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Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

ABSTRACT: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted.Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02).The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

SUBMITTER: Desai M

PROVIDER: S-EPMC4762476 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

Desai Meghna M Gutman Julie J Taylor Steve M SM Wiegand Ryan E RE Khairallah Carole C Kayentao Kassoum K Ouma Peter P Coulibaly Sheick O SO Kalilani Linda L Mace Kimberly E KE Arinaitwe Emmanuel E Mathanga Don P DP Doumbo Ogobara O Otieno Kephas K Edgar Dabira D Chaluluka Ebbie E Kamuliwo Mulakwa M Ades Veronica V Skarbinski Jacek J Shi Ya Ping YP Magnussen Pascal P Meshnick Steve S Ter Kuile Feiko O FO

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20151020 3

<h4>Background</h4>Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.<h4>Methods</h4>Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites ...[more]

PMID: 26486699

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Project description:BackgroundIntermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy.MethodsThe cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women's loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken.ResultsFor HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet.ConclusionsAddition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price.Trials registrationClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440.

Project description:Malaria in pregnancy poses a great risk to both mother and fetus. In Ghana, malaria accounts for 3.4% of deaths and 16.8% of all hospital admissions in pregnant women. In 2014, Ghana updated her policy on intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to reflect the updated policy of the WHO. This study determined the level of uptake of sulfadoxine pyrimethamine (SP) to serve as baseline for monitoring progress and also reviewed stock levels of SP, a key factor in the programme implementation.A cross-sectional hospital-based study was carried out among nursing mothers who had delivered within 12 weeks and were seeking postnatal care at Osu Government Maternity Home in Accra. Antenatal record books of the mothers were reviewed and data collected on number of visits and receipt of IPTp-SP. Mothers were interviewed and data collected on their background characteristics and obstetric history. Data on SP stock levels for the past 6 months were also reviewed. Logistic regression analysis was carried out to determine antenatal indicators on uptake of IPTp-SP using Stata version 12.The proportion of uptake of three-five doses of SP were: IPT3 (87.5%), IPT4 (55.7%) and IPT5 (14.5%). The proportion of women who received the first dose of SP at 16 weeks of gestation was 21.3%. Women who made ≥4 visits were more likely to receive ≥3 doses of SP than those who made <4 visits (AOR = 4.57, 95% CI 1.15-18.16, p < 0.05). Women receiving the first dose of SP in the third trimester were less likely to receive ≥3 doses of SP than those who received the drug in the second trimester (AOR = 0.04, 95% CI 0.01-0.16, p < 0.05). Stock levels of SP were adequate to meet the demands by the pregnant women at the Maternity Home for the period under review.The uptake of ≥3 doses of SP was high in the study area. Frequent visits to the antenatal clinic and early uptake of the first dose of SP by pregnant women are necessary to achieve the new target of five or more doses of SP.

Dataset Information

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

Publications

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

Similar Datasets

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