Pandemic preparedness: What can epidemiological modelling offer policy? Nim Arinaminpathy Department of Zoology University of Oxford

Talk plan Influenza: a background From today to emergence of a novel influenza virus Antiviral drugs for control of pandemic influenza

Influenza RNA virus Clinical manifestations: Headache, sore throat, chills, fever, myalgia, anorexia, malaise Transmission By contact with respiratory droplets, generated by coughing or sneezing Infectiousness can start a day before symptoms and continue for 3 – 5 days after symptoms developing in adults

The seasonal influenza burden Disease: 5 – 15% of population affected with upper respiratory tract infections in annual flu season Estimated 3-4,000 annual deaths in UK caused by influenza infection (mainly elderly and immunocompromised) The Economy: Europe: flu accounts for ~10% of sick leave Costs US estimated $90bn a year

Influenza family tree Orthomyxoviridae Influenza ABC H1N1 H3N2 … Type Subtype From …

Pandemic and seasonal influenza Taken from

Social and economic disruption

H5N1: Future pandemic? Wild bird reservoir Poultry Humans Transmitted from bird to human by inhaling dried aerosolised faeces First major outbreak in 1997, Hong Kong Resurgence in 2003 has seen virus established in poultry in South-East Asia So far human-to-human spread is non-existent or very limited 387 human cases, 245 deaths to date Wide geographical spread, from S.E.Asia (inc. Indonesia, Viet Nam) to Africa (Nigeria, Egypt) However, H7N7 and N9N2 are also pandemic candidates

Evolution and emergence of pandemic influenza Each human case is an opportunity for an avian virus to adapt for human transmission

Antiviral drugs for pandemic control No vaccine for at least first 6 months Oseltamivir (Tamiflu) is main antiviral drug of choice UK stockpile: Currently enough for 25% of population Drugs intended mainly for treatment, not prophylaxis For all clinical cases How best to minimise epidemic size and impact with a limited stockpile?

A simple compartmental model S ITIT ININ RTRT RNRN γTγT γNγN αλ (1-α)λ

A simple compartmental model S ITIT ININ RTRT RNRN γTγT γNγN αλ (1-α)λ

1957 Asian Flu pandemic 30/11/57 22/02/58

1957 Asian Flu pandemic

25% stockpile exhausted CFR 0.16% R Asian Flu pandemic

How many drugs are needed? Secondary effect of mass antiviral treatment is to reduce the spread of infection in the community Its strength depends on drug efficacy and disease transmissibility

Antiviral programmes By shortening infectious period and reducing infectiousness, antiviral drugs can influence the course of infection Broadening and delaying epidemic peak Reducing numbers of cases If there is a risk-group for whom the drug has little protective effect, the stockpile is better deployed in the general population. Priority shifts to protection from infection rather than from illness.

The social element Potential wastage of drugs on the worried well Personal stockpiles Non-compliance with treatment regime may lead to drug resistance Pressing ethical questions, eg distributive justice

Conclusions Mathematical models can offer valuable insights into disease control Transmission dynamics are often fundamental to epidemic outcomes and effects of interventions …sometimes offering counterintuitive results! However models always entail simplifications, often about human behaviour (important factors) Effective pandemic preparedness could involve a synergy between such models and the social sciences