A Randomized, Controlled Trial of Intermittent Preventive Treatment with Sulfadoxine‐Pyrimethamine, Amodiaquine, or the Combination in Pregnant Women in Ghana

Clerk, Christine; Bruce, Jane; Affipunguh, Pius Kaba; Mensah, Nathan Kumasenu; Hodgson, Abraham; Greenwood, Brian; Chandramohan, Daniel

doi:10.1086/591944

Cited by 56 publications

(49 citation statements)

References 38 publications

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“…These findings may partially explain why IPTp-SP has demonstrated noninferiority against more potent antimalarial compounds in several randomized clinical trials of IPTp, particularly in studies measuring LBW and preterm birth as endpoints [20–24]. Sulfadoxine is a broad-spectrum antibiotic that likely exerts an inhibitory effect against nonmalaria causes of LBW and preterm birth [25].…”

Section: Discussionmentioning

confidence: 99%

Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections

Chico

Ariti

et al. 2017

Clinical Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections

Chico

Ariti

et al. 2017

Clinical Infectious Diseases

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“…Most studies of IPTp-SP efficacy have been done in areas with either minimal or very high prevalences of the quintuple mutant [15,25,28,29]. For example in Ghana where triple, but no quintuple mutations have been found, an in vivo study confirmed good efficacy of IPTp-SP [30,31]. In Benin where prevalence of the quintuple mutation was less than 10% prior to ITPp-SP treatment, one study found 11% of patients had parasitological failure at 1 month of follow up [32].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia

Tan

Katalenich

Mace

et al. 2014

Malar J

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BackgroundIntermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases adverse effects of malaria during pregnancy. Zambia implemented its IPTp-SP programme in 2003. Emergence of SP-resistant Plasmodium falciparum threatens this strategy. The quintuple mutant haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps genes), is associated with SP treatment failure in non-pregnant patients with malaria. This study examined efficacy of IPTp-SP and presence of the quintuple mutant among pregnant women in Mansa, Zambia.MethodsIn Mansa, an area with high malaria transmission, HIV-negative pregnant women presenting to two antenatal clinics for the 1st dose of IPTp-SP with asymptomatic parasitaemia were enrolled and microscopy for parasitaemia was done weekly for five weeks. Outcomes were parasitological failure and adequate parasitological response (no parasitaemia during follow-up). Polymerase chain reaction assays were employed to distinguish recrudescence from reinfection, and identify molecular markers of SP resistance. Survival analysis included those who had reinfection and incomplete follow-up (missed at least one follow-up).ResultsOf the 109 women included in the study, 58 (53%) completed all follow-up, 34 (31%) had incomplete follow-up, and 17 (16%) were lost to follow-up after day 0. Of those who had complete follow-up, 15 (26%, 95% confidence interval [CI] [16–38]) had parasitological failure. For the 92 women included in the survival analysis, median age was 20 years (interquartile range [IQR] 18–22), median gestational age was 22 weeks (IQR range 20–24), and 57% were primigravid. There was no difference in time to failure in primigravid versus multigravid women. Of the 84 women with complete haplotype data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50–70]) had quintuple mutants (two with an additional mutation in A581G of dhps). Among women with complete follow-up and quintuple mutants, 22% had parasitological failure versus 0% without (p = 0.44).ConclusionsWhile underpowered, this study found 26% failure rates of SP given the moderate prevalence of the quintuple mutant haplotype. Despite the presence of resistance, SP retained some efficacy in clearing parasites in pregnant women, and may remain a viable option for IPTp in Zambia.

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“…Where adverse events due to SP have been assessed in trials these have been seen in a high proportion of women 48% and 41% in Ghana [21], [22]. The side effects have included general body weakness, dizziness, vomiting, nausea, abdominal pain, diarrhoea, body itch, and body rash.…”

Section: Discussionmentioning

confidence: 99%

A Qualitative Health Systems Effectiveness Analysis of the Prevention of Malaria in Pregnancy with Intermittent Preventive Treatment and Insecticide Treated Nets in Mali

et al. 2013

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IntroductionDelivery of intermittent preventive treatment with sulphadoxine-pyrimethamine to pregnant women (IPTp-SP) through antenatal clinic (ANC) in Mali is low, and whilst ANC delivery of insecticide treated nets (ITNs) is higher, coverage is still below national and international targets. The aim of this study was to explain quantitative data from a related study which identified ineffective processes in the delivery of these interventions in one district in Mali.MethodsIn-depth interviews were conducted with health workers at the national, regional, district and health facility levels on their perceptions of reasons for the ineffective processes identified in the quantitative study, and their reported practices. Themes were coded for each ineffective process, and within these a health systems lens was used. Content analysis was used for emergent themes within this framework. MindMaps were used to display the findings.ResultsIntervention specific factors for the ineffective delivery of IPTp-SP included misunderstanding of the upper limit of the gestational age at which SP could be given and side effects of SP. Incorrect practices had been recommended in training and supervision of health workers. Pregnant women who were ill on attendance at ANC were not consistently managed across health facilities. The most common reason for not offering women an ITN on their first ANC visit was if they were from outside the health facility catchment area. Broader health systems issues influencing the effectiveness of delivery of each of these interventions were also identified.ConclusionIn this setting, intervention-specific factors resulted in the ineffective delivery of IPTp-SP. These relate to complex policy guidelines, lack of guidance on how to implement the guidelines, and the institutionalising of practices that undermine the national guidelines. Interventions may be implemented and show real gains in the shorter-term whilst waiting for broader health systems issues to be addressed.

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A Randomized, Controlled Trial of Intermittent Preventive Treatment with Sulfadoxine‐Pyrimethamine, Amodiaquine, or the Combination in Pregnant Women in Ghana

Abstract: Clinicaltrials.gov identifier: NCT00146783 .

Cited by 56 publications

References 38 publications

Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections

Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections

Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia

A Qualitative Health Systems Effectiveness Analysis of the Prevention of Malaria in Pregnancy with Intermittent Preventive Treatment and Insecticide Treated Nets in Mali

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