1. Comparison of guidance for public health management of Hib, pneumococcal and meningococcal disease Dr Mary Slack HPA Centre for Infections London MRF20 Bristol Meningitis Training Seminar June 2009

2. The New Guidelines for Hib Haemophilus influenzae type b (Hib) was the leading cause of meningitis and other serious infections in young children before the introduction of routine Hib immunisation in 1992

3. Hib clinical syndromes CDC: Haemophilus influenzae type b http://www.cdc.gov/nip/publications/pink/hib.pdf *Prevaccination Era Disease of children under 5 years Highest incidence in children < 2 y

4. Invasive Hib infections by age group, 1990-2004 Source: England and Wales, HPA CfI 3 12

5. Case Definition for Hib Confirmed case Clinical infection AND isolation of Hib from a normally sterile site Probable case (if serotyping takes too long / unavailable) Isolation of untyped Haemophilus influenzae from a normally sterile site from (i) any child <10 years with infection, OR (ii) a patient of any age with a clinical diagnosis of epiglottitis

6. Household Contacts Age of secondary case Attack rate % (95% CI) Any invasive HibHib meningitis <2 years 1.8 (0.04-9.4) 3.8 (1.4-8.0) <4 or <5 years 2.0 (0.5-5.0) 2.1 (1.1-3.5) >4 years 0.0 (0-0.8) 0.02 (0.001-0.13) Secondary cases within 60 days of index case hospitalisation

7. Household and pre-school contacts Household contacts of a case of invasive Hib disease are at increased risk of developing secondary Hib infection- –especially if they are young children or immunosuppressed Pre-school contacts are at increased risk –but this appears to be lower than the risk for household contacts

8. Risk of a second episode of invasive Hib disease Uncommon but recognised, usually within 6 months Even if index case receives antibiotic prophylaxis Re-infection +/- Relapse Relapse: usually related to inappropriate or inadequate antibiotic therapy of initial infection Re-infection occurs weeks/months after infection

9. Vulnerable Individuals (i) Any child <10 years, irrespective of vaccination status (ii) Immunosuppressed or asplenic person (any age) ** Vulnerable individual may be the index case **

10. Chemoprophylaxis for Hib RIFAMPICIN: 20 mg/kg (max. 600 mg) once a day for 4 days for adults and children >3 months (lower dose if <3 months) Pregnant women should also receive chemoprophylaxis because benefits outweigh risks ALTERNATIVE: Once daily IV or IM ceftriaxone x 2 days ? Ciprofloxacin – may work but limited evidence

11. RECOMMENDATIONS for Hib Index Case - Public Health intervention required for confirmed and probable cases only

12. INDEX CASE Rifampicin Prophylaxis After Infection (i) All index cases <10 years of age with confirmed or probable Hib (to eradicate CARRIAGE) (ii) Index cases of any age with confirmed or probable invasive Hib disease if there is a vulnerable individual in the household

13. INDEX CASE Hib Vaccination After Infection Unvaccinated + partially vaccinated children <10 years should complete primary immunisation Children aged 4-10 months who have received 3 doses in infancy: one dose of vaccine after infection + scheduled booster dose at 12 months

14. INDEX CASE Vaccine Failure Cases (RARE!) FULLY VACCINATED (4 doses) cases <10 YEARS: measure Hib antibody levels ~4 weeks after infection & vaccinate if levels <1  g/ml If unable to measure antibodies or concerns that child may be lost to follow-up, then VACCINATE before discharge Consider immune function tests (e.g. Ig levels)

15. RECOMMENDATIONS Household Contacts Close contact with index case in the 7 days prior to the index case developing Hib Antibiotic Prophylaxis – INDICATION? If there is a Vulnerable person (<10y or immuno- suppressed) in the household  this may be the index case

16. HOUSEHOLD CONTACTS Antibiotic Prophylaxis – WHEN TO GIVE? Rapid serotyping available (up to 48 hrs after diagnosis): give prophylaxis as soon as Hib confirmed Delay in serotyping (>48hr): give prophylaxis if index case considered to be a probable case of Hib. If Hib identified in index case up to 4 weeks after infection, give prophylaxis to household contacts

17. HOUSEHOLD CONTACTS VACCINATING HOUSEHOLD CONTACTS Unimmunised / partially immunised children <10 years should receive recommended UK vaccination course Children <10 year with primary Hib immunisation only (2,3,4 months and no booster at 12 months)  extra dose of vaccine

18. RECOMMENDATIONS Pre-School = Playgroup, nursery, day care, crèche, primary school. Each situation assessed separately to identify those at increased risk of invasive Hib disease E.g. staff & children in same room

19. PRE-SCHOOL CONTACTS Single episode in a child <10 years: – Advise families of children attending the same group to seek medical advice if their child becomes unwell Outbreak (>1 case within 120 days): – Chemoprophylaxis to all room contacts, including staff –Unimmunised / partially immunised children <10 years should receive the recommended vaccination courses –Children <10 years only immunised in infancy (2, 3 + 4 mo) should receive an extra dose of Hib vaccine

20. Pneumococcal guidelines for CLUSTERS of pneumococcal infection

22. Pneumococci Over 90 serotypes of pneumococci Plain polysaccharide vaccine (PPV) contains polysaccharide from 23 serotypes Conjugated pneumococcal vaccine (PCV) contains 7 serotypes

23. Invasive pneumococcal disease (IPD) incidence rate per 100,000 population by age grouping England and Wales, 1996-2005

24. Definitions Confirmed case: Clinical infection/pneumonia AND Pneumococcus isolated from a normally sterile site Pneumococcal DNA or antigen from a normally sterile site (except blood from children < 2 years) Pneumococcal antigen detected in urine (except blood from children < 2 years) Probable Case: Clinical infection/pneumonia AND Doctor considers infection to be IPD (eg. lobar pneumonia or empyema)

25. SECONDARY CASES Limited data (26 clusters in literature) Median outbreak: 4 cases (range 2-46) 81% of cases within 14 days of index case Most common serotypes: 14 (n=7), 4 (n=5), 9 (n=4), 1 (n=4) and 9V (n-4) Median attack rate: 8.9% (0.18%-66%) No secondary cases reported in health-care staff

26. GUIDELINES Guidelines are for clusters (not single cases): ≥2 confirmed cases (with same serotype) suspected cluster: ≥2 probable, or 1 confirmed & ≥1 probable  aim to confirm as soon as possible Invasive pneumococcal disease Not otitis media or conjunctivitis Closed setting hospitals, long-term care facilities, prisons, military settings, child day-care centres Within 14 day period (may be extended in some cases)

27. Infection Control Measures Isolation Cohorting Hand and Respiratory Hygiene Respiratory protection Face masks not usually required, except for activities that release aerosols (chest physiotherapy, etc.)

28. Antibiotics for Close Contacts Index cases do not need antibiotic prophylaxis Pregnant women should get prophylaxis Antibiotics given as soon as cluster is confirmed Ideally within 24 hours Choice of Antibiotic: 1 st Line: Amoxycillin (twice daily for 7 days) 2 nd Line: Azithromycin (once daily for 3 days) Note: breakthrough cases Alternative: Rifampicin (once daily for 4 days)

29. Vaccinating close contacts In a cluster setting, protection from vaccination takes at least 10-14 days  antibiotic prophylaxis mandatory

30. 23-valent plain polysaccharide vaccine (PPV) 23-PPV: currently recommended for children at increased risk of IPD and the elderly Close contacts aged ≥2 years old should be offered a single dose of 23-PPV if -They fulfil current national recommendations -Their last 23-PPV dose was ≥2 years ago -Cluster due to a serotype in 23-PPV, or -Serotype causing the cluster not known Offered as soon as serotype confirmed & up to 14 days after onset of infection in last case in cluster 23-PPV should NOT be given to <2 year olds

31. 7-valent Pneumococcal conjugate vaccine (PCV7) PCV-7: currently part of UK national immunisation programme & given at 2, 4 and13 months In a cluster setting, PCV-7 can be offered to: -Unimmunised or partially immunised children in the vaccine-eligible group -All close contacts if cluster serotype in PCV-7 Offered as soon as serotype confirmed & up to 14 days after date of onset of last case in the cluster

32. Meningococcal guidelines

33. Case Definition Confirmed case Clinical diagnosis of meningitis, septicaemia or other invasive disease AND at least ONE of: isolation of meningococci from a normally sterile site Gram-ve diplococci in normally sterile site Meningococcal DNA in normally sterile site Meningococcal antigen in CSF, blood or urine Probable case Clinical diagnosis of meningitis, septicaemia or other invasive disease where meningococcal infection most likely diagnosis

