World Health Organization 26 April 2017 Global capacity and responses to pandemics WHO's global strategy – N. Shindo MD, PhD. Coordinator Pandemic and Epidemic Diseases Department Epidemic Clinical Management ERS International Congress 2015, Amsterdam

Asclepius – Greek god of medicine His daughters are Hygieia ("Hygiene"), Iaso ("Medicine"), Aceso ("Healing"), Aglea ("Healthy Glow"), and Panacea ("Universal Remedy").

HSE cluster and PED Department World Health Organization 26 April 2017 DG FWC GMG IHS HSE PED FOS GCR HTM NMH PEC Pandemic and Epidemic Diseases Food safety and zoonosis Global Capacity and Respnse

How many pathogens able to infect humans? World Health Organization 26 April 2017 1400 pathogens1 are known to infect human, other are discovered /identified every year Some of them are responsible of global public health problems e.g. SARS, in 2003, pandemic influenza in 2009 70% from animal origin HIV (1983) Discovery curve for human virus species2 Hendra virus (1994) Chikungunya virus (1956) Monkeypox virus (1972) Ebola virus (1976-7) 1Jones, K, Nature (2008) 2Woolhouse, ME, Proc. R. Soc. B (2008)

Pandemic and Epidemic diseases department Improve shared knowledge and evidence-base for epidemic diseases to inform policies at international and national levels Perform timely risk assessment and monitoring of infectious epidemic diseases of international concern to define emergency intervention strategies.   Support countries throughout the epidemic cycle: Preparedness, Response and Resilience to epidemics   Optimize treatments and diagnostics to reduce infectious diseases mortality   Implement global mechanisms and processes to deal with the international dimension of epidemic diseases  

Cross-cutting initiatives and network PED activities Diseases Cholera Emerging diseases Hendra virus infection Influenza (avian, seasonal, pandemic) Leptospirosis Meningitis Nipah virus infection Plague Rift Valley fever SARS and coronavirus infections Smallpox and human monkeypox Tularemia Viral Haemorrhagic fevers (Ebola, Marburg, Lassa, CCHF) Yellow fever Cross-cutting initiatives and network Antimicrobial resistance (AMR) Battle against Respiratory Viruses (BRaVe) initiative Communicable Disease Control in Humanitarian Emergencies (DCE) Emerging and Dangerous Pathogens Laboratory Network (EDPLN) International Coordinating Group (ICG) for yellow fever, meningitis and cholera Global Infection Prevention and Control Network (GIPCN) Global influenza Surveillance and Response System (GISRS) Global Leptospirosis Environmental Action Network (GLEAN) and Meningitis Environmental Risk Information Technologies (MERIT) project Pandemic Influenza Preparedness framework (PIP) Weekly Epidemiological Record (WER)

Evidence to reduce disease transmission e.g. Role of pigs in the transmission/ amplification of some deadly viruses (viral haemorrhagic fever, Influenza) Impact on preventive measures and cross sectorial work(OIE/FAO) e.g. Bats in haemorrhagic fever transmission

Develop public health research agenda WHO is streamline research efforts done by academia or industry to answer public health questions How useful it is to stockpile mask for pandemic preparedness? What is the actual risk to face an avian influenza pandemic? How can we foster research on new treatments for viral respiratory diseases to save 700 million children under 5 each year ? (BRAVE initiative)

What do we do ? Perform timely risk assessment and monitoring of infectious epidemic diseases of international concern to define emergency intervention strategies.

Outbreaks on the African continent (2007-2013) A total of 174 epidemics Number of epidemic by year in Africa Number of epidemics (2007-2013) Analysis excluded Poliomyelitis, HIV, TB and malaria A total of 15 diseases cause(d) outbreaks include: Avian Influenza Lassa Fever Plague Chikungunya Marburg Rift Valley Fever Typhoide Cholera Meningitis Ebola Monkeypox West Nile Fever Hepatitis E Nodding disease Yellow Fever The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO 2013. All rights reserved Source: WHO/PED, March 2013

Preventive interventions, 2012 Prepositioning of reagents and treatments: meningitis Preventive vaccination campaigns (GAVI support) yellow fever

Epidemic responses, 2014 Global stockpile of vaccine and antivirals Epidemic responses for MERS CoV (Middle East) Avian influenza H7N9 (China) Ebola (West Africa) Global stockpile of vaccine and antivirals

New approaches for old disease: cholera Close partnership with water sector to reduce cholera transmission Rational use of oral cholera vaccine during emergencies (e.g. global oral cholera vaccine stockpile)

What do we do ? Optimize treatments and diagnostics to reduce infectious diseases mortality

Differential mortality and access to care Cholera Treatment Unit (2003) Hospitalized patient during SARS outbreak (2003)

Improvement of clinical management and infection control Guidance for treatment and infection control Access to medicine (prequalification, essential list of medicine) Partnership with experts networks: ISARIC, INFACT

