Plasmodium vivax Relapse Rates in Allied Soldiers during the Second World War: Importance of Hypnozoite Burden.

Allied soldiers suffered repeated relapses of Plasmodium vivax malaria during and immediately after the Second World War. This surprised many military medical officers who had underestimated the huge casualties produced by P. vivax malaria. Tropical (Philippines) strains of P. vivax were known to relapse more frequently than those from temperate regions (the United States). Intense exposure to mosquito infection likely increased the absolute number of hypnozoites in soldiers' livers. Both quinine and quinacrine were used as chemosuppressive agents, but their inconsistent use until at least 1943 promoted intermittent parasitological failures. Fear of hemolytic reactions after a mass casualty event in 1943 engendered fear and avoidance of the only 8-aminoquinoline pamaquine then available to cure relapses. Variable chemosuppression likely prevented acquisition of effective parasitological immunity. Unexpectedly high relapse rates in soldiers were likely an indirect measure of the high hypnozoite burden and suggest how difficult it will be to eliminate P. vivax malaria from endemic areas.