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From
Medscape Infectious Diseases
Pediatric ID Update: Reducing Hepatitis A Infection by Immunizing Infants
Robert W. Steele, MD
[Medscape Infectious Diseases, 2001. © 2001 Medscape, Inc.]
Active immunization against hepatitis A began in 1995 when the US Food and
Drug Administration (FDA) gave licensure to the first vaccination for this
disease. The following year, the Centers for Disease Control and Prevention
(CDC) Advisory Committee on Immunization Practices (ACIP) recommended routine
vaccination of children who live in those areas of the United States with the
highest rates of infection and disease.
Yet despite the success typically noted when routine immunization is
instituted, hepatitis A remains one of the most common vaccine-preventable
diseases in the United States.[1]
Data gathered during community-based hepatitis A vaccination programs these
past several years have shown that the original ACIP recommendations that
targeted specific high-risk groups would most likely not make a significant
impact on the overall incidence of the disease.[2] To understand why this is the case, it is important
to recognize the latest epidemiologic and clinical aspects of this disease.
 Who
Gets Hepatitis A, and How?
The hepatitis A virus (HAV) is transmitted almost
exclusively through the fecal-oral route by direct contact from an infected
person or from ingestion of contaminated food or water. Although the virus
has been demonstrated in the saliva of viremic primates and humans,
transmission through saliva has not been shown to occur.[3]
The majority of cases occur during community outbreaks, the identified
source usually being either a household or sexual contact who has hepatitis
A.[4] The highest incidence
of infection occurs in children between the ages of 5 and 14 years.[2] However, children clearly play a
significant role in transmission, since they typically have subclinical
infection and essentially serve as a vector to adults. In communities with
the highest rates of hepatitis A, approximately one third of children acquire
the infection before age 5, and almost all of them are infected before
reaching adulthood.[5,6] In
fact, when routine vaccination is instituted for preschool and school-aged
children in these high-prevalence communities, outbreaks are not only
interrupted, but subsequent outbreaks are prevented.[7]
A
Focus of Attention: Daycare Centers
A number of factors seem to be involved in the spread of
HAV by children. The diagnosis may be delayed or missed entirely in children
due to the lack of specific symptoms such as jaundice. The greatest risk of
infecting others occurs when the virus is shed in the stool in the highest
concentration, and this may last several months in some children.[8] In addition, it is possible for HAV
to remain stable and infectious outside of the host for months if conditions
are optimal.
It is therefore understandable why daycare centers receive so much
attention as areas of high risk for transmission. It is estimated that 11% to
16% of reported cases occur among children or employees in daycare centers or
among their contacts.[4]
While daycare centers utilize many infection control measures, a few have
been shown to work. The virus may be rendered permanently inactive if it is
heated for 1 minute at 85oC
(185oF). There are multiple
commercial products that are effective in inactivating the virus, but a
simple 1:100 solution of household bleach is also a common effective method
for disinfecting hard surfaces.[9,10]
Parallels
With Polio
Even though infection control measures can have a large
impact on reducing the spread of hepatitis A, immunization remains the most
effective method for preventing its transmission. The epidemiology of
poliomyelitis has many similarities to that of HAV disease, with regard to
the age of both the persons who are reservoirs and those who are most often
infected. Extrapolating from the data gathered in the effort to eradicate
polio leads one to realize that immunizing a large proportion of children
could significantly reduce the overall incidence of disease in the general
population.[11] Although other
risk groups are currently targeted for immunization, including travelers, men
who have sex with men, drug users, and daycare workers, children remain the
largest priority group identified for immunization.[2]
Boosting
Vaccine Efficacy in Infants
There are currently 2 inactivated hepatitis A vaccines
licensed in the United States. These are VAQTA (Merck & Co.,
Inc.) and HAVRIX (SmithKline Beecham Biologicals). These vaccines
are highly immunogenic in children and adolescents, giving virtually 100%
protective antibody levels after 2 doses.[12,13]
These vaccines are immunogenic in infants who have not received
transplacental passive antibody, but children younger than 2 years who do
have passive antibody have reduced geometric mean concentration (GMC) after
vaccination.[14]
Researchers are now evaluating higher-dose hepatitis A vaccine candidates
to be used in an attempt to "overpower" the presence of maternal
antibodies in infants. One such study examined antibody responses of infants
given the usual immunizations along with a high-dose hepatitis A vaccine.[15] Babies were divided into those
with maternal antibodies present and those who were seronegative. Both groups
were given the vaccine at 2, 4, and 6 months, but seropositive individuals
were given a booster at 12 months. Notably, those with maternal antibodies
present showed clear interference when GMC was measured at 11 months of age.