34. Close Household contacts Increased risk for close household contacts Risk highest in first 7 days after index case Falls rapidly over next 3 weeks If prophylaxis NOT given absolute risk of a household contact developing meningococcal disease is 1 in 300

35. Contacts outside household Risk of linked cases is low After 1 case in a school setting the absolute risk of a second case in that institution within 4 weeks is: Pre-school : 1 in 1,500 Primary school: 1 in 18,000 Secondary school: 1 in 33,000

36. Chemoprophylaxis RIFAMPICIN: 600mg bd for 2 days infants <12m 5mg/kg Children 1-12y 10mg/kg CIPROFLOXACIN : 500mg single dose children 2-4 y 125mg children 5-12 y 250mg CEFTRIAXONE: 250mg single dose im In pregnancy and breastfeeding can use rifampicin or ceftriaxone (avoid ciprofloxacin)

37. Chemoprophylaxis indicated Close prolonged contacts of a case, irrespective of vaccination status; In household type setting during 7 days BEFORE onset of illness Transient close contact with case if DIRECTLY exposed to large droplets/secretions from respiratory tract of case around time of admission Give as soon as possible ( within 24 h) after diagnosis of index case

38. Chemoprophylaxis for Index case Indicated unless patient has been treated with ceftriaxone IF treated with cefotaxime should be given prophylaxis because insufficient evidence that cefotaxime eliminates carriage

39. Chemoprophylaxis NOT indicated Staff and children attending same school/nursery/college Friends Residents of nursing home Kissing on cheek or mouth Travelling in same vehicle Sharing food or drink

40. Vaccination Close contacts of cases due to vaccine preventable meningococcal infection should be offered vaccine Men C: offer to all unvaccinated close contacts if contacts are partially immunised complete course if Men C given >1 y before offer booster dose Men A: quadrivalent polysaccharide vaccine (if >3m) W135 and Y: quadrivalent polysaccharide vaccine (if >2y) Also offer Men C vaccine to index case before discharge from hospital

41. Infection Control Measures After starting treatment with benzyl penicillin or ceftriaxone carriage rates decrease rapidly and meningococci undetectable in nasopharyngeal swabs after 24 hours treatment Recommend face masks and eye protection where risk of secretions splashing into face and eyes Use closed suction when carrying out airway procedures to minimise exposure to large particle droplets

42. Chemoprophylaxis for Health Care Workers Chemoprophylaxis ONLY for those whose mouth or nose directly exposed to large particle droplets/secretions from respiratory tract of confirmed/probable case before patient has received 24 hours of systemic antibiotics Rifampicin 600mg bd for 2 days OR Ciprofloxacin 500mg one dose Exposure of eyes to respiratory droplets is NOT an indication for prophylaxis BUT there is a low risk of meningococcal conjunctivitis Seek early treatment for conjunctivitis within 10 days of exposure

43. Management of Clusters In educational setting after a second case the risk of a third case is 30- 50% If 2 cases due to different strains = sporadic cases offer prophylaxis to close contacts of each case If 2 cases due to same strain = cluster Inform parents and students Prophylaxis –Pre-school usually both staff and children –Schools/colleges: if clear subgroup defined offer prophylaxis to them alone –If not may have to offer prophylaxis to whole institution Use rifampicin or ciprofloxacin +/- vaccine

44. Conclusions Public Health management of invasive Hib disease: Probable case = infection more likely to be due to Hib Rifampicin remains antibiotic prophylaxis of choice Vulnerable group = immunosuppressed or child <10 yrs Fully Immunised = four doses of Hib vaccine Public Health management of IPD: Only relevant for clusters (at least 2 confirmed cases) Amoxycillin is the antibiotic prophylaxis of choice Vaccination should be offered but is of limited use

45. Conclusions Public Health management of meningococcal disease Probable case = infection more likely to be meningococcal Rifampicin, ciprofloxacin or ceftriaxone may be used Vaccination should be offered if appropriate

46. HPA Guidelines Recommendations for the prevention of secondary Haemophilus influenzae type b (Hib) disease –Ladhani et al. Journal of Infection, 2009; 58: 3-14 Interim UK guidelines for the public health management of clusters of serious pneumococcal disease in closed settings –http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1226652138810 Guidance for public health management of meningococcal disease in the UK –http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1194947389261