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COMMENTARY: Plasmodium in the Human Spleen

June 1, 2021 - 04:13 -- Miles Markus

The remarkable discovery of considerable plasmodial life cycle activity in the human spleen has been reported [1,2]. There is also recent non-microscopic evidence suggestive of malaria parasite accumulation there [3].

Thus, parasites in the human spleen are now a proven part of a large, non-circulating, asexual, erythrocytic parasite reservoir that was uniquely proposed to be (but lately is more widely believed to be) a non-hypnozoite source of recurrences of Plasmodium vivax (inter alia) malaria [46].

Three intriguing questions come to mind:

(A) Do plasmodial merozoites occur in dendritic cells in human spleens – as found by M.N. Wykes and M.F. Good et al. in dendritic cells in murine spleens [69]?

(B) Do plasmodial "merophores" occur in human spleens – as described by I. Landau and G. Snounou et al. in rodent spleens and elsewhere [69]?

(C) To what extent are non-circulating, asexual, human plasmodial parasites (especially in the spleen) killed in vivo by the 8-aminoquinoline drugs primaquine or tafenoquine, particularly when administered together with e.g. chloroquine (possible synergistic effect) [10]?

Perhaps researchers will in the future be able to shed light on these matters. To quote from the legend for Figure 2 in [9] (a human spleen section showing abundant, intact P. falciparum parasites): "Investigation is needed to determine whether parasites comparable to those found in rodents ... can persist in the primate spleen ... in both relapsing ... and nonrelapsing malaria ...".   

 

REFERENCES

1. Kho S et al. 2021. Hidden biomass of intact malaria parasites in the human spleen. New Engl J Med 384: 2067–2069. https://doi.org/10.1056/NEJMc2023884

2. 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. https://doi.org/10.1371/journal.pmed.1003632

3. 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. https://doi.org/10.1371/journal.pmed.1003567

4. Markus MB. 2017. Malaria eradication and the hidden parasite reservoir. Trends Parasitol 33: 492–495. https://doi.org/10.1016/j.pt.2017.03.002

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

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

7. Markus MB. 2012. Dormancy in mammalian malaria. Trends Parasitol 28: 39–45. https://doi.org/10.1016/j.pt.2011.10.005

8. Markus MB. 2015. Do hypnozoites cause relapse in malaria? Trends Parasitol 31: 239–245. https://doi.org/10.1016/j.pt.2015.02.003

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

10. Markus MB. 2019. Killing of Plasmodium vivax by primaquine and tafenoquine. Trends Parasitol 35: 857–859. https://doi.org/10.1016/j.pt.2019.08.009