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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 Miles Markus on

The November 2019 drug article (listed in the blog), in which a connection was made with the 9-year-old recurrence concept, was highlighted by Andrew Lover in a tweet earlier this year. Click, in his tweet, on the "cell.com" link to the article. Inter alia, note the 5th bullet point under "Open Questions" in Box 1 in the article. Perhaps not obvious, but the answers might (or might not) have implications in respect of the conclusions reached in a large number of papers that have been published on aspects of malaria. Long story. Anyway, if the link below is "clickable", it should bring up the tweet.

https://twitter.com/AndrewALover/status/1232719396516368385?ref_src=twsrc%5Etfw%7Ctwcamp%5Etweetembed%7Ctwterm%5E1232719396516368385&ref_url=https%3A%2F%2Fplu.mx%2Fplum%2Fa%2F%3Fdoi%3D10.1016%2Fj.pt.2019.08.009%26theme%3Dplum-sciencedirect-theme%26hideUsage%3Dtrue

 

Submitted by Miles Markus on

With reference to the blog (see above), I appreciate the comments received in the meantime from some leading malariologists who thought I had gone mad when, years ago, I came up with the alternative P. vivax malarial recurrence hypothesis. The number of people who now “believe” it has increased.

Submitted by Miles Markus on

Further to the "Comment" concerning the paper to which there was a link in Andrew Lover’s tweet (the clickable website appears in the blog as well): The answers to the "Open Questions" in Box 1, bullet point 5, in the article could indirectly affect (in part) interpretational matters arising from, inter alia, studies involving mathematical modelling and molecular characterization of parasites. Notably, the answers might (or might not) have implications in respect of conclusions related to the origin of P. vivax recurrences as based on recurrence patterns following drug treatment.

Submitted by Miles Markus on

To belabour the point made in the blog above, check out this previous blog; and particularly the Comments that follow it:

https://malariaworld.org/blog/why-does-vivax-malaria-recur

Reading between the lines in the Comments relating to the earlier blog will reveal that the non-citation scenario which has now manifested had been a premonition (strong gut feeling that the citation deficiency would occur)! It was anticipated partly because of previous experience. That former experience is described in an illuminating paragraph in the following publication:

https://doi.org/10.1016/j.pt.2020.01.011

There is evidence that both "then" and "now", not all of the authors concerned were aware (at least not initially, anyway) that there were seemingly blatant literature-associated omissions from their own papers.

The weird phenomenon of clearly inappropriate and counterproductive failure to give credit where credit is due (turning what might otherwise have been good publications into defective ones) has euphemistically been explained away in the past as follows: "The malaria field is competitive". Although that is an accurate statement, I would express things differently, especially when phrasing has carelessly been "lifted" from the non-cited paper(s), thereby giving the game away! But be this as it may.

The interesting citation irregularity circus surrounding P. vivax malarial recurrences that is reflected above obviously includes a classical example of insult having been added to injury.

Submitted by Miles Markus on

Concerning this malarial recurrence subject: What will be revealing for posterity (including historians) as regards the integrity of authors is what papers they cite (and how, exactly) or do not cite in future publications of theirs. Time will tell.

Submitted by Miles Markus on

This (see the Blog and Comments) is not merely a trivial matter of omission of inconsequential literature references. It is indistinguishable from plagiarism of important and hitherto unique new Plasmodium vivax recurrence-associated ideas ("unique" meaning NEVER previously raised or discussed by any other authors in the context concerned).

Even though further (i.e. confirmatory) information and analysis surrounding some of those original ideas has now been added by (in) the offending paper(s), active plagiarism is still involved if the non-citation of ideas was intentional. Readers familiar with (or who become familiar with) the content of the publications listed at the end of the Blog, and the earlier ones mentioned in the Blog, can very easily form their own opinions as to whether or not they think that something dodgy happened. That is, if they encounter and have perused such a "suspect" journal article(s) – as I have done.

In the event that ethical authors should choose to cite, in relation to the biology of P. vivax malarial recurrence, a literature-deficient publication(s) in any manuscript of theirs, they should henceforth also include a primary 2011–2019 malaria recurrence-related reference(s). Otherwise, original pertinent literature will by default again be conspicuous by its absence, especially following the revelations made above in the Blog and Comments.

