Avian Influenza A (H7N9): Status and Initiatives

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1 Avian Influenza A (H7N9): Status and Initiatives Subhash Morzaria, Kachen Wongsathaporn, Pawin Padungtod, Wantanee Kalpravidh, John Edwards and Guo Fusheng

2 Background 31 March 2013: report of the first 3 human cases of H7N9 in China First ever detection of H7N9 subtype in humans Later detected in domestic birds in live bird markets through active surveillance Up to today, 450 human cases with a case fatality rate (CFR) of 36% H5N1 since 2003 (as of 24 January 2014): human cases worldwide (CFR = 59%) - 45 cases in China

3 Characteristics of A (H7N9) Chickens and quail

4 Influenza A(H7N9) Virus (Gao et al., 2013; Shi et al., 2013; Chen, 2013) PB1, PB2, PA, NP, M, NS genes H9N2 (Brambling, Beijing) (BJ16) HA gene (H7) A/duck/Zhejiang/12/2011 (H7N3) One basic AA (Gao) at HA cleavage site (virulence marker). Indicating low pathogenicity to birds. (No basic AA at HA cleavage site, Chen et al.,??) NA gene (N9) A/wildbird/Korea/A14/2011 (H7N9) (Shi et al., 2013) or Dongting Lake (H4N9)( Shi et al., 2013) or H11N9 (Butler, 2013) Five amino acid deletion at NA residue (adaptation to gallinaceous birds) PB2 gene changes enhances replication in mammals

5 Chronological distribution Weekly distribution of H7N9 human cases based on onset date Wave 1 (135 cases) Wave 2 (315 cases)

6 Spatial distribution

7 Surveillance in animals Ministry of Agriculture is doing surveillance in most Chinese provinces Extremely low prevalence (under 0.02%) 184 positive surveillance findings, all from bird or environmental samples (no pigs; only 1 wild bird) Most virological findings in LBMs (only 1 in a farm and 1 in a chicken)

8 Surveillance in animals Species distribution Provincial distribution of positive findings in birds/environment Additional 218 virological findings reported in peer reviewed articles (including 1 wild bird) and 346 positive samples mentioned in press releases

9 Critical role of Live Bird Markets LBMs play a role in transmission of H7N9 to humans via direct or indirect contact with live poultry Most existing live bird markets present a significant risk for the transmission of zoonotic pathogens, including influenzas Increased organization/structuring of LBM, centralized slaughter or (temporary) closures of LBM will reduce human exposure

10 Control measures in China On live bird markets: one wash a day, one disinfection a week, one market rest day a month Temporary closure (3 to 21 days) of infected markets with culling of all birds present (compensation: buying poultry off traders) need for providing alternative marketing options Ban of live bird trade in big cities Ban of poultry imports from affected areas or systematic serological testing of imported birds Market restructuring (improve biosecurity; poultry traceability) Permanent market closure and switch to centralized slaughter?

11 Effect of control measures in China Onset curve for the two most affected provinces and market closure in their main cities

12 Implications of H7N9 silent infection in poultry Unique LPAI with high infectivity and virulence in humans mammals Asymptomatic infections in birds, thus silent infection in birds presents increased risk of incursion, spread and human infections Low prevalence (surprising for LPAI, difficult to detect), presents surveillance challenge

13 H7N9: A significant risk to poultry industry Economic Estimated direct cost $1.6 billion Indirect costs unknown: culling, compensation, trade, live bird markets closures, replacement stock, vaccines, etc Enhanced biosecurity Market shocks Food security and livelihoods

14 Ongoing initiatives by FAO-WHO-OIE Coordination Regular tripartite teleconferences (information sharing) FAO China, Regional Office and HQ Country teams coordination with governments (PH/AH) OIE/FAO OFFLU Emergency expert consultation on surveillance, risk assessment and risk management Development of a surveillance framework and risk ranking of countries WHO and OIE visits to China

15 Concrete outputs in form of guidance documents Surveillance Risk assessment Risk management Laboratory protocols 15

16 Risk-based surveillance for H7N9 Risk Assessment for H7N9 Risk Management for H7N9 Laboratory Protocols and Algorithms Provided by participating laboratories and validated by the OIE and/or FAO Reference Centres and WHO Collaborating Centres. 16

