3rd year 3rd rotation

2. HEPATITIS B

3. HEPATITIS CKAMARULZAMAN BIN MUZAINI 2008402286

4. What Is Hepatitis? Hepatitis is an inflammation of the liver. It may be caused by drugs, alcohol use, or certain medical conditions. But in most cases, it's caused by a virus that infects the liver. This is known as viral hepatitis, and the most common forms are hepatitis A, B, and C introduction

5. Hepatitis A virus is a small, RNA-containing enterovirus (piconavirus) Hepatocyte is the only site of viral replication HAV is identified in stool and liver preparations It can be destroyed by boiling in water for 20-30 min, dry heat, formalin, chlorine and UV radiation Hepatitis A HEPATITIS A VIRUS

6. Fecal-oral transmission Close personal contact (e.g., household contact, child day care centers) Contaminated food and water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion) HEPATITIS A VIRUS TRANSMISSION

7. IP:4 weeks (range 2-6 weeks) Oral cavity -> GI tract (replicates in the alimentary tract and spreads to infect the liver via blood) Replicates in hepatocytes and released via bile to intestines 7-10 days prior to clinical symptoms Liver damage and clinical syndrome result of immune response and not direct effect of virus. HEPATITIS A:PATHOGENESIS

8. Clinical features of hepatitis A, B & C are much or more likely same: Jaundice vomiting, nausea and fever Lost of apetite Pain in area of liver (RUQ) fatigue Severe vomiting can lead to dehydration Most cases resolve spontaneously in 2-4 weeks Complete recovery 99% HEPATITIS A:CLINICAL FEATURES Jaundice in newborn Dark urine

10. Hepatitis A almost always goes away on its own, and no medication is needed Supportive treatment ( relieve symptoms)- no specific role of antiviral therapy Drink water or juice to stay hydrated. And avoid strenuous exercise until symptoms start to improve. Lifelong immunity likely after infection or vaccination HEPATITIS A: TREATMENT

11. General measures- prevention of fecal contamination of food , water and other sources by infected patients Personal hygiene- hand washing before/after meals and after toilet Use of disinfectants to prevent spread of HAV Health education Vaccination – Harvix , contain no live virus and are very safe. HEPATITIS A: PREVENTION AND CONTROL

12. Serum hepatitis or long IP hepatitis It is an enveloped, DNA, hepadnaviridae family 3 important antigens- surface antigen (HBsAg) - core antigen (HBc Ag) - e antigen (HBe Ag) IP- 6weeks to 6 months HEPATITIS B

13. Sexual Parenteral (IVDU) Perinatal (Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not) HEPATITIS B VIRUS: MODE OF TRANSMISSION

14. Virus enters hepatocytes via blood Sensitized Immune response (cytotoxic T cell) to viral antigens that expressed on hepatocyte cell surface responsible for clinical syndrome The virus persists in the hepatocytes and on-going liver damage occurs because of the host immune response against the infected liver cells. 5% become chronic carrier Higher rate of hepatocellular carcinoma in chronic carriers, especially those who are “e” antigen positive Hepatitis B surface antibody likely confers lifelong immunity HEPATITIS B: PATHOGENESIS

15. Acute hepatitis b infection 95% of infant-acquired infections ↓ 3-5% of adult-acquired infections Chronic HBV infection ↓ Chronic hepatitis ↓ 12-25% in 5 yrs Cirrhosis 6-15% in 5 yrs ↙ ↘20-23%in 5 yrs Hepatocellular carcinoma Liver failure ↙ ↘ ↙ ↘ Death Liver transplant Death HEPATITIS B: POSSIBLE OUTCOMES

18. USG

19. CT Scan

21. Lamivudine (reverse transcriptase inhibitor) Adefovir Interferon alfa-2b (inhibit viral growth) HEPATITIS B: TREATMENTS

23. If mother HBsAg positive: HBV vaccine and Hep B immune globulin within 12 hours of birth, 1-2 months, < 6 monthsHEPATITIS B: VACCINE

