Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali

Maiga, Hamma; Lasry, Estrella; Diarra, Modibo; Sagara, Issaka; Bamadio, Amadou; Traoré, Aliou; Coumare, Samba; Bahonan, Soma; Sangare, Boubou; Dicko, Yeyia; Diallo, Nouhoum; Tembely, Aly; Traoré, Djibril; Niangaly, Hamidou; Dao, François; Haidara, Aboubecrine Sedhigh; Dicko, Alassane; Doumbo, Ogobara K.; Djimdé, Abdoulaye

doi:10.1371/journal.pone.0162718

Cited by 39 publications

(37 citation statements)

References 35 publications

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“…Here resistance remains a major concern, and studies are examining the impact of SMC campaigns on the prevalence of SP resistance in local parasite populations 66 . Recently, a next-generation DHFR inhibitor, P218, has been designed that has pyrimidine side-chain flexibility and additional binding features that render it equally effective at inhibiting DHFR isoforms that are wild type or quadruple mutants.…”

Section: Resistance To Antifolatesmentioning

confidence: 99%

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Blasco

Leroy

Fidock

2017

Nat Med

441

419

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The global adoption of artemisinin-based combination therapies (ACTs) in the early 2000s heralded a new era in effectively treating drug-resistant Plasmodium falciparum malaria. However, several Southeast Asian countries have now reported the emergence of parasites that have decreased susceptibility to artemisinin (ART) derivatives and ACT partner drugs, resulting in increasing rates of treatment failures. Here we review recent advances in understanding how antimalarials act and how resistance develops, and discuss new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria.

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Section: Resistance To Antifolatesmentioning

confidence: 99%

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Blasco

Leroy

Fidock

2017

Nat Med

441

419

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“…Attempts to implement mass treatment in endemic communities SMC are presently limited to children under 5 in the Sahelian region of Africa. SMC has been shown to reduce the burden of malaria in children below 5 years in Senegal, Mali and Burkina Faso and has further been proven to be affordable if extended to 10 year old children [29,[37][38][39][40]. While SMC has targeted the Sahelian region with marked seasonal transmission, strategies for reducing malaria parasitaemia towards elimination in other endemic transmission areas of Africa, which cover the broader population are needed.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Cheng

Okyere

Enos

et al. 2019

Preprint

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Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Intermittent Preventive Treatment and Test, Treat and Track (T3) using ACTs. Intermittent preventive treatment of children (IPTc) in Ghana has demonstrated a parasite load reduction of 90%. However, unanswered questions include – whether mass treatment of population sub-groups such as IPTc could be scaled-up to whole populations as in mass testing, treatment and tracking (MTTT)? What is needed to implement MTTT at scale? Can MTTT reduce asymptomatic parasitaemia levels in children under 15? And whether MTTT of populations complemented by community-based management of malaria (CBMm) using volunteers could be an effective strategy for malaria control at a lower cost. Methods: A population of 5,000 asymptomatic individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers (CBHVs) who conducted house-to-house testing using RDTs every four months and treated positive cases with ACTs. Between interventions, CBMm was done on symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 1,795 (36.3%) in July 2017 to 1,303 (32.9%) in July 2018. Implementing MTTT significantly averted asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and temperature (OR=0.76, CI=0.67, 0.85 p ≤ 0.001). In comparison, treatment of symptomatic patients at the Health Centre reduced parasitaemia by 9% over the same period which was however, not statistically significant (OR=0.91, CI=0.67, 1.38 p = 0.672). A total of 223 (5.1%) cases were averted in children under 15 years (X² = 9.7, p < 0.002). An important observation was a decrease in hospital attendance, which negatively affected the internally generated funds (IGF) scheme of the participating health facilities. Conclusion: This study has demonstrated that implementing MTTT was feasible and could reduce prevalence of malaria asymptomatic parasitaemia in children under 15 years of age. Furthermore, the use of CBHVs could ensure high coverage at lower cost.

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“…As reported in other studies [9,23,24], a major concern with the use of SMC is an increase in the proportion of parasites carrying AQ and SP resistance-mediating polymorphisms, jeopardizing the future of malaria prevention and control. However, it is not yet well established whether the prophylactic failure of SMC is associated with emergence of resistance.…”

Section: Discussionmentioning

confidence: 76%

Investigating host and parasite factors surrounding seasonal malaria chemoprevention in Bama, Burkina Faso

Somé¹,

Bazié²,

Hanna³

et al. 2020

Preprint

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Background: Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. We report in this paper the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under five years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC. Methods: Two sequential cross-sectional surveys were carried out in the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 and 93 children under five, respectively, at the start of SMC and again three weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethyl-amodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility. Results: 2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p=0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95%CI=10.0-24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3. Conclusion: This study showed a moderate prevalence of low-level malaria parasitemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. Our findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.

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Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali

Cited by 39 publications

References 35 publications

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Investigating host and parasite factors surrounding seasonal malaria chemoprevention in Bama, Burkina Faso

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