HiBand Hep B


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  • We can do very little to help all those who are already infected. It is possible to protect the future generations by vaccinating infants. Hepatitis B vaccine in India’s UIP could help prevent about 10 lakh chronic infections and 1.5 lakh deaths in each year’s birth cohort.
  • To stimulate interest put the choices to voting. Most people are unlikely to select the second choice. And they are surprised to know it when you show the last line creating interest. Child to Child (including Adult to child) also known as horizontal transmission accounts for most HBV infections. It is supported by the fact that there is familial clustering of HBsAg positivity among small children is frequently noticed in families where adults (usually a male adult) are HBsAg positive and there is no contact through blood/ sex.
  • Infections in first year of life almost always (90%) end up in becoming chronic
  • Please note the Age of Infection on the x-axis—the major epidemiological change occurs after the 1 st to 4 th year of life.
  • Immunization provided to infants has the highest impact on reducing the chronic infections in the community.
  • Etiology study locations: Deivanayagam, 1993, Chennai; Singhi, 2002, Chandigarh; Mani, 2007, Banglalore; Chinchankar, 2002, Pune; Steinhoff, 1998, New Delhi, Lucknow, Madras, Nagpur, Trivandrum and Vellore
  • Remember you’ll need to say Haemophilus influenzae type b (“or Hib”) first time you use the terms
  • Undetected disease Example: False Negative (C ulture Negative)
  • In persons with cirrhosis, the liver tissue is found replaced with fibrous and fatty tissue. The liver appears nodular. Hepatocellular carcinoma (HCC or liver cancer) may also develop in the chornically infected liver tissue.
  • HiBand Hep B

    1. 1. Epidemiology of HepB and Hib diseases in India Dr Pradeep Haldar AC(I) SEPIO meeting 18-20 May 2011
    2. 2. <ul><li>India has intermediate endemicity: 2- 8% prevalence* </li></ul><ul><li>4 crore estimated chronic carriers </li></ul><ul><li>Of 2.6 crore children born each year, </li></ul><ul><ul><li>10 lakh are at the risk of becoming chronic carriers </li></ul></ul><ul><ul><li>1.5 lakh at risk of developing serious complications and premature death </li></ul></ul><ul><li>Hepatitis B vaccine would prevent these chronic infections </li></ul>Hepatitis B: Disease Burden * References: Batham et al. Ind Pediatrics 2007
    3. 3. Hepatitis B Virus – Modes of Transmission From mother to baby (perinatal transmission) From child to child during play or from an adult to child by contact of body fluids; (Most common cause in India) Unscreened blood transfusions and organ transplant Through unsafe needles and injections Through unprotected sexual contact
    4. 4. HBV transmission.. <ul><li>100 times more infectious than HIV </li></ul><ul><li>HBV is able to remain active on surfaces (e.g. table tops, razor blades, blood stains etc) for about a week without losing infectivity; </li></ul>
    5. 5. <ul><li>Persistence of infection for > 6 months </li></ul><ul><li>Silent killer: asymptomatic for decades </li></ul><ul><li>90% infections in infancy become chronic. </li></ul><ul><li>30% infections at 1-4 yr age and 6% at 5 yr and above become chronic </li></ul><ul><li>Infected person may look healthy until complications develop and may continue to spread the disease. </li></ul>Chronic Hepatitis B infection
    6. 6. Hepatitis B infection: Age and outcome Infection during infancy – very high chance of becoming chronic
    7. 7. Why infant immunization with Hep B? <ul><li>Most chronic infections are due to infections during infancy and childhood </li></ul><ul><li>Infant immunization reduces chronic HBV burden in the community </li></ul><ul><li>This reduces reservoir and future infections </li></ul>