Global Health Security IHR(2005), a paradigm shift International legal instrument, 194 countries Aim: help the international community prevent and respond to acute public health risks that have the potential to cross borders and threaten people worldwide Increased emphasis on early source control rather than borders Applicability to all hazards From preset measures to adapted response based upon risk assessment, facilitated by communication Includes an obligation to build national capacities to detect and respond to potential public health events

Implementation of the PIP framework Sharing of influenza Viruses GISRS Sharing of benefits Vaccines Antivirals Diagnostics Publications Equal footing

Pandemics of the 21rst century World Health Organization 26 April 2017 Pandemics of the 21rst century

Some recent emerging and re-emerging diseases Viral haemorrhagic fever : Marburg (1967), Ebola (1976) HIV –AIDS (1980s- now pandemic disease) Yellow fever (re-emergence in west Africa 2000) SARS (2003) H5N1 (2003), H1N1 pdm (2009), H7N9 (2013) MERS-Cov (2012)

Rapid spread of infectious diseases Zones infected with Aedes aegypti New York city 16 h Miami 20 h Nelle- Orléans 22 h Sao Paulo 26 h Brisbane Sydney Bangkok Delhi 14 h Les durées moyennes de voyage, incluant le temps de transit, ont été fournies par Carlson Wagons-lits ®. Abidjan Lagos, Nigeria (Source : Carlson Wagons-lits ) YELLOW FEVER INITIATIVE

Modeling EID events: Relative risk of an EID Hot Spots: global distribution of relative risk of an EID event caused by zoonotic pathogens from wildlife, (Jones Nature, 2008).

Recent influenza pandemics World Health Organization 26 April 2017 Recent influenza pandemics A(H1N1) 1918: « Grippe espagnole» 50-100 millions de décès Credit: US National Museum of Health and Medicine A(H2N2) 1957: « Grippe asiatique» 1-4 millions de décès A(H3N2) 1968: « Grippe de Hong Kong» 1 million de décès 2009: « Grippe A (H1N1) » ≈ 200 000 décès A (H1N1) Grippe asiatique 1957: Chine en 56, puis Singapour en 02/ 57, HG 04/57, US 06/57, canard sauvage Grippe de Hong Kong 1968: Fin 07 Vietnam et Singapour, September Inde, Philipines, Australie, Europe, US (en même temps que le retour des soldats de la guerre du VN) en 69 Japon, Afrique, Amérique Latine, cochon hôte intermédiaire, origine aviaire

Laboratory-confirmed human avian influenza infections since 1999

Avian Influenza A(H7N9) Novel Coronavirus (MERS-CoV) World experiencing emergence of 2 exceptional new virus infections Avian influenza A(H7N9) Novel coronavirus MERS-CoV Unusual global situation Unrelated, highly pathogenic Potential to evolve & spread No comparable situation since 2003 when SARS & H5N1 (re)emerged H7N9 EM courtesy of China CDC nCoV EM courtesy of U.S. CDC,

Sustainable Person-to-Person Transmission Crossing of a Threshold 25 April: PHEIC announcement 4 April: outbreak of ILI in Veracruz 27 April: WHO phase 4 March April May June July August September October 15-17 April: clusters of severe pneumonia in Mexico 27 April: Canada and Spain report H1N1 cases 23 April: H1N1 confirmed in several patients in MX

This is a map showing the availability of PP plans globally in April 2009. These are publicly available plans accessed through country websites. Almost all of this preparedness started around 2005 and in about 5 years 141 countries had publicly accessible PP plans. Were they all in pristine condition? No. However many countries had exercised and revised their plans, even had inter-country preparedness activities. For instance Japan, Korea and China from this region were already holding inter-country exercises and planning activities. Similarly Israel, Jordan and Palestine were coming together to work under difficult political circumstances. And G7+Mexico came together to form a GHSAG under which is a PIWG to coordinate and communicate about PP activities. Looking back at the PP plans at the beginning of the pandemic, we see that while 71% had national pandemic committees, only 21% addressed sub-national planning which showed that there was still room for improvement in implementation. This is an on-going analysis within my group right now and the results should be available shortly.

