G6PD deficiency alleles in a Plasmodium vivax-endemic region of Western Brazilian Amazon

Background: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which unfortunately can induce haemolytic anaemia in people with glucose-6-phosphate dehydrogenase (G6PD)-deficient, leading to several and fatal complications. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria endemic areas. This is particularly important as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. Materials and Methods: A total of 516 males volunteers from Amazonian region of the “Alto do Juruá”valley (Acre, Brazil) were enrolled in a cross-sectional study was carried out from June to August 2016. Blood samples were drawn to evaluate G6PD enzymatic activity by using the qualitative Beutler test and a subset of samples were genotyped using the Kompetitive Allele Specific PCR (KASP) assay. Ethical clearance was provided (Plataforma Brasil, CAAE: 34988014.3.0000.5467). Results:516 male volunteers were screened for G6PDd using the Beutler test. Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported hemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the GP6D A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. Conclusions:Our data indicate that ~1/23 males from the Alto do Juruá valley could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening before primaquine administration should be considered, particularly as complete treatment of patients with P. vivax malaria is crucial for malaria elimination.