XII-2 Contributes to Transcriptional Repression for Sexual Commitment.

Toxoplasma gondii is a widespread protozoan parasite that has a significant impact on human and veterinary health. The parasite undergoes a complex life cycle involving multiple hosts and developmental stages. How Toxoplasma transitions between life cycle stages is poorly understood yet central to controlling transmission. Of particular neglect are the factors that contribute to its sexual development, which takes place exclusively in feline intestines. While epigenetic repressors have been shown to play an important role in silencing the spurious gene expression of sexually committed parasites, the specific factors that recruit this generalized machinery to the appropriate genes remain largely unexplored. Here, we establish that a member of the AP2 transcription factor family, AP2XII-2, is targeted to genomic loci associated with sexually committed parasites along with epigenetic regulators of transcriptional silencing, HDAC3 and MORC. Despite its widespread association with gene promoters, AP2XII-2 is required for the silencing of relatively few genes. Using the CUT&Tag (cleavage under targets and tagmentation) methodology, we identify two major genes associated with sexual development downstream of AP2XII-2 control, AP2X-10 and the amino acid hydroxylase AAH1. Our findings show that AP2XII-2 is a key contributor to the gene regulatory pathways modulating Toxoplasma sexual development. IMPORTANCE Toxoplasma gondii is a parasite that undergoes its sexual stage exclusively in feline intestines, making cats a major source of transmission. A better understanding of the proteins controlling the parasite's life cycle stage transitions is needed for the development of new therapies aimed at treating toxoplasmosis and the transmission of the infection. Genes that regulate the sexual stages need to be turned on and off at the appropriate times, activities that are mediated by specific transcription factors that recruit general machinery to silence or activate gene expression. In this study, we identify a transcription factor called AP2XII-2 as being important for the repression of a subset of sexual stage genes, including a sexual stage-specific AP2 factor (AP2X-10) and a protein (AAH1) required to construct the infectious oocysts expelled from infected cats.

Deciphering the complex trophic relationship of the black-spotted croaker (Teleostei: Sciaenidae) and its parasites using stable isotope analysis

The stable isotope values of nitrogen (δ15N) and carbon (δ13C) have been widely used in ecological studies to decipher the trophic relationships and interactions that occur between living organisms. The aim of this study was to determine the trophic relationship between a commercially important tropical Australian marine fish ( Protonibea diacanthus (Lacepède, 1802)) (Sciaenidae) and its associated parasites, through stable isotope analysis of nitrogen and carbon (δ15N and δ13C). We examined the stable isotope ecology of four parasitic organisms: adult ectoparasitic copepods, and endoparasitic adult digeneans and nematodes and plerocercoids. Nitrogen in endoparasites was consistently depleted when compared with the host; however, digeneans expressed nitrogen signatures almost equivalent to those of the host. Ectoparasitic copepods were the only parasite that was substantially enriched in nitrogen compared with the host. All adult parasitic organisms were carbon depleted when compared with the host tissue associated with the site of infection; however, plerocercoids were enriched. Our findings emphasize the complexity of parasite–host interactions and the varying values of isotopic discrimination between parasite type, life-cycle stage, and location in host.

A Microtubule-Associated Protein Is Essential for Malaria Parasite Transmission.