Any repetition of the bizarre and irresponsible reference omission act that has taken place will inevitably lead to unprecedented aggravation of the debacle, by "putting a match to a powder keg". That would not do anybody any good. What would be best is to wisely avoid precipitating further drama in the first place, by ensuring that ethical citation practice is the order of the day.

Submitted by Anonymized User (not verified) on

Any questionable future citation events concerning this subject (including inaccurate self-citations) will clearly and justifiably go down in history, to the detriment of the citing authors.

Submitted by Anonymized User (not verified) on

It is obvious that correct future citing would nip this problem in the bud and, therefore, make it quietly go away.

Submitted by Miles Markus on

The immediate outcome of citation inaccuracy is the following (although this is self-evident):

As indicated somewhere above, it is no secret that other authors in the overall malaria field have likewise experienced unacceptable goings-on in relation to the citation of publications that they have authored. Thus, the curious P. vivax recurrence-related, reference omission phenomenon, both old (going back 4 decades) and more recent, is not unique.

In cases where non-citation or seemingly devious (dishonest) citation in connection with something "new" (i.e. not yet accepted malariological knowledge) has been inadvertent, this is perfectly understandable if very little had previously been published on the particular malarial topic concerned.

When there is an existing body of literature, however, the reader cannot necessarily discern, depending partly on the size of the body of literature: (A) Whether inaccurate citation or non-citation was intentional. Or (B) Whether it is purely profound ignorance (of the specific malarial subject area) that is on display.

Submitted by Anonymized User (not verified) on

In regard to the saga (see above), this publication teaches us what an ethically correct paper looks like citation-wise:

Obaldía N 3rd & Nuñez M. 2020. On the survival of 48 hr Plasmodium vivax Aotus monkey-derived ex vivo cultures: the role of leucocytes filtration and chemically defined lipid concentrate media supplementation. Malaria Journal 19: 278.

https://doi.org/10.1186/s12936-020-03348-9

Submitted by Anonymized User (not verified) on

One notes that the ethical handling of literature in the paper highlighted in the previous Comment here (see above) does not apply only to the matter of the origin of recurrences.

It is at the same time a shining example of an antidote to the following situation:

"Some parasitologists have been puzzled by the fact that the coining of the term 'hypnozoite' ... is rarely appropriately credited in publications. The explanation is that the omission appears to be largely habitual, since the first half of the 1980s, when papers either did not mention or downplayed (inadvertently or otherwise) the matter of the name's origin. Thirty years of dormancy, so to speak, elapsed before attention was first drawn in the literature (in 2010) to the original anomaly – which dates from 1980, the time of the discovery of the Plasmodium hypnozoite".

This paragraph is quoted from: https://doi.org/10.1016/j.pt.2020.01.011

Submitted by Anonymized User (not verified) on

It is a good thing to now be aware that citations are often inappropriate ones (or are missing) where the word "hypnozoite" is first mentioned in papers – especially when largely irrelevant publications are referred to pseudo-authoritatively instead of those that actually discuss hypnozoite-related matters from the most informed perspective. However, many authors lately have, no doubt, simply been following, uncritically, what other authors in the new millennium have done; the hypnozoite having been named before malariologists younger than 42 years of age were born. So when authors (particularly young ones) have cited literature poorly or inaccurately in the hypnozoite context, they will probably have done this unintentionally in most instances.

Submitted by Anonymized User (not verified) on

Re the previous comment here, it often happens in science. A paper that has little or nothing to do with the price of eggs gets cited (frequently self-citation that reflects an exercise in self-delusion), and then other people re-cite it. Poor citation of this kind does not necessarily go unnoticed, however; in which case the intended purpose has effectively backfired. For one thing, respect amongst peers is not elicited.

Submitted by Anonymized User (not verified) on

Arising from comments here – this trait, in the eyes of some of us who have discussed it, makes Nicanor Obaldia a respected researcher.

