Malaria Treatment schedules and Socio- economic implications of mutation in the pfmdr1 and pfcrt genes of Plasmodium falciparum isolates in asymptomatic carriers in Nigeria

Mutation in the pfcrt and pfmdr-1, genes have been implicated both to be putative CQ resistance markers. Blood samples from 130 volunteers were obtained and genotyped by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for pfmdr1 and pfcrt genes. A total of 40(30.8%) questionnaires were administered to the adults and 90(69.2%) were administered to the school children. 14(10.8%) had microscopically detectable parasites on day zero with a mean parasites counts of 40,231 parasites/µL. CQ was administered to all infected, higher parasite density was observed in the poorer population. PCR-RFLP analysis on 14 parasite positive samples for pfcrt and pfmdr genotypes showed polymorphism around pfmdr1 N86Y. The parasite count decreased progressively from day 0 to day 14 to negligible levels. Conversely, our subjects still harboured sensitive strains of the parasite. Our PCR analysis of the pfcrtK76T yielded no result. A significant relationship was observed between respondents’ treatment behaviour and mutation in the pfmdr1 genes of Plasmodium falciparum. Keywords: Polymorphism, falciparum, Genotyped, mutation, Chloroquin

Schistosoma haematobium and Plasmodium falciparum co-infection in Nigeria 2001–2018: A systematic review and meta-analysis

Malaria and schistosomiasis continue to contribute a big burden to infectious disease prevalence in the tropical areas, mainly in sub Saharan African countries. We previously reported high levels of schistosome specific antibody IgG3 in children coinfected with malaria and schistosomiasis. The aim of the current study was to examine the current co-infection rates of these diseases in Nigeria. Published and unpublished studies on coinfection of human urogenital schistosomiasis and malaria carried out in Nigeria between 2001 and August 2018 were retrieved through literature searches in PubMed, Google Scholar, AJOL, and university theses repositories. The filtered and relevant articles were reviewed and combined in a meta-analysis. Studies involving children reported higher rates of coinfection. The fourteen research articles involving 6,559 individuals were combined in a meta-analysis. Our analyses revealed an estimated 15% co-infection for the country, though with wide variability depending on location. In addition, there are few and welldesigned research publications in Nigeria on prevalence and mechanism of malaria and schistosomiasis coinfection

A study of the M235T variant of the angiotensinogen gene and hypertension in a sample population of Calabar and Uyo, Nigeria

Open Access JournalA common molecular variant of the angiotensinogen gene had been reported to predispose some ethnic groups to hypertension. This case–control study was designed to determine the frequency and association of the angiotensinogen M235T allele with hypertension in residents of Calabar and Uyo cities, south–south Nigeria. The study involved 1308 subjects, 612 patients and 696 controls. The M235T variant was investigated using an allele specific polymerase chain reaction and enzymatic digestion to determine allele frequencies. Hypertensinogenic factors such as dietary habits, physical activity, smoking and drinking habits were assessed using questionnaires. Descriptive statistics, chi-square and multiple regression analysis were used to analyze the data obtained. The M235T allele frequency was high (0.94 for hypertensives and 0.96 for controls) though it was not associated with hypertension status. The odds ratio for hypertension was 0.64 (95% confidence interval: 0.39–1.06) there were no significant differences between the genotype frequency of hypertensives and controls. By multiple regression, Hypertension was observed to be associated with age and was a predictor for systolic blood pressure in both patient r2 = 0.359; p < 0.05 and control groups r2 = 0.26. Age and body mass index were predictors for diastolic blood pressure in the control group, r2 = 0.28. Although the frequency of the M235T variant was high, it was not a significant risk factor for hypertension in the study population

Variation in Arsenic metabolism in schistosomiasis associated bladder pathology in a rural community, Eggua, Ogun State, Nigeria

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T&gt;C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P&gt; 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology

IL4, IL13, GSTM1 and T1 variants and susceptibility to Schistosomiasis and associated bladder pathologies in Eggua, Nigeria

