Issues

1
Aggarwal Epidemiology of HEV infection

• Issues
• What is the established global epidemiology of
  HEV infection?
• Has there been a recent change in HEV
  epidemiology in the last 5 years?
• What is the role of immunoglobulins in high-risk
  groups till vaccine is available?
• What are the major contributions from Indian
  studies?

2
Hepatitis E global distribution
3
Aggarwal Epidemiology of HEV infection

• Epidemiology
• In endemic regions, two forms a) large outbreaks
  affecting hundreds to thousands b) 30-70 of
  sporadic acute hepatitis
• In non-endemic regions, occasional sporadic
  cases usually related to travel to endemic
  regions some indigenous
• Fecal-oral transmission, often via contaminated
  water supply
• Vertical transmission possible
• Incubation period 2-9 wk
• High attack rate among young adults
• Self-limited course, low mortality (0.07-0.6)
• No chronic infection
• High attack rate and mortality rate among
  pregnant women
• Person-to-person spread uncommon during outbreaks

4
Aggarwal Epidemiology of HEV infection

• Newer knowledge
• HEV infection in animals
• Transmission by transfusions and food
• Subclinical HEV infection among healthy humans
• HEV superinfection in cirrhosis

5
Aggarwal Epidemiology of HEV infection

• HEV antibodies in animals
• Country ve/tested ve Reference
• Nepal 18/55 33 Clayson, 1995
• USA 50/75 70 Meng, 1997
• China 4/21 19 Meng, 1999
• Thailand 3/25 12 Meng, 1999
• Korea 12/20 60 Meng, 1999
• Canada 46/172 27 Meng, 1999
• Taiwan 102/175 58 Hsieh, 1999
• Australia 12/40 30 Chandler, 1999
• Also, in rats, lambs, chicken, domestic cattle

Swine HEV relation to human HEV
Study Infection Hepatitis Swine HEV in SPF pigs
Yes /- Swine HEV in primates Yes /- Human
(US2) in SPF pigs Yes No Human (Sar55/Mex 14)
in pigs No No
Phylogenetic relationships between hepatitis E
virus isolates Expert Reviews in Molecular
Medicine, 1999 Cambridge Univ. Press
6
Aggarwal Epidemiology of HEV infection

• HEV transmission by transfusions
• Prospective follow-up of 22 transfusion
  recipients 3 developed post-transfusion HEV
  infection
• 107 blood units transfused to these patients
  tested for HEV RNA 4 ve (3 also IgM anti-HEV)
• No sequencing data, however
• Overall importance of this route unclear
• HEV transmission by food
• Cases of HEV infection in Japan following
  ingestion of inadequately cooked meat
• Genomic sequences from patients similar to those
  recovered from food sources
• Importance of food transmission in endemic
  regions unclear
• Khuroo MS, et al. J Gastroenterol Hepatol 2004
  19 778-84. Tei S, et al. Zoonotic transmission
  of hepatitis E virus from deer to human beings.
  Lancet 2003 362371-3

7
Aggarwal Epidemiology of HEV infection
Urban
Rural
Mathur P, et al. Indian Pediatr 200138461-75.
Genelabs assay
Burnet assay
Some of the IgM anti-HEV ve persons also HEV RNA
ve
8
Aggarwal Epidemiology of HEV infection

• Implications
• Subclinical HEV infection is common in healthy
  individuals in endemic regions
• Should lead to much higher anti-HEV prevalence
  rates than those observed ? Ab wanes
• High rate of infection among healthy persons
• No intrafamilial spread Aggarwal R, et al. J
  Hepatol 1994 21 718-23, Somani S, et al. J
  Viral Hepatitis 200310446-9.
• What is the mechanism of spread of infection
  among healthy persons?
• ? Route other than fecal-oral

9
Aggarwal Epidemiology of HEV infection
HEV superinfection in cirrhosis
Illness More often, more severe, longer duration
Hamid SS et al. Hepatology 2002 36 474-8.Kumar
A, et al. Indian J Gastroenterol 2004 23 59-62
10
Aggarwal Epidemiology of HEV infection

• Prevention using immune globulin
• Two studies. No clear evidence in support.
• Immune serum globulin 16.5, 2 ml, IM, India

845 men
Hepatitis 239incl. clinical (206)subclinical
(33)
Hepatitis 2/262
Hepatitis 8/287
Joshi YK, et al. IJMR 1985 81 18-9.
11
Aggarwal Epidemiology of HEV infection
Prevention using immune globulin
62 household contacts
Hepatitis 2/32
Hepatitis 2/30

• Both studies failed to show any efficacy
• ? Too late in outbreak, ? Too small a dose used

Khuroo MS, Dar MY. Indian J Gastroenterol 1992
11 113-6.
12
Aggarwal Epidemiology of HEV infection

• Indian contributions
• Description of the first large outbreak (Delhi)
• Discovery of enteric non-A, non-B
• Epidemiology of HEV outbreaks
• Severe disease in pregnancy
• Lack of intrafamilial spread
• No chronic disease
• Routes of transmission water-borne, vertical,
  transfusions
• Duration of persistence of antibodies
• Animal HEV may not be important in endemic
  regions
• High rate of subclinical infection