G6PD deficiency, primaquine treatment, and risk of haemolysis in malaria-infected patients

Abstract

BackgroundThe incidence of malaria in the Americas has decreased markedly in recent years. Honduras and the other countries of Mesoamerica and the island of Hispaniola have set the goal of eliminating native malaria by the year 2020. To achieve this goal, Honduras has recently approved national regulations to expand the possibilities of a shortened double dose primaquine (PQ) treatment for vivax malaria. Considering this new shortened anti-malarial treatment, the high frequency of G6PDd genotypes in Honduras, and the lack of routinely assessment of the G6PD deficiency status, this study aimed at investigating the potential association between the intake of PQ and haemolysis in malaria-infected G6PDd subjects.MethodsThis was a prospective cohort and open-label study. Participants with malaria were recruited. Plasmodium vivax infection was treated with 0.25 mg/kg of PQ daily for 14 days. Safety and signs of haemolysis were evaluated by clinical criteria and laboratory values before and during the 3rd and 7th day of PQ treatment. G6PD status was assessed by a rapid test (CareStart™) and two molecular approaches.ResultsOverall 55 participants were enrolled. The frequency of G6PD deficient genotypes was 7/55 (12.7%), where 5/7 (71.4%) were hemizygous A− males and 2/7 (28.6%) heterozygous A− females. Haemoglobin concentrations were compared between G6PD wild type (B) and G6PDd A− subjects, showing a significant difference between the means of both groups in the 3rd and 7th days. Furthermore, a statistically significant difference was evident in the change in haemoglobin concentration between the 3rd day and the 1st day for both genotypes, but there was no statistical difference for the change in haemoglobin concentration between the 7th day and the 1st day. Besides these changes in the haemoglobin concentrations, none of the patients showed signs or symptoms associated with severe haemolysis, and none needed to be admitted to a hospital for further medical attention.ConclusionsThe findings support that the intake of PQ during 14 days of treatment against vivax malaria is safe in patients with a class III variant of G6PDd. In view of the new national regulations in the shortened treatment of vivax malaria for 7 days, it is advisable to be alert of potential cases of severe haemolysis that could occur among G6PD deficient hemizygous males with a class II mutation such as the Santamaria variant, previously reported in the country.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2564-2) contains supplementary material, which is available to authorized users.

The prevalence of glucose-6-phosphate dehydrogenase deficiency in the Cape Verdean population in the context of malaria elimination

“…These results are consistent with results from a preliminary study in the country in 2010 [36], and similary to the reports from other studies conducted in other African countries, as Mauritania [37], Uganda [38], Mozambique [39] Senegal [40,41] and Gambia [42]. The high G6PDd prevalence in the African or Afro-descendant population as shown by several studies [39][40][41][42][43] may reflect the population's exposure to malaria endemicity or ethnicity related [8][9][10][11][12][13][14][15][16]. However, our results do not allow drawing any conclusions of this nature since almost all the participants of this study were of Cape Verdean citizenship and no ethnic classification was made.…”

“…The schizontocidal treatment for non-falciparum malaria is done with the AL or Artesunate + Amodiaquine, following the WHO guidelines [7]. Nevertheless, this use of primaquine is carried out regardless the knowledge of the frequency of the Glucose-6-phosphate-dehydrogenase (G6PD) deficiency among the target population, which endangers all the patients harbouring this deficiency with the risk of haemolysis [8][9][10][11][12].…”

Study of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Genotype Polymorphism of G6PD B and G6PD (A+/A-) in Patients Treated for Plasmodium vivax Malaria in a Tertiary Care Hospital in North East India

“…Vivax malaria has been reported in almost all states of North East India, attributing up to 60-80% of all malaria cases in some states [17]. G6PD deficiency often follows geographic distribution similar to that of falciparum malaria, but studies associating G6PD deficiency and P. vivax malaria distribution are sparse [1,[7][8][9]21].…”

“…This deficiency offers selective protection against P. falciparum [6]. Trends of G6PD deficiency in Plasmodium vivax (P. vivax) endemic areas have been less revealing, with a weak association between the two being reported from around the world [7][8][9].…”

What Will Happen to Biomedical Research in Low-and-Middle Income Countries in the PostCOVID-19 World?

“…Their works have provided insight into the epidemiology and impact of HIV/AIDS [ 11 – 13 ], and vector-borne viral diseases [ 14 – 16 ]. As well, laboratory technology from UNAH to laboratories in the public health system has been transferred regularly [ 17 – 19 ]. Moreover, work from these research groups have contributed to the understanding of antimicrobial resistance and to malaria elimination in the country [ 20 – 22 ].…”