Seroprevalence of Hepatitis A Virus among people born before and after implementation of universal vaccination in Argentina

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In 2005, a single dose of HAV vaccine was implemented for one-year-old children. However, despite vaccination success, a proportion of cases persists. This study aimed to assess the seroepidemiology of HAV in Argentina, analyzing IgG and IgM antibodies against HAV in a sizable population, both vaccinated and unvaccinated. Methods : This retrospective analysis involved 16,982 patients attending a tertiary-care hospital in Buenos Aires, Argentina. Patients were divided into two groups: those evaluated before vaccination and those suspected of having acute hepatitis. Results : Anti-HAV IgG was detected in 9,403 out of 16,587 (56.7%). A higher rate was observed in those individuals born after vaccine implementation (77.7%) compared to those born before (56.3%), p<0.001. The groups aged 19 to 40 and 41 to 60 exhibited the lowest anti-HAV IgG rates. Out of the 3,956 patients assessed for acute hepatitis, 100 (2.5%) tested positive for Anti-HAV IgM. Remarkably, none of the patients covered by mandatory vaccination showed positive Anti-HAV IgM. Conclusions : This large study outlines the seroepidemiology status of HAV in Argentina and underscores the impact of vaccination in reducing infections. Despite the success of the vaccine, certain groups of susceptible individuals still persist, particularly among unvaccinated adults. These findings reveal the importance of targeting vaccination campaigns towards the most vulnerable age groups and emphasize the effectiveness of universal vaccination in reducing the incidence of HAV. This comprehensive analysis provides essential insights for public health planning and guides future immunization strategies against HAV in Argentina. Hepatitis A Virus Epidemiology Vaccine immune response Seroprevalence. Introduction Hepatitis A infection is a global public health problem, particularly in developing countries with shortages in sanitary conditions and hygienic practices [1]. The hepatitis A virus (HAV) is transmitted mainly by the fecal-oral route as a result of ingesting contaminated water or food, although it can also be transmitted through direct contact with an infected person [2]. HAV causes self-limiting infections that are usually asymptomatic in children, However, in adulthood the rate of symptoms and complications is higher, significantly increasing morbidity and mortality. The endemicity of HAV in different regions of the world is classified, according to the age-specific seroprevalence of IgG anti-HAV in the population, as high (≥90% at 10 years), intermediate (≥50% at 15 years, with <90% at age 10 years), low (≥50% at 30 years, with <50% at 15 years) or very low (<50% at 30 years) [3]. Hepatitis A is an infection that can be prevented by vaccination and depending on the levels of endemicity. The World Health Organization (WHO) recommends its mandatory implementation for children ≥12 months of age in countries with high/intermediate endemicity, while in countries with very low and low endemicity only for those people with a higher risk of infection and/or severe disease [4]. Currently, only 23 countries worldwide have fully incorporated HAV vaccination into the national scheme, 3 partially and 20 in risk groups [5]. In Argentina, in 2005, a single-dose of HAV vaccination was introduced into the mandatory schedule for children at 12 months of age since HAV was the leading cause of fulminant hepatic failure in children [6]. After the implementation of vaccination in the schedule, a drastic decrease in incidence was observed. Furthermore, the measure produced a great impact on the behavior of the disease, marking the disappearance of annual epidemic outbreaks and associated complications, such as fulminant hepatitis and liver transplantation [7]. However, despite the success achieved through vaccine implementation, hepatitis A cases still represent 5% of hepatitis [8] and in recent years, there have been, as in other regions of the world, outbreaks in the population that remain unvaccinated [9,10]. It is established that IgG antibodies against HAV, whether because of natural infection or induced by a vaccine, provide long lasting protection against the disease. Argentina has been a highly endemic country until the incorporation of the vaccine into the national calendar. For this reason, it is plausible that currently, due to natural infection or vaccination, a large proportion of the population has protective antibodies. Currently, there is a paucity of data on the HAV antibodies coverage rate, both in the population reached by the implementation of the vaccine and in those who were not. Aimed to assess the seroepidemiology of HAV in Argentina, in vaccinated and unvaccinated people, IgG and IgM antibodies against HAV were determined in a large sample size from the population of Argentina. Material and Methods Study population A retrospective study was carried out on patients who attended at Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), a hospital located in the city of Buenos Aires, Argentina. The studied cohort included 16,982 patients divided in two main groups, - individuals evaluated for HAV status before HAV vaccination, with or without chronic liver diseases and - patients suspected of acute hepatitis, whose samples were tested for the presence of anti-HAV IgG and anti-HAV IgM. Furthermore, 344 of these samples were from children reached by the 2005 vaccine implementation, and 16,638 samples from individuals collected from September 2001 until September 2023. In addition, participants were grouped according to their age: under 18 years old, 19-40 years old, 41-60 years old, 61-80 and older than 80 years old. Laboratory determinations Qualitative determination of IgG antibodies against HAV (anti-HAV IgG) were tested by Axsym System HAVAb 2.0 (Abbott diagnostics, Wiesbaden, Germany), Architect System HAVAb-IgG (Abbott diagnostics, Wiesbaden, Germany) and Elecsys Anti-HAV IgG immunoassay (Roche Diagnostics International Ltd, Switzerland) according to availability and following the manufacturer’s instructions. Additionally, in accordance with medical requirements, anti-HAV IgM testing was performed to determine the presence of an ongoing infection using the Elecsys Anti-HAV IgM immunoassay (Roche Diagnostics International Ltd, Switzerland). Statistical analysis Frequencies were compared using the chi-square test or the Fisher’s test. The Student’s t-test and the Mann-Whitney U were used for comparing continuous variables. In order to identify predictors of seroprotective status in the analyzed population, a logistic regression analysis adjusted for age and sex was performed. Factors associated with seroprotective status in the bivariate analysis with a p value 0.2 were entered as covariates. The statistical analysis was carried out using the SPSS statistical software package release 23.0 (IBM SPSS Inc., Chicago, IL, USA). Results Characteristics of the study population A cohort of 16,982 patients was analyzed, median (Q1-Q3) age was 38 (27-52) years old and 9.314 (54.8%) were female. Of them, 13,026 were tested for anti-HAV IgG, 402 for anti-HAV IgM, and 3,554 for both IgG and IgM. Thus, anti-HAV IgG was determined in 16,587 patients and anti-HAV IgM in 3,956 patients. The epidemiological characteristics of the population under analysis, those individuals evaluated for anti-HAV IgG status prior to HAV vaccination (N= 13,026) and those patients suspected of experiencing acute hepatitis (N=3,956), are shown in Table 1. Moreover, from this analyzed population, 344 patients (2.0%) were born after the mandatory HAV vaccine implementation in 2005, and 16,638 (98.0%) were born before. The median age (Q1-Q3) of the patients reached by the vaccine implementation was 6 years (2-14) and 163 (47.4%) were women. The age of those not reached by the vaccine was 38 years (28-53), with 9,151 (55%) being women. Seroprevalence of Anti-HAV IgG Overall, anti-HAV IgG was detected in 9,403 out of 16,587 patients (56.7%). Anti-HAV IgG tended to be higher in women (57.3%) than in men (55.9%), p=0.073. Anti-HAV IgG seropositive population was older [39 years (29-48)] when compared to the seronegative one [37 years (26-56)], (p<0.001). Additionally, the groups with significant lower rates of HAV IgG antibodies were those aged 19-40 and 41-60 years (Table 2). Among the population under suspicion of acute infection, the prevalence of HAV IgG antibodies was 58.0%, whereas in the screening-tested population, it stood at 56.3%, with a p-value of 0.073 (refer to Table 2) When anti-HAV IgG rates were compared between those born after vaccine implementation and those before, a significantly higher seroprevalence was observed in the former group, 77.7% vs 56.3%, p<0.001. Moreover, in individuals under 18 who were covered by the vaccine, the seroprevalence rate of anti-HAV IgG was significantly higher with 255 out of 328 (77.7%). This contrasted with the same age group among those born prior to the introduction of the vaccine, where 524 out of 785 (66.8%) exhibited anti-HAV IgG. This difference was statistically significant (p < 0.001), even in a region characterized by high endemicity. The characteristics of the analyzed population by Anti-HAV IgG are shown in Table 2. Seroprevalence of Anti-HAV IgM Anti-HAV IgM was detected in 100 out of 3956 patients (2.5%). Remarkably, when comparing the presence of anti-HAV IgM between the patients born before or after the vaccine’s introduction, all cases testing positive for anti-HAV-IgM correspond to the population not reached by the vaccine. While 2.6% of patients not reached by the vaccine tested positive for anti-HAV IgM, none of the 153 patients covered by mandatory vaccination showed positive HAV IgM results, p=0.033. The characteristics of the analyzed population by anti-HAV IgM are shown in table 3. On the other hand, in order to evaluate whether the implementation of the HAV vaccine had an effect on viral circulation, irrespective of whether they have received the vaccine or not, the number of infections detected in the test conducted before and after 2005 was compared. In this regard, it was observed that 23 out of 317 (7.3%) anti-IgM tests conducted before 2005, yielded reactive results, while the rate of reactive results after the vaccine implementation dropped to 2.1% (77 out of 3639), p<0.001. Discussion HAV infection remains a public health problem despite the availability of a safe and effective vaccine since the 1990s. Although the mortality rate has decreased in recent decades, a global increase in incidence has recently been reported, with HAV being the main causative agent of acute viral hepatitis worldwide [11]. Those countries that in recent years have significantly reduced the incidence of HAV, thanks to improvements in sanitary and socioeconomic conditions, as well as the implementation of different vaccination strategies, undergo a drastic change in endemicity. Paradoxically, this has implied an epidemiological shift from mainly childhood and mostly asymptomatic infections to the older population and, consequently, the number of symptomatic cases has increased [12]. This event has also been described for other vaccine-preventable infections [13]. To our knowledge, this study constitutes the largest cohort analyzed in Argentina with almost 17,000 individuals. The results obtained in this study reveal an anti-HAV IgG seroprevalence (56.3%) within previously published ranges: higher than that found by Lopez et al in 2000 (42.2%) among 360 individuals from the same geographical region [14] but lower than those reported by Yáñez in 416 individuals (73.5%) or Angeleri in 3,833 individuals (63.9%) from other regions of the country [15,16]. Differences among these studies could be attributed to socio-economic disparities, diverse geographical settings, variations in access to safe drinking water and sanitation, as well as discrepancies in the timing of the conducted research. In the populationborn afterthe introduction of the vaccine, the antibody rate was 77.7%. In this regard, it must be considered that the country's health authorities reported a HAV vaccine coverage rate ranging between 94 and 100% from 2005 to 2014. However, a gradual decline was observed, reaching its lowest level of 78% in 2020, potentially influenced by the SARS-CoV-2 pandemic. Subsequently, coverage remained below 90% for both 2021 and 2022 [17]. In this context, two Argentine studies, published in 2015 and 2016, demonstrated a high prevalence of anti-HAV IgG after 4 and 9-years post-vaccination (93.0% and 97.4%, respectively) [18,19]. Notably, despite showing antibodies waning over time, no association has been established with HAV outbreaks or breakthrough infections. This observation underscores the significant role of memory immunity in providing sustained protection [20]. Therefore, those children and adolescents with undetectable levels of anti-HAV IgG who have been vaccinated would be protected against infection. On the other hand, a lower seroprevalence of anti-HAV IgG (56.3%) was observed in the population born before HAV vaccine implementation. Furthermore, a correlation was noted between the antibody rate and age, with a higher prevalence (≥70%) observed in patients aged 60 and above. A possible explanation for this phenomenon could be related to the longer exposure time in a country that maintained a medium to high endemicity until 2005. It´s important to mention that, between 2017 and 2019, different outbreaks were reported, mainly in the central region of the country and predominantly affecting adults aged between 20 and 39 years [9,10]. These investigations revealed that most of the cases involved unvaccinated men who have sex with men. This data agrees with the seroprevalence observed in our study, where the age group most susceptible to HAV infection, given the low prevalence of anti-HAV IgG (just above 50%), was observed to be individuals aged 19 to 40 years. All