    8. 8. HepB vaccine introduction framework <ul><li>Government of India decided to expand the Hepatitis B in the entire country by 2011. </li></ul>
    9. 9. Overview of Hepatitis B Expansion GAVI support areas where Hepatitis B vaccination Started Sno On going States Districts Covered Sno Added States Hepatitis B Vaccination 1 Andhra Pradesh Entire State 22 Uttarakhand States Proposed for Expansion 2 Himachal Pradesh 23 Arunachal Pradesh 3 Jammu & Kashmir 24 Bihar 4 Karnataka 25 Chandigarh 5 Kerala 26 Chattisgarh 6 Madhya Pradesh 27 D & N Haveli 7 Maharashtra 28 Daman & Diu 8 Punjab 29 Tripura 9 Tamil Nadu 30 Sikkim 10 West Bengal 31 Manipur 11 A & N Islands* 32 Meghalaya 12 Delhi* 33 Mizoram 13 Goa* 34 Nagaland 14 Lakshadweep* 35 Jharkhand 15 Puducherry* 16 Assam Selected Area(s) Jorhat, Sibsagar Remaining districts 17 Gujarat Ahmedabad, Surat, Vadodara 18 Haryana Panchkula, Ambala 19 Orissa Sundergarh 20 Rajasthan Jaipur 21 Uttar Pradesh Kanpur, Lucknow
    10. 10. Haemophilus influenzae b disease
    11. 11. Under 5 mortality in India <ul><li>Approximately 1.3 million deaths under 5 deaths occurs in children age 1-59 months </li></ul><ul><li>Pneumonia in the post-neonatal period is the leading cause of death in children (16% of all <5 deaths), followed by diarrhea (13%). </li></ul><ul><ul><li>In 2005, approximately 370,000 pneumonia deaths occurred in children 1-59 months of age </li></ul></ul><ul><li>Meningitis accounts for an additional 4% of deaths among children age 1-59 months. It also causes a significant amount of morbidity, with 30% of survivors living with a long term disability. </li></ul>Source: India’s Million Death Study, National Mortality Estimates, 2005
    12. 12. Causes of <5 mortality in India, 2005 Neonatal deaths 43% Bassani 2010, Million Death Study Total pneumonia 23%
    13. 13. Hib diseases in India <ul><li>W.H.O. estimates that India has more than 72,000 deaths due to Hib diseases, each year. </li></ul><ul><li>60,000 children die due to Hib pneumonia in India and another 9,000 due to Hib meningitis; </li></ul><ul><li>Studies using, culture, Latex Agglutination Test (LAT) and Polymerase Chain Reaction (PCR) show 23-73% of confirmed bacterial meningitis in children due to Hib 1-4 </li></ul><ul><li>Studies show Case fatality Ratio of 21-29% 4,5 </li></ul><ul><li>About 30% of Indian children, who survive suffer from permanent disabilities such as deafness, paralysis and mental retardation </li></ul>1 Deivanayagam 1993 2 Singhi 2002 3 Mani 2007 4 Chinchankar 2002 5 Steinhoff 1998
    14. 14. Hib - A difficult organism to study <ul><ul><li>Organism factors </li></ul></ul><ul><ul><ul><li>fastidious, sensitive to environment </li></ul></ul></ul><ul><ul><li>Laboratory challenges </li></ul></ul><ul><ul><ul><li>Lack of adequate infrastructure </li></ul></ul></ul><ul><ul><ul><li>Lack of reagents </li></ul></ul></ul><ul><ul><ul><li>Lack of expertise </li></ul></ul></ul><ul><ul><li>Clinical issues </li></ul></ul><ul><ul><ul><li>Readiness to perform lumbar puncture </li></ul></ul></ul><ul><ul><ul><li>Specimen transport delays </li></ul></ul></ul><ul><ul><ul><li>Use of antibiotics </li></ul></ul></ul>
