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Epidemiology of hepatitis Presenter : Dr.L.Karthiyayini Moderator: Dr. AbhishekV Raut Framework Introduction Hepatitis A,E,B,C,D&G Magnitude Natural history of the disease Epidemiological determinants Mode of transmission Clinical feature Sero epidemiology Prevention & control Hepatitis & HIV Global policy report on hepatitis-status of India WHO position of hepatitis vaccine Introduction VIRAL HEPATITIS IS A MAJOR PUBLIC HEALTH PROBLEM Hepatitis A & E - 0.5-4 % mortality World wide 500 million people have chronic HBV & HCV infection In India, 45 million people with HBV 500,000 to 1,000,000 people die every year of HBV-related chronic Hepatitis, cirrhosis or liver cancer Out of nearly 22.6 million children born in India every year, over 9 million will acquire the infection in their lifetime. Hepatitis is the inflammation of liver by any cause Viral hepatitis is mainly caused by Hepatitis A & E virus - Faeco-oral route - Acute & self limiting Hepatitis B,C & D virus- Parenteral route -Acute & chronic Other viruses- cytomegalovirus, rubella virus, epstein barr virus, yellow fever virus ,herpes zoster virus,etc. Other hepatitis Alcoholic hepatitis (50% of CLD)(mortality : M11/100000 & F-6/10000) Auto immune hepatitis, toxic & drug induced hepatitis, Natural history of acute hepatits HEPATITIS A Source:CDC MAGNITUDE GLOBAL: Prevalence of anti-HAV antibodies in general population -15%-100% Worldwide 1.5 million clinical cases yearly Outbreaks INDIA: seroprevalence of anti-HAV: 54.5%- high socio-economic status 85% in low socio-economic status EPIDEMIOLOGICAL DETERMINANTS AGENT: Picarnovirus family 4 human genotypes 1 serophytype HOST: Low endemic area Adolescents & adults(homosexual, IV drug users) Travellers Intermediate endemic area Late childhood(faeco oral route) Early adult hood High endemic area Early childhood ENVIRONMENTAL FACTORS: Water borne & food borne epidemics Sanitation & overcrowding MODE OF TRANSMISSION: Faeco-oral route Parentral route – stage of viremia Sexual transmission- homosexual due to ano-oral contact Secondary attack rate among household contacts is 30% INCUBATION PERIOD 28 days CLINICAL FEATURES Symptoms & signs Fever Anorexia Malaise Nausea Abdominal discomfort Dark urine Jaundice Complications: Relapsing hepatitis Cholestatic hepatitis Fulminant hepatitis(0.1%) SERO EPIDEMIOLOGY IgM- Detectable from 5 days prior to onset of symptoms & declines to undetectable levels within 6 months. IgG-Detect previous infection, persists life long Elevated levels of serum bilirubin Elevated hepatic enzymes(AST,ALT) HAV INFECTION-TYPICAL SEROLOGICAL COURSE Source:Yim, H. J., et al., (2006). Hepatology. PREVENTION & CONTROL Control of reservoir: Complete bed rest Disinfection of faeces & fomites 0.5% sodium hypochlorite Control of transmission: promoting personnel & community hygiene Purification of community water supplies Proper sanitation & waste disposal During epidemics, boiling of water is preferred Active immunization Inactivated vaccines & live attenuated vaccines Parenterally (IM), 2 dose,6-18 months apart. Combined vaccine(inactivated hepatitis A & recombinant hepatitis B) -0,1,6 mths. Passive immunization HAV IG –Pre & Post exposure prophylaxis -single I.M dose,0.02 ml/kg within 2 weeks HEPATITIS E MAGNITUDE GLOBAL SEAR INDIA MAHARASHTRA Source:CDC MAGNITUDE GLOBAL: Overall attack rates during hepatitis E outbreaks - 1% to 15%. The rates are highest among young adults (3%-30% Case-fatality rates - 0.5% to 4% During outbreaks mortality rates - 0.07–0.6% INDIA: Proportion- 10% Seroprevalence of anti-HEV antibodies-upto 50% EPIDEMIOLOGICAL DETERMINANTS AGENT Hepatitis E like virus HOST 15-40yrs Pregnant mothers-20% fulminant(0.5% mortality) MODE OF TRANSMISSION: Faeco oral route Water borne disease Ingestion of raw or uncooked shell fish- sporodic cases Vertical transmission Secondary attack rates 0.7-2.2% INCUBATION PERIOD: 2-9 weeks CLINICAL FEATURES Symptoms Abdominal pain Nausea Vomiting Anorexia Signs Jaundice Hepatomegaly SERO EPIDEMIOLOGY Elevated antibody levels-RT-PCR Hepatitis E Virus Typical Serologic Infection Course Symptoms IgG anti-HEV ALT Titer IgM anti-HEV Virus in stool 0 1 2 Source: Yim, H. J., et al., (2006). Hepatology. 