Varicella-Related Deaths Among Adults -- United States, 1997

During January-April 1997, state health departments reported three fatal cases of varicella (chickenpox) to CDC. All three cases occurred in young adult women who were unvaccinated and susceptible to varicella and who were infected by exposure to unvaccinated preschool-aged children with typical cases of varicella. This report summarizes these three cases, which indicate that preventable varicella-related deaths continue to occur in the United States. In addition, the report re-emphasizes the recommended strategies for preventing varicella. Case 1

On January 19, 1997, a 23-year-old woman in good health had onset of a classic varicella rash. In early January, her 2- and 5-year-old unvaccinated children had had varicella. On January 22, she had onset of shortness of breath and hemoptysis. When she was admitted to a local hospital on January 23, a chest radiograph indicated diffuse alveolar density consistent with varicella pneumonia, and treatment was initiated with oxygen and intravenous acyclovir. Her condition worsened, and she required intubation several hours after admission. Because of increasing respiratory distress, she was transferred to a referral hospital where treatment continued with oxygen, antibiotics, and intravenous acyclovir. On January 31, her rash became hemorrhagic, and she developed disseminated intravascular coagulation (DIC) and renal failure, followed by progression to multiple system failure; she died on February 2. Varicella zoster virus was cultured from skin lesions and from a tracheal aspirate. Case 2

On March 11, 1997, a 25-year-old woman in good health had onset of a classic varicella rash, fever, and headache. Her 4-year-old unvaccinated child had had onset of a varicella rash on February 23. On March 12, the woman had onset of cough, and on March 13, shortness of breath. On March 14, she sought care at a local emergency department (ED) because of increasing respiratory difficulty and confusion. Chest radiograph indicated bilateral infiltrates consistent with varicella pneumonia, and arterial blood gases indicated hypoxemia. Varicella encephalitis and pneumonia were diagnosed; she was admitted to the hospital, and treatment was initiated with oxygen and intravenous acyclovir. Four hours after admission, her respiratory difficulty increased, and she required intubation. On March 15, a computerized tomography of the brain revealed severe, diffuse cerebral edema, and she developed renal failure and coma. On March 16, she was transferred to a referral hospital for renal dialysis; an electroencephalogram indicated absence of electrical brain activity, and repeat chest radiographs indicated diffuse infiltrates. She died on March 17. Case 3

On April 3, 1997, a 32-year-old woman with Crohn's disease sought medical evaluation at a local ED because of onset of abdominal and back pain. On March 7, therapy was initiated with 40 mg prednisone daily for an exacerbation of her Crohn's disease. By April 3, her steroid therapy had been tapered to 20 mg prednisone daily. On physical examination, she had mild, generalized abdominal tenderness with no specific signs or abdominal guarding. She was afebrile, and a white blood cell (WBC) count was normal. A benign abdominal syndrome was presumptively diagnosed, and she was discharged.

Her symptoms persisted, and on April 4, she sought medical evaluation at the office of her health-care provider. Findings on physical examination were unchanged. Although an abdominal radiograph, abdominal and pelvic ultrasounds, and a WBC count were normal, because of her underlying medical condition, she was referred for surgical consultation. On April 5, the abdominal pain persisted, and she returned to the ED for evaluation. A WBC count was 15,000/mm3 (normal: 3200-9800/mm3), and she was admitted to the hospital. Diagnoses of colitis and ileitis with possible perforation and intraabdominal abscess were considered, and treatment was initiated with broad-spectrum antibiotics. On physical examination, a maculopapular, vesicular rash with crusted lesions was observed on her trunk, head, and neck. Varicella was presumptively diagnosed, and she was placed in isolation. The patient reported that she had had onset of a mild macular, nonpruritic rash on her back on April 3 and that she had been exposed on March 12 and 13 to her 4-year-old unvaccinated niece with varicella. On April 6, the vesicles became hemorrhagic, and she began bleeding from intravenous sites. She rapidly developed hypotension and DIC, and died from shock the same day. On autopsy, evidence of viral inclusion bodies in multiple organs was consistent with varicella, and varicella was determined to be the cause of death.

Reported by: B Watson, MBChB, K Goodnow, MPH, R Levenson, MBA, City of Philadelphia Dept of Public Health, Pennsylvania. R Todd, DrPH, D Nelson, D Banghart, MSPH, State Health Div, Nevada Dept of Human Resources. Child Vaccine Preventable Disease Br, Epidemiology and Surveillance Div, National Immunization Program, CDC.

Editorial Note

Editorial Note: The three cases described in this report indicate that, despite the licensure of varicella vaccine in 1995 (1) and availability of antiviral therapies since the early 1980s, varicella-related deaths continue to occur in the United States. Varicella national mortality data for 1990-1994 indicate that, although less than 5% of varicella cases occur among adults aged greater than 20 years, 55% of varicella-related deaths occur among persons in this age group (CDC, unpublished data, 1997). During the prevaccine era in the United States, approximately 4 million varicella cases were reported annually, including 4000-9000 hospitalizations and 100 deaths.

