In Thailand, there is a high risk of Plasmodium vivax parasitaemia following treatment of P. falciparum infection. To inform the benefits of universal radical cure for patients with P. falciparum, the risk of P. vivax after P. falciparum was quantified across a range of co-endemic settings.
A systematic review identified prospective clinical studies of antimalarial efficacy for uncomplicated P. falciparum malaria, published before January 2018 undertaken in areas co-endemic for P. vivax. The primary outcome was risk of P. vivax parasitaemia following P. falciparum infection at day 42. Secondary outcomes were risk of P. vivax at day 28 and 63 and risk of any parasitaemia. Estimates were pooled using meta-analysis and heterogeneity was investigated using meta-regression.
We included 153 studies enrolling 31,262 patients. The risk of any recurrent parasitaemia by day 42 was 18.4% (95%CI 15.2-21.8; I2=94.8%; 117 estimates) with 37.1% (28.2-46.2, I2=92.2%) of these due to P. vivax. The risk of P. vivax parasitaemia was 5.6% (4.0-7.5; 92.7%; 117 estimates) by day 42 and 24.0% (18.0-30.6; 95.2%; 30 estimates) by day 63. P. vivax appeared later than P. falciparum recurrences and the risk was greater following rapidly-eliminated drugs and in studies undertaken in areas of short-relapse periodicity. The risk of P. vivax parasitaemia within 42 days of treatment with artemether-lumefantrine was 15.3% (4.1-31.4; 97.8%; 10 estimates). Partner drugs such as mefloquine or piperaquine delayed recurrence compared to lumefantrine, however, the risk of P. vivax parasitaemia was >15% by day 63 following all ACTs.
Following P. falciparum treatment, the risk of P. vivax parasitaemia is far greater than expected from reinfection alone. In co-endemic settings, universal radical cure with an ACT and hypnozoitocidal agent, for patients with P. falciparum or P. vivax, has the potential to reduce all-cause recurrent parasitaemia and facilitate malaria elimination.