Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria.

Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α0.05. Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria.

BACKGROUND: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency. METHODS: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0. RESULTS: The mean age of the recruited women was 28.6±5.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%. CONCLUSION: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values <33% and those infected with HIV.

Genetic variants of tumor necrosis factor-α -308G/A (rs1800629) but not Toll-interacting proteins or vitamin D receptor genes enhances susceptibility and severity of malaria infection.

Susceptibility to malaria infection has been associated with host genetic polymorphisms that differs between groups. We hypothesize that Toll-interacting proteins (TOLLIP), vitamin D receptor (VDR) and tumor necrosis factor-α (TNF) genes are significant contributors to susceptibility and disease severity in Plasmodium falciparum (Pf) infection. Our aim is to explore the genomic diversity and haplotype frequency of these genes, as well as extrapolate possible association with markers of severity, between malaria-infected and healthy controls. Genomic DNA samples extracted from the blood of 107 malaria-infected patients and 190 uninfected controls were analyzed, with no difference in genotypic or allelic frequencies of TOLLIP and VDR polymorphisms. However, a significant difference in the genotypic (p = 2.20E-16) and allelic frequencies (p = 2.20E-16) of the TNF-α (snp rs1800629) polymorphism was found. The preponderance of the mutant variant among the malaria-infected show a possible impaired capacity to mount an effective immune response, potentially confirmed by our association results. This result calls for analysis of clearly delineated uncomplicated versus severe disease groups, including serum assays, providing a basis to conclude that susceptibility to malaria infection and potential contribution to disease severity is significantly associated with polymorphisms of the tumor necrosis factor-α but not TOLLIP or VDR genes.

Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.

There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd ß-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.

Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.

The antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (MENS) were investigated against established malaria infection in vivo using Swiss albino mice. The antimalarial activity of the extract against Plasmodium yoelli nigeriensis (P. yoelli) was assessed using the Rane test procedure. Chloroquine (CQ)-treated group served as positive control. The extract, at a dose of 1.25 g/kg body weight significantly (p<0.05) suppressed P. yoelli infection in the mice by 94%, while CQ, the reference drug, produced 86% suppression when compared to the untreated group after the fifth day of treatment. P. yoelli infection caused a significant (p<0.05) increase in the levels of red cell and hepatic malondialdehyde (MDA), an index of lipid peroxidation (LPO) in the mice. Serum and hepatic LPO levels were increased by 71% and 113%, respectively, in the untreated infected mice. Furthermore, P. yoelli infection caused a significant (p<0.05) decrease in the activities of superoxide dismutase, catalase, glutathione-S-transferase and the level of reduced glutathione in tissues of the mice. Treatment with MENS significantly (p<0.05) attenuated the serum and hepatic MDA levels in P. yoelli-infected mice. In addition, MENS restored the activities of red cell antioxidant enzymes in the infected mice to near normal. Moreover, MENS was found to be more effective than CQ in parasite clearance and, in the restoration of altered biochemical indices by P. yoelli infection. These results suggest that N. sativa seeds have strong antioxidant property and, may be a good phytotherapeutic agent against Plasmodium infection in malaria.