Howes Rosalind E, Chan Ernest R, Rakotomanga Tovonahary Angelo, Schulte Seth, Gibson John, Zikursh Melinda, Franchard Thierry, Ramiranirina Brune, Ratsimbasoa Arsène, Zimmerman Peter A
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
Nuffield Department of Medicine, Oxford Big Data Institute, University of Oxford, Oxford, UK.
Malar J. 2017 Apr 4;16(1):139. doi: 10.1186/s12936-017-1771-6.
The prevalence and variants of G6PD deficiency in the Plasmodium vivax-endemic zones of Madagascar remain unknown. The admixed African-Austronesian origins of the Malagasy population make it probable that a heterogeneous mix of genetic variants with a spectrum of clinical severity will be circulating. This would have implications for the widespread use of P. vivax radical cure therapy. Two study populations in the P. vivax-endemic western foothills region of Madagascar were selected for G6PD screening. Both the qualitative fluorescent spot test and G6PD genotyping were used to screen all participants.
A total of 365 unrelated male volunteers from the Tsiroanomandidy, Mandoto, and Miandrivazo districts of Madagascar were screened and 12.9% were found to be phenotypically G6PD deficient. Full gene sequencing of 95 samples identified 16 single nucleotide polymorphisms, which were integrated into a genotyping assay. Genotyping (n = 291) found one individual diagnosed with the severe G6PD Mediterranean mutation, while the remaining G6PD deficient samples had mutations of African origin, G6PD A- and G6PD A.
Deployment of P. vivax radical cure in Madagascar must be considerate of the risks presented by the observed prevalence of G6PDd prevalence. The potential morbidity associated with cumulative episodes of P. vivax clinical relapses requires a strategy for increasing access to safe radical cure. The observed dominance of African G6PDd haplotypes is surprising given the known mixed African-Austronesian origins of the Malagasy population; more widespread surveying of G6PDd epidemiology across the island would be required to characterize the distribution of G6PD haplotypes across Madagascar.
马达加斯加间日疟原虫流行地区葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的患病率和变异情况尚不清楚。马达加斯加人群具有非洲-南岛语系混合起源，这使得一系列临床严重程度各异的遗传变异可能广泛传播。这将对间日疟原虫根治疗法的广泛应用产生影响。在马达加斯加间日疟原虫流行的西部山麓地区，选取了两个研究人群进行G6PD筛查。采用定性荧光斑点试验和G6PD基因分型对所有参与者进行筛查。
对来自马达加斯加齐拉诺曼迪、曼多托和米亚德里瓦佐地区的365名无亲属关系的男性志愿者进行了筛查，发现12.9%的人表型为G6PD缺乏。对95个样本进行全基因测序，鉴定出16个单核苷酸多态性，并将其整合到基因分型检测中。基因分型（n = 291）发现1例个体被诊断为严重的G6PD地中海突变，而其余G6PD缺乏样本具有非洲起源的突变，即G6PD A-和G6PD A。
在马达加斯加开展间日疟原虫根治治疗时，必须考虑到观察到的G6PD缺乏症患病率所带来的风险。间日疟原虫临床复发累积发作相关的潜在发病率需要制定一项增加安全根治治疗可及性的策略。鉴于已知马达加斯加人群具有非洲-南岛语系混合起源，观察到的非洲G6PD缺乏单倍型占主导地位令人惊讶；需要在全岛更广泛地调查G6PD缺乏症流行病学，以确定马达加斯加G6PD单倍型的分布情况。
