ORIGINAL ARTICLE

Outbreak of hepatitis E with bimodal peak in rural area of Bhavnagar, India, 2010
Devang A. Raval, Naresh T. Chauhan, Rajesh S. Katara1, Pankhuri P. Mishra2, Dharmendra V. Zankar
Departments of Community Medicine, 1Microbiology, Government Medical College, Bhavnagar, 2Epidemiologist, Integrated Disease Surveillance Project, Bhavnagar, Gujarat, India

Context: Rise in the number of jaundice cases were reported on 24th of June 2010, in Dhola village, India. We investigated the outbreak to identify the source of infection and to facilitate control measures. Materials and Methods: We confirmed the outbreak by reviewing the rate of acute viral hepatitis in the year 2009-10. We defined a case of acute hepatitis as an acute illness with (a) discrete onset of symptoms and (b) jaundice or elevated serum aminotransferase levels, since March 2010 in Dhola village. We described the outbreak in terms of time, place, and person. We tested 20 blood samples of the case patient for hepatitis B surface antigen (HBs Ag), and immunoglobulin M (IgM) antibody for hepatitis A and E. We collected water samples for the bacteriological examination, and to test free chlorine in the water. Results: A total of 137 cases (attack rate 27.2/1000) were reported in this outbreak from March to August 2010. The attack rate was highest among the age group of 2029 years. The attack rate was significantly higher in male (35/1000) than in female (18/1000). Out of 20 case-patients, 19 were found positive for hepatitis E virus (HEV) IgM antibodies. The water samples taken from households contained more than 10 coliforms in 100 ml sample. The relative risk of developing hepatitis E among people using pipeline water against those using ground water was 3.23 (95% CI of RR 1.59, 6.57). Conclusion: Outbreak that affected Dhola village was due to hepatitis E virus. Fecal contamination of water was the most likely source of this bimodal outbreak of hepatitis E.
ABSTRACT

Key words: Bimodal outbreak, cohort study, hepatitis E, India

Introduction
Hepatitis E, formerly known as enterically-transmitted non-A, non-B hepatitis, is an acute, icteric, self-limited disease widely spread in Asia, Africa, Middle East, and Central America.[1-6] Viral hepatitis continues to be a major public health problem in India.[7,8] Evidence of hepatitis E virus (HEV) was first reported in 1980, in India.[9] The fecal-oral route is the primary mode of transmission of HEV[1] and it is associated with both sporadic infections and epidemics in areas with poor sanitation and weak public-health infrastructures.[4]
Access this article online Quick Response Code: Website: www.atmph.org

DOI: 10.4103/1755-6783.98615

HEV is a small RNA virus which belongs to the genus, Hepevirus, of the family, Hepeviridae.[6] Hepatitis E infections occur less frequently in developed countries, and only occur in those individuals who had been infected while traveling in an area where the virus is endemic.[1] However, autochthonous (locally acquired) occurrences of hepatitis E cases were also reported in developed countries, recently.[3,10-12] The virus also spreads through person-to-person, but such a spread is less common, and a secondary attack rate ranges from 0.7% to 2.2% among susceptible household contacts of patient.[13] The incubation period ranges from 2 weeks to 2 months, usually 1 month to 45 days.[7] Pregnant women affected by acute viral hepatitis E are more likely to develop acute liver failure (ALF); however, the fatal outcome may remain same as in non-pregnant women and men with ALF.[14] The treatment remains symptomatic. The identification of specific source of infection is of major importance to control the outbreak, as the standard control measures like chlorination of water may not be effective.[15] Rise in the number of jaundice cases were reported on

Correspondence: Dr. Naresh T. Chauhan, Shivganga Flats, Opp. Bavlia Hanuman Temple, Bhayanini Wadi, Bhavnagar, Gujarat-364003, India. E-mail: drnareshchauhan@rediffmail.com 190 190 Annals of Tropical Medicine and Public Health | May-Jun 2012 | Vol 5 | Issue 3

Raval, et al.: Hepatitis E outbreak in rural area of Bhavnagar, India

24th of June 2010, in Dhola Junction village, which is located 50 km from Bhavnagar city, and having population of 5045. Rapid response team investigated the outbreak to identify the source of infection, and to facilitate possible control measures.

Analytical epidemiology

Materials and Methods

Descriptive epidemiology

We reviewed Integrated Disease Surveillance Project (IDSP) weekly reporting data on acute viral hepatitis for the year, 2009-10, to confirm the outbreak. We defined a case of acute hepatitis as an acute illness with (a) discrete onset of symptoms and (b) jaundice or elevated serum aminotransferase levels, since March 2010 in Dhola village. Data were collected through (1) a door-to-door survey and (2) reporting under IDSP. We also collected information regarding the date of onset, age, sex, place of residence, treatment, and laboratory investigation. We calculated the attack rates of acute hepatitis by age and sex. We analyzed time, place, and person distribution of cases. We constructed an epidemic curve to study the dynamics of the epidemic. We divided the village in to six areas by their location (A to F). We prepared an incidence map to study the distribution of cases, and to formulate hypothesis. We used Epi Info 3.5.1 to analyze our data.
Environmental investigation

Based on the environmental investigation, we generated hypothesis that the presence of open drain, public toilets, and septic tank close to leaking regulatory valves in the pipeline were the most likely sources of this outbreak. We conducted a retrospective cohort study to test the hypothesis regarding the source of this outbreak. We used the sources of water supply to divide the village into two cohorts, 1) areas that were supplied water through pipeline from overhead water tank and 2) ground water supply. We estimated relative risk with 95% confidence intervals (CI), and tested statistical significance by using the chi-square test.

Results
Descriptive epidemiology

We interviewed case-patients to collect information regarding water quality, the source of drinking water, drainage system, and important events before the onset of illness. We also collected information regarding any public gatherings, exposure to outside food, and local food vendors. We examined the underground tank, which collects and stores the water to supply to the village. We used orthotolidine test to detect residual chlorine from water samples taken at various houses.
Laboratory methods

No case of viral hepatitis was reported from Vallabhipur block, where Dhola village was located as per the IDSP data 2009-10. A total of 137 cases (attack rate 27.2/1000) were reported in this outbreak from March to August 2010. There were 95 male and 42 female affected. The disease affected all the age groups. The attack rate was highest among the age group of 2029 years and lowest among children <9 years of age. The attack rates in male were 35/1000, and 18/1000 in female, and the difference was statistically significant (Z = 3.8, P=0.01) [Table 1]. There was no death reported, due to the disease. The rise in number of acute hepatitis cases started from 10 March 2010, reached a peak between 22 and 29 March, and fell thereafter, in the April 2010. Subsequently, from 6 June, again rise in the cases of acute hepatitis reached a peak in the second week of June, and fell in the first week of August 2010 [Figure 1]. Area-wise attack rate per 1000 was highest in the area, B (45.8), followed by C (39.6), D (37.5), A (17.0), E (14.3), and lowest in the area, F (9.5) [Figure 2]. The observed differences in the attack rates between the areas were found to be statistically significant (X2 = 38.8, P< 0.001).

We collected blood samples of 20 case-patients for the detection of immunoglobulin M (IgM) antibodies against hepatitis A and E virus, and for hepatitis B surface antigen (HBsAg), using commercially available enzyme-linked immunosorbent assay (ELISA) kits (Adaltis, Italia, Italy). We collected samples of water that was supplied to the village through pipeline from Rajpipla. We further collected samples from underground water tank and from individual houses. These water samples were tested to detect the presence of coliform bacteria using the most probable number (MPN) method. We considered water as acceptable, if it did not contain more than 10 coliforms in a 100 ml sample.

Table 1: Age and sex distribution of jaundice cases in Dhola, Bhavnagar, India, in June 2010
Group Age (years) 0 to 9 10 to 19 20 to 29 30 to 39 40 to 49 50 + Male Female Cases 4 44 39 30 11 9 137 95 42 Population Attack rate per Z value 1000 population 1 144 1 018 877 710 524 772 5 045 2 714 2 331 3.5 43.2 44.5 42.3 21.0 11.7 27.2 35.0 18.0

Total Sex

3.8 P= 0.01

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Raval, et al.: Hepatitis E outbreak in rural area of Bhavnagar, India

Laboratory results

A total of 20 sera from case-patients were tested; 19 were found positive for HEV IgM antibodies. Bacteriologically, samples of water that come through pipeline from Rajpipla and underground tank were found satisfactory. Water samples taken from households contained more than 10 coliforms in a 100 ml sample.
Environmental investigation

Dhola village is having two sources of water supply; one is the pipeline from Rajpipla, 60 km away from the village, and second is ground water supply in railway colony. Water that comes from Rajpipla is stored in the underground tank, and supplied, thereafter, through the overhead tank. Chlorination of water in the underground tank is done before it is pumped in the overhead tank. Water supply in the village was intermittent, once in three to four days. Water sample tested from the underground tank had residual chlorine more than 1 ppm (parts per million). Water samples tested for residual chlorine levels at different points in the village were found below 0.5 ppm. Common latrines of village, septic tank, and open drain were located in close vicinity of the water supply system [Figure 2]. Pipelines supplying water were found to be crossed by the drainage pipeline, as later was laid down superficially. Every time, when water is pumped, leakages in regulatory valves results in water lodging around the valves. Intermittent water supply leads to a negative pressure in pipes during periods of no flow, permitting inward suction of contaminated water lodged around valves [Figure 3]. Other possible sources which might cause hepatitis outbreak had been ruled out.
Analytical epidemiology

Figure 1: Cases of acute hepatitis cases by week of occurrence in Dhola, Bhavnagar, India, 2010

Figure 2: Attack rate of acute hepatitis by area in Dhola, Bhavnagar, India, 2010

Higher incidence rate (31.7/1000) was observed among people living in area having water supply from overhead tank as compared to people living in area having ground water supply (9.5/1000). The relative risk for those exposed against those non-exposed was 3.23 (95% CI of RR 1.59, 6.57). The difference in the attack rate was also found to be statistically significant (X2 = 11.9, P<0.001) [Table 2].

Discussion
This outbreak occurred in the rural area of Bhavnagar, India. Outbreaks of viral hepatitis E in rural area were reported from Rajasthan (1994 and 1999),[7] Maharashtra (2004),[16] and Uttarakhand (2005)[17] states of India. Outbreak of hepatitis E usually occurs in the unimodal outbreak with a highly compressed curve of incidence or it may have a prolonged
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Figure 3: Leaking valves in drinking water pipeline, Dhola, Bhavnagar, India, 2010

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Table 2: Incidence rates of acute hepatitis according to suspected exposure in Dhola, Bhavnagar, India, 2010
Suspected exposure Tank water supply (Area A to E, n=4 203) Ground water supply (Area F, n=842) Total (n=5 045) Number Number of of people people not affected affected 129 8 137 4074 834 4908 RR 95% CI P- value

3.23

1.59-6.57 <0.001

epidemic with multiple peaks.[4] This outbreak has a bimodal peak similar to another study reported from India.[18] Rapid response team visited the village during the first peak of this outbreak in March 2010 and recommended the removal of open drain, public toilet, and septic tank present near the water source. We also suggested repairs of regulatory valves in the pipeline. The first peak occurred probably due to initial fecal contamination of water. During the first peak, village was supplied water from alternate source that was through a water tanker till the cessation of cases. The absence of effective corrective measures to repair the leakages resulted in the second peak of acute hepatitis in the month of June. Similar mechanism of continued water contamination reported in other Indian outbreaks.[18,19] We ruled out the possibility of person-to-person transmission during the second peak of this outbreak, by the study of detailed line listing of the all cases. Cases of acute hepatitis halted following extensive repair work in the last week of June 2010. Study of this outbreak suggested that early detection of an outbreak only works if it is followed by immediate control measure taken by the responsible staff. Since outbreak of hepatitis E is usually caused due to contamination of piped water supply, clustering of cases in some area having common water supply will help to identify the point of contamination.[20,21] Results of the cohort study and the bacteriological examination of water revealed that the most likely source of this outbreak was contaminated water supplied through pipeline. Fecal contamination of piped water as a source of hepatitis E outbreak was reported in various studies across the India.[19-22] Few cases of acute hepatitis were also found from the area having ground water supply. This can be explained by the fact that the movement of people in the affected area might have exposed them to contaminated water source. Cessation of outbreak following the repair works supported the hypothesis that fecal contamination of water was the source of this outbreak. IDSP is now established in all the states and union

territories of India. Reporting of outbreaks at weekly interval is done under this system. Analysis of the weekly reporting data of the IDSP showed that 49.6%, 53.8%, and 48.9% of outbreaks, respectively, in the year 2008, 2009, and 2010 were due to acute diarrheal disease, cholera, and acute viral hepatitis (A and E).[23,24] Prevention of hepatitis E and other water borne pathogens require improving bacteriological quality of water at household level, better sanitation, proper sewage disposal, and public education. According to National Family Health Survey-2005-06 data, 66% of households in India drink water without any prior treatment.[25] In this situation, it is necessary to keep water supply free from fecal contamination to prevent outbreak of water borne diseases. At present, there is no system available which can track the quality of water supplied to the population. Even if such systems exist, it only limited at source level and not at household level, which can detect contamination during distribution. World Health Organization (WHO) has described water quality surveillance[26] which can ensure testing of residual chlorine and physical quality of water. If it contains residual chlorine below 0.5 ppm and turbid or foul smelling, then it can be sent to laboratory equipped for performing bacterial analysis of water. Water quality surveillance activity can detect water contamination prior to the occurrence of outbreak; hence, immediate corrective measures can be taken to tackle the source of contamination. In rural areas, village health and sanitation committee can do this water surveillance activity; later, this can be incorporated in IDSP. However, additional studies are needed to evaluate the effectiveness of such a system. The present investigation suffers from limitation that we could not collect water sample from ground water supply for bacteriological examination, which could have further supported our hypothesis of fecal contamination of pipeline water. In conclusion, the outbreak that affected Dhola village was due to hepatitis E virus resulting from fecal contamination of drinking water. The pattern of this outbreak was bimodal, which was suggestive of continued water contamination in the area. This investigation leads the authority to implement the control measures suggested by the team. Cases of acute hepatitis dropped gradually following the repair work.

Acknowledgement
We are thankful to Medical officer, Dr D.B Lohra, and supervisor, Mr R. N. Solanki, Primary Health centre, Dadva, for their support during field work. We acknowledge Mr. Vijay J Miyatra for his help in improving the English of
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this manuscript. We are also thankful to Dr. M P Singh, Head of Community Medicine Department, Government Medical College, Bhavnagar, for his support.

14.

15.

Ethical approval

This study was done as a part of response to public health emergency (outbreak); ethical approval not obtained.

16.

17.

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Cite this article as: Raval DA, Chauhan NT, Katara RS, Mishra PP, Zankar DV. Outbreak of hepatitis E with bimodal peak in rural area of Bhavnagar, India, 2010. Ann Trop Med Public Health 2012;5:190-4. Source of Support: Government of Gujarat, India, Conflict of Interest: None declared.

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