Influenza

TIPRA Frequently Asked Questions, March 2017


1. What is TIPRA?

The Tool for Influenza Pandemic Risk Assessment (TIPRA) was developed to provide a standardized and transparent approach to support the risk assessment of influenza viruses with pandemic potential. TIPRA enables identification of gaps in knowledge so that attention and resources can be dedicated to address those needs.

2. What is an influenza pandemic risk assessment and why is it necessary?

Influenza pandemic risk assessment considers the likelihood and impact of a non-seasonal influenza virus spreading efficiently between people. Advance planning and preparedness are critical to help mitigate the impact of a pandemic. Pandemic risk assessments are critical to decide, clarify and justify public health preparedness, response and recovery actions.

3. Why did WHO develop TIPRA?

As per the WHO’s Pandemic Influenza Risk Management (PIRM) guidance and in accordance with the Pandemic Influenza Preparedness [PIP] framework (section 6.2.2), WHO is mandated to provide timely risk assessments for pandemic influenza preparedness and response. TIPRA supports risk assessment in the inter-pandemic and alert phases to inform on the virus’ pandemic potential, especially the biological aspects underpinning the risk for sustained human to human transmission.

4. How was TIPRA developed?

TIPRA was modelled after the United States Centers for Disease Control and Prevention (US CDC) Influenza Risk Assessment Tool (IRAT). It was developed in a multi-step process including technical expert consultations and four pilot test runs.

5. What are the objectives of TIPRA?

The objectives of TIPRA are to:

  • Support a timely and updatable hazard risk assessment for influenza viruses with pandemic potential;
  • Transparently document features of the virus and the infections they cause;
  • Identify knowledge gaps and prompt further investigations including research and surveillance;
  • Facilitate information sharing and decision making between scientists, policy-makers and other stakeholders.

6. What is the scope of TIPRA?

TIPRA supports risk assessment of influenza viruses with pandemic potential. This is defined as a virus that has been found to infect one or more humans and that have a haemagglutinin gene and potentially also other genes that are distinct from those in seasonal influenza viruses so as to indicate that the virus has potential to spread within human populations.

7. What risk question does TIPRA address?

TIPRA asks the question: "what is the risk of sustained human-to-human transmission of the virus”? To address this question, two components are examined – the likelihood of the event occurring and the impact to public health if that event occurred.

8. Who uses TIPRA?

Globally, WHO will be the key convener and user of TIPRA. The assessment at global level will be done in consultation with international experts in public health, animal health and research academia, and in close collaboration with the Member State(s) affected by the influenza virus. Risk assessments will routinely involve experts from the Global Influenza Surveillance and Response System (GISRS) including the WHO Collaborating Centres (WHO CC), the Food and Agriculture Organization (FAO), and World Organization for Animal Health (OIE).

The benefit of global risk assessment is that information for the assessment is acquired from various international sources including the virus-affected country. In this way, the assessment will likely reflect the most comprehensive and updated knowledge available about the virus.

If TIPRA is used in other settings, substantial caution is needed to ensure that; (a) experts from multiple sectors and disciplines score and evaluate the different virological, animal and public health risk elements; (b) risk assessments are well informed by the latest and most comprehensive knowledge about the virus available from institutions throughout the world; and (c) the process to conduct the risk assessment using TIPRA including risk elements are adhered to without modification. This is to avoid conflicting risk assessment findings.

9. What expertise is needed for appropriate use of TIPRA?

Experts from a variety of disciplines are needed to address the different risk elements in TIPRA. Experts involved should include Clinicians, Ecologists, Epidemiologists, Immunologists, Molecular virologists, Pharmacologists, Phylogeneticists, Veterinarians and Virologists.

10. When should TIPRA be used?

TIPRA should be used to assess the risk of influenza viruses with pandemic potential that are known to have infected one or more humans, and where the population immunity to the virus is low enough to potentially sustain human-to-human transmission. A number of epidemiological and virological triggers can lead to a risk assessment of influenza viruses with pandemic potential.

Possible epidemiological triggers include, but are not limited to:

  • First documented cases of human infection with a non-seasonal or animal influenza virus
  • Cluster of human cases with potential human-to-human transmission of a virus
  • Cluster of human cases involving infections beyond blood-related family members
  • Changes in epidemiological trends associated with the virus infection such as number of cases detected, disease severity, mortality ratio or geographic dispersion

Possible virological triggers include, but are not limited to:

  • Presence of amino acid substitutions at or near the hemagglutinin receptor binding pocket that would increase the capability of the virus to bind to mammalian alpha 2-6 receptors
  • Changes in other viral properties such as virulence and transmissibility, as demonstrated in transmission studies or laboratory assays
  • Increased detection of a virus with reduced antiviral susceptibility

11. How often should TIPRA be used?

There are no prescribed timelines for repeating risk assessments for the same influenza virus. Each time a risk assessment is undertaken for an influenza virus, it builds on the previous assessment. When more information becomes available about the virus or if its’ clinical, epidemiological or virological profile changes, repeating the risk assessment based on updated knowledge is worthwhile.

12. How is TIPRA used for risk assessment?

TIPRA supports risk assessment by asking a risk question about the pandemic likelihood and impact of an influenza virus. Specifically, TIPRA asks: what is the risk of sustained human-to-human transmission of the virus? To conduct this hazard risk assessment, a multi-step process is applied. Information about the virus properties, its attributes in the human population, and its ecology and epidemiology are gathered systematically. Global experts then score these different aspects and characterize the risk based on the available information. They also indicate their confidence in the risk characterised in order to reflect the breadth and quality of information available to make the assessment.

13. What information feeds into the risk characterization using TIPRA?

Technical experts score virus attributes known as ‘risk elements’ according to risk stratification definitions and based on information and knowledge available about the virus at the time of assessment. Nine risk elements, including the properties of the virus (4 elements), attributes in the human population (3 elements) and virus ecology and epidemiology in non-human hosts (2 elements), are used to characterize the virus risk as shown below. Technical experts also document their confidence in the breadth and quality of information used to score the risk elements.

  • Properties of the virus
    • Receptor binding properties
    • Genomic characteristics
    • Transmission in animal models
    • Susceptibility to antiviral treatment
  • Attributes in the human population
    • Human infection
    • Disease severity
    • Population immunity
  • Virus ecology and epidemiology in non-human hosts
    • Geographic distribution in animals
    • Infections in animals

14. How are the analyses of individual risk elements combined in TIPRA to address the risk question?

To answer the risk question, likelihood and impact scores are calculated using a multi-attribute additive model. Scores for the nine risk elements are weighted according to their relative importance to the likelihood and the impact components. The weights and process for combining the scores are explained in the guidance document.

15. Why do experts indicate their confidence in the risk characterised?

Confidence describes how sure the assessment team is of the risk characterized, where the more quality evidence there is to inform the assessment, the greater the confidence in the results. Confidence is important since it reflects the reliability, completeness and quality of the information used, and the underlying assumptions made to complete the assessment.

16. How does TIPRA tie in with other risk assessment tools?

Risk assessment involves assessment of three components: the hazard, the possible exposure(s) to the hazard, and the context in which the event is occurring. For pandemic influenza, the hazard is the influenza virus of concern. Exposure defines the population groups known to have been or likely to be exposed so that a profile of the susceptibility in terms of immunity can be determined. Exposure assessment focuses on epidemiological and susceptibility factors such as incubation period and potential for transmission. Context assessment focuses on the environment in which the event takes place, including social, scientific, economic, ethical, political and policy factors.

Although hazard, exposure and context are assessed separately, there is some overlap in the information required to assess each component.

TIPRA focuses on the risk of the influenza virus itself, that is, the hazard. TIPRA can also feed into risk assessments that characterize hazard, exposure and context collectively. This can be done using tools such as WHO’s Rapid Risk Assessment of Acute Public Health Events which has been applied by WHO and Member States for International Health Regulation (IHR) purposes.

17. How do TIPRA outputs feed into risk management?

TIPRA synthesizes current evidence about an influenza virus to help identify gaps and steer actions, including research and surveillance activities. As TIPRA outputs include a summary level of risk for the virus assessed, findings for one virus may be compared to the level of risk assessed for other viruses. This can help prioritize attention and resources given to address different viruses.

18. What are the benefits of TIPRA?

Influenza pandemics are unpredictable but recurring events that can have consequences on human health and economic well-being worldwide. Advance planning and preparedness are critical to help mitigate the impact of a pandemic. Therefore, TIPRA serves as a supportive tool to appreciate the current risk of an influenza virus with pandemic potential. It also informs understanding on what is known and what is unknown about the virus with pandemic potential in order to guide surveillance and research priorities.

19. What are the limitations of TIPRA?

TIPRA has both scope and methodological limitations:

Scope - TIPRA is designed to be used when an influenza virus has caused at least one human infection. TIPRA is not designed for risk assessment of seasonal influenza viruses as the tool focuses on a virus’ potential for sustained transmission among humans. TIPRA is also not designed for use on influenza viruses for which there is high population immunity, as this would naturally prevent the virus from causing a pandemic.

Methodological - TIPRA applies a qualitative risk assessment methodology, where it relies on expert judgement for risk assessment. This is different to tools used in other disciplines such as food safety and microbiology where quantitative approaches or cut offs are applied.

Early in virus emergence, a mix of quantitative and qualitative data is likely to be used during the assessment process as comprehensive numerical data may not yet be available. The degree of quantification that is possible in a risk assessment depends on factors such as the type and breadth of data available, how quickly the assessment is required and the complexity of the issues. It should be emphasised that a quantitative risk assessment which uses poor data or inappropriate quantitative techniques can be far less scientific and defensible than a well-structured, more qualitative assessment.

To appropriately reflect limitations in the volumes or quality of data available for risk assessment, the risk assessment team describes their confidence in the overall risk characterized as well as for each of the nine risk elements evaluated. In this way, the risk assessment team can communicate the uncertainty in the risk assessed.