Common enzyme deficiency may hinder plans to eradicate malaria

22 November 2012

Source: Wellcome Trust, 15 Nov 2012. 

A Wellcome Trust-funded study estimates that around 350 million people living in malaria-endemic countries are deficient in an enzyme that means they can suffer severe complications from taking primaquine, a key drug for treating relapsing malaria.

This finding is important because primaquine is recommended in the global action plan to eliminate malaria and is the only drug to prevent malaria relapse. The study, funded by the Wellcome Trust, suggests that the benefits of implementing a treatment programme with this drug need to be weighed against the potential harm to a substantial proportion of the population.

People who have a deficiency in the enzyme glucose-6-phosphate dehydrogenase (G6PD) experience severe complications in response to treatment with primaquine, caused by the breakdown of their red blood cells. The deficiency is caused by a mutation in the gene for the enzyme.

Using community surveys and mathematical models to predict geographical distribution of the defective gene, the researchers estimate that up to 8 per cent of people living in malaria-endemic areas could be affected, corresponding to around 350 million people.

Rosalind Howes from the University of Oxford, who led the study, explains: "Malaria control and elimination are a top priority on the global health agenda, yet a key drug to help achieve this goal remains too dangerous for widespread use.

"We have developed a map of this risk factor, G6PD deficiency, and find it to be very common across many malaria-endemic regions. Much work remains to be done to fully understand this disease, notably its genetic diversity."

The international team - from Indonesia, Kenya, the Philippines and the UK - found that the predicted frequency of G6PD deficiency varied considerably over relatively short distances in many areas, but the predicted level is highest in tropical Africa and the Arabian Peninsula (malaria-endemic areas) and lowest in North and South America.

In countries that are currently planning to implement malaria elimination programs, the frequency was 5.3 per cent, corresponding to 100 million affected individuals. When the authors took into account the severity of the G6PD deficiency, associated with a higher risk of red blood cell breakdown, they found that the greatest risk was across Asia where severe G6PD variants are commonly inherited.

The findings of this study suggest that the prominence of G6PD deficiency represents a barrier to current options for malaria elimination therapy. The complexity and diversity of both malaria epidemiology and G6PD deficiency mean that no single solution will be applicable for ensuring safe and effective primaquine treatment, say the authors.

The study was conducted as part of the Malaria Atlas Project, principally funded by the Wellcome Trust, and is published this week in 'PLOS Medicine'.

Reference                                

Howes RE et al. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLOS Med 2012 (epub ahead of print)