Abstracts

Introduction

Hepatitis A virus is most commonly transmitted via oral-fecal exposure, contaminated food, water, or close physical contact with an infected person ¹1. Prasoppokakorn T, Vanichanan J, Chaiteerakij R, Jutivorakool K, Udomkarnjananun S, Pongpirul K, et al. A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients. Sci Rep 2021; 11:50.. People living in poorly sanitized areas are also more likely to be infected ²2. Organización Mundial de la Salud. Hepatitis A. https://www.who.int/es/news-room/fact-sheets/detail/hepatitis-a (accessed on 27/Aug/2021).
https://www.who.int/es/news-room/fact-sh... .

Hepatitis A virus is one of the most common etiologies of acute hepatitis worldwide ³3. Iorio N, John S. Hepatitis A. Treasure Island: StatPearls Publishing; 2021., infecting 212 million people per year, including 55 million symptomatic cases and 35,245 deaths globally ⁴4. Mirzaei J, Ziaee M, Farsad SA, Fereydooni M, Anani Sarab G, Rezvani Khorashad MR. Vaccination against hepatitis A for hemophilic patients: is it necessary? Hepat Mon 2016; 16:e37447.. As the number of asymptomatic infections is unknown, this number may be underestimated ⁵5. World Health Organization. The immunological basis for immunization series: module 18: hepatitis A. https://apps.who.int/iris/handle/10665/44570 (accessed on 22/Oct/2021).
https://apps.who.int/iris/handle/10665/4... .

Regions can be characterized by patterns of hepatitis A virus infection into areas of high, intermediate, or low endemicity ⁶6. Nunes HM, Soares MCP, Silva HMR. Infecção pelo vírus da hepatite A em área indígena da Amazônia oriental brasileira. Rev Soc Bras Med Trop 2004; 37:52-6.. According to the World Health Organization (WHO), hepatitis A endemicity classification is related to the seroprevalence among children aged 10-14 years: > 90% - high, 75-89% - high/medium, 60-74% - medium, 40-59% - low/medium, < 20% - low. The WHO susceptibility rate classification in adults aged 35-44 years at risk is as follows: high: > 40%, medium: 20-39%, low/medium: 10-19%, low: 1-9%, and very low: 0%. A high adult susceptibility rate shows an elevated risk of outbreaks ⁷7. Department of Immunization, Vaccines and Biologicals, World Health Organization. The global prevalence of hepatitis A virus infection and susceptibility: a systematic review. https://apps.who.int/iris/bitstream/handle/10665/70180/WHO_IVB_10.01_eng.pdf (accessed on 17/May/2021).
https://apps.who.int/iris/bitstream/hand... .

Areas of high endemicity are characterized by widespread hepatitis A virus, such as developing countries with poor sanitary conditions. Most infected individuals are young children, aged under 5 years, who are predominantly asymptomatic or show no specific symptoms. Consequently, apparent disease incidence rates are low and outbreaks are rare. In areas of intermediate endemicity, health conditions vary. In this scenario, many individuals escape hepatitis A virus infection during early childhood. However, viral circulation remains, and infection frequently occurs in adolescents or young adults. In these areas, the number of reported hepatitis A virus cases may be higher than in high endemic regions. Countries with good overall sanitary conditions usually have low endemicity. Thus, infection may occur at a later age and outbreaks are possible among adults and children ⁸8. WHO position paper on hepatitis A vaccines - June 2012. Wkly Epidemiol Rec 2012; 87:261-76.^,99. Aggarwal R, Goel A. Hepatitis A: epidemiology in resource-poor countries. Curr Opin Infect Dis 2015; 28:488-96..

