Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana

Abstract

The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRNI-A/FGKGS/T pfdhfr/pfdhps haplotypes, including the pfdhps A581G and A613S/T mutations, was high at delivery among post-SP treatment isolates (18.2%) compared to those of first antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine [IPTp-SP]; 6.1%; P = 0.03). Regarding the pfk13 marker gene, two nonsynonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance of additional mutations associated with increased SP resistance as well as emergence of resistance against artemisinin derivatives.

Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

“…Though not listed as validated SNPs, some of these markers have been associated with reduced susceptibility to artemisinin in vitro. V568G and A481C were identi ed in Kenya and Ghana, respectively (de Laurent et al, 2018;Tornyigah et al, 2020) while A675V was reported in Kenya, Rwanda, and Uganda (Ikeda et al, 2018;Tacoli et al, 2016). The other associated markers identi ed were C469Y/W (Escobar et al, 2015;Talundzic et al, 2017;Uwimana et al, 2020), G538S (Doudou 2021), G449S/C (Ouattara et al, 2014), N672I (Tornyigah et al, 2020) and P574L (Rwanda and Uganda), (Tacoli et al, 2016;Uwimana et al, 2020).…”

“…V568G and A481C were identi ed in Kenya and Ghana, respectively (de Laurent et al, 2018;Tornyigah et al, 2020) while A675V was reported in Kenya, Rwanda, and Uganda (Ikeda et al, 2018;Tacoli et al, 2016). The other associated markers identi ed were C469Y/W (Escobar et al, 2015;Talundzic et al, 2017;Uwimana et al, 2020), G538S (Doudou 2021), G449S/C (Ouattara et al, 2014), N672I (Tornyigah et al, 2020) and P574L (Rwanda and Uganda), (Tacoli et al, 2016;Uwimana et al, 2020). The other Pfk13 mutations reported in African parasites such as C469Y, S522C, R575I/K, and P667R (Uwimana et al, 2020) were found at low frequencies and have not been substantially linked with artemisinin resistance in Africa (WHO, 2019) contrary to what was observed in SEA (WWARN, 2019).…”

“…Majority of the studies collected blood samples for genotyping on lter paper (Abubakar et al, 2020;Ahouidi et al, 2021;Balikagala et al, 2017;Conrad et al, 2019;Djaman et al, 2017) while others did not report the method used for collection (Uwimana et al, 2020;Velavan et al, 2019) P. falciparum polymerase chain reaction positive (PCR+) samples were 18,292 out of 32,406 total samples collected (Mayengue et al, 2018;Nzoumbou-Boko et al, 2020;Oboh et al, 2018;Ocan et al, 2016;Pacheco et al, 2020;Tornyigah et al, 2020;Uwimana et al, 2020). Five studies did not report the number of PCR+ samples (Castaneda-Mogollon et al, 2019;Chebore et al, 2018;de Laurent et al, 2018;Hemming-Schroeder et al, 2018;Ikeda et al, 2018).…”

“…R561H was identi ed in Rwanda and Tanzania (Uwimana et al, 2020), P553L in Angola (Xu et al, 2018), and M476I in Tanzania (Kakolwa et al, 2018). In two isolates from Ghana (Tornyigah et al, 2020), asparagine in position 458 (N458) was found to be replaced by aspartate (D) instead of tyrosine (Y). Though their link with delayed parasite clearance is yet to be established, other non-synonymous mutations reported are A481C in Ghana, A675V in Kenya (3 isolates), Rwanda (2 isolates) and Uganda (2 isolates); C469W/Y/F in Ghana, Kenya, Rwanda and Uganda; G538S in Democratic Republic of the Congo; G449S/C in Mali and Tanzania; N672I in Ghana (2 isolates); P574L in Uganda and Rwanda (1 and 3 isolates respectively); R539I/K in Kenya and Senegal as well as V568G in Kenya (3 isolates).…”

Active case detection of malaria in pregnancy using loop-mediated amplification (LAMP): a pilot outcomes study in South West Ethiopia

“…However, the use of IPT presents several limitations. First, if the treatment is not administered completely or with poor compliance, IPT contributes to the spread of drug resistant parasites [11,12]. Second, gametocytes are detected in pregnant women following the administration of IPT [13], which is one of the contributors to malaria transmission.…”