Anti-malarial resistance in Mozambique: Absence of Plasmodium falciparum Kelch 13 (K13) propeller domain polymorphisms associated with resistance to artemisinins

Authors: Clemente da Silva, Daniela Matias, Brigite Dias, Beatriz Cancio, Miguel Silva, Ruben Viegas, Nordino Chivale, Sonia Luis, Crizolgo Salvador, Denise Duarte, Paulo Arnaldo, Sonia Enosse, Fatima Nogueira

Although the results of this cross-sectional study do not show the emergence of artemisinin resistance in Mozambique, the high number of novel, non-synonymous mutations identified highlights the need for continued molecular surveillance for early detection.

Background

Malaria remains one of the most serious public health problems in sub-Saharan Africa and Mozambique is the world's fourth largest contributor, with 4.7 percent of disease cases and 3.6 percent of total deaths due to malaria. Its control relies on the fight against the vector and treatment of confirmed cases with antimalarial drugs. Molecular surveillance is an important tool for monitoring the spread of antimalarial drug resistance.

Methods

A cross-sectional study recruited 450 participants with malaria infection detected by rapid diagnostic tests, from three different study sites (Niassa, Manica and Maputo) between April and August 2021. Correspondent blood samples were collected on filter paper (Whatman® FTA® cards), parasite DNA extracted and pfk13 gene sequenced using Sanger method. SIFT software (Sorting Intolerant From Tolerant) was used to predict whether an amino acid substitution affects protein function.

Results

No pfkelch13-mediated artemisinin resistance gene mutation was detected in this study settings. However, non-synonymous mutations were detected at prevalence of 10.2 percent, 6 percent and 5 percent in Niassa, Manica and Maputo, respectively. Most (56.3 percent) of the reported non-synonymous mutations were due to substitution at the first base of the codon, 25 percent at the second base and 18.8 percent at the third base. Additionally, 50 percent of non-synonymous mutations showed a SIFT score bellow the cut-off value of 0.05, therefore, they were predicted to be deleterious.

Conclusion

These results do not show an emergence of artemisinin resistance cases in Mozambique. However, the increased number of novel non-synonymous mutations highlights the relevance of increasing the number of studies focused on the molecular surveillance of artemisinin resistance markers, for its early detection.

Published in Malaria Journal

Citation: Malaria Journal, 2023; 22: 160.