Brazil can be classified as having a low/medium or intermediate hepatitis A virus burden ¹⁰10. Secretaria de Vigilância em Saúde, Ministério da Saúde. Hepatites virais 2021. Boletim Epidemiológico de Hepatites Virais 2021; número especial.. Hepatitis A virus incidence rates in Brazil increased until 2005 (14 per 100,000 inhabitants) and since 2006 have been showing a downward trend, reaching 3.2 cases per 100,000 inhabitants in 2014. Cases in children aged up to 9 years correspond to 54.7% of all reported cases in Brazil, and this age group’s incidence rate is also higher than in other age groups ¹¹11. Secretaria de Vigilância em Saúde, Ministério da Saúde. Hepatites virais 2017. Boletim Epidemiológico de Hepatites Virais 2017; 48(24).. In 2021, the incidence rate was estimated to be 0.2 per 100,000 inhabitants, with children accounting for 52.8% of all reported cases and a significant increase in cases in young adults (20-39 years) from 2017 to 2018 ¹⁰10. Secretaria de Vigilância em Saúde, Ministério da Saúde. Hepatites virais 2021. Boletim Epidemiológico de Hepatites Virais 2021; número especial..

Groups at higher risk for hepatitis A virus infection include: travelers to areas of high endemicity, workers in day care centers and institutions for individuals with disabilities, some categories of health workers, military personnel, sewage system workers, intravenous drug users, and men who have sex with men ¹²12. Santos MV, Lopes MH. Vacina inativada contra a hepatite A: revisão da literatura e considerações sobre seu uso. Rev Soc Bras Med Trop 1997; 30:145-57.. Hepatitis A virus seroprevalence can be highly variable according to country or within a country. Evidence shows seroprevalence differences according to age, vaccinated population, and occupation - such as nurses (41.2%), physicians (56.3%), and nursing assistants (73.9%) ¹³13. Ji SK, Jang SH, Park MH, Lee JE, Jeong HS, Park J, et al. A study on seroprevalence of hepatitis A virus among healthcare workers at a University-affiliated Hospital in Deajeon, Korea. Korean J Healthc Assoc Infect Control Prev 2020; 25:54-9.^,1414. Saneian H, Rahimi H, Shoaei P. Hepatitis A seropositivity among first-year students of the medical university in Isfahan, Iran. Int J Prev Med 2014; 5 Suppl 3:S208-12. - the number of household contacts, water quality, place of residence, and family size ¹⁴14. Saneian H, Rahimi H, Shoaei P. Hepatitis A seropositivity among first-year students of the medical university in Isfahan, Iran. Int J Prev Med 2014; 5 Suppl 3:S208-12.. Subjects with non-A hepatitis are also considered a high-risk group, including those with liver cirrhosis ¹⁵15. Özden HT. Hepatitis A seroprevalence in patients with chronic viral hepatitis in Konya, Turkey. Eur J Gastroenterol Hepatol 2016; 28:333-7.^,1616. Cho HC, Paik SW, Kim YJ, Choi MS, Lee JH, Koh KC, et al. Seroprevalence of anti-HAV among patients with chronic viral liver disease. World J Gastroenterol 2011; 17:236-41..

This study aims to estimate the seroprevalence of hepatitis A in subjects attending to a travel medicine and immunization outpatient clinics of the Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil, and to develop and validate a prediction model to estimate hepatitis A virus seroprevalence among these special groups.

Materials and methods

Settings

This is a retrospective observational study conducted at a Reference Center for Special Immunobiologicals (CRIE), a unit of the INI/Fiocruz. INI is a high-complexity hospital specialized in infectious diseases. CRIE is part of the Brazilian National Immunization Program (PNI), with many CRIE units throughout Brazil. CRIE has special immunizations to attend the special populations who require vaccines that are not usually available for the general public in regular health units and are not recommended regularly for healthy children or adults by the manual de vacinação (Brazilian vaccination booklet). Thus, CRIE has a list of health conditions or special situations when these vaccines or immunoglobulins are recommended, including adapted schemes and dosages for these cases. Before the COVID-19 pandemic, travel medicine clinics received around 1,000 appointments per year, with four outpatient shifts per week and five travelers scheduled per shift. Similarly, special populations had around 7,200 appointments yearly, and these were performed every weekday during business hours. The outpatient clinic received patients from the Rio de Janeiro Metropolitan Area, including many neighboring cities.