Mature gametocytes of Plasmodium falciparum display a banana (falciform) shape conferred by a complex array of subpellicular microtubules (SPMT) associated with the inner membrane complex (IMC). Microtubule-associated proteins (MAPs) define MT populations and modulate interaction with pellicular components. Several MAPs have been identified in Toxoplasma gondii, and homologues can be found in the genomes of Plasmodium species, but the function of these proteins for asexual and sexual development of malaria parasites is still unknown. Here, we identified a novel subpellicular MAP, termed SPM3, that is conserved within the genus Plasmodium, especially within the subgenus Laverania, but absent in other Apicomplexa. Conditional knockdown and targeted gene disruption of Pfspm3 in Plasmodium falciparum cause severe morphological defects during gametocytogenesis, leading to round, nonfalciform gametocytes with an aberrant SPMT pattern. In contrast, Pbspm3 knockout in Plasmodium berghei, a species with round gametocytes, caused no defect in gametocytogenesis, but sporozoites displayed an aberrant motility and a dramatic defect in invasion of salivary glands, leading to a decreased efficiency in transmission. Electron microscopy revealed a dissociation of the SPMT from the IMC in Pbspm3 knockout parasites, suggesting a function of SPM3 in anchoring MTs to the IMC. Overall, our results highlight SPM3 as a pellicular component with essential functions for malaria parasite transmission. IMPORTANCE A key structural feature driving the transition between different life cycle stages of the malaria parasite is the unique three-membrane pellicle, consisting of the parasite plasma membrane (PPM) and a double membrane structure underlying the PPM termed the inner membrane complex (IMC). Additionally, there are numerous linearly arranged intramembranous particles (IMPs) linked to the IMC, which likely link the IMC to the subpellicular microtubule cytoskeleton. Here, we identified, localized, and characterized a novel subpellicular microtubule-associated protein unique to the genus Plasmodium. The knockout of this protein in the human-pathogenic species P. falciparum resulted in malformed gametocytes and aberrant microtubules. We confirmed the microtubule association in the P. berghei rodent malaria homologue and show that its knockout results in a perturbed microtubule architecture, aberrant sporozoite motility, and decreased transmission efficiency.

Major drivers of biodiversity loss and their impacts on helminth parasite populations and communities.

The world's biodiversity is in peril. The major threats to biodiversity globally are habitat change, overexploitation, climate change, invasive species and pollution. Not only do these stressors impact free-living organisms, but they affect parasitic ones as well. Herein, this perspective examines the potential consequences of these anthropogenic perturbations on helminth populations and communities, with emphasis on significant developments over the past decade. Furthermore, several case studies are examined in more detail for each of these threats to biodiversity. While effects are widespread and diverse, for the most part all these environmental stressors have negative effects on parasite populations and communities. Those parasites with complex life cycles that are trophically transmitted are often more at risk, although larval parasites with a wide host spectrum, and directly transmitted ectoparasites, appear less threatened and may even benefit. However, differential effects on hosts and parasites, on parasite life cycle stages and on host-parasite interactions made specific predictions difficult and context-dependent. Experimental laboratory and mesocosm studies on specific parasites that test effects on the different life cycle stages, hosts and host-parasite interactions, permitting the determination of net effects of an environmental stressor, yield insightful and sometimes counterintuitive results, although they remain a simplification of real-world complexity. Recent advances in the use of parasites as bioindicators of effects also are discussed.

Antibody-dependent immune responses elicited by blood stage-malaria infection contribute to protective immunity to the pre-erythrocytic stages

Advances in transcriptomics and proteomics have revealed that different life-cycle stages of the malaria parasite, Plasmodium, share antigens, thus allowing for the possibility of eliciting immunity to a parasite life-cycle stage that has not been experienced before. Using the Plasmodium chabaudi (AS strain) model of malaria in mice, we investigated how isolated exposure to blood-stage infection, bypassing a liver-stage infection, yields significant protection to sporozoite challenge resulting in lower liver parasite burdens. Antibodies are the main immune driver of this protection. Antibodies induced by blood-stage infection recognise proteins on the surface of sporozoites and can impair sporozoite gliding motility in vitro, suggesting a possible function in vivo. Furthermore, mice lacking B cells and/or secreted antibodies are not protected against a sporozoite challenge in mice that had a previous blood-stage infection. Conversely, effector CD4+ and CD8+ T cells do not seem to play a role in protection from sporozoite challenge of mice previously exposed only to the blood stages of P. chabaudi. The protective response against pre-erythrocytic stages can be induced by infections initiated by serially passaged blood-stage parasites as well as recently mosquito transmitted parasites and is effective against a different strain of P. chabaudi (CB strain), but not against another rodent malaria species, P. yoelii. The possibility to induce protective cross-stage antibodies advocates the need to consider both stage-specific and cross-stage immune responses to malaria, as natural infection elicits exposure to all life-cycle stages. Future investigation into these cross-stage antibodies allows the opportunity for candidate antigens to contribute to malaria vaccine development.

