|Year : 2019 | Volume
| Issue : 2 | Page : 86-90
Fecal–oral-transmitted hepatitis A and E prevalence in Eastern India: A 3-year retrospective study
Gitanjali Sarangi, Muktikesh Dash, Dharitri Mahapatra, Bimoch Projna Paty, Dibya Prasna Mohanty, Nirupama Chayani
Department of Microbiology, Sriram Chandra Bhanj Medical College and Hospital, Utkal University, Cuttack, Odisha, India
|Date of Submission||31-Aug-2017|
|Date of Decision||05-Dec-2017|
|Date of Acceptance||18-Apr-2018|
|Date of Web Publication||11-Feb-2020|
Department of Microbiology, Sriram Chandra Bhanj Medical College and Hospital, Utkal University, Cuttack - 753 007, Odisha
Source of Support: None, Conflict of Interest: None
Background: Enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV) are responsible for sporadic and epidemic forms of acute hepatitis globally.
Objectives: This retrospective 3-year study was conducted to determine the prevalence of HAV, HEV, and coinfection and its seasonal variations, age- and residence-specific epidemiological characteristics in a tertiary care hospital, Eastern India.
Materials and Methods: Serum samples from clinically suspected acute viral hepatitis cases were collected at peripheral levels and sent to the Department of Microbiology maintaining precautions. These were processed for the detection of HAV- and HEV-specific Immunoglobulin M antibodies carried out by enzyme-linked immunosorbent assays method. Data were analyzed using GraphPad QuickCalcs statistical software Inc, USA.
Results: The seroprevalence of HAV (54.3%) was higher than HEV (43.5%), and the coinfection rate was low (2.2%). The HAV infection was most commonly seen in pediatric and adolescent age group (≤18 years) whereas HEV infection in adults (P < 0.0001). The HAV outbreaks were commonly occurred in rural areas in comparison to HEV in urban areas (P < 0.0001). Both HAV and HEV cases were reported throughout the year.
Conclusion: The enteric viral hepatitis cases are highly prevalent, and outbreaks have occurred throughout the year in coastal plains of Eastern India. There is a need for screening of HAV and HEV, especially among pregnant women and improving levels of personal hygiene. The data generated from this study will help the local authorities to plan for future vaccination strategies, improvement in sanitation program, and safe water supply to the needy population.
Keywords: Coinfection, hepatitis A virus, hepatitis E virus, seroprevalence
|How to cite this article:|
Sarangi G, Dash M, Mahapatra D, Paty BP, Mohanty DP, Chayani N. Fecal–oral-transmitted hepatitis A and E prevalence in Eastern India: A 3-year retrospective study. J Med Soc 2019;33:86-90
|How to cite this URL:|
Sarangi G, Dash M, Mahapatra D, Paty BP, Mohanty DP, Chayani N. Fecal–oral-transmitted hepatitis A and E prevalence in Eastern India: A 3-year retrospective study. J Med Soc [serial online] 2019 [cited 2020 Oct 30];33:86-90. Available from: https://www.jmedsoc.org/text.asp?2019/33/2/86/278105
| Introduction|| |
Enterically transmitted hepatitis A virus (HAV), and hepatitis E virus (HEV) are responsible for sporadic and epidemic forms of acute hepatitis globally, especially in developing countries including India.
Hepatitis A is an acute liver disease caused by infection with HAV, which is transmitted through fecal–oral route. It occurs sporadically as well as in epidemics worldwide, with a tendency of cyclic occurrences. HAV is a member of the hepatovirus genus of the family Picornaviridae and is a nonenveloped 27–32 nm single-stranded positive polarity ribonucleic acid (RNA) virus. The World Health Organization (WHO) estimates that about 1.4 million new cases occur every year and cause approximately 11,000 deaths in 2015 worldwide (accounting for 0.8% of the mortality from viral hepatitis)., HAV is considered to be endemic in India, and the most of the population is infected asymptomatically in early childhood leading to lifelong immunity., The clinical spectrum of the infection varies widely with increasing age over 6 years to adulthood; the probability to develop clinical symptoms relating to acute hepatitis escalates significantly. HAV belongs to a single serotype. The humoral immune response to HAV structural proteins plays pivotal role in the diagnosis of HAV infection and differentiation of hepatitis A from other types of viral hepatitis. Antibodies to HAV (anti-HAV) against capsid proteins which are the primary marker of acute infection can be detected at or before clinical illness. It is predominantly immunoglobulin M (IgM) class and declines in about 3–6 months.
