
A series of experiments in monkeys suggest that drinking raw milk contaminated with highly pathogenic H5N1 avian flu is a risk for infection but may lead to less severe illness than respiratory tract exposure to the virus, researchers reported yesterday in Nature.
The study by virologists with the National Institute of Allergy and Infectious Diseases involved cynomolgus macaques who were exposed via three inoculation routes to the 2.3.4.4b clade of H5N1, the strain of the virus that's been circulating in US dairy cattle since last spring and has infected 40 dairy workers in four states, producing mostly mild illness. The route for cow-to-human transmission so far has been undetermined, and the researchers wanted to use the monkeys— a surrogate model for human infection—to investigate the pathogenesis of different routes of infection.
Using a dose of the virus that's close to what's been found in raw milk samples, the researchers infected 18 macaques, exposing 6 to the virus intranasally to mimic an upper respiratory tract infection, 6 via the intratracheal route (windpipe) to mimic a lower respiratory tract infection, and 6 via the orogastric route (mouth and stomach) to mimic consumption. After 14 days, they found that lower respiratory tract exposure caused systemic infection with severe pneumonia and upper respiratory tract exposure resulted in mild-to-moderate pneumonia.
Limited infection
The macaques exposed via the mouth or stomach, however, had limited infection but showed no signs of illness. All the monkeys showed evidence for oral and limited nasal shedding, but shedding was higher and prolonged in those inoculated in the nose and windpipe.
"Overall, our study shows that lower and upper respiratory tract infection can lead to systemic virus replication, virus shedding and pneumonia with varying degrees of disease outcome," the study authors wrote. "In contrast, orogastric exposure led to virus infection, reduced virus shedding and subclinical disease."
The researchers caution, however, that their model is a surrogate for people drinking raw milk contaminated with H5N1. "To what extent it recapitulates human infection remains, as yet, unclear."