Role of surveillance in the implementation and sustainability of conjugate Hib vaccination

1
Role of surveillance in the implementation and
sustainability of conjugate Hib vaccination

• Brendan Flannery
• Respiratory Diseases Branch,
• U.S. Centers for Disease Control and Prevention
• netSPEAR Foundation Meeting
• 17 November 2003

2
What does not belong?
3
Hib Disease

• 3 million cases and 350,000-700,000 deaths/year
• Hib meningitis
• Leading cause of bacterial meningitisinfants and
  children lt2 years
• High case fatality rate 5-30
• 35 of survivors have long-term sequelae
• Hib pneumonia
• 4-10 times as common as Hib meningitis
• Important cause of mortality in infants

4
Why conduct surveillance?
"It seems like we have been seeing a lot of
Haemophilus influenzae lately"
5
Population-based surveillance for Hib meningitis
in children lt 5, U.S.1959-1970
Source WHO, literature review, 2002
6
National Bacterial Meningitis Surveillance, 27
states, U.S.1978-1981

• Haemophilus influenzae most frequent cause of
  bacterial meningitis (48 of all cases)
• Peak incidence among infants 3-11 months old
• Case-fatality 6 of H. influenzae cases
• Under-reporting resulted in lower estimates of
  incidence than active surveillance

Source Schlech WF, JAMA 1985
7
Vaccine Trials of Hib Conjugate Vaccines1987-1997
8
Decline of Hib meningitis following introduction
of Hib conjugate vaccines, children lt5 yrs,
U.S.1980-1991
18 mo
2 mo
Source Adams WG, JAMA 1993
9
Hib meningitis declined in infants prior to
vaccine licensure for this age group
2 mo
18 mo
Source Adams WG, JAMA 1993
10
How surveillance helped demonstrate vaccine
effect through herd immunity

• Vaccination of older children prevented disease
  in infants
• Vaccination decreased carriage of Hib and
  interrupted transmission
• Herd immunity benefit of having some
  individuals vaccinated on reducing disease in
  unvaccinated
• Hib disease declined 98 with 70-80 coverage

11
Incidence of Hib meningitis in children lt 5,
worldwide
Source WHO, literature review, 2002
12
Incidence of Hib meningitis in children lt 5 years
of age by WHO region
13
Number of studies of Hib meningitis in the
pre-vaccine era, by WHO region
Source WHO, literature review, 2002
14
Number of studies of Hib meningitis by type of
surveillance and WHO region
Source WHO, literature review, 2002
15
Hib from hospital-based studies Children lt5
years, netSPEAR countries
Source WHO, literature review, 2002
16
Contributions of hospital-based studies of causes
of bacterial meningitis

• In countries with greater burden of Hib, higher
  proportion of all cases occur in children lt1 year
• African region has the highest case-fatality rate
  of Hib meningitis (27)
• African region has the highest annual mortality
  rate from Hib meningitis

17
Pre- and post-vaccination surveillance to
demonstrate impact on Hib meningitis
18
Hib meningitis in The Gambia after vaccine
introduction, children lt1 yr
Hib vaccine trial
No vaccine
Routine vaccination
Source Adegbola RA, Lancet, 1999
19
Percent of Hib culture-positive CSFSoweto, South
Africa--1996-2001
Vaccine trial
Routine vaccination
Source Martin M, Respiratory Diseases Branch, CDC
20
Number of culture-confirmed Hib cases2 Hospitals
in Argentina--1996-2000
Hospital A
Hospital B
Hib vaccination
Source Martin M, Respiratory Diseases Branch, CDC
21
Population-based surveillance for H. influenzae
meningitis, Brazil1996-2000Evidence for
serotype replacement?
n78
n8
n3
n0.6
Source Ribeiro GS, Journal of Infectious
Diseases, 2003
22
Hib and nontype b H. influenzae diseaseChildren
lt 5 Years, US1990-2000
Source CDC
23
Obstacles to introducing Hib conjugate vaccine in
developing countries

• High cost of vaccines
• Global Alliance for Vaccines and Immunizations
  (GAVI) has changed the field
• Resources required to deliver vaccine and
  guarantee future supply
• Under-recognition of disease burden
• Importance of Hib as cause of severe pneumonia
• Focus of the Respiratory Diseases Branch at CDC

24
High
Vaccine trials
Complexity, Cost, Rigor, Time
Population-based lab surveillance
Sentinel lab surveillance
Rapid assessment
Low
25
Incidence of Hib meningitis in children lt 5
Rapid assessment vs Pop-based lab surveillance
Rapid Assessment Tool Prospective Surveillance
Source WHO, literature review, 2002
26
Global status of countries using Hib vaccine 2003
Albania Bhutan Burundi Gambia Ghana Guyana Kenya
Malawi Rwanda Senegal Uganda Yemen Zambia Zimbabwe
Routine Hib implementation status
GAVI- approved
Yes
No
27
Ocean of respiratory tract infections
Acute Respiratory Illness
Invasive
Hib
Pneumococcus
Pneumonia
28
How big is a hippopotamus?
Source San Diego Zoo
29
Decline In Invasive Pneumococcal Disease in US
Children, 1998-2001
1 yr
2001 vs baseline
lt1 yr
- 69
- 68
2 yrs
3 yrs
4 yrs
No change
Source Whitney, NEJM 2003
30
Incidence of Invasive Pneumococcal Disease by Age
Group, USA--1998
31
Incidence of Invasive Pneumococcal Disease by Age
Group1998 vs 2002
1998
2002
32

• "Until recently, bacterial meningitis was a
  greatly feared infectious disease because it
  struck and killed rapidly, many of its victims
  were children, and as many as 25 percent of
  survivors had sequelae such as permanent brain
  damage, mental retardation, or hearing loss."
• --Anne Schuchat, Bacterial Meningitis in the
  United States in 1995, NEJM, 1997

33
Additional slides
34
Active Bacterial Core Surveillance (ABCs) for
invasive bacterial infections
Twin cities, MN 2.6 m
Portland,OR 1.4 m
Rochester,NY 1.1 m
Connecticut 3.4 m
San Francisco CA 0.8 m
Baltimore,MD 2.5 m
Atlanta,GA 4.1 m
Total surveillance population in 2002 16.0
million
35
ABCs Methods

• Case Haemophilus influenzae isolated from a
  normally sterile site
• Active contact with clinical laboratories to
  identify cases
• Audits to ensure complete reporting
• Chart review for clinical information
• Typing at reference laboratories