Risk assessment of avian influenza A(H7N9) – eighth update

Question 1

1. Human epidemiology

Accepted Answer

From April 2013 to 26 December 2019, the World Health Organisation (WHO) has confirmed 1,568 cases and at least 616 deaths from avian influenza A(H7N9) ¹, an overall case fatality rate of around 39%. The vast majority of cases have occurred in mainland China, with cases also reported from Hong Kong (20), Taiwan (5), Macao (2), Malaysia (1) and Canada (2). All of the latter were in people who had travelled from mainland China.

Historically, human cases of avian influenza A(H7N9) in mainland China have followed a seasonal pattern beginning each winter and peaking around January and February. This seasonal peak coincides with several weeks of celebrations related to the Chinese Lunar New Year and associated increases in travel to and from China, mass gatherings, and greater interactions between people and poultry.

WHO defines this seasonality into waves, beginning on 1 October until 31 September the following year. During the 2016 to 2017 season, also known as the fifth wave, a total of 766 cases and 292 deaths were reported, the highest number of cases ever reported in a single wave. In Autumn 2017, China initiated a poultry vaccination programme against H5 and H7 avian influenza. The vaccination programme aims to reduce the incidence of H7N9 infection in poultry in China. Subsequently, there were only 3 human cases reported during the sixth wave (1 October 2017 to 31 September 2018). Since 1 October 2018, there has been one human case (reported in April 2019) with exposure in Inner Mongolia province.

The majority of human cases have reported contact with poultry or their environments. The age, sex distribution and case fatality rate has remained similar across the epidemic waves. Transmission between humans remains limited with some evidence of small family clusters and potential for limited nosocomial transmission. However, there is no evidence of sustained human-to-human transmission to date^{1, 2}.

The small number of cases diagnosed among travellers from China to other countries highlights the continued risk of sporadic imported cases with a history of travel to China, particularly given the increased travel to and from China for the Lunar New Year. The UK Health Security Agency (UKHSA) will continue to monitor the situation closely, and update this risk assessment accordingly.

Question 2

2. Virology

Accepted Answer

During the fifth wave, WHO confirmed they had genetic sequences from 3 patients that showed evidence of oseltamivir resistance ³. Oseltamivir-resistant strains have previously been isolated from a minority of human cases of Influenza A(H7N9). The proportion of resistant strains found in the fifth wave (7% to 9% of cases) is similar to previous waves ⁴. These strains were found in patients who were possibly treated with antiviral medications, and therefore the resistant strains are likely to have developed following treatment. This finding does not significantly alter the risk assessment at this time.

The fifth wave of H7N9 cases in humans has also highlighted the emergence of the Yangtze River Delta lineage which has accounted for the majority of cases in this wave ³. This contrasts with previous waves, where cases were associated with strains from the Pearl River Delta lineage. This change has not been specifically associated with a change in transmissibility from poultry to humans or between humans. It has also not significantly altered the demographics of cases or the case fatality - and does not itself change the risk assessment for this virus. However, this change, along with the change in the geographical distribution and number of human cases in mainland China, during the fifth wave, highlight the importance of careful and continued monitoring of this situation. WHO issued new recommendations for candidate vaccine viruses to take account of the emergence of the now dominant strains from the Yangtze River Delta lineage ⁵.

Question 3

3. Animal ecology

Accepted Answer

There is evidence that the increased number and wider geographical distribution of human cases within mainland China during the fifth wave was related to a significant increase in the prevalence of infected poultry and therefore greater potential exposures for humans. There is no evidence that the virus itself has become more transmissible from poultry to humans^{2, 6}.

In September 2017 China initiated a bivalent vaccination campaign against H5 and H7 avian influenza in poultry. The Food and Agriculture Organisation of the United Nations (FAO) has reported that the vaccine appears to be well matched and coverage levels are high (7). Available data suggests there has been a subsequent reduction in detections of A(H7N9) in poultry and their environments across China (8). There has been a concurrent reduction in human cases reported since the implementation of the vaccine programme, suggesting the programme has been successful in reducing human exposure to A(H7N9).

Up until the fifth wave, avian influenza A(H7N9) was considered a low pathogenic avian influenza (LPAI) meaning that infected birds do not always show symptoms. However, during the fifth wave, WHO confirmed evidence of strains of highly pathogenic avian influenza (HPAI) A(H7N9) circulating in birds in China, together with subsequent human infections⁹. This finding alone does not raise the risk assessment for human health, as pathogenicity in birds is not directly related to pathogenicity in humans. So far, human cases of HPAI A(H7N9) have been clinically and epidemiologically similar to LPAI cases; however, numbers of human cases are small so monitoring of future genetic changes in this virus is warranted¹⁰. The emergence of an HPAI strain may have an implication on the control of the disease in birds, if the infection becomes easier to identify clinically in these species.

During early 2017, outbreaks of avian influenza A(H7N9) occurred in poultry in the USA. The strain in these outbreaks was of North American origin and is unrelated to the Asian lineage H7N9 which is associated with human infections in China¹¹. This risk assessment covers the Asian lineage H7N9 only.

Question 4

4. 
UKHSA risk assessment

Accepted Answer

The risk of influenza A(H7N9) infection to UK residents in the UK remains very low (as the virus is not present in the animal reservoir within the UK).

The risk of influenza A(H7N9) infection to UK residents who are travelling to mainland China is very low. If travellers from affected areas meet the case definition, testing for influenza A(H7N9) is indicated. Testing for other avian influenza subtypes may also be indicated.

The probability that a cluster of cases of severe respiratory illness in the UK is due to influenza A(H7N9) is very low, but they would be tested. A history of travel to mainland China would increase the likelihood of influenza A(H7N9).

If compliance with guidance on infection control measures is good, the risk to healthcare workers caring for cases of influenza A(H7N9) in the UK is very low. However, if respiratory illness developed in healthcare workers caring for cases of influenza A(H7N9), they would be urgently tested for influenza A(H7N9). The risk to contacts of confirmed cases of influenza A(H7N9) infection is low but warrants follow up in the 10 days following last exposure and urgent investigation of any new febrile or respiratory illness.

Advice for travellers

No specific restrictions to travel are advised. However, to help reduce the risk of infection, the National Travel Health Network and Centre (NaTHNaC) advise that travellers:

avoid visiting live bird and animal markets (including ‘wet’ markets) and poultry farms
avoid contact with surfaces contaminated with animal faeces
avoid untreated bird feathers and other animal and bird waste
do not eat or handle undercooked or raw poultry, egg or duck dishes
do not pick up or touch dead or dying birds
do not attempt to bring any poultry products back to the UK
maintain good personal hygiene with regular hand washing with soap and use of alcohol-based hand rubs

Travellers to China should be alert to the development of signs and symptoms of influenza for 10 days following their return. It is most likely that anyone developing mild symptoms during this time is suffering from seasonal influenza, a cold or other commonly circulating respiratory infection. However, if they become concerned about the severity of their symptoms, they should seek appropriate medical advice and inform the treating clinician of their travel history. NaTHNaC published information for people travelling to China.

Question 5

5. Advice for clinicians and health professionals

Accepted Answer

Clinicians should retain a high level of suspicion when considering managing patients with confirmed or suspected influenza A and a history of travel to China in the 10 days before the onset of symptoms.