• • • • VIRAL HEPATITIS • •1970 •1960 A “Infectious” “Serum” Viral hepatitis Enterically transmitted Parenterally transmitted other • E “NANB” • B • D;1977 • C •VIRAL HEPATITIS •HISTORICAL PERSPECTIVE Before the discovery of hepatitis A virus (HAV) and hepatitis B virus (HBV) during the 1960s and 1970s, patients with viral hepatitis were classified based on epidemiological studies as having either infectious (transmitted person to person by the fecal-oral route) or serum (transmitted by transfusion of blood products) hepatitis. When diagnostic tests for HAV and HBV infections were developed, HAV was found to be the major cause of infectious hepatitis and HBV was found to be the major cause of serum hepatitis. Hepatitis delta virus (HDV), discovered in 1977, is a defective virus requiring the presence of HBV in order to replicate. However, some patients with typical signs and symptoms of viral hepatitis did not have serologic markers of HAV, HBV, or HDV infection and were categorized based on epidemiological characteristics as having either parenterally transmitted non-A, non-B (NANB) hepatitis or enterically transmitted NANB hepatitis. Subsequently, two additional viruses were discovered: hepatitis C virus (HCV) and hepatitis E virus (HEV). HCV is the major cause of parenterally transmitted NANB and HEV is the major cause of enterically transmitted NANB hepatitis. In addition, some patients with typical signs and symptoms of acute viral hepatitis do not have serologic markers of any of these types of viral hepatitis and can be classified as having non-ABCDE hepatitis. New viruses might be discovered in patients with non-ABCDE hepatitis. •VIRAL HEPATITIS A • • • •HEPATITIS A VIRUS This is an electron micrograph of HAV that causes hepatitis A. See the next slide for specifics about this virus. HEPATITIS A VIRUS •RNA Picornavirus ·Single serotype worldwide ·Acute disease and asymptomatic infection •No chronic infection ·Protective antibodies develop in response to infection - confers lifelong immunity Hepatitis A is caused by HAV, a 27-nm ribonucleic acid (RNA) agent that is classified as a picornavirus. Only one serotype has been observed among HAV isolates collected from various parts of the world. HAV causes both acute disease and asymptomatic infection. HAV does not cause chronic infection. Total antibody to HAV develops in response to infection and confers lifelong immunity from future HAV infection. •HEPATITIS A - CLINICAL FEATURES •Jaundice by <6 yrs <10% age group: 6-14 yrs 40%-50% >14 yrs 70%-80% •Rare complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis •Incubation period: Average 30 days Range 15-50 days •Chronic sequelae: None The average incubation period for hepatitis A is 30 days, with a range of 15 to 50 days. Patients characteristically have abrupt onset of symptoms which can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The severity of clinical disease associated with HAV infection increases with increasing age; jaundice occurs among less than 10% of children younger than 6 years of age, 40%-50% of older children, and 70%-80% of adults. Complications of hepatitis A include fulminant hepatitis, in which the case fatality rate can be greater than 50% despite medical interventions such as liver transplantation; cholestatic hepatitis, with very high bilirubin levels that can persist for months; and relapsing hepatitis, in which exacerbations can occur weeks to months after apparent recovery. Chronic infection does not occur following HAV infection. • 0 •1 •2 •3 •4 •5 •6 •7 •8 •9 •10 •11 •12 •13 •Week • •Clinical illness • •ALT •IgM •IgG •HAV in stool •Infection • •Viremia •EVENTS IN HEPATITIS A VIRUS INFECTION The diagnosis of acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of IgM antibodies to HAV (IgM anti-HAV). IgM anti-HAV is generally present 5-10 days before the onset of symptoms and is no longer detectable in the vast majority of patients 6 months later. IgG anti-HAV, which also appears early in the course of infection, remains detectable for the lifetime of the individual and confers lifelong protection against infection. Commercial tests are available for the detection of IgM and total (IgM and IgG) anti-HAV in serum. In infected persons, HAV replicates in the liver, is excreted in bile, and is shed in the stool. Peak infectivity occurs during the 2-week period before onset of jaundice or elevation of liver enzymes, when