Plasmodium vivax, susceptibility factors and pharmacogenetics of treatment among febrile patients in the West and South Regions of Cameroon

Thanks to the implementation of molecular detection techniques, Plasmodium vivax (Pv) infections have been reported in several sub-Saharan African countries recently, including Duffy-negative populations of West and Central Africa. This work aimed to assess the possible circulation of Pv and factors linked to the susceptibility to Pv and the pharmacogenetics of its treatment (Duffy antigen, G6PD deficiency, CYP450 genetic variability) among outpatients of Santchou, Dschang and Ambam Health Districts. A cross-sectional descriptive and analytical study was performed in 4 healthcare facilities (HCFs). Data was collected in two different periods, the rainy season in Santchou (August 2016-December 2016) and rainy season in Dschang and Kyé-ossi/Ambam (May 2017September 2017). Interviews were conducted using a structured questionnaireand consenting febrile patients were consecutively recruited and drops of blood were collected on dried blood spots and smears. All samples were analysed by molecular and microscopic methods. All data was analysed using Microsoft Excel 2013 and Epi info version 7.2. In total, 1001 samples were collected and Plasmodium spp parasite DNA was detected in 486 (48.6%) samples. In particular, 441 cases of Plasmodium mono-infections (287 P. falciparum, 146 P. vivax, 2 P. ovale, 6 P. malariae) and 45 cases of mixed-infections (37 falciparum/vivax, 2 falciparum/ovale, 4 falciparum/malariae, 2 vivax/malariae) were detected. Globally, Pv has been detected in 185 cases (38.1% of positive samples), mainly from Dschang (n=181) than Santchou (n=2) and Ambam (n=2). Pv occurrence appeared to be linked with environmental factors more than biological factors. Locally used malaria diagnosis methods had less specificity and sensibility to respect to PCR. Duffy blood group genotyping showed alleles frequencies of 0.30% (2/666) positive (-33TC) and 99.70% (664/666) negative (-33CC). All the Pv positive cases have shown a Duffy-negative genotype (-33CC). G6PD 968 SNP did not show any variability (968 A+, TT). G6PD deficiency prevalence was 2.78% (5/180) evaluated according to 202G>A SNP. The deficient allele frequency (G6PD 202A) among females was 2.72%. Two (2) Pv infected people were G6PD heterozygous (202GA; A+/-). Looking at CYP2D6 gene variability, the mutant alleles found were *2 (56.71%), *17 (13.63%) and *4 (4.24%). Most of them were normal metabolizers (98.82%; 504/510). Twelve (12) Pv infected people were intermediate and normal-slow metabolizers. These data show a relatively high circulation of Pv in the West Region of Cameroon among Duffy-negative autochthonous individuals, with a prevalence possibly depending from altitude and seasonality. Further study are necessary, in order to assess the real Pv local circulation and transmission, as well as to identify Duffy-independent Pv erythrocyte invasion pathway. It is important to improve the local malaria control program in Dschang taking in account the challenges of Pv malaria management (therapeutic toxicity, attacks and relapses).