Failure of the human host to elicit adequate immune responses to the adult Schistosoma haematobium worm and continuous strong inflammatory responses to the eggs have been the main causes of bladder pathology in chronic Schistosomiasis. Identification of susceptibility biomarkers for schistosomiasis- associated bladder pathology is necessary in order to detect genetic factors responsible for the infection and spread of the disease. The aim of this study was to identify candidate-biomarkers for susceptibility to schistosomiasis and its associated pathologies. A total of 371 adult participants, comprising 130 males and 241 females from Eggua community, Ogun State, Nigeria, were randomly recruited into a cross sectional study from August 2012 to May 2014. They were screened for S. haematobium ova and bladder pathologies by microscopy and ultrasonography, respectively. Human host susceptibility to schistosomiasis and its associated bladder pathologies were determined by PCR genotyping of Interleukin (IL4 and IL13) genes, and glutathione-S-transferase (GSTT1 and GSTM1) genes. The overall prevalence of S. haematobium in the population was 29.3% (108/369). Bladder pathologies were observed in 32.3% (117/362) of the population. Polymorphisms in IL 4-590 and IL 13-1055 were observed in 24.1% and 9.3% schistosomiasis cases, respectively. The IL 13-1055 polymorphism did not indicate susceptibility to schistosomiasis in males (OR 0.7, 95% CI 0.3-2.1) but a slight risk was found in females (OR 1.1, 95% CI 0.7-1.7). Participants with GSTM1 and GSTT1 polymorphisms expressed elevated risks of bladder pathologies (OR = 4.3, 95% CI 2.0 - 9.2 and OR = 4.2, 95% CI 1.5 – 12.0, respectively), with the pathology and schistosomiasis group having more GST polymorphisms than bladder pathologies. Keywords: Polymorphisms, Cytokines, GST, schistosomiasis and pathologie

Prevalence of HIV and Malaria parasites co-infection in pregnant mothers and their babies post delivery

Worsened perinatal outcomes and increased rates of maternal morbidity are consequences of co-infection of HIV and Plasmodium falciparum in pregnant women. This study was designed to ascertain the proportion of co-infection of both diseases in pregnant mothers and babies born to HIV-infected mothers. A total of 149 pregnant mothers and 30 babies of HIV-infected mothers were engaged in a longitudinal study for 18 months in the endemic area of Saki and Ibadan. Only babies born to HIV infected mothers were enrolled and systematically followed-up for six months post delivery. Determine(R) and Unigold rapid diagnostic tests kits were used for HIV test in mothers whereas HIV screening was conducted on the babies using polymerase chain reaction at six months post delivery. Giemsa stained thick blood smear was used to determine the presence of asexual stages of Plasmodium falciparum. Descriptive statistics was used to determine the percentage of infections status. Chi-square and student t-test was used to compare maternal data and babies six months after birth. The results showed that 85/149(57.0%) mothers and 11/30(36.7%) babies had microscopically detectable malaria parasites whereas the seroprevalence were 64(33.0%) and 19(10.7%) for mothers and infants respectively. In mothers, 19(12.8%) had HIV alone, 51/149(34.2%) malaria only, 34/149 (22.8%) were co-Infected and 45/149(30.2%) had neither HIV nor malaria. In infants, 9/30 (30.0%), 10/30(33.3) had HIV only, 2/30(6.7%) had malaria only whereas 9/30(30.0%) had neither malaria nor HIV. Parasitemia ranged between 251.5 of cells/µL in mothers and 205.7 of cells/µL in babies born to HIV infected mothers. Keywords: Perinatal, Plasmodium falciparum, Seroprevalence, co-infected, Parasitemia

Insertion/deletion polymorphism of the angiotensinconverting enzyme gene and the risk of hypertension among residents of two cities, SouthSouth Nigeria

Background: Hypertension is a public health challenge due to its high prevalence, and is a major risk factor for cardiovascular diseases. This study was designed to determine the frequency of the I/D polymorphism of the angiotensin-converting enzyme gene and its association with hypertension in a sample population of Calabar and Uyo, South-South Nigeria. Materials and Methods: A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls, were randomly recruited from hypertension clinics and the general population. The I/D polymorphism was investigated using polymerase chain reaction. Multiple regression and odds ratio (OR) was applied to test whether the ID genotypes were predictors of hypertension. Results: The I/D genotype frequencies were 73(12%), 262(43%) and 277(45%); 74(12%), 303(50%) and 235(38%) for the II, ID, DD genotype in patient and control groups, respectively. A higher frequency of the ID genotype was observed in controls of which 208(61%) were females. By multiple regression analysis, age was a predictor for SBP in patients, r = 0.596, and DBP in controls, r = 0.555. Gender, Body mass index, I/D genotypes were not significant predictors for hypertension but the I/D polymorpism was associated with an increased risk for hypertension with an OR of 1.15 95%CI (0.924-1.456). Conclusion: The I/D polymorphism of the angiotensin-converting enzyme gene was a risk factor for hypertension in the sample population of Calabar and Uyo. This research will form baseline information for subsequent molecular studies in this population. Key Words: Angiotensin-converting enzyme gene, frequenc