Erythrocyte tropism of malarial parasites: The reticulocyte appeal.

Erythrocytes are formed from the enucleation of erythroblasts in the bone marrow, and as erythrocytes develop from immature reticulocytes into mature normocytes, they undergo extensive cellular changes through their passage in the blood. During the blood stage of the malarial parasite life cycle, the parasite sense and invade susceptible erythrocytes. However, different parasite species display varying erythrocyte tropisms (i.e., preference for either reticulocytes or normocytes). In this review, we explore the erythrocyte tropism of malarial parasites, especially their predilection to invade reticulocytes, as shown from recent studies. We also discuss possible mechanisms mediating erythrocyte tropism and the implications of specific tropisms to disease pathophysiology. Understanding these allows better insight into the role of reticulocytes in malaria and provides opportunities for targeted interventions.

The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria.

Drug resistance to first-line antimalarials-including artemisinin-is increasing, resulting in a critical need for the discovery of new agents with novel mechanisms of action. In collaboration with the Walter and Eliza Hall Institute and with funding from the Wellcome Trust, a phenotypic screen of Merck's aspartyl protease inhibitor library identified a series of plasmepsin X (PMX) hits that were more potent than chloroquine. Inspired by a PMX homology model, efforts to optimize the potency resulted in the discovery of leads that, in addition to potently inhibiting PMX, also inhibit another essential aspartic protease, plasmepsin IX (PMIX). Further potency and pharmacokinetic profile optimization efforts culminated in the discovery of WM382, a very potent dual PMIX/X inhibitor with robust in vivo efficacy at multiple stages of the malaria parasite life cycle and an excellent resistance profile.

Pro- and anti-inflammatory cytokine profiles in Plasmodium Falciparum-infected individuals from Baiyeku, Ikorodu, Lagos, Nigeria

Available evidence indicates that the various stages of the malaria parasite life cycle elicit specific immune responses of which the relative levels of pro-inflammatory cytokines are key to disease progression, killing the parasite and mediating disease outcomes. This study investigated T-cell response in malaria. Four hundred and sixty-two participants were screened in a community survey of Plasmodium falciparum malaria in Baiyeku, Lagos, Nigeria. P. falciparum parasitaemia was determined by microscopy while the serum levels of IL-10, IFNγ and TNFα were determined by Enzyme-linked immunosorbent assay (ELISA). A total of 70 (15.2 %) participants were microscopically positive for P. falciparum of which 70% were females, 30% were males while children aged 1-17 years were 65.7%. The geometric mean parasite density (GMPD) was significantly (p=0.001) higher among females than males. The GMPD of participants <5 years of age was also significantly (p=0.001) higher than other age groups. About 46.8% of the participants were underweight (Body Mass Index, BMI < 18.5) and also had the highest parasite intensity. The TNFα, IFNγ and IL-10 levels were significantly (p< 0.05) higher in the infected than the uninfected participants. IFN-γ values were significantly (p=0.014) elevated among the symptomatic than the asymptomatic participants while there was no significant difference (P>0.053) in the levels of TNF-α and IL-10 (P>0.093) between the symptomatic and asymptomatic participants. The prevalence of P. falciparum obtained in this study area which is endemic to malaria is 15.2% suggesting a significant reduction of the disease over time due to awareness of the disease in the community. The levels of pro-inflammatory cytokines (IFN-γ and TNF-α) in this study were lower due to the down-regulatory action of the anti-inflammatory cytokines (IL-10). These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to the pathogenesis of uncomplicated malaria.