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Am. J. Trop. Med. Hyg., 71(5), 2004, pp. 675-678
Copyright © 2004 by The American Society of Tropical Medicine and Hygiene

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AGE-WISE EXPOSURE RATES TO HEPATITIS E VIRUS IN A SOUTHERN INDIAN PATIENT POPULATION WITHOUT LIVER DISEASE

HUBERT DARIUS J. DANIEL, ASWIN WARIER, PRIYA ABRAHAM, AND GOPALAN SRIDHARAN
Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To determine the age-stratified exposure to hepatitis E virus (HEV) in patients attending a tertiary care hospital in southern India, serum samples from 600 individuals were tested using a commercial HEV IgG enzyme-linked immunosorbent assay. Subjects were composed of blood donors, antenatal women, and pre-operative individuals who were negative for hepatitis B surface antigen and antibody to hepatitis C virus with no evidence of liver disease; 200 each were 1–5 and 6–15 years old and 100 each were 16–40 and ≥ 41 years old. One (0.5%) sample was positive in those 1–5 years old, two (1.0%) in those 6–15 years old, eight (8%) in those 16–40 years old, and 13 (13%) in those ≥ 41 years old. The overall seropositivity rate was 4%. However, there was an age-related increase in exposure to HEV that was statistically significant (P < 0.001), with a higher HEV seropositivity in urban individuals.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Hepatitis E Virus (HEV) is an enterically transmitted hepatitis virus that is endemic in many developing countries where conditions of hygiene and sanitation are poor. Acute hepatitis due to HEV occurs sporadically and epidemics have occurred where food and drinking water supplies have been contaminated by sewage. Sixty percent of sporadic cases of hepatitis in Indian adults have been reported to be caused by HEV.1 In 1994, 17 epidemics of water-borne acute hepatitis in India were investigated using HEV-specific IgM and IgG, and it was found that 16 of these were caused at least in part by HEV.2 Furthermore, recent studies have shown that approximately 32% of patients with chronic liver disease were positive for IgG antibodies to HEV.3,4

Infection with HEV is associated with a significantly higher mortality rate of 10–20% in women in the third trimester of pregnancy compared with 1–2% in the general population.5 Although IgM antibody to HEV is used as an acute phase marker of HEV infection, IgG antibody to HEV is used to study the exposure to HEV in a given population. Currently, there is a paucity of data on exposure to HEV in the southern Indian population. In this study, we investigated the occurrence of an age-stratified exposure rate to HEV in individuals living in southern India.


MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects. Serum samples from subjects were chosen by convenient sampling from an archived collection of samples from southern Indian individuals (Tamil Nadu, Kerala, Karnataka, and Andhra Pradesh) attending a tertiary care hospital of the Christian Medical College in Vellore. The study group was composed of blood donors, antenatal women, and individuals who were screened pre-operatively and found to be negative for hepatitis B surface antigen and hepatitis C virus. Sera from blood donors were collected from July to September 2000, while antenatal women and pre-operative patient samples were collected during a similar period in 2001. All samples were stored at –20°C. None of the study subjects had clinical symptoms of hepatitis. Pre-operative patients, who had deranged liver function as reflected by increased levels of alanine aminotransferase, were excluded from the study. A total of 600 samples were examined: 200 each from those 1–5 and 6–15 years old and 100 each from those 16–40 and ≥ 41 years old. Of the 600 subjects tested, 358 were from urban southern India, 192 were from rural regions of southern India, and the status of 50 individuals could not be established. The study was reviewed and approved by the Institutional Research Committee. The anonymity of all subjects, inclusive of blood donors, was maintained.

IgG antibodies to HEV were detected using an enzyme-linked immunosorbent assay (HEV IgG ELISA; Genelabs Diagnostics, Singapore), which uses recombinant HEV antigens from the open reading frames (ORF2 and ORF3) of the Mexican and the Burmese strains of HEV. Testing of all sera was as per the manufacturer’s instructions. All samples that yielded a positive or an equivocal result were retested in duplicate. The data were analyzed by the chi-square test for proportions using Epi-Info version 6.03 software (Centers for Disease Control and Prevention, Atlanta, GA).


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
IgG antibodies to HEV were found in 0.5% (95% confidence interval [CI] = 0.025, 2.44%) of those 1–5 years old, 1% (95% CI = 0.168, 3.264%) of those 6–15 years old, 8% (95% CI = 3.78, 14.62%) in those 16–40 years old, and 13% (95% CI = 7.426, 20.69%) in those ≥ 41 years old (Figure 1Go). All positive samples were confirmed by re-testing. There were nine samples that yielded an equivocal result, eight of which on repeat testing were found to be negative. The remaining sample was scored as borderline positive because it was consistently equivocal.



