Validity of medical record documented varicella-zoster virus among unvaccinated cohorts

Abstract

Background: A varicella diagnosis or verification of disease history by any healthcare provider is currently accepted for determining evidence of immunity by the Advisory Committee on Immunization Practices (ACIP).

Objective: To examine the accuracy of medical record (MR) documented varicella history as a measure of varicella-zoster virus (VZV) immunity among unvaccinated individuals born after 1980. We also assessed methods to practically implement ACIP guidelines to verify varicella history using medical records.

Study Design: As part of a larger cross-sectional study conducted at three Philadelphia clinics from 2004–2006, we recruited 536 unvaccinated patients aged 5–19 y (birth years: 1985–2001). Varicella history was obtained from three sources: parent/patient interview, any MR documentation (sick and well visits) and MR documentation of a sick visit for varicella. All participants were tested for VZV IgG. For each source and three age groups (5–9, 10–14, 15–19 y old), positive predictive value (PPV) was calculated. Specificity of varicella history was compared between different sources using McNemar’s Chi-square.

Results: Among participants aged 5–9, 10–14 and 15–19 y the PPV for any MR documentation and sick visit diagnosis were 96% and 100%, 92% and 97%, and 99% and 100%, respectively. The specificity for sick visit documentation was higher than any MR documentation and patient/parent recall among all age groups; however, these differences were only statistically significant when comparing sick visit documentation to parent/patient recall for 10-14 y olds.

Conclusion: Sick visit documentation of varicella in the MR is an accurate predictor of varicella seropositivity and useful for confirming disease history among unvaccinated persons (birth years: 1985–2001). This method is a practical way to verify varicella history using the ACIP guidelines.

Keywords: :

• varicella
• chickenpox
• unvaccinated
• medical record documentation
• immunity

Introduction

A diagnosis or verification of typical varicella disease history by any healthcare provider (HCP) (e.g., physician, physician assistant, nurse practitioner, school or occupational clinic nurse) is currently accepted for determining evidence of immunity according to the Advisory Committee on Immunization Practices (ACIP).¹ For persons reporting with an atypical varicella disease history or an atypically mild case of varicella, one of the following should be sought by a physician when verifying disease history: (1) an epidemiologic link to a typical varicella case or to a laboratory confirmed case or (2) evidence of laboratory confirmation if performed at the time of acute disease. When this documentation is missing, persons are not considered immune.¹

Due to a lack of prior studies, it is uncertain if documentation of a history of varicella in a patient’s medical record (MR) should be used to verify a reported disease history among unvaccinated cohorts who grew up in a time when outbreaks of varicella disease were more common. To address this knowledge gap, this study was designed to help HCPs determine the extent to which they can rely on MR documentation to verify a history of varicella disease among unvaccinated cohorts during 1985–2001.

Specifically, the purpose of this study was to examine the accuracy of MR documented varicella history during well and sick visits as a measure of varicella-zoster virus (VZV) immunity among unvaccinated individuals born after 1980. The accuracy of parent/guardian or adolescent reported varicella was compared with MR documentation as a predictor of VZV immunity. We also examined whether using MR documentation of varicella history was a practical method to implement ACIP guidelines for verifying varicella disease history.

Materials and Methods

Data from a prospective, cross-sectional study conducted from June 2004 to May 2006 were collected by the Philadelphia Department of Public Health Varicella Active Surveillance Project in collaboration with the Centers for Disease Control and Prevention (CDC) and The Children’s Hospital of Philadelphia (CHOP).² Participants included unvaccinated 5–19 y olds recruited from three CHOP pediatric primary care clinics. Recruitment and analyses were stratified by age: 5–9 y (birth years: 1994–2001), 10–14 y (birth years: 1989–1996) and 15–19 y (birth years: 1985–1990).

The CDC National VZV Laboratory measured varicella immunity. Serologic specimens were tested for VZV immunoglobulin G (IgG) antibodies using whole-cell enzyme-linked immunosorbent assay (ELISA) methods as previously described.² Participants with negative or equivocal VZV-specific IgG antibody titer levels were considered seronegative and lacking immunity.

Varicella history was obtained from three sources: (1) MR documentation of a sick visit for varicella, (2) any MR documentation of varicella history (sick or well visit) and (3) a reported history of varicella disease. Reported history of varicella disease came from two different sources: parent/guardian reported disease history for participants aged 5–14 y and participants aged 15–19 y self-reported disease history. A sick visit was defined as a reported skin abnormality and a final diagnosis of varicella. While we did examine the MR for rash description, the medical record did not have sufficient detail to distinguish between atypical varicella cases and typical varicella cases; therefore, we could not classify cases by rash presentation based on documentation at sick visits.

Study staff administered standardized questionnaires to obtain information regarding reported varicella history. Staff reviewed electronic and hardcopy MR for all visits (sick and well) starting from the first visit at CHOP for visit complaint, skin description, rash onset, final diagnosis and diagnosing physician’s affiliation.

For each age group and history source, positive predictive value (PPV), negative predictive value, sensitivity and specificity were calculated with 95% confidence intervals (CI) by comparing varicella history to serologic results. McNemar’s Chi-square tests were used to compare sensitivity and specificity of the history sources. Based on findings from pre-vaccine licensure studies, a PPV > 95% was considered highly predictive of immunity and enough to justify exemption from vaccination.^3,4 All analyses were conducted with SAS 9.1.3 (SAS Institute).

Results

Parent/patient recall of varicella history increased with participant’s age from 60% for 5–9 y olds to 91% for 15–19 y olds. MR documentation of varicella history (sick or well visit) followed a similar trend with an increase from 58% for 5–9 y olds to 85% for 15–19 y olds. Of those participants with any MR documentation of varicella history, 79% of 5–9 y olds, 88% of 10–14 y olds, and 93% of 15–19 y olds had their history recorded during a well visit. For all age groups, the proportion with a sick visit for varicella was much lower (6–13%). VZV seropositivity increased with age, from 73% among 5–9 y olds to 98% among 15–19 y olds.

As seen in Table 1, PPV for any MR documentation [96% (CI: 82–100%)] and sick visit documentation [100% (CI: 54–100%)] were highly predictive of immunity for 5–9 y olds. Among 10–14 y olds, only sick visit documentation was highly predictive of immunity [97% (CI: 82–100%)]. Seropositivity was high (98%) for 15–19 y olds and therefore, PPV estimates for each history source were highly predictive of immunity (99–100%).

Table 1. Validity of reported varicella history according to source

Age groups	5- to 9-y-olds (n = 48)			10- to 14-y-olds (n = 305)			15- to 19-y-olds (n = 183)
Source of history	Sick visit	Any MR	Patient/parent	Sick visit	Any MR	Patient/parent	Sick visit	Any MR	Patient/parent
Seropositivity, %	73	73	73	88	88	88	98	98	98
Positive history, n (%)	6 (13)	28 (58)	29 (60)	29 (10)	243 (80)	263 (86)	11 (6)	155 (85)	167 (91)
TP, n^a	6	27	26	28	224	240	11	153	165
FP, n^b	0	1	3	1	19	23	0	2	2
FN, n^c	29	8	9	239	43	27	169	27	15
TN, n^d	13	12	10	37	19	15	3	1	1
PPV (95% CI), %	100 (54–100)	96 (82–100)	90 (73–98)	97 (82–100)	92 (88–95)	91 (87–94)	100 (72–100)	99 (95–100)	99 (96–100)
NPV (95% CI), %	31 (18–47)	60 (36–81)	53 (29–76)	13 (10–18)	31(20–44)	36 (22–52)	2 (0.4–5)	4 (0.9–18)	6 (0.2–30)
Sensitivity (95% CI), %	17 (7–34)*	77 (60–90)	74 (57–88)	10 (7–15)*	84 (79–88)^†	90 (86–93)	6 (3–11)*	85 (79–90)^†	92 (87–95)
Specificity (95% CI), %	100 (75–100)	92 (64–100)	77 (46–95)	97 (86–100)*	50 (33–67)	39 (24–57)	100 (29–100)	33 (0.8–91)	33 (0.8–91)

TP, true positive; FP, false positive; FN, false negative; TN, true negative; PPV, positive predictive value; NPV, negative predictive value; MR, medical record. *p < 0.0001 when history source was compared with Patient/Parent recall. ^†p < 0.05 when history source was compared with Patient/Parent recall. ^aParticipants with positive histories who were seropositive. ^bParticipants with positive histories who were seronegative. ^cParticipants with no/uncertain histories who were seropositive. ^dParticipants with no/uncertain histories who were seronegative.

Due to the low number (≤1) of participants with false positive histories in each age group, PPV and specificity for sick visit documentation were highly accurate indicators of VZV immunity. However, these differences were only statistically significant (p < 0.0001) when comparing sick visit documentation to parent/patient recall for 10–14 y olds. For all age groups, the sensitivity of sick visit documentation was significantly lower (p < 0.0001) than parent/participant recall since many participants reported varicella history before being a patient at CHOP.

