The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents.

Prevalence of Malaria and Predisposing Factors to Antimalarial Drug Resistance in Southwestern Nigeria

Background: Plasmodium falciparum the main causative agent of malaria is an important public health vector. With the use of PCR, its genetic diversity has been extensively studied with dearth information from Nigeria. Methods: In this study, 100 P. falciparum strains merozoite surface protein 1( msp-1), merozoite surface protein 2 (msp-2) and Glutamate rich protein (Glurp) from Ogun State General Hospitals were characterized. The genetic diversity of P. falciparum isolates was analyzed by restriction fragment length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) of their respective allelic families KI, MAD 20, RO33 (MSP-1);FC27, 3D7 (MSP-2) and Glutamate rich protein respectively. Results: Majority of the patients showed monoclonal infections while multiplicity of the infection for msp-1 and msp-2 were 1.1 and 1.2 respectively. The estimated number of genotypes was 8 msp-1 (4 KI; 3 MAD; 1 RO33) and 6 msp-2 (3 FC27; 3 3D7). 80% of the isolates coded for Glurp with allelic size ranged between 700 and 900 bp. Conclusion: The allelic distributions however were similar to those previously reported in other endemic malaria countries. Future studies will be designed to include other malaria endemic regions of Nigeria such as the oil exploration regions. Keywords: Genetic diversity; Plasmodium; Merozoite surface protein, monoclonal infection

Purpose: Effective routine monitoring and surveillance of parasite genes is a necessary strategy in the control of parasites’ resistance to antimalarial drugs, according to the WHO’s recommendation. This cross-sectional study therefore aimed at carrying out an epidemiological analysis on malaria incidence in Ado-Odo/Ota, Ogun State. Patients and methods: Blood and corresponding saliva samples were collected from 1,243 subjects of all ages and sex presenting with fever and a parasitemia level ≥2,000 between September 2016 and March 2018. Samples were collected from selected health facilities in the study area of Ogun state to establish the prevalence of falciparum malaria and determine resistance genes harbored by the parasites. The overall prevalence of falciparum malaria in the study site by microscopic examination was 45.86%. The highest incidence of 57.42% was recorded among male subjects. Point mutations of K76T and N86Y in the Pfcrt and pfmdr-1 genes, as well as non-synonymous mutations in Pfk13 genes, were screened for and sequenced for further analysis. Results: Pfcrt was detectable in 57.42% of blood and 51.02% of saliva samples, respectively. About 34.78% of the subjects that were confirmed microscopically harbored the Pfmdr-1 mutated gene while 26.67% of the saliva samples revealed Pfmdr-1. Epidemiological studies identified the presence of wild-type Pfk13 genes in 21.84% of blood and 44.44% of saliva samples correspondingly. For each of the genes evaluated, saliva portrayed great diagnostic performance when compared with blood. Conclusion: Findings from this study have established the prevalence of malaria and the resistance pattern of P. falciparum in the study area. The findings may help in formulating drug policies and suggest the use of saliva as a noninvasive point-of-care method of diagnosing malaria potentially deployable to rural endemic areas.

Malaria remains a significant global health concern causing numerous fatalities and the emergence of antimalarial drug resistance highlights the urgent need for novel therapeutic options with innovative mechanisms of action and targets. This study aimed to design potential inhibitors of Plasmodium falciparum 6-pyruvoyltetrahydropterin synthase (PfPTPS), synthesize them, and experimentally validate their efficacy as antimalarial agents. A structure-based approach was employed to design a series of novel derivatives, including amidinyl, amidoximyl and hydroxamic acid analogs (1c, 1d, 2b, and 3b), with a focus on their ability to bind to the Zn²⁺ present in the active site of PfPTPS. The syntheses of these compounds were accomplished through various multi-step synthetic pathways and their structural identities were confirmed using ¹H and ¹³C NMR spectra, mass spectra, and elemental analysis. The compounds were screened for their antiplasmodial activity against the NF54 strain of P. falciparum and in vitro cytotoxicity testing was performed using L-6 cells. The in vivo acute toxicity of the compounds was evaluated in mice. Docking studies of the compounds with the 3D structure of PfPTPS revealed their strong binding affinities, with compound 3b exhibiting notable metal–acceptor interaction with the Zn²⁺ in the protein binding pocket thereby positioning it as a lead compound for PfPTPS inhibition. The in vitro antiplasmodial studies revealed moderate efficacies against the Pf NF54 strain, particularly compounds 1d and 3b which displayed IC₅₀ < 0.2 μM. No significant cytotoxicity was noted on the L-6 rat cell line. Moreover, in vivo studies suggested that compound 3b exhibited both safety and efficacy in treating rodent malaria. The identified lead compound in this study represents a possible candidate for antimalarial drug development and can be further explored in the search for alternative antifolate drugs to combat the malaria menace.