Sporadic human cases of human infection with avian influenza A(H7N9) virus have been detected in China since early March. Infections are most likely resulting from exposure to infected poultry, however knowledge about routes of transmission and the extent of the prevalence of this virus in animal populations is limited. To date, there is no sustained human-to-human transmission though limited human-to-human transmission may have occurred in three human clusters. China CDC is interested in using the CONSISE protocols to evaluate the extent of human infection with avian influenza A(H7N9) virus in the general population as well as in specific populations (e.g., contacts of confirmed patients including health care personnel and poultry workers), population immunity to the A(H7N9) virus in the general population, and risk factors for human infection. 

Several members of the Chinese CDC are members of CONSISE. The Epidemiology Working Group Lead has been in contact with Chinese CONSISE colleagues to offer support and to provide updated working drafts of several CONSISE protocols.  These protocols include the following and, can be found in the 'Useful Resources' sidebar on the right hand side of this article, where available. We will be realeasing all draft protocols over the coming weeks.

 

CONSISE Working Draft Protocols for Influenza

1. Prospective longitudinal cohort study of influenza virus infection during epidemic periods

Objective: 

  • Prospective longitudinal cohort study of influenza virus infection during epidemic periods

2. Cross sectional seroprevalence study of a novel influenza virus infection prior and  post epidemic periods

Objectives: 

  • Determine age specific cumulative incidence of infection with a novel influenza virus in the population 
  • Measure prevalence of cross-reactive antibodies to the novel virus

3. Household transmission studies for pandemic influenza

Objectives: 

  • Estimate household secondary infection risk, and factors     associated with variation in the secondary infection risk
  • Characterize secondary cases including clinical presentation and asymptomatic fraction
  • Investigate serological response following confirmed influenza infection

4. Assessment of Health Care Personnel

Objective: 

  • Detect the presence of human-to-human transmission of a novel virus within a health care setting

5.  Investigation of Zoonotic Influenza Infection in Humans

Objectives: 

  • Measure age-specific infection in relation to zoonotic exposure
  • Identify (modifiable) risk factors for human infection

 

Avian influenza A(H7N9) virus seroassay development

Serology assays for A(H7N9) virus are currently being developed by several laboratories worldwide. The CONSISE Laboratory Working Group leads are in discussion with their members to discuss the progress of A(H7N9)-specific assay development and to facilitate information sharing between labs.

Two assays are currently being developed:  Haemagglutination-Inhibition (HI) using turkey or horse red blood cells and the 2 day Microneutralization (MN) ELISA based assay (WHO protocol), however sera from confirmed human cases are urgently needed in order to validate assay specificity and sensitivity.  

From the limited number of assays conducted so far, it appears that HI using either turkey or horse red blood cells and MN using the WHO protocol are suitable for use with A(H7N9) viruses. However, confirmation using specific ferret sera and human post-infection sera is needed before any assay recommendation can be made. The assay protocols will be shared on the CONSISE website. 

The A(H7N9) viruses under investigation for serology assays are:

  • A/Anhui/1/2013
  • A/Shanghai/1/2013
  • A/Shanghai/2/2013
  • Reverse Genetics derivatives of A/Shanghai/2/2013 and A/Anhui/1/2013

Further antigenic analysis is needed before a recommendation can be made on a suitable reference virus. 

Work is in progress at a number of laboratories, including at China CDC, CDC, USA and WHO CC Melbourne, to produce ferret antisera to A(H7N9) viruses.

Laboratory Procedures available

The WHO Collaborating Center for Reference and Research on Influenza at the Chinese National influenza Center, Beijing, China, has made available laboratory procedures for serological detection of avian influenza A(H7N9) infections by haemagglutination-inhibition and microneutralization assays.