3 4 5 6 7 8 9 Weeks after Exposure 1 0 1 1 1 2 1 3 PREVENTION & CONTROL Good personnel hygiene High quality standards of public water supply Proper disposal of sanitary waste Vaccines – undergoing clinical trails HEPATITIS B Source:CDC MAGNITUDE GLOBAL: 2million 240 billion carriers 60-80% of all primary liver cancer High endemicity, intermediate endemicity & low endemicity INDIA: Point prevalence of hepatitis B is 2.1% chronic carrier rate 1.7% HCC 1.6% of all cancers High carrier state among health workers 11% & in general population 5% 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 NATURAL HISTORY OF DISEASE NATURAL HISTORY OF CHRONIC HBV INFECTION - seroepidemiology Source:Yim, H. J., et al., (2006). Hepatology. EPIDEMIOLOGICAL DETERMINANTS AGENT: DNA virus- hepadnaviridae family 3 morphological forms-small spherical particles, tubules & Dane particle(infectious) HBsAg, HBcAg, HBeAg(Viral replication) Only reservoir - Man Infective material-contaminated blood, saliva, vaginal secretions, semen Resistance – stable for 7 days in environmental surface, destroyed by sodium hypochlorite & by heat sterilization 30-60 mins HOST: Age: Acute hepatitis - 1% of perinatal cases,10% of early chidhood, 30% of late childhood Chronic hepatitis – 80-90% -perinatally, 30% in early chilhood, 5% infected after 6 yrs High risk groups: Surgeons have 50% more chance Others- recipients of blood transfusion, health care & laboratory care personnels,percutaneous IV drug abusers, homosexuals, infants of HBV carrier mothers,immunocompromised patients. MODE OF TRANSMISSION Parenteral route -Blood borne disease Perinatal route Sexual transmission Horizontal transmission INCUBATION PERIOD 30-180 days(75 days) COURSE OF SYMPTOMS IN ACUTE HEPATITIS SERO EPIDEMIOLOGY HBsAg: Appears first & persists throughout the illness Indicates infectivity Anti-HBs: Signal recovery, non-infectivity & immunity Anti-HBc: Appears shortly after HBsAg is detected Indicates a diagnosis of acute hepatitis IgM anti-HBc persists for 3-6 mths. Reappears during the flares of previously inactive chronic hepatitis B IgG anti-HBc also appears Persists indefinitely SERO EPIDEMIOLOGY HBeAg: Appears in the incubation period shortly after HBsAg Indicates viral replication & infectivity Persistence beyoun 3 mths – chronic hepatitis B HBV DNA: Parellels the presence of HBeAg Senisitve & precise marker PCR Acute Hepatitis B Virus Infection with Recovery Source:Yim, H. J., et al., (2006). Hepatology. Progression to Chronic Hepatitis B Virus Infection Source:Yim, H. J., et al., (2006). Hepatology. PREVENTION & CONTROL Hepatitis B vaccine Hepatitis B immunoglobulin Passive active immunization Other measures HEPATITIS B VACCINE Recombinant hepatitis B vaccine-1986 Monovalent & Fixed combination(DPT, Hib, hepatitisA, inactivated polio) Storage : 2-8˙C (avoid freezing) Dose: Adults: • 10-20 micrograms • Deltoid Children : • Half the dose • Antero lateral aspect of thigh Schedule: 0,1,6 mths National immunization schedule: 3 dose schedule :At birth, along with 1st & 3rd dose of DPT 4 dose schedule: At birth, 6,10,& 14 weeks Monovalent or combined Minimum interval between the doses are 4 weeks If prevalence is > 8%- within 24 hrs of birth Duration of protection: 15 yrs Protective antibody levels-> 95% (infants, children & young adults) More than 40yrs – protection <90% More than 60yrs- protection 65-75% Low birth weight babies Reduced immunogenicity: Diabetes Chronic renal failure Chronic liver disease HIV infection If interrupted ? as