Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus.

Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus.
E. Johnson, N. Jaax, J. White, and P. Jahrling
US Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA.
Int J Exp Pathol. Aug 1995; 76(4): 227–236.
PMCID: PMC1997182

"Discussion: This study demonstrates aerosol transmission of Ebola virus to non-human primates. Inhalation doses as low as 400 PFU of virus caused a fatal illness clinically similar to that previously reported for monkeys infected by parenteral inoculation (Baskerville et a/. 1978; Bowen et at. 1978; Fisher-Hoch et a/. 1985). The illness was characterized by fever, anorexia and a petechial rash. Fibrin deposition and fibrin thrombi throughout the vascular system in all monkeys suggested that disseminated intravascular coagulation (DIC) may have also played a role in the clinical manifestations of Ebola virus infection.
Our aerosol infectivity findings for Ebola virus support Dalgard's and Pokhodyaev's observations that suggested a role for aerosol transmission of filoviruses in monkeys. Epidemiology studies of human disease outbreaks in sub-Saharan Africa did not suggest that aerosol transmission of filoviruses was likely in that setting."

“Although coughing was common among the human Ebola haemorrhagic fever cases in Africa, there was no direct evidence for the aerogenic spread of Ebola virus in human populations. Several potential explanations might account for this situation. It is possible that the quantity and distribution of the virus within most patient’s respiratory tracts may have been below the level needed to establish effective aerosol transmission. “

“We also demonstrated aerosol transmission of Ebola virus at lower temperature and humidity than normally present in sub-Saharan Africa. Ebola virus sensitivity to the high temperatures and humidity in the thatched, mud and wattle huts shared by infected family members in southern Sudan and northern Zaire may have been a factor limiting aerosol transmission of Ebola virus in the African epidemics."

"Both elevated temperate and relative humidity (RH) have been shown to reduce the aerosol stability of viruses (Songer 1967). Our experiments were conducted at 24 degrees C and less than 40% RH, conditions which are known to favor the aerosol stability of at least two other African haemorrhagic fever viruses, Rift Valley fever and Lassa (Stephenson et al. 1984; Anderson et al 1991)."

"If the same holds true for filo viruses, aerosol transmission is a greater threat in modern hospital or laboratory settings than it is in the natural climatic ranges of viruses. The route of infection, or the degree of the pulmonary involvement of the primary cases may also be an important factor to consider when evaluation the natural aerosol transmissibility of the filoviruses."

"While both parenteral and aerosol exposure to Ebola virus causes systemic disease involving all organs, monkeys exposed to the viral aerosols during our study developed strong immunoreactivity for Ebola Virus antigen in airway epithelium. In oral and nasal secretions, and in bronchial and tracheobronchial lymphoid tissue. By electron microscopy, viral replication after aerosol exposure occurred in the lungs and tracheobronchial lymph nodes, and extracellular virus accumulated in alveoli of the lung."

"Copious extracellular Ebola virus antigen was present in secretions on the mucosal surfaces of the nose, oral cavity and pulmonary airways of aerosol exposed monkeys, strong evidence to support the potential for secondary spread of Ebola virus by aerosol. As previously stated, aerosol spread was implicated in the spread of disease among the monkeys at Reston (Dalgard et al. 1992; Geisbert 1992) and may have occurred between monkeys and animal handlers who were in close contact with infected monkeys (CDC 1990)"

"Finally, host sensitivity to filovirus infections may also be a significant factor influencing the degree of aerosol transmissibility Asian (Macaca fascicularis) and African (Cercopithecus aethiops) monkeys know to be disseminating hosts for filoviruses (Gear et al 197; CDC 1990). Virus replicates extensively in Ebola virus infected non-human primates, reaching high concentrations in tissues (consistently greater than 6 log 10/g of tissue or serum for Reston virus,; P. Jahrling unpublished). Quantitate data for viraemia levels in humans are lacking as are estimates of minimal infections aerosol doses. Certainly filoviruses have infected humans with no known history of parenteral or ocular inoculation of the viruses. (Martini 1971; CDC 1990) and a respiratory route of infection cannot be rule out (Simpson 1977). Those cases may have resulted from exposures to unusual concentrations of aerosolized virus not often encountered naturally. In that regard, retrospective examination of any available archived human tissues by immunocytochemistry could prove to be helpful. “


"Regardless, we have shown that Ebola virus (Zaire strain) can be transmitted by aerosol in an experimental primate model. In light of the pathogenicity of human filovirus infections, health care personnel at risk of exposure should use precautions to minimize the risk of aerosol exposure while managing acutely ill haemorrhagic fever cases of unknown or filoviral etiology. The risk can be markedly reduced by adhering to sound and practical infectious disease management procedures. This requires curtailing aerosol generating procedures; using protective clothing including gloves and masks, adequately decontaminating potentially infectious material, and conducting viral diagnostic procedures in regional containment facilities capable of safely handling highly hazardous infectious agents (Comperts et al 1978; CDC 1988).”