Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria

Journal article

Background:

The 8-aminoquinoline antimalarials, the only drugs which prevent relapse of vivax and ovale malaria (radical cure), cause dose-dependent oxidant haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients with <30% and <70% of normal G6PD activity are not given standard regimens of primaquine and tafenoquine, respectively. Both drugs are currently considered contraindicated in pregnant and lactating women.

Methods:

Quantitative G6PD enzyme activity data from 5198 individuals were used to estimate the proportions of heterozygous females who would be ineligible for treatment at the 30% and 70% activity thresholds, and the relationship with the severity of the deficiency. This was used to construct a simple model relating allele frequency in males to the potential population coverage of tafenoquine and primaquine under current prescribing restrictions.

Findings:

Independent of G6PD deficiency, the current pregnancy and lactation restrictions will exclude ~13% of females from radical cure treatment. This could be reduced to ~4% if 8-aminoquinolines can be prescribed to women breast-feeding infants older than 1 month. At a 30% activity threshold, approximately 8–19% of G6PD heterozygous women are ineligible for primaquine treatment; at a 70% threshold, 50–70% of heterozygous women and approximately 5% of G6PD wild type individuals are ineligible for tafenoquine treatment. Thus, overall in areas where the G6PDd allele frequency is >10% more than 15% of men and more than 25% of women would be unable to receive tafenoquine. In vivax malaria infected patients these proportions will be lowered by any protective effect against P. vivax conferred by G6PD deficiency.

Conclusion:

If tafenoquine is deployed for radical cure, primaquine will still be needed to obtain high population coverage. Better radical cure antimalarial regimens are needed.

Authors: Watson, J; Taylor, W; Bancone, G; Chu, C; Jittamala, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS Neglected Tropical Diseases
• Volume: 12
• Issue: 4
• Pages: e0006440
• Publication date: 2018-04-20
• Acceptance date: 2018-04-10
• DOI: 10.1371/journal.pntd.0006440
• EISSN: 1935-2735
• ISSN: 1935-2727
• Language: English
• Keywords: radical cure; malaria elimination; G6PD deficiency; 8-aminoquinoline; Plasmodium vivax malaria