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Hib Disease Burden – Review of literature Dr Raju Shah 1.

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Presentation on theme: "Hib Disease Burden – Review of literature Dr Raju Shah 1."— Presentation transcript:

1 Hib Disease Burden – Review of literature Dr Raju Shah 1

2 Causes of under-five deaths India: WHO 2008 Pneumonia 20.3% (0.371 million) Diarrhea 12.9% (0.237 million) Others 12.8% (0.218 million) Neonatal 54% (1.003 million) million under-five deaths (20.8% of world) Black RE et al, Lancet 2010;375:

3 Pneumonia deaths: Top 10 countries Black RE et al, Lancet 2010;375: NumberCountryPneumonia deaths (N) (2008) % of world 01India371, % 02Nigeria177, % 03DR Congo112,6557.1% 04Pakistan084,2105.3% 05Afghanistan080,6945.1% 726, % 06China062,2293.9% 07Ethiopia048,8923.1% 08Angola033,0782.1% 09Kenya030,4061.9% 10Indonesia038,3312.4% Total1,031, % World1,575,257100% 3

4 Clinical Pneumonia burden – Top 15 countries CountryPredicted no. of new cases (millions) Estimated incidence (epi/child yr) India China Pakistan Bangladesh Nigeria Indonesia Ethiopia Democratic Republic of the Congo Viet Nam Philippines Sudan Afghanistan United Republic of Tanzania Myanmar Brazil World Rudan I Bull WHO 2008;86:

5 In India, data on Hib particularly on population-based incidence is sparse There is marked variability in reported burden of Hib disease in India However, a number of hospital-based studies have shown that, as in other parts of the world, Hib is the most common endemic cause of bacterial meningitis in children 5

6 Challenges in establishing Hib disease burden Fastidious organism, difficult to grow High threshold for cultures Lack of good microbiology services Antibiotic treatment before culture Only severe cases reach the hospitals 6

7 There is marked variability in reported burden of Hib disease in India A study by Panjarathinam R, Shah RK. (Pyogenic meningitis in Ahmedabad Indian J Pediatr 1993; 60:669–73) - of 135 CSF samples obtained from children with meningitis - cultures yielded no Hib organisms at all Study by Venkatesh VC, Steinhoff MC, Moses P, Jadhav M, Pereira SM. (Latex agglutination: an appropriate technology for the diagnosis of bacterial meningitis in developing countries. Ann Trop Paediatr 1985; 5:33–6) have shown Hib to be a common cause of meningitis in infants and young children 7

8 Incidence of Hib meningitis in India S. Minz, V. Balraj, M. K. Lalitha*, N. Murali**, T. Cherian**, G. Manoharan†, S. Kadirvan†, A. Joseph & M.C. Steinhoff†† Indian J Med Res 128, July 2008, pp Prospective study 1997 to 99 – for 24 months Vellore district with 56,153 U5 children 97 possible meningitis Annual incidence Rate per 100,000 (AIR) – (86 for 0-4y while 357 for 0 to 11 m) 18 ABM (AIR 15.9 for 0-59 months) 8 Hib (AIR 7.1 for 0-59m - 32 for 0-11m, - 19 for 0-23m ) Vellore study site is well-served and not typical of all of India – Vellore data would be underestimating for most other regions* * Indian J Med Res 132, October 2010, pp

9 Hib Meningitis in India 0.5 to 2.6% of all hospital admissions (Kabra SK, et al. Bacterial meningitis in India: an IJP survey. Indian J Pediatr 1991; 58: ) 25% (range: 14-35%) of bacterial meningitis attributable to Hib in India 9

10 Good published studies Author/yearSyndromeAge rangeStudy SiteStudy Size% Hib positive Deivanayaga m, et al suspected meningitis 2 mo - 11 y Chennai11425 Singhi, et al suspected meningitis 1 mo - 12 y Chandigarh10735 Suvarna Devi, et al acute meningitis <15 yBehrampur7019 Mani, et al bacterial meningitis <5 yBangalore5114 Chinchankar, et al bacterial meningitis 1 mo - 5 yPune

11 S.N.Study IDStateYearAge groupNo. of cases Haemophilus Influenza (%) 1 Achar and Rao (1953) Tamil Nadu 1950–1951Paeds9845 (45.9) 2 Taneja and Ghai (1955) Delhi1953–1955<12 years330 (0.0) 3 Ahmed et al. (1964) Tamil Nadu 1953–1960< 12 years8733 (37.9) 4 Paul (1963) Delhi1956–1959<12 years4810 (20.8) 5 Srivastava et al. (1968) Uttar Pradesh 1964<12 years330 (0.0) 6 Gandhi (1969) Gujarat1966–1967<12 years604(6.7) 7 Reddi et al. (1973) Andrha Pradesh 1970–1971Paeds855(5.9) 8Tamaskar and Bhandari (1976) Madhya Pradesh 1971–1972<12 years213(14.3) The proportion of Haemophilus influenzae Type B isolates in case series of endemic bacterial meningitis 11