the concentration of virus in stool is highest. The concentration of virus in stool declines after jaundice appears. Children and infants can shed HAV for longer periods than adults, up to several months after the onset of clinical illness. Chronic shedding of HAV in feces does not occur; however, shedding can occur in persons who have relapsing illness. Viremia occurs soon after infection and persists through the period of liver enzyme (alanine aminotransferase [ALT]) elevation. HAV RNA can be detected in the blood and stool of most persons during the acute phase of infection by using nucleic acid amplification methods, such as PCR, and nucleic acid sequencing has been used to determine the relatedness of HAV isolates. These methods, however, are available in only a limited number of research laboratories and are not used generally for diagnostic purposes. • • •CONCENTRATION OF HEPATITIS A VIRUS •IN VARIOUS BODY FLUIDS •Source: Viral Hepatitis and Liver Disease 1984;9-22 • J Infect Dis 1989;160:887-890 •Feces •Serum •Saliva •Urine •100 •102 •104 •106 •108 •1010 •Infectious Doses per mL Feces can contain up to 10^8 infectious virions per milliliter and are the primary source of HAV. Viremia occurs during the preclinical and clinical phases of illness, and HAV has been transmitted by transfusion (before screening of blood and blood products for HAV was initiated) and by injection drug use. Virus has also been found in saliva and urine during the incubation period in experimentally infected animals, but transmission by saliva or urine has not been reported to occur. •Is estimated that in 2013 HAV caused 14 900 deaths. • •The severity of clinical disease associated with HAV infection increases with increasing age; jaundice occurs among less than: q10% of children younger than 6 years of age, q40%-50% of older children, and q70%-80% of adults. •Complications of hepatitis A include fulminant hepatitis, in which the case fatality rate can be greater than 50% despite medical interventions such as liver transplantation; cholestatic hepatitis, with very high bilirubin levels that can persist for months; and relapsing hepatitis, in which exacerbations can occur weeks to months after apparent recovery. Chronic infection does not occur following HAV infection. • GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION • • HAV infection prevalence is high or intermediate in the areas noted in red, blue, and green. Hepatitis A vaccine is recommended for persons who travel or work in these areas. Yellow indicates the areas where HAV infection prevalence is low (including the United States). HAV infection prevalence is very low in the areas shown in tan. Note: This slide has been generalized from available data. ACUTE HEPATITIS A CASE DEFINITION FOR SURVEILLANCE – –Clinical criteria An acute illness with: •discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting), and •jaundice or elevated serum aminotransferase levels –Laboratory criteria •IgM antibody to hepatitis A virus (anti-HAV) positive –Case Classification •Confirmed. A case that meets the clinical case definition and is laboratory confirmed or a case that meets the clinical case definition and occurs in a person who has an epidemiologic link with a person who has laboratory-confirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15-50 days before the onset of symptoms). Trends in acute viral hepatitis can be monitored through cases reported to surveillance systems using a standard case definition. The surveillance case definition for acute hepatitis A includes both clinical and laboratory criteria. The clinical criteria consist of an acute illness with discrete onset of symptoms AND presentation of jaundice OR elevated liver enzymes. The laboratory criterion is IgM anti-HAV positivity. In addition, the case definition can be met if the person meets the clinical criteria and had an epidemiological link with a person who has laboratory-confirmed hepatitis A (i.e., household or sex contact with an infected person during the 15-50 days before the onset of symptoms). All patients who meet this case definition should be reported to the local or state health department. Case reports of acute hepatitis A are then transmitted weekly by state health departments to CDC via the National Electronic Telecommunications System for Surveillance (NETSS). • • • §Close personal contact (e.g., household contact, sex contact, child