    15. 15. Role of Surveillance for Hib <ul><li>As per previos slide, Hib is a difficult organism to study; </li></ul><ul><li>Therefore, surveillance data alone does not accurately measure burden of Hib disease </li></ul><ul><ul><li>Low sensitivity of culture based methods </li></ul></ul><ul><ul><li>Low specificity of non-culture based methods (NP, PCR, UAg) </li></ul></ul><ul><ul><li>Representativeness depends on many factors </li></ul></ul><ul><ul><li>Poor quality surveillance may hurt evidence-based policy making because it is inaccurate </li></ul></ul><ul><li>Furthermore, surveillance is important for monitoring the impact of vaccination </li></ul><ul><ul><li>Changes in disease pre- and post- vaccine introduction </li></ul></ul><ul><li>Modeling is essential to establish disease burden </li></ul><ul><ul><li>Results of clinical trials with vaccines (i.e. vaccine probe approach) </li></ul></ul><ul><ul><li>Good quality data from surveillance as input variables </li></ul></ul>
    16. 16. Undetected Disease including meningitis and pneumonia Additional cases preventable with vaccination Can be identified by surveillance for invasive disease Surveillance underestimates the burden of Hib disease
    17. 17. Bacterial meningitis surveillance
    18. 18. Sentinel Hospital Based Surveillance for Bacterial Meningitis in India <ul><li>The Government of India is proposing to introduce Pentavalent vaccine (DPT-Hep B- Hib) in the immunization programme in Kerala and Tamil Nadu. </li></ul><ul><li>Sentinel surveillance sites for Hib meningitis proposed to be established </li></ul><ul><li>This opportunity will be used for surveillance of pneumococcal and meningococcal meningitis. </li></ul>
    19. 19. Objectives <ul><li>Primary </li></ul><ul><li>To establish a hospital based sentinel surveillance for bacterial meningitis in children 1 month – 59 months in six States in India </li></ul><ul><li>To determine trends of bacterial meningitis in children 1 month to 59 months of age in these sites in India </li></ul>
    20. 20. Objectives <ul><li>Secondary </li></ul><ul><li>Determine the aetiological profile and invasive bacterial disease in children for </li></ul><ul><li>Haemophilus influenzae type b, Streptococcus pneumonia, Neisseria meningitides </li></ul>
    21. 21. <ul><li>Proposed Sites: </li></ul><ul><li>Kerala: Medical College, Trivandrum </li></ul><ul><li>Medical College, Alapuzha </li></ul><ul><li>Tamil Nadu : Institute of Child Health,Chennai </li></ul><ul><li>Stanley Medical College, Chennai </li></ul><ul><li>Madurai Medical College, Madurai </li></ul><ul><li>Christian Medical College, Vellore </li></ul><ul><li>Karnataka: Kasturba Medical College & Hospital, </li></ul><ul><li>Manipal </li></ul><ul><li>Orissa : Regional Medical Research Centre, </li></ul><ul><li>Bhubaneswar </li></ul><ul><li>Shimla: Indira Gandhi Institute of Medical Sciences, </li></ul><ul><li>Shimla </li></ul><ul><li>Delhi: All India Institute of Medical Sciences, New Delhi & </li></ul><ul><li>Kalawati Saran Children’s Hospital, New Delhi </li></ul>Sentinel Hospital Based Surveillance for Bacterial Meningitis in India
    22. 22. <ul><li>Surveillance will be carried out on project mode. </li></ul><ul><li>Reports will be shared with Central and State Governments. </li></ul><ul><li>Expected that State Govt. will take over surveillance at the end of project period. </li></ul>Sentinel Hospital Based Surveillance for Bacterial Meningitis in India
    23. 23. Hib vaccine introduction in India <ul><li>Planned for introduction in 2 states (Ke, TN) as pentavalent vaccine (DPT+HepB+Hib); </li></ul><ul><li>10 dose liquid formulation to be used in these states; </li></ul><ul><li>May be expanded to other states of the country later on. </li></ul><ul><li>Impact study is also being planned in these states. </li></ul>
    24. 24. Thanks
    25. 25. Extra slides
    26. 26. Hospitalised/severe clinical pneumonia <ul><li>Pneumonia causes 410,000 deaths in India annually among children <5 (UNICEF) </li></ul><ul><li>Rates found in ICMR Part A study are similar to those in other studies/countries </li></ul>Study Incidence (per 100,000 cyo) ICMR Part A 2700-7900 Lombok, Indonesia 3906-4518 Vitamin A (India, Ghana, Peru) 2300 South Africa 1530
