Molecular Epidemiological Characterisation of Hepatitis A Virus in Latvia. Summary of the Doctoral Thesis

Abstract

The doctoral thesis “Molecular Epidemiological Characterization of Hepatitis A Virus in Latvia” is devoted to the viral hepatitis A disease in Latvia, principles of diagnosis and epidemiological monitoring. The incidence of viral hepatitis A in European countries, as well as in the world, is variable. Until the mid -1990s, viral hepatitis A was a very common infectious disease in Latvia. Already in 2000, the number of sick people decreased and the incidence continued to decrease until 2007, when the number of confirmed cases was the lowest (0.66 cases per 100 000 inhabitants). Outbreaks of the hepatitis A were observed between 2008 and early 2010 and again in 2017–2018. Therefore, the risk of infection introducing and spreading remains. The aim of the thesis was to determine the distribution of hepatitis A virus subgenotypes in the territory of Latvia. Based on the obtained sequences and the structure of the phylogenetic tree, to analyze the homology and belonging to different isolated hepatitis A virus clusters from other countries, to identify the sources of infection, to improve laboratory – epidemiological monitoring tactics. In the study, molecular biological investigation and molecular epidemiological investigation were performed in 259 patients whose data were analyzed retrospectively. Demographic data (gender, age; country of birth, country of residence), clinical data of the disease (date of illness, laboratory – confirmed case, hepatitis symptoms, hospitalization, vaccination) and epidemiological data (part of the outbreak, possible source of infection) were collected. As a result of the analysis, it was established that hepatitis A virus subgenotypes IA, IB and IIIA circulate in Latvia, which are also the most common in the world. From the obtained data, it was concluded that hepatitis A virus subgenotype IA has 13 clusters and 12 sporadic cases, hepatitis A virus subgenotype IB has eight clusters and 11 sporadic cases, hepatitis A virus subgenotype IIIA has one cluster and nine sporadic cases. Sequencing data helps to track the spread of infection and any new cases of hepatitis A could be quickly decipherable by phylogenetic tree and already known clusters. It was found that the sources of infection among the investigated cases are different, they were mostly associated with contact with a hepatitis A patient, travel, also occur among people who inject drugs and men who have sex with men. In Latvia, the spread of hepatitis A virus has been observed regularly, but with different intensity, which may indicate the local circulation of the virus. Analyzing the gender of the patients, the majority of patients 54 % were men and 46 % were women, which does not differ from the literature data available to us. But when comparing the age of the patients at the time of diagnosis, the majority of patients were in the age group from 20 to 29 years old, which differs from the general data from the countries of the European Union and the European Economic Area, where from 2008 to 2021, the majority of patients were in the age group from 5 years to 14 years and from 0 years to 4 years. In the analysis, it was established that all patients had symptoms of hepatitis. Average patients were hospitalized 6.9 sick days after the date of illness, with a mean hospitalization of 8.7 days. It was concluded that patients with hepatitis A virus subgenotype IA had the longest number of days of hospitalization with an average of 9.3 days, while patients with hepatitis A virus subgenotype IB 7.3 days, hepatitis A virus subgenotype IIIA 7.7 days. Analysis of our data showed that the median time from the symptom onset to laboratory – confirmed hepatitis A case was 7.9 days. Analysis of vaccination data revealed that 89.6 % of patients included in the study were not vaccinated, 10.0 % had unknown vaccination status, and 0.4 % of patients had received one vaccine dose after contact with a hepatitis A virus patient. All of this has led to the conclusion that the application of molecular biological methods of the hepatitis A virus and the careful analysis of epidemiological data can help to better understand the ways of spread of the infection, investigate local outbreaks, detect cases of imported infection and track the circulation of the virus. This makes it possible to ensure timely and adequate preventive measures against the spread of infection.