Varicella-Zoster Immune Globulin Distribution -- United States and Other Countries, 1981-1983

Since its licensure on February 1, 1981, varicella-zoster immune globulin (VZIG) has been produced and distributed in Massachusetts by the Massachusetts Public Health Biologic Laboratories (MPHBL) and distributed elsewhere by the American Red Cross Services--Northeast Region through regional blood centers (see pages 97-99). Before licensure, VZIG was distributed as an investigational new drug (IND), first by CDC and later by CDC and the Sidney Farber Cancer Institute. Between February 1, 1981, and September 30, 1983, 27,641 vials of VZIG were distributed in the United States (24,190 vials), Canada (1,987), and 15 other countries (1,464). This represents between 9,000 and 10,000 exposures to varicella-zoster (V-Z) virus. During the IND period of January 1, 1978, to November 30, 1980, 5,735 vials (for 2,263 exposures) were distributed using strict eligibility criteria (1) (Table 1). (Data for December 1980 and January 1981 are unavailable.) Distribution increased threefold during the first year after licensure, followed by a 67% increase in 1982. Data available through September 1983 suggest that the observed rate of increase in distribution between 1980 and 1982 has diminished substantially.

Seasonal distribution patterns of VZIG distribution and reported varicella occurrence are similar, with the peak period of distribution (February-May) coinciding with the expected varicella seasonal peak incidence (2) (Figure 1). Based on annual averages, between three (January) and 11 (August and September) times as much VZIG was distributed as a licensed product than as an IND.

Since there was little basis for projecting the potential demand for VZIG as a licensed product, VZIG initially was released on a case-by-case basis to ensure that the available supply was adequate to meet the most critical exposure situations (i.e., exposure involving susceptible, immunocompromised children). When it became evident that supplies were sufficient for all indicated applications, VZIG was distributed for use as physicians deemed appropriate. Although VZIG was intended primarily for use in high-risk neonates and susceptible immunocompromised children 15 years of age or younger (1), some physicians considered certain older individuals at increased risk of serious complications if infection occurred.

Although nationwide data on VZIG use in adults are not available, distribution of VZIG to adults in Massachusetts was evaluated by the MPHBL using information on the patients' underlying conditions, types of exposure, intervals between exposure and the VZIG request, and likelihood of previous infection. Between February 1, 1981, and September 30, 1983, 40 exposures were recorded among adults. These accounted for 12% of the 321 Massachusetts VZIG requests and 19% of the 1,028 vials distributed (five vials per adult exposure). Overall adult usage did not vary over this 3-year period. Age, which was known for 29 individuals, ranged from 16 to 73 years, with a mean and median of 37.4 years and 32.0 years, respectively.

The most frequently recorded indications judged appropriate by the requesting physicians for VZIG use were immunosuppression (secondary to radiation or chemotherapy) and pregnancy (12 patients each) (Table 2). Three of six pregnant women with known gestation were given VZIG in the first trimester. Twenty of the 32 known exposures occurred in households; two involved exposures of hospital personnel. The interval between exposure and VZIG request was known for 23 requests; three were beyond 96 hours (the recommended maximum interval between exposure and prophylaxis). One patient with Hodgkin's disease was given VZIG 8 days after onset of zoster, which is not an indication for VZIG use. Two additional requests were made within 1 week of exposure. All patients had either negative or uncertain histories of previous varicella infection. Serologic testing was performed too infrequently to provide meaningful results.

Varicella developed in two of 29 adults (20 exposed in households) with known outcomes. Both involved household exposures--one in a parent of a child with varicella and one in a pregnant woman (VZIG had been administered 5 days and 2 days, respectively, after exposure). Both infections were mild. The outcome of the pregnancy is unknown. The observed clinical attack rate following household exposure of 10% (2/20) is lower than the expected 30%-50% rate in immunocompromised children with a negative or uncertain history of previous varicella (3,4), implying that many of these VZIG recipients were actually immune. Reported by J Leszczynski, DrPH, M McCabe, MPH, Massachusetts Public Health Biologic Laboratories, Jamaica Plain, PL Page, MD, American Red Cross Blood Services--Northeast Region, Needham, Massachusetts; Div of Immunization, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: As expected, VZIG licensure has led to a substantial increase in VZIG use. Although supplies seem adequate, use should be restricted to high-risk individuals who are likely to be susceptible and who have experienced significant exposures. VZIG is not beneficial in cases of herpes zoster (5,6). Passive immunization also is not indicated for treating varicella (see page 96). It is not known whether the adult VZIG requests for pregnant women in Massachusetts were aimed at preventing maternal or fetal infection. VZIG use has not been shown to protect the fetus from infection and may provide a false sense of security. Decisions regarding VZIG use in pregnant women should be based on preventing serious illness in the mother, not on preventing infection in the fetus (1) (see page 95). Finally, excessive use of VZIG can be minimized by realizing that most adults with negative histories of previous varicella are immune (7-9).

Detailed recommendations for VZIG administration have recently been published by the American Academy of Pediatrics (AAP) (10). The Immunization Practices Advisory Committee (ACIP) recommendations are published in this issue of the MMWR.

References

1. CDC. Varicella-zoster immune globulin--United States. MMWR 1981;30:15-6, 21-3.

2. Preblud SR, D'Angelo LJ. Chickenpox in the United States, 1972-1977. J Inf Dis 1979;140:257-60.

3. Orenstein WA, Heymann DL, Ellis RJ, et al. Prophylaxis of varicella in high-risk children: dose-response effect of zoster immune globulin. J Pediatr 1981;98:368-73.

4. Zaia JA, Levin MJ, Preblud SR, et al. Evaluation of varicella-zoster immune globulin: protection of immunosuppressed children after household exposure to varicella. J Infect Dis 1983;147:737-43.

5. Groth KE, McCullough J, Marker SC, et al. Evaluation of zoster immune plasma. Treatment of cutaneous disseminated zoster in immunocompromised patients. JAMA 1978;239:1877-9.

6. Stevens DA, Merigan TC. Zoster immune globulin prophylaxis of disseminated zoster in compromised hosts. A randomized trial. Arch Intern Med 1980;140:52-4.

7. Ross AH. Modification of chicken pox in family contacts by administration of gamma globulin. N Engl J Med 1962;267:369-76.

8. Myers MG, Rasley DA, Hierholzer WJ. Hospital infection control for varicella zoster virus infection. Pediatrics 1982;70:199-202.

9. Steele RW, Coleman MA, Fiser M, Bradsher RW. Varicella zoster in hospital personnel: skin test reactivity to monitor susceptibility. Pediatrics 1982;70:604-8.

10. Committee on Infectious Diseases. Expanded guidelines for use of varicella-zoster immune globulin. Pediatrics 1983;72:886-9.

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