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HEPATITIS AND THE NEWBORN INFANT. Niraj Patel, MD, MS Department of Pediatrics Section of Infectious Disease Levine Children’s Hospital. Objectives. Know routes of transmission Be able to interpret hepatitis serologies
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HEPATITIS AND THE NEWBORN INFANT Niraj Patel, MD, MS Department of Pediatrics Section of Infectious Disease Levine Children’s Hospital
Objectives • Know routes of transmission • Be able to interpret hepatitis serologies • Know post exposure prophylaxis methods
Total Hepatitis A Hepatitis B Hepatitis C Acute Viral Hepatitis A, B and C by Year, United States, 1952-2000
Acute Viral Hepatitis by Type, 1982-95 2007 53%X 34% X 35% 48% X 9% 15% Hepatitis A Hepatitis B Hepatitis C 3% Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis
Reported Cases of Selected Notifiable Diseases Preventable by Vaccination, United States, 2001 2007 Varicella 22,536 Hepatitis A 10,609 Hepatitis B 7,843 Pertussis 7,580 Meningococcal disease 2,326 H. influenzae, invasive 1,597 Mumps 266 Measles (total) 116 Rubella 23 2,979 4,519
ROUTE OF TRANSMISSION: FECAL - ORAL •Hepatitis E•Hepatitis A
DISEASE BURDEN FROM HEPATITIS AUNITED STATES, 2007 Prevalence of chronic infection: None
HAV-Clinical features • Acute self limited illness • fever, malaise, jaundice, anorexia, nausea • Symptoms in 30% children < 6 years • Usually symptomatic in older children/adults (70% jaundiced) • Fecal-oral route: person-to-person, ingestion of contaminated food or water • Incubation period: 15-50 days • Fulminant hepatitis rare but more frequent in those with underlying liver disease
HAV Diagnosis and Management • HAV total and IgM antibody • Treatment supportive • Post-exposure prophylaxis (household/close contacts)
Post Exposure Prophylaxis for HAV Future Weeks exposure? Age Action§______ 2 No All IG* Yes 1yr IG* HAV vaccine 2 No All None Yes 1yr HAV vaccine § AAP Recommended childhood and adolescent immunization schedule – United States ,2007. Pediatrics. 2007;119:207-8 #IG dose = 0.02ml/kg IM
Newborn Infants of HAV infected mothers • Risk of perinatal transmission rare • IG 0.02ml/kg IM if mother symptomatic within 2 weeks before and one week after delivery; efficacy not established • Severe disease rare in healthy infants
HEV: Epidemiology • Transmitted by fecal-oral route • Contaminated water • Symptoms more common in adults • Sporadic outbreaks Asia, Africa, Mexico • Fecal viral shedding and viremia for 2 weeks after acute infection
Hepatitis E – Clinical Features Incubation period:Average 40 days Range 15-60 days Case-fatality rate:Overall, 1%-3%Pregnant women, 25%-30% Illness severity:Increased with age Chronic sequelae:None
HEV Diagnosis and Treatment • IgM to HEV • HEV RNA by PCR in serum/feces • Supportive Care • Contact precautions • Avoiding potential contaminants • Passive immunoprophylaxis with US prepared immune globulin has not been effective
HCV Epidemiology • Single stranded RNA virus • Multiple genotypes exist • fail to elicit cross neutralizing antibodies in animal models • Incubation period 6-7 weeks (2weeks–6months) • 170 million infected world-wide • Prevalence of 1-2% in women of child-bearing age (CDC)
Risk factors for infection • IV Drug Use • Percutaneous exposure to blood/blood products • hemophilia • haemodialysis patients (10-20%) • risk is 1 in 1 million units of blood transfused • IV and IM immunoglobulin products safe • Sexual transmission (monogamous couples - 1.5%) • Household contacts / HCWs • Perinatal transmission 5-6% • Coinfection with HIV increases risk 17%
HCV Infection, U.S. New infections (cases)/year, 2007 849 Deaths from acute liver failure Rare Persons ever infected (1.8%) 3.9 mill. (3.1-4.8)* Persons with chronic infection 2.7 mill. (2.4-3.0)* Of chronic liver disease - HCV-related 40% - 60% Deaths from chronic disease/year 8,000-10,000 . *95% Confidence Interval
HCV- Clinical features • Acute disease • Indistinguishable from hepatitis • mild and insidious in onset • asymptomatic in most children • Only 25% are jaundiced • fewer abnormalities in LFTs than with HBV
Persistent infection in at least 85% even with normal LFTs Most children with chronic disease are asymptomatic Complications chronic hepatitis cirrhosis Primary hepatocellular carcinoma 40-60% cases of liver transplantation annually HCV (cont)
HCV CHRONIC INFECTION anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Years Months Time after Exposure
HCV Diagnosis • Antibody assays • Screening enzyme immunoassay (EIA) • 80% positive within 5 - 6 weeks of infection(false negative early in infection) • HCV PCR • HCV RNA (highly sensitive) • may be detected intermittently, a single negative is inconclusive • Can detect RNA within 1-2 weeks after exposure
