Hepatitis E in developing countries
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1 Hepatitis E in developing countries Hepatitis E in developing countries Rakesh Aggarwal Department of Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Forms Epidemic Sporadic Transmission Water-borne Human-to-human Genotypes Genotype 1 Genotype 2 Clinical forms Asymptomatic Acute hepatitis Acute liver failure Transmission Water-borne Human-to-human Special situations During pregnancy In persons with chronic liver disease Hepatitis E: Outbreaks (198-7) Hepatitis E outbreaks: HEV genotypes Reported from 29 countries Aggarwal R. Hepatitis E: Outbreaks in India affecting >1 persons Hepatitis E epidemic: Kanpur, India, 1991 Kashmir 1978, 1979, 1981, 1982 Punjab 5-6 Karnal 1987 Delhi Agra 1953 Ahmedabad 1975, 1982, Baroda 1984 Surat 1985 Beed 199 Karad 1993 Kolhapur 1981, 1991 Shimla Saharanpur Kanpur Kolkata 4 Hyderabad 5 Nellore 8 Sample (n = 3,666) Population (n = 2.1 million) 3.76 % 3.76 % Hepatitis ,91 Deaths 1 48 (13 pregnant women) Mortality.7%.6% Naik SR, et al. Bull WHO 1992; 7: ; Ray R, et al. Lancet 1991; 338:
2 Number of cases Hepatitis E epidemic: Kanpur, India, 1991 Hepatitis E epidemic, Kanpur, 1991: Time course 6 25 No. of cases Failure of chlorination 5 Female 4 Male >6 Age group Dec Jan Feb March April Water contamination May June Naik SR, et al. Bull WHO 1992; 7: Naik SR, et al. Bull WHO 1992; 7: Another hepatitis E outbreak in India Epidemic hepatitis E: Transmission Fecal-oral transmission, often via contaminated water supply systems Person-to-person transmission rare Food borne? Vertical transmission Transmission through blood transfusions Zoonotic transmission? Swain SK et al. Trans R Soc Trop Med Hyg 1; 14: HEV outbreaks: Associated factors HEV outbreaks: Control measures Flooding, heavy rainfall Failure of water treatment systems Use of untreated water from river or spring Hot summer >> reduced river water >> increased contaminants Chlorination of water Water boiling Repair of water pipelines Alternative safer water supply Leaking water pipes, with interrupted water supply Leakage of sewage pipes Improving hygiene (e.g. handwashing practices) Improving sewage disposal 2
3 Africa: Outbreaks in humanitarian emergencies Sporadic hepatitis E (198-7) Outbreaks: In refugee camps (humanitarian emergency/conflict zones) Waterborne infection Large, affecting several persons Mainly adults particularly affected Special features: High disease attack rates Prolonged, lasting several months? Person-to-person (intra-familial) transmission CDC. MMWR Morb Mortal Wkly Rep 13; 62: Howard CM, et al. Am J Trop Med Hyg 1; 83: Aggarwal R. Hepatitis E as percent of sporadic acute viral hepatitis Sporadic hepatitis E in endemic areas Animal in India Cases with acute hepatitis E in the absence of outbreak Similar to epidemic hepatitis E in Epidemiologic features Age, gender distribution Exposure to unclean water Relationship with pregnancy Seasonal occurrence Clinical features Outcomes? Micro-outbreaks not recognized as outbreaks Animal species Shukla P, et al. J Viral Hepat 7; 14: n Number (%) of animals testing positive for IgG anti-hev Modified Genelabs assay ORF 2.1 assay Pig 193 (97) 195 (98) Goat (1) 98 (1) Chicken (98) 84 (98) Sheep (1) 45 (78) Buffalo 3 3 (1) 3 (1) Animal and human HEV in India Epidemic hepatitis E: Clinical spectrum Acute icteric viral hepatitis Asymptomatic infection GT 4 GT 1 GT 3 GT 2 Anicteric hepatitis Fulminant hepatic failure Acute worsening of chronic liver disease Shukla P, et al. J Viral Hepat 7; 14: Aggarwal et al. J Gastroenterol Hepatol 9; 24:
4 Liver function (%) Liver function (%) Liver function (%) Liver function (%) Asymptomatic infection Acute hepatitis () Anicteric hepatitis Icteric hepatitis Acute liver failure HEV superinfection in cirrhosis AVH 8 6 AVH AVH + CLD Acute liver failure in cirrhosis: More often, more severe, longer duration HEV superinfection in cirrhosis Patients (Recent worsening) 18 p<.1 Controls (Stable cirrhosis) Group Sample Hepatitis, n (%) Acute liver failure, n (%) Men 3, (2.8%) 3/17 (2.8%) 3,35 71 (2.1%) /71 (%) (17.3%) 8/36 (22.2%) Positive 14 (43%) Negative Positive 3 Negative (6%) Pregnancy associated with Higher disease attack rate More often severe disease Mortality: 15-25% Trimester I: 8.8% II: 19.4% III: 18.6% Kumar et al. Indian J Gastroenterol 4; 23: Khuroo et al. Am J Med 1981; 7:
5 Aggarwal R. Virus Res 11; 161: Aggarwal R. Virus Res 11; 161: Icteric hepatitis E Icteric hepatitis E Fulminant hepatitis E Aggarwal R. Virus Res 11; 161: Aggarwal R. Virus Res 11; 161: Chronic hepatitis E: not in endemic areas of Asia and Africa Aggarwal R. Virus Res 11; 161: Icteric hepatitis E Fulminant hepatitis E Fatal hepatitis E Naik et al. J Viral Hepatitis 13; : e138-e14. 5
6 Characteristic Hepatitis E: Two different faces Asia and Africa (Developing countries) Europe and N America (Industrialized countries) Virus genotype 1, 2, (4) 3, (4) Transmission Waterborne,? food?, food (animal meat) Reservoir Human Animal Outbreaks Small to very large None to small HEV as % of sporadic hepatitis Common Infrequent Age distribution Young Old Co-existent diseases Infrequent Common High mortality No data Chronic infection No Yes (immunosuppressed) Hepatitis E in Asia and Africa: Estimated disease burden Based on seroprevalence data Assumptions: 19.8% of infections are symptomatic 1.9% of non-pregnant and 19.8% of pregnant women with disease die Outcome Mid-estimate 95% credible interval Upper/lower bound ratio Infections.1 million million 13.3 Symptomatic cases 3.3 million million 13.9 Deaths 69,622 12,4 132, Stillbirths 3, , Rein D. Hepatology 12: 55: Hepatitis E in developing countries: Take-home summary Outbreaks, frequent sporadic cases with acute infection Mainly waterborne, possibly food Affects young people have severe disease with frequent fatal outcome Severe disease also among persons with pre-existing liver disease Caused by genotype 1 or 2 virus Very little or no zoonotic transmission No chronic infection Cause significant preventable human morbidity 6
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