±_ Viral Hepatitis: E Prevention

A, B, C, D, and

-

Saul

Krugman,

This is the second part, on infection, R. J. H.

MD* part of a two-pan article about viral hepatitis. appeared in the June 1992 issue of Pediatrics

FOCUS QUESTIONS of the viral hepatitides, the most Important measures to be taken against transmission of the disease? For which of the hepatitides is (are) effective vaccine(s) available? For which of the hepatitides Is passive Immunity available? What therapies are effective against viral hepatitis?

1. For each what are

2. 3. 4.

The article

1992 issue of included a detailed discussion of the etiology, pathogenesis, clinical manifestations, course, complications, epidemiology, and prognosis of hepatitis A, B, C, D, and E. This second section reviews prevention and treatment of these infections.

Pediatrics

in the June

in Review

Prevention GENERAL

of Hepatitis

A

likely to have contact with the virus. However, routine use of immune globulin in schools, offices, and factories is not warranted; disease spread is unlikely under the conditions existing in these open facilities. The recommended 0.02-mLlkg dose of immune globulin should be given within 48 h, if possible, but not later than 1 wk after exposure. Preexposure prophylaxis with standard immune globulin is recommended for persons traveling to or working in areas where type A hepatitis is highly endemic. The recommended dose is 0.02 mLlkg. A repeat dose should be given if exposure is continuous for more than 4 mo. If the serologic test to detect hepatitis A antibody (anti-HAV) is available, frequent travelers to endemic areas should be tested to determine their immune status. If antiHAV is present, immune globulin prophylaxis is unnecessary. ACTIVE

IMMUNIZATION

Studies with inactivated hepatitis A vaccines have confirmed their safety, immunogenicity, and efficacy. These vaccines will be licensed for use in the United States in 1993. At that time, recommendations for their use will be published by the United States Public Health Service and the American Academy of Pediatrics.

Prevention

of Hepatitis

B

IMMUNIZATION

Postexposure prophylaxis with standard immune globulin is recommended for all individuals who have had intimate exposure to a person with the disease. Immune globulin also is indicated for persons living in the same household because they are Professor of Pediatrics, Center, 550 First Avenue, 10016.

Pediatrics

in Review.

MEASURES

Procedures designed to prevent fecaloral spread of hepatitis A virus should be used for control. These include scrupulous handwashing, proper sterilization of food utensils, fly abatement, and exclusion of potentially infectious food handlers. Although close contact is the most common mode of transmission, common source epidemics stemming from contaminated food, milk, and water supplies may occur. PASSIVE

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GENERAL

MEASURES

Contaminated blood, blood products, and needles are the most common sources of hepatitis B infection. The most common mode of transmission is parenteral, but the virus can infect via the oral route and by close physical contact with hepatitis B-contaminated body fluids. Hepatitis B is a sexually transmitted disease. Blood obtained from commercial donors

carries a 10- to 15-fold greater risk of causing hepatitis than blood obtamed from volunteer donors. The indications for administering blood or blood products should be assessed carefully to be sure that the potential advantages warrant the risk. Donor blood should be tested routinely for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc).

IMMUNOPROPHYLAXIS Two types of products are available: hepatitis B immune globulin for passive immunization and inactivated hepatitis B vaccine for active immunization. The vaccine is recommended for both pre- and postexposure prophylaxis. Hepatitis B immune globulin provides temporary protection, and it is recommended for certain postexposure situations. Hepatitis

B Immune

Globulin

Hepatitis B pared from tains a high hepatitis B

immune globulin is prehuman plasma that contiter of antibody to surface antigen (antiHBs), greater than 1 : 100 000 by radioimmunoassay. The human donor plasma is screened for antibodies to human immunodeficiency virus. In addition, the Cohn fractionation process used to prepare hepatitis B immune globulin inactivates and eliminates human immunodeficiency virus from the final product, if present. There is no evidence that acquired immunodeficiency syndrome has been transmitted by hepatitis B immune globulin. Hepatitis B immune globulin is recommended after exposure to the hepatitis B virus in the following situations: 1) perinatal exposure of an infant born to an HBsAg-positive mother, 2) accidental percutaneous or mucosal exposure to HBsAg-positive blood, 3) sexual exposure to an HBsAg-positive person, and 4) intimate household contact. Simultaneous active immunization with hepatitis B vaccine is recommended under these circumstances.

