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Fulminant Hepatitis B among Parenteral Drug Abusers -- Kentucky, California

During the first 10 months of 1983, unrelated clusters of fulminant hepatitis B (HB) deaths occurred in Madisonville, Kentucky, and Porterville, California. Both outbreaks were limited to circles of parenteral drug abusers and their sexual contacts. Thirty-six cases occurred, with five deaths, for a case-fatality ratio (CFR) over 10 times the expected ratio.

Investigations involved active HB case finding, identification of possible risk factors for fulminant HB, and serotesting for HB and the Delta agent (a dependent virus recently implicated as a co-factor in fulminant HB infection). In both outbreaks, a case was defined as: (1) acute clinical symptoms compatible with hepatitis B; (2) acute elevation of serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) two or more times greater than the upper limit of normal; and (3) positive hepatitis B surface antigen (HBsAg) serology.

In Kentucky, 17 outbreak-related cases occurred between January and September 1983. Twelve patients were male, and all 17 were white, non-Hispanic. Ages ranged from 18 to 30 years (median 22 years). Two of the 17 patients (one male, one female) had fulminant disease that resulted in death, for a CFR of 11.8%. Fifteen patients had needle exposures; two were sexual contacts of patients.

In California, 19 HB cases were identified between June and December 1983. Seventeen patients were male; 17 were Hispanic; one, an American Indian; and one, white, non-Hispanic. Ages ranged from 18 to 34 years (median 20.5). Three patients, all male (including two brothers), had fulminant HB that resulted in death, for a CFR of 15.8%. Eighteen patients had needle exposures; one was a sexual contact of a patient.

The combined outbreak-related CFR was 13.9%, as compared with a combined CFR of 4.5% in 22 concurrent nonoutbreak-related cases and a CFR of 1% expected for hospitalized HB patients.

In both outbreaks, the only hepatotoxin identified was alcohol; however, the alcohol intake of patients with fulminant HB did not differ significantly from that of patients with nonfulminant disease. Anti-Delta antibody was detected in one of three patients with fulminant HB from whom serum was still available and in none of 32 patients with nonfulminant HB. This patient had strongly positive IgM-anti-Delta and a biphasic clinical course indicating co-infection with the Delta agent. In addition, at least two hepatitis non-A, non-B (NANB) cases and several previous NANB cases were identified among intravenous-drug users in both outbreaks. Reported by RL Schaefer, MS, Regional Medical Center, RL Wolfe, MD, CM Steinfeld, MD, EE Kawas, MD, DA Martin, MD, Hopkins County Health Dept, Madisonville, MW Hinds, MD, State Epidemiologist, Kentucky Dept of Health Svcs; RH Johnson, MD, Kern County Medical Center, Bakersfield, JR Hayes, MD, J Jacobs, MD, Porterville, J Pendleton, Jr, MD, Tulare County Health Dept, AG Redeker, MD, Los Angeles, RR Roberto, MD, J Chin, MD, State Epidemiologist, California Dept of Health Svcs; Hepatitis Br, Div of Hepatitis and Viral Enteritis, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Hepatitis B is generally a mild disease with a CFR of only 1% in patients ill enough to require hospitalization. In one large, drug-related military outbreak, no deaths occurred among several thousand patients with clinical HB (1). The severity of the current outbreaks might be explained by any of several factors, including an unusually virulent strain of HB, simultaneous infection with other hepatotrophic viruses (NANB virus or the Delta agent) or the action of hepatotoxic chemicals. Although the existence of virulent strains of HB virus have not been clearly documented, each of the other factors has been implicated as a cause of at least one severe hepatitis outbreak.

One previously reported cluster of fulminant HB deaths among parenteral drug users, in which six of nine patients died, occurred in New Bern, North Carolina, in 1979 (2). An extensive investigation implicated the injection of 3,4 methylene diamphetamine (MDA) as a possible co-factor to account for the severity of the outbreak. Follow-up studies in chimpanzees exposed to MDA and HB virus were inconclusive. Two cases of NANB hepatitis in drug users were also associated with the outbreak.

There was no MDA use in either of the two current outbreaks. Although "crank," a locally-produced, amphetamine-like substance, was available in California, it was used to a far lesser extent than heroin, and none of the patients with fulminant HB were known to have used it.

As in the New Bern outbreak, a few cases of NANB hepatitis were associated with both recent outbreaks. NANB hepatitis virus has been implicated, along with HB, in an exceptionally virulent outbreak of hepatitis (11 deaths/42 patients) among hemodialysis patients and staff in Edinburgh, Scotland, in 1969-1970, when stored sera were recently retested using modern serodiagnostic techniques for hepatitis A and B (3). However, until a reliable serologic test for NANB virus(es) is developed, the role of concurrent NANB hepatitis infection in outbreaks of severe HB cannot be clearly defined.

Infection with the Delta agent was recently implicated as the cause of an exceptionally severe hepatitis epidemic among Venezuelan Indians (in which 34 of 149 patients died) (4). The Delta agent is an HB-dependent virus composed of a protein antigen (Delta antigen) and a ribonucleic acid (RNA) of low molecular weight, coated with hepatitis B surface antigen. It is transmissible as an independent infectious agent but may only replicate in the presence of active hepatitis B virus infection (5). Coprimary infection with HB/Delta, or Delta virus superinfection of an HB carrier may cause acute and/or chronic hepatitis; both types of infection have been associated with fulminant hepatitis B in Europe (6). Delta agent infection is endemic in southern Italy and in certain parts of South America and western Africa, but has been limited to hemophilia patients and drug-addict populations in the rest of Western Europe, North America, and Australia (7,8).

Evidence of infection with the Delta agent was found in one of three patients with fulminant HB in whom serum was available for testing (1/1 from California, 0/2 from Kentucky). Although Delta was not clearly defined as the cause of these outbreaks, testing for markers of Delta infection is indicated in any outbreak of fulminant hepatitis.

Control of hepatitis B outbreaks in parenteral-drug-using populations is difficult. Efforts in these outbreaks were focused on physician education with respect to diagnosis of HB by appropriate serotesting and prophylaxis of needle and sexual contacts of patients. Seronegative needle contacts should be offered HB vaccine in addition to standard passive prophylaxis. The Delta agent is transmitted similarly to HB and requires no special precautions other than those recommended for HB.

References

  1. Cates W Jr, Warner JW. Hepatitis B in Nuremberg, Germany. Epidemiology of a drug-associated epidemic among US Army soldiers. JAMA 1975;234:930-4.

  2. CDC. Hepatitis B--New Bern, North Carolina. MMWR 1979;28:373-4.

  3. Marmion BP, Burrell CJ, Tonkin RW, Dickson J. Dialysis-associated hepatitis in Edinburgh; 1969-1978. Rev Infect Dis 1982;4:619-37.

  4. Hadler S, Monzon M, Ponzetto A, et al. Delta virus infection and severe hepatitis: an epidemic in the Yucpa Indians of Venezuela. Ann Intern Med (in press).

  5. Rizzetto M, Canese MG, Gerin JL, London WT, Sly DL, Purcell RH. Transmission of the hepatitis B virus-associated Delta antigen to chimpanzees. J Infect Dis 1980;141:590-602.

  6. Smedile A, Farci P, Verme G et al. Influence of Delta infection on severity of hepatitis B. Lancet 1982;II:945-7.

  7. Rizzetto M, Shih JW-K, Gocke DJ, Purcell RH, Verme G, Gerin JL. Incidence and significance of antibodies to Delta antigen in hepatitis B virus infection. Lancet 1979;II:986-90.

  8. WHO. Hepatitis surveillance: Delta agent. Wkly Epidem Rec 1983;58:391-2.



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