Dennis Shanks and Nick White recently reviewed historical data on the interaction of febrile diseases of known etiology and vivax malaria in the lancet. (http://www.sciencedirect.com/science/article/pii/S1473309913700951#). They conclude that among others S. Typhi and P. falciparum may act as stimuli to reactivate hypnozoites. I was wondering how one would most efficiently design a study to address this?
Consider a hypothetical experiment: You would want a susceptible population (i.e. one with hypnozoites present), then randomly expose half of them to some agent that may lead to reactivation, after which we observe the difference in reactivation over time between two the groups.
In the absence of RCTs, I would look for population where the exposure to the factors on interest is as close to random as possible. This is what is so elegant about the paper by Shanks and White's use of military populations: The exposure to various potential exposures is not a consequences of endogenous characteristics of the individual soldier, but is determined by where the soldier is stationed.
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