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How Many Cases of Plasmodium vivax Malaria are Relapses?

November 17, 2020 - 22:35 -- Miles Markus

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.

The answer is that it is indeed a distinct possibility. The prevailing idea that recurrent bouts of P. vivax malaria are predominantly relapses is an assumption which is extremely tempting to make. It is based primarily on compelling data involving drug treatment with primaquine. Nevertheless, the assumption is not necessarily correct. Reasons why conceivably not are provided here (click on link):

https://doi.org/10.1016/j.pt.2019.08.009

The bottom line is that there is not yet any definitive proof, one way or the other, as to whether non-reinfection P. vivax malarial recurrences are mostly relapses (as opposed to recrudescences). The jury is still out on this.

Comments

Submitted by Anonymized User (not verified) on

It cannot be disputed that what seems likely and something which has actually been proven are different conclusions. The former is a calculated guess and the latter would be (if proven) a fact (hard science).

So considering that there is an additional possible explanation for parasite killing by primaquine (contained in the thought-provoking publication for which a website link is given in the blog), the seemingly entirely logical relapse percentage assumption should nevertheless not at this point be over-interpreted by expressing it as a fact.

It is not a known fact. At least not yet (if the assumption is correct), as indicated in the blog.

Submitted by Miles Markus on

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

It would be wonderful if this (how often recurrences originate from non-circulating merozoites rather than hypnozoites) could be investigated experimentally, such as by (partly) inter-host transfer of selected non-bloodstream parasites.

More than one of the papers referred to raises the question (e.g. in a text box/es) of the use of animal models. Also, is there anything in an additional paper (see below) that can be followed up? Note, amongst other things (although one of the questions posed has been answered in the meantime), the last sentence in the legend for the colour picture of a human malarial spleen section.

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