Splenic Modulation of Plasmodium vivax Relapses and Hypnozoite Activation during the Second World War?

Despite their colonial experience with tropical medicine, Allied (United States, United Kingdom, Australia, and India) Armies in the Indo-Pacific region were surprised by the large number of Plasmodium vivax infections in their soldiers during the Second World War. Even after the institution of effective chemoprophylaxis with quinacrine, multiple cycles of clinical relapses often occurred when months of medication was discontinued. Nearly monthly symptomatic relapses (>10) were not unusual and resulted in important manpower losses after each campaign. Retrospective consideration suggests that small splenic size was associated with the risk of recurrent clinical episodes of vivax malaria. Potential non-mutually exclusive explanations for frequent relapses of vivax malaria in soldiers are reviewed. These include decreased retention of parasitized red blood cells by small spleens through greater filtration stringency preventing relapses from becoming clinically patent; small spleen size being a marker of lower innate and/or acquired immunity, modulating the risk of clinically patent recurrences; or small spleen size increasing the number of relapses through decreased removal of triggers of hypnozoite activation. Apparent splenic modulation of vivax malaria relapses suggests a complex interaction between the parasite and host that might be amenable to manipulation to facilitate malaria elimination.