“These findings are relevant to the thousands of western travellers treated each year for malaria and for non-immune adults in low malaria transmission places like Bangladesh, Thailand and Myanmar,” said Dr Charlie Woodrow, one of the study’s lead authors, based at the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand.
“Using a modified rapid test – a dipstick, if you will – physicians can predict who is at high risk of delayed anaemia and anticipate the need for hospital admission and blood transfusion,” explained Dr Woodrow. “Patients identified as being low risk, on the other hand, can be reassured and told to come back only if their symptoms worsen.”
Artesunate, the most commonly used artemisinin for severe malaria, rapidly cures patients with severe malaria but frequently induces anaemic episodes called post-artesunate delayed hemolysis (PADH) for which a simple predictive method has been needed.
The researchers, based in France, Thailand and Bangladesh, found that the underlying event in PADH, the expulsion of artesunate-exposed parasites from their host red blood cells by “pitting”, leaves behind the parasite component PfHRP2 in the red cell. So using a dipstick to measure the amount of PfHRP2 in the blood just after parasite clearance indicates the number of "deparasitized" red cells – and the risk of life-threatening anaemia.
The finding that PfHRP2 persists in deparasitized red cells also solves a long-standing mystery – why the rapid diagnostic test for falciparum malaria stays positive for so long after treatment.
“Our work hence joins together three separate strands of study – the process of pitting, the persistence of PfHRP2 after treatment and the risk of delayed haemolysis after artesunate,” said Dr Woodrow.
Led by researchers at the National Institute of Blood Transfusion, Paris Descartes University with support from, among others, scientists at the Mahidol Oxford Tropical Medicine Research Unit (MORU) at Mahidol University, Bangkok, Thailand and the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, the study was funded by the French National Research Agency, the Wellcome Trust (UK) and the Bill and Melinda Gates Foundation.
Persistence of the Plasmodium falciparum protein HRP2 in the circulation of artesunate-treated malaria patients predicts post-artesunate hemolysis.Ndour PA, Larréché S, Mouri O, Argy N, Gay F, Roussel C, Jauréguiberry S, Perillaud C, Langui D, Biligui S, Chartrel N, Mérens A, Kendjo E, Ghose A, Hassan MMU, Hossain MA, Kingston HWF, Plewes K, Dondorp AM, Danis M, Houzé S, Bonnefoy S, Thellier M, Woodrow CJ, Buffet PA, French Artesunate Working Group. Sci Transl Med. 2017 Jul 5;9(397). pii: eaaf9377. doi: 10.1126/scitranslmed.aaf9377.