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  		    FIGURE 1. Age-stratified seropositive status of hepatitis E virus in a southern Indian study population.

 
Of the 600 study subjects, 24 were positive for IgG antibody to HEV. Thus, the overall prevalence of IgG antibody to HEV in this study population was 4%. Of the 24 subjects who were positive for HEV IgG, 16 (67%) were men and 8 (33%) were women. There was an age-related increase in HEV exposure (Figure 1Go) that was statistically significant (P < 0.001). In the 550 study subjects for whom an urban/rural origin was documented, 16 positive individuals were identified. Of these 16 individuals positive for IgG antibody to HEV, 14 were from an urban setting and two were from a rural setting. This showed a trend towards urban preponderance; however, this difference was not statistically significant (P = 0.056).


DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In the last few years, commercial serologic assays for detection of IgM and IgG antibodies to HEV have become available with the incorporation of different strains of HEV. IgG antibody to HEV in healthy subjects has been used as a seroepidemiologic tool to measure exposure to this virus. Exposure rates in a given population have implications on future vaccination strategies. In developed countries, a small pro portion of the subjects have circulating antibodies to HEV,6–10 while in countries such as India, which are endemic for HEV, prevalence rates are higher, although with considerable variation between regions (Table 1Go).


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TABLE 1
Anti-hepatitis E virus IgG prevalence studies from India*
 
As per our results, the HEV exposure rate is low in southern Indian states compared with other parts of the country (Lucknow,11 Pune,12 and Kashmir13). A recent study from Chennai in southern India reported seroprevalences of 5.3% and 9% in children less than two years of age and in those 10–12 years old, respectively.14 Our findings show overall lower exposure rates across all age groups studied. However, there was a clear increase in seropositivity with age (Table 1Go). Perhaps the differences in the configuration of HEV antigens used in these studies could have contributed to the differences in exposure rate. Furthermore, the Chennai study was primarily urban in contrast to our study, in which at least 35% (192 of 550) of the subjects were from a rural background. In contrast to a study from Delhi,15 which did not report a preponderance of IgG antibody to HEV among urban dwellers, our study clearly shows an urban trend. This could be attributed to higher population densities and possible contamination of drinking water supplies with sewage, especially during the monsoon season.

Wide ranges of antigens are used in different HEV IgG assays, with varying specificity and sensitivity. The commercial assay used in the present study (Genelabs Diagnostics HEV IgG ELISA) uses specific recombinant epitopes from both the ORF 2 and ORF 3 regions of the viral genome from both the Mexican and the Burmese strains, which expectedly improve the sensitivity of the assay. There is emerging evidence to show that HEV shows considerable genetic heterogeneity globally. Commercial assays may be unsuitable to detect antibody responses among patients in a particular region if antigen configuration is based on strains from a geographically diverse region. Furthermore, human reservoirs of this virus have been recognized.16 A recent report from India suggests an extra-human reservoir of this virus in swine,17 though these strains were distinct from human strains. Potential transmission especially from non-human hosts to humans could occur from such divergent strains. This needs to be further investigated in this country, particularly in rural living conditions.

Although there have been no major epidemics of HEV reported from southern India, it is expected that the sanitary and climatic conditions of this part of India would facilitate dissemination and spread of viral diseases via the feco-oral route. Two earlier studies from this center show that HEV accounts for approximately 30% of all cases of acute hepatitis.18,19 Although the present study shows an age-related increase in HEV seroprevalence as observed in studies from other regions of this country,12,20 the seroprevalence in each age group compared with those in most Indian studies is low (Table 1Go). Our findings are similar to the seroprevalence rates reported in the Andaman and Nicobar Islands.20

Hepatitis E virus is reported to be excreted in low concentrations.21 It is also possible that this phenomenon could contribute to the lower efficiency of transmission of HEV, which is reflected in the lower detection rate of IgG antibody to HEV in this study population. Furthermore, studies have shown that IgG antibody to HEV disappeared within 6–12 months in children who were convalescing from HEV infection.22 The low prevalence of IgG antibody to HEV can also be attributed to the quick decay of levels of antibodies to HEV. Therefore, a person with past HEV infection could test negative for IgG antibody to HEV. Thus, seroprevalence studies could potentially underestimate the exposure to HEV in the population.