12 S.N. Study IDStateYearAge groupNo. of cases Haemophilus Influenza (%) 9 Kalra and Dayal (1977) Uttar Pradesh 1966– month–12 years 1960(0.0) 10 Ayyagari et al. (1980) Chandigarh1976–1978Paeds17611(6.3) 11 Kumar et al. (1980) Chandigarh1977– month–12 years 6617(25.8) 12 Suvarna Devi et al. (1982) Orissa1978–1981<15 years7013(18.6) 13 Pal and Sant (1982) Maharashtr a --640(0.0) 14 Venkatesh et al. (1985)– Tamil Nadu day–12 years 448(18.2) 15 Bhat (1991) Pondicherry1972–1980Paeds2566(2.3) 16Vincent et al. (1987) Kerala1983–19841 month–12 years 510(0.0) The proportion of Haemophilus influenzae Type B isolates in case series of endemic bacterial meningitis (cont) 12

13 S.N.Study IDStateYearAge groupNo. of cases Haemophilus Influenza (%) 17 Kabra et al. (1991) Various1989<12 years8528(0.9) 18 Deivanayagam (1993) Tamil Nadu1989– months–11 years 11428(24.6) 19 Panjarathinam and Shah (1993) Gujarat1990<10 years1350(0.0) 20 Javadekar et al. (1997) Gujarat-Paeds501(2.0) 21 Bhaumik (1998) Delhi-12–75 years Jain et al. (2000) Delhi- 3 months–12 years 327(21.9) 23 Sahai et al. (2001) Pondicherry1994– month–12 years 10017(17.0) 24 John et al. (2001) Tamil Nadu1997–19980–60 years611(1.6) 25 Singhi et al. (2002a) Chandigarh– 1 month–12 years 10723(21.5) 26Singhi et al. (2002b) Chandigarh1998–19993 months–12 years 696(8.7) The proportion of Haemophilus influenzae Type B isolates in case series of endemic bacterial meningitis (cont) 13

14 S.NStudy IDStateYearAge groupNo. of cases Haemophilus Influenza (%) 26 Singhi et al. (2002b) Chandigarh1998– months–12 years 696(8.7) 27 Chinchankar et al. (2002) Maharashtr a 1997– month–5 years 5414(25.9) 28 Hemalatha et al. (2002) Andrha Pradesh 1998–20001–5 years1206(5.0) 29 Shivaprakash et al. (2004) Karnataka–Paeds2043(1.5) 30 Singhi et al. (2004) Chandigarh1993–19961–12 years889(10.2) 31 Mani et al. (2007) Karnataka1996–2005All ages3857(1.8) 32 Shameem et al. (2008) Karnataka2003–2007Paeds23661(25.8) 33Minz et al. (2008) Tamil Nadu1997–19990–4 years976(6.2) The proportion of Haemophilus influenzae Type B isolates in case series of endemic bacterial meningitis (cont) 14

15 Case Fatality Rates Author/YearSyndromeSiteCFR (%) Kabra 1991Hib meningitisJaipur,Jodhpur, Delhi, Kolkata 25 Steinhoff 1998Hib meningitisVellore29 Thomas 2002Hib meningitisIBIS20 Chinchankar 2002Hib meningitisPune21 Thomas 2002Any invasive Hib disease IBIS/ CFR in Hib Meningitis – 20-29% Hib invasive disease CFR – 16% In ICMR study even the 0.03 per cent death rate in spite of hospital treatment amounts to 1 per cent case fatality; 50 times higher would be 50 per cent case fatality (~15 deaths/1000) – very likely if untreated * UNICEF projection of 14 deaths due to pneumonia per 1000 under-five children is not at all inconsistent with the ICMR study data – even though they derive through different routes and from different denominators* * Indian J Med Res 132, October 2010, pp

16 Bacterial Pneumonia A similar pattern is observed in Indian studies of pneumonia also A study by Kumar L, Ayyagari A. (The etiology of lobar pneumonia and empyema thoracis in children. Indian Pediatr 1984; 21:133–137) found no blood or pus cultures positive for Hib for 64 children with acute pneumonia or empyema, - but 2 (8%) of 26 blood and 6 (16%) of 38 pleural fluid specimens were positive for Hib by use of antigen detection methods 16

17 Hib Pneumonia in India Author/YearSyndromeLocationAgeStudy Size% disease due to Hib % isolation rate of any organism Bahl 1995PneumoniaDelhi0-5 years110*1955 Kumar 1984PneumoniaChandigar h < 11 years64*1342 Patwari 1996 PneumoniaDelhi< 12 years132* % to 19% of pneumonia and LRTI due to Hib 17

18 Multi-center surveillance for pneumonia & meningitis among children (<2 yr) for Hib vaccine probe trial preparation in India Indian J Med Res 131, May 2010, pp Chandigarh, Vellore, Kolkata 18 m to 24 m – N Enrollment from July 05 to Dec 06 Parents explained about s/s of pneuonia and meningitis Pneumonia and meningitis admitted to hospitals also enrolled CSF culture, PCR, LAT, Bl culture, CXR 18

