Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

Abstract

According to the WHO, almost two thirds of the Ethiopian population are at risk of contracting malaria, where infection with Plasmodium falciparum accounts for approximately 60% of cases today. The risk of artemisinin resistance spreading from SE Asia to Africa is a major concern. We conducted a 28-day in vivo efficacy trial of Artemether-Lumefantrine (Co-Artem) for treatment of uncomplicated malaria (n = 97) in the Gondar Region, North West Ethiopia in 2017–2018. Our results confirmed 100% adequate clinical and parasitological response (ACPR) with no parasites observed at day 3 by microscopy. Further analysis of day 0 samples showed the expansion of a kelch13 mutation R622I to 9.5% from 2.4% of isolates reported three years earlier. Closer examination of the R622I mutation in vitro is warranted.

Clonal spread ofPlasmodium falciparumcandidate artemisinin partial resistanceKelch13622I mutation and co-occurrence withpfhrp2/3deletions in Ethiopia

“…The presence of K13 622I across all sampled districts signals that parasites are under ACT pressure in Ethiopia and indicates that parasites are evolving to escape antimalarial treatment. The 622I mutation was reported previously in two small studies from one site in northern Ethiopia (Gondar), with associated delay in parasite clearance on day 3 of ACT 26 and increased prevalence over time, from 2.4% in 2014 26 to 9.5% in 2017-18 27 . While not yet peer reviewed, reports of 622I at high prevalence in Eritrea (16.7% in 2016) and association with 6.3% delayed clearance on day 3 of AL treatment raise further concern about this mutation 33 .…”

“…IBD sharing was higher within the K13 622I mutant parasite population compared to wild-type parasites, suggesting that 622I mutation emerged or entered into northern Ethiopia in the recent past 27 and spread to other parts of the country. Highly related parasites are also closely clustered at the district level, a finding expected after clonal transmission.…”

“…However, chloroquine (CQ) is still widely used and efficacious for cases of endemic vivax malaria 24 . Artemether-lumefantrine remains highly efficacious 25 , though detection of the candidate artemisinin resistance K13 622I mutation in northern Ethiopia 26,27 and high prevalence of residual submicroscopic parasitemia following ACT treatment in recent studies raises concern 12,25 .…”

The spread of a validated molecular marker of artemisinin partial resistancepfkelch13R622I and association withpfhrp2/3deletions in Eritrea

“…In Northern Ethiopia, specifically in a town close to the border with Sudan, the prevalence of R622I was found to be 2.4% (3/25) in samples collected during 2013-2014 15 . This prevalence increased to 9.3% (8/86) in samples collected between 2017 and 2018, indicating an expansion of the mutant in the area 16 . The R622I mutation has been shown to possibly affect the function of pfk13 by molecular modelling 15 , and it has recently been reported to associate with higher risk of day-3 positivity and recrudescence following ACT treatment in Eritrea TES 10 .…”