Vivax malaria chemoprophylaxis: the role of Atovaquone-proguanil, compared to other options

Abstract

Background

Atovaquone-Proguanil is considered causal prophylaxis (inhibition of liver-stage schizonts) for Plasmodium falciparum, however, its causal prophylactic efficacy for P. vivax is not known. Travelers returning to non-endemic areas, provide a unique opportunity to study P. vivax prophylaxis.

Methods

A retrospective observational study. For 11 years Israeli rafters who had traveled to the Omo River in Ethiopia, a highly malaria endemic area, were followed for at least one year after their return. Malaria prophylaxis used during this period included: mefloquine, doxycycline, primaquine and atovaquone-proguanil. Prophylaxis failure was divided into early (within a month of exposure) and late malaria.

Results

252 travelers were included.in the study. 62 (24.6%) travelers developed malaria, 56 (91.9%) caused by P. vivax, with 54 (87.1%) cases considered as late malaria. Among travelers using atovaquone-proguanil there were no cases of early P.falciparum or P. vivax malaria. However, 50.0% of atovaquone-proguanil users developed late vivax malaria, as did 46.5% and 43.5% of mefloquine and doxycycline users; respectively; only 2 (1.4%) primaquine users developed late malaria (p<0.0001).

Conclusions

Short-course atovaquone-proguanil appears to provide causal (liver-schizont stage) prophylaxis for P. vivax, but is ineffective against late, hypnozoite-reactivation-related attacks. These findings suggest that primaquine should be considered as the chemoprophylactic agent of choice for areas with high co-circulation of P. falciparum and P. vivax.