17 On-going activities

18 Work on H7N9 and related influenzas in China FAO ECTAD CHINA 联合国粮食及农业组织跨界动物疫病应急中心中国办公室 Partnering with Veterinary Bureau, FAO Reference Centre for Animal Influenzas (Harbin), China Animal Health and Epidemiology Centre (CAHEC), provincial partners and FETPV network Responding to request for assistance with epidemiological studies, advice on surveillance and national planning 18

19 Activities in 2013/14 With CAHEC on Market chain analysis in high risk areas of Jiangsu and Anhui Province National training of provincial directors on improved surveillance, biosecurity and value chain analysis Planning for enhanced biosecurity and value chain analysis in key southern provinces, Hunan, Guangxi and Yunnan Vietnam/China Collaboration meeting held in 2013 Further bilateral, cross border meeting planned

20 Joint Epidemiological Investigation in LBMs in the main H7N9 infected Provinces in 2013

21 Understanding the live poultry market Chain in high risk areas in Eastern China

22 South and Southeast Asia activities Key questions Can we detect incursion early enough to mitigate risk of further spread and public health risk? Can we quickly transfer existing regional capacity (coordination mechanisms, technical expertise) in the region to address the apparent imminent threat of influenza A (H7N9) inursion?

23 Emergency risk-based surveillance Objectives To determine if the H7N9 had been introduced in at risk countries bordering China To determine if the extent of spread of H7N9 if incursion were detected Expected outcomes Early detection of H7N9 Strengthened capacity in diagnostics and surveillance for H7N9

24 Emergency risk-based surveillance Guided by experience in China Understanding of value chains necessary Critical role of LBMs a major virus sink, Mainly found in chickens and environmental Asymptomatic thus active surveillance (serological/virological) Detection by virus nucleic acid using RT-PCR

25 Value chain information from previous H5N1 surveillance Markets where birds from China were sold 25

26 Sampling sites (Trade = Risk) Gansu Shaanxi Qinghai Moderate Risk Level Hubei High Xizang Sichuan Chongqing Uttaranchal Karnali Seti Nepal Bheri Rapti Dhawalagiri Gandaki Lumbini Uttar Pradesh Hunan Bagmati Sikkim Sagarmatha Narayani Janakpur KoshiMechi Guizhou Bhutan Yunnan Manipur Sylhet Jharkhand Dhaka Sagaing Tripura Viet Nam West Bengal Khulna Mizoram KhulnaBarisalBarisal Chittagong BarisalBarisal Barisal BarisalBarisal Chhattisgarh Kachin Nagaland Meghalaya Rajshahi Bangladesh Lao PDR Assam Bihar Madhya Pradesh Myanmar Arunachal Pradesh Ha Giang Cao Bang Chin Shan Cambodia Mandalay Orissa Maharashtra Rakhine Magway Kayah Indonesia Bago Lai Chau Lao Cai Bac Kan Bac Can Tuyen QuangThai Nguyen Lang Son Yen Bai PhôngsaliDien Bien Bac Giang Phu Tho Quang Ninh Son La Ha TayHai Duong Louang Namtha Hoa Binh Hai Phong City Haiphong Thai Binh Bokeo Oudômxai Ninh Binh Nam Dinh Houaphan Thanh Hoa Louangphrabang Xiangkhoang Nghe An Xaignabouri Xaisômboun Vientiane Bolikhamxai Ha Tinh Vientiane [prefecture] Guangdong Hainan KhammouanQuang Binh Andhra Pradesh Puducherry Guangxi AyeyarwadyYangon Kayin Mon Quang Tri Savannakhét Thua Thien - Hue Saravan XékongQuang Nam 8th Regional Steering Committee Meeting of GF-TADs for Asia and the Pacific Paracel Islands

27 Sampling period Countries 1 st Round Sep 12 Apr 13 2 nd Round May 13 Aug 13 3 rd Round Dec 13 Mar 14 4 th Round Jul 14 Sep 14 Lao PDR Myanmar Viet Nam Cambodia Indonesia Bangladesh Bhutan Nepal Testing of retrospective samples collected from H5N1 surveillance Testing of samples collected from H7N9 surveillance

