Hepatitis A virus seroprevalence in Kyrgyzstan
- Authors: Alatortseva G.I.1, Pritvorova L.N.1, Nurmatov Z.S.2, Nesterenko L.N.1, Dotsenko V.V.1, Kabargina V.Y.1, Amiantova I.I.1, Zhukina M.V.1, Abdrakhmanova Z.O.2, Karatayeva U.S.3, Kyuregyan K.K.1,4, Mikhailov M.I.1,4, Zverev V.V.1, Svitich O.A.1
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Affiliations:
- I. Mechnikov Research Institute for Vaccines and Serа
- National Institute of Public Health
- Kyrgyz State Medical Institute for Retraining and Advanced Training named after S.B. Daniyarova
- Central Research Institute of Epidemiology
- Issue: Vol 102, No 6 (2025)
- Pages: 693-701
- Section: ORIGINAL RESEARCHES
- URL: https://microbiol.crie.ru/jour/article/view/19033
- DOI: https://doi.org/10.36233/0372-9311-717
- EDN: https://elibrary.ru/YUNCAG
- ID: 19033
Cite item
Abstract
Introduction. Kyrgyzstan, among other Central Asian countries, is one of the highly endemic regions for hepatitis A. An important tool for assessing the true burden of these infections on the population and the success of ongoing prevention programs is to study the prevalence of markers of past and current hepatitis A in all age groups of the population, as well as the intensity of population immunity to this virus in regions with different morbidity.
Aim. To study the hepatitis A virus (HAV) seroprevalence among residents of the Kyrgyzstan regions.
Materials and methods. Blood serum samples from conditionally healthy individuals (n = 2297) who sought medical attention at medical institutions in Bishkek, Batken, Chüy, Jalal-Abad, Issyk-Kul, Osh, Talas and Naryn regions. IgM and IgG antibodies to hepatitis A virus (anti-HAV IgM, anti-HAV IgG) were determined using the «Vectohep A-IgM» and «Vectohep A-IgG» (Vector-Best) enzyme immunoassay kits. Statistical processing of the results was carried out using Excel and Medcalc programs.
Results. 80.3% of the studied samples contained HAV serologic markers, of which 80.3% contained anti-HAV IgG antibodies and 4.7% contained anti-HAV IgM antibodies. All IgM-positive samples contained specific IgG antibodies. Such samples were identified with the same frequency among women and men. The highest seropositivity rates were observed in the age groups 30–39, 40–49, and 50–59 years. The number of individuals with anti-HAV IgG antibodies in their blood serum increased with their age. An analysis of the immunostructure of the examined individuals by the level of anti-HAV IgG in serum showed relatively stable ratios of low, medium and high levels of antibodies in groups older than 30 years. The most frequently anti-HAV IgM and IgG antibodies were detected in samples from residents of Bishkek. Anti-HAV IgG antibodies were detected in samples from all surveyed regions of Kyrgyzstan, while anti-HAV IgM antibodies were identified in samples from Chüy, Issyk-Kul and Osh regions, as well as Bishkek.
Conclusion. Hepatitis A remains widespread in Kyrgyzstan. The determination of HAV seromarkers in the algorithms of complex hepatitis diagnostics and seroepidemiological studies remains relevant. A decrease in the level of population immunity to HAV in younger age group indicates the country's transition from high to medium endemicity, which suggests an increase in the number of clinically pronounced cases in the future in the absence of a hepatitis A vaccination program for children.
Keywords
Full Text
Introduction
The Kyrgyz Republic (KR), along with other Central Asian countries, is a highly endemic region for hepatitis A. The spread of infection occurs primarily through the fecal-oral route, by consuming food or drinking water contaminated with the virus. Hepatitis A is characterized by territorial unevenness, cyclicity and seasonality of incidence [1]. Changes in the epidemiology of hepatitis A occurring in many countries are mainly linked to improvements in hygiene and sanitation, and consequently, to a decrease in the circulation of the hepatitis A virus (HAV) among children. This leads to an increase in the non-immune segment of the population. In the KR, an increase in the number of children who are not immune to hepatitis A leads to the stable persistence of a trend towards periodic outbreaks of the disease every 3–4 years and large outbreaks every 10–15 years. Morbidity data in the Kyrgyz Republic varies significantly across different periods. For example, the proportion of hepatitis A in the etiological structure of the total number of viral hepatitis cases in the northern regions was 67.38% in the 1990s, while in the southern regions it was 24.5% [2]. According to official reports for the period between 2014 and 2023, it reached an average of 94.6% in northern parts of the country and 96.8% — in southern other [3]. Hepatitis A is classified as an infection that can be managed and controlled with an effective vaccine. In the KR, vaccination against hepatitis A has not yet been included in the immunization schedule, and the introduction of vaccine prevention has become a priority in the fighting the infection. An important tool for assessing the true burden of this infection on the population and the success of ongoing prevention programs is the study of the prevalence of markers of past and current hepatitis A in all age groups of the population, as well as the level of herd immunity to this virus in regions with different incidence rates.
The aim of the study was to investigate the prevalence of serological markers of HAV infection — specific IgG and IgM antibodies — among residents of the Kyrgyz Republic’s regions.
Materials and methods
A total of 2,297 blood serum samples from conditionally healthy individuals who sought medical attention at various medical institutions in the KR in 2022 were examined. Data on the age and sex composition of the subjects and the regions where the samples were collected are presented in Table 1.
Table 1. Main characteristics of the studied blood serum samples
Characteristic | Abs. number | % |
Total number | 2297 | 100 |
Gender | ||
Females | 1358 | 59 |
Males | 939 | 41 |
Age | ||
Up to 20 years | 135 | 5.9 |
20–29 years | 347 | 15.1 |
30–39 years | 502 | 21.9 |
40–49 years | 475 | 20.7 |
50–59 years | 450 | 19.6 |
60–69 years | 290 | 12.6 |
70 years and older | 98 | 4.2 |
Region | ||
Bishkek | 1648 | 71.7 |
Batken region | 30 | 1.3 |
Chüy region | 357 | 15.5 |
Osh city and region | 48 | 2.1 |
Jalal-Abad region | 69 | 3.0 |
Issyk-Kul region | 96 | 4.2 |
Naryn region | 19 | 0.8 |
Talas region | 26 | 1.1 |
Foreigners | 4 | 0.3 |
The levels of specific IgM and IgG antibodies to HAV (anti-HAV IgM, anti-HAV IgG) were determined using the “Vectohep A-IgM” and “Vectohep A-IgG” enzyme immunoassay kits (JSC Vector-Best), according to the manufacturer's instructions. For each serum sample, the positivity coefficient (PCSAM) was calculated using the formula:
PCSAMP = ODSAMP/ODCRIT,
where ODSAMP is the optical density of the test sample; ODCRIT is the critical value of optical density.
The sample was considered negative if the PCSAMP ≤ 1.0, or positive if the PCSAMP > 1.0.
Statistical processing of the results was performed using Microsoft Excel and MedCalc software. The significance of the differences between the groups was assessed using Fisher's exact test (differences were considered significant if p < 0.05).
Results
In 1845 (80.3%) of the samples tested, serologic markers of HAV infection were detected, of which anti-HAV IgG antibodies were found in 1845 (80.3%) samples, and anti-HAV IgM in 109 (4.7%).
The test results for the samples are presented in Table 2. Hepatitis A antibodies were detected slightly more often in women. Anti-HAV IgM was found in 72 seropositive women (66%), and anti-HAV IgG was found in 1095 (59%) seropositive men. The detection rate of anti-HAV IgM was almost similar between men and women - 3.9% (37/939) and 5.3% (72/1358), respectively (p = 0.1356). The rates of anti-HAV IgG detection were almost the same between men and women: 79.9% (750/939) and 80.6% (1095/1358), respectively (p = 0.6695).
Table 2. Distribution of individuals in seropositive groups by sex, age and place of residence
Characteristic | Anti-HAV IgM | Anti-HAV IgG | ||
n | % | n | % | |
Positive samples | 109 | 1845 | ||
Negative samples | 2188 | 452 | ||
Gender | ||||
Females | 72 | 66 | 1095 | 59 |
Male | 37 | 34 | 750 | 41 |
Age | ||||
Up to 20 years | 4 | 3.7 | 39 | 2.1 |
20–29 years | 7 | 6.4 | 186 | 10.1 |
30–39 years | 18 | 16.5 | 391 | 21.2 |
40–49 years | 26 | 23.9 | 435 | 23.6 |
50–59 years | 33 | 30.3 | 416 | 22.5 |
60–69 years | 15 | 13.8 | 282 | 15.3 |
70 years and older | 6 | 5.4 | 96 | 5.2 |
Region | ||||
Bishkek | 82 | 75.2 | 1310 | 71.1 |
Batken region | 0 | 0 | 28 | 1.4 |
Chüy region | 18 | 16.5 | 291 | 15.8 |
Osh city and region | 3 | 2.8 | 37 | 2.2 |
Jalal-Abad region | 0 | 0 | 63 | 3.4 |
Issyk-Kul region | 5 | 4.6 | 73 | 4.0 |
Naryn region | 0 | 0 | 16 | 0.9 |
Talas region | 1 | 0.9 | 24 | 1.3 |
Foreigners | 0 | 3 | 0.2 | |
There is a noted trend in increasing the detection rate of anti-HAV IgM with age of the subjects, from 3.7% in the group of seropositive individuals under 20 years of age to 30.3% among those aged 50–59. Anti-HAV IgM antibodies were found less frequently in older age groups: 13.8% in the 60–69 age group and 5.4% among those over 70.
The frequency of anti-HAV IgG detection also increased with age in seropositive groups: from 2.1% in the under-20 group to 23.6% in those aged 40–49. In older age groups, there was a consistent decrease in the detection rate of anti-HAV IgG: 22.5% in individuals aged 50–59, 15.3% in those aged 60–69, and 5.2% in individuals over 70 years of age.
Anti-HAV IgM and anti-HAV IgG were most frequently detected in samples from residents of Bishkek, as well as in samples from the Chui, Issyk-Kul and Osh regions. Anti-HAV IgG were present in samples from all surveyed regions of the Kyrgyz Republic, while anti-HAV IgM were found in samples from the Chui, Issyk-Kul, Talas, and Osh regions as well as Bishkek (Fig. 1).
Fig. 1. The frequency of detection of samples containing anti-HAV IgM and anti-HAV IgG in the surveyed areas of the Kyrgyz Republic.
There is a trend towards an increase in the number of individuals who are anti-HAV IgM and anti-HAV IgG seropositive with their age (Fig. 2).
Fig. 2. The frequency of detection of samples containing anti-HAV IgM and anti-HAV IgG in the examined age groups.
Figures 3 and 4 graphically present the results of comparing the values of anti-HAV IgM and IgG positive samples between age groups using box plots (Box Plot function), based on the median (Me), as the data for the groups did not have a normal distribution and significant outliers were observed in all groups older than 20 years [4].
Fig. 3. Box plot (Box Plot function) of anti-HAV IgM PCSAMP values by age group.
Fig. 4. Box plot (Box Plot function) of anti-HAV IgG PCSAMP values by age group.
The average value of anti-HAV IgM positive samples was 2.43 (95% CI 2.05–2.80). At the same time, the values of PCSAMP ranged from 1.1 to 10.9. The highest values of anti-HAV IgM Me were observed in the following age groups: under 20 years old - 2.63 (95% CI 1.60–3.70); 30–39 years old — 2.16 (95% CI 1.36–3.18); and over 70 years old — 2.10 (95% CI 1.1–3.5). The lowest mean values for anti-HAV IgM were found in the following age groups: 20–29 years old — 1.31 (95% CI 1.14–5.17); 60–69 years old – 1.4 (95% CI 1.30–3.55); and 40–49 years old — 1.48 (95% CI 1.17–2.19). The mean value for the 50–59 was 1.72 (95% CI 1.26–2.13) (Fig. 3).
The highest mean anti-HAV IgG values were in the 60–69 age group — 10.1 (95% CI 9.73–10.55), those over 70 years old — 10.0 (95% CI 8.87–11.68), and the 50–59 age group — 9.2 (95% CI 8.58–9.67). The lowest mean values of anti-HAV IgG were found in the following age groups: 30–39 years old — 8.1 (95% CI 7.84–8.48), under 20 years old — 8.16 (95% CI 6.28–9.29), and 20–29 years old — 8.21 (95% CI 7.84–8.54). In the 40–49 age group, this figure was 8.92 (95% CI 8.72–9.20). The average anti-HAV IgG value in the samples was 9.3 (95% CI 9.15–9.44). At the same time, the PCSAMP values ranged from 1.1 to 16.3 (Fig. 4).
No significant differences were found between the mean values of anti-HAV IgG in samples containing and not containing IgM antibodies to HAV. For IgM-positive samples, the mean anti-HAV IgG PCSAMP was 9.29 (95% CI 9.28–9.31), while for IgM-negative samples, it was 9.30 (95% CI 9.29–9.32).
Discussion
In countries with a high prevalence of hepatitis A virus, clinically apparent cases of hepatitis A are rare because most of the population has been infected in early childhood and mild or asymptomatic forms of the disease characteristic of childhood predominate. Our study demonstrates a correlation between immunity to hepatitis A and the age of the subjects examined. This, in turn, is likely related to the prevalence of subclinical forms of the infectious process in the disease. Analysis of the immune structure, not only by the proportion of seropositive individuals but also by the level of anti-HAV IgG concentration in the sera, revealed that relatively stable ratios of low, medium, and high antibody levels are reached by the age of 30–40, while the anti-HAV IgG PCSAMP of most seropositive samples have medium values. This state of humoral immunity corresponds to a high degree of immunity after repeated contact with the pathogen [5]. The results of various seroepidemiological studies show that an accurate assessment of hepatitis A frequency can be made based not on statistical data on incidence but on data on population immunity status obtained from testing sufficient serum samples from healthy individuals for anti-HAV IgG and anti-HAV IgM. At the same time, the intensity of the acquisition anti-HAV IgG during the formation of immunity is subject to significant fluctuations depending on geographical location, social, sanitary and hygienic conditions, as well as other factors [6]. Most people who have had hepatitis A, regardless of the form of the disease (jaundiced, anicteric or inapparent), retain anti-HAV IgG antibodies throughout life; over time, if there is no repeat virus exposure the antibody titer decreases [7].
Hepatitis A in the Kyrgyz Republic is characterized by uneven and a wave-like epidemic process. While anti-HAV IgG is generally highly detectable, it is particularly frequent in individuals living in the regions bordering Kazakhstan, Uzbekistan and Tajikistan: Batken, Jalal-Abad and Talas. The geographical heterogeneity of HAV seroprevalence which was identified in the Kyrgyz Republic, corresponds to long-term analysis data that showed a coincidence of peaks in the rise and decline in incidence in these regions [8].
The study results did not reveal a significant association between gender and the presence of anti-HAV antibodies among the surveyed population. This finding somewhat contradicts the data presented by other researchers, who noted a higher prevalence of anti-HAV seropositivity among women [9]. It is likely that this discrepancy can be explained by the complex interaction of socioeconomic and behavioral factors, as well as differences in vaccination coverage among study groups.
In the age structure of registered hepatitis A cases in the Kyrgyz Republic, childhood morbidity traditionally predominates. However, during epidemic peaks, the proportion of the adults was relatively high, ranging from 14.1% in 2007 to 15.1% in 2012 [8]. The cyclical rise and fall in incidence is linked to the accumulation of a non-immune populations among children. From 1985 to 2022, despite the lack of vaccination, there has been a decrease in the incidence due to improved living conditions, especially the implementation of quarantine measures during the COVID-19 pandemic. As a result of the increase in the non-immune layer accumulated during this period, a surge in incidence was subsequently noted. The incidence increased from 42.2 per 100,000 in 2022 to 126.6 per 100,000 in 2023 [2]. Considering the possibility of disease manifesting in unregistered or inapparent forms, detection of a marker for recent infection — specific IgM antibodies — can be considered an indicator of a hidden epidemic process. Thus, in 4.7% of the conditionally healthy individuals that were examined, the simultaneous presence of anti-HAV IgG and anti-HAV IgM was detected. This, with a high level of anti-HAV IgG against a relatively low level of anti-HAV IgM, may indicate recent, mild infection. The fact that such cases are most frequently detected in areas with the lowest HAV seroprevalence (Bishkek, Chüy, Osh, Issyk-Kul regions) may reflect a link between the detection of anti-HAV IgM antibodies and the presence of conditions for the virus to spread among seronegative individuals. Another noteworthy fact is the low detection rate of anti-HAV IgG antibodies among individuals under 20 years old. This suggests an increase in the proportion of adults susceptible to HAV in the future, and unequivocally indicates the feasibility of introducing hepatitis A vaccination among children in the Kyrgyz Republic. This approach, based on global experience in vaccination, could be an effective tool in the fight against this widespread disease [10].
Conclusion
Hepatitis A remains widespread in the Kyrgyz Republic, and the relevance of determining HAV serological markers in algorithms for comprehensive hepatitis diagnosis and sero-epidemiological studies continues. The decline in the level of herd immunity to HAV in younger age group (among individuals under 20 years old) indicates a shift from high to medium endemicity, suggesting an increase in the number of clinically apparent cases in the future without a childhood immunization program against HAV.
About the authors
Galina I. Alatortseva
I. Mechnikov Research Institute for Vaccines and Serа
Author for correspondence.
Email: alatortseva@gmail.com
ORCID iD: 0000-0001-9887-4061
Cand. Sci. (Biol.), leading researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowLyudmila N. Pritvorova
I. Mechnikov Research Institute for Vaccines and Serа
Email: lexx294@yandex.by
ORCID iD: 0000-0002-2997-8892
Cand. Sci. (Med.), leading researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowZuridin Sh. Nurmatov
National Institute of Public Health
Email: logvinenko.nurmatov@gmail.com
ORCID iD: 0000-0003-3481-227X
Dr. Sci. (Med.), Head, Republican Scientific and Practical Center for Viral Infection Control
Kyrgyzstan, BishkekLyubov N. Nesterenko
I. Mechnikov Research Institute for Vaccines and Serа
Email: lnnesterenko3001@gmail.com
ORCID iD: 0000-0002-3825-3906
Cand. Sci. (Chem.), leading researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowVera V. Dotsenko
I. Mechnikov Research Institute for Vaccines and Serа
Email: verramal@gmail.com
ORCID iD: 0000-0002-5866-944X
Cand. Sci. (Biol.), senior researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowVera Yu. Kabargina
I. Mechnikov Research Institute for Vaccines and Serа
Email: v.cabargina@yandex.ru
ORCID iD: 0000-0002-8784-4497
researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowIrina I. Amiantova
I. Mechnikov Research Institute for Vaccines and Serа
Email: amianti@yandex.ru
ORCID iD: 0000-0003-3483-0128
researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowMarina V. Zhukina
I. Mechnikov Research Institute for Vaccines and Serа
Email: dwesome.zhukina@gmail.com
ORCID iD: 0000-0002-2329-5089
researcher, Laboratory of viral genomes cloning, Department of virology named after O.G. Andzhaparidze
Russian Federation, MoscowZamira O. Abdrakhmanova
National Institute of Public Health
Email: abdrahmanova.z@list.ru
ORCID iD: 0000-0002-2645-863X
epidemiologist
Kyrgyzstan, BishkekUulkan S. Karatayeva
Kyrgyz State Medical Institute for Retraining and Advanced Training named after S.B. Daniyarova
Email: u.karataeva@list.ru
ORCID iD: 0009-0009-0252-2690
Head, Interfaculty department of public health, with a course of infection control
Kyrgyzstan, OshKaren K. Kyuregyan
I. Mechnikov Research Institute for Vaccines and Serа; Central Research Institute of Epidemiology
Email: karen-kyuregyan@yandex.ru
ORCID iD: 0000-0002-3599-117X
Dr. Sci. (Med.), Professor of RAS, leading researcher, I. Mechnikov Research Institute for Vaccines and Sera; Head, Laboratory of molecular diagnostics of viral hepatitis, Central Research Institute of Epidemiology
Russian Federation, Moscow; MoscowMikhail I. Mikhailov
I. Mechnikov Research Institute for Vaccines and Serа; Central Research Institute of Epidemiology
Email: michmich2@yandex.ru
ORCID iD: 0000-0002-6636-6801
Dr. Sci. (Med.), Professor, RAS Full Member, Head, Laboratory for viral hepatitis, I. Mechnikov Research Institute for Vaccines and Sera, chief researcher, Central Research Institute of Epidemiology
Russian Federation, Moscow; MoscowVitaly V. Zverev
I. Mechnikov Research Institute for Vaccines and Serа
Email: vitalyzverev@outlook.com
ORCID iD: 0000-0002-0017-1892
Dr. Sci. (Biol.), Professor, RAS Full Member, Head, chief researcher
Russian Federation, MoscowOxana A. Svitich
I. Mechnikov Research Institute for Vaccines and Serа
Email: svitichoa@yandex.ru
ORCID iD: 0000-0003-1757-8389
D. Sci. (Med.), RAS Full Member, Director
Russian Federation, MoscowReferences
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