HEV is also an enterically transmitted virus that causes mostly acute hepatitis. It is a positive-stranded RNA virus which is nonenveloped and belongs to family hepeviridae. Every year, there are an estimated 20 million HEV infections occur worldwide, most commonly in East and South Asia, leading to approximately 3.3 million symptomatic cases of acute hepatitis. The WHO estimates that HEV caused approximately 44,000 deaths in 2015 (accounting for 3.3% of the mortality due to viral hepatitis). Hepatitis E is usually a self-limiting illness; however, some patients may progress to acute liver failure. It has a higher case fatality in pregnant women and with overlaying chronic liver disease. The mortality is 20%–25% and usually occurs in the third trimester. HEV can be diagnosed by detecting serum anti-HEV antibodies. The presence of anti-HEV IgM is a marker of acute infection. It remains at relatively high level for 2 months and falling below the cutoff level among most of the patients in 6–8 months. Commercial enzyme immunoassays kits based on ORF2/ORF3 peptides or recombinant antigens from HEV can detect the presence of IgM, representing a single serotype.,
Although a number of methods have been used to detect virus-specific IgM antibody class, including radioimmunoassay, immunochemical staining, immunoblotting, dot-blot immunogold filtration and enzyme immunoassay, IgM anti-HAV and anti-HEV enzyme-linked immunosorbent assays (ELISA) are available commercially. A laboratory-confirmed outbreak has taken importance because information is needed to make national prevention strategies and appropriate vaccine use. As the unsafe drinking water and poor sanitation are the most commonly reported cause of HAV and HEV, the data generated during and after outbreaks can highlight the need for improved access to clean drinking water and improved sanitation in a particular geographical area. To the best of our knowledge, there is a paucity of study on fecal–oral-transmitted hepatitis in India, especially in the Eastern part. The present study highlights the prevalence of HAV, HEV, HAV, and HEV coinfection and its seasonal variations and age-specific epidemiological characteristics in a tertiary care hospital, Eastern India.
| Materials and Methods|| |
Study design, population, and data collection methods
The state of Odisha extends from 17.49N latitude to 22.34N latitude and from 81.27E longitude to 87.29E longitude on the East Coast of India. It has an area of 155,707 km2 and a population of 4.19 crore according to 2011 census. There are 30 districts, 314 blocks, and 51,349 villages. The Coastal Plain of Eastern Odisha consists of 13 districts, namely Cuttack, Mayurbhanj, Balasore, Khordha, Jajpur, Kendujhar, Puri, Bhadrak, Angul, Dhenkanal, Jagatsinghpur, Kendrapara, and Nayagarh. There are about 2.26 crore people live in these 13 districts. The referral tertiary care hospital is situated in Cuttack district under integrated disease surveillance project (IDSP, Government of India).
The blood samples were collected from patients after clinically suspected as acute viral hepatitis with the following signs and symptoms, i.e., acute jaundice, dark urine, anorexia, malaise, extreme fatigue, and right upper quadrant tenderness. About 10 ml of the blood sample was collected from these patients after obtaining informed consent. All these samples were collected at the time of acute viral hepatitis outbreaks from district headquarter hospitals, community healthcare centers, and primary healthcare centers. Serum was separated at the site of collection and was transported by a district headquarter hospital staff to the Department of Microbiology in an ice-lined box which was maintained at 2°C–8°C within 24 h of collection. Samples were received along with demographic data, address, and clinical presentations from 13 districts of Eastern Odisha during several outbreaks that had occurred between January 2013 and April 2016. The hemolyzed and lipemic serum samples were excluded from the study.
