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Importance of Serology in Plasmodium vivax Infection

November 4, 2020 - 01:31 -- Miles Markus

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 [1].

Depending on its timing, serology can reflect the likely presence in the body of the largest (and newly recognized) putative P. vivax recurrence source; which must certainly be the source of many short-term recurrences, rather than all of these having a hypnozoite [2] origin. This non-hypnozoite source is non-circulating merozoites, such as in the bone marrow [3–5], something that will become clearer when further parasitological information which is in the pipeline is published in the near future. In addition to attacking the vast non-circulating merozoite reservoir, however, it is also important that the very small number (in comparison) of hypnozoites be cleared from the liver [1].

Hypnozoites and liver schizonts are eliminated by primaquine (and tafenoquine) [6,7], the success of which treatment in relation to effective drug dosage is greatly and mysteriously enhanced by concomitant administration of chloroquine [7]. For mode-of-action reasons [8], primaquine probably kills extra-hepatic, non-circulating P. vivax merozoites as well (analogous to its anti-gametocyte activity). However, the extent to which it does so and in what sites [8], especially when used in combination with chloroquine, is currently unclear.

This needs to be investigated somehow. The (directly proven) answer is relevant to the question of what proportion of recurrences of P. vivax malaria [9] are relapses and how many are recrudescences.



1. Longley, R.J. et al. 2020. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat. Med. 26: 741–49.

2. Markus, M.B. 2011. Malaria: origin of the term "hypnozoite". J. Hist. Biol. 44: 781–86.

3. Markus, M.B. 2017. Malaria eradication and the hidden parasite reservoir. Trends Parasitol. 33: 492–95.

4. Obaldia, N. 3rd et al. 2018. Bone marrow is a major parasite reservoir in Plasmodium vivax infection. mBio 9: e00625-18.  

5. Brito, M.A.M. et al. 2020. Morphological and transcriptional changes in human bone marrow during natural Plasmodium vivax malaria infections. J. Infect. Dis. (in press).

6. Commons, R.J. et al. 2020. Estimating the proportion of Plasmodium vivax recurrences caused by relapse: a systematic review and meta-analysis. Am. J. Trop. Med. Hyg. 103: 1094–99.

7. Dembélé, L. et al. 2020. Chloroquine potentiates primaquine activity against active and latent hepatic plasmodia ex vivo: potentials and pitfalls. Antimicrob. Agents Chemother. (in press).  

8. Markus, M.B. 2019. Killing of Plasmodium vivax by primaquine and tafenoquine. Trends Parasitol 35: 857–59.

9. Markus, M.B. 2018. Biological concepts in recurrent Plasmodium vivax malaria. Parasitology 145: 1765–71.


Submitted by Anonymized User (not verified) on

Does the small number of hypnozoites involved (ref. the blog) mean that the mathematical models of relapse in malaria are incorrect?

Submitted by Miles Markus on

Yes, the current models are probably wrong to whatever extent (variably). However, this is the nature of model(l)ing. Inaccuracy goes with the territory and is to be expected, depending on the subject. To go through the motions of mathematical modelling of malarial recurrence is a valid pursuit, nonetheless, provided that the results are taken with a pinch of salt. There is always the chance something important might be revealed by such modelling.

Submitted by Anonymized User (not verified) on

It would seem, from information in this blog, that to say that serology results can be used as a hypnozoite marker is far-fetched. It is speciously and naïvely stretching a point. One could equally (or better) assert that serology can show that parasites are present in the bone marrow.

What serology indicates about Plasmodium vivax malaria is merely infection.