Statistics and Surveillance:

Varicella Active Surveillance Project

Introduction to VASP

VASP is a cooperative agreement funded by the Centers for Disease Control and Prevention (CDC) and implemented by the Philadelphia Department of Public Health and the Los Angeles County Department of Health Services since 1995. The purpose of the active surveillance program is to obtain population-based incidence rates for varicella and herpes zoster diseases in a community with established high varicella vaccination coverage rates and to evaluate the impact of current and future varicella vaccination practices and policies. In addition to active surveillance, numerous epidemiological studies are ongoing throughout the year and information from the studies is presented at various conferences and publications.

General Information

History of VASP

The Varicella Active Surveillance Project (VASP) is a cooperative agreement funded by the Centers for Disease Control and Prevention (CDC) in September 1994 to

1. develop a reporting system to accurately define the baseline incidence and epidemiological profile of varicella disease prior to licensure and wide use of varicella vaccine,
2. identify changes in the epidemiology of varicella as a result of vaccine usage,
3. ascertain the immunization status of cases, and
4. evaluate the demographic and clinical profiles of vaccinated and unvaccinated cases of varicella.

There were originally 3 areas under surveillance: Travis County, TX, Antelope Valley, CA, and West Philadelphia, PA. Currently, only Antelope Valley (implemented by the Los Angeles County Health Department) and West Philadelphia (implemented by the Philadelphia Department of Public Health) project areas are under surveillance.

Purpose

• Implement, conduct, maintain, and evaluate active population-based surveillance systems with capacity to monitor varicella and herpes zoster diseases.
• Perform case investigations for varicella and herpes zoster for all ages and collect, analyze and disseminate information using these data.
• Collect and report information on vaccine doses administered by age group.
• Develop, implement and evaluate varicella prevention and control strategies including outbreak control.
• Provide laboratory specimens for laboratory evaluation needed for varicella and herpes zoster surveillance or as part of epidemiological studies, e.g., virus strain identification, confirmation of breakthrough disease, and molecular epidemiological studies.
• Conduct applied epidemiological studies for varicella and herpes zoster diseases in order to contribute to the immunization program policy and guidelines.

Methodology

Cases of varicella and herpes zoster are reported by 300 participating reporting sites in each surveillance area, including hospitals, public and private schools, primary care practitioners, public health clinics, licensed child-care facilities, prisons, homeless shelters, and universities. Case identification is facilitated through a standardized surveillance system in which each surveillance site reports twice a month to VASP the presence or absence of varicella and herpes zoster within their facility. Billing records are obtained from local healthcare systems and public health clinics to identify cases which may not have been reported during routine surveillance.

After notification, each case, or his/her parent/guardian, is interviewed via telephone or house visit to confirm diagnosis and to obtain detailed clinical and demographic information. The interviewer assesses whether there are additional cases or susceptible contacts within the household. A case investigation is completed for each newly identified case of varicella. To improve case ascertainment, all household contacts without a positive history of varicella disease are re-contacted in 3 weeks (one incubation period) after the onset of the most recent case to investigate potential household spread of varicella infection. If there is more than one susceptible contact living within a household, the contacts are followed for 6 weeks or 2 incubation periods.

Laboratory confirmation of cases has become increasingly important. The VASP offices along with CDC work with the sites to help expand specimen collection for laboratory testing. All specimens are sent to CDC's National Varicella Zoster Virus (VZV) Laboratory for testing. Common diagnostic or confirmatory tests performed include: VZV IgG gpELISA, VZV IgM ELISA, PCR, and RFLP.

Results

Decline in cases
In 1995, there were 2934 verified cases reported in Antelope Valley, CA, 3130 cases in Travis County and 1197 cases in West Philadelphia. The number of cases declined in all sites in 1996 and remained stable until 1998. In 1999, the number of cases began to dramatically decrease and in 2000, there were 837, 491, and 250 cases in Antelope Valley, Travis County, and West Philadelphia respectively. Between 1995 and 2000, the total number of cases in the three surveillance areas declined 71% to 84%, with the most considerable reduction in preschool children (1-4 year olds). By 2004, the number of cases declined by about 85% in both Antelope Valley and West Philadelphia combined.