24. Avoidance of high-risk behavior such as multiple sex partners, homosexual Screening of women in late pregnancy for HBV Active immunization with Hep B vaccine (hepavaxx B) Passive immunization with Hep B Ig before/after exposure -Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions. HEPATITIS B: PREVENTION

25. Small enveloped,single stranded RNA virus, members of flavivirus family Most new infections are subclinical Majority patients develop chronic hepatitis are at risk of progressing to chronic active hepatitis, cirrhosis and high risk of hepatocellular carcinoma HEPATITIS C

26. Injecting drug use Transfusion, transplant from infected donor Occupational exposure to blood (mostly needle sticks) Iatrogenic Birth to HCV-infected mother HEPATITIS C: TRANSMISSION

27. Blood-borne pathogen that infects hepatocytes Much like Hep B, liver damage and clinical illness due to more to elicit immune response as opposed to direct cytopathic effect of the virus Likely cytotoxic T cells that mediate most of the damage Like other chronic liver diseases (Hep B and chronic alcoholism), can cause HCC HEPATITIS C: PATHOGENESIS

30. Recombinant immunoblot assay (RIBA)- looks for 2 or more antibodies to HCV viral antigensHEPATITIS C: DIAGNOSIS

31. Screening and test of donor’s blood or organs Implementation and maintenance of infection control practices in healthcare settings- sterilization of medical and dental equipments Promotion of behavior changes among the general public and health workers to injections and to use safe injection practices Risk reduction counseling for sexual practices No vaccine for HCV HEPATITIS C: PREVENTION

32. The most common treatment for chronic hepatitis C is a combination of antiviral medications called *Pegylatedinterfronalfa *Ribavirin HEPATITIS C: TREATMENT

33. Tuberculosis

34. Etiology Mycobacterium tuberculosis

35. Transmission Respiratory droplets becomes airborne: coughs, sneezes, laughs, sighs or breathes droplet nuclei (dried infected droplet) Vertical transmission (congenital TB) Rare, but suspected if infant born to TB mother fails to thrive or is symptomatic Breast milk is not a source of infection Infective TB mother X breastfeed, but expressed breast milk can be given.

37. NO sputum production (>12yrs old only able to expectorate sputum)

38. lack tussive force necessary to suspend infectious particles of the correct size in the air

41. Clinical Features Nearly half of infants and 90% of older children – minimal signs & symptoms of infection. Latent – my develop into active disease at later time (reduce in immunity Mantoux test – may become positive initiate treament Systemic symptoms (due to CMI): Fever Anorexia & weight loss cough Failure to thirve Night sweats Primary pulmonary TB Hilarlympadenopathy (Ghon complex) : compress bronchia or trachea cause bronchial obstruction, collapse & consolidation of affected lung Dyspnea, Progressive primary disease Primary pneumonia  pulmonary disease/ disseminated miliary disease CNS granulomas  meningitis Most common in 1st year of life Reactivation pulmonary tuberculosis Common in adolescent, typical in adult Fever, night sweats, malaise, & weight loss Productive cough & hemoptysis often herald cavitation & bronchial erosion

42. Extrapulmonary TB Meningitis TB – low grade fever, headache, subtle personality change, photophobia Tuberculosis pericarditis Lymphadenopathy Miliary TB Skeletal TB - hunchback Abdominal TB Urogenital TB – dysuria, frequency, urgency, hematuria, ‘sterile’ pyuria

43. Investigations Pulmonary TB Chest radiographearly morning gastric aspirates Sputum (>12yrs old) Pleural fluid/ biopsy CNS TB CXR CSF for AFB smear & TB culture CT head with contrast TB adenitis CXR Excisional biopsy or FNA Abdominal TB CXR CT abdomen with contrast Biopsy of mass/ mesentric LNs TB osteomyelitis CXR CT/MRI of affected limb Biopsy of affected site Miliary/ Disseminated TB As for pulmonary TB Early morning urine CSF

