Mass primaquine treatment to eliminate vivax malaria: lessons from the past

Recent successes in malaria control have put malaria eradication back on the public health agenda. A significant obstacle to malaria elimination in Asia is the large burden of Plasmodium vivax, which is more difficult to eliminate than Plasmodium falciparum. Persistent P. vivax liver stages can be eliminated only by radical treatment with a ≥ seven-day course of an 8-aminoquinoline, with the attendant risk of acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Primaquine is the only generally available 8-aminoquinoline. Testing for G6PD deficiency is not widely available, and so whilst it is widely recommended, primaquine is often not prescribed. In the past, some countries aiming for vivax malaria eradication deployed mass treatments with primaquine on a massive scale, without G6PD testing. In Azerbaijan, Tajikistan (formerly USSR), North Afghanistan and DPR Korea 8,270,185 people received either a 14-day "standard" or a 17-day "interrupted" primaquine treatment to control post-eradication malaria epidemics. These mass primaquine preventive treatment campaigns were conducted by dedicated teams who administered the drugs under supervision and then monitored the population for adverse events. Despite estimated G6PD prevalences up to 38.7%, the reported frequency of severe adverse events related to primaquine was very low. This experience shows that with careful planning and implementation of mass treatment strategies using primaquine and adequate medical support to manage haemolytic toxicity, it is possible to achieve high population coverage, substantially reduce malaria transmission, and manage the risk of severe acute haemolytic anaemia in communities with a relatively high prevalence of G6PD deficiency safely.