Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever
K E Russell-Lodrigue1, G Q Zhang, D N McMurray
1Department of Veterinary Pathobiology, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
Abstract:
Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.
Insights
A new guinea pig model effectively mimics human Q fever infection via inhalation. This model, using Coxiella burnetii, shows disease progression and vaccine efficacy, aiding Q fever research.
Area of Science:
- Veterinary Medicine
- Infectious Diseases
- Microbiology
Background:
- Q fever is a zoonotic disease caused by Coxiella burnetii.
- Existing animal models do not fully replicate human Q fever's inhalation route and clinical presentation.
- There is a need for a relevant animal model for Q fever research.
Purpose of the Study:
- To develop and validate a guinea pig aerosol challenge model for Coxiella burnetii.
- To mimic the natural inhalation route of Q fever infection.
- To establish a model that accurately reflects human acute Q fever clinical signs and pathology.
Main Methods:
- A guinea pig aerosol challenge model was established using Coxiella burnetii Nine Mile phase I.
- Animals were exposed to varying doses (10^1 to 10^6 organisms) via a specialized aerosol chamber.
- Clinical signs, weight changes, and lung histopathology were monitored for 28 days post-infection.
- Vaccine efficacy was assessed by challenging vaccinated guinea pigs.
Main Results:
- Clinical signs (fever, weight loss, respiratory distress, death) correlated with the infectious dose.
- Histopathology revealed dose-dependent bronchointerstitial pneumonia, evolving over 28 days.
- Guinea pigs vaccinated with a killed whole-cell vaccine were protected from lethal infection and fever.
Conclusions:
- The guinea pig aerosol model accurately replicates key aspects of human acute Q fever.
- This model provides a valuable tool for studying Q fever pathogenesis and evaluating interventions.
- The model demonstrates the potential efficacy of killed whole-cell vaccines against Q fever.
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