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Decline in hospitalizations

There were 34 to 53 hospitalizations between 1995 though 1998 for all sites, which decreased to 8 hospitalizations in 1999 and 20 hospitalizations in 2000. Hospitalization rates ranged from 2.7 to 4.2 per 100,000 population from 1995 to 1998 and decreased to 0.6 per 100,000 in 1999 and 1.5 per 100,000 in 2000. From the results of the National Immunization Survey (NIS), the annual varicella-related hospitalization rates have shown to have declined to 0.13 hospitalizations per 10,000 U.S. population in 2001 compared to a rate that exceeded 0.5 hospitalizations per 10,000 U.S. population from 1993 to 1995.

Decline in deaths

From data provided by the National Center for Health Statistics (NCHS), the number of deaths with varicella listed as an underlying cause has declined 78%, decreasing from 0.41 deaths per 1,000,000 in 1990-1994 to 0.14 in 1999-2001. The greatest reduction in mortality rates occurred among children aged 1 to 4 years.

Increase in vaccination coverage

Vaccination coverage has increased for children between the ages of 19 and 35 months since 1997. In Los Angeles County, vaccination coverage increased from 40% in 1997 to 95.2% in 2003. In Philadelphia, vaccination coverage increased from 43% in 1997 to 90.0% in 2003. A similar increase in vaccination coverage seen from the VASP sites is reflected nationally: from nation-wide data, vaccination coverage in children aged 19-35 months increased from 25.8% in 1997 to 84.8% in 2003.

References:

1. Seward JF. Watson BM. Peterson CL. Mascola L. Pelosi JW. Zhang JX. Maupin TJ. Goldman GS. Tabony LJ. Brodovicz KG. Jumaan AO. Wharton M. Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002; 287(5):606-11.

2. CDC. National Immunization Survey. Available from:
   www.cdc.gov/vaccines/stats-surv/imz_coverage.htm#NIS

3. CDC. National, state, and urban area vaccination coverage levels among children aged 19-35 months –United States, 2000. MMWR Morb Mort Wkly Rep 2004; 53(29):658-661. www.cdc.gov/mmwr/preview/mmwrhtml/mm5329a3.htm

4. Nguyen HQ, Jumaan AO, Seward JF. Decline in varicella mortality following implementation of varicella vaccination in the United States. NEMJ 2005; 352(5):450-458.

5. Davis MM, Patel MS, Gebremariam A. Decline in varicella-related hospitalizations and expenditures for children and adults after introduction of varicella vaccine in the United States. Pediatrics 2004; 114(3):786-792.

Surveillance Areas

West Philadelphia

[www.phila.gov/health/] (exit)

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At the Philadelphia Department of Public Health, the VASP project is carried out by the Division of Disease Control. West Philadelphia includes 7 zip codes with a total population of approximately 300,000. Twenty-six percent of the individuals in the West Philadelphia surveillance area are less than 18 years of age and there is a 0.85 male to female ratio. Based on the 2002 Census statistics, the population is composed of 75.8% African Americans, 16.4% Caucasians, and 7.8% listed as Asian or other ethnicity/race. Within this surveillance area, there is significant variation in the income, level of education, and presence of risk factors. The median household income for each zip ranges from 15,888 to 38,668. Among the adults over 25, 68% have completed high school.

Antelope Valley of Los Angeles

[http://lapublichealth.org/spa1/index.htm] (exit)

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At the Los Angeles Department of Health Services, VASP project is conducted in the Antelope Valley health district. Antelope Valley is a high desert community located in the northeastern part of Los Angeles County (LAC) and consists of approximately 35 communities, covering approximately 2000 square miles. It is located 35 miles from downtown Los Angeles, and is relatively isolated from the larger, dense areas of LAC. The health district primarily includes the cities, Lancaster and Palmdale, with 63% of the community living in one of these two cities. There are a total of 282 reporting sites, representing 313 surveillance units participating in VASP.

Antelope Valley is an area that has been attracting younger populations, in particular young couples and families. Approximately 34.6% of the population is between 1-19 years of age and 47.6% is between 20-54 years of age. Based on 2003 Census statistics, the total population in Antelope Valley is approximately 348,943 and is composed of 48.9% Caucasians, 31.5% Hispanic, 15.5% African Americans, and 4.1% listed as Asian, American Indian or Pacific Islander

Diseases Under Surveillance

Chickenpox

Chickenpox (varicella) is an infectious disease caused by the varicella zoster virus (VZV), a member of the herpes virus family. Infection usually leads to a blister-like rash, itching, tiredness, and fever. Chickenpox is highly infectious and can spread from person to person from direct contact or through the air from an infected person’s coughing or sneezing. A person with chickenpox is contagious 1-2 days before rash appears and until all blisters have formed scabs. It takes approximately 10-21 days after contact with an infected person for someone to develop chickenpox.

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Image of Wild-type Chickenpox: Adolescent female with varicella lesions in various stages
Source: www.vaccineinformation.org/photos/variaap002.jpg
Copyright: American Academy of Pediatrics

Chickenpox causes an illness that lasts commonly 5-6 days in children. Symptoms can include high fever, severe itching, uncomfortable rash, dehydration, or headache. Occasionally, serious complications from disease can occur, including bacterial infections in the skin, tissues, bone, lungs, joints, or blood; viral pneumonia; bleeding problems; and encephalitis (infection of the brain).

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Image of Wild-type Chickenpox: Adolescent female with varicella lesions in various stages
Source: www.vaccineinformation.org/photos/variaap001.jpg
Copyright: American Academy of Pediatrics

Chickenpox can be usually prevented by receiving the varicella vaccine, Varivax. The vaccine was licensed in 1995 by Merck and has been shown to be 70 to 90% effective against preventing disease. According to recommendations set by the Advisory Committee on Immunization Practices (ACIP), children between the ages of 12 to 18 months should be administered one dose of vaccine, and children between 19 months and 13 years, who have not had the chickenpox should also be vaccinated with a single dose. Children with prior history of chickenpox disease do not need to be vaccinated. Individuals 13 years and older who have not had chickenpox should receive two doses of the vaccine 4 to 8 weeks apart.

Cases of varicella may occur in some vaccinated persons following exposure to wild-type virus. This is called breakthrough infection. Breakthrough infection is varicella disease that occurs more than 42 days after vaccination following exposure to wild-type varicella zoster virus and usually results in mild illness. Nonetheless, breakthrough varicella is contagious and can lead to transmission of virus to those unvaccinated and at risk for complications, such as adults, immunocompromised individuals, and pregnant women.

Image of Breakthrough Chickenpox: Abdomen of child with breakthrough varicella lesions.

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Image of Breakthrough Chickenpox: Back of child with breakthrough varicella.

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Image of Breakthrough Chickenpox: Back of child with breakthrough varicella.

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The skin lesions of breakthrough varicella can be macular rather than vesicular. They are rarely bullous or hemorrhagic, and residual scarring is less common.

References:

1. CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1996;45(No. RR-11). www.cdc.gov/mmwr/preview/mmwrhtml/00042990.htm

2. CDC. Prevention of varicella: update recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48 (No. RR-6). www.cdc.gov/mmwr/preview/mmwrhtml/rr4806a1.htm

3. Watson BM. Piercy SA. Plotkin SA. Starr SE. Modified chickenpox in children immunized with the Oka/Merck varicella vaccine. Pediatrics 1993; 91:17-22.

4. Bernstein HH. Rothstein EP. Watson BM. Reisinger KS. Blatter MM. Wellman CO. Chartrand SA. Cho I. Ngai A. White CJ. Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine. Pediatrics 1993; 92:833-837.

5. Seward JF, Zhang JX, Maupin TJ, Mascola L, Jumaan AO. Contagiousness of varicella in vaccinated cases. JAMA 2004; 292 (6):704-8.

Additional Resources:

Disease topics on National Immunization Program's website:
www.cdc.gov/vaccines/vpd-vac/vpd-list.htm

Varicella information on Immunization Action Coalition's website:
www.vaccineinformation.org/varicel/index.asp (exit)

Vaccine Information Statement on NIP's website:
www.cdc.gov/vaccines/pubs/VIS/vis-varicella.pdf     text-only

Shingles

Shingles (herpes zoster) is a common illness with increasing incidence and severity as age advances. It is caused by the varicella-zoster virus (VZV), which also causes chickenpox. The mechanism of infection is not fully understood, but it involves the reactivation of latent virus activity in the cranial and dorsal root ganglia. Shingles patients can transmit VZV to susceptible individuals (i.e., those who have not had chickenpox or were not vaccinated previously). Some studies have hypothesized that exposure to the virus (mostly by contact with cases of chickenpox) may reduce the likelihood of developing shingles.

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Image of the trunk of a shingles patient with typical dermatomal rash with hemorrhagic vesicles.

Source: Stankus SJ. Dlugopolski M. Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. American Family Physician 2000 April 15; 61(8):2437-44, 2447-8.

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Different dermatomes of the body that can be affected by shingles.

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Image of Herpes Zoster: Image of trunk and back of individual with shingles.
Source: Lau BH. Lin MI. Lin HC. Herpes zoster during varicella. Pediatric Infectious Disease Journal 2001 September; 20(9):915-6.

Herpes zoster can occur after varicella vaccination among otherwise healthy children. However, a population-based study indicated that the incidence of shingles in vaccinated children is lower than compared to unvaccinated children with natural disease.

References:

Guess HA. Broughton DD. Melton LJ 3rd. Kurland LT. Epidemiology of herpes zoster in children and adolescents: a population-based study. Pediatrics 1985 Oct; 76(4):512-7.

Selected Publications

Current Issues

Risk Factors for Vaccine Failure

A live attenuated vaccine to prevent varicella-zoster virus (VZV) infection was licensed in the United States (U.S.) in March 1995. Prior to vaccine licensure, approximately four million cases of varicella were estimated to occur annually in the U.S., including 11,000–13,500 hospitalizations and 100-150 deaths. Varicella vaccine provides 70 to 90% protection against any disease and at least 95% protection against severe disease. Only three studies have documented a vaccine-effectiveness of less than 60%. The varicella vaccination program has been successful in reducing the varicella disease burden in the U.S. Nevertheless, despite its substantial impact on reducing varicella morbidity and mortality, varicella disease among vaccinated school-age children continues to be described.

Some researchers have suggested that possible reasons for varicella disease even among highly vaccinated persons may be related to the age at vaccination and waning immunity after vaccination. However, majority of the studies have not been able to confirm age at vaccination and time since vaccination as risk factors for vaccine failure. Available data do not support a delay in the earliest recommended age of immunization because of the risk of leaving children unprotected for additional months and the possibility that such children might not return later for vaccination. In addition, the vaccine effectiveness estimated in school-based outbreaks has ranged most commonly from 80% to 85% - within the range of pre-licensure efficacy calculated in clinical trials (70%-90%). These observations have been consistent with lack of waning immunity in the vaccinated population.

VASP plays an important role in the monitoring of vaccine effectiveness over time. Although disease is much milder and the number of cases declined substantially due to a vaccine efficacy of 70-90%, varicella continues to occur at a low rate and cause outbreaks. Currently, the Advisory Committee on Immunization Practices (ACIP) is reviewing data to determine whether a second dose of varicella vaccine should be considered.

Herpes Zoster after Widespread Vaccine Use

Concerns have been raised over whether the reduction in circulating VZV due to the varicella vaccination program will increase the incidence of herpes zoster. Mathematical models based on the assumption that protection against reactivation of VZV is a result of external boosting (i.e., exposure to cases of varicella disease) alone have suggested that significant increases in herpes zoster incidence will occur over the next 30-50 years. However, the triggers for reactivation of VZV are poorly understood, and protection may involve external boosting, internal boosting, or other mechanisms.

In response to these concerns, VASP is collecting thorough information on herpes zoster cases. Cases of shingles have been reported to VASP since 1999 among individuals <20 years. Currently, both surveillance areas will expand their reporting system to capture cases of shingles identified in all ages. The surveillance for shingles will also be important with the possible licensure of the new vaccine for herpes zoster.

Challenges in the Diagnosis of Varicella

Prior to the licensure of the vaccine, varicella was primarily diagnosed clinically because wild-type varicella disease is easily distinguishable based on its characteristic vesicular rash. However, it is more difficult to diagnose breakthrough varicella cases using traditional clinical methods because the manifestations of the disease are oftentimes mild and more easily mistaken for other diseases that cause rash, including herpes simplex, rickettsial pox, impetigo, allergic reactions, and insect bites. Although epidemiologic information will still play an important role, laboratory tests will also be more heavily relied on for the diagnosis of varicella, although at this time, some of these tests are still not readily available at all clinics and physician offices. VASP offers the service of laboratory testing for all their reporting units. At this time, there is no published study that examines the characteristics of the rash produced by breakthrough disease and for this reason, VASP is currently conducting studies to examine the epidemiology and the best diagnostic tools for detecting breakthrough disease.

Case-based Reporting

The Council of State and Territorial Epidemiologists (CSTE) recommended that states establish case-based surveillance by 2005. Case-based reporting was implemented in previous years in the two VASP sites, West Philadelphia, PA and Antelope Valley, CA, and has shown to be a useful and feasible component of their surveillance project. Extending case-based reporting nationwide will help to provide more information to monitor the epidemiology of varicella and allow us to better monitor the impact of the immunization program.

