Oral Presentation First Malaria World Congress 2018

Risks in Anti-Relapse Primaquine Therapy with G6PD Deficiency (#44)

John Kevin Baird 1
  1. Eijkman-Oxford Clinical Research Unit, Jakarta, DKI JAKARTA, Indonesia

The problem of infection by Plasmodium vivax and its latent hypnozoites imposes a therapeutic dilemma: primaquine therapy prevents the harm of often multiple relapses but comes with risk of harm by serious hemolytic toxicity in patients deficient in G6PD. While daily primaquine dosing against relapse invariably causes harm in G6PD-deficient patients, the extent of harm hinges upon dosing regimen and the degree to which G6PD enzymatic activity is impaired. Among the many dozens of known G6PDd variants, some are relatively mildly impaired (e.g., >10% of normal) whereas others may be relatively severely impaired (e.g., <1% of normal). When the G6PD variant is severely impaired and exposure to primaquine relatively high (e.g., 0.5mg/kg daily), a deep and threatening hemolytic crisis may occur after just 4 doses. Unless dosing is ceased and blood transfusion initiated, the crisis may progress to death. Among milder G6PDd variants, in contrast, hemolysis affects only older red blood cells with tolerance of continued dosing. Surveys of G6PDd variants reveal dominance of relatively severe enzymatic activity impairment in the Asia-Pacific region where about 90% of the global burden of P. vivax occurs. Primaquine therapy against latency of that infection thus imposes a serious clinical and public health problem. These risks may be appropriately mitigated by G6PD screening or close clinical supervision and access to blood transfusion services. Achieving universal access to safe anti-relapse therapies may be essential to the control and elimination of endemic vivax malaria.