2013-05-30-世界卫生组织-Overview_of_the_emergence_and_characteristics_of_the_avian_influenza_A_H7N9_virus_38页_1mb

Summary of Avian Influenza A(H7N9) Virus Emergence and Characteristics

Core Content

The avian influenza A(H7N9) virus emerged in China in early 2013, causing human infections that raised public health concerns. This document outlines the outbreak's timeline, clinical features, diagnostic methods, biosafety protocols, genetic characterization, animal infection patterns, antiviral treatments, vaccine development, and risk factors.

Main Points

1. The Outbreak

• Initial Report: On 31 March 2013, three human cases of H7N9 infection were confirmed in Shanghai and Anhui.
• Spread: By 29 May 2013, 132 cases and 37 deaths were reported, with cases originating from seven additional provinces and Beijing.
• Transmission: Most cases were linked to exposure to poultry, especially at live bird markets. No sustained human-to-human transmission was observed.
• Demographics: Median age was 61 years, with a male-to-female ratio of 2.4:1. Most patients had underlying chronic conditions.
• Symptoms: Initial symptoms included influenza-like illness, progressing to severe respiratory distress in many cases.

2. Clinical Findings

• Symptoms: High fever, cough, shortness of breath, and signs of lower respiratory tract disease.
• Complications: Included septic shock, respiratory failure, acute respiratory distress syndrome, and bacterial/fungal infections.
• Mild Cases: A small number of mild infections were reported in both children and adults.
• Therapy Impact: Use of high-dose steroids was associated with prolonged viral replication and increased risk of antiviral resistance.

3. Laboratory Diagnosis

• Initial Tests: Real-time RT-PCR tests were initially unable to subtype the virus, leading to reports of "unsubtypable" influenza A.
• Diagnostic Tools: Specific primers and probes for H7N9 were developed and distributed by the China CDC on 3 April 2013.
• Testing Methods: HI tests and microneutralization assays are used to detect specific antibodies in human sera.
• Virus Propagation: H7N9 can be grown in cultured cells and embryonated chicken eggs.

4. Laboratory Biosafety

• Guidelines: Biosafety measures should follow WHO and CEN CWA 15793 standards.
• Risk Assessment: Each country is responsible for its own risk assessment and containment protocols.
• Importance: Compliance with local biosafety regulations is crucial to protect both public and animal health.

5. Characterization of A(H7N9) Viruses

• Genomic Origin: H7N9 viruses are closely related to avian influenza viruses circulating in China, particularly A(H9N2) and A(H7N3) viruses.
• Genetic Features:
  • HA Gene: 95% identity with H7N3 viruses, with a single basic amino acid at the cleavage site.
  • NA Gene: 96% identity with N9 NA from China and Korea, featuring a 15-nucleotide deletion.
  • PB2 Gene: Mutations (e.g., Glu to Lys at position 627) suggest enhanced replication in mammalian hosts.
  • Other Genes: PB1-F2, M1, and NS1 proteins show signs of adaptation to non-avian hosts.
  • M2 Protein: Contains a mutation associated with adamantane resistance.

6. Infection in Animals

• Asymptomatic Infections: H7N9 causes asymptomatic infections in chickens, ducks, and other birds.
• Transmission: The virus spreads via droplets or contact.
• Surveillance: Enhanced monitoring in live bird markets and poultry farms was initiated in response to human cases.
• Reassortment Risk: H7N9 may have arisen through reassortment of avian influenza viruses in poultry.

7. Antiviral Therapy

• Drug Resistance: H7N9 is resistant to adamantane drugs due to M2 mutations.
• Neuraminidase Inhibitors: Susceptible to oseltamivir and zanamivir, though some variants show reduced susceptibility.
• Clinical Recommendations: Early use of neuraminidase inhibitors is recommended for confirmed and probable cases.
• Resistance Development: The R292K mutation in NA was detected in some patients, suggesting possible development of resistance.

8. Vaccines

• Development Efforts: WHO and collaborators are working on vaccine development using HA and NA genes from A/Anhui/1/2013-like viruses.
• Candidate Vaccines: Some vaccine candidates have been made available to manufacturers.
• Live Attenuated Vaccines: Parallel efforts are underway to develop live attenuated influenza vaccines (LAIV).
• Timeline: Vaccine production will likely take several months, with new technologies expected to shorten the process.

9. Risk Factor Assessment

• Primary Risk: Exposure to infected poultry, especially at live bird markets, is the main risk factor.
• Human-to-Human Transmission: No sustained transmission has been observed, but limited spread cannot be ruled out.
• Surveillance Importance: Continued monitoring in both domestic and wild bird populations is essential to track potential mutations and reassortment events.
• Public Health Vigilance: WHO and member states are closely monitoring for signs of high-risk events, including new human cases, mutations, and transmission patterns.

Key Information

• First Human Case: 87-year-old male from Shanghai with flu-like symptoms starting on 19 February 2013.
• Case Fatality Rate: Approximately 25%, with many patients still hospitalized.
• Genetic Origin: H7N9 likely emerged from reassortment of avian influenza viruses in China.
• Diagnostic Tools: Specific PCR reagents and HI tests have been developed for accurate diagnosis.
• Biosafety Protocols: Follow WHO guidelines and national standards for safe handling of H7N9.
• Antiviral Use: Neuraminidase inhibitors are the recommended treatment, with caution due to potential resistance.
• Vaccine Development: Ongoing with the goal of clinical trials and establishing optimal regimens.

Conclusion

The emergence of A(H7N9) in China in 2013 highlights the importance of rapid surveillance, molecular characterization, and biosafety measures in managing zoonotic influenza viruses. While the virus primarily spreads from birds to humans, the potential for human adaptation and further mutations remains a critical concern for global public health preparedness.