References:

1. Galil K. Lee B. Strine T. Carraher C. Baughman AL. Eaton M. Montero J. Seward J. Outbreak of varicella at a day-care center despite vaccination. New England Journal of Medicine 2002; 347(24):1909-15.

2. Galil K. Fair E. Mountcastle N. Britz P. Seward J. Younger age at vaccination may increase risk of varicella vaccine failure. Journal of Infectious Diseases 2002; 186(1):102-5.

3. Lee BR, Feaver SL, Miller CA, Hedberg CW, Ehresmann KR. An elementary school outbreak of varicella attributed to vaccine failure: policy implications. Journal of Infectious Diseases 2004;190(3):477-83. Epub 2004 Jun 29.

4. Centers for Disease Control and Prevention. Outbreak of varicella among vaccinated children--Michigan, 2003. MMWR 2004; 53(No. RR -18):389-92.

5. Vazquez M. Varicella infections and varicella vaccine in the 21st century. Pediatric Infectious Disease Journal 2004; 23(9):871-2.

6. Vazquez M. LaRussa PS. Gershon AA. Niccolai LM. Muehlenbein CE. Steinberg SP. Shapiro ED. Effectiveness over time of varicella vaccine. JAMA 2004; 291(7):851-5.

7. Garnett GP et al. The epidemiology of varicella-zoster virus infections: the influence of varicella on the prevalence of herpes zoster. Epidemiol Infect 1993; 108:513-28.

8. Thomas SL. Wheeler JG. Hall AJ. Contacts with varicella or with children and protection against herpes zoster in adults: a case-control study. Lancet 2002; 360: 678-82.

9. Brisson M. Gay NJ. Edmunds WJ. Andrews NJ. Exposure to varicella boosts immunity to herpes zoster: implications for mass vaccination against chickenpox. Vaccine 2002; 20: 2500-07.

10. Verstraeten T, Jumaan AO, Mullooly JP, Seward JF, Izurieta HZ, DeStefano F, Black SB, Chen RT. Vaccine Safety Datalink Research Group. A Retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles-mumps-rubella vaccination. Pediatrics 2003;112(2):e98-e103.

11. Tugwell BD, Lee LE, Gillette H, Lorber EM, Hedberg K, Cieslak PR. Chickenpox outbreak in a highly vaccinated school population. Pediatrics 2004;113(3):455-459.

12. Perella DM, Watson BM, Heath K, Robinson D, Spain CV. Laboratory confirmation of suspected breakthrough varicella infections. Pediatric Academic Society Meeting, San Francisco, CA, May 2004.

13. Civen RH, Maupin TJ, Xiao H, Seward JF, Jumaan AO, Mascola L. A population-based study of Herpes Zoster (HZ) in children and adolescents post-varicella vaccine licensure. 41^st Annual Meeting of Infectious Disease Society of America, San Diego, CA, October 2003.

14. Civen RH, Maupin TJ, Xiao H, Mascola L, Jumaan AO. Trends in Varicella outbreaks in Antelope Valley, California 1995-2003. 42^nd Annual Meeting of Infectious Disease Society of America, Boston, MA, October 2004.

Additional Information

Contact Information

Centers for Disease Control

National Center for Immunization and Respiratory Diseases
(previously National Immunization Program)
1600 Clifton Rd, Mail Stop E61
Atlanta, GA 30333
For immunization info, call the CDC-INFO Contact Center:
English and Spanish: 1-800-CDC-INFO (1-800-232-4636)
TTY: 1-888-232-6348

West Philadelphia

City of Philadelphia Department of Public Health
Division of Disease Control
500 S. Broad Street
Philadelphia, PA 19146
Main Phone 215-685-6741
Immunization Program Fax 215-685-6806
Disease Control Fax 215-545-8362

Antelope Valley

Department of Health Services- Public Health
High Desert Hospital
44900 N. 60th St. West
Lancaster, CA 93536
Phone: (818) 487-0063
Fax: (818) 487-0110

Additional Links

National Center for Immunization and Respiratory Diseases (NCIRD):
www.cdc.gov/vaccines/

Centers for Disease Control and Prevention (CDC):
www.cdc.gov/

Immunization Action Coalition:
www.immunize.org/ (exit)

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