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Pertussis in the UK: The more you look the more you find

Pertussis in the UK: The more you look the more you find. Dr Natasha S. Crowcroft Health Protection Agency and the Ontario Ministry of Health and Long Term Care, Central Public Health Laboratory. Outline.

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Pertussis in the UK: The more you look the more you find

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  1. Pertussis in the UK: The more you look the more you find Dr Natasha S. Crowcroft Health Protection Agency and the Ontario Ministry of Health and Long Term Care, Central Public Health Laboratory

  2. Outline • Many countries (Canada The Netherlands, France, Germany, USA) report increases in pertussis • Fewer doses of pertussis vaccine are given in UK • Why? • How is evidence used to make policy? • Any relevance for Ontario?

  3. Routine surveillance data Notifications Laboratory reports Hospitalisation data Death certificates Serosurveillance Vaccine coverage Adverse events Mathematical and economic modelling Special studies Clinical studies in infants and adults What’s the evidence base?

  4. Pertussis burden is hard to measure Crowcroft NS et al, Lancet Infect Dis. 2003 Jul;3(7):413-8

  5. Uncertainty is seen in the sensitivity analysis • Varied: • proportion of children infected by each age • vaccine efficacy against infection or death • case fatality ratio • Cases 24-54 million • Deaths 7-755 thousand

  6. Whooping cough cases and vaccine coverageEngland and Wales 1940-2001 Immunisation introduced

  7. Under-notification • Estimates in epidemic periods: ~ 1 in 10 cases are notified • Ratio of hospitalisations to notifications to laboratory reports in infants <3 months • 2-3 hospital admissions for every notification • 3 notifications for every laboratory report • Ratio of hospitalisations to notifications is reversed in older ages • Van Buynder et al Epidemiol Infect 1999

  8. Paediatricians worried…. • Ranganathan S, Tasker R, Booy R, Habibi P, Nadel S, Britto J. Pertussis is increasing in unimmunized infants: is a change in policy needed? Arch Dis Child. 1999 Mar;80(3):297-9

  9. Paediatric intensive care study 1998-2000 • Infants under 5 months of age admitted to PICU with: • Respiratory failure • Apnoea and/or bradycardia • Acute life threatening episode • Excluded: • Persistent pulmonary hypertension of the new-born, meconium aspiration, hyaline membrane disease

  10. Burden of pertussis • 17% (24/143) had laboratory-confirmed pertussis • 23% (33/142) had pertussis including epidemiologically-linked cases • 4% (6/142) were culture positive • Pertussis was clinically suspected on admission in 28% infants

  11. Culture, PCR, serology • All culture positive cases were PCR positive • Of 12 PCR positive, 7 were negative by serology • Of 8 serology positive 3 were negative by PCR • Methods of diagnosis are complementary

  12. Other features • Length of stay on PICU mean 5.7 days • Stay in hospital mean 15.6 days • Two deaths • 11 had co-infection with RSV

  13. Infants with pertussis compared to those without pertussis • Not more likely to cough • More apnoeas (p=0.03) • More likely to whoop (p<0.005) • Longer duration of cough • 15 versus 11 days p=0.003 • Higher lymphocyte count (p=0.003)

  14. Pertussis vaccination • Most cases unvaccinated or partially vaccinated because of their age • 91% (30/33) adult contacts of cases vaccinated • 97% (29/30) child contacts of cases vaccinated • Same as contacts of non-cases

  15. Source of infection: Who was the first case in the family?

  16. Pertussis in the community • Study in one general practice in UK, 1996-7 investigated (culture/serology) all presentations of whooping cough or acute tracheitis in >4y • Pertussis found in all age groups • Highest in 5-14y (45%) and 15-44y (28%) • Observed incidence 330/100 000 • Notifications <4/100 000 in the same period Miller et al Commun Dis Public Health 2000;3:132-4

  17. Overlap Between Deaths in Enhanced pertussis Surveillance System (ES), ONS Mortality Database (ONS), and Hospital Episode Statistics (HES) 1994-9 • Total 33 deaths observed • ONS = 18 • ES = 22 • HES = 9 • Estimate true number is 46 (95% CI 37-71) or ~ 9 per yr • Official statistics detected 18/33 (54%) observed or 18/46 (39%) estimated deaths Crowcroft et al Arch Dis Child 2002;86:336-8

  18. Outcome of analysis in 2001 • Morbidity from pertussis under-recognised • PCR and serology increase ascertainment • Adults and children introduce pertussis into families, even fully vaccinated families • Health economic analysis of options • Outcome: • PCR and serology diagnostics provided by Public Health Laboratory • Pre-school booster in 2001 Crowcroft et al Arch Dis Child. 2003 Sep;88(9):802-6

  19. Summary of changes to the pertussis vaccination programme in the UK

  20. Current vaccination schedules UK and Canada

  21. Questions for the UK in 2007 • What was the impact of the pre-school booster introduced in 2001? • Are boosters needed for older children and adults? • What is the aim of the vaccination programme?

