1. The Influence of Inaccurate Vaccine Brand Identification On the Analysis of Hib Vaccination Coverage Rates From Immunization Information System Data
Karen E. White, MPH
Epidemiologist/Business Analyst
Minnesota Department of Health
Presented by:
Kris Ehresmann, MPH, RN
Division Director, Infectious Disease
Epidemiology, Prevention and Control
April 21, 2010

2. Resurgence of rare disease leads to warning: Vaccinate
Hib infection in children makes a deadly return
In January 2009, the Minnesota Department of Health noted an increase in cases of invasive Haemophilus Influenzae type b, or Hib, in children.
These are some headlines from the Minnesota Star-Tribune, USA-Today, and the Washington Post, describing an unusual increase, and urging parents to vaccinate their children.
At this time, staff in Minnesota and at CDC wondered if “Minnesota was like a canary in a coal-mine”, was an indicator of what might occur throughout the U.S.
During this seminar, I will tell you more about the public health response to possible outbreak.
Infections May Indicate Deadly Bug's Comeback
January 2009

3. Haemophilus influenzae
Gram-negative rod
Encapsulated strains express antigenically distinct capsular polysaccharides
Serotypes a-f
Encapsulated and nonencapsulated cause invasive and non-invasive disease
Type b caused most invasive disease
Haemophilus influenzae is a gram-negative rod.
Encapsulated strains express antigenically distinct capsular polysaccharides, and are referred to as serotypes a through f.
Both encapsulated and non-encapsulated strains can cause invasive and non-invasive disease.
Prior to the availability of the vaccine, type b caused most invasive disease.

4. Haemophilus influenzae type b
Major cause of morbidity and mortality in children < 5 years
> 20,000 cases annually in the United States prior to vaccine introduction
5% case-fatality ratio
Leading cause of bacterial meningitis in countries with no Hib vaccine
In the US, Haemophilus influenzae type b was a major cause of morbidity and mortality in children under five years of age, with over 20,000 cases occurring annually prior to vaccine introduction and a case-fatality ratio of 5%.
It remains a leading cause of bacterial meningitis in countries with no Hib vaccine.

5. Cases of Hib in Children < 72 Months
of Age, Minnesota, 1983–2007
Year of Diagnosis
Number of Cases
Conjugate vaccine licensed for >2 months (1990)
Conjugate vaccine licensed for >15 months (1989)
Polysaccharide vaccine licensed >18 months (1985) 50
100
150
200
250
300
1983
1987
1991
1995
1999
2003
2007
This figure shows the numbers of invasive Hib cases in children <72 months of age reported from 1983 until 2007 in Minnesota.
The first Hib vaccine, a polysaccharide vaccine, was licensed for children greater than 18 months of age in 1985 in the US.
A conjugate vaccine became available for children greater than or equal to 15 months of age in 1989.
Finally, a Hib conjugate vaccine for infants was licensed in 1990, and lead to the near-elimination of this major cause of invasive infections.
After the conjugate vaccine was licensed, cases dropped from hundreds each year to no more than two per year in the past decade.

6. Invasive Hib Cases <5 Years of Age, Minnesota, 1992–2008
This graph shows the number of invasive Hib cases among children less than 5 years of age in Minnesota from 1992 through 2008.
In 2008 the Minnesota Department of Health detected 5 cases of invasive Hib disease, the most since 1992.
MMWR.1/23/09. 58:1-3.

7. Hib Cases, Minnesota, 2008 (n=5)
St. Louis
Fillmore
Dakota
Lyon
Lac Qui Parle
Anoka
All different counties
All in south-central part of state
No known relationship
All of the cases were from different counties but all were found in the south-central part of the state, highlighted in red.
They had no known relationship to each other.

8. Hib-containing Vaccines 2008
Company
Primary Series
Booster Dose
Merck
2 doses
2 and 4 mo
1 booster
12-15 months
Sanofi-Pasteur
3 doses
2, 4, and 6 mo
To give you a better perspective on what complete or incomplete vaccination against Hib means,
this slide summarizes Hib-containing vaccines produced in 2008
Merck and Sanofi-Pasteur were the main vaccine manufacturers.
The Merck product is given as a two dose series at ages 2 and 4 months.
The Sanofi-Pasteur product is given as a three dose primary series at ages 2, 4, and 6 months.
With either type of product, a booster dose was recommended at months of age.

9. Merck PedvaxHib (Hib-OMP) Recall
December 2007
FDA web site “These lots of PedvaxHIB and COMVAX are being recalled due to lack of assurance of product sterility.”
ACIP recommended 4th dose booster be deferred
Manufacture PedvaxHib suspended
Sanofi Pasteur ActHib (Hib-PRP-TT) was still available
Pentacel (DTaP/Polio/Hib) became available late 2008
CDC maintained stores of non-recalled lots of PedvaxHib for high-risk groups (AI/AN) where Hib-OMP is the vaccine of choice with higher antigenicity

10. All Hib Vaccination Brands Given During 2008 by Market Share, Minnesota Sentinel Site, N=7,664
60.0
PedvaxHib
50.0
Comvax
40.0
ActHib
Percent
30.0
Pentacel
20.0
10.0
NOS
0.0
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Month

