Study of H7N9 in macaques shows widespread, sustained replication
H7N9 avian flu, which emerged in humans in China in the spring of 2013 and has since caused more than 450 cases, was found to replicate well in both the upper and lower respiratory tracts of cynomolgus macaques, a model for humans, and to show extended replication in the upper tract, indicating the possibility of prolonged shedding and transmissibility, say findings of a study today in mBio.
Macaques were used because they reflect human physiology and attachment patterns of H7N9, even better than ferrets do, the authors explain.
The researchers inoculated eight 5-year-old cynomolgus macaques via the ocular, oral, intranasal, and intratracheal routes with infectious doses of H7N9. The animals were checked twice daily for clinical signs. Signs of disease began 1 day postinoculation (dpi), and clinical disease peaked at 3 to 4 dpi.
Six of the eight animals had obvious respiratory signs, including increased respirations, abdominal breathing, and coughing; only one had nasal discharge and cough. The induced clinical disease was judged to be moderate.
Chest films showed interstitial infiltration, first in the lower right lung lobe and then spreading. Oropharyngeal swabs were positive by 1 dpi and remained so through 6 dpi. Not all nasal swabs were positive, nor were conjunctival swabs. Bronchoalveolar lavage showed H7N9 virus in the fluid of all animals at 1 dpi that continued through 6 pdi. The authors surmised that virus shedding occurred primarily through the throat.
Lung changes were similar but less severe histopathologically to those in infected humans and included diffuse alveolar damage, infiltration of polymorphonuclear cells, and other changes.
Viral titers in nasal turbinates, oronasopharynges, tracheas, bronchi, and lung tissue samples showed the H7N9 replicated well in both the upper and lower respiratory tracts. However, the titers in samples from tissue other than the lung were higher than those in the lungs, and they did not decrease from 3 dpi to 6 dpi, as did those of the lung samples. The authors say this indicates not only widespread but also sustained viral replication throughout the upper respiratory tract.
Although H7N9 caused mild to moderate disease in the macaques, the authors say it was more pathogenic than seasonal influenza A virus and most 2009 H1N1 isolates but not as pathogenic as the 1918 flu virus or H5N1 avian flu.
H7N9 in humans has tended to be more severe than that induced in macaques in this study. The authors say this may be due to underlying medical complications in infected patients.
Aug 12 mBio study
Australia sees doubling of flu cases over last year, with H1N1 prominent
Nearly three fourths of the rapidly rising number of flu cases in Australia this season have been caused by the 2009 H1N1 strain, and far more than just the elderly are being affected, according to a report today from China's new agency Xinhua.
The Influenza Specialist Group (ISG) puts the number of lab-confirmed cases as of today at 21,060. This is double the number at this time last year, Xinhua reports, and 2009 H1N1 is the cause of almost three fourths of them. SIG chairman Dr. Alan Hampson says that fact is the reason for the severity of cases so far this year.
During the 2009 H1N1 flu pandemic, younger, otherwise healthy people were affected at least as much as the elderly, who are often thought of as the main population at risk for flu. This is true of the influenza hitting Australia this year, said Hampson.
ISG notes that the vast majority of flu cases are not tested. That, plus lag time between confirmation and reporting, may well underestimate flu activity.
Aug 12 Xinhua story
Aug 12 ISG update
Quebec GSK flu vaccine plant gets nod to solve contamination issues
GSK, owners of an influenza vaccine plant in Canada that has been cited as having contamination problems, has received approval from Health Canada on a plan and timetable for solving the issues, says a Canadian Press article today. GSK presented its proposal to Health Canada on Jul 31.
Water purification problems were identified at the plant, which is located in Ste. Foy, Quebec, during inspections by US Food and Drug Administration (FDA) and Health Canada in the spring. Health Canada spelled out seven "major observations," which are items that show required standards are not being met.
The FDA issued a warning letter to GSK on Jun 21. It stated that 21% of the year's vaccine produced at the plant could not be released to market because bacterial counts were above safety limits. A warning letter, says the story, is "the last step before possible suspension of a license to supply to the U.S. market."
The plant, which is the only flu vaccine plant in Canada, manufactures 53% of the seasonal vaccine used in the country and provides 23 million doses for the United States, in addition to having a contract to provide pandemic vaccine to Canada.
Aug 12 Canadian Press story
Jul 23 CIDRAP News scan on the plant