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Published Date: 2013-05-18 17:06:38
Subject: PRO/AH/EDR> Avian influenza, human (81): China CDC/WHO H7N9 Mission Report
Archive Number: 20130518.1722238

AVIAN INFLUENZA, HUMAN (81): CHINA CDC/WHO H7N9 MISSION REPORT
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Date: Sat 18 May 2013
Source: World Health Organisation (WHO), Influenza/Anmal Interace [edited extracts]
http://www.who.int/entity/influenza/human_animal_interface/influenza_h7n9/ChinaH7N9JointMissionReport2013.pdf


Mission Report -- Executive Summary
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Introduction
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On [31 Mar 2013], in accordance with the International Health Regulations (2005) [IHR],the Government of China reported the detection of 3 cases of human infection with a novel influenza A(H7N9) virus (hereafter, H7N9) in Shanghai and the province of Anhui. At the same time, the Chinese Center for Disease Control and Prevention (China CDC) posted full genome sequences of viruses isolated from the 1st 3 cases in a publicly accessible database. Over the next 2 weeks additional cases were confirmed in the municipalities of Shanghai and Beijing, and in the provinces of Anhui, Jiangsu and Zhejiang. Most cases were marked by severe pneumonia and a substantial number of deaths followed. Investigations identified live bird markets as a possible source of human infection. In response to this situation and at the invitation of the National Health and Family Planning Commission of China, a China-WHO Joint Mission on Human Infection with Avian Influenza A(H7N9) Virus was formed to assess the outbreak and provide guidance on its management. The Joint Mission was composed of experts from China and WHO and 4 from Australia, Europe, Hong Kong, Special Administrative Region of China, and the United States of America. The team visited Beijing and Shanghai over 6 days, [19 - 24 Apr 2013], meeting with senior officials and many experts from the human and animal health sectors involved in the continuing outbreak investigation, following an agreed method of work.

Although the team was unable to visit other affected areas because of time constraints, outcomes of the extensive investigations already undertaken in China were openly shared and vigorously discussed. The team's findings, assessment and recommendations were formed on the basis of the data available, site visits and discussions. These are presented in this report.

Main Findings
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Epidemiology
As of [22 Apr 2013], 104 confirmed cases, including 21 deaths, have been reported in Zhejiang (40 cases), Jiangsu (24), Henan (3), Anhui (3) provinces, Shanghai (33), and Beijing (1). Patients are predominantly older (median 62 years) and male (69 percent). Of 77 cases reported nationally for which data are available, 18 (23 percent) reported no identified contact with poultry; 56 (72 percent) reported some recent contact with live poultry and live poultry markets.

An additional case in an asymptomatic four-year-old boy was detected by Beijing CDC during enhanced case finding that followed the identification of the 1st case in Beijing. Almost all cases have been sporadic but 3 family clusters have been identified. Evidence thus far is not sufficient to conclude that person-to-person transmission has occurred. Of more than 3000 close contacts, 19 developed respiratory symptoms. None of these symptomatic patients tested positive for H7N9 by reverse-transcriptase polymerase chain reaction (RT-PCR) testing. Results of serology testing are pending.

On [1 Apr 2013], enhanced surveillance was introduced throughout the country for pneumonia of unknown origin and in sentinel influenza-like illness (ILI) surveillance sites; molecular diagnostic kits were also distributed. Since then, an increase has been observed in the number of ILI consultations in ILI sites. This increase is more likely to be related to concerns among the population than to an increase in H7N9 cases. Enhanced ILI surveillance has identified one ILI case that tested positive for H7N9 by RT-PCR. Although it is too early to confirm the effectiveness of the closure of live bird markets in Shanghai, which took place on [6 Apr 2013], no new cases have been reported there with dates of onset later than [13 Apr 2013].

Areas of major uncertainty
Some important uncertainties remain, including the following: (1) It is unclear why severe disease has been found predominantly in older male urban residents. This pattern could be associated with behavioural factors or, as for seasonal influenza, H7N9 could be causing a larger number of mild and symptomatic infections that have gone undetected to date; (2) Although surveillance for pneumonia of unknown origin is routine, it is impossible to exclude the possibility that these infections have been occurring for some time; (3) Currently, evidence so far is not strong enough to conclude there is person-to-person transmission; (4) The extent of occurrence of unrecognized mild/asymptomatic infections is unclear and may affect estimates of case-fatality. Persons who have mild or asymptomatic illness may not have been tested in any of the testing algorithms outlined.

