Oral Presentation 8th International Conference on Plasmodium vivax Research 2022

Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria (80182)

Benedikt Ley 1 , Mohammad S Alam 2 , Ari W Satyagraha 3 , Ching S Phru 2 , Kamala Thriemer 1 , Dagimawie Tadesse 4 , Tamiru Shibiru 4 , Asrat Hailu 4 , Mohammad G Kibria 2 , Mohammad S Hossain 2 , Hisni Rahmat 3 , Jeanne R Poespoprodjo 5 , Wasif A Khan 2 , Julie A Simpson 6 , Ric N Price 1
  1. Menzies School of Health Research, Casuarina, NT, Australia
  2. International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
  3. Eijkman Institute for Molecular Biology, Jakarta, Indonesia
  4. College of medicine & Health Sciences, Araba Minch University, Arba Minch, Ethiopia
  5. Timika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Timika, Indonesia
  6. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia

Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites (radical cure) but cause haemolysis in Glucose–6–Phosphate Dehydrogenase (G6PD) deficient patients. Malaria also causes haemolysis, leading to the replacement of older red blood cells with low G6PD activity by younger ones with higher activities. We quantified this change.

Selected patients with uncomplicated malaria were recruited in Bangladesh (n=99), Indonesia (n=75), and Ethiopia (n=173); G6PD activity was measured by spectrophotometry at enrolment and again 889 days later in Bangladesh, 168 days later in Indonesia, and after 176 days in Ethiopia. G6PD activity fell by 79.1% (95%CI: 40.4 to 117.8) between enrolment and follow up in 6 patients classified as deficient (<30% activity) during follow up, 44.6% (95%CI: 35.3 to 53.8) in 41 intermediate patients (30% to <70%), and by 5.1% (95%CI: 2.0 to 8.2) in 300 G6PD normal patients (≥70%). In Bangladesh 41.4% of participants had <70% activity during follow and the country specific activity fell by 39.3% (95%CI: 32.3 to 46.2), in Indonesia 6.7% of participants had activities <70% and the difference was 7.4% (95%CI: 0.2 to 14.6), in Ethiopia 0.6% of participants had reduced activities and activity was lower during enrolment (-3.6%, 95%CI: -1.0 to -6.1). Mean activity change was more pronounced among P.vivax patients with intermediate activity during follow up (51.7%, 95%CI: 40.1 to 63.3) compared to intermediate patients with  P. falciparum infection (38.9%, 95%CI: 25.9 to 52.0). In total 4/6 of deficient and 36/41 of participants with intermediate activity during follow up had normal activities when enrolled.

If confirmed, these findings suggest that G6PD activity rises during malaria, the risk of drug induced haemolysis is probably lower than assumed, and all patients with a history of deficiency or normal activity when parasitemic must be retested prior to deciding on radical cure.