Skip to main content
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 2026 Feb 20;104(5):290–300. doi: 10.2471/BLT.25.293642

Hepatitis A virus endemicity and vaccine policy, India

Endémicité du virus de l’hépatite A et politique vaccinale, Inde

Endemicidad del virus de la hepatitis A y política de vacunación en la India

استشراء فيروس التهاب الكبد أ وسياسة التطعيم، الهند

印度甲型肝炎病毒地方性流行水平和疫苗接种政策

Эндемичность вируса гепатита А и политика вакцин, Индия

Avinash R Deoshatwar a, Anisha Pulinchani a, Basavaraj Mathapati a, Madhu Sudan a, Suman Manohar Mhatre b, Anuradha Patil a, Supriya Hundekar a, Ganesh Chandra Sahoo c, Ashish Kumar c, Sahil Sharma d, Amrit Virk d, Mushtaq Khan Kayamkhani e, Suresh Choudhary f, Preet Khona g, Jagadish Nuchin Nuchin h, Gopal Dutt i, Prashant Kumar j, Ragini Mishra k, Laisram Raichandra Singh l, Johnson Moirangthem l, Mruga Dave m, Abhijeet V Jadhav a, B Shrinivasa n, Vidya Arankalle o, Kavita S Lole a,
PMCID: PMC13123430  PMID: 42058610

Abstract

Objective

To estimate the age-stratified, hepatitis A virus (HAV) seroprevalence in eight Indian states.

Methods

A cross-sectional seroprevalence survey was conducted in 120 rural and 105 urban population clusters across eight Indian states between 12 December 2022 and 28 November 2023. In each cluster, ten participants were randomly selected from each of the age groups: (i) 2 to 4 years; (ii) 5 to 9 years; (iii) 10 to 14 years; (iv) 15 to 30 years; and (v) > 30 years. Serum samples were tested for anti-HAV antibodies.

Findings

Overall, the HAV seroprevalence in the five age groups was 33.2% (95% confidence interval, CI: 30.4–36.2), 51.9% (95% CI: 49.0–54.8), 69.2% (95% CI: 66.6–71.8), 89.7% (95% CI: 88.6–90.8) and 97.4% (95% CI: 96.9–97.8), respectively. The female-to-male ratio was 1.52 : 1 and the HAV seroprevalence was 73.0% (4940/6768) in females versus 63.2% (2821/4453) in males. Overall, HAV endemicity was found to be high-intermediate in study groups in Gujarat, Jammu, Karnataka, Punjab and Rajasthan, high in Bihar, intermediate in Assam and low-intermediate in rural Manipur. As the overall seroprevalence for all children younger than 15 years was 51.9%, substantially more than 40% were at risk of HAV infection.

Conclusion

Although HAV endemicity varied widely across urban and rural study populations in the eight Indian states, it was generally high-intermediate, providing evidence that HAV endemicity in India has declined in recent years. The study’s findings could help Indian policy-makers decide on HAV vaccination for children.

Introduction

Since the 1990s, many low- and middle-income countries have reported declining transmission of the hepatitis A virus (HAV).1 The virus’s seroprevalence is inversely proportional to the population’s socioeconomic status and is particularly influenced by water quality, sanitation and hygiene because transmission is largely waterborne in these coutries,2 though foodborne outbreaks also occur.3 As socioeconomic conditions improve, exposure to HAV decreases, leading to a decline in age-related seroprevalence.46 Paradoxically, this decline increases the disease burden: the infection is typically asymptomatic in children younger than 5 years but disease severity rises as age at infection increases.3,7,8 In fact, the age at midpoint of population immunity (i.e. the youngest age at which 50% of individuals have antibodies to the virus) is considered as a reliable indicator of HAV disease burden in the community.7

In recent years, hepatitis A has placed a considerable public health burden on low- and middle-income countries, including India. The Global Burden of Disease initiative estimated that the burden of HAV infection in India in 2013 was over 30 disability-adjusted life-years (DALYs) lost per 100 000 population per year;9 in 2021, the burden was over 70 DALYs per 100 000 population per year for children aged 5 to 14 years.10 India has one of the highest disease burdens globally, and that burden has been increasing rapidly as indicated by rising HAV outbreaks and hospitalizations.4,1115 Weekly outbreak surveillance data collected by the Indian government’s integrated disease surveillance programme recorded a marked increase in HAV outbreaks after 2012, a trend likely to continue as water quality, sanitation and hygiene improves.12 In 2019, HAV caused 10–30% of acute hepatitis cases in the country and 5–15% of cases of acute liver failure.16

Historically, HAV was highly endemic in India, as reported by many studies performed before 2010: the seroprevalence in 10-year-olds was over 90% and the age at midpoint of population immunity was younger than 5 years.1720 Moreover, a 2014 study of 4175 healthy young adults from various parts of India documented a seroprevalence of 92.7% (95% confidence interval, CI: 91.8–93.5).21 However, a systematic review of studies from South-East Asian countries published between 1980 and 2016 included only 14 articles from India, although it did confirm high HAV endemicity in the country.6

In low- and middle-income countries, the transition from high to intermediate endemicity has been characterized by HAV infection outbreaks.7 Since 2004, Kerala State in India has reported an increasing number of outbreaks involving severe disease and deaths and, in the past decade, there have been around 300 HAV outbreaks.12,22 A recent study indicates that HAV vaccination would be cost-effective in Kerala.23 In addition, many other Indian states, including Himachal Pradesh, Jammu and Kashmir, Maharashtra, Punjab and Uttarakhand, have also reported a rise in outbreaks since 2012.12

According to a 2022 World Health Organization (WHO) position paper on hepatitis A vaccines,7 the inclusion of HAV vaccination in national programmes in low- and middle-income countries is likely to be cost-effective and is recommended when a country transitions from high to intermediate endemicity. Moreover, a national expert committee recently recommended that HAV vaccination should be introduced into India’s universal immunization programme.24

As age-stratified seroprevalence estimates are essential for deciding on vaccination policy,25 we conducted a population-based, cross-sectional study of HAV seroprevalence in India with the aim of determining whether populations in different states have experienced a decline from high to intermediate HAV endemicity.