Clinical features and management
The most common presenting signs and symptoms were those characteristic of influenza. Encephalopathy and conjunctivitis were uncommon, and nasal congestion and rhinorrhoea were not reported as initial presentations. Common laboratory findings included normal white cell count, leukocytopenia, lymphocytopenia, thrombocytopenia, and mildly elevated liver enzymes. Most cases were severe, and a number of these rapidly deteriorated within 1 to 2 days of hospitalization to acute respiratory failure, leading to refractory hypoxemia and multiple organ failure, the major cause of death. A few mild cases were reported, especially in children. Neuraminidase inhibitors (NAIs) were given to almost all patients but only after a median of 6 days after disease onset. NHFPC developed a risk-based management protocol for areas where confirmed cases are reported so that NAIs could be given earlier to symptomatic cases, even before the confirmatory result of laboratory tests for H7N9 virus. Infection prevention and control measures in fever clinics and designated hospitals complied with national and WHO guidance.

Characteristics of avian influenza A(H7N9) viruses
The novel viruses are reassortants, comprising H7 HA, N9 NA and the 6 internal genes of H9N2 influenza A viruses. This combination of influenza genes has not previously been identified among viruses obtained from birds, humans or any other species, although individual genes are related to those of recent avian influenza viruses circulating in East Asia. H7N9 viruses obtained from human cases, poultry and environmental samples are closely related and contain a number of genetic signatures previously associated with low pathogenicity in poultry, enhanced capacity for mammalian infection and resistance to the adamantane class of antiviral drugs. Several human H7N9 viruses were shown to be sensitive to the NAIs oseltamivir and zanamivir in vitro. It is important to note that one mammalian adaptation (E627K in the PB2 gene) occurred in many of the human H7N9 viruses but did not occur in any of the non-human viruses. Continuing analyses are essential to improve understanding of these viruses and to detect any future changes affecting their transmissibility between humans and their pathogenicity in birds. Preliminary analyses suggest that many people lack antibodies to this virus and that production of an effective vaccine will require the selection of a new candidate H7 vaccine virus.

Animal health
The detection of H7N9 virus in live poultry markets in the vicinity of human cases in Shanghai, the contact history with live poultry or live poultry markets in a substantial number of cases, and the apparent reduction in human cases after the closure of live poultry markets in Shanghai, suggest exposure to live poultry as a key risk factor for human H7N9 infection. Although the H7N9 virus has not been detected in poultry farms so far, it is likely that they provide the source of infection, with subsequent amplification within live poultry markets leading to human infections. Although data are limited at this early stage of the investigation, it may be that the H7N9 virus is currently sustained through intra-€ and inter-€provincial trading of live poultry. If infection in poultry is not controlled the H7N9 virus may spread to additional provinces in China, leading to an even greater zoonotic threat, and thus increasing its pandemic potential. It may also facilitate the emergence of a virus that is highly pathogenic in poultry. The human and poultry viruses genetically sequenced thus far show that this H7N9 virus has adaptations that allow it to infect humans, although virological information is limited as the animal A(H7N9) test and the test strategy in China remain to be validated.

Response strategies and measures
A joint multi-sectoral prevention and control mechanism (JPCM) has been established at national and local levels to lead and coordinate the emergency response to H7N9 virus. The national JPCM, led by the National Health and Family Planning Commission, consists of 13 governmental ministries and commissions, including the Ministry of Agriculture, the State Forestry Administration, and the Ministry of Science and Technology. An inter-regional JPCM has also been established to support sharing of information and coordinated response among the affected provinces and municipalities, including Anhui, Jiangsu, Shanghai, and Zhejiang. Significant efforts are being made to ensure that the emergency response to the newly detected H7N9 virus is based on laws and regulations, the principle of transparency, prioritization and international collaboration. An approach based on risk assessment and evidence is being applied to inform coordinated, balanced public health interventions. Coordinated but tailored response strategies and guidance have been provided to the different provinces based on the epidemiological situation and local needs. Early detection, early reporting, early diagnosis and early treatment ("the Four Earlys") have been the general guiding principles for the operational response. Response measures include close collaboration between public health and animal health sectors, enhanced surveillance in humans and animals, case investigation, field investigation, risk assessment, clinical management, hospital infection prevention and control, public health interventions, risk communication, and research. Reagents for PCR detection of H7N9 viruses in humans have been distributed to more than 400 laboratories throughout China. Several national guidelines have been issued for surveillance and epidemiological investigation, including contact tracing, laboratory testing and patient isolation and treatment.

The priority response measures have been focused on the following:
- Field investigations, including source of infection
- Enhanced surveillance in humans and animals
- Clinical management, infection prevention and control
- Risk communication
- Scientific research.

The current response at national and local levels seen by the Team has been excellent and appears to be effective. The risk assessment and evidence-based response to H7N9 virus could serve as a model of emergency response to similar events.

Remainder of Document
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[The remainder of the document concerns: International collaboration, Assessment and Recommendations, all of which can be accessed via the source URL . - Mod.CP]

[This document provides an authoritative record of the outbreak of H7N9 influenza virus infection in China up to at least 22 Apr 2013 and is recommended to readers as an accurate reference source. - Mod.CP]

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