Brief Reports

Indian Pediatrics 1999;36: 11142-1144

Prevalence and Persistence of Hepatitis A Antibody During the First Year of Life, in Turkish Infants

From the Department of Pediatrics, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey and Department of Microbiology, ®Ystanbul Faculty of Medicine, University of ®Ystanbul, ®Ystanbul, Turkey.
Reprint requests: Mujgan Alikasifoglu, Icadiye mah. Imam Galip sok. No:4/7, ¨Uskudar, 81200, ®Ystanbul, Turkey. Fax: (216) 341 2530
Manuscript received: March 10, 1999;
Initial review completed: April 26, 1999;
Revision accepted: June 21, 1999

Hepatitis A virus (HAV) has a world-wide distribution. Because of the strong association between the transmission rates and the hygiene and sanitation levels, different patterns of infection are seen in different parts of the world. Although the frequency of HAV infection has declined dramatically in developed countries, it is still endemic in many of the developing countries(1). In Turkey, where the infection is endemic, the seropositivity rate varies between 70-90% in early adulthood (40% by 10 years old, 70-90% by 20 years old)(2), but the incidence of HAV infection in the first year of life is very low probably as a result of neonatal protection by maternal antibodies. The purpose of this study was to determine the persistence  of transplacentally acquired anti-HAV antibody during infancy.

Subjects and Methods

A total of 47 term healthy newborns (gestational age: 39.4±0.9 weeks; 14 male, 33 female) who were born at the Cerrahpasa Medical Faculty, Department of Obstetrics and Gynecology between January 1997-April 1997 were recruited in this longitudinal study with oral consent from parents. Demographic and medical data were obtained by interviewing mothers. Sixty-eight per cent of the fathers and 60% of the mothers graduated from high school or university, 63.8% of the infants were the mothers' first born child and all infants were living in metropolitan area of Istanbul. Blood samples for the determination of anti-HAV antibody were drawn at 1 month (mean: 39.1±5.8 days), 2 months (mean: 70±5.7 days), 6 months (mean 6.2±0.25 months), and 12 months of age (mean: 12.1±0.24 months). Sera were stored at -20°C until the serologic analysis. All specimens were tested simul-taneously using enzyme immunoassay (HAV Total, Pasteur-Merieux, France, spectro-photometer: Pasteur-LP400) which is a quali-tative method for the detection of total antibodies to HAV (both immunoglobulin G and immunoglobulin M). A sample is consi-dered positive for anti-HAV total antibody if its absorbance value is less or equal to the cutt-off value. Chi-square test was used for statistical analysis.

Results

Forty-seven infants were enrolled to the study and 14 of them did not complete the study because of loss during follow up (n=10) or parental request (n=4). Forty-one (87%) of the 47 returned at 2 months, 39 (82%) returned at 6 months, 33 (70.2%) returned at 12 months of age for antibody determination. The prevalence of anti-HAV total antibodies is presented  in Table I.

Table I^__ Percentage of Infants Seropositive for Hepatitis A Antibodies

The prevalence of anti-HAV antibodies in infants at 1 month of age was 87.2% (41 subjects) and a progressive decline was observed up to 12 months of age. Thirty-six (87.8%) of the 41 anti-HAV positive infants returned for antibody determination at two months of age and one of them was found negative for the anti-HAV antibody. Thirty-one (88.5%) of the 35 antibody positive infants returned at six months of age and 16 of them were found negative for anti-HAV antibody. Two infants who did not come for antibody determination at two months of age returned at six months of age and one of them was found to be negative and the other was found to be positive for anti-HAV antibody. Thirteen (81.2%) of the 16 antibodies positive infants returned at twelve months of age and 12 of them was found negative for anti-HAV antibody. One infant was still positive for anti-HAV at 12 months of age. The seropositivity rates at 6 and 12 months of age were significantly lower, compared to those determined at the previous months (p=0.0001). None of the seronegative infants antibody became seropositive during the follow up.

Discussion

Our study shows that 87.2% of the infants born in a metropolitan area in Turkey have anti-HAV antibody at one month of age. We can  suggest that the majority of the study group acquired the anti-HAV antibodies from their mothers relying on very high seropositivity rate among Turkish population older than 20 year old(2). This result also confirms the high prevalence of anti-HAV antibodies among their mothers. However, the antibody prevalence steadily declined thereafter and by age of 12 months there was only one infant who was still seropositive without history of jaundice and, any signs and symptoms of the HAV infection. It could be reasonable to consider that this infant acquired the antibodies passively since his serum absorbance values had been steadily rising to the cut-off value indicating progressive decrease in HAV antibodies. Although 13% of the infants without maternal antibody were susceptible to HAV infection, none of them became seropositive during the study period. Our study population consisted of inner-city children who were not living in crowded conditions nor attending day care centres. Thus, they were not at high risk for HAV infection.

During the literature research we could find only a few studies evaluating the duration of persistence of maternal anti-HAV-antibody in infants. In a study from Spain, 98% of the newborns were shown to be positive for anti-HAV-antibodies at birth. This percentage decreased with age and by the age of 9-12 months all were seronegative(3). Another study conducted in Mexico demonstrated that 100% of the Mexican newborns had anti-HAV-antibodies at birth but at 5 months of age none of them had detectable antibody levels(4). Our results are similar to those of spanish infants.

Currently an effective and safe vaccine against HAV is available that can induce long lasting immunity in both children over two years of age and adults(5,6). Since the studies reporting the reactogenicity and immuno-genicity of the vaccine under two years of age are limited, and the efficacy of the vaccine in  infants who have circulating maternal antibody to HAV is not well known, inactivated HAV vaccine is still not used in this age group(7). The epidemiologic data show that young children facilitate the fecal-oral spread of HAV because they usually have asymptomatic infection(8). Therefore hepatitis A vaccine would have to be used for widespread immunization of infants, if our goal is to decrease the incidence of HAV infection in any population.

Data concerning the duration of persistence of maternal antibodies such as this study and further studies from different geographic regions are necessary to find out the duration of persistent of maternal antibodies. Also studies designed to evaluate the effect of the HAV antibody on immunogenicity of the vaccine should be encouraged.

References

1. Gust ID. Epidemiological patterns of hepatitis A in different parts of the world. Vaccine 1992; 1: 56-58.

2. Yenen Op, Aldeniz SC, Yuksel D. Sero-epidemiology of hepatitis A and E in Istanbul  Turkey. IX Triennial International Symposium on Viral hepatitis and Liver disease April 21-25 1996 Rome, Italy.

3. Vargas V, Pedreira JD, Esteban R. Maternal fetal transmission of hepatitis A antibody. Acta Pediatr Scand 1980; 69: 533.

4. Ruiz-Gomez J, Bustamante-Calvillo E. Hepatitis A antibodies: Prevalence and persistence in a group of Mexican children. Am J Epidemiol 1985; 1: 116-119.

5. Innis BI, Snitbhan R, Kunasol P. Protection against hepatitis A by an inactivated vaccine. JAMA 1994; 271: 1328-1334.

6. Lee SD, Lo KJ, Chan CY. Immunogenicity of hepatitis A vaccine in children. Gastro-enterology 1993; 104: 1129-1132.

7. Troisi CL, Hollinger FB, Krause DS. Immuniza-tion of seronegative infants with hepatitis A vaccine (HAVRIX@; SKB): a comparative study of two dosing schedules. Vaccine 1997; 15: 1613-1617.

8. Margolis HS, Shapiro CN. Consideration for the development of recommendations for the use of hepatitis A vaccine. J Hepatol 1993; 18 (Suppl 2): 56-60.