Some studies have shown IgG antibody to HEV to be protective.23,24 If the low detection rate of IgG antibody to HEV in this study is truly a reflection of the existing seroprotection, there is an immense potential for HEV epidemics to occur in southern India. Compounding this are the prevailing sanitary conditions in some parts of this region, which are far from satisfactory. Thus, such a situation warrants the urgent consideration for a vaccine to evade a major HEV epidemic.

However, prior to implementation of vaccination strategies, an urgent appraisal of the circulating strains of HEV in southern India, along with the development of suitable indigenous immunoassays to detect IgG antibody may provide us with more realistic insights into levels of seroprotection in the southern Indian population. Molecular epidemiologic studies will further assist in localizing the loci of spread of infection in this population and help in curtailing its spread.

Received April 30, 2004. Accepted for publication June 16, 2004.

Financial support: This study was partially supported by a Fluid Research Grant (grant number 5000) from the Christian Medical College, Vellore.

Authors’ addresses: Hubert Darius J. Daniel, Department of Clinical Virology, Christian Medical College, Vellore Tamil Nadu, India, Telephone: 91-416-228-2616, Fax: 91-416-223-2035, E-mail: hubertdariusj{at}yahoo.com. Aswin Warier, Department of Clinical Virology, Christian Medical College, Vellore Tamil Nadu, India, Telephone: 91-416-228-2616, Fax: 91-416-223-2035, E-mail: aw21{at}rediffmail.com. Priya Abraham, Department of Clinical Virology, Christian Medical College, Vellore Tamil Nadu, India, Telephone: 91-416-228-2772 or 91-416-228-2616, Fax: 91-416-223-2035, E-mails: priyaabraham{at}cmcvellore.ac.in and apriya_98{at}yahoo.com. Gopalan Sridharan, Department of Clinical Virology, Christian Medical College, Vellore Tamil Nadu, India, Telephone: 91-416-228-2070 or 91-416-228-2312, Fax: 91-416-223-2035, E-mail: g_sridharan{at}yahoo.com.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Arankalle VA, Chobe LP, Jha J, Chadha MS, Banerjee K, Favorov MO, Kalinina T, Fields H, 1993. Aetiology of acute sporadic non-A, non-B viral hepatitis in India. J Med Virol 40: 121–125.[ISI][Medline]
  2. Arankalle VA, Chadha MS, Tsarev SA, Emerson SU, Risbud AR, Banerjee K, Purcell RH, 1994. Seroepidemiology of water-borne hepatitis in India and evidence for a third enterically-transmitted hepatitis agent. Proc Natl Acad Sci U S A 91: 3428–3432.[Abstract/Free Full Text]
  3. Nakai K, Win KM, Oo SS, Arakawa Y, Abe K, 2001. Molecular characteristic-based epidemiology of hepatitis B, C and E viruses and GB virus C/Hepatitis G virus in Myanmar. J Clin Microbiol 39: 1536–1539.[Abstract/Free Full Text]
  4. Ramachandran J, Eapen CE, Kang G, Abraham P, Hubert DD, Kurian G, Hephzibah J, Mukhopadhya A, Chandy GM, 2004. Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease. J Gastroenterol Hepatol 19: 134–138.[ISI][Medline]
  5. Yarbough PO, 1998. Diagnosis. Zuckerman AJ, Thomas HC, eds. Viral Hepatitis. Second edition. Churchill Livingston, London: 411–416.
  6. Karetnyi YV, Favorov MO, Khudyakova NS, Weiss P, Bar-Shani S, Handsher R, Aboudy Y, Varsano N, Schwartz E, Levin E, Mendelson E, Fields HA, 1995. Serological evidence for hepatitis E virus infection in Israel. J Med Virol 45: 316–320.[ISI][Medline]
  7. Zanetti R, Dawson GJ, 1994. Hepatitis type E in Italy: a seroepidemiological survey. J Med Virol 42: 318–320.[ISI][Medline]
  8. Zaaijer HL, Yin MF, Lelie PN, 1992. Seroprevalence of hepatitis E in The Netherlands (letter). Lancet 340: 681.
  9. Thomas DL, Mahley RW, Badur S, Palaoqlu KE, Quinn TC, 1993. Epidemiology of hepatitis E virus infection in Turkey. Lancet 341: 1561–1562.[ISI][Medline]
