Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia

Abstract

Plasmodium falciparum and P. vivax co-exist at different endemicity levels across Ethiopia. For over two decades Artemether-Lumefantrine (AL) is the first line treatment for uncomplicated P. falciparum, while chloroquine (CQ) is still used to treat P. vivax. It is currently unclear whether a shift from CQ to AL for P. falciparum treatment has implications for AL efficacy and results in a reversal of mutations in genes associated to CQ resistance, given the high co-endemicity of the two species and the continued availability of CQ for the treatment of P. vivax. This study thus assessed the prevalence of Pfcrt-K76T and Pfmdr1-N86Y point mutations in P. falciparum. 18S RNA gene based nested PCR confirmed P. falciparum samples (N = 183) collected through community and health facility targeted cross-sectional surveys from settings with varying P. vivax and P. falciparum endemicity were used. The proportion of Plasmodium infections that were P. vivax was 62.2% in Adama, 41.4% in Babile, 30.0% in Benishangul-Gumuz to 6.9% in Gambella. The Pfcrt-76T mutant haplotype was observed more from samples with higher endemicity of P. vivax as being 98.4% (61/62), 100% (31/31), 65.2% (15/23) and 41.5% (22/53) in samples from Adama, Babile, Benishangul-Gumuz and Gambella, respectively. However, a relatively higher proportion of Pfmdr1-N86 allele (77.3–100%) were maintained in all sites. The observed high level of the mutant Pfcrt-76T allele in P. vivax co-endemic sites might require that utilization of CQ needs to be re-evaluated in settings co-endemic for the two species. A country-wide assessment is recommended to clarify the implication of the observed level of variation in drug resistance markers on the efficacy of AL-based treatment against uncomplicated P. falciparum malaria.

High prevalence of Pfcrt 76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia

“…Wild-type Pfcrt K76 allele was only detected in 8.4% P. falciparum isolates. The high proportions of Pfcrt 76T allele in this study is in agreement with studies from various parts of Ethiopia [ 6 , 13 , 26 ]. This persistence of high frequency of 76T allele in Ethiopia may be associated with incomplete withdrawal of CQ as it is currently the first-line anti-malarial drug for the treatment of P. vivax which accounts nearly for 40% of malaria cases in Ethiopia.…”

“…Then, due to widespread of CQ resistant P. falciparum , the country changed its treatment policy from CQ to sulfadoxine–pyrimethamine (SP) in 1998 which in turn was replaced by artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in 2004; however CQ is retained and still continued to be used as a first-line treatment for vivax malaria [ 6 , 13 ]. Molecular studies from Ethiopia have showed high prevalence of Pfcrt K76T mutation that ranged from 41.5 to 100% [ 6 , 13 , 14 ]. However, only one study has showed the return of CQ sensitive P. falciparum with 84% of Pfcrt K76 sensitive alleles [ 15 ].…”

“…However, only one study has showed the return of CQ sensitive P. falciparum with 84% of Pfcrt K76 sensitive alleles [ 15 ]. On the other hand, in Ethiopia, AL pressure might result in directional selection of Pfmdr1 variants N86, 184 F and D1246 due to LUM partner drug pressure [ 6 , 13 – 15 ]. Therefore, it is important to continue monitoring the prevalence of these markers ( Pfcrt and Pfmdr1 ) that confer resistance to CQ in the hope of possible re-emergence of CQ sensitive P. falciparum as previously observed in Malawi [ 16 ].…”

Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa

“…We identified intriguing areas of remaining pfcrt 76T and pfmdr1 86Y genotype presence, particularly in Madagascar, Ethiopia, the Gulf of Guinea, and parts of West Africa. One potential reason for the persistence in Madagascar and Ethiopia may be related to the usage of chloroquine to treat P. vivax where the species remains endemic (1,20). In the Gulf of Guinea, a region where seasonal malaria chemoprevention (SMC) with AQ and sulfadoxinepyrimethamine (SP) is used in children and higher rates of AS-AQ are used for treatment than in many other parts of Africa, the added pressure of AQ may explain the higher prevalence of these alleles (1).…”

Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis

“…Nucleic acid-based diagnosis and differentiation studies have also exhibited the identification of polymorphs in different parasite genes leading to resistance against antimalarials, accurate diagnosis, and efficient medication [ 65 , 66 , 67 , 68 , 69 ], and create a mode of disguise from known RDTs such as deletions of PfHRP2/3 [ 70 , 71 , 72 , 73 , 74 , 75 ]. There are various reports on specific gene sequencing for understanding the polymorphism [ 76 , 77 , 78 ] of satellite genes leading to multidrug resistance and predicting the lineage of distribution across the globe [ 79 ]. In many cases, it may also predict or indicate the cases of malaria relapse [ 80 ].…”