Clinical complications of G6PD deficiency in Latin American and Caribbean populations: systematic review and implications for malaria elimination programmes

Abstract

BackgroundAlthough G6PDd individuals are generally asymptomatic throughout their life, the clinical burden of this genetic condition includes a range of haematological conditions, including acute haemolytic anaemia (AHA), neonatal jaundice (NNJ) and chronic non-sphaerocytic anaemia (CNSA). In Latin America (LA), the huge knowledge gap regarding G6PDd is related to the scarce understanding of the burden of clinical manifestation underlying G6PDd carriage. The aim of this work was to study the clinical significance of G6PDd in LA and the Caribbean region through a systematic review.MethodsA systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Only original research was included. All study designs were included, as long as any clinical information was present. Studies were eligible for inclusion if they reported clinical information from populations living in LA or Caribbean countries or about migrants from these countries living in countries outside this continent.ResultsThe Medline search generated 487 papers, and the LILACS search identified 140 papers. After applying the inclusion criteria, 100 original papers with any clinical information on G6PDd in LA were retrieved. Additionally, 16 articles were included after reading the references from these papers. These 116 articles reported data from 18 LA and Caribbean countries. The major clinical manifestations reported from LA countries were those related to AHA, namely drug-induced haemolysis. Most of the published works regarding drug-induced haemolysis in LA referred to haemolytic crises in P. vivax malaria patients during the course of the treatment with primaquine (PQ). Favism, infection-induced haemolysis, NNJ and CNSA appear to play only a minor public health role in this continent.ConclusionHaemolysis in patients using PQ seems to be the major clinical manifestation of G6PDd in LA and contributes to the morbidity of P. vivax infection in this continent, although the low number of reported cases, which could be linked to under-reporting of complications. These results support the need for better strategies to diagnose and manage G6PDd in malaria field conditions. Additionally, Malaria Control Programmes in LA should not overlook this condition in their national guidelines.

G6PD deficiency in Latin America: systematic review on prevalence and variants

“…A recent systematic review has shown that among all published cases of haemolysis triggered by various oxidative agents in LA, none have involved Amerindians (Monteiro et al 2014). Reinforcing these results, in Nicaragua, the administration of 10-20 mg of PQ base during 14 days to 321 Miskito Amerindians with chronic malaria did not lead to any report of secondary haemolysis (Thaeler Jr et al.…”

“…A broad free text search was made using a previously published search strategy (Monteiro et al 2014). Potentially relevant papers in all languages were accessed from MEDLINE and LILACS for a review of the full texts.…”

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

“…A large burden of P. vivax, which is more difficult to eliminate than P. falciparum,poses a significant barrier to malaria elimination [18]. The latent hepatic stages of P. vivax are mainly responsible for subsequent relapses after the first clinical episode [19]. Primaquine is an important medication for case management, whether it is P. vivax or P. falciparum malaria.…”

The potential nephrotoxic effect of single tablet of 15 mg primaquine in G6PD deficient Hadoti region population of India

“…[4][5][6] In patients with the X-linked erythrocyte enzyme disorder glucose-6-phosphate dehydrogenase deficiency (G6PDd), primaquine causes dose-dependent acute haemolytic anaemia (AHA) that is greater in the more severe deficient G6PD variants, AHA can be potentially life threatening but primaquine-related deaths are very rare. [7][8][9][10][11][12][13] This toxicity is a significant public health concern because G6PDd affects approximately 400 million people who live mostly in malaria-endemic countries where the median G6PDd allele prevalence is 8%. Testing for G6PDd is not performed in the majority of malariaendemic countries.…”