Wednesday, January 28, 2015

EID Journal: H7N9 Antibodies In Close Contacts Of Known Cases


# 9637


Two big questions we always ask when we see human infections with novel viruses are 1) How easily is it transmitted to others?  and  2) What is the spectrum of illness produced by infection? 


While seemingly simple and straightforward questions, answering them isn’t easy. 


Most human infections with MERS-CoV, or Avian Flu (H5N1, H7N9, H10N8, etc.) look very much like any other respiratory infection – except that they often carry a higher mortality rate than seasonal influenza.  Unless you are specifically testing for these novel viruses, there really isn’t any way to accurately diagnose them. 


And testing, assuming it is available at all, is usually reserved for those sick enough to be hospitalized.


So we tend to get a skewed view of the severity of these novel viruses, as moderate, mild, or even sub-clinical infections are rarely documented. And if these less-than-severe cases aren’t being tested, we are also apt to under appreciate possible chains of transmission.


The `practical solution’ (as opposed to trying to test every ILI patient for an increasing array of novel viruses) is to monitor, and test, close contacts of the limited number of known (and usually severe) novel flu cases.  That way we can get an idea of the transmissibility of the virus, and can catalog its severity in secondary cases.


PCR testing is normally done during the contact’s incubation period to check for infection and/or viral shedding, and while usually applied to those showing physical symptoms, can sometimes pick up asymptomatic infections as well.


Several weeks post-exposure, it is also desirable to test a contact’s blood for virus-specific antibodies, which would indicate the patient had been exposed to, and fought off the virus.  Serological testing can often turn up mild, or sub-clinical infections that would otherwise not have been detected.


There are, of course, limitations to serological testing, just as there are to PCR tests and viral cultures.  No lab test is perfect.  


Disagreements exist over what constitutes a `positive’  serological test (usually defined as a 4-fold increase in post-exposure antibody titer levels), and there are always concerns over potential cross-reactive antibodies and false positives.


But serological studies are generally regarded as the best way to determine the incidence of a viral infection in a population, as you don’t have to depend upon a `perfect catch’ of a biological sample while the patient is actively shedding virus particles. 


All of which brings us to an EID Journal Letter, published ahead of print, that details serological testing of 225 close contacts of 7 H7N9-infected patients during China’s first two epidemic waves. The authors found 22 contacts (9.8%) with elevated HI H7N9 antibody titers (>1:40).


While none of these contacts were overtly symptomatic during the incubation period, the authors believe this finding suggests that H-2-H transmission of the H7N9 virus may occur among close contacts of infected cases.


Some excerpts follow, click the link to read the entire letter.


Volume 21, Number 4—April 2015

Avian Influenza A(H7N9) Virus Antibodies in Close Contacts of Infected Persons, China, 2013–2014

To the Editor: From early 2013 (1) through November 2014, >460 human cases of laboratory-confirmed avian influenza A(H7N9) virus infection occurred in China. Although human-to-human transmission of subtype H7N9 virus is not common, evidence has been reported of probable transmission among several family clusters (2), between 2 household contacts (3), and between a doctor and an infected patient (4). Taken together, these observations suggest that family members, health care providers, and other close contacts (hereafter called contacts) of H7N9-infected persons may be at risk for infection.

In China, national guidelines regarding H7N9-infected patients call for observation of contacts for 7 days after exposure for signs and symptoms of infection and, if any occur, collection of throat swab specimens for testing by molecular assays (5). The guidelines do not call for serologic testing. Because human avian influenza infections may be mild or asymptomatic, we sought to determine whether serologic testing would show evidence of H7N9 virus infection among contacts of infected persons during the 2013–2014 epidemic in China. Contacts were defined in accordance with China’s guidelines for prevention and control of human H7N9 virus infection (5,6). The institutional review board of Wuxi Center for Disease Control and Prevention, Wuxi, Jiangsu Province, China, reviewed and approved this study.


Serologic assay results showed that, 14–28 days after their earliest exposure to an H7N9-infected patient, 22 (9.8%) contacts had elevated HI antibody titers (>1:40) against H7N9 virus; titers were 1:40 for 17 contacts and 1:80 for 5 contacts. Positive results for all 22 serum samples were validated by microneutralization assay; 15 (68.2%) samples had microneutralization antibody titers of >1:10 against H7N9 virus antigen (Table). Of the contacts with an HI titer of >1:80 and microneutralization titer of >1:40, 3 were nurses, 1 was a nurse assistant, and 1 was a family member (a patient’s daughter). All 5 of these contacts had antibody titers of <1:40 to influenza subtype H1N1, H5N1, and H9N2 viruses, and 2 of the nurses had HI antibody titers of 1:80 against subtype H3N2 virus. All contacts denied having influenza-like respiratory symptoms during the 28 days of follow-up and also denied recent exposure to poultry or pigs or their environments. Of contacts with an HI titer of >1:80 to seasonal H1N1 virus, 3 had titer of 1:80, and 1 each had titer of 1:160 or 1:640. Of the 225 contacts, 108 had HI titers >1:80 against seasonal H3N2 virus (1:80 for 63 contacts, 1:160 for 27 contacts, 1:320 for 9 contacts, and >1:640 for 8 contacts). All contacts had influenza subtype H5N1 and H9N2 antibody titers of <1:80.


A limitation of our study is that we did not collect serum samples from all contacts of infected persons or from controls; therefore, we could not assess the possibility of false-positive results or asymptomatic infections. However, our findings of elevated levels of subtype H7N9 antibody among 6.7% of contacts during this epidemic in China offer evidence that human-to-human transmission of H7N9 virus may occur among contacts of infected persons.

Mai-Juan Ma1, Guang-Yuan Ma1, Xiao-Xian Yang1, Shan-Hui Chen1, Gregory C. Gray, Teng Zhao, Jing Bao, Jing-Jing Zhou, Yan-Hua Qian, Bin Lu, Xia Ling2, and Wu-Chun Cao2Comments to Author

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