Substantial increase in mutations in the genes <i>pfdhfr</i> and <i>pfdhps</i> puts sulphadoxine–pyrimethamine‐based intermittent preventive treatment for malaria at risk in <scp>B</scp>urkina <scp>F</scp>aso

Geiger, Carolin; Compaoré, Guillaume; Coulibaly, Boubacar; Sié, Ali; Dittmer, Martin; Sánchez, Cecilia P.; Lanzer, Michael; Jänisch, Thomas

doi:10.1111/tmi.12305

Cited by 20 publications

(34 citation statements)

References 35 publications

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“…Both the Pfdhfr I164L and the Pfdhps K540E mutations were not detected in the present study, suggesting that these are still absent in Burkina Faso. This is consistent with previous reports in the country [17, 18, 22, 23, 28, 29] as well as in other settings in West Africa [8, 13, 14, 25]. However, a low proportion of Pfdhps K540E mutation (0.37%) has been recently reported in Mali [17].…”

Section: Discussionsupporting

confidence: 92%

“…The prevalence of Pfdhfr triple mutation N51I + C59R + S108N in the present study (25.7%) was low compared to the rates of 44.9 and 50% reported in pregnant women at the same period in Ziniaré [17] and in the general population [22], respectively. However, Tahita et al [18] reported a lower prevalence of 11.4% in pregnant women during the same period in Nanoro, a small town in Burkina Faso.…”

Section: Discussioncontrasting

confidence: 81%

“…However, Tahita et al [18] reported a lower prevalence of 11.4% in pregnant women during the same period in Nanoro, a small town in Burkina Faso. Those studies had been carried out in rural settings where malaria transmission is high and seasonal, mainly occurring during the months of August–December [17, 18, 22]. In Burkina Faso, SP had been used as second-line treatment before 2005, but was increasingly used as a first-line drug after chloroquine was discontinued in 2005, when artemisinin combination therapy (ACT) was not yet readily available [23, 24].…”

Section: Discussionmentioning

confidence: 99%

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Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

Cissé

Awandare

Soulama

et al. 2017

Malar J

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BackgroundThe impact of sulfadoxine–pyrimethamine (SP) used as intermittent preventive treatment during pregnancy (IPTp-SP) on mutant parasite selection has been poorly documented in Burkina Faso. This study sought first to explore the relationship between IPTp-SP and the presence of mutant parasites. Second, to assess the relationship between the mutant parasites and adverse pregnancy outcomes.Methods From September to December 2010, dried blood spots (DBS) were collected during antenatal care visits and at delivery from 109 pregnant women with microscopically confirmed falciparum malaria infection. DBS were analysed by PCR–restriction fragment length polymorphism (PCR–RFLP) for the polymorphisms at codons 51, 59, 108, and 164 of the Pfdhfr gene and codons 437 and 540 in the Pfdhps gene.ResultsBoth the Pfdhfr and Pfdhps genes were successfully genotyped in 92.7% (101/109) of the samples. The prevalence of Pfdhfr mutations N51I, C59R and S108N was 71.3, 42.6 and 64.4%, respectively. Overall, 80.2% (81/101) of samples carried the Pfdhps A437G mutation. None of the samples had the Pfdhfr I164L and the Pfdhps K540E mutations. The prevalence of the triple mutation N51I + C59R + S108N was 25.7% (26/101). The use of IPTp-SP was associated with a threefold increased odds of Pfdhfr C59R mutation [crude OR 3.29; 95% CI (1.44–7.50)]. Pregnant women with recent uptake of IPTp-SP were at higher odds of both the Pfdhfr C59R mutation [adjusted OR 4.26; 95% CI (1.64–11.07)] and the Pfdhfr intermediate-to-high resistance, i.e., ≥ 2 Pfdhfr mutations [adjusted OR 3.45; 95% CI (1.18–10.07)]. There was no statistically significant association between the presence of the Pfdhfr intermediate-to-high resistance and parasite densities or both maternal haemoglobin level and anaemia.ConclusionThe data indicate that despite the possibility that IPTp-SP contributes to the selection of resistant parasites, it did not potentiate pregnancy-associated malaria morbidity, suggesting the continuation of SP use as IPTp in Burkina Faso.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1695-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

Cissé

Awandare

Soulama

et al. 2017

Malar J

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“…[8][9][10] In east Africa, where resistance is the highest of sub-Saharan Africa, 11 the efficacy of IPTp-SP seems already compromised. 12-15 Therefore, it is important to explore alternative or additional preventive measures.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Malaria Screening during Pregnancy with Rapid Diagnostic Tests Performed by Community Health Workers in Burkina Faso

Ruizendaal

Schallig

Scott

et al. 2017

The American Journal of Tropical Medicine and Hygiene

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Abstract.One of the current strategies to prevent malaria in pregnancy is intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). However, in order for pregnant women to receive an adequate number of SP doses, they should attend a health facility on a regular basis. In addition, SP resistance may decrease IPTp-SP efficacy. New or additional interventions for preventing malaria during pregnancy are therefore warranted. Because it is known that community health workers (CHWs) can diagnose and treat malaria in children, in this study screening and treatment of malaria in pregnancy by CHWs was evaluated as an addition to the regular IPTp-SP program. CHWs used rapid diagnostic tests (RDTs) for screening and artemether-lumefantrine was given in case of a positive RDT. Overall, CHWs were able to conduct RDTs with a sensitivity of 81.5% (95% confidence interval [CI] 67.9-90.2) and high specificity of 92.1% (95% CI 89.9-93.9) compared with microscopy. After a positive RDT, 79.1% of women received artemether-lumefantrine. When treatment was not given, this was largely due to the woman being already under treatment. Almost all treated women finished the full course of artemether-lumefantrine (96.4%). In conclusion, CHWs are capable of performing RDTs with high specificity and acceptable sensitivity, the latter being dependent on the limit of detection of RDTs. Furthermore, CHWs showed excellent adherence to test results and treatment guidelines, suggesting they can be deployed for screen and treat approaches of malaria in pregnancy.BACKGROUND

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“…The WHO recommends IPTp with sulfadoxine-pyrimethamine (SP) at each ante-natal visit after the first trimester in moderate and high-malaria transmission regions [11]. Nevertheless, resistance to SP is widespread, especially in East Africa, and evidence from a study in Burkina Faso has shown that the use of SP in IPTp led to an increase in the prevalence of resistant infections from 1.3% in 2000 to 35.3% in 2009, and 54.3% in 2011 ( p ≤0.001) [12]. An additional concern is that SP is unsafe for administration during the first trimester of pregnancy [13–15].…”

Section: Introductionmentioning

confidence: 99%

Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa

et al. 2016

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BackgroundMalaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority.Methods and FindingsThis was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In general, the mean concentrations of serum AZ, plasma CQ, and plasma DECQ showed large CV% values (ranges of 33–156%, 42–228%, and 57–109%, respectively). There were 157 live births, three stillbirths, and eight pregnancies of unknown outcome: 7 due to withdrawal of participant consent and 1 lost to follow-up. The most frequent treatment-emergent adverse events were vomiting (20.8%) and dizziness (19.6%).ConclusionsThese results suggest that a 3-day course of AZCQ can lead to an adequate 28-day parasitological response.

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Substantial increase in mutations in the genes pfdhfr and pfdhps puts sulphadoxine–pyrimethamine‐based intermittent preventive treatment for malaria at risk in Burkina Faso

Cited by 20 publications

References 35 publications

Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

Evaluation of Malaria Screening during Pregnancy with Rapid Diagnostic Tests Performed by Community Health Workers in Burkina Faso

Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa

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