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

Frederik Von Wowern, Geofrey Makenga, Sarah Wellmann Thomsen, Louise Wellmann Thomsen, Emma Filtenborg Hocke, Vito Baraka, Benjamin H. Opot, Daniel T.R. Minja, John P.A. Lusingu, Jean Pierre Van-geertruyden, Helle Hansson, Michael Alifrangis*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

4 Citationer (Scopus)
27 Downloads (Pure)

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%) (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.

OriginalsprogEngelsk
Artikelnummer107102
TidsskriftInternational Journal of Infectious Diseases
Vol/bind146
Antal sider6
ISSN1201-9712
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We thank the National Institute for Medical Research (NIMR) Director General and his staff for coordination of the study team and external stakeholders to the school health programme; NIMR Tanga Centre staff for their cordial support during the preparation and implementation of the study; Global Health Institute staff (Universiteit Antwerpen, Belgium) for their administrative and logistical support; Guilin Pharmaceuticals Tanzania for the donation of dihydroartemisinin\u2013piperaquine drugs (D-Artepp); Sarah J Ngede for her important work as a study clinician. We thank the schoolteachers, parents and guardians of children, the participants, the Muheza District officials, the District Medical Officer, and district school health coordinators, for their collaboration and support in the conduct of the study. We also thank stakeholders for the school health programme: The Ministry of Health; the Ministry of Education, Science and Technology; the President's Office-Regional Administration and Local Government and the National Malaria Control Programme (NMCP) for their cordial inputs with regard to the study implementation and policy. The study was funded by the Flemish Interuniversity Council (VLIRUOS), Belgium (TEAM initiative, grant number TZ2017TEA451A102). Additional funding was provided by the MaReCa project as part of the EDCTP2 programme supported by the EU (grant number TMA2015SF-998-MaReCa, awarded to JPAL). The study was granted ethical clearance by the Medical Research Coordinating Committee (MRCC, Tanzania) with approval number NIMR/HQ/R.8a/Vol.IX/2818 and NIMR/HQ/R.8c/Vol.I/668 (for amendment) also NIMR/HQ/R.8c/Vol.I/1276 for ethical clearance renewal. The regulatory approval was obtained from the Tanzania Medicines and Medical Devices Authority (TMDA) with approval number TFDA0017/CTR/0018/07. This study is registered with ClinicalTrials.gov, number NCT03640403. GM, JPAL, DTRM JPVG, HH and MA conceptualized the study and developed the study design. GM, VB and DTRM assisted in the recruitment of patients and collection of samples and reporting the characteristics of participants. FVW, SWT, LWT, BHO, EFH and HH performed the molecular analyses and validated the results. FVW, SWT, LWT, EFH, HH and MA performed the statistical and bioinformatics analysis of data and FVW, GMK, HH and MA drafted the manuscript. All authors read and approved the final draft of the manuscript.

Funding Information:
The study was funded by the Flemish Interuniversity Council (VLIRUOS) , Belgium (TEAM initiative, grant number TZ2017TEA451A102 ). Additional funding was provided by the MaReCa project as part of the EDCTP2 programme supported by the EU (grant number TMA2015SF-998- MaReCa , awarded to JPAL).

Publisher Copyright:
© 2024 The Author(s)

Citationsformater