Impact of Malnutrition on Serum Levels of Pro-inflammatory Cytokines among Plasmodium falciparum Malaria Subjects in Nigeria.

BACKGROUND: Understanding the impact of malnutrition on innate immune response in Plasmodium falciparum (Pf)-infected subjects is critical for malaria control. AIMS AND OBJECTIVES: This study aims to investigate the nutritional status and innate immune response of Pf-infected subjects in Lagos, Nigeria. MATERIALS AND METHODS: A total of 1183 patients with a history of fever or axillary temperature ≥37°C were screened microscopically for Pf at Ijede General Hospital, Lagos, Nigeria. Malnutrition was determined according to the U.S National Center for Health Statistics (NCHS) as stunting, wasting, or underweight when the Z-score is <-2 in the participants aged <20 years. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-12 were determined by capture ELISA while hematological parameters were measured using an automated hematology system. RESULTS: A total of 384 volunteers were positive for Pf, of which 114 were <20 years with a median age of 10 years. Overall malaria prevalence was 20.89%. The malnutrition rate was 89.5%; 24 (21.05%) were stunted, 30 (26.32%) were underweight, and 48 (42.11%) were wasted. Pro-inflammatory cytokine responses were not affected by the type of malaria. TNF-α was higher in participants <5 years (P = 0.001) and in malnourished patients (P < 0.05). CONCLUSION: Together, it could be deduced that nutritional status influences Plasmodium falciparum malaria outcomes and progression pattern.

Résumé Contexte:Comprendre l'impact de la malnutrition sur la réponse immunitaire innée chez les sujets infectés par Plasmodium falciparum (Pf) est essentiel pour la lutte contre le paludisme.Buts et objectifs:Cette étude vise à étudier l'état nutritionnel et la réponse immunitaire innée des sujets infectés par Pf à Lagos, au Nigeria.Matériels et méthodes:Un total de 1183 patients ayant des antécédents de fièvre ou une température axillaire ≥37°C ont fait l'objet d'un dépistage microscopique de Pf à l'hôpital général Ijede, Lagos, Nigeria. La malnutrition a été déterminée selon le National Center for Health Statistics (NCHS) des États-Unis comme un retard de croissance, une émaciation ou une insuffisance pondérale lorsque le score Z est <-2 chez les participants âgés de moins de 20 ans. Les taux sériques de facteur de nécrose tumorale alpha (TNF-α), d'interleukine-1ß (IL-1ß) et d'IL-12 ont été déterminés par capture ELISA, tandis que les paramètres hématologiques ont été mesurés à l'aide d'un système d'hématologie automatisé.Résultats:Au total, 384 volontaires étaient positifs pour le Pf, dont 114 étaient âgés de moins de 20 ans avec un âge médian de 10 ans. La prévalence globale du paludisme était de 20,89 %. Le taux de malnutrition était de 89,5 %; 24 (21,05 %) souffraient d'un retard de croissance, 30 (26,32 %) d'une insuffisance pondérale et 48 (42,11 %) d'émaciation. Les réponses des cytokines pro-inflammatoires n'ont pas été affectées par le type de paludisme. Le TNF-α était plus élevé chez les participants de moins de 5 ans ( P = 0,001) et chez les patients souffrant de malnutrition ( P < 0,05).Conclusion:On peut en déduire que l'état nutritionnel peut influencer les résultats et le schéma de progression du paludisme.

Detection of novel Plasmodium falciparum coronin gene mutations in a recrudescent ACT-treated patient in South-Western Nigeria.

Background: Routine surveillance for antimalarial drug resistance is critical to sustaining the efficacy of artemisinin-based Combination Therapies (ACTs). Plasmodium falciparum kelch-13 (Pfkelch-13) and non-Pfkelch-13 artemisinin (ART) resistance-associated mutations are uncommon in Africa. We investigated polymorphisms in Plasmodium falciparum actin-binding protein (Pfcoronin) associated with in vivo reduced sensitivity to ART in Nigeria. Methods: Fifty-two P. falciparum malaria subjects who met the inclusion criteria were followed up in a 28-day therapeutic efficacy study of artemether-lumefantrine in Lagos, Nigeria. Parasite detection was done by microscopy and molecular diagnostic approaches involving PCR amplification of genes for Pf18S rRNA, varATS, telomere-associated repetitive elements-2 (TARE-2). Pfcoronin and Pfkelch-13 genes were sequenced bi-directionally while clonality of infections was determined using 12 neutral P. falciparum microsatellite loci and msp2 analyses. Antimalarial drugs (sulfadoxine-pyrimethamine, amodiaquine, chloroquine and some quinolones) resistance variants (DHFR_51, DHFR_59, DHFR_108, DHFR_164, MDR1_86, MDR1_184, DHPS_581 and DHPS_613) were genotyped by high-resolution melting (HRM) analysis. Results: A total of 7 (26.92%) cases were identified either as early treatment failure, late parasitological failure or late clinical failure. Of the four post-treatment infections identified as recrudescence by msp2 genotypes, only one was classified as recrudescence by multilocus microsatellites genotyping. Microsatellite analysis revealed no significant difference in the mean allelic diversity, He, (P = 0.19, Mann-Whitney test). Allele sizes and frequency per locus implicated one isolate. Genetic analysis of this isolate identified two new Pfcoronin SNVs (I68G and L173F) in addition to the P76S earlier reported. Linkage-Disequilibrium as a standardized association index, IAS, between multiple P. falciparum loci revealed significant LD (IAS = 0.2865, P=0.02, Monte-Carlo simulation) around the neutral microsatellite loci. The pfdhfr/pfdhps/pfmdr1 drug resistance-associated haplotypes combinations, (108T/N/51I/164L/59R/581G/86Y/184F), were observed in two samples. Conclusion: Pfcoronin mutations identified in this study, with potential to impact parasite clearance, may guide investigations on emerging ART tolerance in Nigeria, and West African endemic countries.