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Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin
Seth H Pincus1, Manoj Bhaskaran2, Robert N Brey3
1Departments of Pediatrics and Microbiology, Louisiana State University School of Medicine, Children's Hospital, 200 Henry Clay Ave, New Orleans, LA 70118, USA. spincu@lsuhsc.edu.
Abstract:
Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome.
Insights
Ricin aerosol exposure causes severe toxicity, including fever and breathing difficulties. Early diagnosis and treatment are crucial for improving outcomes in ricin poisoning.
Area of Science:
- Toxicology
- Biodefense
- Pulmonary Medicine
Background:
- Ricin toxin poses a significant bioweapon threat, with aerosol inhalation being the most dangerous exposure route.
- Early detection of ricin exposure is critical for effective medical intervention and treatment.
- Syndromic diagnosis, based on clinical and laboratory patterns, is key to guiding further diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the pathological effects of lethal and sublethal ricin aerosol exposure in rhesus macaques.
- To identify early clinical and laboratory indicators of ricin toxicity.
- To understand the long-term pulmonary consequences of sublethal ricin exposure.
Main Methods:
- Rhesus macaques were exposed to lethal and sublethal concentrations of aerosolized ricin.
- Clinical monitoring included telemetry, laboratory analyses, and post-mortem examinations.
- Pathological findings were correlated with clinical signs and blood work.
Main Results:
- Lethal exposure led to fever, tachycardia, dyspnea, neutrophilia, lymphopenia, hemoconcentration, and decreased serum albumin.
- Pathological findings included pulmonary hemorrhages, inflammatory exudates, and edema, consistent with fluid shifts.
- Sublethal exposure resulted in chronic pulmonary fibrosis, potentially mediated by M2 macrophages.
Conclusions:
- Ricin aerosol exposure induces distinct, recognizable clinical and hematological changes.
- Understanding these early signs is vital for prompt diagnosis and management of ricin poisoning.
- Interventions like supportive care, antidotes, or vaccines could mitigate ricin's severe health impacts.