day-care centers) •Contaminated food, water (e.g., infected food handlers) •Blood exposure (rare) (e.g., injection drug use, rarely by transfusion) • •HEPATITIS A VIRUS TRANSMISSION Transmission of HAV generally occurs when susceptible persons put anything in their mouths that has been contaminated with the feces of an infected person. Close personal contact is the most common mode of HAV transmission, as demonstrated by infections among household and sex contacts of persons with hepatitis A and among children in day-care center outbreaks. Contaminated food and water can also serve as vehicles of HAV transmission. HAV transmission can occur when an infected food handler directly handles uncooked or cooked foods. Outbreaks have also been reported in association with foods contaminated before wholesale distribution, such as fresh vegetables contaminated at the time of harvesting or processing. HAV transmission can occur as a result of blood exposures such as injecting drug use or blood transfusion because viremia can occur prior to the onset of illness in infected persons. Screening of blood products for HAV has essentially eliminated the already extremely low risk associated with transfusion. •RISK FACTORS ASSOCIATED WITH •REPORTED HEPATITIS A, •1990-2000, UNITED STATES •Source: NNDSS/VHSP From 1990 through 2000, the most frequently reported source of infection was personal contact (household or sex) with an infected person (14%). Two percent of cases involved a child or employee in day-care; 6% of cases were a contact of a child or employee in day-care; 5% of cases reported recent international travel; and 4% of cases reported being part of a recognized foodborne outbreak. Injection drug use was a reported risk factor in 6% of cases; men who have sex with men represented 10% of cases. Forty-six percent of reported hepatitis A cases could not identify a risk factor for their infection. Note: Risk factor percentages rounded to nearest percent PREVENTING HEPATITIS A • •Hygiene (e.g., hand washing) •Sanitation (e.g., clean water sources) •Hepatitis A vaccine (pre-exposure) •Immune globulin (pre- and post-exposure) – – Good hygienic practices and adequate sanitation are important elements in the prevention of HAV infection, particularly in the developing world. However, hepatitis A vaccine is the key component in the overall strategy to prevent HAV infection in the United States. Immune globulin is also available for pre-exposure and post-exposure prophylaxis. PREPARATION OF INACTIVATED HEPATITIS A VACCINES •Cell culture adapted virus grown in human fibroblasts • •Purified product inactivated with formalin • •Adsorbed to aluminum hydroxide adjuvant In the United States, highly immunogenic and efficacious inactivated hepatitis A vaccines were first licensed in 1995 by the Food and Drug Administration (FDA). These vaccines are prepared by methods similar to those used for inactivated poliovirus vaccine. Cell culture-adapted virus is propagated in human fibroblasts, purified from cell lysates by ultrafiltration and exclusion gel chromatography or other methods, inactivated with formalin, and adsorbed to an aluminum hydroxide adjuvant. •Highly immunogenic •97%-100% of children, adolescents, and adults have protective levels of antibody within 1 month of receiving first dose; essentially 100% have protective levels after second dose • •Highly efficacious •In published studies, 94%-100% of children protected against clinical hepatitis A after equivalent of one dose • • HEPATITIS A VACCINES The two inactivated vaccines licensed in the United States, HAVRIX^® * (manufactured by GlaxoSmithKline) and VAQTA^® * (manufactured by Merck & Co., Inc.), are highly immunogenic. Approximately 97%-100% of children, adolescents, and adults develop protective levels of antibody within 1 month after the first dose of vaccine; essentially 100% of vaccinees develop protective antibody with high geometric mean concentrations after completing the two-dose series. The vaccines are highly efficacious: In published studies, 94%-100% of children were protected against clinical hepatitis A after receiving the equivalent of one dose. *Use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services. DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION •Persistence of antibody •At least 5-8 years among adults and children •Efficacy –No cases in vaccinated children at 5-6 years of follow-up •Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years •Other mechanisms, such as cellular memory, may contribute Among adults and children, studies have demonstrated that detectable antibody persists for at least 5-8 years after completing the vaccination series. Although data regarding long-term efficacy are limited, no cases among vaccinated children were observed in one community at 5-6 years of follow-up. Estimates of antibody persistence derived from mathematical models of antibody decline indicate that protective levels of anti-HAV persist for at least 20 years. Whether other mechanisms such as cellular memory also contribute to long-term protection is unknown. •VIRAL HEPATITIS B • • • • • •The hepatitis B virus is a DNA virus belonging to the Hepadnaviridae family of viruses. VIRAL HEPATITIS TYPE B •Hepatitis B virus, HBV, Hepadnavirus, the so-called Dane particle with a core (formed by DNA, DNA polymerase, and a nucleocapsid protein with the hepatitis B core antigen (HBcAg) and a coat of hepatitis B surface antigen (HBsAg) ). The whole virus is infectious with a diameter of 42 nm. • •Two months in the ende of incubation period, the sick or carriers. •Parenteral transmission - blood, blood products and inoculation of the infectious material are of principal significance in the transmission. •Professional risk to medical personnel (injury by needle - transmission in 7 - 30 %, contaminated instruments, blood transfusions - transmission in 90 %). •i.v. drug addicts - injury during tattooing, possibly other minute injuries of the skin and mucosa. •By sexual intercourse in homosexuals, bisexuals, and prostitutes. •Vertical - perinatal transmission from mother to child when the mother is the virus carrier or the sick person. About 95 % of newborns infect intranatally and 5 % intrauterinely. • •General • • • •General The source of infection Route of transmission Susceptibility • Etiology: Preventive measures: • VIRAL HEPATITIS TYPE B • • • Preventive measures: Health education - to emphasize the extent of risk Observance of epidemic measures in medical establishments. Handling biological material and contaminated instruments, consistent disinfection and sterilization, application of single-use needles and syringes, use of closed hemodialysis systems, smoking and drinking in workplaces with biological material is forbidden. Postexposure prophylaxis - passive and active immunization (newborns). Examination of blood-donors - exclusion of HBsAg carriers from blood donation Designation and inspection of sanitary-epidemic measures in non-medical establishments (hair-dressing salons, barber shops, etc.) Active immunization in persons with a high risk of infection (stated by public notice) . . •The disease occurs worldwide. •In 2013, HBV caused: v686 000 deaths, including 68 600 deaths from fulminant hepatitis, v300 000 deaths from hepatocellular carcinoma v317 400 deaths from cirrhosis •with a very high burden among an estimated 280 million carriers (prevalence 3,7 %). •The symptoms can vary greatly and many of those infected with HBV never develop any symptoms at all. •Those who do get symptoms (30-50% of cases) usually suffer from tiredness, loss of appetite, abdominal discomfort, nausea, vomiting and fever. The vast majority of healthy adults who get acute hepatitis B will recover with no liver damage in 4–12 weeks but the death rate can reach 2% in the elderly. Chronic infection is most likely to develop in young babies. •The disease occurs worldwide. •In 2013, HBV caused: v686 000 deaths, including 68 600 deaths from fulminant hepatitis, v300 000 deaths from hepatocellular carcinoma v317 400 deaths from cirrhosis • •Estimated - 280 million carriers (prevalence 3,7 %). •The symptoms can vary greatly and many of those infected with HBV never develop any symptoms at all. •Those who do get symptoms (30-50% of cases) usually suffer from tiredness, loss of appetite, abdominal discomfort, nausea, vomiting and fever. The vast majority of healthy adults who get acute hepatitis B will recover with no liver damage in 4–12 weeks but the death rate can reach 2% in the elderly. •Chronic infection is most likely to develop in young babies. •Incubation period: Average 60-90 days • Range 45-180 days •Clinical illness <5 yrs, <10% (jaundice): >5 yrs, 30%-50% •Acute case-fatality rate: 0.5%-1% •Chronic infection: <5 yrs, 30%-90% >5 yrs, 2%-10% •Premature mortality from