  22. Accelerated schedule Pre-school booster Notifications, deaths and vaccine coverage by 2nd birthday **provisional

  23. Accelerated schedule Pre-school booster Notification rate per 100,000 population (England and Wales)

  24. Pre school booster Pertussis hospital admission rates by age, 1998-2006

  25. Pre school booster Introduction of testing by serology and PCR Total laboratory confirmed cases by age group and year – all methods

  26. Incidence of culture confirmed cases of pertussis in all age groups

  27. Laboratory confirmed cases by serology by age and year

  28. Rates of pertussis in infants <3 months in different systems

  29. Notifications and deaths from pertussis **provisional

  30. Deaths from all sources (not reconciled) *provisional data

  31. Immunisation status of laboratory confirmed cases aged ≥6 months

  32. Detection of B. pertussis:traditional methods Culture: • traditional ‘gold standard’ • poor sensitivity • slow • isolates useful for reference

  33. Pertussis Serotypes

  34. Enhanced methods: PCR • Correct samples:nasopharyngeal aspirates or swabs • Criteria: • Child age =< 1 year admitted to PICU or paediatric ward with respiratory illness compatible with pertussis

  35. Enhanced methods: serology • Correct samples: not less than 400ul of serum • Criteria: Single serum sample taken >2 weeks after onset for any individuals with prolonged cough without a recent history of vaccination

  36. Enhanced methods: Oral fluid assay • Correct sample: oral fluid • Criteria: to be used following notification (when serum specimen is not available) • 80% sensitivity compared to serum assay New

  37. Oral fluid: Pilot study • Aim: to improve evidence base for pertussis vaccination policy decision-making through; • improved case ascertainment, • increased rates of confirmation and • more detailed information on notified cases of pertussis • Two areas: Leicestershire and Thames Valley • Some swabs mailed to patients, some used by family doctor

  38. Oral fluid results May-July 2007

  39. Outcome of pilot study • Oral fluid follow-up of notified pertussis cases improves laboratory confirmation rates • Yields extra information about cases • No excessive burden on the workload of clinicians or public health departments • Oral fluid is more convenient to collect than serum • Since June 2007, available routinely in England

  40. Impact of vaccination on pertussis transmission • When coverage was low in the UK, epidemic cycles continued at 3-4 yearly intervals • The inter-epidemic period has not lengthened greatly • Reducing transmission of pertussis may reduce boosting of immunity and increase disease severity (Aguas et al Lancet Infect Dis 2006)

  41. Pertussis: increasing disease as a result of reducing transmission Aguas et al Lancet Infect Dis 2006

  42. Something to worry about… • Vaccine efficacy in preventing secondary cases in households estimated at 85% (46-95) (Preziosi & Halloran Vaccine 2003) • More severe cases are more infectious • If vaccinating 14-15 year olds then immunity will wane over 10 years • expect infections around 10 years later • 25 years and over • Could future parents be more infectious? • Need robust models for better predictions

  43. Conclusions for UK • The current vaccination schedule seems effective • But pertussis is a challenge, and cannot be eradicated by current vaccines • Different immunisation strategies have direct and indirect (herd immunity) effects • Reducing incidence in one age group can lead to increases in another • Need for good surveillance

  44. Considerations for Ontario • How well is pertussis controlled in Ontario? • Current surveillance in Ontario relies on clinical reports, culture and PCR diagnosed cases – what about other diagnostic methods? • Serology • Oral fluid • Are other surveillance and disease burden studies needed? • eg data linkage, deaths, modelling

  45. Acknowledgments • Thanks to Helen Campbell, Norman Fry, Tim Harrison, Elizabeth Miller, Robert George, Nalini Rawal, Karen Wagner, Joanne White, Tony Nardone, Andrew Vyse • And to Jean-François Aguilera, Katy Davison, John Edmunds, Nigel Gay, Scott Halperin, Herb Hethcote, Mark LaForce, Richard Pebody, Angie Rose, Gaston de Serres, Francois Simondon

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