Discussion

Our findings suggest that documentation of a sick visit in the MR is highly predictive of VZV immunity and is a practical way to confirm history for unvaccinated individuals in the cohort studied. When sick visit documentation is available from the diagnosing provider our results support that it should be used to confirm disease history. This approach is a practical way to satisfy ACIP guidelines for verifying history of disease. When sick visit documentation or other criteria for verifying disease (e.g., epidemiological links to other cases) are not available, HCPs should vaccinate individuals born during 1985–2001 who report a disease history in order to ensure protection against severe varicella upon entering adulthood. Serologic testing for VZV immunity may also be incorporated into the varicella vaccination screening process; however, presumptive vaccination is preferred for populations who are less likely to return to the provider’s office for vaccination.⁵ Given the variability of PPV by age and source, any MR documentation during a well visit and patient/parent recall should not be used broadly to confirm varicella disease history.

The consequences of an unreliable history become serious as this cohort enters settings with increased exposure risk (e.g., international travel, healthcare occupations). As shown with the increased number of measles cases in the United States (US) during 2011, importations into the US from countries where a vaccine-preventable disease remains endemic can occur, and in the case of varicella, could disproportionately affect persons who remain unvaccinated and have an unreliable history.⁶ While the morbidity of varicella overall has decreased, there has been a shift in the age distribution of disease with older, unvaccinated individuals comprising an increased proportion of cases.⁷ Between 2006 and 2010, the proportion of adult (>19 y old) varicella cases from two active surveillance sites who were unvaccinated due to a reported disease history was 22%, which is of particular concern since adults are most likely to experience complications and severe disease.⁸

This study has several limitations. First, with the changing epidemiology of varicella and noticeable reductions in disease due to varicella vaccine impact, these results may not apply to individuals born after 2001. Among younger cohorts in the US, who usually present with atypical varicella due to high varicella vaccine coverage, immunity screening based on vaccination or verification of vaccination should be used instead of history verification.⁹ Second, the low number of participants aged 5–9 y and 15–19 y olds with sick visit documentation may have affected the precision of the PPV estimates in these subgroups. Also, variation in MR documentation practices among clinicians may have impacted our findings for any MR documentation.

We found that sick visit documentation of varicella in the MR is an accurate predictor of varicella seropositivity and useful for confirming disease history among unvaccinated persons born during 1985–2001. Policy makers should consider providing specific guidelines on how the verification process can be implemented using medical record documentation.

Acknowledgments

We gratefully acknowledge the following staff members from the Philadelphia Department of Public Health, the Centers for Disease Control and Prevention and the Children's Hospital of Philadelphia (CHOP) who contributed to the study: Kathleen Beyer, Denise Brown, Shelly Campbell, Teenu Cherian, Jonathan Crossette, MPH, Sharon Cyburlarz, Robert Grundmeier, MD, Caroline Hernandez, Andrea Hopkins, Ifeomah Inneh, MPH, Anuja Kulkarni, MPH, Caitlin LaRussa, Kalita Miller, Asad Moten, MPH, Rodrerica Pierre, Natalie Price, Mark Ramos, Randy Tang, Martha Thieme, LaShae Williams, and Kristina Ziolowkowski. We also acknowledge C. Victor Spain, DVM, PhD, Paul Gargiullo, PhD, and Jonathan Pletcher, MD for their participation and guidance as co-investigators for the main study objective. Lastly, we thank the network of primary care physicians, their patients and families for their contribution to clinical research through the Pediatric Research Consortium (PeRC) at CHOP.

Disclosure of Potential Conflicts of Interest

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services or the Philadelphia Department of Public Health.

In July 2003, before the start of this study, the non-profit foundation of the Philadelphia Department of Public Health, the Fund for Philadelphia, received consulting fees from Merck and Co, Inc., manufacturer of Varivax^®, a live varicella vaccine, for a summary of active varicella surveillance data Ms. Perella prepared. The Fund for Philadelphia also has received fees from Merck for Dr. Watson’s service on the company’s speaker’s bureau and varicella vaccine advisory board.

The Centers for Disease Control and Prevention funded this study through cooperative agreement 3U01IP000019 with the Philadelphia Department of Public Health for active varicella surveillance and epidemiological studies. The Craig-Dalsimer Fund and the Mary D. Ames Chair for Child Advocacy funded the salary of Ms. Forke.

Notes

† During study period this author was affiliated with the Craig-Dalsimer Division of Adolescent Medicine; Children’s Hospital of Philadelphia; Philadelphia, PA, USA.