1992

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245

r

INFECTIOUS DISEASE H.patltls

Hepatitis

B Vaccine

Two types of hepatitis B vaccine are licensed in the United States: plasma. derived and yeast recombinant. Extensive experience to date has confirmed the safety, immunogenicity, and efficacy of these vaccines in adults and in infants. Plasma-derived vaccine is no longer produced in the United States. Primary vaccination consists of three intramuscular doses of vaccine given at 0, 1, and 6 mo of age. An alternate schedule of four doses at 0, 1, 2, and 12 mo of age also has been recommended. Because various hepa. titis vaccines are not generic, the age-specific doses may be variable (Table). All hepatitis B vaccines are mactivated (noninfective) products. There is no evidence of interference with other vaccines administered simultaneously. There has been no evidence of risk to the fetus following vaccine given during pregnancy. In contrast, hepatitis B infection in a pregnant woman may cause severe disease in the mother and chronic infection of the newborn infant. Therefore, preg. nancy and lactation are not a contraindication for use of the vaccine in women who are at high risk of contracting hepatitis B. Hepatitis B vaccine is recommended for the following individuals who are at increased risk: healthcare professionals exposed to blood or blood products, patients who have hemophilia or thalassemia, children

Table.

Recommended

Dosis

or staff at institutions for the developmentally disabled, promiscuous homosexual males, intravenous drug abusers, and household contacts of chronic carriers. OF NEONATAL

PREVENTION

HEPATITIS

B

Postexposure tal hepatitis

prophylaxis B infection

B immune

globulin

for perinawith hepatitis

and hepatitis

B

vaccine has proved to be effective because intrauterine infection is rare (about 5%), most infants are exposed at the time of birth, and the incubation period of hepatitis B may range between 6 wk and 6 mo. Consequently, active immunization with hepatitis B vaccine can induce an antibody response before onset of infection. Several studies have confirmed the efficacy of combined passive (hepatitis B immune globulin) and active (hepatitis B vaccine) immunization for the prevention of pennatally acquired infection. Results of these studies revealed that the following regimen should prevent 85% to 90% of chronic infections in infants born to mothers whose blood is positive for HBsAg and hepatitis E core antigen (HBeAg): 1) Hepatitis B immunoglobulin, 0.5 mL given intramuscularly within the first few hours after birth, and 2) hepatitis B vaccine, given intramuscularly before the baby leaves the hospital (Table). Combined hepatitis B immune globulin and hepatitis B vaccine prophy-

of Currently

Ucnssd

Infants of carrier mothers infected hepatitis B virus

HEPATITIS AND

B CARRIER

BREAST

MOThERS

FEEDING

The milk of hepatitis B carrier mothers may contain HBsAg. In addition, serum from cracked nipples may contam infectious hepatitis B virus. Nevertheless, breast feeding should not be discouraged because hepatitis B immune globulin and hepatitis B vaccine are very effective in preventing neonatal hepatitis B infection.

B Vaccines

Hipatitis VACCINE

PLASMADERIVED1 ig [mU

GROUP

la.xis is recommended for all infants whose mothers are HBsAg-positive, regardless of their HBeAg status. It is essential that HBsAg-positive pregnant women be identified during the prenatal period. Notification of the obstetric staff will enable them to protect themselves and other patients from infectious blood or secretions. Notification of the pediatric staff will alert them to institute therapy immediately after birth. During 1988, the United States Public Health Service recommended that all pregnant women in the United States be tested routinely for HBsAg. However, routine screening of all pregnant women is neither feasible nor recommended for those living in developing areas of the world where hepatitis B infection is hyperendemic. Under these circumstances, routine immunization with hepatitis B vaccine is indicated for all newborn infants. This strategy should prevent perinatallyor postnatally-acquired hepatitis B infection.

DOSE

RECOMBINANT RECOMBIVAX p.g [mL]

-

RECOMBINANT ENGERIX B g [mU

HB2

with 10

[0.5]

5

[0.5]

10

[0.5]

Other infants and children (19

y)

20

Adapted from Centers of Disease Control. Protection against Committee (ACIP). MMWR. 1190;39 (No. RR-2):1-26. ‘Available only for hemodialysLc and other immunocompromised 2Mek Shaip & Dohme. 3SmithKline Beecham.

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hepatitis: patients

Recommendations and for

persons

of the with

known

Pediatrics

Immunizations allergy

Practices

Advisory

to yeast.