Enzyme-linked immunosorbent assay for detection of Immunoglobulin M hepatitis A virus and hepatitis E virus
For the confirmation of clinical diagnosis, the presence of anti-HAV IgM in patient's sera was determined by using a commercial HAV ELISA kit according to the manufacturer's instructions (DIA.PRO Diagnostic Bioprobes Srl, Milano, Italy). Briefly, 1:101 diluted 100 μl of each serum sample was added to the respective microwells in microplate along with negative and positive controls and the calibrator. The microwells were incubated for 60 min at 37°C and washed with an automatic washer. About 100 μl of prepared HAV antigen/antibody complex was pipetted into each well, except the first blank well and was incubated for 60 min at 37°C. Microwells were then washed. About 100 μl of chromogen/substrate mixture was added into each well including the blank well and was incubated at room temperature (18–24°C) for 20 min. The color-developing enzymatic reaction was stopped by adding 100 μl of sulfuric acid into all the wells. The color intensity or the absorbance of each well was measured at 450 nm filter using a microplate reader.
The presence of anti-HEV IgM in patient's sera was determined using a commercial HEV ELISA kit according to the manufacturer's instructions (DIA.PRO Diagnostic Bioprobes Srl, Milano, Italy). First, 50 μl of neutralizing reagent was dispensed in all the wells of the samples. Then, 1:101 diluted 100 μl of each serum sample was added to the respective microwells in microplate along with negative and positive controls. The microwells were incubated for 60 min at 37°C and washed with an automatic washer. About 100 μl of enzyme conjugate was pipetted into each well except the blank well and was incubated for 60 min at 37°C. The microwells were washed. About 100 μl of chromogen/substrate mixture was added into each well including the blank well and was incubated at room temperature (18°C–24°C) for 20 min. The color-developing enzymatic reaction was stopped by adding 100 μl of sulfuric acid into all the wells, and the absorbance of each well was measured as described above.
The data were analyzed using GraphPad QuickCalcs statistical software Inc., 2236 Avenida de la Playa La Jolla, CA 92037 USA. Inferential statistics were calculated by Chi-square test with Yates' correction and P< 0.05 was defined as statistically significant.
| Results|| |
During the period of 3 years from January 2013 to April 2016, a total of 585 serum samples were received and processed in the Microbiology Department of a tertiary care hospital, Eastern India [Figure 1]. The nonrepeated serum samples were collected from clinically diagnosed acute viral hepatitis patients at several outbreaks during the study period from different parts of Eastern Odisha. The mean age of the patients was 18.68 years (standard deviation = 14.07, 95% confidence interval = 17.54–19.82, minimum 2 years and maximum 74 years). Out of 585 patients, 323 (55.2%) were males, and 262 (44.8%) were females. The majority of patients, i.e., 364 (62.2%) were belonged to pediatric and adolescent age group (≤18 years), and the rest 221 (37.8%) were adults (>18 years). Maximum 390 (66.7%) number of patients were detected from rural areas, and 195 (33.3%) were from urban areas. From 585 patients, 499 (85.3%) were confirmed by laboratory tests. Out of 499 laboratory-confirmed fecal–oral-transmitted viral hepatitis cases, 271 (54.3%) were HAV cases, 217 (43.5%) were HEV cases, and 11 (2.2%) were coinfected with both HAV and HEV [Figure 2]. The analysis of seasonal trend showed outbreaks of HAV and HEV occurred throughout the year with peaks in the winter and beginning of the summer season (November to April) and another peak of HAV in the rainy season (July to October) [Figure 3].
|Figure 1: Year-wise distribution of acute hepatitis, hepatitis A, hepatitis E, hepatitis A+ hepatitis E (coinfection) cases (up to April 2016) |
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|Figure 2: Acute hepatitis cases in a tertiary care hospital Eastern Odisha|
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| Discussion|| |
The present study highlights the seroprevalence of HAV and HEV as well as the coinfection of both the viruses in the 13 Eastern coastal districts of Odisha. A total of 585 number of acute viral hepatitis cases were included in the study population from January 2013 to April 2016 among which 323 (55.2%) were males, and 262 (44.8%) were females.
