Carriage of Mutant Dihydrofolate Reductase and Dihydropteroate Synthase Genes among Plasmodium falciparum Isolates Recovered from Pregnant Women with Asymptomatic Infection in Lagos, Nigeria.

OBJECTIVE: To assess N51I, C59R and S108N polymorphisms of dihydrofolate reductase (dhfr) and A437G and K540E of dihydropteroate synthase (dhps) genes of P. falciparum isolates recovered from pregnant women with asymptomatic malaria in a coastal setting in Nigeria. SUBJECTS AND METHODS: A total of 107 consenting and consecutively enrolled pregnant women (mean age ± standard deviation, 26.6 ± 4.5 years) attending antenatal care at the Iru/Victoria Island Primary Health Centre, Lagos, were screened for peripheral malaria by microscopy, by a histidine-rich protein-2-based rapid diagnostic test (RDT) and by polymerase chain reaction (PCR) using finger-pricked and dot blood samples. DNA was extracted from the blood and used for dhfr and dhps gene polymorphism analyses by PCR and restriction fragment length polymorphism. The sociodemographic and parasite data obtained were analysed. RESULTS: Of the 107 patients, 34 (31.8%), 46 (43%) and 40 (37.4%) were found to be P. falciparum infected using microscopy, RDT and corrected RDT-PCR, respectively (p < 0.05). The prevalence of P. falciparum isolates with mutant and mixed genotypes of dhfr at codons 51, 59 and 108 was 70, 75 and 80%, respectively, and the triple mutation in the homozygous form was 35%. The prevalence of the homozygous quintuple dhfr plus dhps mutant was 5%, while that of the P. falciparum isolates with mutant or mixed genotypes of dhps at codons 437 and 540 was 37.5 and 22.5%, respectively. CONCLUSION: This study revealed the emergence of the K540E mutation among the parasite population in Lagos. However, it supports the implementation of the intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine with continuous effectiveness monitoring in the study area.

Serum levels of leptin in Nigerian patients with sickle cell anaemia.

BACKGROUND: Several studies have shown that the pathophysiology of homozygous sickle cell anaemia (SCA) results in a myriad of metabolic, nutritional, haematological and clinical effects that interact with other co-morbid factors to determine the quality of life and life expectancy of afflicted patients. Because of its critical roles in nutrition and metabolism, inflammation, haematopoiesis and cellular immunity, this study determined the plasma levels of leptin in steady and unsteady states of HbSS in Nigerian patients. METHODS: A total of 51 SCA patients aged 5 - 35 years with 34 (61.8%) being females who were either on admission or visiting four medical centres in Lagos, Nigeria together with 22 non-SCD controls aged 5 -30 years comprising 12 (54.5%) females were enrolled after obtaining their informed consent and ethical approval. Patients were further stratified into steady and unsteady cases of SCA based on clinical presentations, while blood samples collected by venipuncture from each of the study participants were analyzed haematologically for full blood count and HbF level and microscopically for malaria, while plasma leptin was assayed using ELISA method. Body composition defined by weight, fat mass and body mass index (BMI) was determined using standard methods. Data obtained for cases and controls were analyzed statistically. RESULTS: Twenty - one patients had unsteady HbSS and elicited greater and significant (P < 0.05) reduction in fat mass, BMI, HbF and eosinophil count but elevated mean total leukocyte, count, level of irreversibly sickled cells and P. falciparum parasitaemia (4613.7 vs. 749.6 - 1078.4 parasites/uL), pyrexia rate (58.3 vs. 25.8%) when compared with steady state patients or non-SCD controls. Compared to the control, significant decreases in plasma leptin before and after controlling for body fat that was worsened by crisis were observed among the SCD patients. Unlike the non-SCD controls, leptin correlated non-significantly (P > 0.05) with all body composition indices measured in the patients except for fat mass in unsteady cases. Multivariate regression analysis identified ESR and RC as independent predictor of low plasma leptin concentration in the SCA patients. CONCLUSIONS: Base on these findings, we conclude that plasma level of leptin is further decreased in the unsteady state of HbSS, shows poor correlation with adiposity and malarial infection but has inflammation and poor reticulocyte response as independent predictors among Nigerian patients.

Association between erythrocyte Na+K+-ATPase activity and some blood lipids in type 1 diabetic patients from Lagos, Nigeria.

BACKGROUND: Altered levels of erythrocyte Na+K+-ATPase, atherogenic and anti-atherogenic lipid metabolites have been implicated in diabetic complications but their pattern of interactions remains poorly understood.This study evaluated this relationship in Nigerian patients with Type 1 diabetes mellitus. METHODS: A total of 34 consented Type 1 diabetic patients and age -matched 27 non-diabetic controls were enrolled. Fasting plasma levels of total cholesterol, triglycerides and HDL-cholesterol were determined spectrophotometrically and LDL-cholesterol estimated using Friedewald formula. Total protein content and Na+K+-ATPase activity were also determined spectrophotometrically from ghost erythrocyte membrane prepared by osmotic lysis. RESULTS: Results indicate significant (P < 0.05) reduction in Na+K+-ATPase activity in the Type 1 diabetic patients (0.38 +/- 0.08 vs. 0.59 +/- 0.07 microM Pi/mgprotein/h) compared to the control but with greater reduction in the diabetic subgroup with poor glycemic control (n = 20) and in whom cases of hypercholesterolemia (8.8%), hypertriglyceridemia (2.9%) and elevated LDL-cholesterol (5.9% each) were found. Correlation analyses further revealed significant (P < 0.05) inverse correlations [r = -(0.708-0.797] between all the atherogenic lipid metabolites measured and Na+K+-ATPase in this subgroup contrary to group with good glycemic control or non-diabetic subjects in which significant (P < 0.05) Na+K+-ATPase and HDL-C association were found (r = 0.427 - 0.489). The Na+K+-ATPase from the diabetic patients also exhibited increased sensitivity to digoxin and alterations in kinetic constants Vmax and Km determined by glycemic status of the patients. CONCLUSION: It can be concluded that poor glycemic control evokes greater reduction in erythrocyte Na+K+-ATPase activity and promote enzyme-blood atherogenic lipid relationships in Type 1 diabetic Nigerian patients.