The automated bioaerosol exposure system: Preclinical platform development and a respiratory dosimetry application with nonhuman primates

Hartings, Justin M.; Roy, Chad J.

doi:10.1016/j.vascn.2003.07.001

Cited by 130 publications

(118 citation statements)

References 47 publications

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“…First, an intramuscular (IM) exposure study was performed using a standard challenge dose of 1000 plaqueforming units (PFU). Two subsequent studies were performed using the aerosol exposure method 7,17,37 , the first using a target dose of 1000 PFU and the second using target doses of 100 and 10 000 PFU. For each study, animals were randomly selected from the colony for enrollment.…”

Section: Methodsmentioning

confidence: 99%

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

Bell

Shaia²,

Bunton

et al. 2014

Vet Pathol

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Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection.

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Section: Methodsmentioning

confidence: 99%

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

Bell

Shaia²,

Bunton

et al. 2014

Vet Pathol

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“…The actual dose received by guinea pigs in each exposure run was determined using calculations previously described. 12 A mean mass aerodynamic diameter of 1-3 microns for arenaviruses was used in the calculations. The actual inhaled doses for each group are listed in Supplemental Table 1.…”

Section: Macv Aerosol Exposure and Sampling Schemementioning

confidence: 99%

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs

et al. 2015

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Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virusChicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development.

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“…The macaque was then inserted into a class III biological safety cabinet inside a biosafety level 4 suite and exposed in a head-only aerosol chamber for 10 minutes to an aerosol created by a 3-jet Collison nebulizer (BGI, Inc, Waltham, MA) controlled by an automated bioaerosol exposure system. 40 Hank's buffered saline solution containing 1% fetal calf serum and 0.001% antifoam A was used as the collection medium in the all-glass impinger (AGI, Ace Glass, Vineland, NJ). Virus concentrations in starting solutions and AGI were determined by plaque assay.…”

Section: Aerosol Exposurementioning

confidence: 99%

Aerosol Exposure to the Angola Strain of Marburg Virus Causes Lethal Viral Hemorrhagic Fever in Cynomolgus Macaques

et al. 2010

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Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg virus (MARV) by aerosol to examine disease course and lethality. Macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. Gross pathologic lesions included maculopapular cutaneous rash; pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), were observed in the mediastinal lymph nodes and spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen, and liver of all animals examined. In infected macaques, nuclear expression of interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high endothelial venule endothelial cells; interleukin-33-positive fibroblastic reticular cells in the mediastinal lymph node were consistently negative for MARV antigen. These macaques exhibited a number of features similar to those of human filovirus infections; as such, this model of aerosolized MARV-Angola might be useful in developing medical countermeasures under the Animal Rule.

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The automated bioaerosol exposure system: Preclinical platform development and a respiratory dosimetry application with nonhuman primates

Cited by 130 publications

References 47 publications

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs

Aerosol Exposure to the Angola Strain of Marburg Virus Causes Lethal Viral Hemorrhagic Fever in Cynomolgus Macaques

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