Different studies on acute viral hepatitis caused by HAV and HEV have reported varying prevalence of these viruses. The prevalence of HAV varies from 1.7% to 67% and HEV from 16.3% to 66.3%. In the present study, 85.3% of the suspected acute viral hepatitis cases showed a positive viral marker for one or both the viruses. Higher prevalence rate like our study was reported by Arora et. al. This may be due to the inclusion of clinically suspected acute viral hepatitis cases from the outbreaks, in both the studies. The seroprevalence of HAV was 54.3% followed by HEV 43.5%, and the coinfection was 2.2%. This is in contrast to other studies where authors have reported higher prevalence of HEV in comparison to HEV.,,
Coinfection due to both HAV and HEV was detected in 11 (2.2%) cases in this study. However, Vidsmiya et. al. and Joon et. al. reported higher rates of coinfection, i.e., 5.6% and 11.5%, respectively.,
Analyzing the age-specific seroprevalence, the present study showed HAV infection is more common in pediatric and adolescent age groups (≤18 years) than adults (>18 years), P< 0.0001. Regarding the epidemiological data in developing countries, the infection of HAV is acquired during early life due to overcrowding and poor sanitation, and by the age 10, 90% of the population possesses antibody to the virus, thereby showing immunity to infection. Hence, HAV infection is less commonly seen in adults mitigating the finding of this study. The infection rate of HEV is higher in adults (>18 years) in comparison to the pediatric and adolescent age groups (≤18 years) showing a significant P= 0.0001. Our result was well correlated with the results of other studies., It is possible that HEV infection is usually anicteric and goes unnoticed in children [Table 1] and [Table 2].
|Table 1: Distribution of IgM hepatitis A virus seropositive cases in Eastern Odisha according to age, sex and residency|
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|Table 2: Distribution of IgM hepatitis E virus seropositive cases in Eastern Odisha according to age, sex and residency|
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The overall prevalence of both HAV and HEV were higher in males, in the present study than the females, which has correlated with other studies., It could be explained by the fact that men have a higher risk of exposure due to their professional and outdoor activities.
The present study showed a significantly higher prevalence of HAV in rural areas compared to urban areas (P < 0.0001). This may be due to the poverty, overcrowding, and inadequate sanitation seen in most villages. However, in our study, more HEV cases (62.1%) were detected from urban area in comparison to rural area (24.6%), P < 0.0001. This could be due to improper drainage system in the towns and cities leading to sewage contamination of drinking water [Table 1] and [Table 2].
Considering the seasonal variation, both HAV and HEV cases were seen all around the year in this region. Both HAV and HEV have a peak rise during winter and beginning of summer whereas HAV cases have a second peak in rainy season. Joon et. al. in South India have reported the similar peaks of HAV and HEV cases in winter; however, in contrary to this study they found another peak of HEV during the beginning of rainy season. Al-Naaimi et. al. in Baghdad, Iraq have reported more HAV cases in winter and HEV cases more common in summer.
| Conclusion|| |
The seroprevalence of HAV (54.3%) is higher than HEV (43.5%), and the coinfection rate is low (2.2%). From all clinically suspected acute viral hepatitis outbreak cases, the HAV infection is most commonly seen in pediatric and adolescent age group (≤18 years) whereas HEV infection in adult age group (>18 years). The HEV outbreaks have commonly occurred in urban areas whereas HAV in rural areas. The findings of this present study can identify local hepatitis outbreaks, monitor disease trends and can evaluate the effectiveness of sanitation, safe water supply, and other prevention and control measures. As it is evident from this study, the enteric HAV and HEV are common in our geographical area, i.e., Coastal Plains of Eastern Odisha, India, and periodic outbreaks have occurred throughout the year. There is a need for screening of HAV and HEV, especially among pregnant women and improving levels of personal hygiene. These data will be essential for planning future vaccination strategies, better sanitation program, and safe water supply in this part of the country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]