Ehrman Archives: Saul Krugman Exhibit

Most-cited article:
Infectious Hepatitis
Evidence for Two Distinctive Clinical, Epidemiological, and Immunological Types of Infection
Saul Krugman, MD, Joan P. Giles, MD, and Jack Hammond, MD

(Abstract posted courtesy of the Journal of the American Medical Association)

The identification of two types of infectious hepatitis with distinctive clinical, epidemiological, and immunological features provided an explanation for the occurrence of second attacks of the disease. One type resembled classical infectious hepatitis (IH); it was characterized by an incubation period of 30 to 38 days, a relatively short period of abnormal serum transaminase activity (3 to 19 days), a consistently abnormal thymol turbidity, and a high degree of contagion. The other type resembled serum hepatitis (SH); it was characterized by a longer incubation period (41 to 108 days), a longer period of abnormal transaminase activity (35 to 200 days) and a relatively abnormal thymol turbidity. Contrary to commonly accepted concepts, the SH type was moderately contagious. Patients with IH type were later proved to be immune to the same type. Patients with the SH type were not immune to the IH type infection.

Viral Hepatitis
New Light on an Old Disease
Saul Krugman, MD, and Joan P. Giles, MD

(Abstract posted courtesy of the Journal of the American Medical Association)

Tests for the presence of Australia or hepatitis-associated antigen (HAA) and antibody (anti-HAA) were performed on more than 25,000 serum specimens from more than 700 patients with viral hepatitis. Hepatitis-associated antigen was consistently present in sera from patients with MS-2 strain of serum hepatitis (SH); it was not present in MS-1 infectious hepatitis (IH). Hepatitis-associated antigen was detected earlier after a parenteral exposure to SH than after an oral exposure. Antigen appeared two weeks to two months before onset of jaundice; it was transient in 65% of patients, but persisted for four months to 13 years in 35% of children. The average incubation period of IH (MS-1) was essentially the same following an oral or parenteral exposure (32 to33 days); in SH (MS-2) it was 65 days after parenteral exposure and 98 days after oral exposure. Gamma-globulin consistently neutralized the infectivity of IH (MS-1) serum; in most cases it did not neutralize the infectivity of SH (MS-2) serum.

Viral Hepatitis
Relation of Australia/SH Antigen to the Willowbrook MS-2 Strain
Joan P. Giles, MD, Robert W. McCollum, MD, L.W. Berndtson, Jr., and
Saul Krugman, MD.

(Abstract posted courtesy of the New England Journal of Medicine)

Serial serum specimens (before infection through 200 days after infection) in 31 MS-1 (short incubation) and 19 MS-2 (long incubation) cases of viral hepatitis were examined for the presence of Australia/SH antigen. An agar-gel double-diffusion technic was used. The antigen was not detected in any serum from the MS-1 series, but it appeared regularly after MS-2 infection, usually well in advance of evidence of hepatitis. In approximately half the MS-2 infections the antigen was present only transiently (up to 68 days), but in the remainder it persisted throughout the period of intensive observation and for at least three years subsequently.

New England Journal of Medicine, July 17, 1969, Vol. 281, pp. 119-122.
Copyright Massachusetts Medical Society, 1969.

Viral Hepatitis, Type B
Studies on Natural History and Prevention Re-examined
Saul Krugman, MD, Lacy R. Overby, Ph.D., Isa K. Mushawar, Ph.D., Chung-Mei Ling, Ph.D., Gert G. Frösner, MD, and Friedrich Deinhardt, MD

(Abstract posted courtesy of the New England Journal of Medicine)

Frozen serial serum specimens obtained from past studies on the natural history and prevention of Type B hepatitis in children were retested by a radioimmunoassay for the following markers of hepatitis B infection: hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc).
The interval between exposure and evidence of viremia (HBsAg) was as short as six days. HBsAg and HBeAg persisted for two to five months and occasionally for more than one year after recovery. After the disappearance of their respective antigens, anti-HBc and anti-HBs pesisted for more than seven years and anti-HBe for one to two years. Treatment with hepatitis B immune globulin after exposure induced complete or partial protection or prolongation of the incubation period. Administration of heat-inactivated hepatitis B virus, MS-2 strain, to 29 children induced an inapparent infection in three, characterized by a transient appearance of HBsAg and HBeAg, and the persistence of anti-HBc, anti-HBe and anti-HBs for more than two years.

New England Journal of Medicine, January 18, 1979, Vol. 300, pp. 101-106.
Copyright Massachusetts Medical Society, 1979.

Viral Hepatitis, Type B (MS-2 Strain)
Studies on Active Immunization
Saul Krugman, MD; Joan P. Giles, MD, and Jack Hammond, MD

(Abstract posted courtesy of the Journal of the American Medical Association)

Viral hepatitis, type B (MS-2) was prevented by active and passive immunization. Active immunization was induced by inoculation of a boiled, inactivated preparation of a 1:10 dilution of MS-2 serum in distilled water; two inoculations at four month intervals were more effective than one. However, one inoculation gave enough protection to prevent some cases and modify others.

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