For further information please contact us at: gisrs-whohq@who.int

Protocol: Serological detection of avian influenza A(H7N9) virus infections by turkey haemagglutination-inhibition assay (UPDATE Note added September 2013: The link for this protocol is no longer active as there is an updated and recommended HI protocol using horse RBC available below)

Protocol: Serological detection of avian influenza A(H7N9) infections by microneutralization assay

 

JULY 9 2013 UPDATE: Improved Haemagglutination-Inhibition Procedure available

The WHO Collaborating Center for Reference and Research on Influenza at the Centers for Disease Control and Prevention, USA has made available laboratory procedures for serological detection of avian influenza A(H7N9) infections by haemagglutination-inhibition (HI) using horse red blood cells (RBCs). Use of horse RBCs improves HI assay sensitivity to detect H7 antibodies over assays using turkey RBCs and the assay includes procedures that are necessary to remove non-specific agglutinins to horse RBCs as well as non-specific inhibitors that may also be present. In tests of human sera to H7 vaccines, the modified HI assay detected 2-8 fold higher titres than assays using turkey RBCs and yielded generally comparable titers as microneutralization assays.

Protocol: MODIFIED HEMAGGLUTINATION-INHIBITION (HI) ASSAY USING HORSE RBCS FOR SEROLOGIC DETECTION OF ANTIBODIES TO H7 SUBTYPE AVIAN INFLUENZA VIRUS IN HUMAN SERA

For further information please contact Min Levine at mwl2@cdc.gov or CONSISE at consise@tghn.org.

 

A(H7N9) Serologic Investigations on-going and planned

A number of A(H7N9)-specific seroepidemiology studies are ongoing and planned.  These are described by organization planning the studies.  Please note that the information below is not meant to represent an exhaustive list of all A(H7N9) serologic investigations planned/ongoing. 

China CDC

  • China CDC has tested the prevalence of A(H7N9) antibodies using sera collected from an A(H5N1) serosurvey of poultry workers from Shanghai, Anhui, Jiangsui and Zhejiang provinces in 2012.  Results are pending.
  • China CDC has tested close health-care workers contacts’ sera of one confirmed case in Shanghai province, all were sero-negative for A(H7N9) using HI serologic assay using turkey red blood cells. 
  • China CDC is collecting paired sera from contacts of confirmed cases. Further A(H7N9) seroepidemiologic studies are planned and will be implemented in the coming weeks in China, including: 

        –  Serology analysis for A(H7N9) subclinical study on poultry workers and health-care workers in China

       –  Extended surveillance study (with sentinel hospitals; ILI patients to be tested)

       –  Investigations of close contacts of confirmed cases


US CDC

  • Human subject approval pending for sera from previous studies, e.g. National Health and Nutrition Examination Survey of 2010 tested for A(H1N1)pdm09. Also trying to partner with other groups who have left-over sera. Aiming for ca 1000 samples, population immunity studies of all ages within US population.

WHO CC Melbourne

  • WHO CC Melbourne has approval to test a set of sera/plasma collected from Australian children and adults in late 2011 for cross-reactivity to the A(H7N9) virus.  Approvals have been granted, awaiting positive control sera for assay.

*Participants on the teleconference: Tian Bai (WHO CC, China CDC, Beijing), Eeva Broberg (ECDC, Stockholm; notes), Othmar Engelhardt (NIBSC, Potters Bar, UK, laboratory working group co-lead), Jackie Katz (US CDC, Atlanta, USA), Karen Laurie (WHO CC, VIDRL, Melbourne, Australia), Anthony Mounts (WHO HQ, Geneva), Angus Nicoll (ECDC, Stockholm), Maria Van Kerkhove (Imperial College, London, UK; chair and epidemiology working group lead), and John Wood (NIBSC, Potters Bar, UK, laboratory working group co-lead); Apologies: Wenqing Zhang (WHO HQ, Geneva), Malik Peiris (University of Hong Kong, Hong Kong); Yu Honjie (China CDC, Beijing); Yuelong Shu (WHO CC, China CDC, Beijing), Sirenda Vong (WPRO, Beijing)

 

More information about human cases of A(H7N9) can be found here: http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/index.html

 

 

 

 

 

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