Evaluation of the adhesion of pregnant women to intermittent presumptive treatment with Sulfadoxine-Pyrimethamine in a rural area of Gabon.

Background: Gestational malaria remains one of the most complex forms of malaria. To fight it, several African countries adopted intermittent presumptive treatment with Sulfadoxine-Pyrimethamine (IPT-SP) and the use of preventive measures such as insecticide-treated bed nets (ITNs), indoor residual sprays (IRS) and popular education on good practices to fight against malaria. In Gabon a country of central Africa, no study has investigated the use of IPT-SP in rural areas since its implementation. The aim of this study was to investigate the adhesion level of pregnant women to IPT-SP, coverage of ITNs and IRS, and knowledge on the good practices about malaria in a rural area of Gabon. Using a questionnaire, we led a retrospective study including pregnant women from January 5th 2016 to January 31st 2018 and a cross-sectional survey including women seen for antenatal care and all febrile patients in consultation from February 2nd to May 31st 2018. Malaria was diagnosed using rapid diagnostic tests. Statistical analyses were done. Results: We included 607 pregnant women before their delivery. Women between 20 and 25 years old were the most prevalent (37.26%, n=229). Among them, 74.53% were unemployed and 47.21% living in the villages surrounding the rural town of Fougamou. The rate of adhesion to IPT-SP was 94.37% (n=573). Among them, 47.8% (n=274) had received 3 doses of IPT. Among the pregnant women included during the cross-sectional survey, only 8.7% (n=14) were infected with Plasmodium. Bed nets were used by 80.12% (n=129) of women. Conclusion: Data showed a near complete adhesion of IPT-SP in the rural area of Fougamou. Clinical trials are needed to investigate the efficacy of IPT-SP and antimalarial drug markers.

Pharmacokinetics of Chloroquine and Monodesethylchloroquine in Pregnancy

ABSTRACT In order to determine the pharmacokinetic disposition of chloroquine (CQ) and its active metabolite, desethylchloroquine (DECQ), when administered as intermittent presumptive treatment in pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were administered three daily doses of 450 mg CQ (8.5 mg/kg of body weight/day) in addition to a single dose of sulfadoxine-pyrimethamine. For all women, blood was taken at baseline; at 1, 2, 4, 6, 12, 18, 24, 30, 48, and 72 h posttreatment; and at 7, 10, 14, 28, and 42 days posttreatment. Plasma was subsequently assayed for CQ and DECQ by high-performance liquid chromatography, and population pharmacokinetic modeling was performed. Pregnant subjects had significantly lower area under the plasma concentration-time curve for both CQ (35,750 versus 47,892 μg·h/liter, P < 0.001) and DECQ (23,073 versus 41,584 μg·h/liter, P < 0.001), reflecting significant differences in elimination half-lives and in volumes of distribution and clearances relative to bioavailability. Reduced plasma concentrations of both CQ and DECQ could compromise both curative efficacy and posttreatment prophylactic properties in pregnant patients. Higher IPTp CQ doses may be desirable but could increase the risk of adverse hemodynamic effects.

Pharmacokinetic Properties of Sulfadoxine-Pyrimethamine in Pregnant Women

ABSTRACT To determine the pharmacokinetic disposition of sulfadoxine (SDOX) and pyrimethamine (PYR) when administered as intermittent presumptive treatment during pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were given a single dose of 1,500 mg of SDOX plus 75 mg of pyrimethamine PYR. Blood was taken at baseline and 1, 2, 4, 6, 12, 18, 24, 30, 48, and 72 h and at 7, 10, 14, 28, and 42 days posttreatment in all women. Plasma samples were assayed for SDOX, N-acetylsulfadoxine (NASDOX), and PYR by high-performance liquid chromatography. Population pharmacokinetic modeling was performed using NONMEM v6.2.0. Separate user-defined mamillary models were fitted to SDOX/NASDOX and PYR. When the covariate pregnancy was applied to clearance, there was a significant improvement in the base model for both treatments. Pregnancy was associated with a significantly lower area under the concentration-time curve from 0 to ∞ for SDOX (22,315 versus 33,284 mg·h/liter), NASDOX (801 versus 1,590 mg·h/liter), and PYR (72,115 versus 106,065 μg·h/liter; P < 0.001 in each case). Because lower plasma concentrations of SDOX and PYR could compromise both curative efficacy and posttreatment prophylaxis in pregnant patients, IPTp regimens incorporating higher mg/kg doses than those recommended for nonpregnant patients should be considered.