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1992

INFECTIOUS

DISEASE

Hepatitis UNIVERSAL

OF

IMMUNIZATION

INFANTS

Hepatitis B vaccine has been used extensively throughout the world since its licensure in November 1981 Extensive experience involving many millions of vaccinees has confirmed its safety and efficacy. Hepatitis B vaccine currently is being incorporated into the Expanded Program on Immunization of the World Health Organization. The first dose of vaccine is given to all infants soon after birth. Additional doses are given at subsequent routine visits. Universal immunization of all infants in the United States is now recommended by the Advisory Committee on Immunization Practices of the Centers for Disease Control and the Committee on Infectious Diseases of the American Academy of Pediatrics. The preferred schedule is to give: 1) the first dose of vaccine at birth before discharge from the hospital; 2) the second dose at the first routine visit 1 to 2 mo later; and 3) the third dose at a routine visit between 6 and 18 mo of age. An alternative schedule would include the first dose at 2 mo of age, the second dose at 4 mo of age, and the third dose at 6 to 18 mo of age. It is anticipated that in the future multiple antigen preparations will include hepatitis B, diphtheria-tetanus toxoids-pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis A. .

therapy for chronic hepatitis B and C infections has been documented in various controlled trials. About 30% to 40% of patients respond to therapy. However, 50% of patients may relapse when therapy is discontinued. Patients receiving therapy should be monitored for the possibility of adverse psychological effects.

1 Measures .

hepatitis A include each of the following, e.vcep:: A. Vigorous handwashing. B. Administration of standard immune globulin. C. Avoiding raw shellfish from

Suggested

Reading

in Review

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7

D.

of a vaccine antigen. for hepatitis

transfusion. Administration of standard immune globulin.

3. Each

of the following statements the prevention of hepatitis B in newborn infants of car-

regarding

ncr mothers is true, A. An effective

except:

protocol

vention involves tion of immune

for pre-

a combinaglobulin and

hepatitis B vaccine. B. Breast feeding is contraindicated. C. The first dose of hepatitis B vaccine is given at birth (before discharge from the hospital). D. The United States Public

:1501-1506

Health

Service

has recom-

mended routine testing of pregnant

1989;321:1506-1510

women

for hepatitis

B surface antigen.

MR. Buynak EG, Roehm RR, Tytell AA, Bertland AU, Lampson OP. Purified and inactivated hepatitis B vaccine. Am J

4.

1975;270:401-404

Hoofnagle JH, DiBisceglie AM. Serologic diagnosis of acute and chronic viral hepatitis. Semin LiverDis. 1991;11:73-83 Kuo 0, Choo Q-L, Alter Hi, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989;244:362-364 McMahon BI, Rhoades ER, Heyward WL, et al. A comprehensive programme to reduce the incidence of hepatitis B virus infection and its sequelae in Alaskan natives. Lance:. 1987;2: 1134-1136 Rizzetto M. The delta agent. Hepatology. 1983;3:729-737 Stevens CE, Taylor PE, Tong Mi, et al. Yeast-recombinant hepatitis B vaccine: Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission. JAMA. 1987;257:2612-2616

July 1992

recommended

B surface antigen prior to

Hilleman

Sci.

currently

vectors.

using recombinant C. Testing of blood

DiBisceglie AM, Martin P. Kassianides C, et al. Recombinant interferon alpha therapy for chronic hepatitis C: A randomized, doubleblind, placebo-controlled trial. N EngI J

Med

of insect

B. Administration

25

Med.

waters.

Control

for prevention of transmission of hepatitis B include each of the following, except: A. Use of clean needles by drug abusers.

Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B hepatitis genome. Science. 1989;244:359-362 Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alpha: A multicenter randomized, controlled trial. N EngI J Med. 1989;321

polluted 2. Measures

Alter MJ, Hadler SC, Margolis HS, Ct al. The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies. JAMA. 1990;263:12181222 centes for Disease Control. Protection against viral hepatitis: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR. 1990;39:5-22 Centers for Disease Control. Hepatitis B virus: A comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee. MMWR. 1991;40:l-

Each of the following

statements regarding treatment of viral hepatitides is true, except: A. There is no specific therapy for hepatitis A, B, C, or D. B. Alpha-interferon is helpful in cases of chronic hepatitis due to hepatitis B. C. Corticosteroid administration

is advised to prevent complications in children who have hepatitis. D. Return of appetite is an appropriate guide to reinstitute feeding of a normal diet.

Thim

Pediatrics

currently recommended for prevention of transmission of

D.

Treatment There is no specific treatment for children who are infected with hepatitis A, B, C, or D. The disease is generally so mild that bed rest is unnecessary after the acute stage. The child’s diet and return to activity usually are gauged by the child’s desire. When anorexia is present, food is rejected; broths and fruit juices should be offered. A normal diet is recommended when appetite returns. Corticosteroids and other drugs are not indicated for children who have uncomplicated hepatitis. The efficacy of alpha-interferon

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Viral Hepatitis: A, B, C, D, and E−−Prevention Saul Krugman Pediatrics in Review 1992;13;245 DOI: 10.1542/pir.13-7-245

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Viral Hepatitis: A, B, C, D, and E−−Prevention Saul Krugman Pediatrics in Review 1992;13;245 DOI: 10.1542/pir.13-7-245

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pedsinreview.aappublications.org/content/13/7/245

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 1992 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0191-9601.

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