Submitted by Anonymized User (not verified) on

In the malaria field, citation of papers e.g. by friends of the authors (or self-citations), to the exclusion of literature that is more pertinent, has occurred not only in relation to hypnozoites.

Various researchers know from personal experience that the habit is more widespread than this – as has been stated in at least one of the postings here. However, the point bears repeating.

Submitted by Anonymized User (not verified) on

Relevant to this thread is, clearly, the following statement (link below) in the MalariaWorld Newsletter by the eminent, late Professor Wallace Peters. He wrote: "... it is often forgotten that he [Miles Markus] was the first to apply this term [hypnozoite] in relation to Plasmodium vivax."

https://malariaworld.org/comment/278#comment-278

Submitted by Miles Markus on

With reference to the previous posting, something comes to mind re Prof. Wallace Peters, who was an old school, true gentleman, and highly respected by everyone.

When I uttered the word "hypnozoite" in public for the first time upon introducing it for Plasmodium at the Spring Meeting of the British Society for Parasitology (University of Kent, Canterbury, UK, 5–7 April 1978), a titter was audible in the room, no doubt because the unfamiliar name sounded strange (if not absurd) to the audience initially. One could almost sense some people thinking: "WHAT is this guy doing?" Then suddenly the word wasn’t so funny anymore, apparently, because there was dead silence (which prevailed for the rest of the talk).

Afterwards, Prof. Peters came to speak to me. He had nice things to say; and indicated that he strongly supported the coining of the term "hypnozoite".

Submitted by Miles Markus on

As regards honesty in the citing of literature on malaria, graduate student advisors do not always set a good example!

Submitted by Miles Markus on

Well, that is the view of some students, anyway (rightly or wrongly), who have commented to me.

Submitted by Miles Markus on

I stand corrected by the students (and others), who say they are right!

Submitted by Miles Markus on

The previous comment is somewhat cryptic, so to speak. Note that what the commenter is referring to is the following comment on another blog.

In relation to malarial recurrences, the focus of biological research on Plasmodium vivax and associated theorizing has, lately, been very hypnozoite-orientated. There needs to be a partial change of mindset amongst the general population of malariologists at large. More work that involves non-hypnozoite, asexual parasite reservoirs should be carried out. For some of the reasons, see:

Markus, M.B. 2017. Malaria eradication and the hidden parasite reservoir. Trends in Parasitology 33: 492–495. http://dx.doi.org/10.1016/j.pt.2017.03.002

Markus, M.B. 2018. New evidence for hypnozoite-independent Plasmodium vivax malarial recurrences. Trends in Parasitology 34: 1015–1016. https://doi.org/10.1016/j.pt.2018.08.010

Markus, M.B. 2018. Biological concepts in recurrent Plasmodium vivax malaria. Parasitology 145: 1765–1771. https://doi.org/10.1017/S003118201800032X

Monteiro, W. et al. 2020. Cryptic Plasmodium chronic infections: was Maurizio Ascoli right? Malaria Journal 19: 440. https://doi.org/10.1186/s12936-020-03516-x

 

Submitted by Anonymized User (not verified) on

A matter concerning such Plasmodium vivax recrudescences (from non-circulating merozoites) arises. The indications are that it could prove to be very damaging and embarrassing for authors who try to climb on the bandwagon without citing any of the primary literature. This has been attempted at least three times for papers published in 2020. To push one’s luck by playing this dirty game would not be a good idea.

Submitted by Anonymized User (not verified) on

Clearly, be cautious about how you cite a bandwagon paper on this subject.

An even bigger mistake could be for the authors of such a bandwagon paper to subsequently do an inappropriate self-citation.

Submitted by Miles Markus on

Related to this subject and the comment thread here, some plasmodial phenomena covered in the two (taken together) pre-2017 publications listed below include, inter alia, the following:

Parasite nidus in the placenta (photomicrographs included); asymptomatic parasitaemia; drug-associated quiescence of erythrocytic parasites; extrapolation from long-term Plasmodium falciparum and P. malariae recurrences; merozoites in dendritic cells; Plasmodium in the skin; and merophores.

 

REFERENCES

Markus, M.B. 2012. Dormancy in mammalian malaria. Trends in Parasitology 28: 39–45. https://doi.org/10.1016/j.pt.2011.10.005

Markus, M.B. 2015. Do hypnozoites cause relapse in malaria? Trends in Parasitology 31: 239–245. https://doi.org/10.1016/j.pt.2015.02.003

Submitted by Miles Markus on

The following recently published article contains some little-known, interesting and very pertinent information concerning the spleen in relation to recrudescent malaria:

Monteiro, W. et al. 2020. Cryptic Plasmodium chronic infections: was Maurizio Ascoli right? Malaria Journal 19: 440.

Submitted by Miles Markus on

According to the Ascoli references in the informative paper by Monteiro et al. (Malaria Journal 2020, 19: 440), Ascoli published between about three and five decades before the hypnozoite was discovered. Therefore, unlike post-1980 malariologists, Ascoli had the advantage of not being exposed to the possibility of distraction by the hypnozoite concept of malarial relapse.

Submitted by Anonymized User (not verified) on

The number of papers in which there has been possible misinterpretation to some or other extent within a hypnozoite box (perhaps not having taken merozoites into account sufficiently or at all) is mind-boggling.

Is a proportion of the 1980–2020 literature on malaria redundant?

Some laboratory research that has been carried out during the past few years is relevant to this question. We await publication of the results with interest.

Submitted by Anonymized User (not verified) on

There is interesting information on plasmodial parasites in the spleen in the following two publications (even though the splenic content is not reflected by their short abstracts):

Markus MB. Mouse-based research on quiescent primate malaria parasites. Trends Parasitol. 2016; 32, 271–273. https://doi.org/10.1016/j.pt.2016.02.006

and

Markus MB. New evidence for hypnozoite-independent Plasmodium vivax malarial recurrences. Trends Parasitol. 2018; 34, 1015–1016. https://doi.org/10.1016/j.pt.2018.08.010

Submitted by Anonymized User (not verified) on

Two people were having a sword fight, when one of them cut off his opponent’s head. The victim was someone who believed only in a hypnozoite origin of non-reinfection Plasmodium vivax malarial recurrence, and refused to entertain the probability that non-circulating merozoites are also a source thereof. The victor announced: "You’re dead". True to form, the other man replied (with his head lying on the ground in front of him): "Oh no, I’m not".

Submitted by Anonymized User (not verified) on

As most of us now know, the first person in the post-hypnozoite-discovery era to have published on the subject of a non-hypnozoite, non-circulating parasite theory of Plasmodium vivax malarial recurrence was Professor Miles Markus. He expounded upon this many times, starting in about 2010. As from around 2018, other people started to agree (directly or indirectly) with his hypothesis.

Irrespective of what information gets added in the meantime, Prof. Markus remains the father of this dual recurrence origin (both a hypnozoite and a merozoite source) idea – just as he is also the father of the term "hypnozoite", in fact.

Maurizio Ascoli lived in pre-hypnozoite-discovery times, having died in 1958, as reported by Monteiro et al. in a 2020 article that is referred to elsewhere in this thread. Ascoli thought that parasites in the spleen can give rise to recrudescences but, of course, he did not know about the existence of hypnozoites.

Submitted by Anonymized User (not verified) on

Perhaps Prof. Markus’s broad background in apicomplexan biology helps.

Submitted by Anonymized User (not verified) on

This dual (hypnozoite + merozoite) recurrence theory was Prof. Markus’s second main prediction in regard to malaria.

His first main prediction was based on laboratory research of his that was of an original nature. He suggested that a hypnozoite stage might well occur in the life cycle of Plasmodium (1). Within fewer than 5 years, that prediction proved to be correct. To quote one of the hypnozoite researchers from the late 1970s and early 1980s, Miles Markus’s ideas strongly influenced our thinking (2).

1. Markus MB. Possible support for the sporozoite hypothesis of relapse and latency in malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1976; 70, 535.

2. Markus MB. Biological concepts in recurrent Plasmodium vivax malaria. Parasitology 2018; 145, 1765–1771.

Submitted by Miles Markus on

The upshot of all this is that perhaps the focus of recurrence-associated research should henceforth be heavily on asexual parasites and not involve only the small hypnozoite reservoir.