soon as possible restarting not required Recommnended for: < 18 yrs of age High risk group International travellers Contraindicated: H/O allergy to vaccine components Hepatitis B immunoglobulin Immediate protection Used for acutely exposed: surgeons, lab workers, nurses, newborns of carrier mothers, sexual contacts of hepatitis B patients, liver transplanted patients Within 6 hrs-48 hrs Recommended dose: 0.05-0.07 ml/kg (2 doses,30 days apart) Short term passive protection – 3 mths No long term prophylaxis limited availability High cost Risk complications Passive-active immunization Combined HBIG & hepatitis B vaccine more efficacious Recommended: newborn babies of carrier mothers Accidental exposure Dose: 0.05-0.07 ml/kg within24 hrs Hepatitis B vaccine 1.0ml, IM within 7 days of exposure, 2nd & 3rd dose at 1 & 6 months after 1st dose Other measures Screening of blood donors Adequate sterilization Practice simple hygiene measures Carriers- no sharing, barrier contraception, no blood donation HEPATITIS C MAGNITUDE GLOBAL: worldwide 3% infected 3-4 million persons newly infected every year 70% among newly infected- chronic hepatitis INDIA: 1/4th of all chronic liver cases 12.5 million carriers Seroprevalence among donors- 0.48%(Vellore) – 1.85%(Delhi) NATURAL HISTORY OF DISEASE EPIDEMIOLOGICAL DETERMINANTS AGENT: Flaviviridae family 6 genotypes & 100 sub types HOST: High risk group - recipients of blood transfusion, health care personnel, homosexuals, drug abusers & infants of carriers MODE OF TRANSMISSION: Parenteral route Perinatal route Sexual transmission INCUBATION PERIOD: 15-150 days CLINICAL FEATURES 80% -asymptomatic 15-30% - develop jaundice 80% of newly infected develop chronic hepatitis Cirrhosis-10-20% Liver cancer-5-10% (in 20-30 yrs) SERO EPIDEMIOLOGY Enzyme immunosorbant assay(EIA): Detection of HCV specific antibodies Detects 95% of chronic cases & 50-70% of acute cases Recombinant immunoblot assay (RIBA): Identifies antibodies that react with individual HCV antigens Supplement test for confirmation of positive EIA PCR: Confirmation of serological results Assessing effectiveness of antiviral therapy Hepatitis C Virus Infection Typical Serologic Course antiHCV Symptoms Titre ALT Normal 0 1 2 3 4 5 6 Month s Time after Exposure 1 2 3 Years 4 TREATMENT : Interferon alone effective in 10-20% Interferon with Ribavirin effective in 30-50% New therapeutic agents : Telaprevir boceprevir PREVENTION & CONTROL Screening blood donors Virus inactivation in plasma derived products Promotion of behaviour change HEPATITIS D Source:CDC MAGNITUDE GLOBAL: Global pattern corresponds to prevalence of HBV Highest prevalence in Amazon basin & Romania(20% of chronic HBV & 90% of HBV-chronic liver disease) Moderate prevalence-Spain, northern Italy, Turkey & Egypt(asymptomatic HBVcarriers10-20% & 30-50% of HBVchronic liver disease) Low prevalence-southeast Asia & china INDIA: Acute hepatitis-10.7- > 30% Chronic hepatitis-8-21% Cirrhosis-15-19%: EPIDEMIOLOGICAL DETERMINANTS AGENT: RNA virus Satellite virus or sub viral agent HOST: high risk group MODE OF TRANSMISSION: Parenteral route Perinatal route Sexual transmission INCUBATION PERIOD: 30-180 days CLINICAL FEATURES Co-infection: Simultaneous infcetion Acute form of HBV & HDV Self limiting Chronic form -< 5% Super infection: HDV infection of chronically infected HBV Severe acute hepatitis – chronic hepatitis (80%) Associated – fulminant acute hepatitis, severe chronic active hepatitis-cirrhosis HBV - HDV Coinfection Typical Symptoms Serologic Course ALT Elevated Titre anti-HBs IgM anti-HDV HDV RNA HBsAg Total anti-HDV Time after Exposure HBV - HDV Superinfection Typical Serologic Course Jaundice Symptoms Titre Total anti-HDV ALT HDV RNA HBsAg IgM anti-HDV Time after Diagnosis: RT-PCR EIA Treatment: A-interferon (9million units, TDS weekly for 12 months or 5 million units daily for 12 months) Prevention & control: Pre & post exposure prophylaxis of HBV Health education to reduce risk behaviour HEPATITIS G 1995-Flavivirus family GBV-A,GBV-B,GBV-C GBV-C affects man. Transmission : blood transfusion Sexual contact Vertical transmission Intravenous drug users Globally 1-3% in volunteer blood donors Incubation period-30-120 days HGV co-infection is observed in 6% of chronic HBV infections & in 10% of chronic HCV infections. HEPATITIS & HIV About one-third of HIV-infected persons are coinfected with hepatitis B or hepatitis C, which can cause long-term (chronic) illness and death. 