Monday, November 23, 1998

1. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.

Outbreaks reported to DHMH from 11/16 - 11/20/98:

2 foodborne gastroenteritis: one at assisted living facility, one at catered dinner

1 Hepatitis C in a dialysis facility, 1 sepsis in a hospital

2. The Johns Hopkins Hospital. Information provided by Dr. Ann Smith, Dr. John Ticehurst, and Cindy Merz, Department of Pathology.

Case Report: An 18 year old woman came into the clinic for a routine prenatal check up. By report she had been screened for hepatitis B infection [1] and was negative for hepatitis B surface antigen (HBsAg) as of one month ago. Because she was exposed to an individual with hepatitis, it is decided that she should be tested again and a "HBsAg protocol" is ordered. Over a period of months the following test results are obtained:

(anti-HBs assay was ordered but canceled on 8/24, 9/21, 12/2/93 and 1/6/94)

Her results follow a temporal pattern typical of acute HBV infection: positive only for HBsAg on 8/24; positive for both HBsAg and HBeAg on 9/21; and subsequently positive for HBsAg, HBeAg, and anti-HBc IgM (with no evidence of infection with hepatitis viruses A or C). These results are communicated by written and oral report to her physician, who makes the diagnosis of acute HBV infection. By law, the lab and physician report this HBV infection to the Maryland Department of Health & Mental Hygiene. The woman's contacts are counseled by public health personnel. The woman had no other complications during her pregnancy and within 12 hours of delivery, the infant was treated with hepatitis B immunoglobulin (HBIG) and given hepatitis B vaccine [I].

Discussion: During 1987-1989 the reported U.S. incidence of HBV increased by 37% in spite of strategies to vaccinate high risk populations. Between 1980 and 1991 there were approximately 250,000 new cases of HBV per year and 4000 to 5000 deaths from chronic HBV and its sequelae. The apparent source of many new infections was 1.25 million chronic carriers of the virus. Comprehensive strategies for eliminating HBV transmission include testing of pregnant women for HBsAg, immunizing infants born to HBsAg positive mothers, routine vaccination of children and adolescents, and vaccination of certain high risk adults.

HBV, archetype of the family Hepadnaviridae, is an enveloped, partially double-stranded DNA virus that replicates via RNA intermediates. Its very small (3.2-kb) genome encodes three proteins on which serologic assays are based. HBsAg is the envelope protein, detection of which indicates active HBV replication and infectivity; anti-HBs nearly always indicates recovery from infection and protection from HBV. (Current hepatitis B vaccines consist only of HBsAg-envelope particles produced in yeast via recombinant DNA technology.) The nucleocapsid protein, HBcAg, is not detectable unless the virion envelope is disrupted; however, IgM anti-HBc is a marker of acute infection (but detectable during <15% of chronic hepatitis B exacerbations) [2]. "Total" (IgM+IgG) anti-HBc also develops during the acute phase - but not in response to vaccination - and usually persists for life (during continued HBV replication or after apparent recovery). HBeAg, not a virion component, is expressed into the blood during high-level replication and thus correlates with high infectivity; anti-HBe is usually the first marker of recovery from acute or chronic infection [2,3]. While HBV is oncogenic and readily integrates into hepatocellular DNA, causal links between HBV and hepatocellular carcinoma are not well understood.

Serologic testing: There has recently been increasing confusion regarding JHMI serologic testing for the hepatitis virus markers specifically the (HBsAg) protocol. Several physicians have raised concern regarding this "protocol" and whether it represents excessive or inappropriate testing that leads to automatic testing without a physician's order. Presently, hepatitis testing is being performed in the Microbiology/Immunology Division. Each test for an individual hepatitis-virus marker can be individually ordered. The first two columns of the following table list test codes and testing descriptions from the purple "Pathology 4 Immunology" requisition form (except for anti-HAV IgM, which is not on the form):

* ACIP recommends testing of all pregnant women for HBsAg, the results of which determine if the infant receives routine hepatitis B vaccination (HBsAg-neg) or HBIG plus vaccine within 12 hr of birth (HBsAg-pos) [1]; however, the state of every HBV infection should be evaluated for management of that individual and her contacts.

** Chronic HBV infections uncommonly cocirculate HBsAg and anti-HBs [2].

When the HBsAg protocol is requested and the specimen is shown to contain HbsAg, an automatic testing algorithm is put into place. This process eventually yields results for two other HBV antigen/antibody systems; the HBsAg confirmatory assay is performed only if "core" and "e" results are negative "core" (testing for IgM anti-HBc), and "e" (testing for HBeAg and if negative, for anti-HBe). This algorithm provides appropriate information that confirms the specificity of an HBsAg positive result and usually allows for conclusive interpretation regarding the temporal state of the HBV infection. The algorithm was developed more than five years ago in conjunction with Transfusion Medicine and Gastroenterology personnel to help guide physicians and to eliminate the "check-all-the-boxes" ordering, thus preventing over-ordering of tests inappropriate for many patients. It is important to emphasize that all the tests can be ordered individually and serologic tests for other markers can be written in as necessary.

1. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports 1991; 40: RR-13.
2. Hollinger FB. Hepatitis B virus. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, Roizman B, Straus SE, eds. Fields Virology, 3rd ed. Philadelphia: Lippincott Raven Press, 1996: 2739-2807.
3. "Hepatitis slide rule," an Abbott Diagnostics Educational Services pocket aid (revised 1997) that charts typical temporal patterns of serologic markers. Available by calling (800) 323-9100, from an Abbott representative; this statement does not purport to represent policies of the US Food & Drug Administration or Department of Health & Human Services.