44. Diagnosis Diagnosis in children is usually difficult. Confirmatory of diagnosis: isolation of M.tuberculosis by culture from appropriate specimens Features suggestive of TB: Recent contact with person (usually adult) with active TB S&S suggestive of TB : Infants – nonspecific symptoms ; low grade fever, cough, weight loss, failure to thrive & signs like wheezing, reduced breath sounds, tachypneoa & occasionally frank respiratory distress Positive Mantoux test Suggestive X-ray: Enlarged hilar lymph nodes +/- localized obstructive emphysema Persistent segmental collapse consolidation not responding to conventional antibiotics Pleural effusion Calcification of LNs, usually >6mnths after infection Laboratory test: Presence of AFB on smears of clinical specimens & positive histopathology or cytology on tissue specimens

47. inactivated antigen; poor storage, inadequate administration

49. Treatment DOTS (directly observed therapy) Short course therapy (6mnths): For pulmonary TB, non-severe extrapulmonary TB [LN disease, unilateral pleural effusion, skin & bone/ joint (single site) excluding spine], x drug resistant TB Intensive phase (2mnths): Daily isoniazid, Rifampicin & Pyrazinamide 4th drug (Ethambutol/ Streptomycin) is added if + initial drug resistance or high burden of organism Maitenance phase (4mnths): Isoniazid & Rifampicin Daily (preferred) / biweekly/ thrice weekly Severe extrapulmonary TB Includes: meningeal, CNS & spinal TB, abdominal TB, bilateral pleural or pericardial effusion, bone & joint TB (>1site) & miliary TB Similar intensive phase (2mnths), diff continuation phase; for 7-10mnths

50. Corticosteroids Indicated : children with TB meningitis Others: pleural & pericardial effusion, severe miliary disease (if hypoxic) & endobronchial disease Only given with appropriate anti-TB therapy Monitoring of drug toxicity Baseline & routine monitoring of serum transaminases & bilirubin only if: Severe TB disease Underlying hepatic disease Other hepatotoxic drugs (anticonvulsant) Clinical symptoms of hepatotoxicity HIV infection Ethambutol: Monitor visual acqutiy & colour discrimination

51. Prevention Contact tracing Screening of family members Chemoprophylaxis: e.g. Isoniazid & Rifampicin for 3mnths BCG (BacilleCalmette-Guerin) immunization: C/I: immunocompromisedpx; HIV (+)ve X full protection ;

52. HIV / AIDS in Paediatrics and Adolescents

53. HIV The human immunodeficiency virus (HIV) is a retrovirus that infects cells of the immune system, destroying or impairing their function. As the infection progresses, the immune system becomes weaker, and the person becomes more susceptible to infections. The most advanced stage of HIV infection is acquired immunodeficiency syndrome (AIDS).

55. Spherical in shape

56. HIV Viral Subtype – HIV-1. HIV-2

57. Single –stranded RNA virus

58. Reverse transcriptase – enables viral RNA to act as template for DNA transcription and integration into host genome.

61. 5 groups of drugs use in HIV patients.

62. HIV Effect to CD4 cell. Depletion of CD4 lymphocytes due to :- Direct cytotoxic effects of HIV replication Cell-mediated immune cytotoxic Thymic damage that impairs lymphocyte production Infected CD4 cells have shorter half live (2days) If CD4 count drop < 200/microL can cause variety of opportunistic pathogen and cause clinical disease.

63. Modes Of Transmission HorizontaL Unprotected heterosexual/homosexual contact IV drug use Contact of abraded skin/mucosa with body secretions eg. blood, semen Blood tranfusion Transplantation VERTICAL Mother to child transplacentally during utero, during birth or breast feeding. (25-30%) Risk factor of perinatal transmission – prematurity, rupture of membranes more than 4 hours and high maternal HIV load

64. Reduction of vertical transmission Elective caesarean section Total substitution of breastfeeding with infant formula. Antiretroviral(ARV) prophylaxis

65. NEW !!! 2010 WHO infant Feeding Guidelines Mothers known to be HIV-infected should be provided with lifelong antiretroviral therapy or antiretroviral prophylaxis interventions to reduce HIV transmission through breastfeeding continue breastfeeding for the first 12 months of life. Exclusive breastfeeding for 6 months. Mixed (complementary) feed after 6 months.

66. Pediatric classification system : immunology categories.

67. Clinical menifestationHIV pediatric classification system : clinical categories.

69. Primary infection Acute retroviral syndrome Incubation period : 2-6 week Lasting for 3-14days May be misdiagnosed as mononucleosis or nonspecific viral syndrome Symptom:- Fever Malaise Weight loss General lymphadenopathy Aseptic meningitis Clinical menifestation

70. HIV in children Clinical features: Persistent lympadenopathy Failure to thrive Recurrent infection(respiratory, skin, GIT) Hepatosplenomegaly Dev. Delay Diagnosis >18month old : 2 consecutive ‘+’ve HIV antibody test <18 month old : 2 ‘+’ve HIV DNA PCR test Monitoring Progression through clinical, immunology(CD4 count) and viral load. CD4 count and viral load after change of ART and every 3-4 month thereafter.

71. Treatments. There are treatments provided to HIV patient BUT it is not a cure. drugs action is to stop people to become more ill for many years. The drug’s aim is to keep the viral amount at the lower level. Drug always reffered to:- antiretrovirals anti-HIV or anti-AIDS drugs HIV antiviral drugs ARVs

72. 5 groups of drugs use in HIV patients.

73. Treatments.(continued) typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART

75. MALARIA MohdIz’aan Hassan bin Haron

76. WHAT IS MALARIA? Malaria is an infectious disease cause by a parasite, Plasmodium which infect RBC. Malaria is characterized by cycle of chills, fever, pain and sweating. 1 million child death in Africa per year

77. TRANMISSION Malaria is a vector-borne disease (female Anophelesmosquito) Parasites Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi

78. INCUBATION PERIOD P. Falciparum : 12 days P. malariae : 30 days P. ovale and P. Vivax : 14 days Inadequate or inappropriate prophylaxis may lengthen.

79. PATHOGENESIS Plasmodium derived energy from anaerobic glycolysis of glucose to lactic acid, contributing to clinical manifestation of hypoglycemia and lactic acidosis. They also make the red cell membrane less deformable, resulting hemolysis & accelerated spleenic clearance, which ultimately contribute to anemia. Alteration to uninfected RBC, such as the addition of P. falciparumglycosylphosphatidylinosotol (GPI) to the membrane may play a role in increase clearance of uninfected cell & contribute to anemia

81. CLINICAL FEATURES

82. DIAGNOSIS Light microscopy of thick and thin stained blood smears Thick smears - diagnose Thin smears – species confirmation blood smear examination of the Red Blood Cells for intracellular malarial parasites. Rapid Malaria Antigen Test Detect species-specific circulating parasite antigen Initial negative result does not exclude malaria

83. Uncomplicated Malaria Symptomatic infection without vital organ dysfunction Complicated Malaria almost always due to P. falciparum suspect mixed infections if vivax / malariae malaria appear unusually severe TYPE OF MALARIA

84. DANGER SIGN OF SEVERE MALARIA changes in behaviour impaired consciousness jaundice parasitaemia > 2% continued vomitting hyperpyrexia oliguria severe metabolic acidosis

85. COMPLICATION OF SEVERE MALARIA cerebral malaria pulmonary edema / ARDS renal failure haemoglobulinemia haemorrhage due to DIVC shock hypoglycaemia severe anemia

86. TREATMENT (P. falciparum) Uncomplicated Malaria 1st Line : Artesunate/mefloquine 2nd Line : Quinine : Clindamycin/Doxycycline Alternative treatment : Artemether / lumefantrine Complicated Malaria 1st line : Artesunate 2nd line : Quinine : Clindamycin/Doxycycline

87. P. VIVAX INFECTION 1st line : Chloroquine, Primaquine If relapse, repeat Chloroquine and primaquine P. KNOWLESI or MALARIAE INFECTION 1st Line : Chloroquine 2nd line : Treat as complicated Plasmodium falciparum MIXED INFECTION Treat as for Plasmodium falciparum TREATMENT

88. PREVENTION Avoid going to endemic area Use bed netting, insecticide MALARIA CHEMOPROPHYLAXIS* Prefered : Mefloquine Alternatif : Doxycycline *Prophylaxis does not eliminate risk of infection *Start one week before travel and continued until 4 weeks after leaving endemic area