19 Severe clinical pneumonia – 2717 to 7890 per 100,000 child-years Suspected meningitis – 1971 to 2433 per 100,000 child-years NP carriage – 6 to 7.6 % Incidence of clinical pneumonia comparable with other studies from India and a higher incidence of suspected meningitis 19

20 Drug Resistant Hib 1 st cases of Drug resistant Hib from Chandigarh (1990) 1 Vellore study (1992) reported – 42.5% of Hib isolate MDR strains 2 Nagpur study (1996) reported – 80% MDR srains 3 IBIS (1999) reported – 56% resistance to Chloramphenicol - 40% resistance to Ampicillin 4 1. Singh N et al. Multiple resistant Hib meningitis. Indian Pediatrics 1990;27: John TJ et al. Hib disease in children in India.Pediatric Infec Dis J. 1998;17(9): Agarwal v et al. Characterisation of invasive hemophilus Influenza isolated in Nagpur, Central India. Indian J Med Res. 1996;103: Invasive Hemophillus Influenza disease in India: a preliminary report of prospective multihospital surveillance IBIS. Pediatr Infect Dis J. 1998; 17:

21 HIB-Multicentric Study (IBIS) Antimicrobial % of Isolates agents Resistant Intermediate Total Ampicillin Cefotaxime Chloramphenicol Trimetho.-sulfamethox Erythromycin Antibiotic Resistance of 57 Haemophilus influenzae isolates from 6 IBIS centres, 1993 to

22 Nasopharyngeal Carriage Hib nasopharyngeal carriage among infants was found to be common in India Study from Chandigarh, researchers found 11.2% of 1000 children below 2 years were carriers of H. influenza - 69% belonged to type b and the rest were non-typable* Hib carriage rates increases throughout infancy and into the second year of life, peaking at age months at a prevalence of 20.3%* * Sekhar S, Chakraborti A, Kumar R. Haemophilus influenzae colonization and its risk factors in children aged <2 years in northern India. Epidemiol Infect. 2009; 137:

23 Estimates From available studies reviewers estimated that there may be as many as 75 to 100 cases of meningitis caused by this organism per year per 100,000 children <5 years of age 1 Hib vaccine probe - total pneumonia cases caused by Hib would be 2,083,333 or 2 million cases per year. These are crude extrapolations from the multi-centre study 2 1.John TJ, Cherian T, Raghupathy P. Haemophilus influenzae disease in children in India: a hospital perspective. Pediatr Infect Dis J 1998; 9: S169–71 2. Gupta M, Kumar R, Deb AK, Bhattacharya SK, Bose A, John J et al. A multi-centre surveillance for pneumonia and meningitis among children (<2 yr) for Hib vaccine probe trial preparation in India. Indian J Med Res 2010; 131;

24 Prospective culture based studies for pneumonia in world Pneumococcus: 30-50% Hib: 10-30% Others: – NTHi: New Papua Guinea (Lung culture) Pakistan (Blood isolates) – S. Aureus: Chile (Lung aspirate) WHO 42% (Blood aspirate) – Non-typhoid salmonella: Africa, Malawi (severe pneumonia) Viruses: 30-50% – RSV: 15-40% – Others: Rudan I Bull WHO 2008;86:

25 Vaccine probe studies Pneumococcus and Hib are two important vaccine preventable causes of pneumonia Vaccine effectiveness against radiological proven pneumonia studies in developing countries – Hib: 15-30% (Hib conjugate vaccine) Rudan I Bull WHO 2008;86:

26 3 Hib probe studies Pilot or Probe introduction of specific vaccine, with measurement of syndromes pre-and post-vaccination, necessary to quantify the pre-vaccination prevalence/incidence Gambia, Chile, Indonesia – % of hospitalized pneumonia cases with radiographic infiltrates were prevented 26

27 Hib impact studies >95% efficacy- Europe, US and Gambia Also in Chile, Brazil, Columbia, Kenya, Malawi Lombok – Measurable impact on clinical pneumonia but no impact on radiological pneumonia Bangladesh (SEA) – Meningitis reduced by 90% – Radiological pneumonia reduced by 16-32% 27

28 The Gambia Hib vaccine program resulted in virtual disease elimination Adapted from Adegbola R et al. Lancet, 2005 Incidence of Hib Meningitis/ 100,000 (children <5 years) in the Western Region of the Gambia Despite supply interruptions, disease has been virtually eliminated Hib trialNational Immunization with Hib 28

29 Hib Cases and Incidence CHILE, Children <5 years of age Source: Notificación Obligatoria, MINSAL. 29

30 WHO statement The lack of local surveillance data should not delay the introduction of the vaccine especially in countries where regional evidence indicates a high burden of disease 30

31 THANKS 31

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