For the past 40 years, we have readily ascribed recurrences of Plasmodium vivax malaria to hypnozoite activation.
But during this 40-year period, we have been completely unaware that there are extremely large numbers of merozoites (compared to only a few hypnozoites) hiding outside the peripheral bloodstream – not only sequestered but happily multiplying extravascularly in tissues.
It is likely that these merozoites give rise to recrudescences. Primaquine or tafenoquine could kill them to whatever extent, however (not being exclusively hypnozoitocidal). That is, in addition to eliminating hypnozoites. If many or most of the merozoites are indeed inactivated by primaquine or tafenoquine, then this means that the vast majority of P. vivax recurrences which take place despite drug treatment (or occur in untreated cases) might not be relapses (i.e. hypnozoite-mediated recurrences), as is currently thought.
To elaborate, it has been rationalized that when there hasn’t been any recurrence, it is because hypnozoites were successfully killed, e.g. when therapy involved a synergistic primaquine + chloroquine combination. Conversely, if recurrences take place when prior drug treatment did not include primaquine (i.e. it was with chloroquine only), we have automatically blamed hypnozoites for the recurrences – not taking the hidden merozoites into account, because we have not known that they exist.
So what is going on?
The most recent discussion appears here: