Most ten-year-old children with negative or unknown histories of chickenpox are immune

To evaluate the proportion of children to vaccinate against varicella in a catch-up program targeting 9- to 10-year-old children, a study was conducted among children age 10 years to assess the age-specific incidence of varicella and document the immunity against varicella in those with negative or unknown chickenpox history. Of the latter 62% were seropositive for varicella.

Although chickenpox is usually benign, it has been estimated that ∼1 of 70 to 500 patients with chickenpox is hospitalized for complications. ¹ A universal immunization program against varicella should include vaccination of young children and catch-up immunization of older ones to prevent accumulation of susceptible adults. To estimate the cost of these catch-up programs, it is important to know the proportion of children to be vaccinated and to document the validity of the clinical history as reported by individuals or parents so that immunization would be offered only to the vulnerable children. We estimated the age-specific incidence rates of chickenpox in 10-year-olds and tested for antibodies against varicella those with negative or unknown histories of the disease to determine the negative predictive value of a self-reported clinical history of varicella.

Subjects and methods.

Subjects were participants of a cohort of 2255 fourth grade elementary school children who were enrolled in a long term immunogenicity study of hepatitis B vaccines in the Quebec City region. ² The cohort was composed of 2 groups: 1129 were recruited in the fall of 1995; and 1126 were recruited in the spring of 1997. Children were 8 to 10 years at the time of recruitment. In May, 1997, a questionnaire assessing the child’s clinical history of chickenpox was mailed to the parents of the first group, whereas the parents of the second group were interviewed directly by nurses during home visits. The information obtained from the questionnaire included gender, birth date, the past clinical history of chickenpox and whether or not a physician was consulted during the episode. Parents who stated either that they were certain their child had not had chickenpox or that they did not know if he or she had were invited to participate in a serologic survey for varicella antibodies. Those who agreed signed an informed consent form. The sera already collected in May, 1996, or May, 1997, for the immunogenicity study were used for this analysis.

Varicella IgG was assessed by VIDAS Varicella-Zoster IgG assay (BioMérieux Canada, Inc., St.-Laurent, Quebec, Canada). A test value threshold of ≥0.9 was considered positive. The age-specific rates of chickenpox (incidence among all children), the incidence density (incidence among the susceptible) and the cumulative incidence per 1000 children were calculated up to age 10 years. Those rates were calculated after distributing the 118 children whose parents were unable to provide an accurate date of illness with the same disease-acquiring age distribution as observed in the rest of the children.

Results.

Among the initial cohort 2227 agreed to participate in the varicella study. The average age of the children in May, 1997, was 10.6 ± 0.5 years in the first group of children and 9.7 ± 0.5 years in the second group of children. At that time 2023 (90.8%) parents reported that their children had had chickenpox, 151 reported a clear negative history and 53 did not know whether their child had sustained the disease.

Among the whole cohort 51% (1146 of 2227) of children developed the disease before entering kindergarten. The age-specific rate was highest at 4 to 5 years old and decreased afterward, but the incidence density remained high up to age 9 years (Fig. 1). The reported cumulative incidence of chickenpox was 92% at 10 years old.

Fig. 1: Age-specific incidence, incidence density and cumulative incidence of chickenpox in children of the Quebec area.

Forty-seven percent of the children who had chickenpox consulted a physician during their illness. This proportion was not significantly different with the age at the time of disease.

Of 204 parents who reported negative or unknown chickenpox histories in their children, 181 agreed to enroll their children for serologic testing. Among these 63% had IgG antibodies against varicella. This proportion was higher among those who reported an unknown history of varicella than among those with negative history (82%vs. 56%;P = 0.002). It was also higher among those who filled a self-administered questionnaire than among those questioned directly by the study nurse (70%vs. 53%P = 0.023).

Discussion.

In this study 92% of children acquired varicella before 11 years of age, and about one-half (51%) developed the disease before entering kindergarten. The incidence density of the illness was very high until age 9 years but decreased rapidly afterward. Because chickenpox evolves in epidemic cycles every 2 to 3 years ³ the age-specific incidence and incidence density could vary according to year of birth. This cohort effect could explain variations among studies in age of peak incidence but is not likely to have a large impact on the cumulative incidence rate at 10 years old. The incidence rates are based on parental recall. Because information was collected at age 10 years and many cases occurred before 5 years of age, there could be imprecision on the age at disease. Our 50% cumulative incidence at the fifth birthday is quite similar to results from other authors, ^{4, 5} but our cumulative incidence at age 10 year was slightly higher (92%vs. 80%). ⁵

In young adults the positive predictive value of a clinical history of varicella is high ranging from 96 to 99%, leaving only 1 to 4% of false positives. ^6–8 In our study we did not test children with a history of varicella, assuming that the positive predictive value would be as high as or even higher than in adults. In contrast the negative predictive value in adults is poor, ranging from 23 to 36%. In our study 63% of the 10-year-old children without positive history had antibodies against varicella. This is higher than the estimates from Lieu et al. ⁹ in the United States who observed 28 to 50% of seropositivity in children without a positive history of chickenpox. The difference between these findings could be partly explained by the difference in setting. In Lieu’s study, parents were interviewed by a professional in the context of deciding about immunization of their children, with a second interview by telephone. We also observed a higher negative predictive value of the history of chickenpox in the group interviewed by a nurse than in the group with self-administered questionnaires in particular for those with unknown history.

Catch-up programs are important with the introduction of universal varicella vaccination to avoid the risk of creating a pool of susceptible adolescents and adults who are at greater risk of severe and complicated chickenpox. Mathematical modeling has demonstrated that this phenomenon can be minimized by implementing catch-up immunization programs targeting adolescents and children entering school. ¹⁰ Given our data a catch-up targeting preschool children would involve the vaccination of ∼50% of them, whereas catch-up for preadolescents age 10 years would vaccinate 8.4% of them if only those without a positive history are vaccinated. On the basis of the serologic data at that age, two of three children with negative or unknown history of chickenpox would be vaccinated needlessly. This low negative predictive value suggests that testing before vaccination can be attractive. However, prevaccination testing could be difficult to implement and could reduce vaccine coverage. ⁹ Considering the better negative predictive value of the face-to-face interview, an alternative to improve the validity of chickenpox history would be to call parents who report negative or unknown history of varicella in their children in a self-administered questionnaire.

In conclusion our data do not support the perception that a negative/unknown history of varicella in 10-year-old children is well-correlated with an absence of immunity.

Acknowledgments.

We thank Colette Couture, Louis Rochette, Martyne Nadeau, Sophie Auger, France Lavoie, Claude Boulianne and Ramak Shadmani for their valuable contribution to this study. This study was supported by Laboratory Centre for Disease Control of Health Canada, Merck Frost and SmithKline Beecham.

Nicole Boulianne, M.Sc.

Bernard Duval, M.D.

Gaston De Serres, M.D.

Michel Couillard, Ph.D.

Institut National de Santé Publique du Québec

Nicole Boulianne, M.Sc.

Bernard Duval, M.D.

Gaston De Serres, M.D.

Genevieve Deceuninck, M.D.

Public Health Research Unit; CHUL Research Center; Laval University

Richard Massé, M.D.

Ministère de la Santé et des Services Sociaux du Québec; Quebec, Canada