Methods

Study design and participants

Fig. 1 presents a flow diagram of the selection of study participants. Instead of grouping Indian states according to their geographical location, we divided them into groups according to their epidemiological transition level, which is the ratio of DALYs due to communicable diseases versus noncommunicable diseases in a population. Like HAV seroprevalence, the epidemiological transition level is correlated with socioeconomic status.26

Fig. 1.

Selection of participants, hepatitis A virus endemicity study, India, 2022–2023

Notes: we defined the epidemiological transition level as the ratio of disability-adjusted life-years lost due to communicable diseases versus noncommunicable diseases in a population. Epidemiological transition levels for 2016 were used for district selection.26

Fig. 1

Participants were recruited in five age groups: (i) 2 to 4 years; (ii) 5 to 9 years; (iii) 10 to 14 years; (iv) 15 to 30 years; and (v) > 30 years. We did not enrol children younger than 2 years because of feasibility and ethical issues, which avoided including infants with maternal antibodies. For the statistical analysis, we considered the seroprevalence in the group aged 2 to 4 years to represent that for all children younger than 5 years.

Based on the findings of a study we conducted in Pune District in 2017,5 and assuming 75% seroprevalence, 7.5% precision for the 95% CIs and a design effect of 2, we derived a sample size of 256 participants per age group over 30 clusters, or 8.53 participants per age group in each cluster, using Epi Info v. 7.2.6.0 (Centers for Disease Control and Prevention, Atlanta, United States of America). After adjustment for issues associated with sample quality, transport and handling, we rounded the number up to 10 participants per age group in each cluster, which corresponded to a total of 300 participants per age group over 30 clusters in each district (Fig. 1). Thus, the study was planned to involve eight districts containing 30 clusters of five age groups with 10 participants in each age group, making a total sample size of 12 000. Guidance on vaccination coverage cluster survey design from WHO was used as the reference to validate the sample size calculations.27

In the literature,2830 the endemicity level is assigned according to the age at midpoint of population immunity, as follows: (i) younger than 5 years (high endemicity); (ii) 5 to 10 years (high-intermediate endemicity); (iii) 11 to 15 years (intermediate endemicity); (iv) 16 to 20 years (low-intermediate endemicity); (v) 21 to 30 years (low endemicity); and (vi) older than 30 years (very low endemicity).

We included people living in a particular cluster for more than 6 months in the study. In urban areas, the clusters comprised municipal wards, whereas in rural areas, they were villages. Simple random sampling was used to select clusters because the most recent population data were from the 2011 census and large changes may have occurred since then.

We informed state and district health authorities and local community leaders about the study’s activities and sought their cooperation. A supervisor and coordinator and a team of technicians were selected from study staff and staff at collaborating local institutions. Local health department staff, such as assistant nurse midwives or workers at Anganwadi (i.e. rural childcare centres) informed the population about the study at least 1 day before field activities. For villages with a population under 1000, neighbouring villages were included to achieve the desired sample size, particularly for the age groups 2 to 4 years and 5 to 9 years. Within each cluster, the study team established a data and sample collection base at a convenient place for sample collection, preferably near the centre of the location, and villagers residing in households in all compass directions from the base were invited to participate. Initially, we included one family member. However, if not enough families within a cluster were willing to participate, we included more members from willing families until the sample size of 10 participants per age group was reached.

We amended recruitment early in the study because of the surprisingly low HAV seroprevalence we found in districts with a low epidemiological transition level: we replaced one district with a high epidemiological transition level by an additional district with a low epidemiological transition level to reflect the decline in seroprevalence. We could not include the urban population in Manipur because of an eruption of social unrest in the region midway during field activities; however, 762 individuals in rural areas were enrolled before the unrest manifested.

Data and blood sample collection

After giving informed consent, the participant or parent (if the participant was younger than 18 years) filled in a questionnaire on risk factors. Sex of the participant was recorded as reported by them or parents. In addition, we collected venous blood samples: 3 to 5 mL from individuals older than 5 years and 1 to 2 mL from younger children. The samples were stored in containers at 4 °C 30 minutes after drawing. Following separation, serum samples were stored at 4 °C until couriered to the Indian Council of Medical Research National Institute of Virology on dry ice for testing. Samples were tested for the presence of anti-HAV antibodies using the HAV Ab competitive enzyme-linked immunosorbent assay (DIA.PRO, Milan, Italy). The sensitivity and specificity reported by the manufacturer were 100% and over  98%, respectively.

Statistical analysis

We calculated overall age- and gender-weighted seropositivity rates for various sociodemographic and hygiene variables across study districts categorized by socioeconomic status. In addition, we also determined the overall seroprevalence for each age group, for urban and rural areas and for both sexes in total and for individual study districts. To derive weighting, we used age and sex distributions for India from the 2021 National Health Profile.31 To determine age at the midpoint of population immunity, we created smaller 3-year age groups (e.g. 2 to 4 years, 5 to 7 years and 8 to 10 years) and plotted the seroprevalence in these groups. The statistical analysis was performed using R v. 4.3.1 (The R Foundation, Vienna, Austria).