What might or might not be relevant is that in a recent in vitro study (reference provided below), hypnozoite activation events were found to be infrequent in relation to the number of hypnozoites present.

So what happens in humans infected with Plasmodium vivax?

REFERENCE: Voorberg-van der Wel, A.M. et al. 2020. A dual fluorescent Plasmodium cynomolgi reporter line reveals in vitro malaria hypnozoite reactivation. Communications Biology 3: 7.

Submitted by Anonymized User (not verified) on

Why did it take as long as 8 or so years for the penny to start dropping re this bimodal (hypnozoite + non-circulating merozoite) P. vivax malarial recurrence concept? The signs were there.

Submitted by Anonymized User (not verified) on

Literature has been incorrectly cited by some authors, giving the impression that persisting Plasmodium ovale hypnozoites were found in the humanized mouse host.

This has apparently happened for P. vivax, but not in fact in initial P. ovale research, although late hepatic P. ovale schizonts were observed. See:

https://doi.org/10.1016/j.pt.2016.02.006

If persisting P. ovale hypnozoites have been detected by anyone in the meantime, is there a journal reference(s) for this?

Submitted by Anonymized User (not verified) on

This looks like the way to go:

Pending further research, stop simplistically repeating, parrot-fashion, that hypnozoites are the cause of relapse in Plasmodium ovale malaria (even though that could possibly prove to be correct).

Also, consider stating that non-reinfection malarial (P. vivax, etc.) recurrences "might" (if you want to err on the side of caution) also have a non-hypnozoite, non-circulating parasite origin(s).

But as regards this concept, carefully cover yourself (to avoid comeback, since it is not yet a "standard" view malariologically) by citing chapter and verse ethically and correctly. Be seen to be civilized. Don’t credit the concept to the wrong authors. Finally, don’t try to fool the reader, by reference omission or otherwise, into thinking that it is your own idea.

Submitted by Miles Markus on

Re the P. ovale matter, this makes sense (at least for now). It is a reminder that in 2010, J. Richter et al. published a paper entitled: "What is the evidence for the existence of Plasmodium ovale hypnozoites?"

Submitted by Anonymized User (not verified) on

When all these background details are taken into consideration, it seems pretty obvious how to correctly cite (and how not to cite) Plasmodium vivax recurrence-related literature in the context of hypnozoites and so on.

Logically, with numerous malaria researchers now being in the true picture, failure to get this right will simply result in authors making idiots of themselves (or worse).

Submitted by Anonymized User (not verified) on

The following statement appears in an appendix to a 2017 (refreshed) Malaria Eradication Research Agenda (malERA) paper: "... some experts suggest that relapse may arise from both hypnozoites and quiescent merozoites ...". See:

https://doi.org/10.1371/journal.pmed.1002455.s004

The reference provided there and listed at the end of the appendix is a paper by Markus, which was included in the original (2011) malERA, probably with slightly different associated wording. Whoever made this malERA input at whatever stage(s), perhaps a member(s) of a panel(s), was wide awake, not doing what hypnozoites do.

The 2017 supplementary document (link provided above) says, in the same place, that the number of persisting non-hypnozoites will be small; but the number is now known to be large (for some non-hypnozoite parasites).

Otherwise, the various 2017 malERA articles published in PLoS Medicine are, in the same recurrence respect, hypnozoitophilic only. Perhaps the next malERA version will be different.

Submitted by Anonymized User (not verified) on

Checking re part of the second-last comment above (for citations in past publications where “hypnozoite” is first mentioned) reveals the following:

Sometimes, references are appropriate.

Often, there isn’t any reference.

Then there are cited papers which had no connection with hypnozoites other than having mentioned them. Thus, there was no primary connection with the naming or discovery of hypnozoites. This is ridiculous. Self-citations stand out in this regard.

There is certainly a need, here, for citation practice reform.

Submitted by Miles Markus on

Remember, though, that some of this hypnozoite history became generally known only 10 years ago.

