France Nice October 2008 2nd Congress of European Academy of Paediatrics EAP

1. France Nice October 2008 2nd Congress of European Academy of Paediatrics EAP Bosnia and Herzegovina

2. . COMPLICATIONS AND COVERAGE OF HEPATITIS A VACCINA AMONG KIDS IN BOSNIA AND HERZEGOVINA-ASPECTS

3. COMPLICATIONS AND COVERAGE OF HEPATITIS A VACCINA AMONG KIDS IN BOSNIA AND HERZEGOVINA-ASPECTS Bajraktarevic Adnan 1* , Trninic Slobodan 1*, Penava Semira 1*, Skopljak Amira 1*, Putica Sanja 1*, Miokovic Milan 1*, Korac Sakip 2*, Djurdjevic–Djulepa Aida 2*, Hamamdzic Meliha 3*, Begic Zijo 3*, Djukic Branka 4*, Vranic Haris 5*, Vranic Bisera 6*. Public Health Institution of Canton Sarajevo-Health Center Vrazova Department for preeschool children 1*,General Hospital Sarajevo 2*, Pediatrics Clinic Sarajevo 3*, First Medical Aid Sarajevo Pediatrics Department 4*, Clinical Medical center Sarajevo 5*, Infective Clinics Sarajevo 6* .

4. ABSTRACT • OBJECTIVE : A hepatitis A vaccine is available, but is not routinely given as part of a child's normal immunization schedule. Viral hepatitis A is infection and inflammation of the liver caused by a virus hepatitis A. This type of hepatitis is usually spread in Bosnia by fecal-oral contact, or fecal-infected food and water, and may also be spread by blood-borne infection which is rare. METHODS: Blood test results can usually determine exactly what type of hepatitis child has, but the test takes several days in capital city Sarajevo . RESULTS: Children under 6 years old often have no symptoms. Teens and adults usually have symptoms. Complications are fulminant hepatitis is rare: 0.2% of cases in Sarajevo. Hepatitis A vaccination coverage rates for children aged 18--36 months are lower than overall rates for other vaccines recommended for children in Bosnia and Herzegovina. DISCUSSION: Vaccination coverage also varied by ethnicity, urbans economics situations, epidemiologics situations and pediatrics departments in public health system in each part of Canton Sarajevo. Higher coverage among Gypsy population , Chinese and Bosniacs refugees children, becouse vaccination is not obligate in schedule program. CONCLUSIONS: Usually this vaccine (Havrix) is given to children in areas at high risk for getting the disease or to children over age two years traveling outside the Bosnia. If a child has been exposed to hepatitis, an antibody preparation can be administered to help protect them from contracting the disease. In the Bosnia and Herzegovina , hepatitis A can occur in situations ranging from isolated cases of disease to widespread epidemics. • Key words: Havrix , Vaccina, Kids Morbidity, Hepatitis A, Management.

5. OBJECTIVE • Mortality of hepatitis A is beetween 0.1%-0.2% in kids (1). Oral or parenteral administration of the virus caused hepatitis A after an incubation period ranging from 15 to 40 days, averaging approximately month (2). The fully developed stage of hepatitis is characterized by degeneration and death of liver cells, proliferation of the Kupffer’s cells, mononuclear cell infiltration, and bile duct proliferation (3,4) . As lesion progress, there may be a variable degree of collapse, condensation of reticulin fibers and accumulation of ceroid pigment and large phagocytic cells, first within the lobules and later in the portal tracts(Picture 1). Hepatitis A antigen detected in the cytoplasm of hepatocytes shortly before onset of acute hepatitis(5)(Picture 2).

6. OBJECTIVE • The clinical picture shows great variation. In children the acute disease is generally milder and its course is shorter than in adults. Jaundince may be inapparent or evanecsent, or it may persist for many weeks. The course of the disease often may be separated into two phases: preicteric and icteric(Picture 3). Even with prolonged acute illness lasting several months, complete resolution of hepatitis usually occurs(6). • Duration of abnormal ALT levels in children is brief, rarely exceeding 2 or 3 weeks(7). The serum bilirubin value usually becomes abnormal when ALT reaches peak levels. • The following tests are available for the detection of hepatitis A antibody : IAHA, RIA and EIA. Initially, RIA anti-HAV is predominantly IgM; later it is exclusively IgG(8,9).

