Pakistan has an estimated annual burden of approximately 1.5 million malaria cases each year. Pakistan is among seven countries of the WHO Eastern Mediterranean Region sharing approximately 95% of the total regional malaria burden WHO, 2017.
In Pakistan malaria in humans is caused by two plasmodia species plasmodium falciparium and plasmodium vivax (Guerra et al. 2010).Plasmodium vivax is endemic and is more common (89%), while malaria with Plasmodium falciparum is not common and seen only during rainy seasons and accounts for 12% of the malaria burden (khattak et al, 2013). G6PD deficiency is frequently quoted as an example of natural selection, with malaria being considered a evolutionary force. The geological distribution of G6PD deficiency variants really overlaps with historically malaria-endemic areas such as Africa, Asia, and Mediterranean region .G6PD deficiency is relatively rare in populations where malaria is rare but where malaria is common it may exceed 10% in prevalence (Nkhoma et al.
, 2009). It has been estimated that G6PDd affects around 353 million people worldwide, with 95 million in the malaria endemic countries (Howes et al., 2012). The association of G6PD and malaria is that G6PDd is associated with protection against P. falciparum (Clark et al.
2009) and P. vivax infections (Leslie et al. 2010, Santana et al. 2013).Currently the only drug that is used for the treatment of malaria is primaquine (an 8-aminoquinoline) that kills P. vivax hypnozoites (0.5 mg/kg/d for 14 days) (Barid and Hoffman,.
2004) and P. falciparum gametocytes (0.25 mg/kg in a single dose)(WHO, 2010). However the use of PQ or other 8-aminoquinolines such as tafenoquine in G6PDd individuals cause serious risks, as these compounds may induce life-threatening haemolytic events and their intensities depends on the individual’s enzyme activity profile (Llanos-Cuentas et al. 2013).
Therefore WHO recommends that in mild-to-moderate G6PDd, PQ (0.75 mg base/kg) should be given once a week over eight weeks, while in severe G6PDd patients, PQ is contraindicated (WHO 2010), because the administration of primaquine in severe conditions shortens RBC life span in G6PD-deficient persons. Evidence from large case control studies also indicates that G6PD deficiency protects against cerebral malaria (Clarke et al., 2017) and against high parasitamias (Bienzleet al.
, 1972). The potentially life-threatening interaction between the enzyme deficiency and anti-hypnozoite drugs places a major constriction on the ability of endemic countries to control or eliminate vivax malaria, because in most areas G6PD testing is not available with vivax malaria, so safe treatment of hypnozoite infections with 8-aminoquinoline drugs is not possible (Cappellini et al,.2008).