Komentar Eksperta
Epidemiologija infekcija Hepatitisom A i Hepatitisom E
( accepted March 31st, 2001 )
Institute for Infectious and Tropical Diseases,
Clinical Center of Serbia,
Bul JA 16, YU-11000 Belgrade, Serbia
Yugoslavia
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In the last issue of Arch Gastroenterohepatology, Turk Aribas et al. reported seroprevalence data of Hepatitis A virus (HAV) and Hepatitis E virus (HEV) in children aged 1-15 years living in Konya, Turkey (1). In order to estimate past HAV and HEV infection, sera samples from 162 children were examined for antibodies to both viruses. Some other patient , s records were studied: age, gender and socio-economic status. Investigated children were outpatients, attending the paediatric service for other reasons than jaundice. Acute HAV infection was excluded in all children.
Among well-known hepatitis viruses HAV and HEV are primarily transmitted by faecal-oral route and cause self-limited disease. Both viruses share some similarities but also, some differences.
Hepatitis A virus is an RNA virus classified in the Picornavirus family (2). Only one serotype of HAV has been isolated in sera collected from various parts of the world. The severity of clinical disease associated with HAV, increases with increasing ages; icteric disease occurs among < 10% of children younger than 6 years old. Since many children have unrecognized asymptomatic infection, they likely represent the major reservoir for HAV transmission. The overall reported case-fatality rate in hepatitis A is low, from 0.2-0.4%. Higher case-fatality rates have been reported among children < 5 years of age and among persons > 50 years (3,4,). Recent data confirmed that HAV had produced significant morbidity in endemic countries (5). Patients with chronic liver disease are at a high risk for morbidity, also (6). Hepatitis A virus infection is vaccine preventable. As a fecal-oral infection, HAV infection is acquired either person to person contact (close household or sexual contact with patients who have hepatitis), or ingestion of contaminated food or water. Outbreaks of acute hepatitis caused by HAV are exclusively linked to common sources, e.g. contaminated food or water.
In this study, the authors reported the overall prevalence of HAV infection, detected by IgG antibodies to HAV, in 154/162 (95.0%) of cases. Prevalence correlated with age of the patients and the most vulnerable age group was children between 1-4 years (93.7%). This result shows a very high prevalence rate and very early HAV infection, which is usually seen in different world regions where HAV infection is endemic (e.g. Central and South America, Africa, Asia and some Mediterranean countries (7,8,9). In the United States, approximately 33% of population has serological evidence of past HAV infection in studies conducted during 1988-1991 (10,11). Among racial/ethnic groups in US, rates in American Indians and Alaska Natives are highest, ten times more than in overall population (11,12). Generally, these communities with high rates of HAV infection, according to epidemiological survey, has prevalence of 30-40% in children younger than 5 years old and 70-100% in children younger than 15 years old. The age of most patients is between 5-14 years. Epidemics of hepatitis A occur every 5-10 years and may last for several years. In contrast to communities with high rate of HAV infection, in communities with intermediate rate, most disease occurs among older children, adolescents and young adults. Surveillance data indicates that epidemics in these communities also may be periodic and last for several years (9).
In the last two years, high overall prevalence (from 85% to 99.1%) of HAV infection in general population, similar to this Turkey study, was reported by some authors, mostly from India, Pakistan, Nepal, Vietnam, Africa, but also, from Spain and Czech Republic (13,14,15,16,17,18,19,20,21,22). Authors concluded that age and socio-economic status significantly affected prevalence of HAV (13,16,20). On the contrary, some authors reported low prevalence of HAV infection and/or dramatic drop from high to low rate in the last decade (15,19,20, 23,24,25,26,27,28). It is obvious that HAV epidemiology in some geographic regions has been changed, mainly in Western Europe but also in India, Korea etc. (15,19,22,23). This is the result of successful epidemiological measures for prevention and controls of the disease (15,19,22,24). But, these epidemiological changes suggest that immunity against HAV infection generally decreased and large outbreaks could be expected, particularly in adult persons. As a consequence, there is a possibility in the future for older children and young adults, to be at higher risk for more severe course of the clinical disease. Because of that, routine vaccination is recommended.
Interestingly, although the incidence of HAV infection is very dependent of socio-economic status, a strong statistical correlation between HAV prevalence and income was not seen in this study. Belgian authors have been shown that HAV prevalence in health care workers at high risk for viral hepatitis (paediatric nurses and day nursery workers) was lower than in general population between 25 years and 45 years (29). The authors explained their result in better education of health care workers and avoidance of HAV infection. Another study in an urban middle class area in Argentina, also showed than not only classical epidemiological measures such as use of tap water, sanitary controls etc., but higher level of education, could be efficient to prevent HAV infection (30).
Another preventive measure should be in routine vaccination of this highest risk group. Fortunately, actual inactivated vaccine is very safe and produces adequate immune response in children older than two years. But, few data are still available regarding the use of hepatitis A vaccine in younger children.
Hepatitis E virus is the major aetiologic agent of enterally transmitted non-A, non-C hepatitis worldwide. Based on similar physico-chemical and biologic properties, HEV has been provisionally classified in the Caliciviridae family. However, the organization of the HEV genome is substantially different from that of other caliciviruses, HEV may eventually be classified in a separate family (2,31). Hepatitis E virus infection is mainly spread by fecally contaminated water. Person to person transmission is minimal. The clinical hallmark of HEV infection is its extremely high mortality rate when the infection occurs in pregnancy, particularly in the third trimester. No commercial HEV vaccine is yet available.
Hepatitis E is endemic in many regions of Asia, Africa and Central America. In these regions, hepatitis E mainly occurs as outbreaks associated with fecally contaminated drinking water. Sporadic cases can be also seen. In industrialized countries, HEV infection is detected as imported cases in returning travelers and recent immigrants from endemic regions. But, the discovery of individuals with non-imported infection, lead to a possibility that animal reservoirs exist. Recently, the discovery of swine Hepatitis E virus from pigs in US, and its close relation to human HEV strain, confirmed this hypothesis (32). Antibodies to HEV were detected as well as, in other animals such as rats, sheep, chickens, dogs etc., in other countries, too. (33,34). Moreover, authors from Spain demonstrated that human strains were more closely related to swine strains isolated from pigs, than to other human strains isolated worldwide (35). These very recent data prove the existence of clusters of similar HEV strains between humans and pigs and provide current working hypothesis that hepatitis E is zoonosis (36).
Reporting prevalence of HEV in 12.3% of children by Turk Aribas at al., seems that HEV is endemic in that region. Its presenting prevalence in age distribution differs from HAV. The highest risk group is older than the highest risk group for HAV. For HEV, this group is between 10–15 years and has prevalence rate 21%. The result is expected because it is characteristic for developing countries that HEV is the most sporadic hepatitis in young adults (2,3,31).
The authors reported strong correlation of HEV prevalence rate to income level in and co-infection with both viruses in 11.1% of cases. It confirms a significant influence of socioeconomic status and some common peculiar routes of HAV and HEV enteral transmission. Many of them are still unknown. Therefore, because of high prevalence rate reported in this study, it could be very important to examine whether domestic and/or wild animals are infected with HEV. Also, it would be of special interest if the authors have data about of hepatitis Non A-C outbreaks in the past. It could help for better explanation this high-endemic situation for HEV.
In conclusion, study of Turk Arabis et al. gave us very important and interesting seroprevalence results of HAV and HEV in children. The authors discussed possibilities for very high prevalence rate for both infections but further investigation would help to explain all confusions connecting many questions and problems in epidemiology of these two viruses.
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