The study was approved by the institutional ethics committee of the Indian Council of Medical Research National Institute of Virology in January 2020. Written informed consent was obtained from participants 18 years or older, parental consent was obtained for younger participants, and children aged between 7 and 17 years gave assent.

Results

Between 12 December 2022 and 28 November 2023, a total of 11 380 individuals were recruited from eight districts across eight states: Bhilwara (Rajasthan), Bhavnagar (Gujarat), Patna (Bihar), Bishnupur (Manipur), Dibrugarh (Assam), Reasi (Jammu), Gadag (Karnataka) and Sahibzada Ajit Singh Nagar (Punjab).

Blood samples from 11 231 individuals were of sufficient quantity and quality; 54 individuals refused to give samples. The planned sample size of 12 000 was not reached because of social unrest in Manipur.

Table 1 shows the demographic details of the participants; 6050 (53.9%) were from rural areas, 4586 (41.3%) reported a family size greater than five, 7633 (68.0%) of mothers had no or only primary school education and the female-to-male ratio was 1.52 : 1 (6768 : 4463). The higher enrolment of females was probably due to the timing of field work, usually between 9:00 am and 4:00 pm. Details of analyses by gender and urban or rural location are available from the corresponding author on request.

Table 1. Sociodemographic and hygiene characteristics of participants, study of hepatitis A virus endemicity, India, 2022–2023.

Characteristic No. participants (%)
(n = 11 231)
Age group, years
2 to 4 2 080 (18.5)
5 to 9 2 273 (20.2)
10 to 14 2 233 (19.9)
15 to 30 2 344 (20.9)
Over 30 2 301 (20.5)
Sex
Female 6 768 (60.3)
Male 4 463 (39.7)
Residence location
Rural 6 050 (53.9)
Urban 5 181 (46.1)
Mother’s educational level
No formal education 6 031 (53.8)
Primary school 1 602 (14.3)
Secondary school 627 (5.6)
High school 2 569 (22.9)
Undergraduate school 215 (1.9)
Graduate school 157 (1.4)
Data missing 30 (NA)
Family size
≤ 5 6 524 (58.7)
> 5 4 586 (41.3)
Data missing 121 (NA)
House type
Brick or concrete (i.e. pucca) house 6 991 (62.5)
House made from natural materials (i.e. kutcha house) 4 186 (37.5)
Data missing 54 (NA)
Drinking water supply
Government or municipal supply to tap 6 951 (62.2)
Common community source 2 141 (19.2)
Well 2 088 (18.7)
Data missing 51 (NA)
Drinking water processing
None 9 394 (84.0)
Reverse osmosis filter 1 013 (9.1)
Boiling 774 (6.9)
Data missing 50 (NA)
Toilet available
Yes 9 764 (87.3)
No 1 417 (12.7)
Data missing 50 (NA)
Reported handwashing with soap after defecation
Yes 10 244 (91.6)
No 937 (8.4)
Data missing 50 (NA)
Reported handwashing with soap before eating
Yes 9 995 (89.4)
No 1 186 (10.6)
Data missing 50 (NA)

NA: not applicable.

Notes: inconsistencies arise in some values due to rounding. Data missing values not included in the percentage calculation.

The HAV seroprevalence in the study population for different socioeconomic and hygiene variables is reported in Table 2 for districts of low and high socioeconomic status, respectively. The overall age- and gender-weighted seroprevalence was 81.4% (95% CI: 80.6–82.1). For urban and rural areas combined, the gender-weighted seroprevalence was 33.2% (95% CI: 30.4–36.2) in participants aged 2 to 4 years; 51.9% (95% CI: 49.0–54.8) in those aged 5 to 9 years; 69.2% (95% CI: 66.6–71.8) in those aged 10 to 14 years; 89.7% (95% CI: 88.6–90.8) in those aged 15 to 30 years; and 97.4% (95% CI: 96.9–97.8) in those older than 30 years. In addition, the seroprevalence was 73.0% (4940/6768) in females and 63.4% (2821/4453) in males. Notably, we found that the seroprevalence in all age groups under 15 years was 51.9% (3416/6586).

Table 2. Hepatitis A virus seroprevalence, by district socioeconomic status and participants’ sociodemographic and hygiene characteristics, India, 2022–2023.

Characteristic Participants in districts with a high socioeconomic status (n = 4530)
Participants in districts with a low socioeconomic status (n = 6701)
No. tested for anti-HAV antibodies in blood No. who tested positive for anti-HAV antibodies in blood HAV seroprevalence, % (95% CI) No. tested for anti-HAV antibodies in blood No. who tested positive for anti-HAV antibodies in blood HAV seroprevalence, % (95% CI)
Age group, years
2 to 4 1025 428 41.8 (38.7–44.8) 1432 404 28.2 (25.9–30.6)
5 to 9 725 472 65.1 (61.5–68.5) 1171 567 48.4 (45.5–51.3)
10 to 14 898 691 76.9 (74.0–79.6) 1335 854 64.0 (61.3–66.5)
15 to 30 949 900 94.8 (93.2–96.1) 1395 1203 86.2 (84.3–88.0)
Over 30 933 920 98.6 (97.6–99.2) 1368 1322 96.6 (95.5–97.5)
Sex
Female 2812 2200 78.2 (76.6–79.7) 3956 2740 69.3 (67.8–70.7)
Male 1718 1211 70.5 (68.3–72.6) 2745 1610 58.7 (56.8–60.5)
Residence location
Rural 2281 1653 72.5 (70.6–74.3) 3769 2433 64.5 (59.8–68.2)
Urban 2249 1758 78.2 (76.4–79.8) 2932 1917 65.4 (63.6–67.1)
Mother’s educational level
No formal education or primary school 3408 2703 79.3 (77.9–80.6) 4225 3131 74.1 (72.7–75.4)
Higher than primary school 1114 702 63.0 (60.1–65.8) 2454 1202 49.0 (47.0–51.0)
Family size
≤ 5 2336 1726 73.9 (72.0–75.6) 4188 2674 63.8 (62.4–65.3)
> 5 2113 1619 76.6 (74.7–78.4) 2473 1642 66.4 (64.5–68.2)
Missing data 81 66 81.5 (71.0–88.9) 40 34 85.0 (69.5–93.7)
House type
Brick or concrete (i.e. pucca) house 1098 874 79.6 (77.7–81.9) 3088 1866 60.4 (58.7–62.1)
House made from natural materials (i.e. kutcha house) 3378 2494 73.8 (72.3–75.3) 3613 2484 68.8 (67.2–70.3)
Drinking water supply
Common community source 537 473 88.1 (85.0–90.6) 1604 976 60.8 (58.4–63.2)
Government or municipal supply to tap 3310 2410 72.8 (71.3–74.3) 3641 2451 67.3 (65.8–68.8)
Well 632 485 76.7 (73.2–79.9) 1456 923 63.4 (60.8–65.9)
Drinking water processing
Boiling 106 78 73.6 (64.0–81.5) 668 346 51.8 (47.9–55.6)
None 4042 3024 74.8 (73.4–76.1) 5352 3589 67.1 (65.8–68.3)
Reverse osmosis filter 332 267 80.4 (75.6–84.5) 681 415 60.9 (57.1–64.6)
Toilet available
No 458 403 88.0 (84.6–90.7) 959 674 70.3 (67.3–73.1)
Yes 4022 2966 73.7 (72.3–75.1) 5741 3676 64.0 (62.8–65.3)
Handwashing with soap after defecation
No 322 291 90.4 (86.5–93.3) 615 407 66.2 (59.5–67.1)
Yes 4158 3078 74.0 (72.7–75.3) 6086 3943 64.8 (63.5–65.9)
Handwashing with soap before eating
No 544 474 87.1 (84.0–89.8) 642 418 65.1 (61.3–68.8)
Yes 3936 2895 73.5 (72.1–74.9) 6059 3932 64.9 (63.7–66.1)

CI: confidence interval; HAV: hepatitis A virus.

Fig. 2 shows the overall seroprevalence by age group in the eight study districts for urban and rural areas combined. Interestingly, though the district of Bishnupur in Manipur had a low socioeconomic status, the estimated HAV seroprevalence was only 15.5% (95% CI: 12.1–18.9) among rural children aged 2 to 14 years, the lowest among study districts for that age group.

Fig. 2.

Hepatitis A virus seroprevalence, by study district and age group, India, 2022–2023

HAV: hepatitis A virus.

Notes: the graphs show the seroprevalence for urban and rural areas combined. The dashed line shows the 50% HAV seroprevalence level, which is used to determine age at midpoint of population immunity, an indicator of the level of HAV endemicity. Bars with dotted lines shows the age group for which the midpoint has been passed.

Fig. 2

The mother’s educational level was strongly associated with the estimated HAV seroprevalence (χ2 for trend: 735.2; P < 0.1). The seroprevalence was 79.2% (95% CI: 78.2–80.2; 4777/6031) for no formal education; 66.0% (95% CI: 63.6–68.3; 1057/1602) for primary education; 49.6% (95% CI: 45.6–53.6; 311/627) for secondary school education; 55.6% (95% CI: 53.7–57.6; 1429/2569) for high school education; 41.4% (95% CI: 34.7–48.3; 89/215) for undergraduate-level education; and 47.8% (95% CI: 39.7–55.9; 75/157) for graduate-level education. Seroprevalence was lower in rural population groups than urban population groups, which mostly had a lower socioeconomic status: 67.5% (95% CI: 66.4–68.7; 4086/6050) versus 70.9% (95% CI: 69.7–72.2; 3675/5181), respectively.

Most study participants were from districts with a low socioeconomic status. Overall, 11 281 participants chose to report their annual family income: it was below 250 000 Indian rupees (₹; approximately 3082 United States dollars, US$, in December 2022) for 10 694 participants (94.8%); between ₹250 000 and 600 000 (i.e. US$ 3082 to 7400) for 522 (4.6%); between ₹600 001 and 1 000 000 (i.e. US$ 74010 to 12 330) for 53 (0.5%); and above ₹1 000 000 (i.e. above US$ 12 330) for 12 (0.1%).

Table 3 shows the level of HAV endemicity in rural and urban populations in the study districts. According to the age at midpoint of population immunity, most districts had high-intermediate, intermediate or low-intermediate endemicity. Notably, the age at midpoint of population immunity in rural Dibrugarh in Assam was 3 years but the cumulative seroprevalence at the age of 15 years was 45.7%.

Table 3. Level of hepatitis A virus endemicity and age at midpoint of population immunity, by study district, India, 2022–2023.

District, state Type of community Age at midpoint of population immunity,a years Level of HAV endemicityb
Bhilwara, Rajasthan Urban 9 High-intermediate
Rural 9 High-intermediate
Bhavnagar, Gujarat Urban 6 High-intermediate
Rural 9 High-intermediate
Gadag, Karnataka Urban 9 High-intermediate
Rural 6 High-intermediate
Patna, Bihar Urban 3 High
Rural 3 High
Dibrugarh, Assam Urban 15 Intermediate
Rural 3 High
Sahibzada Ajit Singh Nagar (Mohali), Punjab Urban 9 High-intermediate
Rural 12 Intermediate
Reasi, Jammu Urban 9 High-intermediate
Rural 12 Intermediate
Bishnupur, Manipur Urban NDc NDc
Rural 18 Low-intermediate

HAV: hepatitis A virus; ND: not determined.

a The age at midpoint of population immunity is defined as the youngest age at which 50% of individuals have HAV antibodies.

b We determined the level of HAV endemicity in a district from the age at midpoint of population immunity, as follows: (i) < 5 years (high); (ii) 5 to 10 years (high-intermediate); (iii) 11 to 15 years (intermediate); (iv) 16 to 20 years (low-intermediate); (v) 21 to 30 years (low); and (vi) > 30 years (very low).

c Data for the urban population in Manipur could not be obtained because of social unrest during field activities.

Discussion

Over the past three decades, more than 25 low- and middle-income countries have introduced HAV vaccine into their immunization programmes and universal mass vaccination has been reported to affect disease incidence, mortality and outbreaks in low-, middle- and high-income countries.3236 Both WHO and others have recommended that HAV vaccine be included in national programmes when a country transitions from high to intermediate endemicity.7,37 In India, there are indications that HAV transmission has been declining in recent years.12,13,15 Our community-based study of urban and rural areas in eight different states provides evidence of that decline.

Research indicates that improvements to water quality, sanitation and hygiene can lead to a decline in HAV transmission.38,39 In India, there has recently been a rise in HAV-related hospitalizations among children and young adults.40 Moreover, HAV infection has been associated with worse outcomes in around 7% of chronic liver disease patients.14 However, the lack of accurate data on the HAV disease burden in India remains a major challenge.

Our approach of grouping Indian states according to their epidemiological transition level proved to be useful, as evident from our trend analysis. While studying all Indian states classified by their mix of urban and rural areas and their economic status would have been ideal, this approach would have been expensive and required an unfeasibly large study. Nevertheless, our unexpected findings in Manipur indicate that our approach should be used with caution, as this state neither has high economic status nor high epidemiological transition level. The reasons for the low HAV seroprevalence found in Bishnupur District in Manipur need to be investigated further.

We found that the midpoint of population immunity in some study groups was between 10 and 15 years. Infections in this age range have been reported to be associated with more severe disease and deaths than in younger age groups.2 Consequently, the Indian Academy of Paediatrics has recommended HAV vaccination for children.41 For over a decade, however, vaccination has occurred mostly in cities among population groups with a high socioeconomic status. None of the children in our study, who mostly came from families with a low socioeconomic status, had received an HAV vaccine.

Our risk factor analysis found a strong inverse correlation between the mother’s educational level and HAV seroprevalence, which highlights the importance of girls’ education for improving the health of population groups with a low socioeconomic status. This observation may be helpful for policy-makers working on strategic social interventions against infectious diseases, which can be complex.42 In contrast with a previous study in India,18 we found that HAV seroprevalence was higher in females than males in all study groups. Similar findings have been reported by middle-income countries such as Argentina, Chile, Dominican Republic and Mexico.43

Among some study populations, HAV seroprevalence was higher in urban than rural areas, which is in line with our recent observations in Pune District, Maharashtra.5 According to data from the Indian government,44 17.4% of India’s urban population lived in slums at the time of the 2011 census and the proportion was likely to be considerably higher in 2025. Targeted policies are required for this population. The income distribution of participants in our study differed from that in India’s population as a whole, where over 25% of households had an annual income above ₹250 000 in 2022.45 Consequently, our study findings are predominantly for low-income population groups.

As HAV endemicity progresses through several phases, a single-dose HAV vaccine could be included in the national immunization programme in a phased manner; it could be introduced earlier in states where the age at midpoint of population immunity is high. Although the two-dose regime is more effective,46 experience in Brazil showed that inclusion of a single-dose vaccine can give satisfactory results.47 In addition, modelling in many countries has shown that including an HAV vaccine in childhood vaccination programmes is cost-effective.3235,37 It is reassuring that the vaccine induces robust antibody responses for a long time after vaccination.48

Transmission of HAV in India is likely to decline sharply in the near future because of improved socioeconomic conditions, better water quality due to the Ministry of Jal Shakti’s Har Ghar Jal mission to provide clean tap water to every household, and continuing efforts to build millions of toilets under the Swachh Bharat (Clean India) mission.

Our study has a few limitations. First, seroprevalence estimates weighted by probability proportional to population size were unavailable. Second, in calculating the required sample size, we applied the same assumptions for all socioeconomic categories and age groups. In the absence of national data, we assumed an HAV seroprevalence of 75% for the sample size calculations based on findings in our previous study.5 Although generalizing seroprevalence estimates across the country is a limitation from a statistical point of view, we believe our estimates are appropriate for broad endemicity classifications, considering the epidemiology of HAV infection. Third, we used epidemiological transition levels based on 2016 data. Since then, states probably experienced further changes in epidemiological transition level, at different rates. Fourth, we used simple random sampling to select districts and clusters because the population data available were from the 2011 census, and different population groups would have experienced different demographic changes. We selected rural, or village, clusters randomly to ensure that smaller villages had an equal chance of inclusion. Fifth, participation in the study was voluntary and people with a lower socioeconomic status were more willing to participate. Sixth, as population groups with a high epidemiological transition level and high socioeconomic status were underrepresented, we may have overestimated seroprevalence. Moreover, the study enrolled more females than males. As HAV seroprevalence was higher in females, the sex imbalance may also have contributed to the study overestimating seroprevalence. Consequently, HAV endemicity in India is probably lower than indicated by our study.

In conclusion, we obtained community-based data on HAV endemicity across a wide range of geographical regions in India, which indicate that endemicity has declined. Our findings can help policy-makers reach an evidence-based decision on whether an HAV vaccine should be included in the national childhood immunization programme.

Acknowledgements

We thank health-care staff, including district health officials, in Bhavnagar, Bhilwara, Bishnupur, Dibrugarh, Gadag, Patna, Reasi and Sahibzada Ajit Singh Nagar Districts; technical staff at the ICM-NIV, namely Pranit Ayachit, Kailas Gadekar, Rahul Jagtap, Prakash Jawalkar, Machhindra Karanjawane, Vishal Khond, Avanish Pandey, Satish Ranawade, Kunal Sakhare, Shaikh Shahrukh and Shirish Vaidya; scientists at ICMR-NIV, namely VP Bondre, Tejaswini Deshmukh, BV Tandale and Shilpa Tomar; Vishal Kumar, ICMR Regional Medical Research Center North East; Basant Bordoloi and Dibrugarh Prahlad Das at the DHS; Sabita Devi and Vijay Kumar at the Community Health Center, Katra, Jammu; Pritam Choudhari and Deboshruti Mitra; the late Arvind Pandey, ICMR National Institute of Medical Statistics, New Delhi; Raman Gangakhedkar, ICMR NIV, Pune; Sheela Godbole, ICMR NIV, Pune; Naveen Kumar, Director ICMR NIV, Pune; Manoj Murhekar, ICMR National Institute of Epidemiology, Chennai; Krishna Pandey, ICMR RMRI, Patna; Bhavneet Bharati, AIMS Mohali; Jagepu Kantaria and Jayeshbhai Sheth from Bhavnagar, Gujarat; the National Health Mission Directors and Health Services Directors of Assam, Bihar, Gujarat, Jammu and Kashmir, Karnataka, Manipur, Punjab and Rajasthan; Seema Aggarwal, State IDSP officer, Punjab; and all local phlebotomists, laboratory technicians and volunteers involved in the field work.

Funding:

Indian Council of Medical Research.

Competing interests:

None declared.

