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IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women.

ABSTRACT: Tumour necrosis factor (TNF) and interferon gamma (IFN-?), encoded by TNF-836 C/A (rs 1800630) and IFN-? -1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. The aim of this study was to investigate the relationship between TNF-836 C/A and IFN-?-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women.A prospective cohort (cross-sectional) study was conducted in pregnant women attending the out-patient clinic in King Fahad Specialist Hospital in Jazan (KFSHJ), with a clinical diagnosis of malaria. A total of one hundred and eighty six pregnant women were genotyped for single nucleotide polymorphism (SNP) for TNF and IFN-? using Taqman® MGB Probes. Serum cytokine concentrations were measured by sandwich ELISA method.A hospital case-control study of severe malaria in a Saudi population identified strong associations with individual single-nucleotide polymorphisms in the TNF and IFN-? genes, and defined TNF-836 C and IFN-?-1616 T genotypes and alleles which were statistically significantly associated with severe malaria infection. Furthermore, TNF-836 CC and IFN-?-1616 TT genotypes were associated with higher serum concentration of TNF and IFN-?, respectively, and with susceptibility to severe malaria.This data provides a starting point for functional and genetic analysis of the TNF and IFN-? genomic region in malaria infection affecting Saudi populations.

SUBMITTER: Nasr A

PROVIDER: S-EPMC4137072 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women.

Nasr Amre A Allam Gamal G Hamid Osama O Al-Ghamdi Abdelhamid A

Malaria journal 20140813

<h4>Background</h4>Tumour necrosis factor (TNF) and interferon gamma (IFN-γ), encoded by TNF-836 C/A (rs 1800630) and IFN-γ -1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. The aim of this study was to investigate the relationship between TNF-836 C/A and IFN-γ-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women.<h4>Methods</h4>A prospective cohort (cross-sectional) study was conducte ...[more]

PMID: 25124540

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Project description:BACKGROUND:Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS:Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS:P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. CONCLUSIONS:Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites.

Project description:BACKGROUND:Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. METHODS:Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies. RESULTS:The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches. CONCLUSION:The population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated P. falciparum malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group.

Project description:BackgroundPregnant women living in an area of stable malaria transmission such as Lagos, Nigeria, have been identified as being at an increased risk of the effects of malaria infection. In this area, most of the infections are asymptomatic which means they are overlooked and untreated much to the detriment of the mother and her foetus. The reality of scaled-up malaria interventions with long-lasting insecticide treated nets, vector control, artemisinin combination therapy (ACT) and intermittent preventive treatment of malaria pregnancy (IPTp) using sulphadoxine pyrimethamine (SP) is that it is also essential to determine the risk factors at play in these kinds of circumstances. This study was aimed at identifying the factors associated with risk of malaria infection in pregnant women in Lagos, Southwest Nigeria.MethodsDemographic information and malaria prevention practices of the pregnant women studied were captured using structured questionnaire. Microscopy was used to establish malaria infection, species identification and parasite density. Relative risk and multivariate logistic regression analysis were used to compare factors associated with malaria in pregnant women.ResultsMalaria microscopy details, demographic information and malaria prevention practices of the pregnant women were obtained using a structured questionnaire. The prevalence of malaria using peripheral blood from 1,084 pregnant women that participated in the study was 7.7%. Plasmodium falciparum (P. falciparum) was seen in 95.2% of the cases as either mixed infection with P. malariae (3.6%) or as a mono infection (91.6%). Malaria preventive practices associated with a significant reduction (P<0.05) in the malaria infection was the use of insecticide sprays (RR = 0.36, 95 C.I. 0.24-0.54), and the combined use of insecticide spray and insecticide-treated nets (ITN) (RR= 6.53, 95% C.I. 0.92-46.33). Sleeping under ITN alone (RR = 1.07, 95% C.I. 0.55-2.09) was not associated with significant reduction in malaria infection among the study participants with malaria parasitaemia. Young maternal age (<20years) (RR = 2.86, 95% C.I. 1.48 - 5.50), but not primigravidity (RR = 1.36, 95% C.I. 0.90-2.05), was associated with an increased risk of malaria infection during pregnancy. After a multivariate logistic regression, young maternal age (OR = 2.61, 95% C.I. 1.13 - 6.03) and the use of insecticide spray (OR = 0.38, 95% C.I. 0.24-0.63) were associated with an increase and a reduction in malaria infection, respectively.ConclusionMalaria prevalence was low among the pregnant women studied. Young maternal age and non-usage of insecticidal spray were the main factors associated with an increased risk of malaria infection among pregnant women in Lagos, Nigeria.

Dataset Information

IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women.

Publications

IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women.

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