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Modern Explanation for Plasmodium vivax Malarial Recurrences

April 20, 2020 - 00:04 -- Miles Markus

Malariologists have recently reiterated, in more than one paper, the notion that the non-bloodstream origin of Plasmodium vivax malarial recurrence is both hypnozoites (a term coined by me long ago [1]) and merozoites, not hypnozoites only. It has happened without any acknowledgement relating to the existing literature on the subject. Although the glaring omissions might have been inadvertent, let us nevertheless not become confused as to the background here. What needs to be pointed out is that this is not an original (new) idea. Far from it, in fact.

The opinion was first put forward almost a decade ago. The situation has in a way been vaguely reminiscent of what is said to have occurred in terms of how some people reacted when it was stated that the Earth is round, not flat. The plasmodial scenario was sketched (flogged) in a number of conference presentations between 2010 and 2020 (see [2] for details) and was the subject of a dozen or so papers that incrementally provided supporting rationale (some of the points made have now been repeated by other authors). This body of literature is far too large (and therefore familiar to many people) for any cavalier disregarding or unethical obfuscation thereof to be inconspicuous, i.e. go unnoticed. Such analysis had never been undertaken before in the context concerned. The concept [3–6] was both infamous and unique for about 7 years in that up until 2018, only the originator (see Table 1 in [4]) believed it to be correct. In other words, there were no other adherents. This zero statistic is based on what appeared and did not appear in the literature on malaria. It does not include two privately expressed (oral) comments of agreement, made to me recently by individuals who before that had not yet accepted the malarial recurrence idea which is the subject of this blog.

Some researchers are now, commendably, adding expanded (thus, confirmatory) analysis and excellent data. An example is the finding that there is a greater P. vivax parasite biomass in bone marrow than hitherto appreciated. Such evidence supports the already (i.e. previously) established, but not yet generally accepted, 9-year-old viewpoint regarding the likely parasite niche origins in recurring P. vivax malaria [3–6]. The important experimental and histopathological evidence alluded to above is new but the bimodal recurrence concept per se, which was developed as from 2011 on the basis of multiple criteria and novel extrapolation, is not new. To philosophize in respect of the concept, the wheel was irrefutably invented nearly a decade ago. Therefore, it cannot be re-invented, considering that it irreversibly already exists. Its existence is actually very widely known amongst malariologists (although perhaps not universally so), if only because of the (now in the process of reversing) infamy elicited since 2011 by the conventional hypnozoite dogma-destroying, new recurrence source suggestion. The original hypnozoite recurrence concept [7] is to be regarded as correct, however [8,9], as far as it goes – i.e. correct up to a point.

In conclusion, it is finally albeit slowly becoming recognized that non-circulating parasite sources of recurrent P. vivax malaria are probably both hypnozoites and extravascular/sequestered merozoites, not hypnozoites only. See [3–6] for the 2017–2019 articles concerning this long-standing, dual-origin recurrence concept. Most of the earlier papers on the concept (dating back to 2011) are listed in [4] but they can also be traced easily elsewhere [2].

SOURCES OF RELEVANT INFORMATION

1. “Malaria: origin of the term ‘hypnozoite’” https://doi.org/10.1007/s10739-010-9239-3

2. https://www.researchgate.net/profile/Miles_Markus

3. “Malaria eradication and the hidden parasite reservoir” http://dx.doi.org/10.1016/j.pt.2017.03.002

4. “Biological concepts in recurrent Plasmodium vivax malaria” https://doi.org/10.1017/S003118201800032X

5. “New evidence for hypnozoite-independent Plasmodium vivax malarial recurrences” https://doi.org/10.1016/j.pt.2018.08.010

6. “Killing of Plasmodium vivax by primaquine and tafenoquine” (despite the title, this concerns the latest recurrence concept) https://doi.org/10.1016/j.pt.2019.08.009

7. “The hypnozoite concept, with particular reference to malaria” https://doi.org/10.1007/s00436-010-2072-y

8. “A dual fluorescent Plasmodium cynomolgi reporter line reveals in vitro malaria hypnozoite reactivation” https://doi.org/10.1038/s42003-019-0737-3

9. “Transition from plasmodial hypnozoite to schizont demonstrated” https://doi.org/10.1016/j.pt.2020.01.011

Comments

Submitted by Anonymized User (not verified) on

This parasite origin scenario in Plasmodium vivax malarial recurrence is or is becoming, after a decade of malariological denial, a "Miles Markus told you so" situation!

When he looks in the mirror, he sees a golden halo shining brightly above his head.

No horns are visible.

Submitted by Miles Markus on

As regards comments here, no comment or elaboration from me.

Submitted by Anonymized User (not verified) on

If you think of the historical non-recognition of "the hypnozoite guy" (to use a known description), and add to that the more recent publication-ignoring antics, is it surprising that an "enough is enough" frame of mind could kick in?

No, it isn’t at all surprising.

What is remarkable, though, is that it did not happen sooner.

And don’t lose sight of the fact that he isn’t the naughty boy here.

Submitted by Anonymized User (not verified) on

We are introducing a citation ethics course for students, having discovered that they apparently do not hear about this sort of thing during the course of their training at our institution.

 

Submitted by Anonymized User (not verified) on

Maybe always incorporate ethics matters into the publishing / paper-writing sessions that are occasionally run at malaria conferences by journal editors for early career attendees.

Submitted by Miles Markus on

There is a bad background to particular non-citation deviousness that took place. It tipped a scale, actually, leading to the above blog. But as things stand, the less said about that matter, and others, the better. The skeletons need to be put to rest.

Submitted by Anonymized User (not verified) on

So perhaps it can be concluded that it seems unlikely that future omission of key original references in this whole context would easily go undetected now. Any studious avoidance of referencing appropriately, or creative referencing, would no doubt be horribly conspicuous, i.e. if pertinent citations are not there.

Submitted by Anonymized User (not verified) on

So perhaps it can be concluded that it seems unlikely that future omission of key original references in this whole context would easily go undetected now. Any studious avoidance of referencing appropriately, or creative referencing, would no doubt be horribly conspicuous, i.e. if pertinent citations are not there.

Submitted by Anonymized User (not verified) on

In defence of people who did not cotton on to the dual Plasmodium vivax malarial recurrence idea:

Many or most malariologists are epidemiologists, clinicians, cell biologists, mathematicians, biochemists, molecular biologists, etc., not experienced parasitologists.

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