Disease Risk – Hib

 

Risk to a child from Haemophilus influenzae b (Hib) if not vaccinated until the age of 5:

Factors not considered:

1)      The vaccine failure rate after immunization for Hib is rare at an estimated 2.2 per 100,000 vaccinees [1] and consequently is not considered in this analysis.

2)      The question of overall invasive Hi disease risk changes when employing a mass vaccination strategy involving only a single serotype is one that has been debated and there is at least one study indicating a clear trend toward invasive disease through serotype replacement [2].  However, the complexity of introducing serotype replacement into the disease and vaccine risk assessment precludes it from being included in the analysis at this time resulting in a bias toward higher vaccine efficacy assessment.  The risk of Invasive Hi disease has a large variability in different populations with numerous known risk factors.  For this analysis we have to use average risk rates from large studies but we encourage readers to understand the different risk factors (i.e. breast feeding, socio-economic conditions etc) that can substantially raise or lower individual risks from invasive Hi disease.

Case Fatality Rate: The CDC pink book lists the risk of death from Hib Meningitis at 2-5% [3].  In Schoendorf et al (1994) [4] they document that prior to Hib vaccination in the US from 1980-1987, the fatality rate of Hi Meningitis was dropping despite consistent levels of hospitalizations due to meningitis.  This indicates that medical care was reducing the case fatality rate of this disease.  In 1987, the rate had dropped to about 2% of Meningitis cases.  Meningitis occurs consistently in approximately 50% of Invasive Hi disease cases[5] meaning that the overall fatality case rate from invasive Hi disease had dropped to 1% due to modern medical care.

Rate of Long Term Sequelae or Injury: The CDC pink book lists the case rate of hearing impairment or other neurologic sequelae from Hib Meningitis as 15%-30%.[3]  This number is unreferenced and non-specific as to whether the sequelae is long or short term.  Ladhani et al (2010) performed a unique modern long term follow-up study in the UK of cases of invasive Hib disease following vaccine failure.[6] They found that the rates of long term sequelae in the study group were consistent with invasive Hib cases prior to vaccination at a rate of approximately 10.4%.

Incidence Rates: Prior to vaccination, the vast majority of cases were in children < 12 months of age with the peak incidence rates occurring around 6-7 months of age.[3]  In times of readily circulating virus, infants would receive passive protection through transplacentally acquired maternal IgG antibodies and breastfeeding.[3]  Vaccine protection is typically provided through two or three shots providing full protection at about 6 months of age.    Infants < 6 months are generally considered unprotected by vaccines.[3]  Post vaccination, the vast majority of cases were found in children < 6 months of age, likely due to a loss of maternal immunity and lack of vaccine protection.  In both the pre-vaccine and post-vaccine eras, the incidence rates of invasive meningitis are approximately 5 times higher in the first year of life compared to each of the next 4 years.  Given that the distribution of cases within the first year has changed and depends highly on the state of maternal immunity and breastfeeding status, this analysis will assume a relatively even split between incidence rates from 0-6 months, and 6-12 months of age.  Given that vaccination will only provide protection for infants greater than 6 months of age, only the cases in the first year would be vaccine preventable for this analysis.

Risk in Population with Low Rates of Vaccination: There are varying incidence rates of Hib meningitis from the pre-vaccine era.  This analysis used national mortality and hospital discharges data provided in Schoendorf et al (1994)[4].  The Schoendorf study documented a relatively consistent hospitalization rate in the years immediately prior to vaccination (1980-1987).  The average hospitalization rate for Hib meningitis was calculated for the 8 years at 39.515 per 100,000.  Based on the age distribution noted above, we calculated a meningitis rate of 109.76 per 100,000 for year 0 and 21.95 per 100,000 for years 1-4.  The meningitis rates were doubled to calculate the yearly Invasive Hib disease incidence rate (meningitis occurs in 50% of invasive Hi disease).  The cumulative incremental rate of invasive Hib disease from ages 0-4 was then calculated to be 28.5 per 10,000 or 1 in 350.  (50% of year 0 rate was used because vaccination wouldn’t protect infants < 6 months).  The cumulative risk of death was calculated to be 0.285 per 10,000 or 1 in 35,078.  The cumulative risk of permanent injury was calculated to be 2.96 per 10,000 or 1 in 3,372.

Risk in Highly Vaccinated Population: Post vaccination rates of invasive Hib disease are very low.  This analysis used the incidence rate from 2008 MMWR[7].  Unfortunately, serotyping in the US has over 30% rate of undetermined cases.  The province of Ontario consistently determines most of the serotypes found across the province which was documented in Adam et al (2010).  Using these numbers, they found Hib occurred in about 10% of the cases.  This analysis took the US Serotype B values of 0.42 and 0.29 (year 0 and years 1-4) and adjusted them up to 10% of the total Invasive Hi cases to 0.613 for year 0 and 0.421 for years 1-4.  The cumulative incremental rate of invasive Hib disease from ages 0-4 was then calculated to be 0.199 per 10,000 or 1 in 50,239.  (50% of year 0 rate was used because vaccination wouldn’t protect infants < 6 months).  The cumulative risk of death was calculated to be 0.00199 per 10,000 or 1 in 5,023,903.  The cumulative risk of permanent injury was calculated to be 0.0207 per 10,000 or 1 in 483,067.

 

References:

[1] Heath PT, Booy R, Azzopardi HJ, Slack MP, Bowen-Morris J, Griffiths H, et al.  Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom. JAMA 2000;284:2334–40.

[2] Adam HJ, et al. Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: Evidence for herd effects and strain replacement due to Hib vaccination. Vaccine (2010), doi:10.1016/j.vaccine.2010.03.075

[3] Centers for Disease Control and Prevention: Epidemiology and Prevention of Vaccine-Preventable Disease. Atkinson W, Wolfe S, Hamborsky J, McIntyre L. eds. 11th edition. Washington D.C.: Public Health Foundation, 2009.

[4] Schoendorf, K., Adams, W., Kiely, J., Wenger, J.  National Trends in Haemophilus influenzae Meningitis Mortality and Hospitalization Among Children, 1980 through 1991.  Pediatrics.  1994; 93: 663-668.

[5] Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clinical Microbiology Reviews 2000;13:302–17.

[6] Ladhani S, Heath PT, Aibara RJ, Ramsay ME, Slack MPE, Hibberd ML, Pollard AJ, Moxon ER, Booy R.  Long-term complications and risk of other seious infections following invasive Haemophilus influenza serotype b disease in vaccinated children.   Vaccine 2010;28:2195-2200.  doi:10.1016/j.vaccine.2009.12.057

[7] CDC. Reported cases and incidence* of notifiable diseases,† by age group — United States, 2008. MMWR 57 (No.54);32.