References

  • 1.Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010. Sep 24;28(41):6653–7. 10.1016/j.vaccine.2010.08.037 [DOI] [PubMed] [Google Scholar]
  • 2.Jacobsen KH, Koopman JS. Declining hepatitis A seroprevalence: a global review and analysis. Epidemiol Infect. 2004. Dec;132(6):1005–22. 10.1017/S0950268804002857 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Abutaleb A, Kottilil S. Hepatitis A: epidemiology, natural history, unusual clinical manifestations, and prevention. Gastroenterol Clin North Am. 2020. Jun;49(2):191–9. 10.1016/j.gtc.2020.01.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Zeng DY, Li JM, Lin S, Dong X, You J, Xing QQ, et al. Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990–2019. J Hepatol. 2021. Sep;75(3):547–56. 10.1016/j.jhep.2021.04.035 [DOI] [PubMed] [Google Scholar]
  • 5.Deoshatwar AR, Gurav YK, Lole KS. Declining trends in hepatitis A seroprevalence over the past two decades, 1998–2017, in Pune, western India. Epidemiol Infect. 2020. May 8;148:e121. 10.1017/S0950268820000953 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Gripenberg M, Aloysia D’Cor N, L’Azou M, Marsh G, Druelles S, Nealon J. Changing sero-epidemiology of hepatitis A in Asia-Pacific countries: a systematic review. Int J Infect Dis. 2018. Mar;68:13–7. 10.1016/j.ijid.2017.12.021 [DOI] [PubMed] [Google Scholar]
  • 7.WHO position paper on hepatitis A vaccines – October 2022. Wkly Epidemiol Rec. 2022. Oct 7;97(40):493–512. [Google Scholar]
  • 8.Hundekar S, Thorat N, Gurav Y, Lole K. Viral excretion and antibody titers in children infected with hepatitis A virus from an orphanage in western India. J Clin Virol. 2015. Dec;73:27–31. 10.1016/j.jcv.2015.10.012 [DOI] [PubMed] [Google Scholar]
  • 9.Stanaway JD, Flaxman AD, Naghavi M, Fitzmaurice C, Vos T, Abubakar I, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet. 2016. Sep 10;388(10049):1081–8. 10.1016/S0140-6736(16)30579-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Global burden of disease data 2021. Global dashboard. Seattle: Institute for Health Metrics and Evaluation; 2025. Available from: https://vizhub.healthdata.org/gbd-compare/ [cited 2025 Jun 13].
  • 11.Murhekar MV, Ashok M, Kanagasabai K, Joshua V, Ravi M, Sabarinathan R, et al. Epidemiology of hepatitis A and hepatitis E based on laboratory surveillance data – India, 2014–2017. Am J Trop Med Hyg. 2018. Oct;99(4):1058–61. 10.4269/ajtmh.18-0232 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Integrated disease surveillance program. Weekly outbreaks [internet]. New Delhi: Ministry of Health and Family Welfare, Government of India; 2024. Available from: https://idsp.mohfw.gov.in/index4.php?lang=1&level=0&linkid=406&lid=3689 [cited 2024 Oct 22].
  • 13.Agrawal A, Singh S, Kolhapure S, Hoet B, Arankalle V, Mitra M. Increasing burden of hepatitis A in adolescents and adults and the need for long-term protection: a review from the Indian subcontinent. Infect Dis Ther. 2019. Dec;8(4):483–97. 10.1007/s40121-019-00270-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Raju B, Andani A, Kolhapure S, Agrawal A. Need for hepatitis A prevention in patients with chronic liver disease in the changing epidemiological setting of India. Hum Vaccines Immunother. 2021. May 4;17(5):1520–9. 10.1371/journal.pone.0306293 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Khanna S, Vohra P, Jyoti R, Vij JC, Kumar A, Singal D, et al. Changing epidemiology of acute hepatitis in a tertiary care hospital in northern India. Indian J Gastroenterol. 2006. Mar-Apr;25(2):101–2. [PubMed] [Google Scholar]
  • 16.National action plan combating viral hepatitis in India. New Delhi: Ministry of Health and Family Welfare, Government of India; 2019 p 23. Available from: https://nvhcp.mohfw.gov.in/common_libs/National-Action-Plan-Combating-Viral-Hepatitis-in-India.pdf [cited 2024 Oct 23].
  • 17.Hernandez-Suarez G, Saha D, Lodroño K, Boonmahittisut P, Taniwijaya S, Saha A, et al. Seroprevalence and incidence of hepatitis A in South-East Asia: a systematic review. PLoS One. 2021. Dec 1;16(12):e0258659. 10.1371/journal.pone.0258659 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Mall ML, Rai RR, Philip M, Naik G, Parekh P, Bhawnani SC, et al. Seroepidemiology of hepatitis A infection in India: changing pattern. Indian J Gastroenterol. 2001. Jul-Aug;20(4):132–5. [PubMed] [Google Scholar]
  • 19.Arankalle V, Tiraki D, Kulkarni R, Palkar S, Malshe N, Lalwani S, et al. Age-stratified anti-HAV positivity in Pune, India after two decades: has voluntary vaccination impacted overall exposure to HAV? J Viral Hepat. 2019. Jun;26(6):757–60. 10.1111/jvh.13074 [DOI] [PubMed] [Google Scholar]
  • 20.Kunasol P, Cooksley G, Chan VF, Isahak I, John J, Loleka S, et al. Hepatitis A virus: declining seroprevalence in children and adolescents in South-East Asia. Southeast Asian J Trop Med Public Health. 1998. Jun;29(2):255–62. [PubMed] [Google Scholar]
  • 21.Kotwal A, Singh H, Verma AK, Gupta RM, Jain S, Sinha S, et al. A study of hepatitis A and E virus seropositivity profile amongst young healthy adults in India. Med J Armed Forces India. 2014. Jul;70(3):225–9. 10.1016/j.mjafi.2014.06.016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Jacob John T. Large outbreak of hepatitis A in Kerala. Indian J Med Res. 2006. Oct;124(4):451–2. [PubMed] [Google Scholar]
  • 23.Gurav YK, Bagepally BS, Chitpim N, Sobhonslidsuk A, Gupte MD, Chaikledkaew U, et al. Cost-effective analysis of hepatitis A vaccination in Kerala state, India. PLoS One. 2024. Jun 27;19(6):e0306293. 10.1371/journal.pone.0306293 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Shah N, Faridi MMA, Bhave S, Ghosh A, Balasubramanian S, Arankalle V, et al. Expert consensus and recommendations on the live attenuated hepatitis A vaccine and immunization practices in India. Hum Vaccines Immunother. 2025. Dec 31;21(1):2447643. 10.1371/journal.pone.0306293 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Ozawa S, Privor-Dumm LA, Nanni A, Durden E, Maiese BA, Nwankwo CU, et al. Evidence-to-policy gap on hepatitis A vaccine adoption in 6 countries: Literature vs. policymakers’ beliefs. Vaccine. 2014. Jul 7;32(32):4089–96. 10.1016/j.vaccine.2014.05.026 [DOI] [PubMed] [Google Scholar]
