Hepatitis A Immunity Stays High in Urban India While Hepatitis E Exposure Remains Age-Dependent

A decade-long comparison of antibody signatures in one of southern India’s closely studied urban populations has delivered a nuanced verdict on how two foodborne and waterborne hepatitis viruses are behaving as the country urbanises. Researchers at the Wellcome Trust Research Laboratory of Christian Medical College in Vellore, working with colleagues from the institution’s departments of Child Health and Community Medicine, measured IgG antibodies against hepatitis A virus and hepatitis E virus in residents of urban Vellore in two cross-sectional serosurveys, one conducted in 2013 and the other in 2022. Their findings, published in BMC Infectious Diseases, show that immunity to hepatitis A remained remarkably stable and nearly universal across the nine-year interval, while hepatitis E exposure stayed low in the young and rose only gradually with age, with a modest and statistically non-significant uptick among adults.

The study rests on a simple but powerful epidemiological premise: antibodies of the immunoglobulin G class persist for years after infection or vaccination, so their prevalence in a population acts as a cumulative record of exposure. Because hepatitis A and hepatitis E are both transmitted primarily through the faecal-oral route, their seroprevalence patterns are tightly coupled to sanitation, water quality, hygiene practices and socio-economic conditions. When a community improves its water and sanitation infrastructure, the age at which children first encounter these viruses tends to rise, shifting the burden of susceptibility toward older individuals in whom infection is more likely to cause symptomatic disease. This phenomenon, known as epidemiological transition, is one of the central concerns for vaccination policy in low- and middle-income countries undergoing rapid urban development.

To test whether such a transition was underway in Vellore, the team drew on biobanked serum samples from 600 participants in the 2013 survey and 558 participants in the 2022 survey, all aged between one and forty years. Each sample was tested for IgG antibodies specific to hepatitis A virus and hepatitis E virus. The investigators then stratified seroprevalence estimates by age, gender and residential cluster, allowing them to detect not only overall changes between the two survey years but also geographic heterogeneity within the city. Statistical comparisons of seropositivity between years were carried out using proportion tests or Fisher’s exact tests, depending on the structure of the data.

The hepatitis A results were striking in their consistency. Seroprevalence exceeded 80 percent among children aged one to five years in both surveys and climbed to 100 percent among individuals aged sixteen and above, in 2013 as well as 2022. No statistically significant differences in hepatitis A seroprevalence were observed between the two survey years in any age stratum. In practical terms, nearly every resident of urban Vellore had been infected with hepatitis A virus by early adulthood in both eras, and infection continued to occur early in childhood. The virus, in this setting, remains firmly endemic, and the population’s collective immunity remains high.

Hepatitis E told a different story. IgG seroprevalence against this virus was low among children and adolescents in both surveys and increased progressively with age, a pattern consistent with sporadic rather than sustained childhood transmission. Among adults aged twenty-six to forty years, seroprevalence rose from 18 percent in 2013, with a 95 percent confidence interval of 12 to 27 percent, to 24 percent in 2022, with a 95 percent confidence interval of 16 to 32 percent. Although this increase suggests a possible gradual accumulation of exposure in adulthood, the change did not reach statistical significance, and the authors are careful not to overinterpret it. Across both viruses, no significant gender-based differences in seropositivity were detected.

Cluster-wise analysis added a spatial dimension to these findings. Hepatitis A seroprevalence was uniformly high across all residential clusters sampled in Vellore, reflecting the pervasive nature of early-life exposure to the virus throughout the urban environment. Hepatitis E seroprevalence, by contrast, was both low and heterogeneous across clusters, indicating that exposure to this virus is patchy and likely driven by localised factors such as intermittent contamination of water supplies, sanitation gaps in specific neighbourhoods, or differences in food handling practices. This heterogeneity matters for surveillance design, because a citywide average can easily mask pockets of elevated risk where outbreaks of hepatitis E, which can be particularly dangerous for pregnant women, may originate.

Beyond simple prevalence counts, the study employed more sophisticated quantitative tools to probe hepatitis A transmission dynamics. The researchers applied contact matrix and mixture modelling to the serological data to estimate the effective reproduction number, Re, for hepatitis A in each survey year. Mixture modelling, which treats the antibody distribution in a population as a blend of distributions from susceptible and immune individuals, allows researchers to infer the force of infection even from cross-sectional snapshots. The analysis yielded an Re below 1 in both serosurveys, indicating that secondary transmission of hepatitis A was not sustaining epidemic growth in either era, despite the accumulation of susceptible individuals in older age groups over time. This finding suggests that while the age profile of susceptibility may be shifting slowly, the underlying transmission intensity has not yet crossed the threshold that would fuel outbreaks among older, more vulnerable populations.

The implications for vaccination policy are significant. In many middle-income countries that have improved sanitation, hepatitis A has transitioned from a disease of early childhood, where infection is usually asymptomatic, to one affecting older children and adults, in whom clinical illness and occasional severe outcomes are more common. This shift is the classic argument for universal childhood hepatitis A vaccination: immunising children early both protects them and reduces circulation, indirectly shielding older susceptible individuals. The Vellore data show that this transition, while anticipated, has not yet materialised in measurable form; immunity remains high and acquired early, and the effective reproduction number remains below one. The authors note that their findings should inform age-specific considerations for hepatitis A vaccination policy in urban India as it undergoes transition, implying that the window for deciding on vaccination strategy remains open but should be monitored with continued serosurveillance.

For hepatitis E, the picture is one of limited but persistent and age-dependent exposure. The low seroprevalence among the young means that a large fraction of the population reaches adulthood without prior immunity, and the gradual rise in seropositivity with age reflects cumulative adult exposure. The authors highlight the need for targeted hepatitis E surveillance, particularly because the virus causes substantial morbidity in pregnant women and can trigger large outbreaks when water supplies are compromised. The modest, non-significant rise in adult seroprevalence between 2013 and 2022 is consistent with continued low-level transmission that could accelerate under adverse conditions, making sustained monitoring essential.

Perhaps the clearest message of the study is a reaffirmation of the value of water, sanitation and hygiene interventions. The stability of hepatitis A immunity over the decade, and the continued containment of hepatitis E transmission below epidemic thresholds, support continued investment in WASH infrastructure as the backbone of enteric virus control in urban India. At the same time, the study demonstrates the power of repeated, geographically stratified serosurveys using biobanked samples to detect epidemiological change before it becomes clinically visible. As Indian cities continue to grow and modernise, the balance between endemic early-childhood infection and emerging adult susceptibility will determine whether hepatitis A vaccination becomes a public health priority, and whether hepatitis E remains a smouldering, localised threat or flares into wider outbreaks. The Vellore data provide a rigorous baseline against which that future can be measured.

Subject of Research: Decadal changes in IgG seroprevalence of hepatitis A and E virus in urban Vellore, India

Article Title: Decadal changes in IgG seroprevalence of hepatitis A and E virus in Urban Vellore, India: Persistent Endemicity or Epidemiological Shift?

Article References: Decadal changes in IgG seroprevalence of hepatitis A and E virus in Urban Vellore, India: Persistent Endemicity or Epidemiological Shift?. (n.d.). https://doi.org/10.1186/s12879-026-14413-0

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14413-0

Keywords: Hepatitis A, Hepatitis E, IgG seroprevalence, serosurvey, enteric infections, WASH, epidemiological transition, urban India, effective reproduction number, vaccination policy, Decadal, changes