Flu Virus binding to Receptor Cells – Credit CDC
In the summer of 2013 Taiwan reported the first known human infection with an avian H6N1 virus, in a a 20-year-old female who was hospitalized with mild pneumonia on the May 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on the 11th.
Were it not for the enhanced surveillance for H7N9, which had only recently broken out in Mainland China, there is a pretty good chance this novel flu infection would have gone unnoticed.
And that’s why we really don’t have a good handle on just how often these novel flu viruses jump to humans. Often, these infections present just like any other flu or respiratory infection, and only rarely are the right tests done to determine the cause.
Over the years we’ve seen heated debates and scientific `guesstimates’ that have attempted to quantify the number of people who have been infected with novel H5N1 (see The Great CFR Divide), H3N2v (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012), and H7N9 (see Lancet: Clinical Severity Of Human H7N9 Infection) with varying results.
Although difficult to mount, expensive, and subject to some limitations – serological testing of a large cohort of individuals is undoubtedly the best way to determine what the level of exposure to a particular virus a community has experienced. Infections – even mild or asymptomatic ones – generally leave behind strain-specific antibodies which may be detectable months or even years later.
Assuming your test is sensitive enough to detect the right antibodies, and specific enough not to produce false positives, you can get a pretty good idea how many people in a community have had a previous exposure.
Categorize your test subjects by age, gender, location, and occupation – and you can not only get an idea how common infection with this novel virus is across a population, you can begin to tease out some interesting information about relative exposure risks.
Which is exactly what researchers in China have done, looking for evidence of previous H6 influenza exposure among a cross section of people from both Northern and Southern China. Yesterday, the EID Journal published the following letter, which describes a small, but significant number of people in their serological study who tested positive for H6 influenza antibodies (indicating previous exposure).
While the overall number of positives was low (298 by HI, 63 by MN) out of 15,689 samples, not unexpectedly, people with frequent exposure to poultry and/or live birds were more likely to test positive.
Seroprevalence was noticeably higher in the southern provinces than in the north. Interestingly, this same study found a far lower seropositivity for H5N1 (only 2 positive results), but a much greater seropositivity for H9N2 (3.4% positive).
Follow the link below to read this letter, and view its data, in its entirety:
Volume 21, Number 7—July 2015
Li Xin, Tian Bai, Jian Fang Zhou, Yong Kun Chen, Xiao Dan Li, Wen Fei Zhu, Yan Li, Jing Tang, Tao Chen, Kun Qin, Jing Hong Shi, Rong Bao Gao, Da Yan Wang, Ji Ming Chen, and Yue Long Shu
To the Editor: Influenza virus subtype H6 was first isolated from a turkey in 1965 in the United States (1) and was subsequently found in other parts of the world (2). Over the past several decades, the prevalence of H6 virus has dramatically increased in wild and domestic birds (2–4). In China, highly pathogenic influenza A(H5N1), low pathogenicity influenza (H9N2), and H6 are the most prevalent avian influenza viruses among poultry (5). Although only 1 case of H6 virus infection in a human has been reported worldwide (6), several biological characteristics of H6 viruses indicate that they are highly infectious to mammals. Approximately 34% of H6 viruses circulating in China have enhanced affinity to human-like receptors (ɑ-2,6 NeuAcGal) (2). H6 viruses can also infect mice without prior adaptation (2,7), and some H6 viruses can be transmitted efficiently among guinea pigs (2). To evaluate the potential threat of H6 viruses to human health, we conducted a systematic serologic study in populations occupationally exposed to H6 viruses.
During 2009–2011, a total of 15,689 serum samples were collected from live poultry market workers, backyard poultry farmers, large-scale poultry farmers, poultry-slaughter factory workers, and wild bird habitat workers in 22 provinces in mainland China. A/chicken/Y94/Guangdong/2011 (H6N2), a representative isolate of predominant H6 viruses in mainland China, was used for the serologic testing (Technical Appendix[PDF - 155 KB - 4 pages] Table 1). Hemagglutination inhibition (HI) assay was performed for all serum samples, and samples with an HI titer ≥20 were verified by a microneutralization (MN) assay, as indicated by World Health Organization guidelines (8). An MN result of ≥20 was considered positive.
The HI result was ≥20 for H6N2 virus in 298 of the 15,689 specimens, and the MN result was positive in 63 of the 298 specimens (overall seropositivity range 20–320, mean 32.7, 0.4%) (Technical Appendix[PDF - 155 KB - 4 pages] Table 2). The proportion of group members who were seropositive differed significantly according to occupational exposure (p = 0.0125). Seropositivity was highest among workers in live poultry markets, backyard poultry farmers, and workers in wild bird habitats (s0.66%, 0.42%, and 0.51%, respectively) (Table). According to χ2 test results, seropositivity among workers in live poultry markets was significantly higher than that among large-scale poultry farmers (p = 0.0015, adjusted ɑ = 0.005. Analysis by unconditional logistic regression model showed that exposure to live poultry markets was a risk factor for human infection with avian influenza H6 virus (odds ratio 2.1, 95% CI 1.27–3.47).
Seropositivity did not differ significantly among male and female persons tested (p = 0.08) (Table). No children were positive for the H6N2 virus. For other age groups, seropositivity ranged from 0.25% to 0.45%, but differences were not significant (p>0.05) (Table).
Of the 22 provinces from which serum specimens were collected, 11 were northern provinces and 11 were southern provinces. Positive specimens were detected in all southern provinces. In northern China, no seropositive results were detected in Henan, Liaoning, or Jilin Provinces. According to χ2 test results, seropositivity in southern China was significantly higher than seropositivity in northern China (p = 0.0375) (Table).
Human infection with influenza H6 virus in mainland China has not been reported, but 63 serum specimens tested in our study were positive for the H6 virus. This level of seropositivity is much higher than that for highly pathogenic avian influenza A(H5N1) virus, for which only 2 of the serum specimens we tested were positive (data not shown), but much lower than the seropositivity level for low pathogenicity avian influenza A(H9N2) virus; 3.4% of the samples tested were positive for A/Chicken/Hong Kong/G9/1997(H9N2)–like virus (data not shown). A previous US study has reported H6N2-positive antibodies in veterinarians (9). Our results and the veterinarian study indicate that the H6N2 virus could infect humans.
In our study, positive samples were detected in 19 of 22 provinces and in all tested worker populations, suggesting that the H6 virus has been broadly circulating in birds in China. Live poultry market exposure is the major risk factor for human infection with avian influenza H6 virus. The limitation of this study is that antigen selection may not accurately detect neutralization antibodies for different subtypes of H6 viruses. Surveillance of the H6 virus in birds and occupationally exposed populations should be strengthened for pandemic preparedness.