PEDIATRICS Vol. 104 No. 3 September 1999, pp. 561-563

EXPERIENCE AND REASON:
Varicella Outbreaks After Vaccine Licensure: Should They Make You Chicken?

	ABSTRACT

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In 1998, 3 years after vaccine licensure, child care centers (CCC) in Los Angeles County continued to report varicella outbreaks. We investigated outbreaks at 2 CCCs to determine the cause for them, such as low vaccination coverage levels or unexpected low vaccine effectiveness. We collected information on past history of varicella, illness during the outbreak, and prior varicella vaccination among CCC attendees. We found that CCC "H" had a vaccination coverage of 87% (34/39) compared with 30% (6/20) in CCC "L." The overall attack rate was lower in CCC "H" (31%) than in "L" (61%; P value = .03). Vaccine effectiveness for any varicella was 71% in "H" and 100% in "L." Vaccinated children with varicella had milder disease than unvaccinated. In conclusion, we found varicella outbreaks in CCCs with both high and low vaccination coverage. Vaccine effectiveness was within the range predicted by the literature. Vaccination led to a lower attack rate in the highly vaccinated CCC and appeared to protect from severe disease.

More than 3 years ago, the varicella vaccine (Varivax; Merck and Company, Westpoint, PA) was licensed. It was anticipated that increasing vaccination coverage would reduce the number of varicella cases and outbreaks, particularly in child care centers (CCC). In March 1998, the Los Angeles County Health Department, Acute Communicable Disease Control Unit, received repeated telephone calls from distressed parents and CCC directors expressing doubts about the effectiveness of the vaccine because of the continued occurrence of varicella outbreaks. We investigated outbreaks of varicella at 2 CCCs to determine if low vaccination coverage levels or unexpectedly low vaccine effectiveness explained the outbreaks.

	METHODS

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For purposes here, the 2 CCCs are designated "H" and "L." Information on history of varicella, illness during the outbreak, and previous varicella vaccination were collected either from parents or health care providers. "Mild" disease was defined as illness with <50 lesions, "moderate" with 50-500 lesions, and "severe" with >500 lesions (normal skin not visible between areas with lesions). A "breakthrough" case of varicella was defined as varicella disease in a child despite previous varicella vaccination >42 days preceding rash onset. A child with a history of varicella was excluded from the calculations of coverage rate, attack rate (AR), and vaccine effectiveness. Vaccine effectiveness is the "efficacy" of a vaccine determined under real life conditions, as opposed to under the conditions of a trial. We calculated the varicella AR in each institution as well as the ARs for vaccinated and unvaccinated children. We determined the vaccine effectiveness using the formula:

	RESULTS

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Forty-one children attended CCC H, and 30 attended CCC L. The mean age of the children in CCC H was 50 months, and ranged from 31-66 months. The mean age of the children in CCC L was 53 months with a range from 41-64 months. Each CCC had 12 cases of varicella. Two children (5%) in CCC H and 10 children (33%) in CCC L had a history of varicella and were excluded from further calculations, leaving 39 children in CCC H and 20 children in CCC L for the denominator. Before the outbreak, 34 of the remaining 39 children (87%) attending CCC H had been vaccinated, but only 6 of 20 children (30%) in CCC L (P < .001; [Table 1]). The overall AR was significantly lower in CCC H (31%) than in CCC L (60%; P = .03). The AR among the unvaccinated children was 80% in CCC H versus 86% in CCC L and among the vaccinated children 24% in H versus 0% in L. The 8 breakthrough cases in CCC H were vaccinated by 6 different health care providers. We contacted 5 of the 6 providers; 1 provider was retired. All providers stored and handled the vaccine correctly. The vaccine effectiveness in CCC H was 71% (95% confidence interval [CI] = 38%-86%) whereas in CCC L it was 100% (95% CI = 67%-100%) preventive for any case of varicella. For moderate-to-severe disease, vaccine effectiveness was 93% in CCC H (95% CI = 33%-99%) and 100% in CCC L (95% CI = 0%-100%). In CCC H, 2 (40%) of 5 unvaccinated children had moderate-to-severe disease, compared with only 1 (3%) of 34 vaccinated children. This was similar in CCC L, where 6 of 14 (43%) unvaccinated children had moderate-to-severe disease, but none (0%) of the 6 vaccinated children. In the combined CCCs, the proportion of children with moderate-to-severe disease among the vaccinated case children was 13%, compared with 50% of case children who were unvaccinated.

Assuming the same ARs for any disease and moderate-to-severe disease that was observed among the unvaccinated children in CCC H (L), had no vaccination been given in either CCC, 31 cases would have been expected in CCC H and 17 would have been expected in L; 16 moderate-to-severe cases would have been expected in CCC H and 9 moderate-to-severe cases would have been expected in CCC L. Therefore, the observed 24 (12+12) cases would have doubled to 48 (31 + 17), and the 9 (3 + 6) moderate-to-severe cases almost tripled to 25 (16 + 9).

