Correspondence

Transmission of Hepatitis A Virus Infection despite Vaccination

N Engl J Med 2000; 343:301-302July 27, 2000

Article

To the Editor:

In 1989, a killed hepatitis A virus (HAV) vaccine produced from cell culture was described.1 Today, several vaccines are available commercially in countries all over the world. The World Health Organization and other advisory committees now recommend the use of these vaccines for prophylactic purposes as well as for intervention during epidemics.2 It is uncertain whether persons who are vaccinated after coming into contact with patients with hepatitis A can nevertheless become infected and possibly excrete infectious HAV without clinical symptoms, thus posing a risk to others. We describe the spread of symptomatic hepatitis A infection among the relatives of an infected five-year-old girl who had been vaccinated.

The girl had been vaccinated after coming into contact with a child (the index patient) in her kindergarten who had acute hepatitis A, and she had had no signs of clinical illness thereafter. Symptoms of severe hepatitis A occurred in her 7-year-old sister, 43-year-old father, and 39-year-old mother within 35 to 37 days after she had been vaccinated (Figure 1Figure 1Transmission of Hepatitis A Virus (HAV) from a Child to Her Sister, Father, and Mother and the Duration of Excretion of the Virus in Feces.).

We examined samples of serum and feces from all family members for antibodies to HAV (anti-HAV) by means of routine serologic tests and for HAV RNA by means of a nested reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay.3 We assumed that the vaccinated child had been infected by the index patient at least one week before the index patient had had symptoms. The vaccinated child could therefore have excreted HAV even one to two weeks after vaccination, thus infecting her sister, mother, and father, who presented with symptoms four weeks later. Tests for anti-HAV IgM were highly positive in the serum samples from the child and her sister, mother, and father, and the serum levels of alanine aminotransferase and aspartate aminotransferase were elevated, demonstrating the presence of an acute hepatitis A infection. Serum levels of alanine aminotransferase and aspartate aminotransferase were normal in the child during the period in which HAV was excreted in her feces. Her three clinically ill relatives excreted the virus in feces for at least seven weeks after the onset of the disease, as determined by means of RT-PCR. The sequences of all isolates were 100 percent identical, as determined according to previous descriptions,4 and represented members of genotype 1B. This finding of 100 percent sequence identity establishes that the virus was transmitted from the vaccinated child to her family.

We conclude on the basis of these findings that vaccination should be recommended to family members and others who are in close contact with persons who may be infected with hepatitis A.

Bertram Flehmig, M.D., Ph.D.
Andrea Normann, Ph.D.
University of Tübingen Hygiene Institute, 72076 Tübingen, Germany

Daniela Bohnen, M.D.
Krankenhaus Siegburg, 53721 Siegburg, Germany

4 References

1. 1

   Flehmig B, Heinricy U, Pfisterer M. Immunogenicity of a killed hepatitis A vaccine in seronegative volunteers. Lancet 1989;1:1039-1041
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2. 2

   The Viral Hepatitis Prevention BoardVHPB consensus statement on the control of hepatitis A. Viral Hepatitis 1999;8:16-16
   

3. 3

   Normann A, Graff J, Gerritzen A, Brackmann HH, Flehmig B. Detection of hepatitis A virus RNA in commercially available factor VIII preparations. Lancet 1992;340:1232-1233
   CrossRef | Web of Science | Medline

4. 4

   Normann A, Pfisterer-Hunt M, Schade S, et al. Molecular epidemiology of an outbreak of hepatitis A in Italy. J Med Virol 1995;47:467-471
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Andrea Normann, Selim Badur, Derya Önel, Ayse Kilic, Müjgan Sidal, Bernard Larouzé, Veronique Massari, Julia Müller, Bertram Flehmig. (2008) Acute hepatitis A virus infection in Turkey. Journal of Medical Virology 80:5, 785-790
   CrossRef

2. 2

   Susan Shoshana Weisberg. (2007) Hepatitis A. Disease-a-Month 53:9, 447-452
   CrossRef

3. 3

   Grace M.S. Tjon, Roel A. Coutinho, Anneke van den Hoek, Sylvia Esman, Clementine J. Wijkmans, Christian J.P.A. Hoebe, Bert Wolters, Corien Swaan, Ronald B. Geskus, Nicole Dukers, Sylvia M. Bruisten. (2006) High and persistent excretion of hepatitis A virus in immunocompetent patients. Journal of Medical Virology 78:11, 1398-1405
   CrossRef

4. 4

   A.M. Hauri, E. Fischer, J. Fitzenberger, H. Uphoff, C. Koenig. (2006) Active immunisation during an outbreak of hepatitis A in a German day-care centre. Vaccine 24:29-30, 5684-5689
   CrossRef

5. 5

   Andrea Normann, Christian Jung, Angelika Vallbracht, Bertram Flehmig. (2004) Time course of hepatitis A viremia and viral load in the blood of human hepatitis A patients. Journal of Medical Virology 72:1, 10-16
   CrossRef

6. 6

   Gloria Taliani, Giovanni Battista Gaeta. (2003) Hepatitis A: post-exposure prophylaxis. Vaccine 21:19-20, 2234-2237
   CrossRef

7. 7

   Robert Steffen. (2001) Immunization against Hepatitis A and Hepatitis B Infections. Journal of Travel Medicine 8:s1, s9-s16
   CrossRef