Editorial & Research: Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation

British Medical Journal
10 August 2013 (Vol 347, Issue 7920)
http://www.bmj.com/content/347/7920

Editorial
Human to human transmission of H7N9
BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f4730 (Published 6 August 2013)
Cite this as: BMJ 2013;347:f4730
http://www.bmj.com/content/347/bmj.f4730
James W Rudge, lecturer1, Richard Coker, professor12
Limited transmission between humans is not surprising
Since the new avian influenza virus, H7N9, first emerged in China, a primary concern has been whether it might spread between humans. The vast majority of the 133 confirmed cases reported so far seem to be epidemiologically unconnected, with many patients reporting a recent history of exposure to live poultry, which are suspected to be a main reservoir for the virus. Although an earlier study did report two family clusters of H7N9 cases, it was unclear whether these clusters resulted from person to person transmission or simply from exposure to a common animal source of infection.1

In the linked paper (doi:10.1136/bmj.f4752) by Qi and colleagues, a detailed investigation into one of these clusters provides the strongest evidence yet of H7N9 transmission between humans.2 The index case, a 60 year old man, was likely to have been infected at a nearby live poultry market, and subsequently developed a severe and ultimately fatal respiratory illness. His 32 year old daughter, who provided prolonged bedside care for her father before his admission to intensive care, later also became fatally infected. With no indication that the daughter was exposed to live poultry within the days before becoming sick, along with almost 100% genetic similarity between the viruses isolated from each patient, the evidence points to transmission from father to daughter.

As the authors acknowledge, there are some limitations to the study but, on balance, human to human transmission looks probable. So does this imply that H7N9 has come one step closer towards adapting fully to humans? Probably not. Crucially, there is still no evidence of sustained transmission among humans—all 43 close contacts of these two patients, including a son in law who also helped care for the father, tested negative for infection. In addition, the receptor binding sites of the viruses from the two patients are no more adapted towards humans than those of other available H7N9 isolates. In many ways, the evidence corroborates, rather than challenges, previous assertions that the transmissibility of H7N9 between humans is currently low.

Indeed, the occasional transmission event from human to human appears to be the norm rather than the exception for influenza viruses that sporadically cross the species barrier into humans. Limited human to human transmission has been reported for highly pathogenic avian influenza H5N1,3 4 which continues to cause (usually fatal) infections in humans, as well as another bird flu subtype, H7N7, which caused an outbreak of mostly mild infections in the Netherlands in 2003.5 To observe some transmission of H7N9 from human to human is therefore not surprising, and does not necessarily indicate that the virus is on course to develop sustained transmission among humans.

Nevertheless, several traits of H7N9 are of particular concern. The linked paper2 comes close on the heels of studies showing airborne transmissibility of H7N9 between ferrets in the laboratory, a mammalian model.6 7 Also, it is now well documented that owing to its non-lethality in birds, H7N9 can spread undetected through avian populations. In addition, Chinese surveillance data suggest that the number of confirmed human cases is just the tip of the iceberg—many mild cases are likely to have passed undetected.8 The upside of this is that the actual fatality rate among H7N9 cases is likely to be substantially lower than that observed among confirmed cases.9 The flipside is that the incidence of human infections, and therefore opportunities for H7N9 to adapt to humans or to re-assort through mixed influenza infections, could be much greater than for other bird flu viruses such as H5N1.

Although the number of H7N9 cases has fallen abruptly since April 2013, with no new cases reported for several weeks, we have been warned to expect a resurgence later in the year owing to seasonal effects on transmission.10 Thus, while the paper by Qi and colleagues2 might not suggest that H7N9 is any closer to delivering the next pandemic, it does provide a timely reminder of the need to remain extremely vigilant: the threat posed by H7N9 has by no means passed.

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Research
Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation
BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f4752 (Published 6 August 2013)
Cite this as: BMJ 2013;347:f4752
http://www.bmj.com/content/347/bmj.f4752

Abstract
Objective  To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency.
Design  Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013.
Setting  Wuxi, Eastern China.
Participants  Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays.
Main outcomes measures  Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains.
Results  The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9.
Conclusions  The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable