|BRIEF RESEARCH ARTICLE
|Year : 2018 | Volume
| Issue : 3 | Page : 231-234
Hepatitis E infection in Odisha, India: A descriptive analysis
Shantanu K Kar1, Bhagirathi Dwibedi2, Vijayalaxmi V Mogasale3, Jyotsnamayee Sabat4, Vittal Mogasale5, Thomas F Wierzba6
1 Director (Research) Medical and Life Sciences, Directorate of Medical Research, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Additional Professor, Department of Peadiatrics, AIIMS Bhubaneshwar, Bhubaneswar, Odisha, India
3 Formerly Associate Research Scientist, Departments of Epidemiology, International Vaccine Institute, Seoul, South Korea; Assistant Professor, Department of Peadiatrics, Srinivas Institute of Medical Sciences and Research Centre, Mangalore, India
4 Research Scientist, Regional Medical Research Center, Bhubaneswar, Odisha, India
5 Head, Policy and Economic Research Department, Development and Delivery, International Vaccine Institute, Seoul, South Korea
6 Deputy Director General, Development and Delivery, International Vaccine Institute, Seoul, South Korea
|Date of Web Publication||12-Sep-2018|
Vijayalaxmi V Mogasale
Department of Peadiatrics, Srinivas Institute of Medical Sciences and Research Centre, Srinivasnagar, Mukka, Mangalore - 575 021, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Up to 25% of hepatitis E virus (HEV)-infected pregnant women in their third trimester die. Despite HEV being an important cause of viral hepatitis, no robust surveillance exists in India. We reviewed jaundice outbreaks records and hospital records from jaundiced individuals seeking treatment and linked those records to laboratory results (HEV immunoglobulin M enzyme-linked immunosorbent assay) for January 2012 to September 2013 in Odisha state. A total of 14 HEV confirmed outbreaks were identified, of which 33% of 139 jaundiced cases were HEV positive. There were two deaths. An additional 495 jaundiced cases were identified through hospital records, of which 18% were HEV positive. Among HEV-positive women (n = 35), 34% were of childbearing age. While one may not be able to generalize our results, this finding suggests HE is widespread in Odisha and may represent hidden disease burden in this region. The policymakers should monitor HEV infections in similar geographical areas, especially among population of childbearing age women to initiate evidence-based control measures.
Keywords: Hepatitis E, outbreak, surveillance, vaccine
|How to cite this article:|
Kar SK, Dwibedi B, Mogasale VV, Sabat J, Mogasale V, Wierzba TF. Hepatitis E infection in Odisha, India: A descriptive analysis. Indian J Public Health 2018;62:231-4
|How to cite this URL:|
Kar SK, Dwibedi B, Mogasale VV, Sabat J, Mogasale V, Wierzba TF. Hepatitis E infection in Odisha, India: A descriptive analysis. Indian J Public Health [serial online] 2018 [cited 2019 Jul 15];62:231-4. Available from: http://www.ijph.in/text.asp?2018/62/3/231/241100
Hepatitis E virus (HEV) induces acute and fulminant life-threatening liver inflammation. While HE produces significant disease burden in developing countries, it is a global infection. About 3.4 million HE cases occurred worldwide in 2005 with 70,000 deaths and 3000 stillbirths. The estimated deaths in 2010 were about 56,600 (23,300–113,300). Although deaths occur at any age, HE mortality is highest during pregnancy. Up to 25% of HEV-infected women in their third trimester die.
While India has made substantial progress in providing potable water and sanitation, many areas remain underserved allowing waterborne diseases to circulate. In the absence of routine surveillance, only a few HE outbreaks have been reported from India,,, underrepresenting the importance of the disease. Although HEV outbreaks are known to occur frequently in Eastern regions of India like Odisha State, there is only one outbreak reported in the literature. The objective of this article is to identify and report HE outbreaks from routine surveillance data and hospital case reports in Odisha State.
We conducted this study in Odisha state of India which has a population of 42 million as per 2011 census. This is an observational study that describes the routine data collected and generated by staff working at various levels of government health system. To identify HEV outbreaks, we used routinely collected data from the Integrated Disease Surveillance Project (IDSP). Surveillance is based on weekly reporting from primary health centers to district and state surveillance units and to a National Surveillance Unit. District hospitals, municipal hospitals, medical college hospitals, and private hospitals also provide data. When medical personnel suspects an outbreak, the outbreak response team of state health department and Regional Medical Research Center (RMRC) investigates. The medical officer will classify patients as “probable viral hepatitis” based on clinical characteristics including acute jaundice, dark urine, anorexia, malaise, fatigue, and right upper quadrant abdominal tenderness.” Under IDSP, “an outbreak sample collection triggering event” for probable viral hepatitis is defined as “clustering of cases from a particular village or urban ward where more than two cases of jaundice occur in different households or >10 jaundice cases per week per primary health centers.” Using a sample of convenience, blood samples and basic demographic characteristics were collected from the first ten probable cases. About 5 ml of the blood sample is collected; serum is separated and transported in reverse cold chain to the designated referral laboratory located at RMRC for testing. The etiology is identified based on an enzyme-linked immunosorbent assay (ELISA) test (MP Diagnostics, MP Biomedicals Asia Pacific, Singapore) for HEV immunoglobulin M (IgM) antibodies.
For this analysis, we identified outbreaks by linking laboratory results to probable viral hepatitis cases in surveillance reports based on time, place, age, and sex for the year 2012 and 2013 (until September). If ELISA test was found positive in one or more probable viral hepatitis cases in any outbreak, it was considered an HE outbreak. We also linked laboratory results of probable hepatitis from patients seeking treatment, 12 health facilities (10 hospitals and 2 health centers) that tested the samples at the RMRC. All probable hepatitis cases with available ELISA test results at RMRC during the study period were included. We extracted results and age-sex characteristics from laboratory records.
The locations of outbreaks were marked on a map based on geographical information system (GIS) coordinates. We identified the location where probable viral hepatitis outbreaks were reported by name (village/block/district) on Google map and extracted the GIS coordinates from the website. The GIS coordinates were used to plot outbreak map using ARC GIS software (version 10.2). Because of HEV infection is associated high mortality among pregnant women, we stratified HE cases by age groups with a separate group of 15–45-year-old representing women in reproductive ages. Characteristics of independent variables were examined by cross-tabulation using a Chi-square test (P < 0.05). Kruskal–Wallis nonparametric test was used for continuous variables. Data analysis was conducted in Stata 12 (College Station, Texas, USA).
Government authorities collected this data from IDSP and informed consent was not required by the government. All personal identifications were delinked to ensure confidentiality.
From January 2012 to September 2013, we identified 32 probable viral hepatitis outbreaks in 12 districts. Patient laboratory results for 15 outbreaks were not available. Of the remaining 17 outbreaks, 296 probable viral hepatitis cases were identified. Of these 296 cases, 139 cases were sampled and 46 (33.1%) were found HEV positive. These 46 confirmed cases were from 14 different outbreaks in eight districts [Figure 1]. Forty-one percent of the confirmed cases were aged 16–45 years representing women in reproduction age group [Table 1]. The mean age in HEV IgM in females was significantly lower than males (13.5 vs. 27.6; P < 0.05). There were two deaths; however, further details could not be obtained. Most HEV outbreaks were on the East coast (Jagatsinghpur, Khordha, and Cuttack) and Western region including tribal areas (Bargarh and Kalahandi).
|Figure 1: Odisha map showing laboratory-confirmed hepatitis E virus outbreaks from January 2012 to September 2013.|
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|Table 1: Demographic characteristics of laboratory-confirmed probable viral hepatitis cases from outbreaks and selected hospitals reports|
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Laboratory results were available for 507 sporadic probable viral hepatitis cases from hospital reports, of them 18.2% were positive by HEV-IgM ELISA. Of these 507 cases, age and sex characteristics were available for 495 sporadic cases [Table 1]. Of hospital-reported cases among females, 34.3% reported HE cases in women 16–45-year-old, while 77.1% of all cases occurred in 6–45 years.
The HEV outbreaks indicated two seasonal peaks. Seven out of 14 (50.0%) laboratory-confirmed outbreaks were reported between August and October, while another four (28.6%) were reported from January to March (data not shown). As detailed information on individual outbreaks was not available, epidemic curves could not be drawn.
We identified a number of HEV outbreaks and patients seeking treatment for HE infections in Odisha, suggesting significant underreporting of HE infection. Given that 14 of 17 probable viral hepatitis outbreaks were HE, it is possible that a majority of the 15 untested outbreaks were also due to HEV resulting in underrepresentation bias. Among cases seeking care at medical facilities, we also found that four of every ten laboratory-confirmed HEV cases were in females and more than one-third were women of childbearing age. While these women were not followed up and deaths were not documented, it would not be unreasonable, given the high case fatality rate among pregnant women and the significant number of women of childbearing age who sought treatment for HE infection, that some maternal deaths may be due to HEV in this and other endemic areas.
The use of GIS approach in this analysis has helped to locate geographical proximity of probable hepatitis outbreaks. For example, some geographical locations standout because of the outbreak clustering mainly due to positive cases and untested cases [Figure 1]. Such GIS approach can be used in risk visualization, geographical targeting, and planning evidence-based disease control measures.
Although a worldwide systematic literature report showed highest number of reported HE outbreaks from India, the reported number of outbreaks are considered underestimation of disease burden. A descriptive analysis of IDSP data available at national level from 2011 to 2013 showed 19,508 reported cases and 78 HEV outbreaks. In that analysis, <4 hepatitis outbreaks (includes both hepatitis A and E) were identified from Odisha. Whereas, our descriptive study identified 14 HEV outbreaks alone in Odisha in a shorter period. This was possible because we performed an additional step in the analysis to link probable hepatitis cases and outbreaks to laboratory reports which yielded more patients. Another laboratory-based study from Virology Research and Diagnostic Laboratory, Government Medical College, Amritsar that received samples from surrounding districts during the study period of January 2015–March 2016, found 68.4% (n = 65) of 95 sample received were positive for HEV. In our study, positivity rate in hospital reports was far lower at 18.2% potentially due to variation in clinical criteria of blood sampling, sending sample for testing, difference in ELISA kits, and epidemiological differences. We did not find other studies in India that described HE cases and outbreaks at regional, state, or national levels although there were many studies across India that described single outbreaks or hospital records.,,,,,,,,
The information on the actions taken to control outbreak was unavailable. The recommended viral hepatitis outbreak actions by IDSP are clinical verification, standard case management, active search of cases, serological investigations, and ensuring safe water supply. In addition, active search of pregnant women having jaundice in the second or third trimester is recommended. Such pregnant women are to be observed and referred to district hospital as and when required for the better management. It is also recommended to investigate water treatment plant to ensure safe water supply.
While in the long-term, providing safe water and sanitation will reduce HE incidence, in the short-term, the morbidity and mortality can be reduced by vaccination. For HE, a randomized placebo-controlled trial among adults in China showed 100% efficacy, 13-month postvaccination. The vaccine was approved in 2011 by China Food and Drug Administration for participants 16 years and older, but not licensed in India or prequalified by the World Health Organization.
This study has limitations as the data used here were collected through routine surveillance system. The depth of investigation may have varied between outbreaks, and it is likely that many outbreaks and sporadic cases were not investigated or reported. Such underreporting of infections is common and expected with passive surveillance system. The clinical background of cases, other associated infections such as hepatitis A and reasons for outbreak and details related to death were not available. Field staff may have obtained blood from a sample of convenience, not a random sample. Thus, these results are likely biased by choice of patients selected for sampling and caution should be exercised in generalizing it to other population. The occurrence of HE infection among pregnant women could not be ascertained, as pregnancy status was undocumented. The laboratory specimens of sporadic hospital cases originated from facilities located in two populous cities of Odisha. This may over represent cases from urban areas. Although misclassification of HEV infection may be possible, sensitivity and specificity of ELISA test is 98% and 96.7%, respectively. On the other hand, many samples came from geographically distant places, which involves operational and logistics challenges in the shipment of samples in ideal conditions may have contributed to the negative results. Despite the limitations, the routine surveillance system is the main source of information that can help to understand epidemiology of HE infection in the region.
HE infection appears to be prevalent, yet grossly underestimated in Odisha state suggesting the need for robust surveillance and disease prevention activities for HE in similar geographical locations in India and elsewhere.
The authors sincerely thank for the time and efforts of health staffs in Odisha who generated the information used in the manuscript. The authors also thank Dr. Prameela Baral for providing data, Mr. Kang-Sung Lee for data analysis and generating the figure, and Florian Marks and Dr. Laura Digilio for their inputs and contributions to this manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kmush B, Wierzba T, Krain L, Nelson K, Labrique AB. Epidemiology of hepatitis E in low- and middle-income countries of Asia and Africa. Semin Liver Dis 2013;33:15-29.
Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology 2012;55:988-97.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2095-128.
Teshale EH, Hu DJ. Hepatitis E: Epidemiology and prevention. World J Hepatol 2011;3:285-91.
Acharya SK, Madan K, Dattagupta S, Panda SK. Viral hepatitis in India. Natl Med J India 2006;19:203-17.
Vivek R, Nihal L, Illiayaraja J, Reddy PK, Sarkar R, Eapen CE, et al.
Investigation of an epidemic of hepatitis E in Nellore in South India. Trop Med Int Health 2010;15:1333-9.
Sailaja B, Murhekar MV, Hutin YJ, Kuruva S, Murthy SP, Reddy KS, et al.
Outbreak of waterborne hepatitis E in Hyderabad, India, 2005. Epidemiol Infect 2009;137:234-40.
Swain SK, Baral P, Hutin YJ, Rao TV, Murhekar M, Gupte MD, et al.
A hepatitis E outbreak caused by a temporary interruption in a municipal water treatment system, Baripada, Orissa, India, 2004. Trans R Soc Trop Med Hyg 2010;104:66-9.
Integrated Disease Surveillance Project, Government of India, Ministry of Health and Family Welfare; 2014. Available from: http://www.idsp.nic.in/
. [Last accessed on 2014 Jan 01].
Hakim MS, Wang W, Bramer WM, Geng J, Huang F, de Man RA, et al.
The global burden of hepatitis E outbreaks: A systematic review. Liver Int 2017;37:19-31.
Kumar T, Shrivastava A, Kumar A, Laserson KF, Narain JP, Venkatesh S, et al.
Viral hepatitis surveillance – India, 2011-2013. MMWR Morb Mortal Wkly Rep 2015;64:758-62.
Kaur M, Sidhu SK, Singh K, Devi P, Kaur M, Singh NJ, et al.
Hepatitis E virus: A leading cause of waterborne viral hepatitis in Northwest districts of Punjab, India. J Lab Physicians 2017;9:121-4.
] [Full text]
Murthy KA, Khan IM, Kiran PK, Hakeem H. A study of viral hepatitis e infection in a tertiary care hospital in Mysore, South India. Open Forum Infect Dis 2014;1:ofu036.
Chandra NS, Ojha D, Chatterjee S, Chattopadhyay D. Prevalence of hepatitis E virus infection in West Bengal, India: A hospital-based study. J Med Microbiol 2014;63:975-80.
Majumdar M, Singh MP, Goyal K, Chawla Y, Ratho RK. Detailed investigation of ongoing subclinical hepatitis E virus infections; occurring in outbreak settings of North India. Liver Int 2015;35:826-33.
Arora D, Jindal N, Shukla RK, Bansal R. Waterborne hepatitis a and hepatitis e in Malwa region of Punjab, India. J Clin Diagn Res 2013;7:2163-6.
Martolia HC, Hutin Y, Ramachandran V, Manickam P, Murhekar M, Gupte M, et al.
An outbreak of hepatitis E tracked to a spring in the foothills of the Himalayas, India, 2005. Indian J Gastroenterol 2009;28:99-101.
Nandi B, Hadimani P, Arunachalam R, Ganjoo RK. Spectrum of acute viral hepatitis in Southern India. Med J Armed Forces India 2009;65:7-9.
Prinja S, Kumar S, Reddy GM, Ratho RK, Kumar R. Investigation of viral hepatitis E outbreak in a town in Haryana. J Commun Dis 2008;40:249-54.
Bali S, Kar SS, Kumar S, Ratho RK, Dhiman RK, Kumar R, et al.
Hepatitis E epidemic with bimodal peak in a town of North India. Indian J Public Health 2008;52:189-93, 199. [Full text]
Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, et al.
Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: A large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 2010;376:895-902.
Wu T, Li SW, Zhang J, Ng MH, Xia NS, Zhao Q, et al.
Hepatitis E vaccine development: A 14 year odyssey. Hum Vaccin Immunother 2012;8:823-7.
Alter MJ, Mares A, Hadler SC, Maynard JE. The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis. Am J Epidemiol 1987;125:133-9.