  10. Lavanchy D, Morel B, Freip C, 1994. Seroprevalance of hepatitis E virus in Switzerland. Lancet 344: 747–748.
  11. Aggarwal R, Shahi H, Naik S, Yachha SK, Naik SR, 1997. Evidence in favour of high infection rate with hepatitis E virus among young children in India. J Hepatol 26: 1425–1426.[ISI][Medline]
  12. Arankalle VA, Tsarev SA, Chadha MS, Alling DW, Emerson SU, Banerjee K, Purcell RH, 1995. Age-specific prevalence of antibodies to hepatitis A and E viruses in Pune, India, 1982 and 1992. J Infect Dis 171: 447–450.[ISI][Medline]
  13. Khuroo MS, 1991. Hepatitis E: the enterically transmitted non-A, non-B hepatitis. Indian J Gastrolenterol 10: 96–100.
  14. Mohanavalli B, Dhevahi E, Menon T, Malathi S, Thyagarajan SP, 2003. Prevalence of antibodies to hepatitis A and hepatitis E virus in urban school children in Chennai. Indian Pediatr 40: 328–331.[Medline]
  15. Mathur P, Arora NK, Panda SK, Kapoor SK, Jailkhani BL, Irshad M, 2001. Sero-epidemiology of hepatitis E virus (HEV) in urban and rural children of north India. Indian Pediatr 38: 461–475.[Medline]
  16. Huang FF, Haqshenas G, Guenette DK, Halbur PG, Schommer SK, Pierson FW, Toth TE, Meng XJ, 2002. Detection by reverse transcription-PCR and genetic characterization of field isolates of swine hepatitis E virus from pigs in different geographic regions of the United States. J Clin Microbiol 40: 1326–1332.[Abstract/Free Full Text]
  17. Arankalle VA, Chobe LP, Walimbe AM, Yergolkar PN, Jacob GP, 2003. Swine HEV infection in south India and phylogenetic analysis (1985–1999). J Med Virol 69: 391–396.[ISI][Medline]
  18. Radhakrishnan S, Raghuraman S, Abraham P, Kurian G, Chandy G, Sridharan G, 2000. Prevalence of enterically transmitted hepatitis viruses in patients attending a tertiary-care hospital in south India. Indian J Pathol Microbiol 43: 433–436.[Medline]
  19. John R, Abraham P, Kurien G, Chandy G, Sridharan G, 1997. Sporadic hepatitis E in southern India. Trans R Soc Trop Med Hyg 91: 392.[ISI][Medline]
  20. Murhekar MV, Sehgal SC, Murhekar KM, Padbhidri SP, Chitambar SD, Arankalle VA, 2002. Changing scenario of hepatitis A virus and hepatitis E virus exposure among the primitive tribes of Andaman and Nicobar Islands, India over the 10-year period 1989–99. J Viral Hepat 9: 315–321.[ISI][Medline]
  21. Ticehurst J, Popkin TJ, Bryan JP, Innis BL, Duncan JF, Ahmed A, Iqbal Malik I, Kapikian AZ, Legters LJ, Purcell RH, 1992. Association of hepatitis E virus with an outbreak of hepatitis in Pakistan: serologic responses and pattern of virus excretion. J Med Virol 36: 84–92.[ISI][Medline]
  22. Goldsmith R, Yarbough PO, Reyes GR, Fry KE, Gabor KA, Kamel M, Zakaria S, Amer S, Gaffar Y, 1992. Enzyme-linked immunosorbent assay for diagnosis of acute sporadic hepatitis E in Egytian children. Lancet 339: 328–331.[ISI][Medline]
  23. Bryan JP, Tsarev SA, Iqbal M, Ticehurst J, Emerson S, Ahmed A, Duncan J, Rafiqui AR, Malik IA, Purcell RH, Legters LJ, 1994. Epidemic hepatitis E in Pakistan: Patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease. J Infect Dis 170: 517–521.[ISI][Medline]
  24. Chadha MS, Walimbe AM, Arankalle VA, 1999. Retrospective serological analysis of hepatitis E patients: a long-term follow-up study. J Viral Hepat 6: 457–461.[ISI][Medline]
  25. Khuroo MS, Rustgi VK, Dawson GJ, Mushahwar IK, Yattoo GN, Kamili S, Khan BA, 1994. Spectrum of hepatitis E virus infection in India. J Med Virol 43: 281–286.[ISI][Medline]
  26. Das K, Agarwal A, Andrew R, Frosner GG, Kar P, 2000. Role of hepatitis E and other hepatotropic virus in aetiology of sporadic acute viral hepatitis: a hospital based study from urban Delhi. Eur J Epidemiol 16: 937–940.[ISI][Medline]



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