UPDATE COMMENTARY: Acquisition of novel insights has been taking place (reflected especially in 2018 reports) in relation to where plasmodial parasites go in the mammalian body. This new understanding has led to the hypnozoite hypothesis of relapse in malaria becoming partly out of date insofar as it is now a theory that is (in the way it has been applied since 1980) too restrictive. To elucidate:
What is meant by this statement is that as time passes, it is increasingly becoming apparent that it is unlikely that hypnozoites are the sole NON-CIRCULATING parasite source in homologous vivax malarial recurrences (first questioned in 2010/2011; see “Table 1” in article via link provided below). This applies to homologous recurrences of some other kinds of primate plasmodial infection as well, such as simian cynomolgi malaria. Until recently, nobody seemed to take this matter seriously, despite its importance in practical terms (if correct). One’s impression is that the suggestion that over-attribution to hypnozoite activation of e.g. vivax and cynomolgi malarial recurrences probably takes place, was generally regarded as a crackpot idea. Perhaps it was seen by some as a question to be ignored on the principle that it might go away; which it hasn’t, if only because it has by default just become highly topical. This aside, it would certainly now (in 2018) be simplistic to assume with confidence that only one NON-CIRCULATING parasite source (hypnozoites) explains ALL such recurrences. Although many of these relapse-like recurrences could indeed be relapses (hypnozoite origin), others might well be recrudescences (EXTRA-VASCULAR merozoite origin in the hypothetical but likely instances now under consideration). This is argued at length from various technical angles, including drug-wise, in the following 2018 publication. (Link to new and other explanatory information).