A Comparative Study of the Pathology and Pathophysiology of Severe Malaria in a Non-Human Primate Model

Lombardini, Eric Desombre (2017). A Comparative Study of the Pathology and Pathophysiology of Severe Malaria in a Non-Human Primate Model. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000c157

Abstract

With the rise in plasmodial drug resistance throughout the world, a dwindling arsenal of anti-malarials and a predilection for use of less than ideal murine models, the need for effective, applicable and established animal models through which to understand severe malarial disease and test potential treatments is becoming increasingly crucial. Plasmodium coatneyi was discovered in the Philippines in the early 1960s in Rhesus macaque monkeys and has been evaluated sporadically as a potential platform for comparative studies of Plasmodium falciparum induced severe and cerebral malaria in humans. Using 30 years worth of archival samples at the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, compounded with data and material from a series of prospective experimental studies, the work in this thesis sought to fully characterize and describe the pathology and pathobiology of the P. coatneyi/Rhesus macaque model. This included a thorough examination of the parasite host interaction, clinical symptomology, hematology and clinical pathology, gross pathology, histopathology, immunohistochemistry, cerebrospinal fluid cytokine profiles, transmission and scanning electron microscopy and atomic force microscopy of the disease in 45 adult rhesus macaques. The study further compared P. coatneyi with existing P. falciparum infected human material maintained at the National University of Singapore’s Vivax laboratory and Oxford University’s Ultrastructural Morphology Group, Nuffield Division of Clinical Laboratory Sciences. The study culminated in a successful clinical drug trial which evaluated the efficacy of varying doses of methylene blue as a radical cure for malaria in this non-human primate model. In many ways, the model mirrors P. falciparum, however the benefit of this evaluation is that it highlights not only the similarities but also the divergences. The successful completion of this description of the pathology and pathobiology of the P. coatneyi/Rhesus macaque model of severe and cerebral malaria adds a complex but effective animal model to the armamentarium in the ongoing war against malaria.

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About

  • Item ORO ID
  • 49495
  • Item Type
  • PhD Thesis
  • Keywords
  • Plasmodium coatneyi; rhesus macaque; animal model; severe malaria; cerebral malaria; Plasmodium falciparum
  • Academic Unit or School
  • Faculty of Science, Technology, Engineering and Mathematics (STEM)
  • Associated Research Centre
  • Mahidol-Oxford Tropical Medicine Research Unit (MORU)
  • Copyright Holders
  • © 2016 The Author
  • Depositing User
  • Eric Desombre Lombardini

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