FIMDP 2013 DEPT OF COMMUNITY MEDICINE SRM MEDICAL COLLEGE,SRM UNIVERSITY & UNSW AUSTRALIA 9 TH & 10 TH JAN 2013

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1 FIMDP 2013 DEPT OF COMMUNITY MEDICINE SRM MEDICAL COLLEGE,SRM UNIVERSITY & UNSW AUSTRALIA 9 TH & 10 TH JAN 2013

2 Pandemic influenza and emerging infections Public health management and planning School of Public Health and Community Medicine Raina MacIntyre

3 Background Infectious diseases are unique because they have the capacity to be transmitted (from human to human or animal to human) Humans exist in mutually exclusive states of susceptibility, infection or immunity. Potential for epidemics Immunity results from natural infection OR vaccination

4 The meaning of R - the n of secondary cases generated from one index case The lower the Ro, the easier it is to eradicate or control a disease

5 Factors affecting Ro Characteristics of the organism Infectivity of organism Duration of infectiousness Asymptomatic transmission Population characteristics Demographics Social mixing patterns Population density

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7 Examples of R (Anderson & May 1982, 1988) Pertussis Measles Mumps Varicella 7-12 Rubella 6-10 Scarlet fever 5-8 Polio 5-7 Diphtheria 4-5 HIV 2-5 (men who have sex with men in UK) (heterosexuals in Uganda and Kenya)

8 Hospitalisations Interpreting R If R>1 the number of cases increases (an epidemic will occur) If R<1 the number of cases decreases (infection cannot be sustained and dies out) R=1 is the epidemic threshold Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr

9 Elimination graph % Herd Immunity required for elimination 93 Measles 60 Small pox 3 15 R

10 Herd immunity Herd immunity is when the entire population is protected, whether they have been immunized or not, because the number of susceptible individuals is too small for infection to spread. The higher the R, the higher the herd immunity required to control disease. Key concept for control of vaccinepreventable infections

11 R value of pandemic influenza Critical to the success of control strategies Many recent scientific papers suggest the R of an emergent pandemic will be 1.5 to 1.8. Some estimates as high as 6.7* If R > 3, all bets off If R <3 or 2, the cumulative impact of strategies may Delay the impending pandemic arriving in Australia Reduce the impact of the pandemic once it arrives *Mathews JD, McCaw CT, McVernon J, McBryde ES, McCaw JM (2007) A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity. PLoS ONE 2(11): e1220. doi: /journal.pone

12 What is an emerging or re-emerging infection New, evolving or re-emerging infections As long as microorganisms have the capacity to mutate, emerging infectious diseases (EID) will remain a threat to humans 335 EID events between * 72% originate in wildlife* Approximately half are viral, half bacterial/rickettsial* * Jones JE et al. Nature, 2008; 451:21.

13 Some EIDs Pandemic influenza SARS Anthrax Antimicrobial Resistance Botulism Campylobacteriosis Dengue Fever E. coli Lyme disease Plague Prion Diseases Smallpox

14 Infectious diseases societal impact Infectious epidemics have a unique capacity to cause major, almost instant economic disruption During SARS, near-bankruptcy of travel related industries US Anthrax letter bombs in 2001 shut-down of the US Postal System Issues of law and order and public demand Critical infrastructure Major investments globally in planning for the health, economic and societal impacts of a pandemic

15 Influenza Orthomyxovirus Enveloped SS RNA virus Types A, B, C Reservoirs include humans, birds and animals Main antigenic determinants of immunity are haemagluttinin (HA) and neuraminidase (NA) Neutralising antibodies against HA are the main defence against influenza; vaccines contain HA and NA antigens

16 Transmission of influenza Large particle respiratory droplets produced when someone coughs or sneezes inhaled by someone who is in close proximity (usually 1m or less) commonest way of transmitting influenza virus Large particle respiratory droplets travel only short distances (usually 1 m or less) through the air; droplets do not remain suspended in the air Requires close contact (usually 1m or less) between source (sick person) and recipient (well person).

17 Other modes of transmission Self-contamination through hand-to-nose, hand-to-eye, hand-to-mouth transmission Direct contact Indirect contact Small particle transmission at several metres (aerosol)

18 Antigenic drift Minor antigenic changes Explains seasonal influenza epidemics and the need for a new vaccine annually. Eg: H3N2 Hong Kong, H3N2 Fujian, H3N2 Wisconsin

19 Seasonal influenza Responsible for high morbidity and mortality annually, particularly at extremes of age

20 Antigenic shift Emergence of a new HA antigen in human influenza (eg H5 or H7) Occurs when a cell is infected by 2 different influenza viruses (animal and human) and their genome segments are exchanged during replication. Causes pandemics (global epidemic) because of lack of immunity to the new HA in the population 2009 pandemic not due to a new H (shift), but severe antigenic drift.

21 Wild birds with avian flu People or pigs with flu New pandemic strain Genetic mixing Domestic birds get avian flu

22 Past pandemics Documented since 1889 Occur in year cycles Historical anecdotes as far back as 1100 s Spanish flu (probably H1N1): million deaths, more than WW1, young adults worst affected 1957 Asian flu 1 million deaths Hong Kong flu 1 million deaths 2009 Swine flu H1N109

23 1918 Pandemic

24 1918 pandemic Caused more deaths than WW1 ( million, or 6% of the world s population) Trench warfare and WW1 a factor in spread High mortality in young adults Medical care far less advanced than current times (antibiotics, vaccines, intensive care)

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26 Morbidity and mortality Direct viral effects (early) Bacterial superinfection Cytokine storm (healthy young adults) Abrahams A, Hallows N, French H. A further investigation into influenza pneumococcal and influenza-streptococcal septicaemia: epidemic influenzal pneumonia of highly fatal type and its relation to purulent bronchitis. Lancet 1919; 1: 1 11.

27 Predicted impact of a pandemic Rapid entry in any country following overseas emergence 20-30% attack rate U or W shaped mortality curve High rates of work absenteeism Hospitals over capacity Two waves possible Transient but sharp economic impact

28 Recent pandemics H1N1 09 swine influenza Highly pathogenic H5NI avian influenza ( bird flu ) Highly pathogenic to birds First human cases in 1997 in Hong Kong and again in Major culling of poultry was carried out, but widespread re emergence in 2003

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30 Wild birds with avian flu People or pigs with flu High probability of Genetic mixing New pandemic strain Domestic birds get avian flu

31 Indicators Indicators Estimates from past pandemics Attack rate 15 35% (of the general population) Secondary bacterial pneumonia Health-care seeking - outpatients Hospitalization rate - inpatients 2.5 5% (of those ill) 30 50% (of those ill) 1 2% (of those ill) Case-fatality rate 1 2% (of those ill) Estimates for crowded, low-resource settings Up to 50 60% 5 10% 30 50% Up to 10% 4% or more

32 Public health management of pandemic Early surveillance and detection Communication with public and HCWs Pharmaceutical Vaccines Antivirals Antibiotics and supportive care Non-pharmaceutical Social distancing Travel restrictions Border control, screening, quarantine Infection control measures

33 Challenges of vaccines Grown in embryonated hens eggs Slow, rate limited process 2 doses, 4x antigen content (unadjuvanted) H5N1 pathogenic to the eggs vaccine yield low Matched vaccine delay ~ 3-6 months to availability of vaccine Limited impact on a pandemic due to delay Supply may be limited even in countries with guaranteed manufacturing capacity

34 Advances in vaccines Novel adjuvants reduce the required antigen content (<4mcg) New vaccine manufacturing methods being developed (cell culture based, DNA vaccines etc) Other vaccines? Pneumococcal?

35 Prepandemic vaccines Not matched, but may provide some protection Choice of antigen (eg H5 or H7) driven by probabilities, but no guarantees Choice of strategies Piggy-back on adult program for population (add H5 antigen to seasonal vaccine) increased reactogenicity; feasibilty First line responders priming Reactive vaccination at OS phase 3/4

36 Antivirals H5N1 resistant to adamantanes Sensitive to neuraminidase inhibitors (NI) (oseltamivir and zanamivir) High rates of primary NI resistance in seasonal flu H1N1 Low resistance to swine flu Can be used as treatment or prophylaxis Modelling shows good impact if drug sensitive

37 When to use antivirals Early phase stamp out crucial first line defence before vaccine available Focus on cases, contact tracing, prophylaxis Mid phase contain Focus on protection of front line responders (health care workers)

38 Influenza A outbreak in a nursing home ARC Linkage grant: Booy, MacIntyre, Dwyer, Lindley

39 Influenza A outbreak; prophylaxis ARC Linkage grant: Booy, MacIntyre, Dwyer, Lindley

40 Influenza A outbreak, treatment ARC Linkage grant: Booy, MacIntyre, Dwyer, Lindley

41 Antibiotics and supportive care Antibiotics for treatment of secondary complications (bacterial pneumonia) Critical care (Ventilation, ECMO, ICU beds, HD, stepdown beds) Hospital capacity = limiting factor Alternative clinics, home care

42 Social distancing Closure of schools modelling shows impact, mainly on transmission among children - only if done very early in the pandemic. Minimal impact if delayed.* Banning of mass gatherings Working from home arrangements Economic implications of these measures need to be considered *Glass K, Barnes B. Epidemiology Sep;18(5):623-8.