chronic liver disease: 15%-25% • • • •Hepatitis B – Clinical Features Outcome of HBV Infection Infection Asymptomatic Symptomatic acute hepatitis B Resolved Immune Chronic infection Asymptomatic Cirrhosis Liver cancer Resolved Immune Chronic infection Asymptomatic Cirrhosis Liver cancer • •Weeks after Exposure • 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 [SLIDE 34] Acute Hepatitis B Virus Infection with Recovery: Typical Serologic Course Serologic markers of HBV infection vary depending on whether the infection is acute or chronic. The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30‑60 days) after exposure to HBV. In persons who recover, HBsAg is no longer detectable in serum after an average period of about 3 months. HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity. A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti‑HBc) in serum; IgM anti‑HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti‑HBc persists indefinitely as a marker of past infection. Anti‑HBs becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti‑HBs following acute infection generally indicates recovery and immunity from reinfection. • •IgM anti-HBc •Total anti-HBc •HBsAg •Acute •(6 months) •HBeAg •Chronic •(Years) •anti-HBe •0 •4 •8 •12 •16 •20 •24 •28 •32 •36 •52 •Weeks after Exposure •Progression to Chronic Hepatitis B Virus Infection •Typical Serologic Course [SLIDE 35] Progression to Chronic Hepatitis B Virus Infection: Typical Serologic Course In patients with chronic HBV infection, both HBsAg and IgG anti‑HBc remain persistently detectable, generally for life. HBeAg is variably present in these patients. The presence of HBsAg for 6 months or more is generally indicative of chronic infection. In addition, a negative test for IgM anti‑HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV infection. • • • • • • •Sexual •Parenteral •Perinatal • •HBV Modes of Transmission 45216 006015D • • • • • • • •Low/Not •High •Moderate •Detectable •semen •serum •vaginal fluid •blood •wound exudates •saliva •urine •feces •sweat •tears •breast milk •Concentration of HBV •in Various Body Fluids • • • • • §Prevent perinatal HBV transmission §Routine vaccination of all infants §Vaccination of children in high-risk groups §Vaccination of adolescents —all children up through age 18 §Vaccination of adults in high-risk groups •Strategy •Elimination of HBV Transmission, United States [SLIDE 47] Elimination of Hepatitis B Virus Transmission, United States: Strategy The hepatitis B elimination strategy includes the following components: 1) preventing perinatal HBV transmission by screening all pregnant women for hepatitis B surface antigen (HBsAg) and providing hepatitis B immune globulin (HBIG) and hepatitis B vaccine to infants of HBsAg‑positive mothers; 2) providing hepatitis B vaccine to all infants as part of the routine childhood vaccination schedule; 3) making special efforts to provide catch‑up vaccination for children in high risk groups, including Alaska Natives, Pacific Islanders and infants of immigrants from countries with a high prevalence of chronic HBV infection; 4) providing hepatitis B vaccine to adolescents, including a) all previously unvaccinated children at 11‑12 years of age and b) adolescents of all ages who are at high risk for infection (see adult high‑risk groups below); and 5) vaccinating adults in high‑risk groups including a) men and women with a history of other sexually transmitted diseases and persons who have a history of multiple sex partners (>1 partner/6 months), b) household contacts and sex partners of persons with chronic HBV infection and health care and public safety workers who have exposure to blood in the workplace, d) clients and staff of institutions for the developmentally disabled, e) international travelers who plan to spend >6 months in countries with high rates of HBV infection and who will have close contact with the local population, f) injecting drug users, g) sexually active homosexual and bisexual men, and h) recipients of clotting‑factor concentrates. •Licensed in 1982; currently recombinant (in US) • •3 dose series, typical schedule 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart) • •2 dose series (adult dose) licensed by FDA for 11-15 year olds (Merck) • •Protection ~30-50% dose 1; 75% - 2; 96% - 3; lower in older, immunosuppressive illnesses (e.g., HIV, chronic liver diseases, diabetes), obese, smokers • •Hepatitis B Vaccine Vaccine advisory groups that have endorsed this strategy include the Immunization Practices Advisory Committee to the U.S. Public Health Service (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Physicians (ACP). •Routine infant •Ages 11-15 “catch up”, and through age 18(VFC eligible) •Over 18 – high risk –Occupational risk (HCWs) –Hemodyalisis patients –All STD clinic clients –Multiple sex partners or prior STD –Inmates in Correctional settings –MSM –IDU –Institution for developmental disability •Pre-vaccination testing – if cost effective •Post-vaccination testing – 1-2 months after last • shot, if establishing response critical (HCW) Hepatitis B Vaccination ACIP Recommendations VIRAL HEPATITIS C VIRAL HEPATITIS TYPE C B • •Hepatitis C virus is a RNA-virus measuring 50 nm. It is classed into a separate genus, Hepacavirus of the Flaviviridae family. • • •Long-term in viremia (in the ende IP), chronic infections. • • • • •Parenteral transmission. Sporadically, vertical and sexual transmissions were reported carrier or the sick person. • • •Susceptibility is general. • • • The source of infection Route of transmission Susceptibility • Etiology: Preventive measures: The same as for HBV, exclusive immunization. • Features of Hepatitis C Virus Infection •Incubation period Average 6-7 weeks • Range 2-26 weeks •Acute illness (jaundice) Mild (<20%) •Case fatality rate Low •Chronic infection 60%-85% •Chronic hepatitis 10%-70% (most asx) •Cirrhosis <5%-20% •Mortality from CLD 1%-5% •Age- •related Chronic Hepatitis C Factors Promoting Progression or Severity •Increased alcohol intake • •Age > 40 years at time of infection • •HIV co-infection • •Other –Male gender –Chronic HBV co-infection • • • • •Serologic Pattern of Acute HCV Infection •with Recovery •Symptoms +/- •Time after Exposure •anti-HCV •ALT •Normal •0 •1 •2 •3 •4 •5 •6 •1 •2 •3 •4 •Years •Months •HCV RNA • •Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection • •Symptoms +/- •Time after Exposure •anti-HCV •ALT •Normal •0 •1 •2 •3 •4 •5 •6 •1 •2 •3 •4 •Years •Months •HCV RNA • • Exposures Known to Be Associated With HCV Infection •Injecting drug use •Transfusion, transplant from infected donor •Occupational exposure to blood –Mostly needle sticks •Iatrogenic (unsafe injections) •Birth to HCV-infected mother •Sex with infected partner –Multiple sex partners – Injecting Drug Use and HCV Transmission •Highly efficient –Contamination of drug paraphernalia, not just needles and syringes •Rapidly acquired after initiation –30% prevalence after 3 years –>50% after 5 years •Four times more common than HIV • Posttransfusion Hepatitis C •All volunteer donors •HBsAg •Donor Screening for HIV Risk Factors •Anti-HIV •ALT/Anti-HBc •Anti-HCV •Improved •HCV Tests •Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997 • Occupational Transmission of HCV •Inefficient by occupational exposures •Average incidence 1.8% following needle stick from HCV-positive source –Associated with hollow-bore needles •Case reports of transmission from blood splash to eye; one from exposure to non-intact skin •Prevalence 1-2% among health care workers –Lower than adults in the general population –10 times lower than for HBV infection HCV Related to Health Care Procedures • •Recognized primarily in context of outbreaks –Chronic hemodialysis –Hospital inpatient setting –Private practice setting –Home therapy •Unsafe injection practices –Reuse of syringes and needles –Contaminated multiple dose medication vials – Perinatal Transmission of HCV •Transmission only from women HCV-RNA positive at delivery –Average rate of infection 6% –Higher (17%) if woman co-infected with HIV –Role of viral titer unclear •No association with –Delivery method –Breastfeeding •Infected infants do well –Severe hepatitis is rare Sexual Transmission of HCV •Case-control, cross sectional studies –Infected partner, multiple partners, early sex, non-use of condoms, other STDs, sex with trauma, BUT –MSM no higher risk than heterosexuals •Partner studies –Low prevalence (1.5%) among long-term partners •infections might be due to common percutaneous exposures (e.g., drug use), BUT –Male to female transmission more efficient •more indicative of sexual transmission Sexual Transmission of HCV •Occurs, but efficiency is low –Rare between long-term steady partners –Factors that facilitate transmission between partners unknown (e.g., viral titer) •Accounts