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  • PA-426 Genetic profiling of molecular markers of antimalarial resistance in areas targeted for school-based malaria chemoprevention strategies in North-Eastern, Tanzania

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PA-426 Genetic profiling of molecular markers of antimalarial resistance in areas targeted for school-based malaria chemoprevention strategies in North-Eastern, Tanzania
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  1. Vito Baraka1,
  2. Geofrey Makenga1,
  3. Filbert Francis1,
  4. Reginald A Kavishe2,
  5. Daniel TR Minja1,
  6. Didier Ménard3,4,5
  1. 1National Institute for Medical Research (NIMR), United Republic of Tanzania
  2. 2Kilimanjaro Clinical Research Institute (KCRI), Kilimanjaro Christian Medical College of Tumaini University, United Republic of Tanzania
  3. 3Institut Pasteur, Université Paris Cité, Malaria Genetic and Resistance Unit, France
  4. 4Institut Pasteur, Université Paris Cité, Malaria Parasite Biology and Vaccines, France
  5. 5Université de Strasbourg, Institute of Parasitology and Tropical Diseases, France

Abstract

Background Recently, WHO has recommended expansion of the malaria preventive chemotherapies to include intermittent preventive treatment of school children (IPTsc). However, there is concern due to the emergence and spread of partial artemisinin resistance based on PfKelch13 mutations in Eastern Africa. This study was conducted to determine the baseline prevalence of molecular markers of artemisinin-based combination therapies (ACTs) and Sulfadoxine-Pyrimethamine (SP) resistance prior to implementation of IPTsc intervention in a highly malaria endemic area.

Methods Pre-intervention assessment of the prevalence of molecular markers of artemisinin, partner drugs, SP resistance and Histidine Rich Protein 2/3 (HRP 2/3) genes deletion was conducted in Handeni and Kilindi districts from July 2020-December 2021. The districts implemented programmatic IPTsc trial using Dihydroartemisinin-Piperaquine. Dried Blood Spot were collected from children (5–15 years). DNA was extracted from malaria positive samples using commercial kits. NGS sequencing was used for the analysis of molecular markers.

Results Out of the SNPs detected at low frequency in the Pfkelch13 gene (A578S, K568T, N489Y), none have been validated as molecular markers of artemisinin partial resistance, majority 95.5% (340/356) was the wildtype. The majority of Pfcrt haplotype (n=356) was CVMNKTHFIMCGI (75.5%), other occurred at low frequency, CVIETTHFIMCGI (11.8%), CVIETTHFIMCGT (7%), SVMNTTHFIMCGI (0.8%), SVMNTTHFIMCGT(2.2%). Pfmdr1 haplotypes (n=355) NYSND (71.5%) and NFSND (20.6%) were predominant; others were at low frequency. Quintuple Pfdhfr-Pfdhps haplotypes (n=134) was at high frequency (70.1%). Parasites with HRP2 and 3 gene deletion was detected in 4.5% (15/335) and 20.9% (70/335), respectively.

Conclusion The lack of validated artemisinin resistance markers is reassuring and confirms targeted areas are suitable for malaria chemoprevention implementation. The baseline assessment is essential in implementing drug resistance monitoring during scaling up of the IPTsc intervention.

Funding: EDCTP-TMA2018CDF-2398 and co-supported by Global Fund, French Government, French Parasitology Alliance for Health Care (ANR-11–15 LABX-0024-PARAFRAP) and University of Strasbourg (IdEX 2022).

https://doi.org/10.1136/bmjgh-2023-EDC.196

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