Systematic review of the clinical manifestations of glucose-6-phosphate dehydrogenase deficiency in the Greater Mekong Subregion: implications for malaria elimination and beyond

INTRODUCTION: To achieve malaria elimination in the Greater Mekong Subregion (GMS) by 2030, proper case management is necessary. 8-aminoquinolines, such as primaquine, are the only available medicines effective in preventing relapse of the hypnozoite stage of Plasmodium vivax, as well as the onward transmission of Plasmodium falciparum. However, primaquine can cause haemolysis in individuals who have glucose-6-phosphate dehydrogenase deficiency (G6PDd). We conducted a systematic review on the reported clinical manifestations of G6PDd to provide a comprehensive overview of the situation in the GMS. METHODS: The protocol for this systematic review was registered on PROSPERO: International prospective register of systematic reviews (CRD42016043146). We searched the PubMed/MEDLINE, CINAHL, and Web of Science databases for published articles describing the clinical manifestations of G6PDd in the GMS. We included articles of all study designs from inception until 31 July 2016, reporting the clinical manifestations of G6PDd. We then performed a narrative synthesis of these articles. RESULTS: We included 56 articles in this review, 45 of which were from Thailand. Haemolysis in G6PD-deficient individuals was caused not only by primaquine but also by other medicines and infections. Other clinical manifestations of G6PDd that were found were favism, neonatal jaundice and chronic non-spherocytic haemolytic anaemia. G6PDd also influenced the clinical presentations of genetic disorders and infections, such as thalassemia and typhoid fever. CONCLUSION: As G6PDd also affects the clinical presentations of other infections, the benefits of G6PD testing and proper record keeping transcend those of malaria case management. Therefore, healthcare workers at the community level should be made familiar with complications resulting from G6PDd as these complications extend beyond the scope of malaria.