The document discusses hepatitis B virus (HBV) infection and the hepatitis B vaccine. Some key points: - HBV is a major global health problem that can cause acute and chronic liver disease. It is transmitted through blood and bodily fluids. - The hepatitis B vaccine is highly effective and provides long-lasting protection against HBV infection. It has been part of routine infant vaccination programs worldwide since the 1990s. - Vaccination is also recommended for at-risk groups like healthcare workers, injection drug users, and those with multiple sexual partners to prevent HBV transmission.

1. Vaccines D-r Mitova MU-Sofia

2. Hepatitis B and Hepatitis B vaccine Epidemic jaundice described by Hippocrates in 5th century BCE Jaundice reported among recipients of human serum and yellow fever vaccines in 1930s and 1940s Australian antigen described in 1965 Serologic tests developed in 1970s

3. Hepatitis B Virus Hepadnaviridae family (DNA) Numerous antigenic components Humans are only known host May retain infectivity for at least 1 month at room temperature

4. Hepatitis B Virus Infection > 200 million carriers worldwide Established cause of chronic hepatitis and cirrhosis Human carcinogen—cause of up to 80% of hepatocellular carcinomas

5. HBsAg HBcAg HBeAg Hepatitis B Virus

6. Hepatitis B Clinical Features Incubation period 6 weeks to 6 months (average 120 days) Nonspecific prodrome of fever, malaise, headache, myalgia Illness not specific for hepatitis B At least 50% of infections asymptomatic

7. Symptoms HBeAg anti-HBe Total anti-HBc IgM anti-HBc anti-HBs HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titre

8. Hepatitis B Complications Fulminant hepatitis Hospitalization Cirrhosis Hepatocellular carcinoma Death

9. Chronic Hepatitis B Virus Infection Chronic viremia Responsible for most mortality Overall risk 10% Higher risk with early infection

10. Risk of Chronic HBV Carriage by Age of Infection

11. Hepatitis B Epidemiology Reservoir Human. Endemic Transmission Bloodborne Subclinical cases transmit Communicability 1-2 months before and after onset of symptoms Chronic carriers

12. Hepatitis B Perinatal Transmission If mother positive for HBsAg and HBeAg 70%-90% of infants infected 90% of infected infants become chronic carriers If positive for HBsAg only 20% of infants infected 90% of infected infants become chronic carriers *in the absence of postexposure prophylaxis

13. Global Patterns of Chronic HBV Infection High ( > 8%): 45% of global population lifetime risk of infection >60% early childhood infections common Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups

15. Age of Infection of Acute and Chronic Hepatitis B Virus Infection Acute infection Chronic infection CDC Sentinel Sites.

16. Risk Factors for Hepatitis B CDC Sentinel Sites. 2001 data.

17. Hepatitis B Virus Infection by Duration of High-Risk Behavior 0 3 6 9 12 15 Years at Risk 0 20 40 60 80 100 Percent infected IV drug user Homosexual men HCWs Heterosexual

18. Strategy to Eliminate Hepatitis B Virus Transmission Prevent perinatal HBV transmission Routine vaccination of all infants Vaccination of children in high-risk groups Vaccination of adolescents Vaccination of adults in high-risk groups

19. Hepatitis B Vaccine 1965 Discovery of Australian antigen 1973 Successful HBV infection of chimpanzees 1981 Licensure of plasma-derived vaccine 1986 Licensure of recombinant vaccine 1991 Universal infant vaccination 1996 Universal adolescent vaccination

20. Hepatitis B Vaccine Composition Recombinant HBsAg Efficacy 95% (Range, 80%-100%) Duration of Immunity >15 years Schedule 3 Doses Booster doses not routinely recommended

21. Hepatitis B Vaccine Formulations Recombivax HB (Merck) - 5.0 mcg/0.5 mL (pediatric) - 10 mcg/1 mL (adult) - 40 mcg/1 mL (dialysis) Engerix-B (GSK) - 10 mcg/0.5 mL (pediatric) - 20 mcg/1 mL (adult)

22. Protection* by Age Group and Dose * Anti-HBs antibody titer of 10 mIU/mL or higher ** Preterm infants less than 2 kg have been shown to respond to vaccination less often *** Factors that may lower vaccine response rates are age >40 years, male gender, smoking, obesity, and immune deficiency 90%-95% 98%-100% 3 75%-80% 80%-95% 2 20%-30% 16%-40% 1 Teens and Adults*** Infants** Dose

23. Recommended Dose of Hepatitis B Vaccine Infants and children <11 years of age Adolescents 11-19 years Adults > 20 years (16) Recombivax HB Dose (mcg) 0.5 mL (5) 0.5 mL (5) 1.0 mL (10) Engerix-B Dose (mcg) 0.5 mL (10) 0.5 mL (10) 1.0 mL (20)

24. Hepatitis B Vaccine.Long-term Efficacy Immunologic memory established following vaccination Exposure to HBV results in anamnestic anti-HBs response Chronic infection rarely documented among vaccine responders

25. Hepatitis B Vaccine Routine booster doses are NOT routinely recommended for any group

26. Hepatitis B Vaccine Recommendations Year 1981 1991 1995 Recommendation Persons at high risk All infants Adolescents

27. Indications for Hepatitis B Vaccine Infants Adolescents 11-12 years of age Selected adults

28. Dose Primary 1 Primary 2 Primary 3 Usual Age 0 months 1 months 6 months Minimum Interval - - - 4 weeks 8 weeks* Hepatitis B Vaccine Routine Infant Schedule *and at least 16 weeks after the first dose

29. Very Low Birthweight Infants Infants <2000 grams respond poorly to vaccine Delay first dose until chronological age 1 month if mother HBsAg negative Birth dose and HBIG if mother HBsAg positive

30. Pediarix DTaP – Hep B – IPV combination Approved for 3 doses at 2, 4 and 6 months Not approved for booster doses Licensed for children 6 weeks to 7 years of age

31. Pediarix May be used interchangeably with other pertussis-containing vaccines if necessary Can be given at 2, 4, and 6 months in infants who received a birth dose of hepatitis B vaccine (total of 4 doses) May be used in infants whose mothers are HBsAg positive or status not known

32. Hepatitis B Vaccine Adolescent Vaccination Routine vaccination recommended through age 18 years Integrate into routine adolescent immunization visit Flexible schedules

33. Dose Primary 1 Primary 2 Primary 3 Minimum Interval - - - 4 weeks 8 weeks* Usual Interval --- 1 month 5 months Hepatitis B Vaccine Adolescent and Adult Schedule *third dose must be separated from first dose by at least 16 weeks

34. Adult Hepatitis B Vaccine Candidates Men who have sex with men Heterosexual with multiple partners Prostitutes Injection drug users Inmates of long-term correctional facilities Persons receiving dialysis Healthcare workers

35. Adult Hepatitis B Vaccine Candidates Staff of institutions for developmentally disabled Alaskan Natives, Pacific Islanders Immigrants/refugees* Adoptees, orphans, unaccompanied minors* Household members and sexual partners of HBV carriers Extended travel to areas of high endemicity Recipients of certain blood products *from countries of high or intermediate HBV endemnicity

36. Prevaccination Serologic Testing Not indicated before routine vaccination of infants or children May be considered when vaccinating adolescents in groups with high rates of HBV infection Alaskan Natives Pacific Islanders Children of immigrants from endemic countries Family members of HBV carriers

37. Postvaccination Serologic Testing Not routinely recommended following vaccination of infants, children, adolescents, or most adults Recommended for: Infants born to HBsAg+ women Dialysis patients Immunodeficient persons Certain healthcare workers

38. Postvaccination Serologic Testing Healthcare workers who have contact with patients or blood should be tested for antibody after vaccination.

39. Management of Nonresponse to Hepatitis B Vaccine Complete a second series of three doses Should be given on the usual schedule of 0, 1 and 6 months Retest 1-2 months after completing the second series

40. Persistent Nonresponse to Hepatitis B Vaccine <5% of vaccinees do not develop anti-HBsAg after 6 valid doses May be nonresponder or &quot;hyporesponder&quot; Check HBsAg status If exposed, treat as nonresponder with postexposure prophylaxis

41. Prevention of Perinatal Hepatitis B Virus Infection Begin treatment within 12 hours of birth Hepatitis B vaccine (first dose) and HBIG at different sites Complete vaccination series at 6 months of age Test for response at 9-15 months of age

42. Twinrix Combination hepatitis B (adult dose) and hepatitis A vaccine (pediatric dose) Schedule: 0, 1, 6-12 months Approved for persons > 18 years

43. Hepatitis B Vaccine Adverse Reactions Pain at injection site Mild systemic complaints (fatigue, headache) Temperature >99.9 ° F (37.7 ° C) Severe systemic reactions Adults 13%-29% 11%-17% 1% rare Infants and Children 3%-9% 0%-20% 0.4%-6% rare

44. Hepatitis B Vaccine Contraindications and Precautions Severe allergic reaction to a vaccine component or following a prior dose Moderate or severe acute illness

45. Tuberculosis HIV/AIDS, TB and malaria kill 6 million people every year; nearly 2 million deaths are caused by TB 2 billion people — one third of the world's population — are infected with TB bacilli, the microbes that cause TB. 1 in 10 people infected with TB bacilli will become sick with active TB in their lifetime; people with HIV are at a much greater risk Almost 9 million new TB cases occurred in 2004 — 80% of them in 22 countries

46. Persons at Risk for Developing TB Disease Those who have been recently infected Those with clinical conditions that increase their risk of progressing from LTBI to TB disease Persons at high risk for developing TB disease fall into 2 categories

48. Bacillus of Calmette and Guérin (BCG) is a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially cultured in an artificial medium for years. The bacilli have retained enough strong antigenicity to become a somewhat effective vaccine for the prevention of human tuberculosis. At best, the BCG vaccine is 80% effective in preventing tuberculosis for a duration of 15 years.

49. BCG Contraindications Contraindicated in persons with impaired immune response from HIV infection Congenital immunodeficiency Leukemia Lymphoma Generalized malignancy Receiving high-dose steroid therapy Receiving alkylating agents Receiving antimetabolites Receiving radiation therapy

51. After having the injection, it is normal to develop a red lump over the injection site.

52. It is not necessary to cover the site with a bandage unless it oozes

53. This may increase in size for a few weeks before settling down into a scab.

54. BCG vaccine may cause side effects . swollen lymph nodes small red areas at the site of injection. (These usually appear 10-14 days after injection and slowly decrease in size. They should disappear after about 6 months.) fever blood in the urine frequent or painful urination upset stomach vomiting

55. Testing for M. tuberculosis Mantoux tuberculin skin test (TST) Skin test that produces delayed-type hypersensitivity reaction in persons with M. tuberculosis infection

56. Administering the TST Inject 0.1 ml of 5 TU PPD tuberculin solution intradermally on volar surface of lower arm Produce a wheal 6 to 10 mm in diameter

57. Reading the TST (1) Measure reaction in 48 to 72 hours Measure induration, not erythema Record reaction in millimeters, not “negative” or “positive” Ensure trained health care professional measures and interprets the TST

58. TST Interpretation (1) 5-mm induration is interpreted as positive in HIV-infected persons Close contacts to an infectious TB case Persons with chest radiographs consistent with prior untreated TB

59. TST Interpretation (2) 5-mm induration is interpreted as positive in (cont.) Organ transplant recipients Other immunosuppressed patients (e.g., those taking the equivalent of >15 mg/d of prednisone for 1 month or those taking TNF- α antagonists )

60. TST Interpretation (3) 10-mm induration is interpreted as positive in Recent immigrants Injection drug users Residents or employees of congregate settings Mycobacteriology laboratory personnel

61. TST Interpretation (4) 10-mm induration is interpreted as positive in (cont.) Persons with clinical conditions that place them at high risk Children < 4 years; infants, children, and adolescents exposed to adults at high-risk

62. TST Interpretation (5) Persons with no known risk factors for TB.* *Although skin testing programs should be conducted only among high-risk groups, certain individuals may require TST for employment or school attendance. Diagnosis and treatment of LTBI should always be tied to risk assessment. 15-mm induration is interpreted as positive in ____________________________________________________

63. Factors That May Cause False-Positive TST Reactions Nontuberculous mycobacteria Reactions caused by nontuberculous mycobacteria are usually  10 mm of induration BCG vaccination Reactivity in BCG vaccine recipients generally wanes over time; positive TST result is likely due to TB infection if risk factors are present

64. Factors That May Cause False-Negative TST Reactions (1) Anergy Inability to react to a TST because of a weakened immune system Usefulness of anergy testing in TST-negative persons who are HIV infected has not been demonstrated

65. Factors That May Cause False-Negative TST Reactions (2) Recent TB infection Defined as 2 to 10 weeks after exposure Very young age Newborns

66. Factors That May Cause False-Negative TST Reactions (3) Live-virus vaccination For example, measles or smallpox Can temporarily suppress TST reactivity Overwhelming TB disease Poor TST administration technique For example, TST injection too shallow or too deep, or wheal is too small

67. DTaP Vaccination Pertussis Highly contagious respiratory infection caused by Bordetella pertussis Outbreaks first described in 16th century Bordetella pertussis isolated in 1906 Estimated 285,000 deaths worldwide in 2001

68. Whole-Cell Pertussis Vaccine Developed in mid-1930s and combined as DTP in mid-1940s 70%-90% efficacy after 3 doses Protection for 5-10 years Local adverse reactions common

69. Acellular Pertussis Vaccine (DTaP) Purified &quot;subunit&quot; vaccines Intended to reduce adverse reactions Licensed for fourth and fifth doses in 1991 Licensed for full series in 1996

70. Diphtheria Greek diphtheria (leather hide) Recognized by Hippocrates in 5th century B.C. Epidemics described in 6th century C. diphtheriae described by Klebs in 1883 Toxoid developed in 1920s

71. Corynebacterium diphtheriae Aerobic gram-positive bacillus Toxin production occurs only when C. diphtheriae infected by virus (phage) carrying tox gene If isolated, must be distinguished from normal diphtheroid

72. Tetanus First described by Hippocrates Etiology discovered in 1884 by Carle and Rattone Passive immunity used for treatment and prophylaxis during World War I Tetanus toxoid first widely used during World War II

73. Clostridium tetani Anaerobic gram-positive, spore-forming bacteria Spores found in soil, dust, animal feces; may persist for months to years Multiple toxins produced with growth of bacteria Tetanospasmin estimated human lethal dose = 2.5 ng/kg

74. Tetanus Clinical Features Incubation period; 8 days (range, 3-21 days) Three clinical forms: Local (not common), cephalic (rare), generalized (most common) Generalized tetanus: descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms Spasms continue for 3-4 weeks; complete recovery may take months

75. Neonatal Tetanus Generalized tetanus in newborn infant Infant born without protective passive immunity High fatality rate without therapy Estimated >215,000 deaths worldwide in 1998

76. Tetanus Complications Laryngospasm Fractures Hypertension Nosocomial infections Pulmonary embolism Aspiration Death

77. Tetanus Epidemiology Reservoir Soil and intestine of animals and humans Transmission Contaminated wounds Tissue injury Temporal pattern Peak in summer or wet season Communicability Not contagious

78. Tetanus Toxoid Formalin-inactivated tetanus toxin Schedule Three or four doses + booster Booster every 10 years Efficacy Approximately 100% Duration Approximately 10 years Should be administered with diphtheria toxoid as DTaP, DT, or Td

79. Routine DTaP Primary Vaccination Schedule (Pentaxim in Bulgaria) Dose Primary 1 Primary 2 Primary 3 Primary 4 Age 2 months 3 months 4 months 16-24 months Interval --- 4 wks 4 wks 6 mos

80. 6 years ( DTaP polio) Tetraxim 12 years of age (Td) 17 years of age (Td) Every 10 years thereafter (Td) Booster Doses

81. Routine Td Schedule Unvaccinated Persons > 7 Years of Age Booster dose every 10 years Dose Primary 1 Primary 2 Primary 3 Interval --- 4 wks 6-12 mos

82. Diphtheria and Tetanus Toxoids Adverse Reactions Local reactions (erythema, induration) Exaggerated local reactions (Arthus-type) Fever and systemic symptoms not common Severe systemic reactions rare

83. Diphtheria and Tetanus Toxoids Contraindications and Precautions Severe allergic reaction to vaccine component or following prior dose Moderate or severe acute illness

84. DTaP Adverse Reactions Local reactions Low grade fever More severe adverse reactions not common Local reactions more common following 4 th and 5 th doses

85. Adverse Reactions Following the 4th and 5th DTaP Dose Local adverse reactions and fever increased with 4th and 5th doses of DTaP Reports of swelling of entire limb Extensive swelling after 4th dose NOT a contraindication to 5th dose

86. DTaP Contraindications Serious allergic reaction to vaccine component or following prior dose Encephalopathy occurring within 7 days after vaccination not due to another identifiable cause

87. DTaP Precautions Moderate or severe acute illness Temperature > 40 C or higher within 48 hours with no other identifiable cause Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours Persistent, inconsolable crying lasting > 3 hours, occurring within 48 hours Convulsions with or without fever occurring within 3 days *may consider use in outbreaks

88. Pertussis Vaccine Use in Children with Underlying Neurologic Disorders Underlying Condition Prior seizure Suspected neurologic disorder Neurologic event between doses Stable/resolved neurologic condition Recommendation Delay and assess* Delay and assess* Delay and assess* Vaccinate * vaccinate after treatment initiated and condition stabilized

89. Tetanus Wound Management * Yes, if >10 years since last dose ** Yes, if >5 years since last dose Vaccination History Unknown or <3 doses 3+ doses Td TIG Yes No No* No Td TIG Yes Yes No** No Clean, minor wounds All other wounds