  • 26.Dandona L, Dandona R, Kumar GA, Shukla DK, Paul VK, Balakrishnan K, et al. ; India State-Level Disease Burden Initiative Collaborators. Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study. Lancet. 2017. Dec 2;390(10111):2437–60. 10.1016/S0140-6736(17)32804-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.World Health Organization vaccination coverage cluster surveys: reference manual. Geneva: World Health Organization; 2018. Available from: https://www.who.int/publications/i/item/WHO-IVB-18.09 [cited 2024 Oct 22].
  • 28.Mohd Hanafiah K, Jacobsen KH, Wiersma ST. Challenges to mapping the health risk of hepatitis A virus infection. Int J Health Geogr. 2011. Oct 18;10(1):57. 10.1186/1476-072X-10-57 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Jacobsen KH. Globalization and the changing epidemiology of hepatitis A virus. Cold Spring Harb Perspect Med. 2018. Oct 1;8(10):a031716. 10.1101/cshperspect.a031716 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Saffar F, Sellaoui F, Hechaichi A, Chelly S, Bouguerra H, Cherif A, et al. Epidemiologic patterns of hepatitis A infection during the pre-vaccination era: a population-based survey in Tunisia in 2015. Int J Infect Dis. 2022. Apr;117:162–8. 10.1016/j.ijid.2022.01.004 [DOI] [PubMed] [Google Scholar]
  • 31.National health profile 2021. New Delhi: Central Bureau of Health Intelligence; 2021. Available from: https://cbhidghs.mohfw.gov.in/sites/default/files/NHP/National-health-2021.pdf [cited 2025 Oct 9].
  • 32.Sartori AMC, de Soárez PC, Novaes HMD, Amaku M, de Azevedo RS, Moreira RC, et al. Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: regional analyses according to the endemic context. Vaccine. 2012. Dec 14;30(52):7489–97. 10.1016/j.vaccine.2012.10.056 [DOI] [PubMed] [Google Scholar]
  • 33.Hayajneh WA, Daniels VJ, James CK, Kanıbir MN, Pilsbury M, Marks M, et al. Public health impact and cost effectiveness of routine childhood vaccination for hepatitis A in Jordan: a dynamic model approach. BMC Infect Dis. 2018. Mar 7;18(1):119. 10.1186/s12879-018-3034-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Carlos F, Gómez JA, Anaya P, Romano-Mazzotti L. Health economic assessment of universal immunization of toddlers against hepatitis A virus (HAV) in Mexico. Hum Vaccin Immunother. 2016;12(1):52–63. 10.1080/21645515.2015.1065362 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Suwantika AA, Beutels P, Postma MJ. Cost-effectiveness of hepatitis A vaccination in Indonesia. Hum Vaccin Immunother. 2014;10(8):2342–9. 10.4161/hv.29353 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Stuurman AL, Marano C, Bunge EM, De Moerlooze L, Shouval D. Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – a systematic review. Hum Vaccin Immunother. 2017. Mar 4;13(3):724–36. 10.1080/21645515.2016.1242539 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Gurav YK, Bagepally BS, Thakkinstian A, Chaikledkaew U, Thavorncharoensap M. Economic evaluation of hepatitis A vaccines by income level of the country: a systematic review. Indian J Med Res. 2022. Sep;156(3):388–410. 10.4103/ijmr.IJMR_1631_20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Progress on household drinking water, sanitation and hygiene 2000–2022: special focus on gender. New York & Geneva: United Nations Children’s Fund & World Health Organization; 2023. Available from: https://data.unicef.org/resources/jmp-report-2023/ [cited 2025 Mar 5].
  • 39.State of the world’s sanitation: an urgent call to transform sanitation for better health, environments, economies and societies. New York & Geneva: United Nations Children’s Fund & World Health Organization; 2020 p 48. Available from: https://www.unicef.org/media/86836/file/State-of-the-world%E2%80%99s-sanitation-2020.pdf [cited 2025 Jan 1].
  • 40.Grover M, Gupta E, Samal J, Prasad M, Prabhakar T, Chhabra R, et al. Rising trend of symptomatic infections due to hepatitis A virus infection in adolescent and adult age group: an observational study from a tertiary care liver institute in India. Indian J Med Microbiol. 2024. Jul-Aug;50:100653. 10.1016/j.ijmmb.2024.100653 [DOI] [PubMed] [Google Scholar]
  • 41.Guidelines for parents. Recommendations for vaccination. Mumbai: Indian Academy of Pediatrics; 2021. Available from: https://iapindia.org/pdf/Ch-11-IAP-Parental-Guide-on-Vaccination.pdf [cited 2024 Nov 1].
  • 42.Buckee C, Noor A, Sattenspiel L. Thinking clearly about social aspects of infectious disease transmission. Nature. 2021. Jul;595(7866):205–13. 10.1038/s41586-021-03694-x [DOI] [PubMed] [Google Scholar]
  • 43.Tanaka J. Hepatitis A shifting epidemiology in Latin America. Vaccine. 2000. Feb 18;18 Suppl 1:S57–60. 10.1016/S0264-410X(99)00466-1 [DOI] [PubMed] [Google Scholar]
  • 44.State/UT-wise number of towns, slum households and slum population under Pradhan Mantri Awas Yojana – Urban (PMAY-U) as per census-2011 as on 29-07-2024. New Delhi: National Informatics Centre (NIC), Ministry of Electronics and Information Technology, Government of India; 2025. Available from: https://www.data.gov.in/resource/stateut-wise-number-towns-slum-households-and-slum-population-under-pradhan-mantri-awas [cited 2025 Dec 21].
  • 45.The distribution of household income, 2019–2024. Bengaluru: Azim Premji University; 2025. Available from: https://ruralindiaonline.org/ta/library/resource/the-distribution-of-household-income-2019-2024/ [cited 2025 Dec 29].
  • 46.Andani A, van Damme P, Bunge EM, Salgado F, van Hoorn RC, Hoet B. One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: a systematic review. Vaccine. 2022. Jan 21;40(2):196–205. 10.1016/j.vaccine.2021.01.038 [DOI] [PubMed] [Google Scholar]
  • 47.Souto FJD, de Brito WI, Fontes CJF. Impact of the single-dose universal mass vaccination strategy against hepatitis A in Brazil. Vaccine. 2019. Feb 4;37(6):771–5. 10.1016/j.vaccine.2018.12.054 [DOI] [PubMed] [Google Scholar]
  • 48.Bhave S, Sapru A, Bavdekar A, Jain R, Debnath K, Kapatkar V. Long-term immunogenicity of single dose of live attenuated hepatitis A vaccine in Indian children – results of 15-year follow-up. Indian Pediatr. 2021. Aug 15;58(8):749–52. 10.1007/s13312-021-2285-4 [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES