# Session Overview By the end of this session, you should be able to: · Understand the nature, epidemiology and history of the influenza virus; · Analyse the various factors that contribute to and/or mitigate the risk of pandemic influenza; · Identify the key actors and institutions in global efforts to control and mitigate the threat of pandemic influenza; · Assess national measures to enhance pandemic influenza preparedness; and · Explain the contemporary debates/issues inhibiting effective governance of pandemic influenza. ## Key terms Antigenic drift – This occurs when there is a minor change (mutation) during virus replication in the same sub-type of the influenza virus, resulting in a new strain of the virus emerging. Antigenic shift – This occurs when there is a major change during virus replication resulting in an entirely new sub-type of the influenza virus emerging that may or may not be capable of crossing the species barrier, but which has pandemic potential. # 1. Background # 2. Influenza pandemics - Historically humans are infected by influenza. The important part is what makes it a pandemic: when a new strain—be it from antigenic drift/shift—the strain is highly infectious with little to no human immunity, that causes severe illness which is easily transmissible - There are two measures: pharmaceutial (such as vaccines) and non-pharmaceutical such as social distancing. - Vaccine is hard because the limited capacity to produce globally, and mutation keeps happening. # 3. The International Response to Influenza The lead actor in global efforts is one, [[World Health Organization (WHO)]], FAO, OIE, [[World Bank (WB)]], and private stakeholders. in 1952 WHO launched [[Global Influenza Programme]] GIP provides member states with strategic guidance, technical support and coordination of activities to make their health systems better prepared against seasonal, zoonotic and pandemic influenza threats. The goals of GIP: 1. Monitor and track influenza outbreaks; 2. Generate and transfer knkowledge and technical guidance about influenza; 3. Guide and support countries to develop and strengthen influenza control programmes; 4. Identify gaps in knowledge about the disease and foster research to fill these gaps; 5. Facilitate more equitable access to vaccines and antiviral medicines; 6. Provide global health leadership to prevent and control influenza ## Global Influenza Surveillance and Response System ([[GISRS]]) Established in 1952 and formerly known as the Global Influenza Surveillance Network (GISN), the WHO GISRS: · Monitors the evolution of influenza viruses and provides recommendations and risk assessment; · Acts as a global alert mechanism for the emergence of influenza viruses with pandemic potential. There are 153 National Influenza Centers based in 114 countries. NICs collect data and samples and forward the information to one of six Collaborating Centres of four Essential Regulatory Laboratories (ERLs) for influenza, based in five countries: the UK, the US, China, and japan. There are also four WHO H5 Reference Laboratories which deal specifically with public health needs arising from avian influenza A (H5N1) infection in humans. The CCs and ERLs have responsibility for isolating and identifying which strains of the influenza virus are currently circulating and which are the most prevalent. They then make a recommendation to national licensing authorities and pharmaceutical manufacturers on which strains should be contained in the vaccines for seasonal influenza. Based on the WHO recommendation, which is made twice a year, each vaccine is developed to contain the three most dominant strains. This information is then used to inform the development of vaccines, which National Licensing Agencies have responsibility for authorising prior to any national vaccination campaign being launched. WHO: Global Outbreak Alert and Response Network: [[GOARN]] The Global Outbreak Alert and Response Network ([[GOARN]]) was created by WHO in April 2000. GOARN’s role is to bring together technical expertise from around the world to rapidly respond to disease outbreaks as they are occurring. Since 2000 GOARN has responded to over 50 events worldwide, helping to deploy numerous Rapid Response Teams or RRTs, to assist national health authorities in containing outbreaks within their territories by sending technical experts to advise on the implementation of public health measures. While GOARN provides support for all types of disease outbreaks (such as Ebola), it has been involved in several influenza-related events, assisting a number of southeast Asian countries in 2003 and 2004 following multiple outbreaks of H5N1. GOARN was also mobilised to respond to the 2009 H1N1 influenza pandemic and most recently the COVID-19 pandemic. It is, in many senses, the practical “hands on” side of WHO’s work. ### WHO: FluNet ### WHO: IHR 2005 WHO’s mandate to protect human health against influenza, is reinforced by the organisation’s authority under the **International Health Regulations (2005)** – or IHR. The IHR were originally developed in 1952 to help strike the balance between preventing the spread of infectious diseases, while minimising disruption to international traffic and trade. Although originally only covering a limited number of diseases, in 2005 the IHR underwent substantial revision and the scope of the Regulations was expanded to include any disease that may cause a “**public health emergency of international concern**”, or PHEIC.  Pandemic influenza now falls under the scope of the IHR 2005 framework, and this gives both WHO and all member states certain roles and responsibilities.  The IHR sets guidelines for preparedness and response measures for a public health emergency of international concern and it is intended to be binding on all WHO member states. The most recent influenza pandemic was the H1N1 outbreak in 2009, which was declared a PHEIC.  Subsequent epidemics of Ebola, Zika, COVID-19 and the Monkeypox virus were also declared PHEICs. An obligation imposed by the IHR is the need for national pandemic preparedness plans to be in place.  Virtually every member state of WHO now has a national pandemic plan, and we have also seen the emergence of regional pandemic plans such as the North American Plan for Avian and Pandemic Influenza, that seeks to encourage close collaboration between Mexico, the United States and Canada.  We will discuss national plans later on in the session. ### WHO: The Pandemic Influenza Preparedness (PIP) Framework The WHO and its Member States commit to virus sharing obligations, in return for benefits in vaccine access. It is innovative in involving the private sector which is required to provide benefits to low-income countries (via the WHO) in exchange for access to biological materials which support industry research and development. The PIP Framework aims to regain the trust of developing countries such as Indonesia. In 2005 Indonesia had been particularly badly hit by the H5N1 avian flu outbreak in South East Asia. Indonesia stopped sharing A (H5N1) viruses with WHO collaborating centres because the resulting vaccines produced by commercial companies were likely to be unavailable to developing countries such as itself. Although Indonesia was criticised, the controversy exposed the inequitable position of lower income countries which tend to be more vulnerable to infectious disease outbreaks, while being least able to purchase vaccines or compete with high income countries for medications in an influenza pandemic when supplies will be limited. The PIP framework enables cash benefits to be channelled through WHO to countries most in need and there are in-kind contributions, including pledges of pandemic vaccine and antivirals in real time in the event of a pandemic and capacity building. ## Other institutions FAO and OIE focused on assisting animal disease surveillance capacity for highly pathogenic avian influenza (HPAI) and have established the OFFLU network, which fulfills a similar function to GISRS but in terms of animal health. The World Bank makes funds available for pandemic influenza-related initiatives by means of: 1. The Global Program (GPAI), and 2. Trust funds, notably the multidonor Avian and Human Influenza Facility (AHIF) The GPAI permits countries to access loans, credit or grants from the Bank to strengthen pandemic preparedness for both animal and human health. Countries can apply to the Bank for funding to strengthen their veterinary and health services to deal with avian flu outbreaks among animals, to minimise the threat to people, as well as initiating projects that prepare for and respond to any potential human flu pandemic. The AHIF was established to help developing countries meet financing gaps in their integrated county programmes, to minimise the risk and socioeconomic impact of avian and potential human pandemic influenza. ## North American Plan for Animal and Pandemic Influenza (NAPAPI) Launched in 2012 as a joint initiative of the USA, Canada and Mexico, NAPAPI is a regional and cross-sectoral health-security framework to strengthen these countries’ emergency response capacities and to ensure a quick and coordinated response to outbreaks of pandemic influenza or animal influenza. ## Global Health Security Initiative (GHSI) Established in November 2001, the GHSI is an informal partnership of eight countries (France, Germany, Italy, Japan, Mexico, the UK and the US) and the European Union to strengthen global preparedness and response to threats to health security, including pandemic influenza. With WHO acting as technical advisor, the GHSI is intended to work with, rather than replace or duplicate the work of other groups. The GHSI has five working groups including a Pandemic Influenza Working Group which “is responsible for sharing and comparing respective national approaches to pandemic preparedness, including vaccine and anti-viral stockpiling and use, surveillance and epidemiology, diagnostics, and public health measures”. ## The Challenge of Vaccine Production Gostin [2014] has identified as the five “factors at play in pandemic vaccine shortages”, namely: - Vaccine design, production and registration: the time lag between identifying a pandemic strain and designing a vaccine which has been tested for safety and effectiveness will allow the virus to spread, and lead to increased demand and cost when the vaccine is available. This will disadvantage the poor and increase inequity. - Intellectual property rights: Any point in vaccine production where pharmaceutical companies can exert IP rights (e.g. by patenting viral genetic sequences) will restrict access to the vaccine to those able to afford the increased cost. - Production capacity: Despite an increase in vaccine production capacity, it remains below pandemic demand. The largest vaccine companies are located in wealthy countries. Even if lower-income countries can obtain IP rights, they may be unable to produce vaccines domestically. - Prepurchase agreements: High income countries often have contracts with industry to secure pandemic vaccine supplies, exacerbating shortages for countries without such agreements. - Multiple stakeholders: Vaccine production requires the coordination of diverse stakeholders with varied interests and motivations. This requires improved global governance. ## Activity 2 Choose either GISRS or GOARN and write a few paragraphs on the Moodle discussion forum giving an example of its activities during a recent outbreak - GOARN is a WHO network of technical institutions and networks globally that respond to acute public health events with the deployment of staff and resources to affected countries. It aims to deliver rapid and effective support to prevent and control infectious diseases outbreaks and public health emergencies when requested. - In WHO Western Pacific Region, GOARN was deployed during COVID-19 pandemic as international technical assistance to strengthen COVID-19 response operations within the Region. There were 72 experts deployed on 89 missions through GOARN to 12 countries and areas in the region. - The GOARN area of technical of expertise were epidemiology and surveillance, laboratory, infection prevention and control, information management, and clinical case management. # 4. National Influenza Preparedness Countries are advised to designate a national pandemic planning committee, to develop national emergency structures, and to clearly delineate a coherent chain of command to identify who takes charge and how decisions taken will be implemented. WHO member states are then encouraged to test those plans to identify any areas in need of improvement. Governments have also been encouraged to strengthen links with neighbouring countries, to ensure that the actions and activities taken by one government will not adversely affect neighbouring countries and vice versa. A majority of member states have now developed national plans, but surveys of these plans indicate considerable inconsistency in the different approaches taken. It is not clear if some countries have simply missed some elements of pandemic planning, or if they had reviewed the various options and decided they were inappropriate or did not fit with their national arrangements. ## 4.2 Challenges in National Pandemic Preparedness Planning There are a number of challenges in planning for a pandemic. These include: · Ethical considerations: rationing of limited medical resources, enforcement of quarantine, seizure of property, information privacy, information sharing, border controls · Lack of cross-border consistency: it is unclear to what extent many plans have been developed in consultation with neighbouring countries. · Lack of testing of plans · Variation in health system structures and public health arrangements · Need for a “whole-of-society” approach · Capacity building: In the aftermath of the 2014-15 Ebola outbreak, in 2016 the WHO established the [[Joint External Evaluation (JEE)]] tool to test national capacity and compliance with the IHR. This is a voluntary exercise which combines national self-assessment with evaluation by a team of experts appointed by WHO. Core capacities required by the IHR such as surveillance, human resources and laboratory facilities are measured and scored, and a report is published on the WHO website. · Legislative authority: ==Although the IHR is described as “legally binding”, there is no enforcement mechanism at the international level==. Therefore, national laws need to be in place to provide the legislative authority to do what needs to be done. # 5. Integrating activity # 6. Summary # 7. References ## 7.1 [[Essential readings]] Gostin L. Global Health Law. Cambridge, MA: Harvard University Press; 2014. Chapter 12: Pandemic Influenza: [[@gostinPandemicInfluenzaCase2014]], pp359-378 [[@kamradt-scottChangingPerceptionsPandemic2012]] [[Kamradt-Scott]], A., 2012. Changing perceptions: of pandemic influenza and public health responses. American journal of public health, 102(1), pp.90-9 ## 7.2 [[Recommended reading]] [[@finebergPandemicPreparednessResponse2014]] Fineberg, H.V., 2014. Pandemic preparedness and response—lessons from the H1N1 influenza of 2009. New England Journal of Medicine, 370(14), pp.1335-1342. Gilbert, J.A., 2018. Seasonal and pandemic influenza: global fatigue versus global preparedness. The Lancet Respiratory Medicine, 6(2), pp.94-95. Potter, C.W., 2001. A history of influenza. Journal of applied microbiology, 91(4), pp.572-579.