for 15-20% of acute and chronic infections •Sex is a common behavior –Large chronic reservoir provides multiple opportunities for exposure to potentially infectious partners Household Transmission of HCV •Rare but not absent •Could occur through percutaneous/mucosal exposures to blood –Contaminated equipment used for home therapies •IV therapy, injections –Theoretically through sharing of contaminated personal articles (razors, toothbrushes) Other Potential Exposures to Blood •No or insufficient data showing increased risk –intranasal cocaine use, tattooing, body piercing, acupuncture, military service •No associations in acute case-control or population-based studies •Cross-sectional studies in highly selected groups with inconsistent results –Temporal relationship between exposure and infection usually unknown –Biologically plausible, but association or causal relationship not established • Sources of Infection for Persons With Hepatitis C •Sexual 15% •Other 1%* •Unknown 10% •Injecting drug use 60% •Transfusion 10% •(before screening) •* Nosocomial; iatrogenic; perinatal •Source: Centers for Disease Control and Prevention •Occupational 4% Reduce or Eliminate Risks for Acquiring HCV Infection •Screen and test donors •Virus inactivation of plasma-derived products •Risk-reduction counseling and services –Obtain history of high-risk drug and sex behaviors –Provide information on minimizing risky behavior, including referral to other services –Vaccinate against hepatitis A and/or hepatitis B •Safe injection and infection control practices •MMWR 1998;47 (No. RR-19) Reduce Risks for Disease Progression and Further Transmission •Identify persons at risk for HCV and test to determine infection status –Routinely identify at risk persons through history, record review •Provide HCV-positive persons –Medical evaluation and management –Counseling •Prevent further liver damage •Prevent transmission to others • •HCV Prevention and Control •MMWR 1998;47 (No. RR-19) HCV Testing Routinely Recommended •Ever injected illegal drugs •Received clotting factors made before 1987 •Received blood/organs before July 1992 •Ever on chronic hemodialysis •Evidence of liver disease • •Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood •Children born to HCV-positive women •Based on increased risk for infection •Based on need for exposure management Postexposure Management for HCV •IG, antivirals not recommended for prophylaxis •Follow-up after needlesticks, sharps, or mucosal exposures to HCV-positive blood –Test source for anti-HCV –Test worker if source anti-HCV positive •Anti-HCV and ALT at baseline and 4-6 months later •For earlier diagnosis, HCV RNA at 4-6 weeks –Confirm all anti-HCV results with RIBA •Refer infected worker to specialist for medical evaluation and management • • Routine HCV Testing of Uncertain Need •Recipients of transplanted tissue •Intranasal cocaine or other non-injecting illegal drug users •History of tattooing, body piercing • •History of STDs or multiple sex partners •Long-term steady sex partners of HCV-positive persons • •Not confirmed as risk factor/prevalence low or unknown • •Confirmed risk factor but prevalence of infection low HCV Infection Testing Algorithm for Diagnosis of Asymptomatic Persons Screening Test for Anti-HCV •Negative •STOP •Positive •OR RIBA for Anti-HCV •NAT for HCV RNA •Negative •STOP Additional Laboratory Evaluation (e.g. PCR, ALT) •Negative •Positive •Indeterminate Medical Evaluation •Positive •Negative PCR, •Normal ALT •Positive PCR, •Abnormal ALT •Source: MMWR 1998;47 (No. RR 19) Mother-to-Infant Transmission of HCV •Postexposure prophylaxis not available •No need to avoid pregnancy or breastfeeding –Consider bottle feeding if nipples cracked/bleeding •No need to determine mode of delivery based on HCV infection status •Test infants born to HCV-positive women –>15-18 months old –Consider testing any children born since woman became infected –Evaluate infected children for CLD •HCV Counseling •Persons with One Long-Term Steady Sex Partner •HCV Counseling Sexual Transmission of HCV •Do not need to change their sexual practices •Should discuss with their partner –Risk (low but not absent) of sexual transmission –Counseling and testing of partner should be individualized •May provide couple with reassurance •Some couples might decide to use barrier precautions to lower limited risk further – •Persons with High-Risk Sexual Behaviors •HCV Counseling Sexual Transmission of HCV •At risk for sexually transmitted diseases, e.g., HIV, HBV, gonorrhea, chlamydia, etc. •Reduce risk –Limit number of partners –Use latex condoms –Get vaccinated against hepatitis B –MSMs also get vaccinated against hepatitis A – Other Transmission Issues •HCV not spread by kissing, hugging, sneezing, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact •Do not exclude from work, school, play, child-care or other settings based on HCV infection status •HCV Counseling •VIRAL HEPATITIS D • • • • • • •Hepatitis D (Delta) Virus • •HBsAg •RNA •d antigen > • • • • • • • • •Coinfection –severe acute disease –low risk of chronic infection •Superinfection –usually develop chronic HDV infection –high risk of severe chronic liver disease • • •Hepatitis D - Clinical Features • • • • • • •Percutanous exposures –injecting drug use •Permucosal exposures –sex contact • • •Hepatitis D Virus •Modes of Transmission • • • • • • •HBV - HDV Coinfection •Typical Serologic Course •Time after Exposure •anti-HBs •Symptoms •ALT Elevated •Total anti-HDV •IgM anti-HDV •HDV RNA •HBsAg • • • • • • •HBV - HDV Superinfection •Typical Serologic Course •Time after Exposure •Jaundice •Symptoms •ALT •Total anti-HDV •IgM anti-HDV •HDV RNA •HBsAg • • • • • • •Geographic Distribution of HDV Infection •HDV Prevalence •High •Intermediate •Low •Very Low •No Data •Taiwan •Pacific Islands • • • • • • •HBV-HDV Coinfection •Pre or postexposure prophylaxis to prevent HBV infection •HBV-HDV Superinfection •Education to reduce risk behaviors among persons with chronic HBV infection • • •Hepatitis D - Prevention •VIRAL HEPATITIS E • • • • • • > •Hepatitis E Virus • • • • • • • •Hepatitis E - Clinical Features • •Incubation period: Average 40 days • Range 15-60 days •Case-fatality rate: Overall, 1%-3% Pregnant women, 15%-25% •Illness severity: Increased with age •Chronic sequelae: None identified • • • • • • •Hepatitis E Virus Infection •Typical Serologic Course •Weeks after Exposure •Symptoms •ALT •IgG anti-HEV •IgM anti-HEV •Virus in stool •0 •1 •2 •3 •4 •5 •6 •7 •8 •9 •10 •11 •12 •13 • • • • • • •Most outbreaks associated with fecally contaminated drinking water •Minimal person-to-person transmission •U.S. cases usually have history of travel to HEV-endemic areas • • •Hepatitis E - •Epidemiologic Features • • • • • • •Geographic Distribution of Hepatitis E •Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis > • • • • • • •Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler •IG prepared from donors in Western countries does not prevent infection •Unknown efficacy of IG prepared from donors in endemic areas •Vaccine? • • •Prevention and Control Measures for Travelers to HEV-Endemic Regions Key characteristics of HAV, HBV, HCV, HDV, HEV A B C D E Causative agent Picornaviridae Hepadnaviridae Raviviridae Deltaviridae Hepeviridae RNA DNA RNA RNA RNA Incubation period 2 – 6 weeks 2 - 6 months 2 - 6 months 3-7 weeks 2 - 10 weks Characteristic of acute hepatitis Case fatality increases with age Acute hepatitis more common in adults Acute hepatitis uncommon, almost never fulminant Superinfection with HDV in chronic heptitis B may lead to fulminnat disease High case fatality in pregnant women -10-20 %; other 1 -2 % Biomarker of recent infection IgM anti-HAV IgM anti-HBc None IgM anti-HDV IgM anti-HEV Chronic infection none Chronic infection leading to sequelae Chronic infection leading to sequelae Chronic hepatitis that copmlicated chronic hepatitis B Very rare Cirrhosis and hepatocelular Ca No Yes; 0,1 -1,0 % are fulminant Yes; 50 % can be fulminant Yes; 5 - 20 % can be fulminant NO The period of infectivity last 2 weeks of incubation period last 2 months of incubation period last 2 months of incubation period ?? ?? first day of acute stage entire period of acute stage entire period of acute stage chronic disease, carriers chronic disease, carriers Infectious biological material faeces blood blood blood faeces viremia - 1. day of illnes genital secretions genital secretions meat of animals Mode of transmission Person-to person Perinatal Blodborne Blodborne Waterborne Foodborne Bloodborne Perinatal Foodborne Waterborne Sexual Sexual Person-to person Imunization Inactivated hepatitis A vaccines are safe and effective for both pre- and post-exposure prophylaxis Active (recombinant vaccine) and passive imunization no no Vaccine licensed in China; not widely available