Lack of selection of antimalarial drug resistance markers after intermittent preventive treatment of schoolchildren (IPTsc) against malaria in northeastern Tanzania

Objective: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. Methods: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379). Results: The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, P=0.013), but no differences were observed between the treatment arms (χ2=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, P=0.32). Conclusions: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended

Lack of selection of antimalarial drug resistance markers after intermittent preventive treatment of schoolchildren (IPTsc) against malaria in northeastern Tanzania

Abstract: Objective: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. Methods: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13 , and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n = 74) and 20 months (visit 6, n = 364) after initiation of IPTsc and compared with the baseline prevalence (n = 379). Results: The prevalence of Pfmdr1 N86 and Pfexo 415G was > 99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (chi 2 = 6.11, P = 0.013), but no differences were observed between the treatment arms (chi 2 = 0.05, P = 0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (chi 2 = 0.98, P = 0.32). Conclusions: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Identification of the PfK13 mutations R561H and P441L in Democratic Republic of Congo (DRC).

BACKGROUND: Partial artemisinin resistance, mediated by P. falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa which are historically associated with high-level antimalarial resistance. DRC borders these areas in the East. OBJECTIVES: To determine the prevalence of resistance markers in six national malaria control programme (NMCP) surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi and Rutshuru. METHODS: The SNPs in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1 and Pfcrt were assessed using targeted NGS of isolates collected at enrolment in therapeutic efficacy studies. RESULTS: PfK13 SNPs were detected in two samples; in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced SP chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). CONCLUSIONS: R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed ACT-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal