Hepatitis A is still a great problem in developing countries, especially those in which vaccination is not obligatory. It is well known that hepatitis A is associated with risk factors such as poor sanitation and inadequate hygiene. However, some investigations (e.g. in Spain and Greece) showed that the seroprevalence of antibodies against hepatitis A virus (HAV) in recent decades has decreased, especially in the younger adults, most likely due to improvements in living standards and hygienic conditions [1-4]. This raises the question of the possible emergence of this disease at an older age, highlighting the necessity of applying appropriate preventative strategies.

Although similar studies have not been performed in Serbia, we assume that the improvement of hygienic conditions (which are not optimal but better than 20 years ago) has led to reduced numbers of individuals protected by antibodies against hepatitis A virus also in the Serbian population.

Hepatitis A situation in Nis, Serbia
In Nis, as in the whole of Serbia, hepatitis A is the most common type of viral hepatitis. It occurs every year sporadically and in the form of small home-centred clusters. A total number of 694 serologically confirmed hepatitis A cases had been registered in Nis from 1987 to 2006 (average annual incidence rate of about 14/100,000). In the non-epidemic years (from 1987 to 2006, except 1987, 1994, and 2003) the average incidence rate of hepatitis A in Nis was about 10/100,000 population.

The last large epidemic of this disease occurred in Nis in 1987, with 123 serologically confirmed cases and an incidence rate of 50/100,000. Two smaller outbreaks were reported in 1994 and 2003, with 70 (incidence 28/100,000) and 60 cases (incidence 24/100,000), respectively. In addition, a large number of non-serologically confirmed cases (1,170) for whom diagnosis was based on clinical signs, biochemical parameters (AST, ALT and bilirubine levels) and epidemiological data were registered in this period (1987-2006).

In Nis, serological diagnosis for hepatitis B has been performed since 1986 and for hepatitis C since 1992. No serologically confirmed cases of hepatitis B and C were included among the non-differentiated hepatitis cases. Serodiagnosis of the other hepatitis infections (G, E) has not yet been introduced in Nis. Assuming that most (but not all) of non-differentiated hepatitis cases were hepatitis A the total number of cases in the observed period would be about 1,800 (average annual incidence rate of 37/100,000). The disease predominantly occurred among those aged 7 to 19 years of both sexes (Figure 1). In the past 20 years, in south east Serbia where Nis is located, no food-borne or water-borne epidemics of hepatitis A have been reported. Vaccination against hepatitis A is not mandatory in Serbia.

Ongoing outbreak of hepatitis A in Nis
Since 2006, large outbreaks of hepatitis A have occurred in the towns surrounding Nis (Prokuplje in 2006; Pirot, Bela Palanka, Leskovac, Aleksinac and Prokuplje in 2007). The inhabitants of these towns have frequent contacts with citizens of Nis. Figure 2 shows the number of reported cases of hepatitis A in Nis in 2006 and 2007 indicating that 2006 was a non-epidemic year with a total of 45 cases from January to December 2006 (incidence 18/100,000).

From January 2007 to October 2007 hepatitis A occurred sporadically in Nis. However, in the end of October, the hospital for infectious diseases in Nis reported a higher number of cases than usual. Subsequent epidemiological investigation revealed that from 8 October to 30 November 2007, the total number of reported hepatitis A cases in Nis was 716 (Figure 3). About 150 of them (21%) were hospitalised. The highest number of cases (44) was registered on 1 November. The diagnosis was made on the basis of clinical symptoms, biochemical parameters (AST, ALT and bilirubine levels) or serological findings (anti-HAV IgM).

All cases were living in Nis or in the neighbouring rural municipalities and had many contacts with the town’s inhabitants. The geographical distribution of cases was even.

There were significant differences between the rates of disease in men and women. Among the cases, there were 527 males (74%) and 189 females (26%). Persons aged 20 to 35 years, male and female, made up the majority of cases (378 or 53%). The highest incidence rate was among men aged 20 to 24 years (1,258/100,000) (Figure 4).

The occupation of the cases varied, as did their socio-economic status and educational level.

Conclusion
Initially, the shape of the outbreak epi curve indicated that the way of infection (viral transmission) could be a result of a point source, i.e. drinking water or food. However, the results of drinking water analyses performed in 2007 demonstrated no problems. The control of drinking water was done in the Public Health Institute in Nis and residual chlorine in the investigated samples of drinking water was always on the recommended level.

Epidemiological investigations, including food questionnaires, demonstrated that cases had bought and consumed food in various places all over the city and no specific product was implicated in the investigation. The distribution of cases by age and sex showed that young males were most often infected. However, no special risk factors could be associated with this group.

Therefore, considering the hepatitis A epidemiological situation in south east Serbia, especially in Nis and the neighbouring towns, we can presume that the viral transmission in this outbreak occurred via direct contact with cases (with or without clinical symptoms). The spread of disease was facilitated by long, hot and dry summer and poor hygienic and environmental conditions. Also, the relatively low incidence of hepatitis A in Nis over the past 20 years, low vaccination coverage and overall better hygiene practices are thought to have increased the number of persons susceptible to hepatitis A and contributed to this large and ongoing epidemic.