11. MN Children Under-Vaccinated?
Initial estimates of Hib coverage rates
Cohort examined contained children who would be vaccinated after recall 11/01/2007-3/31/2008
Compared to other vaccines received at 2, 4 and 6 months of age: DTaP and PCV7
Rates appeared up to 10% lower at 12 months of age than other vaccines given on the same schedule

12. Happening in other states?
Sentinel Site Area
Cohort 11/2007-3/2008
Hib
DTaP
PCV7
% Difference N
UTD %
p-value
Arizona
4,642
56.4
55.7 NS
54.0
+1.6
Colorado
843
52.6
62.3
<0.01
60.0
-8.6
Michigan
34,405
64.0
72.9
70.6
-7.8
Minnesota
7,664
53.4
62.6
62.0
-8.9
NY City
58,919
44.4
56.3
50.7
-9.1
N. Dakota
3,778
61.8
72.4
71.4
-10.1
Oregon
7,216
56.9
67.6
65.2
-9.5
Wisconsin
6,094
66.6
78.1
75.7
-10.3

13. Problems with the data…
Reporting of discontinued brands
Hib-PRP-D
Hib-HbOC
Merck lot numbers on Sanofi vaccinations
9999A
Sanofi lot numbers on Merck vaccinations
AA999AA
Non-brand-specific vaccination data
Historical shots
Incomplete data submitted for administered shots

14. Data cleanup included Recoding based on lot number
Calling provider organizations to see what they really gave instead of discontinued brands – always turned out to be ActHib
Estimation of unknown brands
Proportion Merck vs Sanofi distributed through Vaccines for Children program

15. Minnesota – Sentinel Site Data, n=7664 UTD Hib vaccine at 9 months, 07-08 cohort
UTD with 2 doses of Merck or 3 doses of other brands
Hib vaccine doses*
9 months
2 Merck doses1
337
3 Sanofi doses2
1471
1 Merck + 1 Sanofi or 1 NOS + 1 Merck (in that order) 40
1 Merck only + 2 Sanofi
283
1 Merck only + 2 Hib NOS3
223
1 Merck only + 1 Sanofi only + 1 Hib NOS 70
1 Sanofi only + 2 Hib NOS
293
2 Sanofi only + 1 Hib NOS
299
3 Hib NOS
1013
Total
4029 (53%)
Not UTD with only 2 Hib vaccine doses
Hib vaccine doses
9 months
2 Sanofi doses only
560
1 Merck only + 1 Sanofi only
111
1 Merck only + 1 NOS only
246
1 Sanofi only + 1 NOS only
241
2 NOS only
459
Total
1617
Vaccines for
Children 2008
Merck %
Sanofi 90.8%
UTD
+4029
4094/7664 = 53.4%

16. Minnesota – Sentinel Site Data, n=7664 UTD Hib, PCV and DTaP at 9 months, 07-08 cohort
Vaccine
UTD at 9 months
Hib
4094/7664 (53.4%)
PCV7
4749/7664 (62.0%)
DTaP
4797/7664 (62.6%)
- 8.9%
Hib percent is 8.9% lower than the average of PCV7 and DTaP

17. Minnesota – Sentinel Site Data, n=7059 UTD Hib vaccine at 9 months, 06-07 cohort
UTD with 2 doses of Merck or 3 doses of other brands
Hib vaccine doses*
9 months
2 Merck doses
3425
3 Sanofi doses2
284
1 Merck + 1 Sanofi or 1 NOS + 1 Merck (in that order) 45
1 Merck only + 2 Sanofi 11
1 Merck only + 2 Hib NOS3 32
1 Merck only + 1 Sanofi only + 1 Hib NOS 6
1 Sanofi only + 2 Hib NOS 17
2 Sanofi only + 1 Hib NOS 7
3 Hib NOS
164
Total
3991 (56.5%)
Not UTD with only 2 Hib vaccine doses
Hib vaccine doses
9 months
2 Sanofi doses only
125
1 Merck only + 1 Sanofi only 52
1 Merck only + 1 NOS only
131
1 Sanofi only + 1 NOS only 24
2 NOS only
972
Total
1304
Vaccines for
Children 2007
Merck 89.9%
Sanofi 10.1%
UTD
+3991
4983/7059 = 70.6%

18. Minnesota – Sentinel Site Data, n=7059 UTD Hib, PCV and DTaP at 9 months, 06-07 cohort
Vaccine
UTD at 9 months
Hib
4983/7059 (70.6%)
PCV7
4648/7059 (65.8%)
DTaP
4718/7059 (66.8%)
Hib percent is 4.3 percent higher than the average of PCV7 and DTaP
+ 4.3%

19. Why was the rate lower in 2008?
Not enough vaccine available to cover the primary series?
CDC had evidence that there was enough
Confusion regarding schedules in vaccinators?
Force of habit – used to giving 2-dose Merck product

20. Schedule Differences by Brand for the Same Vaccine Type
Rotavirus
Rotarix – 2 doses at 2 and 4 months
Rotateq = 3 doses at 2, 4, and 6 months

21. Proactive Measures to Prevent Vaccine Type Confusion in IIS Data
Continuous update of codes available on-line at MIIC technical web page
Notification of IT specialists via “GovDelivery” when changes occur
Prompt follow-up with provider organizations who continue to use deleted codes