Primaquine (PQ) is the only widely available treatment for the prevention of Plasmodium vivax relapse. Malaria causes anaemia that can be compounded by primaquine-induced haemolysis, particularly in glucose-6-phosphate-dehydrogenase (G6PD) deficient individuals. The aim of this study was to determine the haematological response following P. vivax malaria and the attributable haemolysis induced by primaquine.
We conducted a systematic review to identify all prospective P. vivax therapeutic clinical trials published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology and the haematological response estimated using a linear mixed effects model with non-linear terms, controlling for confounding factors.
In total, 3,421 patients from 29 studies were included in the analysis, the majority of which had normal or unknown G6PD status. In the 1,975 patients treated with chloroquine (CQ) alone, Hb fell to a nadir on day 2, before subsequently recovering rapidly and plateauing after day 7. Higher baseline Hb was associated with a greater absolute fall in Hb; in those with a baseline Hb £11.5 g/dL, 72.2% (182/252) had no fall in Hb during early follow-up. In the 1,446 patients treated with CQ+PQ, the Hb nadir was 0.13 g/dL (95%CI -0.19 to 0.45; p=0.414) less than in patients treated with CQ alone. However, by day 42 patients treated with CQ+PQ had an Hb 0.64 g/dL (95%CI 0.32 to 0.95; p<0.001) higher than those treated with CQ alone. The Hb on day 42 was significantly lower in those patients with recurrent parasitaemia (0.69 g/dL, 95%CI 0.47 to 0.91; p<0.001).
The fall in Hb following the treatment of vivax malaria primarily relates to malaria, rather than treatment with PQ. Treatment with PQ leads to a higher overall Hb by day 42, likely due to prevention of recurrence.