The activation of vivax malaria hypnozoites by infectious diseases

The periodicity of vivax malaria relapses may be explained by the activation of latent hypnozoites acquired from a previous malarial infection. The activation stimulus could be the febrile illness associated with acute malaria or a different febrile infection. We review historical records to examine the association between relapses of Plasmodium vivax and febrile infectious diseases. In data from British soldiers in Palestine, epidemic falciparum malaria triggered a smaller epidemic of P vivax relapses only in those who had been extensively exposed to malaria previously. Relapses did not follow pandemic influenza infection. Evidence from three simultaneous typhoid and malaria epidemics suggest that typhoid fever might activate P vivax hypnozoites. Some data lend support to the notion that vivax malaria relapse followed febrile illness caused by relapsing fever, trench fever, epidemic typhus, and Malta fever (brucellosis). These observations suggest that systemic parasitic and bacterial infections, but not viral infections, can activate P vivax hypnozoites. Specific components of the host's acute febrile inflammatory response, and not fever alone, are probably important factors in the provocation of a relapse of vivax malaria.