Submitted by Anonymized User (not verified) on

I reviewed a recurrent malaria-associated manuscript (MS) for a journal. It included diverse references that had previously been unearthed and gathered together (maybe 20 or so of the references listed in the MS) and published together with discussion in more than one paper (different authorship from that of the MS, however). Here and there in the MS section concerned, small bits of the published phrasing had been used verbatim, thereby revealing the sources (with which I am familiar) of the information. There was one citation in that part of the MS to the earlier authorship, but to the wrong paper. I pointed this out and changed it to the correct reference.

The MS was rejected by the journal (although not by me as a referee). A modified version appeared later on in another journal, but without any acknowledgement regarding what had originally been published. This is unfortunate. Credit needed to be given for what had been published previously because an original compilation and related “eureka” matters on the part of the subsequent authors were not involved (contrary to how things will seem to the reader), although the authors did provide useful additional input of their own. The presence of the single citation in that particular place in the article would probably have dealt with the normal previous literature crediting requirement sufficiently, had it not been omitted.

This experience of mine reinforces the validity of some of the comments in this whole MalariaWorld Newsletter thread. The comments are not figments of the imagination. Unethical stuff has been going on. Some people don’t seem to know any better.

It would be understandable if the cat suddenly leaps out of the bag one day in relation to a future non-citing recurrent malaria-type publication(s), should any such non-crediting paper(s) indeed be published in due course. Alternatively, the same thing could occur if an already existing, likewise seriously citation-deficient article were to become cited to the academic disadvantage of whoever originally came up with whatever it was that they came up with, and they quite rightly object.

Let’s hope that neither of the above happens and that everyone will live happily ever after.

Submitted by Anonymized User (not verified) on

Is it always authors who are to blame if their citations are inadequate or incorrect? Could journal manuscript reviewers sometimes be messing things up?

Submitted by Miles Markus on

The dual (both a hypnozoite and a merozoite origin) Plasmodium vivax malarial recurrence concept that is the subject of this blog (see above) has been correctly credited in an informative 2021 review. Details and the website link are provided below. It has happened where references 67–69 are cited.

However, just to be clear, it should be noted that the rationale in the sentence quoted below from the end of the paragraph in which references 67–69 are cited is part of what is entirely attributable, in the post-hypnozoite-discovery era, to the author of references 67–69. That author very explicitly propounded the dual recurrence origin idea (both in publications and at international conferences) when the hypnozoite theory of malarial relapse was overtly prevailing. Nobody took much notice.

The dual recurrence idea is not attributable to any authors of references 70–72, who provided interesting information, but did not cite the author of references 67–69; partly because of when, time-wise, the respective papers were published.

QUOTATION FROM THE ARTICLE: "Because P. vivax does not persist as sporozoites in human blood, no hypnozoites could have developed in the recipients. Thus, these records may suggest that P. vivax malaria can recur independent of hypnozoites".

This is, precisely, one of the reasons (but not the only one) that were stated repeatedly between 2010 and 2020 by the author of references 67–69 in support of the bimodal P. vivax malarial recurrence hypothesis. He gave additional examples in other papers of his of recurrent plasmodial parasitaemia that followed blood-stage parasite inoculation, indicating a non-hypnozoite origin.

SOURCE: Sato, S. 2021. Plasmodium – a brief introduction to the parasites causing human malaria and their basic biology. Journal of Physiological Anthropology 40: 1.

https://doi.org/10.1186/s40101-020-00251-9

Submitted by Miles Markus on

I became aware of the article (ref. the previous comment here) because of a citation notification.

I was not a manuscript reviewer.

Submitted by Anonymized User (not verified) on

Looking closely, this "Clarification re P. vivax malarial recurrences" comment reveals something important.

It indirectly indicates HOW (unrelated to the new P. vivax review as such) we should NOT, either "accidentally" or on purpose, cite the no. 70–72 publications which are listed in the new P. vivax biology paper. That is, if we do cite any of those three references.

It should be easy to intelligently avoid a misattribution (or ambiguous attribution) bungle in this regard. Such an error could lead to prompt post-publication reaction and correction thereof which, needless to say, would not be desirable.

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