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Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

ABSTRACT: Ex vivo assays are usually carried out on parasite isolates collected from patients with uncomplicated Plasmodium falciparum malaria, from which pregnant women are usually excluded as they are often asymptomatic and with relatively low parasite densities. Nevertheless, P. falciparum parasites infecting pregnant women selectively sequester in the placenta and may have a different drug sensitivity profile compared to those infecting other patients. The drug sensitivity profile of P. falciparum isolates from infected pregnant women recruited in a treatment efficacy trial conducted in Burkina Faso was determined in an ex vivo study.The study was conducted between October 2010 and December 2012. Plasmodium falciparum isolates were collected before treatment and at the time of any recurrent infection whose parasite density was at least 100/µl. A histidine-rich protein-2 assay was used to assess their susceptibility to a panel of seven anti-malarial drugs. The concentration of anti-malarial drug inhibiting 50% of the parasite maturation to schizonts (IC(50)) for each drug was determined with the IC Estimator version 1.2.The prevalence of resistant isolates was 23.5% for chloroquine, 9.2% for mefloquine, 8.0% for monodesethylamodiaquine, and 4.4% for quinine. Dihydroartemisinin, mefloquine, lumefantrine, and monodesethylamodiaquine had the lowest mean IC(50) ranging between 1.1 and 1.5 nM respectively. The geometric mean IC(50) of the tested drugs did not differ between chloroquine-sensitive and resistant parasites, with the exception of quinine, for which the IC(50) was higher for chloroquine-resistant isolates. The pairwise comparison between the IC(50) of the tested drugs showed a positive and significant correlation between dihydroartemisinin and both mefloquine and chloroquine, between chloroquine and lumefantrine and between monodesethylamodiaquine and mefloquine.These ex vivo results suggest that treatment with the currently available artemisinin-based combinations is efficacious for the treatment of malaria in pregnancy in Burkina Faso.ClinicalTrials.gov ID: NCT00852423.

SUBMITTER: Tahita MC

PROVIDER: S-EPMC4474342 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

Tahita Marc C MC Tinto Halidou H Yarga Sibiri S Kazienga Adama A Traore Coulibaly Maminata M Valea Innocent I Van Overmeir Chantal C Rosanas-Urgell Anna A Ouedraogo Jean-Bosco JB Guiguemde Robert T RT van Geertruyden Jean-Pierre JP Erhart Annette A D'Alessandro Umberto U

Malaria journal 20150620

<h4>Background</h4>Ex vivo assays are usually carried out on parasite isolates collected from patients with uncomplicated Plasmodium falciparum malaria, from which pregnant women are usually excluded as they are often asymptomatic and with relatively low parasite densities. Nevertheless, P. falciparum parasites infecting pregnant women selectively sequester in the placenta and may have a different drug sensitivity profile compared to those infecting other patients. The drug sensitivity profile o ...[more]

PMID: 26088768

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Project description:BackgroundMalaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region.MethodsTwo cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis.ResultsA total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine-pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14-0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39-0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31-4.91, p = 0.006).ConclusionsThe prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.

Project description:BACKGROUND: Malaria during pregnancy remains a serious public health problem. The aim of this study was to determine the prevalence and possible risk factors for malaria in pregnant women attending antenatal clinic at two primary health facilities in Bobo-Dioulasso. METHODS: We conducted a cross sectional study from September to December 2010 in two primary health facilities located in the periurban area of Bobo-Dioulasso. Pregnant women attending antenatal clinic (ANC) were included in the study after signing informed consent. For each participant, the social-demographic profile, malaria and obstetric histories were investigated through a questionnaire. Peripheral blood was collected and thick and thin blood smears were prepared to check Plasmodium falciparum parasitaemia. Hemoglobin concentration was measured. The associations between age, parity, gestational age, schooling, number of ANC visits, use of IPTp-SP, use of insecticide-treated nets (ITN) and anemia with the occurrence of P. falciparum malaria infection during pregnancy were analyzed through logistic regression. RESULTS: During the period of study, 105 (18.1%) out of 579 pregnant women were infected by P. falciparum. The hemoglobin concentration mean was 10.5?±?1.7/dL and was significantly lower in pregnant women with malaria infection (9.8 g/dL ±1.6) than in those who had no malaria infection (10.6 g/dL ±1.7) (P?<?0.001). Multivariate analysis indicated that, education (AOR 1.9, 95% CI?=?[1.2-3.2]), parity [primigravidae (AOR 5.0, 95% CI?=?[2.5-9.8]) and secundigravidae (AOR 2.1, 95% CI?=?[1.2-3.8])], and anaemia (AOR 2.1, 95% CI?=?[1.3-3.5]) were significantly associated with P. falciparum malaria infection. The use of IPTp-SP was not associated with P. falciparum malaria infection. CONCLUSIONS: P. falciparum malaria infection is common in pregnant women attending antenatal clinic and anaemia is an important complication. The results show that the use of IPTp-SP does not reduce the risk of malaria incidence during pregnancy.

Project description:BackgroundInvestigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso.MethodsBlood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction.ResultsIn the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation.ConclusionsIn high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.

Project description:Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women, resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver status (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development, especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008).

Dataset Information

Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

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Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

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