Influenza H7N9 – a summary of available information at 29 June 2017.

Overview:

There have been five waves of the H7N9 epidemic since the first outbreak in humans in February 2013. Most cases have been clustered in the eastern coast of China. Human cases of H7N9 virus infection acquired in China also have been identified in Taiwan, Malaysia and Canada.1

The first wave commenced February 2013 and continued through to September 2013. Wave 2 extended from October 2013 through to September 2014. Wave 3 commenced in October 2014 through to September 2015. Wave 4 was from October 2015 to September 2016. The current fifth wave had its onset in October 2016.The outbreaks usually started in October, significantly increased in late December and then peaked in January of the next year.

Most of the reports of human infection with H7N9 have been very serious including severe pneumonia, acute respiratory distress syndrome, multi organ shutdown and a case fatality rate of 40% has been reported across the first four waves. The illness in humans usually commences with cough and fever.

The Virus:

“H7N9” is a subtype of influenza A viruses that is sometimes found in birds, but that does not usually infect humans. Like all influenza A viruses, there are many different strains of H7N9 virus. Many H7 virus have circulated in poultry for centuries.

There have been human cases with H7 influenza in the past but bearing other neuraminidase types.  These have been mild respiratory infections often with conjunctivitis.  One death was recorded in The Netherlands in an apparently immunocompromised person. 

Beginning at the end of March 2013, China reported the first known cases of zoonotic infections with a new strain of H7N9 virus that was very different from previously known H7N9 viruses. The virus was found to be circulating in poultry in the area. Since 2013, H7N9 viruses have continued to cause infections of poultry in China, with associated annual increases in the number of human infections with H7N9 viruses during the autumn, winter, and spring months.

H7 viruses exist as low pathogenic (LPAI) and highly pathogenic (HPAI) forms in poultry.  Previous human infections have usually involved HPAI viruses, the current virus is an LPAI strain.

Genetic Analysis:

Genetic analysis by Chinese scientists suggest that the virus is a genetic reassortant containing H7 and N9 genes derived from wild birds (possibly separately) and its remaining genes from an H9N2 influenza isolate also from a wild bird. Early reports indicate that the virus possesses some of the genetic characteristics that may favour adaptation to mammals. [http://www.nejm.org/doi/full/10.1056/NEJMoa1304459?query=OF#t=articleTop]

Researchers have known that H7N9 forms two lineages, the Pearl River Delta (PRD) and the Yangtze River Delta (YRD). Most human cases in the current wave are from the YRD lineage, which aren't as reactive to existing candidate vaccine viruses. The YRD viruses have formed two subsets, YRD-1 and YRD-2.

Within the YRD-2 subset, the team observed two clades, one (YRD-2a) circulating in central and eastern China and the other (YRD-2b) mainly found in eastern Guangdong province, its likely origin. They said the YRD-2b clade also includes the recently identified highly pathogenic H7N9 viruses.2

Treatment:

The virus is reported by the Chinese CDC to be sensitive to the neuraminidase inhibitors (Zanamivir and oseltamivir) and the Chinese have announced that they have licensed intravenous peramivir, a related antiviral, for use against it.

The Source:

Human infections with bird flu viruses are rare, but have happened in the past, usually after close contact with infected birds (both live and dead) or exposure to environments contaminated with bird flu virus, such as visiting a live poultry market.

If someone touches an infected bird or an environment contaminated with virus and then touches their eyes, nose or mouth, they may be infected with bird flu virus. There is some evidence that infection may also occur if the flu virus becomes aerosolized in contaminated material, such as when an infected bird flaps its wings. If someone were to breathe in airborne virus, it’s possible they could get infected.

Poultry infected with H7N9 virus do not experience any illness signs or symptoms. H7N9 virus-infected poultry appear well, but transmission to humans can occur. H7N9 virus has been found in birds (poultry) and contaminated environments in China in some of the same areas where human infections have happened. Available evidence suggests that most people have been infected with H7N9 virus after having contact with infected poultry or contaminated environments, including visiting a live poultry market.3

Current findings from review published in the Lancet Infectious Diseases (Feb 2013-Feb2017)

A research team based in China published its findings in the Jun 2 2017 early online edition of The Lancet Infectious Diseases. The group's review includes 1,220 lab-confirmed cases in humans reported from February 2013 to February 2017. For the fifth wave, they include 447 cases reported in mainland China as of Feb 23 2017.4

The review found that the fifth wave began earlier than usual and has seen a steep increase in the number of illnesses. The current wave has also witnessed the emergence of a highly pathogenic version of H7N9 in poultry and in humans that contains genetic mutations, including one that is resistant to neuraminidase inhibitors, the most commonly used flu antivirals.

When the virus first emerged in humans in 2013, older people were impacted the most. According to the new analysis, however, the proportion of cases in middle-aged adults has increased steadily, from 41% during the first wave to 57% in the fifth wave.

During the first three waves of H7N9 illnesses, a large percentage of the human cases were among those living in urban areas. Over the past two waves, the proportion of cases from semi-urban and rural residents has grown, making up about 60% of the cases, reflecting a steady rise from 39% reported during the first wave.5

Vaccine:

A number of candidate H7 vaccine strains had been prepared previously as a part of the WHO pandemic preparedness program.  However, reports indicate that the current virus is sufficiently different to require a new vaccine strain. 

There is currently no publicly available vaccine for the prevention of H7N9. WHO and its partners are testing some candidates for safety and efficacy.

WHO Risk Assessment:

As of 15 June 2017, a total of 1533 laboratory-confirmed cases of human infection with avian influenza A(H7N9) viruses, including at least 592 deaths, have been reported to World Health Organization (WHO). The number of human infections with avian influenza A(H7N9) viruses and the geographical distribution of human cases in the fifth epidemic wave (i.e. onset since 1 October 2016) is greater than in any earlier wave. This suggests that the virus is spreading, and emphasizes that further intensive surveillance and control measures in both the human and animal health sectors are crucial. However, the number of reported confirmed cases has continued to decline over the past few weeks indicating that the peak of cases for this wave was reached in mid-February 2017.

Most human cases are exposed to avian influenza A(H7N9) virus through contact with infected poultry or contaminated environments, including live poultry markets. Since the virus continues to be detected in animals and environments, and live poultry vending continues, further human cases can be expected. Although small clusters of cases of human infection with avian influenza A(H7N9) virus have been reported including those involving patients in the same ward, current epidemiological and virological evidence suggests that this virus has not acquired the ability of sustained transmission among humans. Therefore, the likelihood of further community level spread is considered low.6

WHO have prepared a risk analysis and summary of known information – see: [http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/index.html

WHO Advice to travellers:

WHO advises that travellers to countries with known outbreaks of avian influenza should avoid, if possible, poultry farms, contact with animals in live poultry markets, entering areas where poultry may be slaughtered, or contact with any surfaces that appear to be contaminated with faeces from poultry or other animals. Travellers should also wash their hands often with soap and water, and follow good food safety and good food hygiene practices.6

Australian perspective:

In the absence of human to human transmission there is little likelihood of an infected person arriving in Australia but travel history of acute respiratory illness in recently returned travellers is always important (note also the occurrence of novel coronavirus infections in people visiting the middle-east).

Chance of poultry/bird infections is essentially nil due to active quarantine and no evidence of migratory bird transmission of avian influenza from China to Australia.

H7N9: AusCMC Interview