HCV Management • Monitor liver function • Vaccination against Hepatitis A & B (all patients) • Interferon ribavirin in adults • IFN monotherapy sustained response in 10-40% • Combined therapy sustained response in 30-80% • Lower sustained responses in genotype 1 • Interferon-2b + ribavirin in children 3-17 yrs • Referral to specialist in management of HCV
HCV Perinatal transmission • Antenatal screening if risk factors • Transmission occurs in 5-6% (0-25%) • Factors possibly associated with transmission • Maternal HIV co-infection • Maternal viral load during pregnancy unclear • No evidence to date that breast-feeding increases the risk • Mode of delivery not a risk factor
HCV - Perinatally Exposed Infant • PCR testing may identify infected infants earlier but defer until after one month of age* • Maternal passively acquired antibody persists for 18 months - defer antibody testing • Immune globulin for post exposure prophylaxis is not recommended • HBV vaccination (all infants) + HAV vaccination (if infected) • Referral to specialist if infected *Dunn et al. Pediatr Infect Dis J. 2001;20(7):715-6
HEPATITIS B • DNA virus • Circular genome encoding: • 3 envelope proteins (HBsAg) • nucleocapsid proteins • HBeAg - secreted from the infected hepatocyte • HBcAg- translated from the core sequence / not found in serum
Modes of transmission include: • Homosexual/heterosexual activity • Sharing or re-using needles or syringes • Percutaneous/mucous membrane exposure to blood/body fluids • Person to person e.g. household, sharing toothbrushes, razors, skin lesions etc. • Transfusion • Occupational risk • HCW/needlestick • Mother to infant
HBV Clinical Features • Wide spectrum of illness • asymptomatic • subacute illness • non-specific, abnormal LFTs • Clinical hepatitis • 10% immune complex mediated illness • polyarthritis, angiodema • urticaria and jaundice • maculopapular eruptions & glomerular involvement • Clinical hepatitis with jaundice • Fatal fulminant hepatitis
HBV Clinical Features • Incubation period 45-180 days (90 days) • Age at acquisition most important factor in determining chronic infection • 90% perinatally infected infants • 25-50% children infected age 1-5 years • 6-10% older children, adolescents, adults
HBV Chronic Infection • Increased risk of chronic liver disease, cirrhosis, hepatocellular carcinoma • Risk of death is 25% in those acquiring chronic infection in childhood
HBsAganti-HBsTotal anti-HBcInterpretation 1)— + + Resolved infection — 2)+ + Chronic infection 3) — + — Hep B vaccination
HBV Diagnosis and Treatment • Serology • Hybridization and gene amplification assays to measure HBV-DNA correlates with HBeAg and infectivity • TreatmentAdults IFN-2a: remission in 25-40% Lamivudine, adefovir, entecavir Children INF-2a: remission in 35% Lamivudine (2 years and older) • Monitor LFTs, serum fetoprotein, abd US
Perinatal transmission • 70-90% risk of transmission if mother HBsAg and HBeAg+ (a reportable disease) • 90% infants become chronic carriers • 95% of neonatal infections preventable by • HBV vaccination in the neonatal period • Hepatitis B immune globulin • Vaccinate within 12 hours after birth • Breast feeding poses no additional risk to infant
HBV Infection by Year, United States 1982-2005 HBsAg screening of pregnant women recommended HBV Vaccine licensed Infant Immunization recommended Adolescent Immunization recommended Modified from Long et al: Principles and Practice of Pediatric Infectious Diseases, 3ed
Preventing Neonatal Infection • Antenatal screening • early in pregnancy for all women • near delivery for women at high risk
Algorithm for Preventing Neonatal Infection • If term infant (>2kg) and mother HBsAg+ • Then: • HBV vaccine + HBIG within 12 hours at different sites • 2nd, 3rd vaccine doses at 1-2 mo and 6 mo • Test at 9-15 mo for HBsAg and anti-HBs • If negative, reimmunize with 3 doses at 2 mo intervals and retest
Algorithm for Preventing Neonatal Infection • If preterm infant (<2kg) and mother HBsAg+ • Then: • HBV vaccine + HBIG within 12 hours • 1st vaccine dose not counted in series, so infants need 4 doses in total (0, 1, 2-3, 6-7mo)
If term infant and mother HBsAg unknown Then: Test mom ASAP Vaccinate infant within 12h of birth HBIG if mom HBsAg+ within 7 days at birth Algorithm for Preventing Neonatal Infection
Algorithm for Preventing Neonatal Infection • If preterm infants <2kg and mother HBsAg unknown • Then • Test mom ASAP • Vaccinate infant and give HBIG within 12h if mom’s status still unknown • *95% of neonatal transmission can be prevented by following the above guidelines