Haemophilus influenzae type b Using vaccines to measure disease burden: A Tale of Two StudiesPresentation to PABIO 550Diseases of Public Health Importance and Their Control David Mercer, Ph.D.Hib - characteristicsGram negative coccobacillicarried by 3% to 15% of young children in the worldcauses disease in young childrenmeningitispneumoniaepiglottitisseptic arthritisHib diseaseIndustrialized countriesmedian age 12 yearsmost meningitis then epiglottitis?meningitis mortality under 5%affects 12/1000 childrenDeveloping countries (Africa)median age 69 monthsmost pneumonia, then meningitismeningitis mortality 2050%affects 10/1000 children?Gambian PRP-T trial42,000 infants randomized to receive PRPT or placebo at 2, 3 and 4 months of agepopulation studied for:Hib meningitisHib pneumoniaall pneumoniaHib carriageGambia slides courtesy of Kim Mulholland, MD University of MelbourneStudy designindividually randomized, double blind studymajor effort to detect Hib pneumoniarandomization in 10 groups numbered 0 through 9:DTP + PRP-TDTP + placeboat 2, 3 and 4 months of age5 numbers5 numbersFinal results, March 199642,848 infants enrolledPRPT group21,490 infants1272 possible Hib disease616 chest radiographs173 lumbar punctures71 lung aspiratesControl group21,358 infants1342 possible Hib disease653 chest radiographs192 lumbar punctures75 lung aspiratesDid the vaccine actually prevent pneumonia?*cough + fast breathing or lower chest wall indrawingWhat did the Gambia trial tell us about the epidemiology of Hib pneumonia in West Africa?Hib is responsible for about 20% of radiological pneumonia in Gambian infantsPrevious studies had suggested 510% of pneumonia due to HibVery little “WHO pneumonia” which is not radiologically obvious is due to HibConclusionsPRPT effectively prevented meningitis and pneumonia due to Hib in The GambiaHib vaccines have been proven in Finland, USA, UK, Chile and other countries Why arent Hib vaccines used everywhere?Why are Hib vaccines not used all over the world?costvaries, currently $2 per doseaffordable for most Asian countriesunderstanding of burden of disease is the major problem in AsiaAsiaMany Asian countries can afford Hib vaccineHib was known to be an important cause of bacterial meningitis in AsiaBut:Microbiologically confirmed Hib incidence lower than elsewhere ( one color vaccineAverage age at enrollment (i.e., first vaccine plus 2 week delay): 13 weeksAll incidences are per 100,000 childyearsPneumonia OutcomesAll incidences are per 100,000 childyearsPneumonia OutcomesAll incidences are per 100,000 childyearsMeningitis OutcomesAll incidences are per 100,000 childyearsMeningitis OutcomesPublished rates of Hib meningitis(Children under 5 years per 100K person-years)Mortality rates are per 100,000 childyearsMortality after at least 1 doseMortality rates are per 100,000 childyearsMortality after 3 dosesConclusionsHib vaccine not an effective intervention against ALRI (pneumonia) in LombokHib meningitis burden underestimated by microbiology true burden 10X greaterHib vaccine may significantly reduce meningitis mortality1 in 33 unvaccinated children on Lombok develop invasive Hib disease before age 2.Comparison of Gambia and Lombok ResultsHib vaccine prevents about 20% of radiological pneumonia in Gambian infantsVery little “WHO pneumonia” which is not radiologically obvious is due to HibProtection conferred after 3rd doseHib vaccine prevents little to no radiological pneumonia in Lombok infantsThe predominant pneumonia prevented by Hib vaccine is nonsevere WHO pneumonia.Protection conferred after first dose.For every case of laboratorydiagnosed Hib disease on Lombok, there were 10 cases of Hib meningitis, and 100 cases of Hib pneumonia.GambiaLombok