Emerging Plasmodium falciparum K13 gene mutation to artemisinin-based combination therapies and partner drugs among malaria-infected population in sub-Saharan Africa
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The continuous Plasmodium falciparum kelch13 (PfK13) genetic alterations conferring resistance to artemisinin-based combination therapies and partner drugs pose a significant threat to effective treatment and control of P. falciparum infection in developing countries. This review evaluates the emergence and epidemiology of the PfK13 mutation associated with artemisinin resistance in the sub-Saharan Africa (SSA) population. Despite empirical control and artemisinin combination therapy, the PfK13 gene mutation, previously described in Southeast Asia, has been reported in the SSA. Eight of these validated markers, including P553L, M476I, C580Y, A675V, P574L, R561H, R622I, and F446I, were reported among the SSA population. Novel and unvalidated markers, such as P615S, M472I, F434S, A578S, P570L, Y558C, K563R, A569T, I684N, M472I, and C473F spread among the population with low frequency. We provide insight into the emergence and spread of validated and unvalidated PfK13 mutations among the SSA population, which could lead to high artemisinin resistance. Investigating the verified PfK13 mutations will improve prophylactic strategies, prognostic diagnosis and guide effective population-based surveillance for effective P. falciparum malaria control in SSA.
Abstract
The continuous Plasmodium falciparum kelch13 (PfK13) genetic alterations conferring resistance to artemisinin-based combination therapies and partner drugs pose a significant threat to effective treatment and control of P. falciparum infection in developing countries. This review evaluates the emergence and epidemiology of the PfK13 mutation associated with artemisinin resistance in the sub-Saharan Africa (SSA) population. Despite empirical control and artemisinin combination therapy, the PfK13 gene mutation, previously described in Southeast Asia, has been reported in the SSA. Eight of these validated markers, including P553L, M476I, C580Y, A675V, P574L, R561H, R622I, and F446I, were reported among the SSA population. Novel and unvalidated markers, such as P615S, M472I, F434S, A578S, P570L, Y558C, K563R, A569T, I684N, M472I, and C473F spread among the population with low frequency. We provide insight into the emergence and spread of validated and unvalidated PfK13 mutations among the SSA population, which could lead to high artemisinin resistance. Investigating the verified PfK13 mutations will improve prophylactic strategies, prognostic diagnosis and guide effective population-based surveillance for effective P. falciparum malaria control in SSA.