the aforementioned is in line with the evolving epidemiology of HAV infection, transitioning from isolated outbreaks associated with contaminated food to large community outbreaks associated with person-to-person transmission as documented in different regions worldwide [21-25]. This scenario highlights the need to strengthen vaccination, not only through compliance with the national calendar, but also among vulnerable adults who currently make up sporadic outbreaks with the risk of progressing to severe forms. After evaluating nearly 4,000 cases of acute hepatitis, the prevalence of anti-HAV IgM was 2.5%, and positive cases were only observed in patients born before the implementation of the vaccine. Moreover, even when cases of acute HAV were only detected in the population not covered by the vaccine, it's important to highlight that the positive impact of vaccination was also evident in reducing the number of cases in the overall population. This was reflected in our study, since the positivity rate of anti-HAV IgM decreased by more than threefold when comparing test conducted before and after 2005. It is worth mentioning that, since 2005, there has been just one reported outbreak in the northwest region of the country among individuals born after the vaccine's inclusion in the schedule. This outbreak primarily impacted children who had not received the vaccination [26]. The main limitations of this study are that there is no additional information available about the cohort such as socioeconomic characteristics, behaviors and other factors associated with the transmission of the infection. On the other hand, although the vaccination coverage rate has been broad since its incorporation into the scheme, information is not available for each case on the immunization status in the population born after 2005. Conclusions This study provides new insights into the HAV epidemiology in Argentina in a large cohort. The findings highlight the effect of the vaccine implementation on the calendar and stress the importance of focus vaccination campaigns in the population between 19 and 60 years old. Likewise, it serves as an example regarding the effectiveness of the single-dose vaccination strategy implemented in Argentina. Finally, the findings of this study contribute to the planning of the national public health system and are useful to control and evaluate the effectiveness of vaccination plans and campaigns, as well as to guide future immunization programs against HAV in our country. Declarations Acknowledgements DMF, ER, PB, E Ramírez and FAD are members of the National Research Council (CONICET) Research Career Program. The authors want to thank to María Ferreyra for technical assistance. Author contributions: DMF and FAD: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, final approval of the version to be submitted. ER and PB: Analysis and interpretation of data, Data curation, Validation, drafting the article, revising the article critically for important intellectual content, final approval of the version to be submitted. FG, E Ramirez and APM: Data curation, Validation, drafting the article, final approval of the version to be submitted. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Competing interest : On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical Approval and Informed Consent The study was designed and performed according to the Helsinki declaration. Study protocol 11935, Ethics Committee of Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC. References Bhadoria AS, Khwairakpam G, Grover GS, et al. Viral Hepatitis as a Public Health Concern: A Narrative Review About the Current Scenario and the Way Forward. 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Tables TABLE 1: Characteristics of the analyzed population by groups of patients. Characteristic Total (N=16982) Anti-HAV IgG Screening (N=13026) Suspected of acute infection (N=3956) Age in year (Q1-Q3) 38 (27-52) 37 (27-51) 39 (28-55) Age Range (%) 80 226 (1.3) 117 (0.9) 109 (2.8) Sex (%) F M 9314 (54.8) 7668 (45.2) 7,307 (56.1) 5,719 (43.9) 2007 (50.7) 1949 (49.3) HAV Vaccine roll-out (%) Born before Born after 16638 (98.0) 344 (2.0) 12835 (98.5) 191 (1.5) 3803 (96.1) 153 (3.9) TABLE 2: Characteristics of the analyzed population by Anti-HAV IgG Characteristic Total (N=16587) Anti-HAV IgG Negative (N=7184) Anti-HAV IgG Positive (N=9403) p Age in year (Q1-Q3) 38 (27-52) 37 (29-48) 39 (26-56) <0.001 Age Range (%) 80 212 (1.3) 45 (21.2) 167 (78.8) <0.001 Sex (%) F M 9116 (54.9) 7471 (45.1) 3891 (42.7) 3293 (44.1) 5225 (57.3) 4178 (55.9) 0.073 HAV Vaccine roll-out (%) ▲ Born before Born after 16259 (98.0) 328 (2.0) 7111 (43.7) 73 (22.3) 9148 (56.3) 255 (77.7) <0.001 IgG Reactive (%)* Anti-HAV IgG Screening Evaluated for acute HAV 13026 (78.5) 3561 (21.5) 5689 (43.7) 1495 (42.0) 7337 (56.3) 2066 (58.0) 0.073 ▲ Anti-HAV IgG was determined in 16,587 cases, of which 16,259 were born before and 328 after the implementation of the vaccine * Of the total tests, 13,026 cases were performed as routine screening and 3,561 in suspected cases of acute infection. TABLE 3: Characteristics of the analyzed population by Anti-HAV IgM Characteristic Total (N=3956) Anti-HAV IgM Negative (N=3856) Anti-HAV IgM Positive (N=100) p Age in year (Q1-Q3) 38 (30-58) 39 (29-57) 42 (31-60) 0.070 Age Range (%) 80 109 (2.8) 103 (94.5) 6 (5.5) 0.081 Sex (%) F M 2007 (50.7) 1949 (49.3) 1965 (97.9) 1891 (97.0) 42 (2.1) 58 (3.0) 0.085 HAV Vaccine roll-out (%) Born before Born after 3803 (96.1) 153 (3.9) 3703 (96.0) 153 (100) 100 (4.0) 0 (0) 0.033 Anti-HAV IgG* Positive Negative 2066 (58.0) 1495 (42.0) 1996 (96.6) 1477 (98.8) 70 (3.4) 18 (1.2) <0.001 * Anti-HAV IgG was determined in 3561 samples (3473 patients with negative anti-HAV IgM and 88 patients with anti-HAV IgM) Additional Declarations No competing interests reported. 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Lello","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBAC9gYGgwMPGCxkGNgbH3xgbGBgMCCkhecAUEsCgwQPA89hwxlEa2EAa5FIJlYL++GNBxIqJHj4JR8zNvPuYEjczn6A8XMFPi08aQUHEs5I8EjOTgZqOcOQuLMngVnyDB4t9gw5BgcS2yR4DG7nH3/M28aQuAHoNckGfLbwvwFq+QfUcvMw0BaQlvMPmH/i1SIBsqUBqOUGM1TLjQQ2/LZIPAP65RjQLz3JjI1zz0gY75zxsM0Sv8OSN3/4UGMjx89+mLHh7Q4b2e38yYdv4tOCApiAsQOkGInWAFT7g3i1o2AUjIJRMIIAANSTUJus1aI/AAAAAElFTkSuQmCC","orcid":"","institution":"Universidad de Buenos Aires","correspondingAuthor":true,"prefix":"","firstName":"Federico","middleName":"DI","lastName":"Lello","suffix":""}],"badges":[],"createdAt":"2024-02-21 14:56:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3976025/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3976025/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51655103,"identity":"6893ff8e-23df-4325-a63c-676d859e30c6","added_by":"auto","created_at":"2024-02-26 16:47:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":226016,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3976025/v1/811672e3-e4ff-43fc-a2e3-9b9719669446.