Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal

ABSTRACT Dihydroartemisinin-piperaquine (DHA-PQ) is under study for intermittent preventive treatment during pregnancy (IPTp), but it may accelerate selection for drug resistance. Understanding the relationships between piperaquine concentration, prevention of parasitemia, and selection for decreased drug sensitivity can inform control policies and optimization of DHA-PQ dosing. Piperaquine concentrations, measures of parasitemia, and Plasmodium falciparum genotypes associated with decreased aminoquinoline sensitivity in Africa (pfmdr1 86Y, pfcrt 76T) were obtained from pregnant Ugandan women randomized to IPTp with sulfadoxine-pyrimethamine (SP) or DHA-PQ. Joint pharmacokinetic/pharmacodynamic models described relationships between piperaquine concentration and the probability of genotypes of interest using nonlinear mixed effects modeling. An increase in the piperaquine plasma concentration was associated with a log-linear decrease in risk of parasitemia. Our models predicted that higher median piperaquine concentrations would be required to provide 99% protection against mutant infections than against wild-type infections (pfmdr1: N86, 9.6 ng/ml; 86Y, 19.6 ng/ml; pfcrt: K76, 6.5 ng/ml; 76T, 19.6 ng/ml). Comparing monthly, weekly, and daily dosing, daily low-dose DHA-PQ was predicted to result in the fewest infections and the fewest mutant infections per 1,000 pregnancies (predicted mutant infections for pfmdr1 86Y: SP monthly, 607; DHA-PQ monthly, 198; DHA-PQ daily, 1; for pfcrt 76T: SP monthly, 1,564; DHA-PQ monthly, 283; DHA-PQ daily, 1). Our models predict that higher piperaquine concentrations are needed to prevent infections with the pfmdr1/pfcrt mutant compared to those with wild-type parasites and that, despite selection for mutants by DHA-PQ, the overall burden of mutant infections is lower for IPTp with DHA-PQ than for IPTp with SP. (This study has been registered at ClinicalTrials.gov under identifier NCT02282293.)

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Faculty Opinions recommendation of Antimalarial drug resistance in Africa: the calm before the storm?

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736337650.793573187 ◽

2020 ◽

Author(s):

Toshihiro Horii ◽

Nirianne Palacpac

Keyword(s):

Drug Resistance ◽

Antimalarial Drug ◽

Antimalarial Drug Resistance

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Antimalarial drug resistance: the pace quickens

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/30.5.571 ◽

1992 ◽

Vol 30 (5) ◽

pp. 571-585 ◽

Cited By ~ 157

Author(s):

N. J. White

Keyword(s):

Drug Resistance ◽

Antimalarial Drug ◽

Antimalarial Drug Resistance

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Malaria intermittent preventive treatment in Nigeria: a qualitative study to explore barriers

BMC Infectious Diseases ◽

10.1186/s12879-021-06135-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fatima Mahmud Muhammad ◽

Saharnaz Nedjat ◽

Haniye Sadat Sajadi ◽

Mahboubeh Parsaeian ◽

Abraham Assan ◽

...

Keyword(s):

Qualitative Study ◽

Pregnant Women ◽

Intermittent Preventive Treatment ◽

Sampling Strategy ◽

Preventive Treatment ◽

Group Discussions ◽

Content Analysis Method ◽

Conventional Content Analysis ◽

Sulphadoxine Pyrimethamine ◽

Selection Of

Abstract Background While the use of sulphadoxine pyrimethamine (SP) is effective in preventing malaria infection during pregnancy, there are challenges limiting its uptake in Nigeria. This study aimed at exploring the barriers to IPTp usage among pregnant women in Kano state - Nigeria. Methods This is a qualitative study. The purposive sampling strategy was used for identification and selection of 14 key informants for interviews. In addition, six focus group discussions (FGDs) were conducted with pregnant women (3 FGDs) and married men (3 FGDs). The conventional content analysis method was used to interpret meaning from the content of the data. MAXQDA 10 software was used for data management and analysis. Results Poor policy implementation, poor antenatal care attendance, inadequate access to intermittent preventive treatment at the community levels, lack of sustainable funding, and poor community engagement emerged as major barriers to IPTp use in Nigeria. Conclusion While the political will to allocate sufficient financial resources could help improve service delivery and IPTp usage among pregnant women, community participation is critical to sustain the gains.

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