Browsing by Author "Mosha, Dominic"

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    Effectiveness of intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy on placentalmalaria, maternal anaemia and birthweight in areas with highand low malaria transmission intensity in Tanzania
    (2014 John Wiley & Sons Ltd, 2014-09) Mosha, Dominic; Chilongola, Jaffu; Ndeserua, Rabi; Mwingira, Felista; Genton, Blaise
    objective To assess the effectiveness of IPTp in two areas with different malaria transmission intensities. methods Prospective observational study recruiting pregnant women in two health facilities in areas with high and low malaria transmission intensities. A structured questionnaire was used for interview. Maternal clinic cards and medical logs were assessed to determine drug intake. Placental parasitaemia was screened using both light microscopy and real-time quantitative PCR. results Of 350 pregnant women were recruited and screened for placental parasitaemia, 175 from each area. Prevalence of placental parasitaemia was 16.6% (CI 11.4–22.9) in the high transmission area and 2.3% (CI 0.6–5.7) in the low transmission area. Being primigravida and residing in a high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1–5.0; P = 0.025) and (OR 9.4; CI 3.2–27.7; P < 0.001), respectively. IPTp was associated with a lower risk of placental malaria (OR 0.3; CI 0.1–1.0; P = 0.044); the effect was more pronounced in the high transmission area (OR 0.2; CI 0.06–0.7; P = 0.015) than in the low transmission area (OR 0.4; CI 0.04–4.5; P = 0.478). IPTp use was not associated with reduced risk of maternal anaemia or low birthweight, regardless of transmission intensity. The number needed to treat (NNT) was four (CI 2–6) women in the high transmission area and 33 (20–50) in the low transmission area to prevent one case of placental malaria. conclusion IPTp may have an effect on lowering the risk of placental malaria in areas of high transmission, but this effect did not translate into a benefit on risks of maternal anaemia or low birthweight. The NNT needs to be considered, and weighted against that of other protective measures, eventually targeting areas which are above a certain threshold of malaria transmission to maximise the benefit.
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    Population Pharmacokinetics and Clinical Response for Artemether-Lumefantrine in Pregnant and Nonpregnant Women with Uncomplicated Plasmodium falciparum Malaria in Tanzania
    (American Society for Microbiology, 2014-07) Mosha, Dominic; Guidi, Monia; Mwingira, Felista; Abdulla, Salim; Mercier, Thomas; Decosterd, Laurent Arthur; Csajka, Chantal; Genton, Blaise
    ABSTRACT Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.