However, 1 month after the 1-year booster dose was given, the GMC showed
excellent response. These investigators conclude that priming of the immune
response occurs despite initial interference. If these data hold true in
further studies, universal hepatitis A vaccination of infants may be the next
disease battleground that could be conquered.
References
- Centers for Disease
Control and Prevention (CDC). Summary of notifiable diseases, United
States, 1999. MMWR Morb Mortal Wkly Rep. 2000/49(37):841. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4937a5.htm.
- Prevention of
Hepatitis A through active or passive immunization: recommendations of
the ACIP. MMWR Morb Mortal Wkly Rep. 1999/48(RR12):1-37. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4812a1.htm.
- Cohen JI, Feinstone S,
Purcell RH. Hepatitis A virus infection in a chimpanzee: duration of
viremia and detection of virus in saliva and throat swabs. J Infect Dis.
1989;160:887-890.
- Bell BP, Shapiro CN,
Alter MJ, et al. The diverse patterns of hepatitis A epidemiology in the
United States: implications for vaccination strategies. J Infect Dis.
1998;178:1579-1584.
- Shaw FE, Shapiro CN,
Welty TK, et al. Hepatitis transmission among the Sioux Indians of South
Dakota. Am J Public Health. 1990;80:1091-1094.
- Williams R. Prevalence
of hepatitis A virus antibody among Navajo school children. Am J Public
Health. 1986;76:282-283.
- CDC. Hepatitis A
vaccination programs in communities with high rates of hepatitis A. MMWR
Morb Mortal Wkly Rep. 1997/46(26):600-603. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00048313.htm.
- Rosenblum LS,
Villarino ME, Nainan OV, et al. Hepatitis A outbreak in a neonatal
intensive care unit: risk factors for transmission and evidence of
prolonged viral excretion among preterm infants. J Infect Dis.
1991;164:476-482.
- McCaustland KA, Bond
WW, Bradley DW, Ebert JW, Maynard JE. Survival of hepatitis A virus in
feces after drying and storage for 1 month. J Clin Microbiol.
1982;16:957-958.
- Favero MS, Bond WW.
Disinfection and sterilization. In: Zuckerman AJ, Thomas HC, eds. Viral
Hepatitis, Scientific Basis and Clinical Management. New York, NY:
Churchill Livingstone; 1993:565-75.
- Lemon SM, Shapiro CN.
The value of immunization against hepatitis A. Infect Agents Dis.
1994;1:38-49.
- Ashur Y, Adler R, Rowe
M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines
-- VAQTA® and HAVRIX® -- in young adults. Vaccine. 1999;17:2290-2296.
- Balcarek KB, Bagley
MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an
inactivated hepatitis A vaccine in preschool children. J Infect Dis.
1995;171(suppl 1):S70-72.
- Lieberman JM, Marcy M,
Partridge S, Ward JI. Evaluation of hepatitis A vaccine in infants:
effect of maternal antibodies on the antibody response. In: Program and
abstracts of the 36th Annual Meeting of the Infectious Diseases Society
of America; 1998. Abstract 76.
- Dagan R, Amir J,
Mijalovsky A, et al. Immunization against hepatitis A in the first year
of life: priming despite the presence of maternal antibody. Pediatr
Infect Dis J. 2000;19:1045-1052.
Robert W. Steele, MD, Staff Pediatrician
and Staff Physician, St. John's Regional Health Center, Springfield, Missouri
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