43 Travel restrictions >8.5 million arrivals and departures a year in 2003 (most short term travellers) Exponential rise in travel in the past decade International travel - limited impact, prolonged restrictions unfeasible Domestic travel - Limited impact, may benefit small towns Thermoscreening no impact Quarantine some role in stamp out phase

44 Infection control Hand washing RCT evidence of efficacy, a simple procedure available to entire population Cohorting, isolation Cough etiquette Face masks Other PPE

45 Limitations No single intervention is adequate - must be used together Different interventions for different phases All estimates of efficacy of vaccines, antivirals, social distancing and travel restrictions are based on mathematical modelling Models show effectiveness where Ro is 1.7 or less If Ro >3, few interventions will have an impact

46 Risk factors for developing countries Crowding Lack of sanitation Lack of access to health services, vaccines, antivirals Malnutrition HIV co-infection Other co-morbidities

47 Special issues for developing countries Surveillance key Non-pharmaceutical measures more likely to be available Social distancing challenging Lack of running water (alcohol gel) Face masks - supply Vaccination- 1 dose vs 2; prioritisation Antivirals prophylaxis vs treatment Antibiotics Diagnostics - access

48 Stockpiling of food, supplies, fuel etc Surge capacity Restrict movement of people between camps Decentralising food and water distribution Multi-agency co-operation and planning Communication (cultural and language issues) when NGOs intervene

49 Role of humanitarian agencies Reduce human exposure to pandemic virus Strengthen the early warning system Intensify rapid containment operations Build capacity to cope with a pandemic Coordinate global science and accelerate vaccine development and expansion of production capacity

50 SARS SARS Corona virus - positive-strand, enveloped RNA virus Belongs to a group of viruses that cause enteric or respiratory tract infections in humans and other animals.

51 Clinical features Fever Flu like symptoms Shortness of breath Gastrointestinal symptoms CXR infiltrates

52 Epidemiology A nosocomial infection HCWs at greatest risk No/little asymptomatic transmission Peak virus shedding when symptoms maximal Respiratory and gastrointestinal viral shedding Infection control key to disease control

53 8,096 documented cases and 774 deaths November June 2003 CFR 9.6% Identified in early 2003, and spread from the Guangdong province, China to 37 countries. Most cases in China, Hong Kong, Taiwan, Singapore, Canada, Vietnam. Travel a major vector for spread Health workers and WHO staff investigating the outbreak died of SARS

54 Outbreaks Hotel Metropole, Hong Kong Amoy Gardens Hong Kong Mortality <1% - <24 years 6% - 25 to 44 5% - 45 to 64 50% - > 65

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56 Diagnosis and treatment Clinical case definition during outbreak ELISA Supportive treatment Ventilation

57 Prevention Case isolation Contact tracing Handwashing Masks Cohorting

58 Lessons from SARS Early disclosure and action Role of travel and quarantine Role of hospitals in spread of epidemic Impact on health workers as frontline responders (Hanoi) Socioeconomic impact

59 Preparedness planning Is multisectoral and multidisciplinary Law and order Critical infrastructure Health systems approach Whole of government approach Public private partnerships (eg vaccine manufacturers and government)

60 Health aspects of preparedness planning Pharmaceutical interventions Non-pharmaceutical measures Social distancing measures Quarantine, border control Public health legislation

61 Operational considerations Tiered protection - first line responders (military, health workers) Stockpiling of drugs, vaccines and non-pharmaceuticals Shelf-life Rotation of stock Cost-effectiveness considerations Risk assessment vs investment cost Whole of government approach Multi-disciplinary, multi-sectoral Public-private partnerships

62 Summary Emerging infections are a diverse and dynamic threat Travel and globalisation ensure rapid transmission of new infections around the world Developing countries at risk because of crowded conditions, lack of sanitation. Difficult access to antivirals, vaccines, face masks, PPE Multi-sectoral, multi-disciplinary approaches needed

63 Thank you