    27. 27. Bacterial Pneumonia Etiology <ul><li>13% of severe pneumonia is due to Hib (95% CI 9.5-16.4)* </li></ul>*Frequency weighted mean of available methodologically-sound studies Author Syndrome Location Age Study Size % disease due to Hib % isolation rate of any organism Bahl 1995 Pneumonia Delhi 0-5 years 190 19 55 Kumar 1984 Pneumonia Chandigarh < 11 years 64 13 42 Patwari 1996 Pneumonia Delhi < 13 years 132 15 12
    28. 28. Bacterial Meningitis Etiology <ul><li>25% of Bacterial Meningitis is due to Hib (95% CI 20.8-29.6) </li></ul>Author/Year Syndrome Age Study Size % Hib % isolation rate Deivanayagam 1993 Suspected meningitis 2 months to 11 years 114 24.6 48 Singhi 2002 Suspected meningitis 1 month to 12 years 107 35 23 Devi 1982 Acute meningitis <15 years 7 19 41 Mani 2007 Bacterial meningitis <5 years 51 14 76 Chinchankar 2002 Bacterial meningitis 1 month to 5 years 54 26 50 ICMR Part A Chandigarh Bacterial meningitis 1-23 months 90 16.7 22 ICMR Part A Kolkata Bacterial meningitis 1-23 months 98 20.7 43 ICMR Part A Vellore Bacterial meningitis 1-23 months 181 29 50
    29. 29. Outcomes: Case Fatality Author/Year Syndrome CFR (%) Kabra 1991 Hib meningitis 25 Steinhoff 1998 Hib meningitis 29 Thomas 2002 Hib meningitis 20 Chinchankar 2002 Hib meningitis 21 Thomas 2002 Any invasive Hib disease 16
    30. 30. Outcomes: Sequelae <ul><li>Sequelae occur despite prompt and appropriate treatment. </li></ul><ul><li>Mirrors reported rates of neurologic sequelae following Hib meningitis in survivors range of 15-30% in developed and developing countries. </li></ul>Study Site Hib meningitis survivors with neurological sequelae (n) Hib meningitis survivors with neurological sequelae (%) Chinchankar 2002 Pune 5 36% Singhi 2007 Chandigarh 4 31% Bose (unpublished) Vellore 1 6%
    31. 31. Problems in Detection <ul><li>Organism factors </li></ul><ul><ul><li>fastidious growth requirements </li></ul></ul><ul><ul><li>sensitive to environment </li></ul></ul><ul><li>Clinical laboratory challenges </li></ul><ul><ul><li>specimen handling and transport </li></ul></ul><ul><li>Access to health care </li></ul><ul><ul><li>antibiotic use before presentation </li></ul></ul><ul><ul><li>death at home </li></ul></ul><ul><ul><li>diagnostic testing (lumbar puncture) </li></ul></ul>
    32. 32. Issues in Diagnosis <ul><li>Pneumonia: </li></ul><ul><ul><li>Requires lung puncture (most sensitive) but is considered by most experts to be too invasive. </li></ul></ul><ul><ul><li>Blood cultures are only positive in 10-20% of cases of bacterial pneumonia. </li></ul></ul><ul><li>Meningitis: </li></ul><ul><ul><li>Requires lumbar puncture </li></ul></ul><ul><ul><li>Techniques that do not require viable bacteria are most sensitive </li></ul></ul><ul><ul><ul><li>LAT is more sensitive than culture, but kits are expensive </li></ul></ul></ul><ul><ul><ul><li>PCR is most sensitive, but not widely available </li></ul></ul></ul>
    33. 33. Antibiotic Usage Prior to Admission <ul><li>High documented rates of antibiotic use prior to hospital admission </li></ul><ul><ul><li>Singhi et al (2002) found 79% of suspected meningitis cases had taken oral or IV antibiotics prior to admission </li></ul></ul><ul><ul><li>Mathew et al (unpublished) found 33% of urine samples of children with fever and/or cough were positive for at least one of amoxicillin, ciprofloxacin, bactrim, cephalexin, and cefuroxime. They did not test for gentamicin. </li></ul></ul>
    34. 34. Chronic Hepatitis B infection <ul><li>15 -25% of Chronic infections lead to liver cirrhosis and cancer </li></ul><ul><li>Complications develop after several decades (about 30 – 40 years) of infection </li></ul>Chronic HBV infection: Long term and asymptomatic