A detailed epidemiologic study of the first 9 months of the H7N9 avian flu outbreak in China reinforces the image of the illness as one that rarely spreads from person to person but may possibly do so when there is prolonged, close contact between the sick and the healthy.
The lengthy report, released today by The New England Journal of Medicine, covers 139 human H7N9 cases recorded through November of 2013. All but 2 of the patients were hospitalized, and 47 (34%) died. More than 80% of the patients were exposed to animals, mostly poultry, before they got sick.
Monitoring of close to 2,700 contacts of the H7N9 patients turned up no additional cases, according to the report by a large team of mostly Chinese authors. However, they say person-to-person transmission might have occurred in four family clusters involving close contact.
That conclusion is similar to what the World Health Organization said in May 2013, after the first wave of H7N9 cases subsided. The agency reported then that there had been four clusters of two or more case-patients who were in close contact, suggesting the possibility of limited human transmission.
Every case investigated
The report says an epidemiologic investigation was conducted for every confirmed H7N9 case, with the first 82 cases probed by the Chinese Center for Disease Control and Prevention and the rest by local disease-control agencies. All but one of the cases were confirmed by polymerase chain reaction (PCR) or virus isolation; one was confirmed by serologic testing.
Among the 139 cases identified, the median age of patients was 61, 71% were male, and 73% lived in urban areas. Fifty-eight patients (42%) were 65 years or older, and just 4 (3%) were children under age 5, all of whom had mild cases. Of patients with available information, 73% had underlying medical conditions.
A 2-year-old boy and a 25-year-old woman were the only patients who avoided hospitalization. Of the 137 hospital patients, 125 had pneumonia or respiratory failure. For the 47 patients who died, the median duration of illness was 21 days—which contrasts with a median of 11 days for fatal H5N1 cases in China, the authors report.
Data on animal exposures were available for 131 of the 139 patients. Of these, 107 reported recent exposure to animals at live markets, including chickens (82%), ducks (22%), and swine (6%). Nine patients worked with poultry, six of them at poultry markets.
The authors say their findings add to the evidence suggesting that infected poultry are the source of H7N9 infection in patients who had poultry exposure, though this suspicion can't be verified without extensive testing of poultry. Other evidence for this link includes case-control studies and the observed drop in cases after live-poultry markets were closed last spring, they note.
The four family clusters described in the report include two in Shanghai, one in Jiangsu province, and one in Shandong province.
The family groups affected included a father and two sons, a father and daughter, a married couple, and a father and son. In each instance the family members had prolonged, close, unprotected contact, such as eating together, providing care, and going to medical visits together, the report says.
None of the secondary case-patients reported having any contact with animals before they got sick, and in the father-son cluster, neither patient reported any direct contact with poultry.
The researchers observe that three of the clusters, excluding the married couple, involved blood relatives, adding, "Similar family clusters of H5N1 cases that occurred after common exposures to poultry or limited human-to-human transmission have been identified."
They also note that studies have shown that H7N9 viruses can bind to human receptors in both the upper and the lower respiratory tract, and that the pathogen can spread among ferrets via droplets. "These studies support the observation that limited, nonsustained human-to-human transmission of H7N9 virus might occur," the authors comment.
Few illnesses in contacts
The investigators monitored 2,675 contacts of the 139 case-patients, excluding secondary patients in the four family clusters. Of that total, 53% were healthcare workers, 26% were relatives, and 20% were social contacts.
As of Dec 1, all the contacts had been monitored for at least 7 days. Twenty-eight (1%) of them experienced respiratory symptoms during the 7-day period, and PCR testing of throat swabs were negative for H7N9 in all 28 cases.
The findings "suggest that the risk of secondary transmission of H7N9 virus, including to health care personnel, is low at this time," the report says. "However, in four family clusters, limited, nonsustained human-to-human transmission of H7N9 virus could not be ruled out and may have occurred."
In other observations, the researchers comment that the age distribution among H7N9 patients is both older and wider than that among H5N1 patients in China, whereas the case-fatality ratio (CFR) for H7N9 (34%) is lower than for H5N1 in China and globally. (The global CFR for H5N1 is roughly 60%).
The authors also note that some mild H7N9 cases have been reported since surveillance was broadened last April, which suggests that there is a wide clinical spectrum of illness.
Li Q, Zhou L, Zhou M, et al. Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med 2014 Feb 6;370(6):520-32 (Early online release) [Abstract]
Related Feb 4 CIDRAP News story
Dec 9, 2013, CIDRAP News story noting father-son cluster
Aug 6, 2013, CIDRAP News story on father-daughter cluster
Jun 24, 2013, CIDRAP News story on study suggesting a broader clinical spectrum of illness with more mild cases than previously thought
May 31, 2013, CIDRAP News story on WHO report noting four case clusters