7. OBJECTIVE • A hepatitis A vaccine is available, but is not routinely given as part of a child's normal immunization schedule(10). Viral hepatitis A is infection and inflammation of the liver caused by a virus hepatitis A(Picture 4). This type of hepatitis is usually spread in Bosnia by fecal-oral contact, or fecal-infected food and water, and may also be spread by blood-borne infection which is rare(11)(Picture 5). • Fatal fulminant hepatitis A may occur, but it is an extraordinarly rare phenomenon(12). Chronic hepatitis were no cases reported. • The management of patients with acute hepatitis involves decisions about duration of the bed rest, choice of diet and value of various nonspecifics drugs(13,14).

8. AIM • Aims of this article is showing neccesity including Hepatitis A vaccination in routinely schedule in Bosnia and Herzegovina in kids becouse this country after aggresion war 1992-1995 has one of the highest rate in Europe. Second, Hepatitis A is bigger problem in Bosnia becouse poverty and bad sewage system don't ensure in some parts of country protection for children's health and morbidity. Third treatment of hepatitis A is insufficient and too expensive(15).

9. METHODS • The diagnosis of viral hepatitis usually is based on clinical and epidemiological grounds in Sarajevo and all country Bosnia and Herzegovina. We collected laboaratory data of presence of IgM-specific anti HAV indicates hepatitis A infection where it was possible with exanimation and pediatricians-doctors reports during period 1993 (second war year) until 2007(15 years). Blood test results can usually determine exactly what type of hepatitis child has, but the test takes several days in capital city Sarajevo (16) . Authors used Sigmastat stistics Programme for analyses and Microsoft Office Excel 2003 for graphs and diagrams construction. We excluded all kids cases without serologics confirmation what no case in war’s time. Report for hospitals (three hospital and clinic in Sarajevo for infectious diseases and specially for hepatitis A sick kids) where in function of explanations of morbidity in children. All reports of vaccination showed only periodics vaccination with bad coverage without routine schedule programme(17). Some epidemics situation recently in Vogošća near Sarajevo 2006 and in Bosnian Krajina or Central Bosnia in the beginning of this millenium or in Sarajevo during 1993-1994 showed insufficient vaccination by hepatitis A vaccine.

10. RESULTS • Children under 6 years old often have no symptoms(18). Teens and adults usually have symptoms. Complications are fulminant hepatitis is rare: 0.2% of cases in Sarajevo of hepatitis. Hepatitis A vaccination coverage rates for children aged 18--36 months are lower than overall rates for other vaccines recommended for children in Bosnia and Herzegovina. No routine schedule and temporary action after the epidemiologics situation showed bad level of vaccination (only less 1% to 7% percent of population depends of part Bosnia and Herzegovina)(Figure 1, Figure 2A, 2B, 2C, 2D, 2E, 2F,2G). Results showed that area with history of epidemics hepatitis A or parts with better standard has more percent of vaccinated kids(as munipalicity Sarajevo specially Center Sarajevo with 7%)(Figure 3). Cause of this is higher number children from abroad and children who were refuges in Europe and they came back home with their parents. No exactly facts for all parts of Bosnia, no computer electronic documentation, only assesstments of regional parts of Bosnia and Herzegovina.

11. RESULTS • Splits of results and its distribution didn't depend from political dividing of country, it was used natural and specifics regional caracteristics of seven parts of Bosnia( Sarajevo region, East Bosnia, Herzegovina, Bihać region, Central Bosnia-Zenica region, Tuzla region and Banja Luka region) and comparasion in ten munipalicity of Sarajevo. Some estimation and assessment didn't cover political arteficial abnormal partition of country. Results of complication in hospitals were too high if we compared with epidemiological reports(19). Results showed only relative number and percentage becouse exactly documentations were not accurate for assessment in absulute numbers. The well defined autumn-winter seasonal incidence has changed, no consistent seasonal patterns have been observed. . Mortality is higher than other parts of Europe and estimated from 0.19 in peace time to 0.26 in war's times.In prelicensure clinical trials of both Havrix (GlaxoSmithKline, Rixensart, Belgium) and Vaqta (Merck & Co Inc, Whitehouse Station, NJ), adverse events were uncommon and mild when they occurred, with resolution typically in less than 1 day.

12. DISCUSSION • The duration of protection may exceed seven years after only one dose and eleven years after receiving a booster dose(20,21). Models of antibody decline suggest that protection may actually exceed twenty years(22). A study of vaccination of children as young as five months of age showed that immunogenicity was excellent when the mothers were anti-HAV negative, but titers only a tenth as good were seen when children to born anti-HAV positive mothers, suggesting some interference by antibody (23,24). Vaccination coverage also varied by ethnicity, urbans economics situations, epidemiologics situations and pediatrics departments in public health system in each part of Canton Sarajevo. Higher coverage among Gypsy population , Chinese and Bosniacs refugees children, becouse vaccination is not obligate in schedule program.Hepatitis A vaccine is contraindicated in children with a history of severe allergic reaction to a previous dose of hepatitis A vaccine or to a vaccine component. Because the hepatitis A vaccine is an inactivated product, no special precautions are needed for administration to kids who are immunocompromised.

13. CONCLUSIONS • Although no age group is immune the highest incidence in civilian populations occurs among persons less than 15 years of age(25-27). The geographic distribution of hepatitis A is worldwide. It is endemic parts of the world such as the Mediterran that Bosnia and Herzegovina belongs. Usually this vaccine (Havrix) is given to children in areas at high risk for getting the disease or to children over age two years traveling outside the Bosnia(28-30). If a child has been exposed to hepatitis, an antibody preparation can be administered to help protect them from contracting the disease. In the Bosnia and Herzegovina, hepatitis A can occur in situations ranging from isolated cases of disease to widespread epidemics. Fatal fulminant hepatitis A may occur, but it is an extraordinarly rare phenomenon. Mortality is higher than other parts of Europe and estimated from 0.19 in peace time to 0.26 in war's times. The well defined autumn-winter seasonal incidence has changed, no consistent seasonal patterns have been observed.Hepatitis A vaccination is being targeted successfully to children at higher risk of infection; however, overall vaccination coverage remains lower for hepatitis A vaccination, compared with other routine childhood vaccinations.

14. REFERENCE • 1.Hepatitis in USA http://www.cdc.gov/ncidod/diseases/hepatitis/ for information about hepatitis in the United States 2007. • 2.Borkowsky W. Viral Hepatitis. In Gellis&Kagan's Current Pediatric Therapy 116-118. W.B.Saunders company An Imprint of Elsevier Science, Philadelphia, London, New York, St. Louis, Sydney, Toronto, 17th edition, 2003. • 3.Hochman JA, Balistreri WF. Viral hepatitis : Expanding the alphabet. Adv Pediatr 46:207-243, 1999. • 4.Laufer M, Siberry G. Hepatitis. In Comprehensive Pediatric Hospital Medicine. 68. Mosby Inc. Elsevier. Philadelphia, Pennsylvania. 2007. • 5.Berenguer M et al. Viral Hepatitis. In Fieldman M et al, editors. Sleisenger and Fordtans’ gastrointestinaland liver disease, ed 7, Philadelphia , 2002 Saunders. • 6.Demmler GJ. Hepatitis. In Feign RD, Cherry JD (eds). Textbook of Pediatric Infectious Diseases, 5th ed. Philadelphia, WB Saunders, 2004. • 7.Koff RS. Hepatitis A. Lancet 35: 1643-1649, 1998. • 8.Hoofnagle JH, Lindsay KL. Acute viral hepatitis . In Goldman L, Ausiello D, editors: Cecil textbook of medicine, ed 22, Philadelphia, 2004, Saunders. • 9.Huang JS, Kleinman RE. Hepatitis A. In Gellis&Kagan's Current Pediatric Therapy 611-612. W.B.Saunders company An Imprint of Elsevier Science, Philadelphia, London, New York, St. Louis, Sydney, Toronto, 17th edition, 2003 • 10.American Academy of Pediatrics. Active and passive immunization. In Pickering LK (ed). 2003 Red Book: Report of the Committee o Infectious Diseases, ed 26. Elk grove Village, Ill:American Academy of Pediatrics, 2003. • 11.Hall AJ. Hepatitis in travellers. Epidemiology and prevention. Br Med Bull 49:382. 1993. • 12.Snyder JD, Pickering LK. Hepatitis through E. In Nelson Textbook of Pediatrics. 221. W.B. Saunders Company. Philadelphia, London, Toronto, Montreal, Sydney, Tokyo. 17th edition, 2004 • 13.Hasse JM, Matarese LE. Disease of liver. Hepatitis A. In Krause's Food&Nutrition Therapy Chapter 28 international Edition 12.Saunders Elsevier, St Louis, 2008. • 14. McCullough AJ, Tavill AS. Disordered energy and protein metabolism in liver disease, Semin Liver Dis 11:265,1999. • 15. Palmer A, Feldman S. Passive Immunization for Infectious Diseases In Gellis&Kagan's Current Pediatric Therapy 213-214. W.B.Saunders company An Imprint of Elsevier Science, Philadelphia, London, New York, St. Louis, Sydney, Toronto, 17th edition, 2003. • 16.Wald ER, Marcy MS. Infections in Daycare Environments Hepatitis A In Gellis&Kagan's Current Pediatric Therapy 219. W.B.Saunders company An Imprint of Elsevier Science, Philadelphia, London, New York, St. Louis, Sydney, Toronto, 17th edition, 2003. • 17. Recommended childhood and adolescent immunization schedule. In Gershon AA, Hotez PJ, Katz SL Krugman’s Infectious Diseases of Children. 11 ed. B. 995-999, Mosby An Affiliate of Elsivier, Inc, Philadelphia 2004. • 18.Borkowsky W, Krugman S. Viral hepatitis: A, B, C, D,E and newer hepatitis agents. In Gershon AA, Hotez PJ, Katz SL Krugman’s Infectious Diseases of Children. 11 ed. 42: 817-853, Mosby An Affiliate of Elsivier, Inc, Philadelphia 2004. • 19.Wright R. Viral hepatitis: Comparative epidemiology. Br Med Bull 46:548, 1999. • 20.Bancroft WH. Hepatitis A vaccine.N Engl J Med 327:488, 1992. • 21.Craig AS, Schaffner W. Prevention of hepatitis A with the hepatitis A vaccine. N Engl J Med 2004; 350:476-481. • 22.Cardell K, Åkerlind B, Sällberg M, Frydén A (2008). "Excellent response rate to a double dose of the combined Hepatitis A and B vaccine in previous nonresponders to Hepatitis B vaccine". J Infect Dis 198 (3): 299–304. doi:10.1086/589722 • 23.Van Damme P, Van Herck K (2007). "A review of the long-term protection after hepatitis A and B vaccination". Travel Med Infect Dis 5 (2): 79–84. doi:10.1016/j.tmaid.2006.04.004. PMID 17298912 • 24. Immunization Action Coalition (September 2007). "Hepatitis A & B Vaccines (Be sure your patient gets the correct dose!)". • 25. Bell BP, Shapiro CN, Margolis HS. Hepatitis A virus. In: Textbook of Pediatric Infectious Diseases. 2004:2069-86. • 26. AAP. Hepatitis A vaccine recommendations. Pediatrics. Jul 2007;120(1):189-99. [Medline]. • 27. AAP. Hepatitis A. In: Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2006:326-35. • 28. CDC. Notice to readers: FDA approval of Havrix (hepatitis A vaccine, inactivated) for persons aged 1-18 years. MMWR. December 9, 2005;54(48):1235-1236. [Full Text]. • 29. Frenck RW. Universal hepatitis A immunization recommendation made by ACIP. AAP News. 2005;26 (12):1. [Full Text]. • 30. Jacobs RJ, Greenberg DP, Koff RS, et al. Regional variation in the cost effectiveness of childhood hepatitis A immunization. Pediatr Infect Dis J. Oct 2003;22(10):904-14

15. DR MED ADNAN BAJRAKTAREVICPEDIATRICIAN SARAJEVOBOSNIA AND HERZEGOVINATHANKS!!! . France 2008 Nice

16. Figure 1 Graphic

17. Legend-Region (Natural) of Bosnia and Herzegovina • 1. SARAJEVO REGION • 2. CENTRAL BOSNIA-ZE-DO-TRAVNIK • 3. TUZLA REGION • 4. EAST BOSNIA • 5. HERZEGOVINA • 6. BANJA LUKA REGION • 7. BIHAC REGION

18. Figure 2 Graphic 2A

19. Figure 2 Graphic 2B

20. Figure 2 Graphic 2C

21. Figure 2 Graphic 2D

22. Figure 2 Graphic 2E

23. Figure 2 Graphic 2F

24. Figure 2 Graphic 2G

25. Figure 3 Graphic

26. Legend- Munipalicity of SARAJEVO • 1. CENTER SARAJEVO • 2. OLD TOWN • 3. NEW SARAJEVO • 4. NEW TOWN • 5. VOGOSCA • 6. ILIDZA • 7. ILIJAS • 8. HADZICI • 9. TRNOVO BJELASNICA REGION (NO FACTS)

27. Picture 1 Hepatitis A Electronic Photo Microscopy • *

28. Picture 2 Hepatitis A virus • *

29. Picture 3Clinical course of Hepatitis A disease • .

30. Picture 4Hepatitis A prevalence in world • *

31. Picture 5-Bosnia and Herzegovina-Population dispersity • *