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Seroprevalence of Hepatitis A Virus among people born before and after implementation of universal vaccination in Argentina","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatitis A infection is a global public health problem, particularly in developing countries with shortages in sanitary conditions and hygienic practices [1].\u003c/p\u003e\n\u003cp\u003eThe hepatitis A virus (HAV) is transmitted mainly by the fecal-oral route as a result of ingesting contaminated water or food, although it can also be transmitted through direct contact with an infected person [2].\u003c/p\u003e\n\u003cp\u003eHAV causes self-limiting infections that are usually asymptomatic in children, However, in adulthood the rate of symptoms and complications is higher, significantly increasing morbidity and mortality.\u003c/p\u003e\n\u003cp\u003eThe endemicity of HAV in different regions of the world is classified, according to the age-specific seroprevalence of IgG anti-HAV in the population, as high (\u0026ge;90% at 10 years), intermediate (\u0026ge;50% at 15 years, with \u0026lt;90% at age 10 years), low (\u0026ge;50% at 30 years, with \u0026lt;50% at 15 years) or very low (\u0026lt;50% at 30 years) [3].\u003c/p\u003e\n\u003cp\u003eHepatitis A is an infection that can be prevented by vaccination and depending on the levels of endemicity. The World Health Organization (WHO) recommends its mandatory implementation for children \u0026ge;12 months of age in countries with high/intermediate endemicity, while in countries with very low and low endemicity only for those people with a higher risk of infection and/or severe disease [4]. Currently, only 23 countries worldwide have fully incorporated HAV vaccination into the national scheme, 3 partially and 20 in risk groups [5].\u003c/p\u003e\n\u003cp\u003eIn Argentina, in 2005, a single-dose of HAV vaccination was introduced into the mandatory schedule for children at 12 months of age since HAV was the leading cause of fulminant hepatic failure in children [6]. After the implementation of vaccination in the schedule, a drastic decrease in incidence was observed. Furthermore, the measure produced a great impact on the behavior of the disease, marking the disappearance of annual epidemic outbreaks and associated complications, such as fulminant hepatitis and liver transplantation [7].\u003c/p\u003e\n\u003cp\u003eHowever, despite the success achieved through vaccine implementation, hepatitis A cases still represent 5% of hepatitis [8] and in recent years, there have been, as in other regions of the world, outbreaks in the population that remain unvaccinated [9,10].\u003c/p\u003e\n\u003cp\u003eIt is established that IgG antibodies against HAV, whether because of natural infection or induced by a vaccine, provide long lasting protection against the disease. Argentina has been a highly endemic country until the incorporation of the vaccine into the national calendar. For this reason, it is plausible that currently, due to natural infection or vaccination, a large proportion of the population has protective antibodies.\u003c/p\u003e\n\u003cp\u003eCurrently, there is a paucity of data on the HAV antibodies coverage rate, both in the population reached by the implementation of the vaccine and in those who were not.\u003c/p\u003e\n\u003cp\u003eAimed to assess the seroepidemiology of HAV in Argentina, in vaccinated and unvaccinated people, IgG and IgM antibodies against HAV were determined in a large sample size from the population of Argentina.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective study was carried out on patients who attended at\u0026nbsp;Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), a hospital located in the city of Buenos Aires, Argentina.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe studied cohort included 16,982 patients divided in two main groups, - individuals evaluated for HAV status before HAV vaccination, with or without chronic liver diseases and - patients suspected of acute hepatitis, whose samples were tested for the presence of anti-HAV IgG and anti-HAV IgM.\u0026nbsp;Furthermore, 344 of these samples were from children reached by the 2005 vaccine implementation, and 16,638 samples from individuals collected from September 2001 until September 2023. In addition, participants were grouped according to their age: under 18 years old, 19-40 years old, 41-60 years old, 61-80 and older than 80 years old.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLaboratory determinations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eQualitative determination of IgG antibodies against HAV (anti-HAV IgG) were tested by Axsym System HAVAb 2.0 (Abbott diagnostics, Wiesbaden, Germany), Architect System HAVAb-IgG (Abbott diagnostics, Wiesbaden, Germany) and Elecsys Anti-HAV IgG immunoassay (Roche Diagnostics International Ltd, Switzerland) according to availability and following the manufacturer’s instructions. Additionally, in accordance with medical requirements, anti-HAV IgM testing was performed to determine the presence of an ongoing infection using the Elecsys Anti-HAV IgM immunoassay (Roche Diagnostics International Ltd, Switzerland).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFrequencies were compared using the chi-square test or the Fisher’s test. The Student’s t-test and the Mann-Whitney U were used for comparing continuous variables. In order to identify predictors of seroprotective status in the analyzed population, a logistic regression analysis adjusted for age and sex was performed. Factors associated with seroprotective status in the bivariate analysis with a p value 0.2 were entered as covariates. The statistical analysis was carried out using the SPSS statistical software package release 23.0 (IBM SPSS Inc., Chicago, IL, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eCharacteristics of the study population\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA cohort of 16,982 patients was analyzed, median (Q1-Q3) age was 38 (27-52) years old and 9.314 (54.8%) were female. Of them, 13,026 were tested for anti-HAV IgG, 402 for anti-HAV IgM, and 3,554 for both IgG and IgM. Thus, anti-HAV IgG was determined in 16,587 patients and anti-HAV IgM in 3,956 patients. The epidemiological characteristics of the population under analysis, those individuals\u0026nbsp;evaluated for anti-HAV IgG status prior to HAV vaccination (N= 13,026) and those patients suspected of experiencing acute hepatitis (N=3,956), are shown in\u0026nbsp;Table 1.\u003c/p\u003e\n\u003cp\u003eMoreover, from this analyzed population, 344 patients (2.0%) were born after the mandatory HAV vaccine implementation in 2005, and 16,638 (98.0%) were born before. The median age (Q1-Q3) of the patients reached by the vaccine implementation was 6 years (2-14) and 163 (47.4%) were women. The age of those not reached by the vaccine was 38 years (28-53), with 9,151 (55%) being women.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSeroprevalence of Anti-HAV IgG\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOverall, anti-HAV IgG was detected in 9,403 out of 16,587 patients (56.7%). Anti-HAV IgG tended to be higher in women (57.3%) than in men (55.9%), p=0.073. Anti-HAV IgG seropositive population was older [39 years (29-48)]\u0026nbsp;when compared to the seronegative one [37 years (26-56)], (p\u0026lt;0.001). Additionally, the groups with significant lower rates of HAV IgG antibodies were those aged 19-40 and 41-60 years (Table 2).\u003c/p\u003e\n\u003cp\u003eAmong the population under suspicion of acute infection, the prevalence of HAV IgG antibodies was 58.0%, whereas in the screening-tested population, it stood at 56.3%, with a p-value of 0.073 (refer to Table 2)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhen anti-HAV IgG rates were compared between those born after vaccine implementation and those before, a significantly higher seroprevalence was observed in the former group, 77.7% vs 56.3%, p\u0026lt;0.001.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMoreover, in individuals under 18 who were covered by the vaccine, the seroprevalence rate of anti-HAV IgG was significantly higher with 255 out of 328 (77.7%). This contrasted with the same age group among those born prior to the introduction of the vaccine, where 524 out of 785 (66.8%) exhibited anti-HAV IgG. This difference was statistically significant (p \u0026lt; 0.001), even in a region characterized by high endemicity. The characteristics of the analyzed population by Anti-HAV IgG are shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSeroprevalence of Anti-HAV IgM\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAnti-HAV IgM was detected in 100 out of 3956 patients (2.5%). Remarkably, when comparing the presence of anti-HAV IgM between the patients born before or after the vaccine’s introduction, all cases testing positive for anti-HAV-IgM correspond to the population not reached by the vaccine. While 2.6% of patients not reached by the vaccine tested positive for anti-HAV IgM, none of the 153 patients covered by mandatory vaccination showed positive HAV IgM results, p=0.033. The characteristics of the analyzed population by anti-HAV IgM are shown in table 3.\u003c/p\u003e\n\u003cp\u003eOn the other hand, in order to evaluate whether the implementation of the HAV vaccine had an effect on viral circulation, irrespective of whether they have received the vaccine or not, the number of infections detected in the test conducted before and after 2005 was compared. In this regard, it was observed that 23 out of 317 (7.3%) anti-IgM tests conducted before 2005, yielded reactive results, while the rate of reactive results after the vaccine implementation dropped to 2.1% (77 out of 3639), p\u0026lt;0.001.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHAV infection remains a public health problem despite the availability of a safe and effective vaccine since the 1990s. Although the mortality rate has decreased in recent decades, a global increase in incidence has recently been reported, with HAV being the main causative agent of acute viral hepatitis worldwide [11].\u003c/p\u003e\n\u003cp\u003eThose countries that in recent years have significantly reduced the incidence of HAV, thanks to improvements in sanitary and socioeconomic conditions, as well as the implementation of different vaccination strategies, undergo a drastic change in endemicity. Paradoxically, this has implied an epidemiological shift from mainly childhood and mostly asymptomatic infections to the older population and, consequently, the number of symptomatic cases has increased [12]. This event has also been described for other vaccine-preventable infections [13].\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this study constitutes the largest cohort analyzed in Argentina with almost 17,000 individuals. The results obtained in this study reveal an anti-HAV IgG seroprevalence (56.3%) within previously published ranges: higher than that found by Lopez et al in 2000 (42.2%) among 360 individuals from the same geographical region [14] but lower than those reported by Yáñez in 416 individuals (73.5%) or Angeleri in 3,833 individuals (63.9%) from other regions of the country [15,16]. Differences among these studies could be attributed to socio-economic disparities, diverse geographical settings, variations in access to safe drinking water and sanitation, as well as discrepancies in the timing of the conducted research.\u003c/p\u003e\n\u003cp\u003eIn the populationborn afterthe introduction of the vaccine, the antibody rate was 77.7%. In this regard, it must be considered that the country's health authorities reported a HAV vaccine coverage rate ranging between 94 and 100% from 2005 to 2014. However, a gradual decline was observed, reaching its lowest level of 78% in 2020, potentially influenced by the SARS-CoV-2 pandemic. Subsequently, coverage remained below 90% for both 2021 and 2022 [17]. In this context, two Argentine studies, published in 2015 and 2016, demonstrated a high prevalence of anti-HAV IgG after 4 and 9-years post-vaccination (93.0% and 97.4%, respectively) [18,19]. Notably, despite showing antibodies waning over time, no association has been established with HAV outbreaks or breakthrough infections. This observation underscores the significant role of memory immunity in providing sustained protection [20]. Therefore, those children and adolescents with undetectable levels of anti-HAV IgG who have been vaccinated would be protected against infection.\u003c/p\u003e\n\u003cp\u003eOn the other hand, a lower seroprevalence of anti-HAV IgG (56.3%) was observed in the population born before HAV vaccine implementation. Furthermore, a correlation was noted between the antibody rate and age, with a higher prevalence (≥70%) observed in patients aged 60 and above. A possible explanation for this phenomenon could be related to the longer exposure time in a country that maintained a medium to high endemicity until 2005.\u003c/p\u003e\n\u003cp\u003eIt´s important to mention that, between 2017 and 2019, different outbreaks were reported, mainly in the central region of the country and predominantly affecting adults aged between 20 and 39 years [9,10]. These investigations revealed that most of the cases involved unvaccinated men who have sex with men. This data agrees with the seroprevalence observed in our study, where the age group most susceptible to HAV infection, given the low prevalence of anti-HAV IgG (just above 50%), was observed to be individuals aged 19 to 40 years.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the aforementioned is in line with the evolving epidemiology of HAV infection, transitioning from isolated outbreaks associated with contaminated food to large community outbreaks associated with person-to-person transmission as documented in different regions worldwide [21-25]. This scenario highlights the need to strengthen vaccination, not only through compliance with the national calendar, but also among vulnerable adults who currently make up sporadic outbreaks with the risk of progressing to severe forms.\u003c/p\u003e\n\u003cp\u003eAfter evaluating nearly 4,000 cases of acute hepatitis, the prevalence of anti-HAV IgM was 2.5%, and positive cases were only observed in patients born before the implementation of the vaccine. Moreover, even when cases of acute HAV were only detected in the population not covered by the vaccine, it's important to highlight that the positive impact of vaccination was also evident in reducing the number of cases in the overall population. This was reflected in our study, since the positivity rate of anti-HAV IgM decreased by more than threefold when comparing test conducted before and after 2005. It is worth mentioning that, since 2005, there has been just one reported outbreak in the northwest region of the country among individuals born after the vaccine's inclusion in the schedule. This outbreak primarily impacted children who had not received the vaccination [26].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main limitations of this study are that there is no additional information available about the cohort such as socioeconomic characteristics, behaviors and other factors associated with the transmission of the infection. On the other hand, although the vaccination coverage rate has been broad since its incorporation into the scheme, information is not available for each case on the immunization status in the population born after 2005.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study provides new insights into the HAV epidemiology in Argentina in a large cohort. The findings highlight the effect of the vaccine implementation on the calendar and stress the importance of focus vaccination campaigns in the population between 19 and 60 years old. Likewise, it serves as an example regarding the effectiveness of the single-dose vaccination strategy implemented in Argentina. Finally, the findings of this study contribute to the planning of the national public health system and are useful to control and evaluate the effectiveness of vaccination plans and campaigns, as well as to guide future immunization programs against HAV in our country.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDMF, ER, PB, E Ram\u0026iacute;rez and FAD are members of the National Research Council (CONICET) Research Career Program. The authors want to thank to Mar\u0026iacute;a Ferreyra for technical assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDMF and FAD: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, final approval of the version to be submitted.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ER and PB: Analysis and interpretation of data, Data curation, Validation, drafting the article, revising the article critically for important intellectual content, final approval of the version to be submitted.\u003c/p\u003e\n\u003cp\u003eFG, E Ramirez and APM: Data curation, Validation, drafting the article, final approval of the version to be submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e: On behalf of all authors, the corresponding author states that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and Informed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was designed and performed according to the Helsinki declaration. Study protocol 11935, Ethics Committee of Centro de Educaci\u0026oacute;n M\u0026eacute;dica e Investigaciones Cl\u0026iacute;nicas Norberto Quirno \u0026quot;CEMIC.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBhadoria AS, Khwairakpam G, Grover GS, et al. Viral Hepatitis as a Public Health Concern: A Narrative Review About the Current Scenario and the Way Forward. Cureus 2022, 14 (2): e21907 [PMID: 35265429 doi: 10.7759/cureus.21907].\u003c/li\u003e\n\u003cli\u003eVan Damme P, Pint\u0026oacute; RM, Feng Z, et al. Hepatitis A virus infection. Nat Rev Dis Primers 2023, 9 (1): 51 [PMID: 37770459 doi: 10.1038/s41572-023-00461-2].\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. \u003cem\u003eWHO Immunological Basis for Immunization Series, Module 18: Hepatitis A Update.\u003c/em\u003e WHO, Geneva, Switzerland: 2019\u003c/li\u003e\n\u003cli\u003eWorld Health Organization position paper on hepatitis A vaccines - June 2012. 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Viral hepatitis and Treponema pallidum prevalence in persons who underwent premarital blood tests in Argentina. Sci Rep 2019, 9 (1): 9611. [PMID: 31270342 doi: 10.1038/s41598-019-45891-9].\u003c/li\u003e\n\u003cli\u003eIII informe sobre coberturas nacionales de vacunaci\u0026oacute;n. Ministerio de Salud Argentina. Last accessed in November 2023. https://bancos.salud.gob.ar/sites/default/files/2023-11/iii-informe-coberturas-vacunacion-argentina.pdf\u003c/li\u003e\n\u003cli\u003eVizzotti C, Gonz\u0026aacute;lez J, Rearte A, et al. Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years. J Pediatric Infect Dis Soc 2015, 4 (4): e62-7. [PMID: 26582885doi: 10.1093/jpids/piu068]. \u003c/li\u003e\n\u003cli\u003eUrue\u0026ntilde;a A, Gonz\u0026aacute;lez JE, Rearte A, et al. Single-dose Universal Hepatitis A Immunization in One-year-old Children in Argentina: High Prevalence of Protective Antibodies up to 9 Years After Vaccination. Pediatr Infect Dis J 2016, 35 (12): 1339-1342. [PMID: 27636725 doi: 10.1097/INF.0000000000001322].\u003c/li\u003e\n\u003cli\u003eUrue\u0026ntilde;a A, Badano MN, Bar\u0026eacute; P, et al. Humoral and cellular immune memory response 12 years following single dose vaccination against hepatitis A in Argentinian children. Vaccine 2022, 40 (1): 114-121. [PMID: 34838323 doi: 10.1016/j.vaccine.2021.11.037]\u003c/li\u003e\n\u003cli\u003eBard\u0026oacute;n De Tena P, Tapia Paniagua ST, Vico Sevilla JA, et al. Unusual Surge of Acute Hepatitis A Cases in 2016 and 2017 in Malaga, Southern Spain: Characterization and Relationship with Other Concurrent European Outbreaks. J Clin Med 2023, 12 (20): 6613. [PMID: 37892751 doi: 10.3390/jcm12206613]\u003c/li\u003e\n\u003cli\u003eHelmick MJ, Morrow CB, White JH, et al. Widespread Community Transmission of Hepatitis A Virus Following an Outbreak at a Local Restaurant - Virginia, September 2021-September 2022. MMWR Morb Mortal Wkly Rep 2023, 72 (14): 362-365. [PMID: 37022982 doi: 10.15585/mmwr.mm7214a2]\u003c/li\u003e\n\u003cli\u003eHofmeister MG, Xing J, Foster MA, et al. Hepatitis A Person-to-Person Outbreaks: Epidemiology, Morbidity Burden, and Factors Associated With Hospitalization-Multiple States, 2016-2019. J Infect Dis 2021, 223 (3): 426-434. [PMID: 36173747 doi: 10.15585/mmwr.mm7139a1]\u003c/li\u003e\n\u003cli\u003eBeebeejaun K, Degala S, Balogun K, et al. Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017. Euro Surveill 2017, 22 (5): 30454. [PMID: 28183392 doi: 10.2807/1560-7917]\u003c/li\u003e\n\u003cli\u003eRivas V, Barrera A, Pino K, et al. Hepatitis A outbreak since November 2016 affecting men who have sex with men (MSM) in Chile connected to the current outbreak in MSM in Europe, situation up to October 2017. Euro Surveill 2018, 23 (9): 18-00060. [PMID: 29510780 doi: 10.2807/1560-7917.ES.2018.23.9.18-00060]\u003c/li\u003e\n\u003cli\u003eBolet\u0026iacute;n N\u0026ordm;4. Hepatitis Virales en la Argentina, A\u0026ntilde;o IV \u0026ndash; Diciembre de 2022. Ministerio de salud Argentina. https://bancos.salud.gob.ar/recurso/boletin-de-hepatitis-virales-en-la-argentina-ndeg-4-dic-2022.