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Is temporal Plasmodium vivax malarial recurrence information useful?

December 30, 2020 - 23:12 -- Miles Markus

A lot of attention has been paid over the years to when exactly recurrent clinical Plasmodium vivax malarial episodes take place, both old and recent literature on this subject often being cited by authors today. Does this recurrence information prove much, however? In other words, how important is it to know details of the timing and frequency of non-reinfection recurrences when these recurrences are of unknown origin (as explained below)?

There has been a marked tendency to assume that non-reinfection P. vivax malarial recurrences are usually relapses (hypnozoite origin). In recent years, this idea has been indirectly based on very plausible but not-yet-proven grounds. Moreover, to confuse the issue, it turns out that an unknown number of non-reinfection recurrences are probably hypnozoite-independent. More specifically, I am thinking of recrudescences that putatively originate from non-circulating merozoites, i.e. from non-hypnozoite, extravascular / sequestered parasite sources.

It was a decade ago that I first suggested this is as a (hypnozoite-unrelated) recurrence origin (see:, eliciting some fascinating knee-jerk reactions and non-reactions from malariologists that perhaps a psychologist would be able to interpret.

Only since about 2018 in the so-called post-hypnozoite-discovery era are such non-circulating merozoites believed more generally (by an increasing number of malariologists) to be, collectively, an additional (to hypnozoites) parasite reservoir associated with recurrences of P. vivax malaria.

So the question is: Does temporal P. vivax malarial recurrence information reveal anything of note, especially considering that it is invariably not known whether a given non-reinfection recurrence was a relapse (hypnozoite origin) or a recrudescence (merozoite origin)?

Perhaps less effort should be devoted to armchair-based consideration of the timing and frequency of P. vivax malarial recurrences, and more energy directed to parasitological research (which is indeed happening currently) that might definitively shed light on recurrence matters.

For instance, we are almost clueless as to inter alia whether the recurrence-precipitating factors are host, parasite, or environmental variables; or a combination of these. It is time to find out.


Submitted by Miles Markus on

The point is that it cannot be assumed that recurrence information for Plasmodium vivax malaria accurately reflects hypnozoite activation.

Compared with the number of other non-circulating, persisting parasites present which might give rise to recurrences, patients harbour relatively few hypnozoites.

To what extent these respective parasite numbers are changed (and how) by drug administration (e.g. chloroquine + primaquine) is uncertain (

Submitted by Miles Markus on

At the risk of repeating myself, what has not been completely figured out is where (and which) persisting Plasmodium vivax parasite stages are killed by the primaquine + chloroquine combination.

The situation might NOT be (or might be) as straightforward as it seems.

Explanation (which is in the article itself, not in the paper cited in the abstract):