Seasonal variations in antibody response to a Plasmodium falciparum recombinant circumsporozoite antigen in two villages in South Western Nigeria.

An Enzyme Linked Immunosorbent Assay (ELISA), employing a recombinant peptide capture antigen (R32tet32) was used to detect antibodies against the circumsporozoite protein (CSP) of the malaria parasite, Plasmodium falciparum in 169 serum samples from 16 subjects from two villages, Afefu (FA) and Tobalogbo (TB), in Igbo-Ora Community of Oyo State, over a period of 12 months. The maximum and mean Ab response for FA was higher than for TB samples (0.511 AU±0.170, 0.124±0.045U and 0.250±0.070 AU, 0.090±0.019AU respectively), with the mean Ab being significantly different (t=2.313; P>0.05). Despite both villages (FA and TB) falling within the same rainfall data zone, the Ab response profile for FA showed a positive (seasonal) relationship with rainfall (r=+0.31, P>0.05) while that of TB was negatively correlated (r=-0.32; P>0.05). Habits and the environment could be prime contributing factors alongside the less controllable immunogenetic factors. Data obtained here would serve as baseline and we suggest other expanded sample size studies to include data on temperature and other climatic factors to help establish sub-populations at risk and better empower malariologists in planning and execution of control programmes

Total immunoglobulin G and IgG1 subclass levels specific for the MSP-1 19 of Plasmodium falciparum are different in individuals with either processing-inhibitory, blocking or neutral antibodies

Background: Some MSP-1 19 specific antibodies that inhibit merozoite invasion also inhibit the secondary processing of MSP-1. However the binding of these inhibitory antibodies can be blocked by another group of antibodies, called blocking antibodies, which recognize adjacent or overlapping epitopes, but themselves have no effect on either MSP-1 processing or merozoite invasion. These antibodies have been reported to be present in individuals living in a malaria endemic area. Methods: Blood samples were obtained from children shown to have processing inhibitory, blocking, and neutral antibodies in a previous study. Enzyme linked immunosorbent assay (ELISA), was used to determine the total IgG, IgM and IgG subtypes. Results: There was a significant difference in anti-MSP-1 19 IgG, while there was no significant difference in the anti-MSP-1 19 IgM. Only anti MSP-1 19 IgG1, amongst the IgG subtypes was significantly different between the groups. Conclusion: This study shows that antibodies against MSP-1 are different not only in specificity and function but also in the amount of total IgG and IgG subtype produced

Co-infection of schistosomiasis, malaria, HBV and HIV among adults living in Eggua Community, Ogun State, Nigeria

Schistosomiasis is a parasitic disease caused by the blood fluke that continues to plague many developing countries in the tropics. The goal of this study was to determine the occurrence of schistosomiasis, malaria, HBV and HIV co-infection among adults in some villages of Eggua Community, Nigeria (Tata, Imoto, Orile and Ebute Igbooro). In cross-sectional surveys, 240 participants were recruited from Orile and Ebute Igbooro and 207 from Tata and Imoto. Urine samples were collected and tested for urinary schistosomiasis by conventional microscopy; blood samples were tested for HBV, HIV and malaria using standard RDTs and microscopy respectively. Prevalence and co-infection of the diseases was analyzed by chi-squared (x2) test. The prevalence of schistosomiasis and malaria was 21.3% and 11.1% in Tata and Imoto respectively; and 14.5% and 19.1% in Orile and Ebute Igbooro, respectively. The overall prevalence of co-infection of urinary schistosomiasis with malaria was 2.5% and 0.4% each with HIV and HBV in the study areas. Schistosoma haematobium and Plasmodium falciparum are prevalent in the study-area, and an integrated control approach directed against the two parasites should be carried out. Keywords: Schistosomiasis; malaria; co-infection; HBV and HIV