Varicella vaccine has been available since March 1995 and is approved for use in healthy susceptible persons aged greater than or equal to 12 months (1). All children should be routinely vaccinated at age 12-18 months, and all susceptible children aged 19 months-13 years should be vaccinated by their 13th birthday (1-3). For persons aged greater than or equal to 13 years, the priority group for vaccination includes those who are susceptible and who are close contacts of persons at high risk for serious complications (e.g., health-care workers and family contacts of immunocompromised persons); however, all susceptible adults may be vaccinated (1,3,4). Because varicella vaccine is an attenuated live virus preparation, it is contraindicated for immunocompromised persons, including those receiving immunosuppressive medications (e.g., systemic steroids greater than 2 mg/kg bodyweight per day or a total of 20 mg prednisone per day). * Therefore, the most effective method to protect immunocompromised persons is to ensure that their potential susceptible contacts have been vaccinated (1).

Based on data obtained from three U.S. sites participating in active surveillance for varicella (West Philadelphia, Pennsylvania; Travis County, Texas; and Antelope Valley, Los Angeles County, California), 0-20% of 2-year-olds received varicella vaccine during 1995-1996 (CDC, unpublished data). Potential barriers to achieving high coverage levels with this vaccine include the perception that varicella is mild and vaccination is not warranted, concerns about long-lasting immunity and effectiveness of the vaccine, stringent vaccine storage and handling requirements, vaccine availability and cost, inadequate insurance coverage (5), and the inherent lag-time in fully incorporating a new vaccine into existing vaccination programs. A recent survey of Connecticut physicians' knowledge, attitudes, and practices regarding recommendations from the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) for universal varicella vaccination of infants suggested similar barriers to vaccine use; in addition, physicians who disagreed with the ACIP and AAP recommendations were less likely to use the vaccine than those who agreed with the recommendations (Connecticut Department of Public Health, unpublished data, 1996). Public health agencies can address perceived barriers by educating health-care providers and the general public about the following: complications associated with varicella, especially in adults; the availability of a vaccine highly effective against severe disease (1); evidence indicating long-lasting vaccine-induced immunity (6,7); and the importance of early antiviral treatment for adults and others with cases of varicella who are at high risk for complications of disease. Beginning in 1997, inclusion of reporting of varicella vaccine coverage in version 3.0 of the Health Plan Employer Data and Information Set (HEDIS) also should assist in accelerating implementation of varicella vaccination in managed-care organizations.

At least three recommended strategies can assist in preventing varicella-related deaths among adults. First, antiviral therapies should be used more optimally. Varicella zoster immune globulin (VZIG) is recommended for postexposure prophylaxis in susceptible persons at greater risk for serious complications from varicella, such as immunocompromised persons (e.g., persons with human immunodeficiency virus infection/acquired immunodeficiency syndrome, malignancies, or receiving steroid therapy). Although VZIG is effective in reducing the severity of varicella when administered up to 96 hours after exposure, the agent should be administered as soon as possible after exposure (1). If varicella develops, infected persons may benefit from effective therapies that reduce disease severity and complications (e.g., acyclovir {8 }). For maximum benefit, such therapy should be initiated within 24 hours of rash onset or as soon thereafter as possible. Second, susceptible adults should be vaccinated with varicella vaccine. Approximately 95% of U.S. adults have acquired natural immunity to varicella (9); therefore, only a small proportion of adults need to be vaccinated. Because only approximately 10%-30% of adults with negative or uncertain histories for varicella are actually susceptible (1), serologic testing followed by vaccination of identified susceptible persons may be more cost effective for adults than administration of two doses of vaccine to adults with negative or uncertain histories for varicella. Two of the decedents in this report were eligible for varicella vaccination. Third, susceptible children should receive routine vaccination for varicella. Although both ACIP and AAP recommend routine or universal varicella vaccination by age 12-18 months, both permit vaccination of susceptible children at any age (1-2). All three deaths in this report may have been prevented by vaccinating the preschool-aged family members to whom the decedents had been exposed.

A comprehensive assessment of the impact of varicella vaccination on varicella-related morbidity and mortality will require establishing surveillance systems to monitor incidence, hospitalizations, and deaths from varicella. Consequently, state public health agencies are encouraged to initiate ongoing surveillance; investigate all varicella-related deaths; and consider establishing reporting systems for varicella cases in schools, day care centers, health-care provider offices, or hospitals.

References

1. CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1996;45(no. RR-11).

2. Committee on Infectious Diseases, American Academy of Pediatrics. Recommendations for the use of live attenuated varicella vaccine. Pediatrics 1995;95:791-6.

3. American Academy of Family Physicians. Summary of policy recommendations for periodic health examination. Kansas City, Missouri: American Academy of Family Physicians, November 1996.

4. Gardner P, Eickhoff T, Poland GA, et al. Adult immunizations. Ann Intern Med 1996;124:35-40.

5. Chew D, Hofmann J, O'Donnell C, Finelli L. Physician attitudes and practices regarding varicella vaccine in New Jersey {Abstract}. In: Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1996:278.

6. Asano Y, Suga S, Yoshikawa T, et al. Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine. Pediatrics 1994;94(4 Pt 1):524-6.

7. Kuter BJ, Weibel RE, Guess HA, et al. Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies. Vaccine 1991;9:643-7.

8. Wallace MR, Bowler WA, Murray NB, Brodine SK, Oldfield EL III. Treatment of adult varicella with oral acyclovir: a randomized, placebo-controlled trial. Ann Intern Med 1992;117:358-63.

9. Van Loon F, Markowitx L, McQuillan G, et al. Varicella seroprevalence in US population {Abstract}. In: Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1993:359.

* The exception is children with leukemia in remission who may be administered the vaccine under a strict protocol. A clinical trial is under way testing the safety and efficacy of the vaccine in asymptomatic children with human immunodeficiency virus infection/acquired immunodeficiency syndrome.

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