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1、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.Haemophilus influenzae type b Hib - characteristicsGram negative cocco-bacillicarried by 3% to 15% of young
2、children in the worldcauses disease in young childrenmeningitispneumoniaepiglottitisseptic arthritisHib - characteristicsGram negaHib diseaseIndustrialized countriesmedian age 1-2 yearsmost meningitis then epiglottitis?meningitis mortality under 5%affects 1-2/1000 childrenDeveloping countries (Afric
3、a)median age 6-9 monthsmost pneumonia, then meningitismeningitis mortality 20-50%affects 10/1000 children?Hib diseaseIndustrialized counb型流感嗜血杆菌英文课件Gambian PRP-T trial42,000 infants randomized to receive PRP-T or placebo at 2, 3 and 4 months of agepopulation studied for:Hib meningitisHib pneumoniaal
4、l pneumoniaHib carriageGambia slides courtesy of Kim Mulholland, MD University of MelbourneGambian PRP-T trial42,000 infaStudy 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 mo
5、nths of age5 numbers5 numbersStudy designindividually randoFinal results, March 199642,848 infants enrolledPRP-T group21,490 infants1272 possible Hib disease616 chest radiographs173 lumbar punctures71 lung aspiratesControl group21,358 infants1342 possible Hib disease653 chest radiographs192 lumbar p
6、unctures75 lung aspiratesFinal results, March 199642,8Did the vaccine actually prevent pneumonia?*cough + fast breathing or lower chest wall indrawingDid the vaccine actually preveWhat did the Gambia trial tell us about the epidemiology of Hib pneumonia in West Africa?Hib is responsible for about 20
7、% of radiological pneumonia in Gambian infantsPrevious studies had suggested 5-10% of pneumonia due to HibVery little “WHO pneumonia” which is not radiologically obvious is due to HibWhat did the Gambia trial tellConclusionsPRP-T effectively prevented meningitis and pneumonia due to Hib in The Gambi
8、aHib vaccines have been proven in Finland, USA, UK, Chile and other countries Why arent Hib vaccines used everywhere?ConclusionsPRP-T effectively pb型流感嗜血杆菌英文课件Why are Hib vaccines not used all over the world?costvaries, currently $2 per doseaffordable for most Asian countriesunderstanding of burden
9、of disease is the major problem in AsiaWhy are Hib vaccines not used AsiaMany 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
10、.e., first vaccine plus 2 week delay): 13 weeksVaccination of childrenVaccinaAll incidences are per 100,000 child-yearsPneumonia OutcomesAll incidences are per 100,000All incidences are per 100,000 child-yearsPneumonia OutcomesAll incidences are per 100,000All incidences are per 100,000 child-yearsM
11、eningitis OutcomesAll incidences are per 100,000All incidences are per 100,000 child-yearsMeningitis OutcomesAll incidences are per 100,000Published rates of Hib meningitis(Children under 5 years per 100K person-years)Published rates of Hib meningib型流感嗜血杆菌英文课件Mortality rates are per 100,000 child-ye
12、arsMortality after at least 1 doseMortality rates are per 100,00Mortality rates are per 100,000 child-yearsMortality after 3 dosesMortality rates are per 100,00ConclusionsHib 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.Conclusi
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