The remarkable discovery of considerable plasmodial life cycle activity in the human spleen has been reported [1,2]. There is also recent non-microscopic evidence suggestive of malaria parasite accumulation there .
Miles Markus's blog
The idea that the non-circulating parasite origin of Plasmodium vivax malarial recurrence is both hypnozoites [1,2] and merozoites (not hypnozoites only) dates from 2011 [3,4]. The history appears in Table 1 in . There is recent (and superb) evidence that my decade-old, bimodal recurrence hypothesis must be correct.
Here is something of fundamental malariological interest:
A past suggestion is that both early and late homologous recurrences of Plasmodium vivax malaria can have a non-circulating merozoite origin [1–4].
There is now revealing new (February 2021) evidence which supports this idea. Some post-28-day recurrences that took place during a recent study appeared to be recrudescences rather than relapses . Thus, it seems likely that a combination of the two types of recurrence can occur after 28 days.
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)?
The misused plural words "malarias" and "plasmodia" have previously been mentioned in the MalariaWorld Newsletter (the former only in passing). Here, I highlight the usage problem by expanding on the subject.
Are up to 80% or more of detectable Plasmodium vivax malarial recurrences relapses (a relapse being a hypnozoite-mediated recurrence)? This is a topical matter and a very interesting question.
Attention has been drawn to the use of serology for revealing subclinical Plasmodium vivax malaria that can lead to ongoing transmission of the disease in human communities if parasite carriers are not treated .
A Blog by Pierre Lutgen in the MalariaWorld Newsletter (https://malariaworld.org/search/site/Malaria%20inhibits%20Covid) refers to the high overall Immunoglobulin E (IgE) levels that have been found in human populations in areas where malaria is endemic. Further to what is explained in his Blog, but on a different subject:
Only a "few" hypnozoites occur in patients who have Plasmodium vivax infections, compared to the large, non-circulating merozoite biomass that is now known to be present.
Therefore, to readily ascribe P. vivax malarial recurrences to hypnozoite activation, as is currently common practice, is no longer appropriate without good reasons for doing so. Forget about what you were taught at university in this context and keep an open mind.
As is well known, long-term malarial recurrences are a feature of human infections caused by species of Plasmodium. The frequency of recurrence varies. In P. falciparum malaria, long-term recurrence is rare, but not (contrary to popular belief) non-existent. P. malariae [Pm] and P. vivax [Pv] only will be considered below; and with reference to only the bone marrow as a site of parasite occurrence.