Pandemic Response Tools PH measures (i.e. school closures, mask, mass gathering) Non-pharmaceutical Interventions Inactivated Influenza Vaccine (IIV) (1944) Improved IIV (1960 purified) IIV (1968 fragmented) (1980 sub-unit) GISN (1952) Cell-based (2007) LAIV (live-attenuated, 1960, Russia) Adjuvanted (1997) Vaccines (2003, USA) 1918 1957 1968 1997 2003 2009 Spanish flu pandemic Asian flu pandemic H5N1 Hong Kong 18 Cases (C) 6 Deaths (D) H5N1 Asia A (H1N1) 2009 pandemic Hong Kong flu pandemic Amatadane for influenza (1966) Rimatadane (1993) Neuraminidase inhibitor Oseltamivir and Zanamivir (1999) Antivirals Sulfonamides (1939) Penicillin (1945) Cephalosporins (1964) Aminoglycosides (1943) Erythromycin (1952) Introduction of other classes of antibiotics Antibiotics

Epidemic Disease Patterns Varied by Location May June Japan - Kinki area 390 confirmed cases No hospitalisation (As of 4 June 2009) Source: Japanese Ministry of Health, Labour and Welfare USA - Utah 489 confirmed cases 35 hospitalisations 2 deaths (As of 4 June 2009) Source: Utah department of Health. April May June

3. Communication Technical scientific communication/ risk communication Naming of the pandemic Communication on global risks

Gap between "technical" and "public" communication It is just a technical definition! But what did that exactly mean? Was it just a technical definition or did it mean more than that? Here the cartoon DG that this declaration was just a technical definition. In order to understand better what the declaration of Phase 6 means, allow me to take a step back and share with you how the WHO PP GL were developed. It all started in November 2007 with a working group meeting in Geneva…

Global availability of vaccines Only high income countries had access to the vaccine in fall 2009 Sources: Media monitoring vaccination annex of 27 November World Bank list of economies July 2009 World economies1 1 World Bank classification 2009

Vaccine deployment to low income countries WHO has received pledges of approximately 200 million doses of vaccine, 70 million syringes and US$ 48 million for operations. 99 countries requested vaccines As off May 2010, deployment of vaccine in 39 countries (approx 20M doses) Extremely complex project: donation agreements, regulatory, supply and timing issues. What mechanism should be put in place for future pandemics to ensure more equitable access to vaccine and medicines?

World Health Organization 26 April 2017 EDCARN: Emerging Disease Clinical Assessment and Response Network Clinical & Infection Control Pandemic & Epidemic Diseases WHO-HQ, Geneva

Genesis: Virtual network of SARS clinicians Clinical information for case definition, public health purposes Virtual network of SARS clinician New disease International spread No vaccine, no medicine, IPC? 50+ clinicians in 14 countries, telephone conference twice a week face-to-face meeting, 14 June 2003 On a more practical side - how was the response co-ordinated? One of the main issues with this outbreak response was to identify the causative organism. To enable this to happen, without too many people 'reinventing the wheel' was to co-ordinate the network on aetiology. This network involved 13 laboratories in 9 countries and involved daily teleconferences. A face to face meeting was organised, with video link up, to enable the sharing of information. The second issue was in the clinical management of these patients. With several hospitals in different countries dealing with SARS patients early on, it was very important to facilitate these groups sharing their knowledge on best clinical practice, infection control practice as well as to try to determine the similarities in what the medical staff were seeing so as to produce an appropriate case definition. This was down through a web site, teleconferencing and a face to face meeting in June.

World Health Organization 26 April 2017 Evolution: IHR(2005), biological threat, pandemic fear, global health security Avian influenza H5N1 MERS CoV 2009 H1N1pdm Avian influenza H7N9 SARS CoV vH3N2, vH1N1

PED's work on clinical management of EID Provide a platform for information exchange and mutual support throughout outbreak/pandemic of infectious diseases of international concern. Promote clinical data collection and the standardization of clinical research protocols; facilitate greater understanding of the natural history and manifestations. Monitor possible changes in illness manifestations and disease patterns that would have implications for initial case recognition/detection and for public health responses. Provide advice to MoH as well as on-site technical support to frontline clinicians to promote best evidence-based practices. Prepare rapid advice guidelines by quick literature reviews and expert consultations Enhance education and readiness of healthcare workers by clinical workshops and trainings.

EDCARN: Emerging Disease Clinical Assessment and Response Network Vision The mortality due to emerging pathogens is reduced through improved clinical management, even in absence of vaccine or specific treatment. Enhance/empower the role of clinical care / clinicians   Mission In the Global Health Security context, To strengthen global collaboration between clinicians, researchers, WHO, medical NGO's, national health authorities and other stakeholders in order to improve clinical management of patients during outbreaks of emerging diseases. Catalyst of new dynamics of PED control – bench to bed and beyond Basic science>animal models>regulatory mechanism>clinical trials>improved patient care>public health>policy

World Health Organization Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009–2010 H1N1 Pandemic: An Ecological Study 26 April 2017 Paula Miller, Aksharananda Rambachan, Roderick Hubbard, Jiabai Li, Alison Meyer, Peter Stephens, Anthony W. Mounts, Melissa Rolfes, Charles Penn

World Health Organization Policy case study: Argentina 2009 World Health Organization 26 April 2017

World Health Organization 26 April 2017 High antiviral use in October and November was observed at the same time as lower proportions of hospitalized patients requiring ICU care and invasive mech ventilation