About this item:

361 Views | 836 Downloads

Author Notes:

Correspondence: mary.galinski@emory.edu

Conceived and designed the experiments: MRG, AM, EVSM, and JWB and members of the MaHPIC Consortium.

Performed the experiments: CJ and MCM, and members of the MaHPIC consortium.

Managed and deposited the data and metadata: JCK and members of the MaHPIC consortium.

Performed data analysis and generated the Figures: CJ.

Interpreted the data analysis: CJ, AM, JWB, and MRG.

Wrote the paper: CJ and MRG.

Provided expert knowledge, viewpoints and manuscript contributions: AM, JWB and JCK, and members of the MaHPIC consortium.

The authors acknowledge faculty and staff of Yerkes National Primate Research Center, especially the Animal Resources and Veterinary Departments, for their assistance. A special thanks is given to veterinarian Jennifer S Wood for her consultations regarding the clinical presentations of the animals.

For a list of MaHPIC Consortium members, please see the full article.

The authors declare no competing interests involved in the generation and assessment of these results.

Subjects:

Research Funding:

This project was funded in part by Federal funds from the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract # HHSN272201200031C (PI: Mary Galinski), which supports the Malaria Host-Pathogen Interaction Center (MaHPIC), as well as the Office of Research Infrastructure Programs/OD P51OD011132.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Infectious Diseases
  • Parasitology
  • Tropical Medicine
  • Plasmodium vivax
  • Host-pathogen interactions
  • Malaria
  • Non-human primates
  • Rhesus
  • Anaemia
  • Thrombocytopaenia
  • Systems biology
  • Animal models
  • UNINFECTED ERYTHROCYTES
  • FALCIPARUM-MALARIA
  • PRIMATE MALARIA
  • TERTIAN MALARIA
  • SCHUFFNERS DOTS
  • MACACA-MULATTA
  • ANEMIA

Plasmodium cynomolgi infections in rhesus macaques display clinical and parasitological features pertinent to modelling vivax malaria pathology and relapse infections

Tools:

Journal Title:

Malaria Journal

Volume:

Volume 15, Number 1

Publisher:

, Pages 451-451

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with P. vivax, including relapses. Here, the haematological dynamics and clinical presentation of sporozoite-initiated P. cynomolgi infections in Macaca mulatta (rhesus macaques) are evaluated over a 100-day period. Methods: Five M. mulatta were inoculated with 2000 P. cynomolgi B strain sporozoites. Parasitological and haematological data were collected daily to study the clinical presentations of primary infections and relapses. Peripheral blood and bone marrow aspirates were collected at specific time points during infection for future and retrospective systems biology analyses. Results: Patent infections were observed between days 10 and 12, and the acute, primary infection consisted of parasitaemias ranging from 269,962 to 1,214,842 parasites/µl (4.42–19.5 % parasitaemia). All animals presented with anaemia, ranging from moderate (7–10 g/dl) to severe (<7 g/dl), based on peripheral haemoglobin concentrations. Minimum haemoglobin levels coincided with the clearance of parasites and peripheral reticulocytosis was evident at this time. Mild thrombocytopaenia (<150,000 platelets/µl) was observed in all animals, but unlike haemoglobin, platelets were lowest whenever peripheral parasitaemia peaked. The animals’ conditions were classified as non-severe, severe or lethal (in one case) based upon their clinical presentation. The lethal phenotype presented uniquely with an exceptionally high parasitaemia (19.5 %) and lack of a modest reticulocyte release, which was observed in the other animals prior to acute manifestations. One or two relapses were observed in the four surviving animals, and these were characterized by significantly lower parasitaemias and minimal changes in clinical parameters compared to pre-infection values. Conclusions: Rhesus macaque infections initiated by P. cynomolgi B strain sporozoites recapitulated pathology of human malaria, including anaemia and thrombocytopaenia, with inter-individual differences in disease severity. Importantly, this study provides an in-depth assessment of clinical and parasitological data, and shows that unlike the primary infections, the relapses did not cause clinical malaria. Notably, this body of research has provided experimental plans, large accessible datasets, and blood and bone marrow samples pertinent for ongoing and iterative systems biology investigations.

Copyright information:

© The Author(s) 2016. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote