Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Malarial liver parasites awaken in culture

Nature Medicine volume 20, pages 237–239 (2014)Cite this article

Subjects

The cure and elimination of malaria caused by Plasmodium vivax is hindered by the threat of relapse infections from undetectable dormant forms of the parasite in the liver. In a new breakthrough, using a related parasite, Plasmodium cynomolgi, it has been shown that the small nongrowing forms of the parasite, termed hypnozoites, can be reactivated in primary simian hepatocytes that have been infected and maintained in culture for 40 days, providing a system to study this parasite form with the development of potential new antihypnozoite drugs in mind (pages 307–312).

Whereas several available antimalarial drugs can kill growing parasites in the liver, only one drug will eliminate hypnozoites. This drug, primaquine, has a long dosing schedule (up to 14 days), which makes it challenging to effectively treat people carrying the hypnozoite reservoir. Primaquine can also cause severe hemolysis in people with glucose-6-phosphate dehydrogenase deficiency, a common condition in areas where malaria is endemic, further limiting the use of this drug3. Furthermore, P. vivax blood-stage parasites cannot be routinely cultured, and it remains uncertain whether the barriers to such cultivation can be overcome4. Liver-stage cultures, first reported in 1984 (ref. 5), have also been problematic and remain underdeveloped as a resource6, mostly because of the lack of reliable, consistent sources of P. vivax sporozoites. Fortunately, an alternative to the difficult-to-obtain P. vivax is available in P. cynomolgi, a relapsing primate malaria parasite of macaque monkeys that readily infects rhesus monkeys. Genetically and phenotypically, these two species are very similar to each other, making P. cynomolgi an unparalleled model for P. vivax7. In this issue of Nature Medicine, Dembélé et al.8 capitalized on the P. cynomolgi model system by developing a method for culturing hypnozoites in primary macaque hepatocytes for up to 40 days. This approach allows the study of this elusive stage of relapsing malaria parasites for the first time and demonstrates that the small, compact uninucleated parasite forms seen inside some hepatocytes are viable forms that can reactivate and resume normal growth and differentiation.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Growth and development of P. cynomolgi or P. vivax.

Marina Corral Spence

References

  1. White, N.J. & Imwong, M. Adv. Parasitol. 80, 113–150 (2012).

    Article  Google Scholar 

  2. Wells, T.N., Burrows, J.N. & Baird, J.K. Trends Parasitol. 26, 145–151 (2010).

    Article  Google Scholar 

  3. Baird, K.J., Maguire, J.D. & Price, R.N. Adv. Parasitol. 80, 203–270 (2012).

    Article  Google Scholar 

  4. Noulin, F. et al. Trends Parasitol. 29, 286–294 (2013).

    Article  Google Scholar 

  5. Mazier, D. et al. Nature 307, 367–369 (1984).

    Article  CAS  Google Scholar 

  6. March, S. et al. Cell Host Microbe 14, 104–115 (2013).

    Article  CAS  Google Scholar 

  7. Galinski, M.R., Meyer, E.V. & Barnwell, J.W. Adv. Parasitol. 81, 1–26 (2013).

    Article  Google Scholar 

  8. Dembélé, L. et al. Nat. Med. 20, 307–312 (2014).

    Article  Google Scholar 

  9. Mota, M.M. et al. Science 291, 141–144 (2001).

    Article  CAS  Google Scholar 

  10. Dembélé, L. et al. PLoS ONE 6, e18162 (2011).

    Article  Google Scholar 

  11. Krotoski, W.A. Prog. Clin. Parasitol. 1, 1–19 (1989).

    CAS  PubMed  Google Scholar 

  12. Schmidt, L.H. Am. J. Trop. Med. Hyg. 35, 1077–1099 (1986).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Parasitic Diseases and Malaria, John W. Barnwell is in the Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.,

    John W Barnwell

  2. Yerkes National Primate Research Center and the Department of Medicine, Division of Infectious Diseases, Mary R. Galinski is at the Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.,

    Mary R Galinski

Authors
  1. John W Barnwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary R Galinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to John W Barnwell or Mary R Galinski.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Barnwell, J., Galinski, M. Malarial liver parasites awaken in culture. Nat Med 20, 237–239 (2014). https://doi.org/10.1038/nm.3498

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.3498

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing