Potential hiddenPlasmodium vivaxmalaria reservoirs from low parasitemia Duffy-negative Ethiopians: molecular evidence

Abstract

AbstractBackgroundThe interaction between thePlasmodium vivaxDuffy-binding protein and the corresponding Duffy Antigen Receptor for Chemokines (DARC) is primarily responsible for the invasion of reticulocytes byP. vivax. The Duffy-negative host phenotype, highly prevalent in sub-Saharan Africa, is caused by a single point mutation in the GATA-1 transcription factor binding site of the DARC gene promoter. The aim of this study was to assess the Duffy status of patients withP. vivaxinfection from different study sites in Ethiopia.MethodsA cross-sectional study was conducted from February 2021 to September 2022 at five varying eco-epidemiological malaria endemic sites in Ethiopia. Outpatients who were diagnosed withP. vivaxinfection (pure and mixedP. vivax/P. falciparum) by microscopy were subjected to qPCR genotyping at the DARC promoter. The associations betweenP. vivaxinfection, host genotypes and other factors were evaluated.ResultIn total, 361 patients withP. vivaxinfection were included in the study. Patients with pureP. vivaxinfections accounted for 89.8% (324/361), while the remaining 10.2% (37/361) had mixedP. vivax/P. falciparuminfections. About 95.6% (345/361) of the participants were Duffy-positives (21.2% homozygous and 78.8%, heterozygous) and 4.4% (16/361) were Duffy-negatives. The mean asexual parasite density in homozygous and heterozygous Duffy-positives was 12,165 p/µl (IQR25-75: 1,640-24,234 p/µl) and11,655 p/µl (IQR25-75: 1,676-14,065 p/µl), respectively, significantly higher than that in Duffy-negatives (1,227p/µl; IQR25-75: 539-1,732p/µl).ConclusionThis study confirms that Duffy-negativity does not provide complete protection againstP. vivaxinfection. The development ofP. vivax-specific elimination strategies, including alternative antimalarial vaccines should be facilitated by a better understanding of the epidemiological landscape ofvivaxmalaria in Africa. More importantly, low parasitemia associated withP. vivaxinfections in Duffy-negative patients may represent hidden reservoirs of transmission in Ethiopia.Author SummaryPlasmodium vivaxgenerally receives less attention thanP. falciparumand was neglected in sub-Saharan Africa. However, the characteristics ofP. vivaxinfection in Duffy-negative individuals, and the distribution of Duffy blood group in different eco-epidemiological zones and ethnic groups of Ethiopia are not well documented. Here, we determined the Duffy genotypes ofP. vivaxinfected patients across broad regions of Ethiopia. It is clear that Duffy negative individuals in Ethiopia are not fully protected againstP. vivaxinfection, and that these infections in Duffy negatives are often associated with low parasitemia. Our findings lend support to the notion thatP. vivaxmay have developed a Duffy-independent erythrocyte invasion pathway and/or evolution in host immune responses.