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Plasmodium vivax Malarial Recurrence Theory Vindicated

May 29, 2021 - 20:03 -- Miles Markus

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 [4]. There is recent (and superb) evidence that my decade-old, bimodal recurrence hypothesis must be correct.

This latest evidence for the validity of the hypothesis is the finding that in non-experimental human P. vivax malaria, a vast, non-phagocytosed, asexual parasite population is present in the spleen [5,6]. Also see [7].

Very few hypnozoites will be present in the liver in comparison. This is not to say that hypnozoites are unimportant as a source of P. vivax malarial recurrence. But non-circulating merozoites might be at least equally important in this regard [3,4].



1. Markus MB. 1980. The malarial hypnozoite. Lancet 1: 936.

2. Markus MB. 2011. Malaria: origin of the term "hypnozoite". J Hist Biol 44: 781–786.

3. Markus MB. 2017. Malaria eradication and the hidden parasite reservoir. Trends Parasitol 33: 492–495.

4. Markus MB. 2018. Biological concepts in recurrent Plasmodium vivax malaria. Parasitology 145: 1765–1771.

5. Kho S et al. 2021. Hidden biomass of intact malaria parasites in the human spleen. New Engl J Med 384: 2067–2069.

6. Kho S et al. 2021. Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: a prospective human splenectomy study. PLoS Med 18: e1003632.

7. Woodford J et al. 2021. Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: a prospective cohort study. PLoS Med 18: e1003567.