Trends in Antimalarial Drug Use in Africa

Flegg, Jennifer A.; Metcalf, C. Jessica E.; Gharbi, Myriam; Venkatesan, Meera; Shewchuk, Tanya; Sibley, Carol Hopkins; Guérin, Philippe J.

doi:10.4269/ajtmh.13-0129

Cited by 45 publications

(40 citation statements)

References 26 publications

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“…Likewise, the temporal trends shown in Figure 5 (illustrating the proportion of sub-Saharan Africa with a predictive median dhps 540E prevalence exceeding various thresholds) will be related to both factors. For instance, the period of rapid increase in the temporal trends shown in Figure 5 corresponds to the years when the highest number of African countries were recommending SP as a first-line therapy [29]. An extension of this work will add SP drug pressure and national anti-malarial drug policy to inform more accurately the spatiotemporal spread of SP resistance.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum

Flegg

Patil

Venkatesan

et al. 2013

Malar J

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BackgroundPlasmodium falciparum has repeatedly evolved resistance to first-line anti-malarial drugs, thwarting efforts to control and eliminate the disease and in some period of time this contributed largely to an increase in mortality. Here a mathematical model was developed to map the spatiotemporal trends in the distribution of mutations in the P. falciparum dihydropteroate synthetase (dhps) gene that confer resistance to the anti-malarial sulphadoxine, and are a useful marker for the combination of alleles in dhfr and dhps that is highly correlated with resistance to sulphadoxine-pyrimethamine (SP). The aim of this study was to present a proof of concept for spatiotemporal modelling of trends in anti-malarial drug resistance that can be applied to monitor trends in resistance to components of artemisinin combination therapy (ACT) or other anti-malarials, as they emerge or spread.MethodsPrevalence measurements of single nucleotide polymorphisms in three codon positions of the dihydropteroate synthetase (dhps) gene from published studies of dhps mutations across Africa were used. A model-based geostatistics approach was adopted to create predictive surfaces of the dhps540E mutation over the spatial domain of sub-Saharan Africa from 1990-2010. The statistical model was implemented within a Bayesian framework and hence quantified the associated uncertainty of the prediction of the prevalence of the dhps540E mutation in sub-Saharan Africa.ConclusionsThe maps presented visualize the changing prevalence of the dhps540E mutation in sub-Saharan Africa. These allow prediction of space-time trends in the parasite resistance to SP, and provide probability distributions of resistance prevalence in places where no data are available as well as insight on the spread of resistance in a way that the data alone do not allow. The results of this work will be extended to design optimal sampling strategies for the future molecular surveillance of resistance, providing a proof of concept for similar techniques to design optimal strategies to monitor resistance to ACT.

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Section: Discussionmentioning

confidence: 99%

Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum

Flegg

Patil

Venkatesan

et al. 2013

Malar J

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“…The malaria mortality rate is 63 per 100,000 population, and amongst the highest in East Africa [3] despite the roll out of control measures, such as insecticide-treated bed nets (ITNs), intensive indoor residual spraying (IRS), and artemisinin-based combination therapy (ACT) [2]. As one of the first African countries to switch from chloroquine to sulfadoxine/pyrimethamine (SP) in 1993, and the last to switch from SP to ACT in 2007, Malawi stands out from the rest of Africa in having a significantly prolonged exposure to SP [4]. Whilst this meant the reduced frequency of chloroquine resistance alleles in the Plasmodium population [5], the same cannot currently be said for SP resistance [6].…”

Section: Introductionmentioning

confidence: 99%

Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi

Ravenhall

Benavente

Mipando

et al. 2016

Malar J

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BackgroundMalawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.MethodsWhole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.ResultsPositive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.ConclusionsSP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1634-6) contains supplementary material, which is available to authorized users.

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“…() show in several pilot studies that there were large increases in ACT availability and market share driven mainly by changes in the private for‐profit sector. This is an important initiative because “CQ and SP are up to 25 times less expensive than an ACT” (Flegg et al., , p. 863). Even traditional healers “command fees exceeding the average treatment cost at most modern practitioners” (Leonard, ).…”

Section: Resultsmentioning

confidence: 99%

“…Especially beginning in 2004, most African countries have transitioned to artemisinin-based combination therapies (ACTs), with South Africa beginning in 2001. Although Malawi was the first in this region to transition out of CQ in 1993 (CQ was replaced with SP as the first-line treatment), it was the last to adopt ACTs together with Botswana in 2007 (Flegg et al, 2013). The sub-Saharan and West African countries included in this study have all adopted artemisinin-based therapies in recent years.…”

Section: Introductionmentioning

confidence: 99%

Biting Back at Malaria: Assessing Health‐service Providers' Compliance with Treatment Guidelines

Paloyo

Reichert

2016

Review Development Economics

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Non‐compliance with established medical treatment guidelines can have dire consequences for public health and economic well‐being. Based on the Demographic and Health Surveys, we examine malaria‐treatment practices of various health‐care providers in sub‐Saharan Africa, where more than 90% of malaria‐induced deaths occur. We estimate each provider's likelihood (i) to comply with guidelines to administer (effective) antimalarial drugs and (ii) to relieve children of fever—a symptom of malaria—after having had a fever episode within the previous two weeks. Our results indicate that, relative to self‐medication, seeking treatment at most providers is positively associated with taking an antimalarial drug and negatively associated with using only ineffective chloroquine. Non‐traditional healers are also associated with fever relief.

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Trends in Antimalarial Drug Use in Africa

Cited by 45 publications

References 26 publications

Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum

Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum

Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi

Biting Back at Malaria: Assessing Health‐service Providers' Compliance with Treatment Guidelines

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