Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Radiologic responses in cynomolgus macaques for assessing tuberculosis chemotherapy regimens
Antimicrobial Agents and Chemotherapy, Volume 57, No. 9, Year 2013
Notification
URL copied to clipboard!
Description
Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Lin, Philana Ling
United States, Pittsburgh
University of Pittsburgh School of Medicine
Tomko, Jaime A.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Dartois, Véronique A.
United States, Newark
Rutgers Biomedical and Health Sciences
Scanga, Charles A.
United States, Pittsburgh
University of Pittsburgh School of Medicine
United States, Pittsburgh
University of Pittsburgh
Frye, Lonnie James
United States, Pittsburgh
University of Pittsburgh
Janssen, Christopher F.
United States, Pittsburgh
University of Pittsburgh
Klein, Edwin C.
United States, Pittsburgh
University of Pittsburgh
Barry, Clifton Earl
United States, Bethesda
National Institutes of Health Nih
Flynn, Jo Anne L.
United States, Pittsburgh
University of Pittsburgh
Statistics
Citations: 136
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1128/AAC.00277-13
ISSN:
10986596
Research Areas
Cancer
Environmental
Infectious Diseases
Noncommunicable Diseases