Human Avian Influenza

Human Disease

Overview

The most recent cases reported in China on the 29th March 2013 involve the A/H7N9 subtype (hereafter referred to as H7N9), which has been shown to be more virulent in people than poultry. China confirmed three initial human cases, all of whom died. Currently (as of 29th April 2013) there are 126 confirmed cases of H7N9 in humans in China7.

The human and animal sequences have been shown to be closely related but diverse enough to conclude that the virus has been circulating for a while (probably amongst animals). The H7N9 strain identified in people has been found to have amino acid substitutions not found in poultry that are associated with further adaptation to humans8. This adaptation to mammals is of concern and suggests that further adaptation may occur22. Currently no animal outbreaks have been identified in the area surrounding the confirmed cases and only a small proportion of birds have tested positive for the virus. However 77% of those people infected with H7N9 have been exposed to poultry/swine (including live bird markets). Three family clusters of 2-3 cases each have been identified where limited human to human transmission may have occurred22. Of 71 cases reported with complete data, 54 had an underlying health condition and the median age was 61 years, compared to median age of 26 years for H5N17.

At the moment it is thought that H7N9 was transmitted from healthy poultry or swine to people either directly or through contaminated environments9. As few H7N9 positive birds have been detected, this may indicate that the virus is widespread in poultry and is asymptomatic which could lead to silent spread of the virus.

The complete virus is a recombination of three viruses found in Asia, H7 of the virus has been found to be closest to that found in domestic ducks in Zhejiang and the N9 closest to the wild bird strain in South Korea. Genetic changes have also been found that lead to increased virus binding and replication in mammalian respiratory cells and thus increased severity of infection. Viral RNA shedding in people with the H7N9 has been prolonged (up to 11, 17 and 20 days) 8. The virus has been shown to be weakly pathogenic in poultry and testing of different populations for H7N9 specific antibodies may be helpful in finding the source, though viruses with H7 HA may not trigger a strong antibody response. No cases have been reported outside of China.

Infection

The incubation period for influenza is relatively short, ranging from 7 to 67 hours with a median of 34 hours for influenza A and a median of 14 hours for influenza B15. people are usually exposed one week prior to the onset of clinical signs. At this point most patients infected with both H5N1 and H7N9 have presented with signs and symptoms of severe respiratory infection, often with pneumonia which progresses to acute respiratory disease syndrome, impaired coagulation, multiorgan dysfunction (similar to that seen with seasonal influenza and H5N1 infection), fever and lymphopenia. However as H7N9 is the first of its type to infect humans the full spectrum of presentations is not well understood at this time. Increased levels of cytokine and chemokine levels were found in patients who died7,8.

Management

Clinical suspicion is essential in symptomatic travellers returning from areas where avian influenza transmission has been confirmed. Local policies will guide identification and management of cases. Current understanding of avian influenza suggests that the potential for human-to-human transmission is unknown and therefore infection control guidance advocates isolation and the use of appropriate PPE in cases under investigation for H7N9 infection17,18.

Diagnostics

The use of reverse transcriptase polymerase chain reaction (RT-PCR) and real time RT-PCR are becoming more frequent in the diagnosis of AI. Tracheal samples have been shown have higher specificity and sensitivity as compared with virus isolation, whereas faecal samples were less sensitive13. The ability to amplify the HA0 region may mean that it can be used for more specific diagnosis. Rapid one-step multiplex RT-PCR assays have been used to detect influenza viruses and the H5 avian virus in people have shown no cross reactivity with respiratory pathogens14.

Rapid antigen detection methods have also been developed, mostly for diagnosing infection in humans though more recently some have been used in birds. Antigen detection methods have the advantage of being quick to use and are able to detect all influenza type A infections (due to the use of a monoclonal antibody against the nucleoprotein), however they have a low sensitivity and are expensive.

Treatment

Humans cases of H7N9 infection are treated with symptomatically7,8. The WHO recommends early treatment with a neuraminidase inhibitor in cases under investigation for H7N9 infection19. The Center for Disease Control echoes this point recommending that a neuraminidase inhibitor be administered at the earliest opportunity, even if more than 48 hours have passed since the onset of symptoms20. Public Health England (formerly the Health Protection Agency) produced an algorithm for the management of contacts of confirmed cases of H5N1 infection in 200921. This recommends that only close contacts of, and healthcare staff caring for a confirmed case require antiviral prophylaxis with Oseltamivir21.

Further Information

Avian Influenza Factoid

Animal AI Disease Sheet

References

7 Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Report, Emergence of Avian Influenza A(H7N9) Virus Causing Severe Human Illness — China, February–April 2013, May 10, 2013 / 62(18);366-371 8 Koopmans, M., de Jong, M.D. (2013), Avian influenza A H7N9 in Zhejiang, China, The Lancet, 26th April 2013. 13 Alexander, D.J.(2008) , Avian Influenza – Diagnosis, Zoonoses and Public Health Volume 55, Issue 1, pages 16–23, February 2008 14 Choi, J-H., Kim M-S., Lee, J-Y., Lee N-J., Kwon, D., Kang, M.G., Kang, C.(2013), Development and evaluation of multiplex real-time RT-PCR assays for seasonal, pandemic A/H1pdm09 and avian A/H5 influenza viruses detection, Journal of Microbiology April 2013, Volume 51, Issue 2, pp 252-257 15 The communicable disease management and control handbook, Hawker, Begg et al 17 Centers for Disease Control and Prevention: Interim Guidance for Infection Control Within Healthcare Settings When Caring for Patients with Confirmed, Probable, or Cases Under Investigation of Avian Influenza A(H7N9) Virus Infection. Avilable at: http://www.cdc.gov/flu/avianflu/h7n9-infection-control.htm Accessed on 23rd June 2013. 18 Public Health England: Investigation & management of possible human cases of avian inuenza A/H7N9, in travellers returning to the UK. Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317138620910 Accessed on 23rd June 2013. 19 World Health Organisation: Overview of the emergence and characteristics of the avian influenza A(H7N9) virus. Available at: http://www.who.int/influenza/human_animal_interface/influenza_h7n9/WHO_H7N9_review_31May13.pdf Accessed on 23rd June 2013 20 Centers for Disease Control and Prevention: Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9). Available at: http://www.cdc.gov/flu/avianflu/h7n9-antiviral-treatment.htm Accessed on 23rd June 2013. 21 Health Protection Agency: Management of asymptomatic contacts of confirmed human case(s) of avian influenza A/H5N1. Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1230540128869 Accessed on 23rd June 2013. 22 World Health Organisation Risk Assessment: Human infections with avian influenza A(H7N9) virus, 7 June 2013 . Available at: http://www.who.int/influenza/human_animal_interface/influenza_h7n9/RiskAssessment_H7N9_07Jun13.pdf Accessed on 23rd June 2013.