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTABLE 1:\u0026nbsp;\u003c/strong\u003eCharacteristics of the analyzed population by groups of patients.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(N=16982)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eAnti-HAV IgG Screening\u003c/p\u003e\n \u003cp\u003e(N=13026)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003eSuspected of acute infection\u003c/p\u003e\n \u003cp\u003e(N=3956)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eAge in year (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e38 (27-52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e37 (27-51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e39 (28-55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eAge Range (%)\u003c/p\u003e\n \u003cp\u003e\u0026lt; 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1151 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e791 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e360 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e19-40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e8345 (49.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e6649 (51.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e1696 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e41-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e4921 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e3768 (28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e1153 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e61-80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e2339 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e1701 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e638 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e\u0026gt;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e226 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e117 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e109 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eSex (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;F\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9314 (54.8)\u003c/p\u003e\n \u003cp\u003e7668 (45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7,307 (56.1)\u003c/p\u003e\n \u003cp\u003e5,719 (43.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2007 (50.7)\u003c/p\u003e\n \u003cp\u003e1949 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003eHAV Vaccine roll-out (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born before\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born after\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.476190476190476%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16638 (98.0)\u003c/p\u003e\n \u003cp\u003e344 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.785714285714285%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12835 (98.5)\u003c/p\u003e\n \u003cp\u003e191 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.952380952380953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3803 (96.1)\u003c/p\u003e\n \u003cp\u003e153 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTABLE 2:\u003c/strong\u003e Characteristics of the analyzed population by Anti-HAV IgG\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"652\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(N=16587)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003eAnti-HAV IgG\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003e(N=7184)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003eAnti-HAV IgG\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003e(N=9403)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eAge in year (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e38 (27-52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e37 (29-48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e39 (26-56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eAge Range (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026lt; 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1113 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e334 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e779 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19-40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e8157 (49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e3970 (48.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e4187 (51.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;41-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e4821 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e2149 (44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e2672 (55.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;61-80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e2284 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e686 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e1598 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026gt; 80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e212 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e45 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e167 (78.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eSex (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;F\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9116 (54.9)\u003c/p\u003e\n \u003cp\u003e7471 (45.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3891 (42.7)\u003c/p\u003e\n \u003cp\u003e3293 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5225 (57.3)\u003c/p\u003e\n \u003cp\u003e4178 (55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eHAV Vaccine roll-out (%)\u003csup\u003e▲\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born before\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born after\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16259 (98.0)\u003c/p\u003e\n \u003cp\u003e328 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7111 (43.7)\u003c/p\u003e\n \u003cp\u003e73 (22.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9148 (56.3)\u003c/p\u003e\n \u003cp\u003e255 (77.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.901840490797547%\"\u003e\n \u003cp\u003eIgG Reactive (%)*\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Anti-HAV IgG Screening\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Evaluated for acute HAV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.56441717791411%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13026 (78.5)\u003c/p\u003e\n \u003cp\u003e3561 (21.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.33128834355828%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5689 (43.7)\u003c/p\u003e\n \u003cp\u003e1495 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.245398773006134%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7337 (56.3)\u003c/p\u003e\n \u003cp\u003e2066 (58.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.957055214723926%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e▲\u003c/sup\u003e Anti-HAV IgG was determined in 16,587 cases, of which 16,259 were born before and 328 after the implementation of the vaccine\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003e Of the total tests, 13,026 cases were performed as routine screening and 3,561 in suspected cases of acute infection.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTABLE 3:\u0026nbsp;\u003c/strong\u003eCharacteristics of the analyzed population by Anti-HAV IgM\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(N=3956)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003eAnti-HAV IgM Negative\u003c/p\u003e\n \u003cp\u003e(N=3856)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003eAnti-HAV IgM Positive\u003c/p\u003e\n \u003cp\u003e(N=100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eAge in year (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e38 (30-58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e39 (29-57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e42 (31-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eAge Range (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026lt; 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e360 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e356 (98.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19-40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e1696 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e1652 (97.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e44 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;41-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e1153 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e1124 (97.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e29 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;61-80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e638 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e621 (97.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e17 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026gt; 80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e109 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e103 (94.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e6 (5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eSex (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;F\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2007 (50.7)\u003c/p\u003e\n \u003cp\u003e1949 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1965 (97.9)\u003c/p\u003e\n \u003cp\u003e1891 (97.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e42 (2.1)\u003c/p\u003e\n \u003cp\u003e58 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eHAV Vaccine roll-out (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born before\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Born after\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3803 (96.1)\u003c/p\u003e\n \u003cp\u003e153 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3703 (96.0)\u003c/p\u003e\n \u003cp\u003e153 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e100 (4.0)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.777609682299545%\"\u003e\n \u003cp\u003eAnti-HAV IgG*\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.27231467473525%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2066 (58.0)\u003c/p\u003e\n \u003cp\u003e1495 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.608169440242058%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1996 (96.6)\u003c/p\u003e\n \u003cp\u003e1477 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.482602118003026%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70 (3.4)\u003c/p\u003e\n \u003cp\u003e18 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.85930408472012%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003eAnti-HAV\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eIgG was determined in 3561 samples (3473 patients with negative anti-HAV IgM and 88 patients with anti-HAV IgM)\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatitis A Virus, Epidemiology, Vaccine, immune response, Seroprevalence.","lastPublishedDoi":"10.21203/rs.3.rs-3976025/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3976025/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: In Argentina, Hepatitis A virus (HAV) used to contribute to 90% of acute hepatitis cases affecting the pediatric population. In 2005, a single dose of HAV vaccine was implemented for one-year-old children. However, despite vaccination success, a proportion of cases persists. This study aimed to assess the seroepidemiology of HAV in Argentina, analyzing IgG and IgM antibodies against HAV in a sizable population, both vaccinated and unvaccinated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This retrospective analysis involved 16,982 patients attending a tertiary-care hospital in Buenos Aires, Argentina. Patients were divided into two groups: those evaluated before vaccination and those suspected of having acute hepatitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Anti-HAV IgG was detected in 9,403 out of 16,587 (56.7%). A higher rate was observed in those individuals born after vaccine implementation (77.7%) compared to those born before (56.3%), p\u0026lt;0.001. The groups aged 19 to 40 and 41 to 60 exhibited the lowest anti-HAV IgG rates. Out of the 3,956 patients assessed for acute hepatitis, 100 (2.5%) tested positive for Anti-HAV IgM. Remarkably, none of the patients covered by mandatory vaccination showed positive Anti-HAV IgM.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This large study outlines the seroepidemiology status of HAV in Argentina and underscores the impact of vaccination in reducing infections. Despite the success of the vaccine, certain groups of susceptible individuals still persist, particularly among unvaccinated adults. These findings reveal the importance of targeting vaccination campaigns towards the most vulnerable age groups and emphasize the effectiveness of universal vaccination in reducing the incidence of HAV. This comprehensive analysis provides essential insights for public health planning and guides future immunization strategies against HAV in Argentina.\u003c/p\u003e","manuscriptTitle":"Seroprevalence of Hepatitis A Virus among people born before and after implementation of universal vaccination in Argentina","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-23 17:46:34","doi":"10.21203/rs.3.rs-3976025/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"138027ed-97a9-4c34-92cf-5009a0f13199","owner":[],"postedDate":"February 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-26T16:47:30+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-23 17:46:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3976025","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3976025","identity":"rs-3976025","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}