Participants (study sample) and data collection

The study population consisted of individuals sequentially attended from April 2011 to June 2019. These subjects were seeking care at the travel medicine clinic and CRIE, and for any reason were requested an hepatitis A virus test (anti-HAV IgG). For CRIE patients, hepatitis A virus tests were requested whenever the patient had a condition and needed vaccination for hepatitis A. For travel medicine appointments, hepatitis A virus tests are requested for all subjects advised to take the hepatitis A virus vaccine. Participants’ data were verified via electronic medical records. An inquiry to the electronic medical records was performed, in which they were first filtered by attendance at the travel medicine and immunization clinic and by availability of hepatitis A virus (anti-HAV IgG) test results, then inclusion and exclusion criteria were manually checked for each record. The inclusion criteria were individuals aged ≥ 18 years, attending to a travel medicine outpatient clinic or CRIE, and a hepatitis A test (anti-HAV IgG) request. The exclusion criteria were subjects who did not collect samples for an hepatitis A virus test or did not have a test result in the electronic medical record and subjects that had serology results without the medical request from a travel medicine outpatient clinic or CRIE (INI/Fiocruz).

Outcome

Different hepatitis A virus tests were used during the research period. The anti-HAV antibodies of the collected samples were analyzed at the INI with a chemiluminescence immunoassay (ARCHITECT HAVAb-IgG, Abbott Diagnostics; https://www.abbott.com/for-healthcare-professionals/diagnostics.html) or EIA (EIA Monolysis Total anti-HAV Plus, Bio-RAD; https://www.bio-rad.com/), according to the manufacturer’s instructions.

Predictors

The predictors with fewer missing data were sex, gender identity, age, year of birth, outpatient clinic attended, requesting physician, clinical indication, current address, and birthplace. For the research purpose, the clinical indication was considered as the main predictor, retrieved from the CRIE list ¹⁷17. Departamento de Imunização e Doenças Transmissíveis, Secretaria de Vigilância em Saúde, Ministério da Saúde. Manual dos centros de referência para imunobiológicos especiais. https://bvsms.saude.gov.br/bvs/publicacoes/manual_centros_imunobiologicos_especiais_5ed.pdf (accessed on 26/Sep/2021).
https://bvsms.saude.gov.br/bvs/publicaco... . The list contained: (1) sexual abuse; (2) accident with biological material; (3) allergy to vaccine or some component; (4) sickle cell anemia and other hemoglobinopathies; (5) functional asplenia; (6) solid organ transplant candidates; (7) heart diseases; (8) coagulopathies; (9) contacts of immunodeficient people; (10) close contacts of viral diseases; (11) hospital contact; (12) severe skin diseases; (13) diabetes mellitus; (14) solid organ donors; (15) bone marrow donor; (16) autoimmune disease; (17) deposit disease; (18) inflammatory bowel disease; (19) neurological disease; (20) previous adverse event; (21) exposure to chickenpox; (22) child of an HIV+ mother; (23) CSF fistula; (24) prison system officers; (25) pregnant; (26) liver disease; (27) chronic arterial hypertension; (28) HIV/AIDS; (29) hospitalized; (30) cochlea implant; (31) primary immunodeficiency; (32) therapeutic immunosuppression; (33) chronic nephropathy; (34) nephropathy in hemodialysis; (35) neoplasm (solid tumor); (36) hematologic neoplasm; (37) lung disease; (38) post-splenectomy; (39) post bone marrow transplant; (40) post solid organ transplantation; (41) pre-splenectomy; (42) pre-immunosuppression by biologicals; (43) pre-transplantation of solid organs; (44) pre-bone marrow transplant; (45) prematurity; (46) prevention of perinatal hepatitis B virus infection; (47) prophylaxis after risky sexual exposure (consensual); (48) health professional; (49) puerperal; (50) genetic syndromes; (51) acetylsalicylic acid allergy.

Analysis plan

The analysis plan consisted of a descriptive analysis with frequencies and dispersion of variables. Prevalence ratio of seropositivity was estimated via a univariate generalized linear model with quasi-Poisson distribution and exponentiating of the regression coefficient. For the continuous variables, the interpretation of prevalence ratio should be an increment in prevalence for each unit of increment of the variable.

The highest missing data within a variable was around 8%. For regression purposes, missing data were imputed with predictive mean matching (multiple imputation). Data were split into development and validation to estimate and eventually correct optimism and generate evidence that the results of the model performance is related to other samples/populations. The development set was defined as all subjects tested for hepatitis A virus from 2011 to 2017 and the validation set was composed of those tested for hepatitis A virus in 2018 and 2019. The regression approach was conducted with a cross-validated, elastic, and generalized linear model with binomial distribution, thus the final model coefficients were converted into odds ratios. This approach allows simultaneous penalization of the model, avoiding overfitting and optimism, using a lasso-type selection and ridge-type penalization. Therefore, the predictors with no contribution for the predictions had their coefficients shrinked to 0. Moreover, this approach does not drop the baseline level for factors, so that the regularization process will shrink the fitted coefficients toward the overall mean rather than toward the estimate for the baseline predictor level. The full model initially tested was year of birth, age, medical indication for immunization, sex, and an interaction of age and year of birth, and the final model was extracted from 100 cross-validated folds from the fold with the least mean squared error. Then, predictions were performed in both the development and the validation sets, and from those the calibration and discrimination measures were estimated: area under the ROC (receiver operating characteristics) curve (AUC - area under the curve), R², Brier score, model intercept, model slope, errors (distances) from the predicted probabilities to observed probabilities. The analysis was conducted using the R-project software (http://www.r-project.org) with the following packages: Hmisc, DiagrammeR, mice, stats, MASS, glmnet, and glmnetUtils. Moreover, the model was implemented on an online calculator with packages shiny and shinydashboardPlus to allow users to estimate individual probabilities for hepatitis A virus antibodies (or the prevalence of hepatitis A virus within groups of desired characteristics): https://pedrobrasil.shinyapps.io/INDWELL/.

Ethics

All measures of protection and confidentiality of the patients were followed, based on the good clinical practice and regulatory standards for research with human beings, following the Resolution n. 466/2012 of the Brazilian National Health Council. The project approval can be accessed on the Brazilian National Ethics System for research with human beings (https://plataformabrasil.saude.gov.br/login.jsf - with the number 85365318.4.0000.5262).

Results

Participants and seroprevalence

In total, 2,976 electronic medical records were verified. After applying the inclusion and exclusion criteria, we analyzed 2,944 records (Figure 1).

From the 2,944 attended participants, hepatitis A virus’s overall seroprevalence was 67.8% from November 21, 2011 to November 11, 2019 (Table 1). The median age was 42 years, and it was higher among hepatitis A virus reagent subjects. As age increased, seroprevalence also increased. Likewise, as year of birth increased, seroprevalence decreased (Table 1). The seroprevalence among travelers (pre-travel) was much lower than among subjects with chronic conditions seeking vaccinations at the CRIE. Moreover, subjects attended up to 2017 (development set) had slightly higher seroprevalence than subjects attended in 2018 and 2019 (validation set) (Table 1).

The travelers group was the biggest group analyzed, making up 39.9% of the sample. From the CRIE list of special populations, four major groups made up 42.1% of the sample: candidates for solid organ transplantation, HIV/AIDS, spleen dysfunction, and therapeutic or cancer-related immunosuppression.

The different groups attending to CRIE for vaccination had a substantial difference in seroprevalence. Some groups had a substantially lower seroprevalence than the overall seroprevalence, namely: health professionals, travelers, and those who had contact with immunocompromised subjects (Table 2). A group characterized as “others”, which is an aggregate of indications, had a low attendance frequency at the CRIE.

Three groups had very high seroprevalence: chronic lung disease, chronic liver disease, and chronic heart disease (Table 2). The lowest seroprevalence was found in healthcare professionals and travelers (Table 2).

Model development

As progressively fewer participants were born before 1960, the year of birth was truncated at 1960, that is, participants born in 1960 or before were considered to have the same effect on predictions. In the adjusted analysis, all initial predictors were retained: year of birth, age, sex, PNI special population list (indication for vaccination), including the interaction of age and year of birth (Table 3). The interaction term had a very small effect, but it is highly significant. The retained interaction term means that there is a cohort effect (typical on hepatitis A virus seroprevalence studies) and a generation effect. For example, a participant aged 20 years, born in 1991 had a different probability of having hepatitis A virus antibodies of an identical participant aged 20 years born in 1999 beyond the usual decrease of seroprevalence due to year of birth alone.

Due to the nature of the modeling, one can see that some categories of the vaccination indication (PNI special group list) were removed (Table 3). This means that these categories had their effect reduced to 0. The retained categories representing the vaccination indications were travelers, HIV/AIDS, spleen dysfunction, transplant candidates, household communicators, cancer-related immunosuppression, health care professionals, others, and not informed (Table 3). Additionally, one must pay attention that, regardless of the presence of odds ratios for many categories, there are mutually exclusive categories (e.g., one cannot be in the female and male categories simultaneously) and the effect is an increase or decrease related to the overall mean.

Model validation

Based on the equation provided by this regression, it is possible to estimate the seroprevalence of a particular group or subject with defined characteristics in the model. The performance measures showed that the calibration and discrimination are good to very good, for both development and validation sets. The calibration is represented by the positive relationship between the actual (observed) probability and the predicted (expected) probability, the small values of errors, the slope close to 1, intercept close to 0, and the non-significant Spigelhalter test; and the discrimination is represented by high values of the R² and AUC and small Brier score values (Figure 2). Moreover, the performance measures are very similar in both sets, meaning that performance travels and gives the user confidence that the model will behave similarly for new predictions.

Discussion

The main results are: (a) hepatitis A virus seroprevalence among the special population was high, with relevant differences across different subgroups; (b) the lowest hepatitis A virus seroprevalence was in the health professionals and travelers groups, and the highest hepatitis A virus seroprevalence were in the chronic conditions group (liver, heart, and lungs) and HIV infected subjects; (c) an instrument to predict the presence of hepatitis A virus antibodies was developed with good discrimination and calibration in both development and validation sets allowing to identify the subjects more likely to be susceptable to hepatitis A virus infection.

Age is an important indicator of the amount of exposure and is present in many studies, even in studies with special populations. The age effect is related to the idea that as one becomes older, they are more exposed over time and the seroprevalence in older subjects is higher. The year of birth effect is related to the idea that modern generations have more access to preventive measures, such as better quality water and food, sanitary conditions, and immunization, thus decreasing seroprevalence in modern generations. Differences in hepatitis A virus seroprevalence exist in health professionals according to age, similarly to the general population ¹³13. Ji SK, Jang SH, Park MH, Lee JE, Jeong HS, Park J, et al. A study on seroprevalence of hepatitis A virus among healthcare workers at a University-affiliated Hospital in Deajeon, Korea. Korean J Healthc Assoc Infect Control Prev 2020; 25:54-9.^,1818. González-Praetorius A, Rodríguez-Avial C, Fernández C, Pérez-Pomata MT, Gimeno C, Bisquert J. Prevalencia de hepatitis A en la provincia de Guadalajara. ¿Es España un país de baja endemia? Enferm Infecc Microbiol Clín 2001; 19:428-31..

Moreover, data reported here showed that subjects with chronic conditions had higher hepatitis A virus seroprevalence when compared with other special groups and the general population even when adjusted to age effect. Other independent determinants may rise even when age is adjusted, bringing more evidence to Brazil’s seroprevalence heterogeneity ¹⁹19. Kury CM, Pinto MA, Silva JP, Cruz OG, Vitral CL. Hepatitis A seroprevalence in public school children in Campos dos Goytacazes, Rio de Janeiro State, Brazil, prior to the introduction of the hepatitis A universal childhood vaccination. Cad Saúde Pública 2016; 32:e00175614.. Hepatitis A virus infection determinants possibly have interactions with characteristics of special groups, such as schooling level, housing conditions, and socioeconomic levels.

