Poster Presentation First Malaria World Congress 2018

Relationship between CYP2D6 allelic types, predicted phenotypes and outcome of primaquine presumptive anti-relapse therapy in Australian Defence Force personnel deployed to Papua New Guinea and East Timor (#415)

Nanhua Chen 1 , Simone Dowd 1 , Alyson Auliff 1 , Michelle Gatton 2 , Dennis Shanks 1 , Michale Edstein 1 , Qin Cheng 1
  1. Australian Defence Force Malaria and Infectious Disease Institute, Enoggera, QLD, Australia
  2. School of Public Health and Social Work, Queensland University of Technology, Brisbane, Queensland, Australia

Primaquine (PQ) is an 8-aminoquinoline compound with anti-hypnozoite activity against Plasmodium vivax relapse. Primaquine is metabolised by human cytochrome P450 2D6 (CYP2D6) to produce active metabolites capable of effectively killing liver stage P. vivax. The gene encoding human CYP2D6 is highly polymorphic, with over 100 different alleles documented. The phenotypes of CYP2D6 are determined by the functionality of alleles, and described as extensive metaboliser (EM), intermediate metaboliser (IM), and poor metaboliser (PM). Recent studies in Papua New Guinea (PNG), Indonesian and Brazilian populations suggested that PM and IM phenotypes may result in insufficient metabolism of primaquine, thus associated with higher risk of relapses of vivax malaria following primaquine presumptive anti-relapse therapy (PART).

To investigate the relationship between CYP2D6 allelic types and outcomes of primaquine PART in an Australian population, CYP2D6 genotypes were determined for two groups of Australian Defence Force (ADF) personnel deployed to Bougainville, PNG in 1999 and East Timor in 2000-2001 who received PART consisting of doxycycline (100 mg daily for 14 days) and primaquine (7.5 mg 3 times daily or 15 mg twice daily for 14 days), commencing before returning to Australia. Samples from PNG and East Timor deployments (n=157) were sourced from personnel who did not develop vivax malaria (n=45) and those that developed vivax malaria (=112) after returning to Australia. CYP2D6 allelic frequency, the active score of CYP2D6 alleles, the percentage of EM, IM and PM phenotypes in relation to the outcome of primaquine PART in each group will be presented.