28 Sampling frame Sampling population: Chicken Sick birds Target sites Live-bird markets primary target sites Farms With value chain connection to China Backyard Types of samples Tracheal swabs Environmental swabs Serum (during the 2 nd 4 th round in Lao and Myanmar)

29 H7N9 molecular diagnosis- laboratory algorithm Oropharyngeal swabs from health poultry Swab from environment RNA Extraction (pool of <5) CDC M (type A) PCR NEG POS Report FLI H7 PCR NEG POS AAHL H5 PCR CNIC N9 PCR POS NEG NEG POS Report REFERENCE LAB Report H & N typing (Confirmation) HA & N Gene Sequencing

30 % flu A positive Results (all H7 negative) 40.00% 35.00% 30.00% 25.00% 20.00% 15.00% 10.00% 5.00% 0.00% * 1,243 2, ,116 1,650 10,839 1, , * Testing yet to be completed 2nd Round % Flu A positive 3rd Round % Flu A positive

31 Proportion of influenza A + samples By Sampling place Market Collecting Point Processing Plant By Sample type OP swab ENV Myanmar Indonesia % 0.2% Myanmar Lao PDR Nepal Bangladesh 31

32 Information sharing USAID meeting: participation from WHO, FAO, OIE, Myanmar, Lao PDR and Viet Nam (PH/AH sectors) Results of surveillance presented by each country Sharing lessons learned from surveillance Sharing of emergency preparedness and response plans Major gaps: Need for training in risk assessment at both public and animal health sectors Difficulty in aligning public health sector surveillance with animal health sector Need for support in emergency preparedness and response plans Joint simulation plans

33 Other ongoing activities Two regional TCPs: ASEAN and SAARC ($ 1 million) Technical support Communication and awareness Active surveillance Provision of diagnostics reagents Capacity building in diagnosis, risk assessment and risk management Emergency preparedness and response plans Support development of national contingency and preparedness plan in high risk countries

34 Conclusions No H7N9 incursion detected (yet) using risk-based virological surveillance using a structured and defined sampling frame and validated molecular diagnostic test Several flu A viruses both HPAI and LPAI identified Active, longitudinal surveillance provides proof of concept that genetic diversity in rapidly evolving flu A viruses can be detected early

35 Conclusions Existing HPAI H5N1 based capacity and knowledge enabled rapid virolgical surveillance Risk of incursion should be reassessed regularly Dynamic nature of value chains require regular monitoring Informal poultry movement information can be used to guide the selection of sampling locations Sampling frames need to be revised based on risk assessment

36 Conclusions Emergency preparedness Multi-sectoral discussion and clear roles and responsibilities Regular joint (AH/PH) risk assessment Enhanced targeted surveillance Aligning SARI/ILI with animal surveillance Public awareness (wholesale markets and collectors yards) Border control Agreement between AH and PH on response to incursion under different scenarios Proactive market management closure, cleaning and disinfection Provision of PPE, disinfectants, training

37 Conclusions Emergency response (scenario based) Reporting (public and animal health sectors) Market closures, humane culling and safe disposal Trace back and forward from the market (surveillance) Prevent new birds from arriving and monitoring secondary marketes Risk communication and awareness (ex and post ante) Reopening of markets

38 Risk factors Intensification farming systems Long value chains, low biosecurity along the value chains Socio-economic conditions Virological risks Several flu A viruses (H9N2, H5N1 (clade 1 x ), H5N6, H5N8, H10N11, etc Sharing of information

39 Future Meeting of high risk countries in Bangkok Tripartite risk assessment group for H7N9 TCPs

40 Acknowledgement National Animal Health Authorities in: Myanmar Lao PDR Viet Nam Indonesia Cambodia Bangladesh Bhutan Nepal FAO ECTAD country units USAID emergency funds US Centers for Diseases Control and Prevention (US CDC) Australian Animal Health Laboratory (AAHL) In-country partners ICDDR, B IP, C