10% of 40 million people of HIV are co-infected with HBV Viral hepatitis progresses faster among persons with HIV infected persons HIV/HBV & HIV/HCV coinfection -leading cause of non-AIDS-related deaths HEPATITIS & HIV Coinfection with hepatitis -complicate the management of HIV infection. To prevent coinfection with hepatitis B, universal hepatitis B vaccination of susceptible patients with HIV infection or AIDS & high risk groups is recommended All persons living with HIV should be tested for hepatitis B and hepatitis C Coinfected persons should be counseled about drug interacions and side efects of hepatitis and HIV treatments. Global policy 2010 World Health Assembly – to generate reliable information as a foundation for building prevention and control measures that match the local epidemiological profile and health system capacities. Survey conducted in mid-2012 by the World Health Organization and the World Hepatitis Alliance. Aim : To gather country-specific baseline data on hepatitis policies in WHO Member States in all six regions. offers insight into conditions in specific countries Gaps that need to be filled are identified Issues addressed National coordination Awareness raising & partnerships Evidence based policy & data for action Prevention of transmission Screening care & treatment National coordination Written national strategy plan-raising awareness, surveillance, vaccination, prevention of transmission via injecting drug use, in health-care settings, in general, and treatment and care. There is a designated governmental department : For coordinating and/or carrying out viral hepatitis related activities Four staff members Not known how many people work full-time in all government agencies/bodies. The government has a viral hepatitis prevention and control programme: activities targeting health-care workers, including health-care waste handlers Awareness raising & partnerships Not known whether the government held events for World Hepatitis Day 2012 Funding-other viral hepatitis public awareness campaigns since January 2011. The government does not collaborate with in-country civil society groups to develop and implement its viral hepatitis prevention and control programme Evidence based policy & data for action There is no routine surveillance for viral hepatitis. There are standard case definitions for hepatitis. Hepatitis deaths are not reported to a central registry. No classification:“undifferentiated” or “unclassified” hepatitis HCC & HIV/hepatitis coinfection cases are registered The government does not publish hepatitis disease reports. Hepatitis outbreaks are reported & investigated There is inadequate laboratory capacity nationally to support investigation of viral hepatitis outbreaks There is no national public health research agenda Viral hepatitis serosurveys are not conducted regularly Prevention of transmission There is a national policy that specifically targets mother-to child transmission of hepatitis B There is no national policy on hepatitis A vaccination. The government has not established the goal of eliminating hepatitis B. It is not known what percentage of newborn infants nationally received the 1st dose of hepatitis B vaccine within 24 hours of birth or what percentage of 1yr received 3 doses of hepatitis B vaccine. It is not known whether there is a specific national strategy for preventing hepatitis in health-care settings. Health-care workers are vaccinated against hepatitis B prior to starting work Contd.. There is a national policy on injection safety in health-care settings-auto-disable syringes Single-use or auto-disable syringes, needles and cannulas are always available in all health-care facilities. Official government estimates of the number and percentage of unnecessary injections administered annually in health-care settings are not known. There is a national infection control policy for blood banks. All donated blood products nationwide are screened It is not known whether there is a national policy relating to the prevention of viral hepatitis among people who inject drugs. The government has guidelines that address how hepatitis A and hepatitis E can be prevented through food and water safety. Screening care & treatment Health professionals obtain the skills and competencies through on the job training. Not known -national clinical guidelines for the management The government does not have national policies relating to screening and referral to care for hepatitis B or hepatitis C. People testing are register by name & are kept confidential Hepatitis testing are free of charge for all individuals and are compulsory for blood donors. Publicly funded treatment is not available for hepatitis The following drug for treating hepatitis B & C is on the national essential medicines list: lamivudine & ribavirin respectively The GOI welcomes assistance from WHO in one or more areas of viral hepatitis prevention and control Who position of hepatitis vaccine All infants should receive their first dose preferably within 24 hrs Delivery of hepatitis B vaccine within 24 hours of birth should be a performance measure for all immunization programmes. To complete the primary series the birth dose should be followed by 2 doses or, if convenient, by 3 doses Minimum interval between doses is 4 weeks. There is no evidence to support the need for a booster dose Catch-up vaccination of children should be considered for cohorts with low coverage. The need for catch-up vaccination in older age groups, including adolescents and adults, is determined by the baseline epidemiology of HBV infection in the country. Contd… The importance of vaccinating people with particular risk factors for acquiring HBV infection is emphasized. Eliminating HBV transmission must address- infections acquired perinatally and during early childhood, by teenagers and adults. WHO strongly recommends that all countries develop goals for hepatitis B control Process indicators and the use of outcome measures are critical to verifying achievement goals. Primary tool to measure the impact of immunizationSerological surveys of HBsAg prevalence supplemented by surveillance for acute disease Collection of mortality data REFERENCE 1. Park k., text book of preventive and social medicine, 20th edition; p186 -189 2. Manson’s text book tropical disease;697-713 3. Harrison’s principles of internal medicine.17(2);p1945-1960 4. Berger SA. Infectious Diseases of India, 2012. 503 pages, 67 graphs, 4248 references. Gideon e-books, http://www.gideononline.com/ebooks/country/infectious-diseases-of-india 5. Berger SA. Hepatitis D, E and G: Global Status, 2012. 99 pages, 36 graphs, 1116 references. Gideon e-books, http://www.gideononline.com/ebooks/disease/hepatitis-d-e-and-g-globalstatus/ 6.heahttp://www.who.int/immunization/topics/hepatitis_b/en/index.htmllth 7. Global policy report on the prevention and control of viral hepatitis in WHO Member States. 8. http://www.who.int/immunization/documents/positionpapers/en/index.html 9.The Global Prevalence of Hepatitis A Virus Infection and Susceptibility:A Systematic Review 10. The Global Prevalence of Hepatitis EVirus Infection and Susceptibility:A Systematic Review THANK YOU