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We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

To determine the need for immunization of health workers with antibody to hepatitis B surface antigen (anti-HBs) as their only serologic marker of previous hepatitis B exposure, we studied the level, persistence, and immunologic specificity of isolated anti-HBs in 46 persons identified during screening for hepatitis B vaccine. We rescreened these persons 1 year later, administered a single dose of hepatitis B vaccine, and determined the anti-HBs level at 1, 2, and 8 weeks after vaccination. Isolated anti-HBs levels were low and antibody did not persist; 22 subjects tested had lost detectable anti-HBs within 19 months even though immunologic specificity was shown in vitro in 34. Anamnestic responses suggesting previous exposure and immunity were seen in only 10 subjects; 5 of these subjects had moderate-level, persistent anti-HBs. Although some persons with naturally acquired, isolated anti-HBs may be protected from hepatitis B, the immunologic specificity and protective value of anti-HBs, especially when levels are low, remain questionable.

Excerpt An intriguing feature of infection with the agent that causes hepatitis B in man is the great variation in host response. The Dane particle, which is 45 nm in diameter and contains an inter...

We tested sera collected between 1976 and 1984 from 362 persons in a variety of epidemiologic categories with acute and chronic hepatitis B and from 76 hemophiliacs and drug addicts with hepatitis B antibodies for hepatitis D markers. Hepatitis D markers were common in hemophiliacs, drug addicts, Afghanistanis, prisoners and hemodialysis patients; rare in persons from other hepatitis-B endemic areas, persons with sporadic hepatitis B and homosexual men; and absent in health-care workers and institutionalized mentally retarded persons. No change was observed in the frequency of this infection during the 9 years of this study. We found hepatitis D markers in 5% of patients with acute hepatitis B, 1 of 3 with fulminant hepatitis and in 4 (1 in a homosexual male) of 12 episodes of acute hepatitis in hepatitis B carriers. Hepatitis D markers were more frequent in chronic liver disease (18%) than in asymptomatic hepatitis B carriage (2%), but there was no association between severity of chronic hepatitis and hepatitis D. These findings indicate that, to date, health-care workers and institutionalized mentally retarded persons have been spared from infection with this agent but suggest that homosexual males may not continue to be spared. Even in an area nonendemic for hepatitis D, this agent contributed to 20 to 30% of chronic hepatitis B and acute hepatitis superimposed on chronic hepatitis B infection.

AUSTRALIA antigen was first identified using an antiserum produced in a transfused patient1,2. The antiserum gave a clear precipitin line in a double diffusion experiment when placed adjacent to the serum from an Australian aborigine. Pending further identification of the antigen, the geographic name “Australian antigen” was given to the reacting material found in the aborigine's serum. Specific antisera against this antigen can be produced by immunizing rabbits with serum containing Australia antigen, and subsequent absorption with serum which does not contain Australia antigen3. The precipitin band which forms between the haemophilia antiserum and the serum containing Australia antigen stains faintly with sudan black, indicating that the antigen contains lipid. It has a specific gravity of less than 1.21 and appears in the first peak in ‘Sephadex G-200’ column chromatography (indicating a high molecular weight)4.

We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.

In the first 10 months of 1974, 26 of 60 susceptible patients in a commercial hemodialysis unit developed asymptomatic infection with hepatitis B virus; 17 (65%) of the 26 cases occurred in 14 weeks from July to October. In a case-control study, 15 of 16 cases for whom records were available were found to be associated with malfunctions of dialysis machines (primarily leaks or ruptures in dialysis membranes) that had occurred before patients converted to hepatitis B surface antigen (HBs Ag) positivity. In comparison, 17 of 34 controls were associated with machine malfunctions (P less than 0.01). In addition, the mean number of malfunctions in machines per patient was significantly greater for cases of infection (2.25 +/- 1.34) than for controls (1.06 +/- 1.39) (P less than 0.01). Furthermore, a direct correlation was demonstrated between an increase in blood leaks in machines used with susceptible patients and subsequent increases in cases of hepatitis for the various beds in the unit (r=0.994, P less than 0.0001). The mean period from the last blood leak to HBs Ag seroconversion was 67 days. Six of the 36 blood leaks associated with cases of infection occurred less than 6 hr after leaks in the contaminated area, whereas only one of 36 leaks associated with controls demonstrated this relationship (P less than 0.05). These data suggest that the conversion to HBs Ag positivity was linked to the occurrence of machine malfunctions (blood leaks) and that events which occurred during these episodes caused the spread of infection.

A proportion of the plasma for the triply inactivated, plasma-derived hepatitis B vaccine produced in the United States is obtained from homosexual men. Because homosexual men are a high-risk group for the acquired immunodeficiency syndrome (AIDS), concern has emerged that the vaccine could harbor the AIDS agent. To evaluate this risk, we tested 15-month postvaccination serum samples for antibodies to human T-cell lymphotropic virus type III in 100 health care workers who had received inactivated hepatitis B vaccine lots made from plasma collected between 1977 and 1979 and 100 who had received placebo injections. None of the 200 health workers had serological evidence of human T-cell lymphotropic virus type III infection. These serological findings lend additional support to earlier epidemiologic and immunologic observations suggesting that hepatitis B vaccine does not transmit infection with an AIDS virus. ( JAMA 1985;254:1064-1066)