	DISCUSSION

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Although the outbreak in CCC L may be easily explainable because of low vaccination coverage, our data confirm that an outbreak occurred in CCC H despite high vaccination coverage. Although vaccine effectiveness in CCC H (71%) was lower than in CCC L, it still was within the predicted range for the varicella vaccine of 70%-90%.² To our knowledge, only one study has been published where postlicensure effectiveness has been assessed. In a CCC outbreak in Atlanta, Georgia, vaccine effectiveness was reported as 86% (95% CI = 73%-92%;).³ Therefore, we do not believe that either unusually low vaccine effectiveness or low vaccination coverage explain the outbreak in CCC H. Because the immunization rate in the population is well below 100%, a child with varicella can still introduce the disease to a CCC despite a high vaccination coverage and cause an outbreak. And because the vaccine is not 100% effective, a proportion of cases will occur among vaccinated children (ie, breakthrough cases). This proportion can be estimated given the proportion of vaccinated children in the CCC (Fig 1). The nomogram can help public health workers to assess with minimal data requirements (percentage of children vaccinated, percentage of cases vaccinated) if the observed picture fits the expectations given the efficacy of the vaccine, and if they should investigate an outbreak because of possible problems with refrigeration or administration.

View larger version (33K): [in this window] [in a new window]   Fig. 1.   Percentage of cases vaccinated (PCV) per percentage of population vaccinated (PPV), displayed for the varicella vaccine with an expected range of vaccine efficacy between 70% (upper line) and 90% (lower line; adapted after Kobayashi [personal communication, February 1999]). For example, if the PPV (vaccination coverage) is 87% (as was the case in CCC H), one would expect that approximately 40%-67% of the varicella cases would have been vaccinated.

In our setting, the value of varicella vaccination was demonstrated in three ways. First, the overall AR in CCC H was significantly lower than in CCC L. Second, the estimated number of cases in both CCCs would have doubled without vaccination and the number of moderate-to-severe cases would have almost tripled. Third, the incidence of moderate-to-severe cases (1 of whom had serious complications requiring hospitalization) was decreased also. Along with a decrease in total cases and in the severity of cases, vaccination may have decreased the number of complications and secondary spread outside the day care centers as well. A previous study among 9 Los Angeles County hospitals demonstrated the high burden of varicella complications requiring hospitalizations, including a rising proportion of group A -hemolytic streptococcal infections among hospitalized varicella cases over the years 1990-1994, during the prevaccine era.⁴ Increasing vaccination coverage is expected to decrease the number of those complications as a consequence of the decreased number of varicella cases and outbreaks. Although information on the total number of varicella cases in Los Angeles County are unavailable, data acquired passively show that the number of varicella outbreaks have already decreased significantly since the introduction of the vaccine in 1995 (1987-1994: mean of 72 outbreaks/year; 1995-1997: mean of 35 outbreaks/year; P = .001 [Los Angeles County, unpublished data]).

	CONCLUSION

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In summary, neither low vaccination coverage nor unexpectedly low vaccine effectiveness was responsible for the outbreak. We found that vaccine effectiveness data from our investigations do agree with efficacy data from the literature, and no evidence of unexpectedly low vaccine effectiveness exists. As Chen and Orenstein⁵ have documented, even with increasing vaccination coverage, varicella outbreaks will still occur, even in CCCs with high vaccination coverage. With a disease as highly contagious as varicella, only very high coverage in the community will prevent them completely. Outbreaks will become smaller in size, however, and the proportion of cases with a history of vaccination will increase (Fig 1). Even when breakthrough cases occur, their severity will more likely be mild whereas varicella in unvaccinated children may cause severe morbidity. The protection of the varicella vaccine against severe disease is excellent and reaches 95%.² This message should be clearly communicated to parents and managers of CCCs until vaccination coverage approaches optimal levels.

Udo Buchholz, MD, MPH
Epidemic Intelligence Service
Epidemiology Program Office
Centers for Disease Control and Prevention
Atlanta, GA 30333

Ron Moolenaar, MD
State Branch
Epidemiology Program Office
Centers for Disease Control and Prevention
Atlanta, GA 30333

Carol Peterson, MD, MPH, and Laurene Mascola, MD, MPH
Acute Communicable Disease Control
Department of Health Services
Los Angeles County
Los Angeles, CA 90012

	FOOTNOTES

Received for publication Dec 8, 1998; accepted Mar 23, 1999.

Address correspondence and reprint requests to Udo Buchholz, MD, MPH, Los Angeles County Department of Health Services, Acute Communicable Disease Control Unit, 313 N Figueroa St, Rm 212, Los Angeles, CA 90012. E-mail: ubuchholz{at}dhs.co.la.ca.us

	ABBREVIATIONS

CCC, child care center; AR, attack rate; CI, 95% confidence interval.

	REFERENCES

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1. Orenstein WA, Bernier RH, Hinman AR Assessing vaccine effectiveness in the field. Epidemiol Rev. 1988; 10:212-241 [Free Full Text]
2. Centers for Disease Control and Prevention Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1996; 45:1-37 [Medline]
3. Izurieta HS, Strebel PM, Blake PA Postlicensure effectiveness of varicella vaccine during an outbreak in a child care center. JAMA. 1997; 278:1495-1499 [Abstract]
4. Peterson CL, Mascola L, Chao SM, Children hospitalized for varicella: a prevaccine review. J Pediatr. 1996; 129:529-536 [CrossRef][Medline]
5. Chen RT, Orenstein WA Epidemiologic methods in immunization programs. Epidemiol Rev. 1996; 18:99-117 [Free Full Text]