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An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei
Published on: February 17, 2014
Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common
Laura E Via1, Danielle M Weiner, Daniel Schimel
1Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.
Insights
The common marmoset (Callithrix jacchus) serves as a novel small primate model for tuberculosis (TB), accurately mimicking human disease pathology, including cavitation. This model aids in studying Mycobacterium tuberculosis infection dynamics and strain virulence.
Area of Science:
- * Primate models in infectious disease research
- * Tuberculosis pathogenesis and immunology
- * Comparative genomics of Mycobacterium tuberculosis
Background:
- * Current small-animal models for tuberculosis (TB) lack cavitary disease, limiting human disease relevance.
- * Cavitary disease is a critical feature of human TB, impacting transmission and treatment.
- * Need for a small primate model that recapitulates human TB pathology.
Purpose of the Study:
- * To develop a small primate model for tuberculosis (TB) that exhibits human-like pathology, including cavitation.
- * To assess the utility of the common marmoset (Callithrix jacchus) for studying TB.
- * To evaluate the impact of different Mycobacterium tuberculosis strains on disease progression and pathology.
Main Methods:
- * Experimental infection of common marmosets (Callithrix jacchus) with diverse Mycobacterium tuberculosis strains (Beijing, X lineage, M. africanum).
- * Real-time monitoring of disease progression using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT).
- * Comparative analysis of pathology, dissemination, and cavitation in sibling marmosets infected with different strains.
Main Results:
- * Marmosets infected with M. tuberculosis developed fulminant disease with a spectrum of progression rates and clinical outcomes.
- * FDG-PET/CT accurately quantified disease burden, correlating with necropsy findings.
- * Lesion pathology recapitulated the spectrum observed in human TB patients, including cavitation and extrapulmonary dissemination.
- * Infection reproducibility and differential strain virulence were confirmed using sibling comparisons.
Conclusions:
- * The common marmoset is a suitable small primate model for studying human tuberculosis (TB).
- * This model accurately reproduces the complex pathology and disease spectrum of human TB, including cavitation.
- * The marmoset model facilitates real-time monitoring and assessment of M. tuberculosis strain virulence.
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