Hepatitis A virus seroprevalence among health professionals is highly variable depending on known seroprevalence determinants such as age and endemic status of an area ¹⁶16. Cho HC, Paik SW, Kim YJ, Choi MS, Lee JH, Koh KC, et al. Seroprevalence of anti-HAV among patients with chronic viral liver disease. World J Gastroenterol 2011; 17:236-41.. In Northern Iran, hepatitis A virus seroprevalence was estimated to be 57.8-86.3% ²⁰20. Bayani M, Sadeghi M, Kalantari N, Sayadmanesh A. Hepatitis A virus seropositivity in nurses and paramedical personnel at a University Hospital in North Iran. Iran Red Crescent Med J 2013; 15:409-13.. Meanwhile, in Turkey, hepatitis A virus seroprevalence was estimated to be 34.9% among first-year students in the health field ²¹21. Acikgoz A, Cimrin D, Kizildag S, Esen N, Balci P, Sayiner AA. Hepatitis A, B and C seropositivity among first-year healthcare students in western Turkey: a seroprevalence study. BMC Infect Dis 2020; 20:529.. The results presented here follow the interpretation that the overall seroprevalence among health professionals was around 40%, and it also increased as age increased and decreased as year of birth year.

The burden of hepatitis A virus is greater among people living with HIV, and the hepatitis A virus viral load is higher and viremia is longer in HIV-infected people than in non-HIV patients ²²22. Gallego M, Robles M, Palacios R, Ruiz J, Nuño E, Márquez M, et al. Impact of acute hepatitis A virus (HAV) infection on HIV viral load in HIV-infected patients and influence of HIV infection on acute HAV infection. J Int Assoc Physicians AIDS Care (Chic) 2011; 10:40-2.. Hepatitis A virus seroprevalence is higher among HIV infected patients and among men who have sex with men than in the general population. Evidence also suggests that the age effect is also present in this group even when adjusted for other determinants, such as regionality and concomitant hepatitis B infection ¹²12. Santos MV, Lopes MH. Vacina inativada contra a hepatite A: revisão da literatura e considerações sobre seu uso. Rev Soc Bras Med Trop 1997; 30:145-57.^,2323. Lee YL, Lin KY, Cheng CY, Li CW, Yang CJ, Tsai MS, et al. Evolution of hepatitis A virus seroprevalence among HIV-positive adults in Taiwan. PLoS One 2017; 12:e0186338.. Hepatitis A virus seroprevalence among people living with HIV is also variable, being estimated from 15% to 97%, as described in several studies ²³23. Lee YL, Lin KY, Cheng CY, Li CW, Yang CJ, Tsai MS, et al. Evolution of hepatitis A virus seroprevalence among HIV-positive adults in Taiwan. PLoS One 2017; 12:e0186338.^,2424. Aloise R, De Almeida AJ, Sion FS, Morais-De-Sá CA, Gaspar AMC, De Paula VS. Changes in hepatitis A virus Seroepidemiology in HIV-Infected Brazilian patients. Int J STD AIDS 2008; 19:321-6.^,2525. Tseng YT, Sun HY, Chang SY, Wu CH, Liu WC, Wu PY, et al. Seroprevalence of hepatitis virus infection in men who have sex with men aged 18-40 years in Taiwan. J Formos Med Assoc 2012; 111:431-8..

Acute hepatitis A in patients with chronic hepatitis B is clinically more severe and has a higher risk of death ²⁶26. Reiss G, Keeffe EB. Hepatitis vaccination in patients with chronic liver disease. Aliment Pharmacol Ther 2004; 19:715-27.. Case fatality rates for acute hepatitis A in hepatitis B antigen carriers are 5.6 times higher when compared with HBsAg-negative patients ²⁷27. Ahmad F, Hamzah NAC, Mustaffa N, Gan SH. Anti-hepatitis A seroprevalence among chronic viral hepatitis patients in Kelantan, Malaysia. World J Gastroenterol 2011; 17:4130-4.. Hepatitis A virus seroprevalence is also variable among this group (with liver disease hepatitis B virus, hepatitis C virus, or liver cirrhosis) being estimated from 55% to 100% ¹⁶16. Cho HC, Paik SW, Kim YJ, Choi MS, Lee JH, Koh KC, et al. Seroprevalence of anti-HAV among patients with chronic viral liver disease. World J Gastroenterol 2011; 17:236-41.^,2828. Shoaei P, Zeidabadinejad L, Hassannejad R, Ataei B, Yaran M, Kassaian N, et al. Seroprevalence of hepatitis A in patients with chronic hepatitis C in Isfahan Province. Int J Prev Med 2012; 3 Suppl 1:S102-6..

Globalization is changing hepatitis A virus epidemiology. Developments arising from the globalization have allowed diseases to spread more easily and more quickly across international borders ²⁹29. Gushulak BD, MacPherson DW. Population mobility and infectious diseases: the diminishing impact of classical infectious diseases and new approaches for the 21st century. Clin Infect Dis Off Publ Infect Dis Soc Am 2000; 31:776-80.. Hepatitis A virus is one of the most common vaccine-preventable diseases among international travelers ³⁰30. Boggild AK, Castelli F, Gautret P, Torresi J, von Sonnenburg F, Barnett ED, et al. Vaccine preventable diseases in returned international travelers: results from the GeoSentinel Surveillance Network. Vaccine 2010; 28:7389-95.. Susceptible travelers can contract the virus and often become ill after returning to their country of origin ³¹31. Jacobsen KH. Globalization and the changing epidemiology of hepatitis A virus. Cold Spring Harb Perspect Med 2018; 8:a031716..

Hepatitis A virus seroprevalence among travelers is also variable, and besides the place and age determinants, vaccination status and the visiting places may also play a role. Hepatitis A virus seroprevalence among European travelers ranged from 57.6% to 78.9% ³²32. Rocha S, Tejo S, Ferreira E, Trindade L, Rabadão E, Marques N, et al. Prevalence of hepatitis A virus antibody in Portuguese travelers: a new paradigm. Acta Med Port 2017; 30:534-40..

The literature has few models to predict hepatitis A outbreaks and hepatitis A-related mortality in special populations, such as liver transplant. We found few multivariable analyses stating hepatitis A virus antibodies as the outcome, however we could not find any published development or validation of a model to predict hepatitis A virus infection or prevalence. The model presented here can be recommended to estimate hepatitis A virus seroprevalence in similar settings, or to estimate the individual probability of hepatitis A virus antibodies. This estimate may help decide if subjects should be further tested/investigated for hepatitis A virus or should be vaccinated.

Some restrictions must be considered. Firstly, this is a retrospective study and some relevant epidemiological data were not available, such as socioeconomic characteristics, schooling level, income, number of households, etc., and were not explored as potential predictors. Moreover, hapatitis A virus seroprevalence may change over time, possibly determining the need for a model update. One may are not be sure if the results observed at an immunization clinic, where subjects seek care on their own, can be inferred to other clinics or special populations that would never seek vaccination.

Conclusions

We conclude that hepatitis A virus seroprevalence was 67.8% in this adult population, but this special group was heterogeneous and seroprevalence may range from 40% to 95.6%. Moreover, hepatitis A virus seroprevalence was slightly decreasing over time, and, as expected, we observed an evident age, year of birth effect, and an interaction between them. The groups with the lowest hapatitis A virus seroprevalence were health professionals and travelers. These groups should be evaluated more carefully regarding their need for vaccination when seeking immunization clinics for other purposes.

The developed model allows for an accurate estimation of the seroprevalence of a particular special group or estimate the probability of a particular subject to have hepatitis A virus antibodies and further consider the need of vaccination or further testing, adjusted for age and birth year.

Acknowledgments

This study was partly supported by the General Coordination of Education, Vice Presidency of Education, Information and Communication (CGE/VPEIC), via a grant from the Rio de Janeiro State Research Foundation (FAPERJ; Grant E-26/210.246/2021) and the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES; finance code 001).

References

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