Chicken Pox & Childbearing ATTENTION HEALTH CARE PROFESSIONALS: HAVE YOU HAD THE CHICKEN POX? H ere s one scenario worth exploring: a neonatal intensive care unit nurse receives a telephone call from a friend, who informs her that he has just come down with the chicken pox. She went to the movies with him just two days before, but hadn t seen him since the outbreak. To the best of her knowledge, she hadn t ever had the chicken pox. How can she find out if she possesses an immunity to the virus? And if she s not immune, when is it safe for her to return to work with the newborns? After an immunoglobulin G (IgG) latex agglutinate test to check her immunity, it was determined that the nurse didn t possess the antibodies to the varicella virus; therefore, she was seronegative. Because the nurse s friend was contagious for five days before his outbreak or until the vesicles had granulated over, she may have been exposed to the virus and should have been considered potentially infectious for the 10th through the 21st day after exposure. Because the nurse was exposed two days ago, she can safely work with newborns for the next eight days, but shouldn t work in a clinical setting for the following 11 days. The nurse could be offered varicella zoster immune globulin (VZIG). If she has an outbreak of the chicken pox, the nurse needs to avoid the clinical setting until all of the lesions have formed scabs. If the nurse doesn t break out during those 11 days, she needs to receive her first varicella vaccination and her second vaccination four to eight weeks later. During this time and for six weeks after the last vaccination, she should not work with newborns or any other patients who may be immunocompromised because of the slight risk of infecting them with the virus. Emiromnental Pemptive Between 5 to 15 percent of adults in the US. don t have immunity to varicella, the virus that causes the chicken pox. The varicella vaccine can significantly reduce the incidence of varicella infections in pregnancy and should be given before women are of childbearing age. Susceptible health care workers can help prevent transmission of VZV by being vaccinated. However, it s not clear how long protection lasts after vaccination. Studies Barbera Hansen Cottrell, ARNP, MSN Carrie C. Carter August 1998 AWHONN Lifelines 33
are ongoing to evaluate the need and timing for booster vaccination. The 1995 development of a vaccine to prevent varicella resulted in new recommendations for health care workers. The first recommendations by the Advisory Committee on Immunization Practices (ACIP) were published in July, 1996. Both the Hospital Infection Control Practices Advisory Committee and the ACIP recommended that all susceptible health care workers ensure that they are immune to varicella, and serologic screening of all health care workers with a negative or uncertain history of varicella was recommended to document immunity (CDC, 1996). These recommendations are particularly important for those working with pregnant women and newborns. Although these recommendations have been available for more than two years, there are still susceptible health care workers who haven't been immunized. Because of the profound effects of gestational varicella, the importance of susceptible health care workers being immunized can't be overemphasized. Health care workers who don't know if they're immune can easily test for immunity. The availability of the varicella vaccine also opened new options for preventing chicken pox in pregnancy. Health care professionals should be asking all women of childbearing age whether they've had the chicken pox, particularly during preconception counseling. For those who aren't sure whether they've had chicken pox, serologic testing or vaccination should be offered if there are no contraindications. For those who have had varicella, there's at least a 97 percent chance that they're immune (Stevenson, 1996). Pregnant women shouldn't receive the vaccine, and pregnancy should be avoided for three months after receiving the vaccine (Merck, 1997). looking at Varicella Varicella is highly contagious and is caused by the DNA varicella zoster virus (VZV). The varicella virus most often manifests as seasonal epidemics, typically in late winter and early spring. Although more than six million doses of vaccine have been administered since licensure of the live attenuated varicella vaccine, there are still millions of cases annually in the U.S. In fact, 10 percent of all varicella cases occur in people 15 years old or older, and as many as 500,000 individuals seek medical care for their symptoms. Approximately 125 deaths occur annually in the U.S. with varicella as an underlying cause (Wharton, 1996). For a normal, healthy child, the mortality rate is less than two per 100,000 and is usually caused by septic complications and encephalitis (Beneson, 1995). For adults, that rate increases more than 15 fold (Whitley, 1995) and mortality risk is due to primary viral pneumonia (Beneson, 1995). Varicella also occurs in as many as five per 10,000 pregnancies (Mclntosh & Isaacs, 1993). VZV is a human herpes virus. The primary infection, Barbara Hansen Cottrell, ARNP, MSN, is an associate professor at Florida State University in Tallahassee, FL. Carrie C. Carter is an undergraduate nursing student at Florida State University. Testing for Immunity A positive history of varicella is 97 percent predictive of a serologic immunity (CDC, 1996). Serologic tests are available for IgG antibodies to VZV. Tests differ in their ability to detect antibody acquired from natural varicella versus antibody acquired from vaccination. Single serologic IgG tests are used to identify the immune status of persons with a negative or uncertain history of varicella who may be candidates for VZlG or vaccination. Factors in selecting an antibody-detection assay include test sensitivity and specificity, the length of time required to obtain results, and availability of the assay (CDC, 1996). The following tests may be ordered (Seward et al., 1997): Enzyme-linked immunosorbent assays (ELISA) Fluorescent antibody to membrane antigen (FAMA) Latex agglutination (LA) lndirect hernagglutination (IHA) Immune adherence hemagglutination (IAHA) Complement fixation (CF) The LA test can be completed in 15 minutes but is less sensitive in detecting the antibody after vaccination, though still more sensitive than commercial ELlSAs (CDC, 1996). The FAMA test is considered the "gold standard" for screening for immune status for VZV, but isn't widely available. varicella, results from exposure of a susceptible individual to the virus. Symptoms include a generalized vesicular rash, low-grade fever, and malaise. A prodrome of symptoms may occur one to two days before breakout. The skin manifestations are the hallmark of chicken pox. They appear as maculopapules, vesicles, and scabs in varying stages of evolution. The lesions initially contain clear vesicular fluid, but quickly pustulate and scab. The first of the lesions appear on the trunk and face and rapidly spread centripetally to involve other areas, and may include the oral mucosa and vagina (Whitley, 1995). Successive crops of lesions appear over a period of two to four days. The scabs fall off within one to two weeks and leave a slightly depressed area of the skin. The healing process can take up to three times longer for immunocompromised persons. Serious complications, like encephalitis and pneumonia, rarely occur. After varicella, VZV persists in a latent form in sensory-nerve ganglia without any symptoms. The latent virus is reactivated in approximately 15 percent of people, who subsequently develop herpes zoster, or "shingles. How Varicella Spreads The varicella virus can be transmitted person-to-person through direct contact, airborne spread of vesicle fluid, or by secretions of the respiratory tract. Congenital infections may also occur. Indirectly, varicella can be transmitted through articles freshly soiled by discharge 34 AWHONN Lifelines Volume 2, Issue 4
Precautions After Vaccination 1. Epinephrine injection (1:lOOO) should be available for immediate use if an anaphylactic reaction should occur 2. Pregnancy should be avoided for 1 month after each dose of the vaccine (AAP, 1997). Because two doses of the vaccine are given four to eight weeks apart, the CDC recommends avoiding pregnancy for three months after the initial vaccination. The manufacturer has strengthened that recommendation and has indicated that pregnancy should be avoided for three months after the completion of vaccination (Merck, 1997). 3. Although rare, persons who have been given Varivax are potentially capable of transmitting the vaccine strain of virus to susceptible close contacts. Secondary transmission from the vaccine virus may be possible as early as five days postexposure (Seward et al., 19971. Therefore, recipients should avoid association with persons with weakened immune systems for six weeks after vaccination. A mild varicellalike rash has been observed in approximately 7 percent of vaccinees, and those with the rash are considered contagious (Merck, 1997). 4. Vaccine recipients should avoid the use of salicyclates for six weeks after vaccination with varicella, because Reye's syndrome has been reported after the use of salicyclates during natural varicella infections (AAP, 1997). from vesicles and mucus membranes of infected people. The scabs from varicella lesions are not infective. The vesicle fluid of patients with herpes zoster can also transmit chicken pox, but this transmission rate is low (Beneson, 1995). Because of the ease of transmission, airborne and contact precautions are necessary. Clients hospitalized with VZV and susceptible patients who have been exposed to the virus should be isolated, preferably in a single room with negative air-pressure ventilation with externally exhausted or high-efficiency particulate air filters if the air is recirculated (American Academy of Pediatrics [AAP], 1977). Masks, gowns, and gloves should be worn. Susceptible personnel who were exposed should be furloughed away from patient care areas and screened daily for skin lesions, fever, and systemic symptoms (CDC, 1996). Only personnel who are immune to varicella should care for patients with VZV. VZV incubates from two to three weeks, and an individual is considered contagious for five days before the appearance of the first lesions until five days after the appearance of the last lesions. Exposed susceptible individuals should be considered infectious for 10 to 21 days after exposure (CDC, 1996). The incubation period may be prolonged for as long as 28 days when varicellazoster immune globulin (VZIG) is given (AAP, 1997). Pox in Pregnancy Chicken pox during pregnancy (gestational varicella) is rare, but can be dangerous for the fetus, mother, and newborn. Varicella in pregnant women is associated with a risk for VZV transmission to the fetus with resulting multiple system damage, clinical varicella in the newborn, or clinical herpes zoster during infancy and early childhood (CDC, 1996). The incidence of premature birth is substantially increased among women with chicken pox (Katz et al., 1995). The fetus of a woman with gestational varicella has a 2 to 3 percent chance of developing varicella embryopathy (Grant, 1996), also known as congenital varicella syndrome (CDC, 1996). Manifestations of this include skin scaring, intrauterine growth retardation, limb hypoplasia and other skeletal lesions, and central nervous system involvement. Cataracts, chorioretinitis, deafness, and microcephaly may result (Katz et al., 1995). The low risk of developing varicella embryopathy suggests a limited ability for the virus to cross the placenta and infect the fetus. Fetal risks are usually limited to fetal exposure before 20 weeks gestation (Katz et al., 1995), but embryopathy has been reported from infection as late as 26 weeks (Jones et al., 1994). Recommended treatment for gestational varicella depends on the number of weeks gestation and the mother's health status. An otherwise healthy woman with mild symptoms should be first treated symptomatically with fluids, antipyretics, and antipruritics. If she is near term, it's best to delay delivery for five to seven days to allow maternal antibodies to develop and transfer to the fetus (Paulman & McLellan, 1990). Pregnant women who are susceptible and exposed to varicella should strongly consider getting VZIG after exposure (CDC, 1996). VZIG is prepared from the plasma of blood donors with a high antibody titer to VZV. Immune globulin may not eliminate the incidence of varicella embryopathy, but, if given before maternal infection develops, it may increase or attenuate fetal disease (Enders et al., 1994). If the woman has a varicella infection and delivers within five days, or has the virus within 48 hours after delivery, VZIG is indicated. It's effective in modifying or preventing further manifestations of the disease if given within 96 hours after exposure to VZV. Typically, VZIG is available from blood centers and costs between $600 and $800 per dose. Because VZIG is considered preventive, it may not be covered by insurance (Grant, Exploring the Vaccine The vaccine is a live, attenuated varicella virus. It must be stored frozen at an average temperature 25 F (15 C). The diluent should be stored separately either at room temperature or in the refrigerator. The vaccine should be reconstituted according to the manufacturer's directions and only the diluent supplied because the diluent supplied doesn't contain preservatives or other antiviral substances that could inactivate the vaccine. The vaccine should be used within 30 minutes after reconstitution or discarded (CDC, 1996). August 1998 AWHONN Lifelines 35
I Dealing With Susceptible Health Care Workers Susceptible health care staff who are not VZV immune and are exposed to varicella should be furloughed or excused from patient contact from day 10 to day 21 after exposure. If the staff member is pregnant and healthy, VZlG should be given. VZlG can be given to healthy, susceptible adults after exposure to varicella, but isn t routinely recommended if the patients are pregnant (AAP, 1997). The administration of VZIG can prolong the average incubation period, so recipients should be furloughed away from patient contact for 10 to 28 days after exposure (CDC, 1996). After this time period, varicella vaccine is recommended for all susceptible staff if varicella doesn t develop. For those in whom varicella does develop, Acylovir should be considered for otherwise healthy health care workers. Acylovir should be given within 24 hours of the onset of the rash to decrease the magnitude and duration of fever and the number and duration of skin lesions. 1996). Protection with VZIG against varicella lasts only about three weeks. If the pregnant woman has a severe case of varicella, marked by a rapid, extensive rash, high fever, and pulmonary involvement, antiviral therapy may be considered during the third trimester. The incidence of varicella pneumonia is highest in the third trimester (approximately 13 percent) with an estimated mortality rate of 40 percent (Katz et al., 1995). Acylovir is the drug of choice for these pregnant women in their third trimester. Acylovir is classified as a Category C by the FDA (because risk can t be ruled out, but potential benefits may justify the possible risk) and is not recommended routinely in pregnant adolescents or adults with uncomplicated varicella because the risks and benefits to the fetus and mother are unknown (AAP, 1997). Controlled studies among pregnant women who have been given Acylovir haven t been conducted (CDC, 1996). Newborns & Chicken Pox Varicella can develop between one and 16 days after birth in infants born to mothers with acute varicella. The interval between the onset of rash in the mother to the onset in the neonate is nine to 15 days (AAP, 1997). Newborns with varicella should be allowed to breastfeed, be isolated with the mother, and should be discharged as soon as possible (Lawrence, 1994). Newborns of women who experience the onset of varicella from five days before to two days after delivery have a 17 to 30 percent chance of severe varicella infection because they don t have sufficient maternal antibody to lessen the severity of disease. For this reason, the AAP (1997) recommends that these infants be given VZIG 125 units as soon as possible after birth. These newborns have up to a 30 percent risk for death if their mothers had onset of rash one to four days before giving birth unless VZIG is given (CDC, 1996). Varicella can be expected to develop in approximately half of the infants given VZIG, but the disease is often modified and much less severe. VZIG recipients should be observed closely. For healthy, full-term newborns exposed postnatally to varicella, including those whose mother s rash developed more than 48 hours after delivery, the AAP (1997) states that VZIG isn t indicated. The newborn of a woman who contracted gestational varicella within three weeks before delivery has a 25 percent chance of being born with a rash. Infants with active varicella should be kept away from other infants and preferably isolated with their mothers (CDC, 1996). Both airborne and contact precautions are recommended for newborns with varicella as long as the rash remains vesicular. Airborne and contact precautions are recommended also for neonates born to women with varicella and, if hospitalized, continued until 21 days or 28 days after VZIG was given. Infants born with varicella embryopathy don t require isolation (AAP, 1997). Premature Infants Premature infants of less than 28 weeks gestation or infants whose mother had onset of chicken pox from five days before to 48 hours after delivery should receive VZIG. Also, VZIG is indicated for infants born before 28 weeks gestation (or who weigh less than 1,000 g) who still require hospitalization for treatment of prematurity or related conditions and are exposed to varicella or zoster. Preterm infants born after 29 weeks of gestation who are exposed in the hospital and whose mothers have no history of infection andlor are seronegative should also be given VZIG (AAP, 1997). Breastfeeding VZV hasn t been found in breast milk in women with varicella (Frederick et al., 1996). Breast milk has tested positive for varicella-zoster DNA in one study (Yoshida et al., 1992), but it s possible that the milk may have been contaminated through direct contact with skin lesions or airborne droplets. Mothers with varicella can maintain lactation with a pump, discarding pumped milk until they are no longer infectious. If a woman decides to breastfeed, the infant should be protected from direct contact with mom s skin rash and the mother should wear a mask. Antibodies appear in milk within 48 hours of the disease onset (Lawrence, 1994). It s not known if the attenuated vaccine is excreted in human milk, and whether the infant could be infected during breastfeeding. For this reason, the vaccine manufacturer recommends that nursing mothers not receive the vaccine (Merck, 1997). The CDC (1996) states the varicella virus vaccine may be considered for a nursing mother. If the risk of exposure to natural VZV is high, the vaccine may be considered (AAP, 1997). Guidelines for Vaccination Nonpregnant Women of Childbearing Age Vaccination of women who aren t pregnant but may become pregnant in the future will reduce the risk for 88 AWHONN Lifelines Volume 2, Issue 4
Reporting Inadvertent Vaccination Inadvertent vaccination of pregnant women with the varicella vaccine should be reported. The manufacturer, in collaboration with the CDC, has established the VARIVAX Pregnancy Registry to monitor the maternal-fetal outcomes of pregnant women who are inadvertently administered the varicella virus three months before or during pregnancy. Health care professionals can call (800) 986-8999 to register their patients. Because the virulence of the attenuated virus used in the vaccine is less than that of the wild-type virus, and because the wild-type virus poses a very small risk to the fetus, the decision to terminate a pregnancy shouldn t be based on whether the vaccine was administered during pregnancy. VZV transmission to the fetus. Women should first be asked if there is any possibility that they may be pregnant and advised to avoid pregnancy for three months after the first dose of the vaccine (CDC, 1996). The drug manufacturer (Merck, West Point, PA) is more cautious; they recommending that women avoid pregnancy for three months after completion of the vaccination. Inadvertent administration of varicella vaccine should be reported. Children The vaccine is recommended for all susceptible children ages 1 year and older before their 13th birthday. Persons younger than 13 years of age should receive 0.5 ml doses of the vaccine subcutaneously. Persons ages 13 and older should receive a 0.5 ml dose on a selected date and a second 0.5 ml dose four to eight weeks later. Results from clinical studies indicate that varicella vaccine can be administered concomitantly with MMR I1 drawn up in separate syringes using separate injection sites (Facts and Comparisons Publishing Group, 1998). If not given on the same day as the MMR vaccine, the interval between the varicella vaccine and MMR should be at least one month (AAP, 1997). A pregnant mother or other member of the household is not a contraindication for vaccination of the child, because more than 90 percent of adults are immune. Although rare, the varicella vaccine virus has been transmitted by a healthy vaccinee to contacts with only mild or symptomatic infection reported (AAP, 1997). However, if the pregnant woman is known to be susceptible, some experts recommend deferring immunization of the child until the third trimester or until after delivery, if feasible (AAP, 1997). Health Care Workers Health care workers who have never had varicella should be immunized with two 0.5 ml doses of vaccine subcutaneously, four to eight weeks apart (CDC, 1996). The outer aspect of the upper arm is the preferred site of injection. Approximately 90 percent of adults seroconvert after two doses and can be expected to be protected against varicella. About 70 percent will be completely protected; the remaining 30 percent will develop modified varicella with an average of 50 skin lesions and rapid recovery (Donowin, 1996). These people should avoid contact with susceptible high-risk persons such as newborns and pregnant women for as long as the rash remains vesicular (Facts and Comparisons, 1998). Approximately 10 percent of those who are immunized and subsequently seroconvert lose detectable antibodies within several years after varicella; those that do are among the 30 percent who are at risk for breakthrough varicella (Donowitz, 1996). If no seroconversion occurs after two doses, a third dose may be given. Seroconversion is often measured by the latex agglutination assay for VZV antibodies and can help in the management of personnel assigned to high-risk areas, such as obstetric areas and newborn nurseries. Contraindications Pregnant women shouldn t be vaccinated because the effects of the varicella virus vaccine on the fetus are unknown (CDC, 1996). Patients who shouldn t be given the varicella vaccine are those who have (Brody& Moyer, 1997; Facts and Comparisons, 1998; Zimmerman, 1996): Leukemia 0 Lymphoma Blood dyscrasia or any other malignant neoplasms affecting the bone marrow or lymphatic systems Immunosuppressive therapy or immunodeficiency A family history of congenital or hereditary immunodeficiency HIV infection Febrile illness (>lol F) Active, untreated tuberculosis A history of hypersensitivity to any vaccine component such as gelatin or anaphylactoid reaction to neomycin Hypogammaglobulinemic and dysgammaglobulinemic states A blood transfusion within the past five months Immune globulin or VZIG within the preceding five months It s not known if the administration of immune globulin can interfere with the immunologic response to varicella vaccination. Immune globulin administration can interfere with the response to other live-virus vaccines. Because of the potential inhibition of the response to varicella vaccination by passively transferred antibodies, varicella vaccine shouldn t be given for at least five months after the administration of immune globulins, VZIG, blood products (excluding red blood cells), or plasma transfusions (AAF, 1997). If an immune globulin is given within five months before vaccination (as in a Rh-negative mother with a Rh-positive infant), the recipient either should be revaccinated five months later or tested for varicella immunity six months later and revaccinated if seronegative (AAP, 1997). + References Adkins, S. B. (1997). Immunizations: Current recommendations. American Family Physician, 56, 865. August 1998 AWHONN Lifelines 37
Acylovir Data Being Collected Data are currently being collected by the Centers for Disease Control and Prevention along with Burroughs Wellcome Company on the fetal-maternal outcomes of pregnant women given Acylovir. All health care providers are encouraged to register pregnant women treated with Acylovir by calling (800) 722-9292. American Academy of Pediatrics. (1997). Red book: Report of the Committee on Infectious Diseases. (24th Ed.). Elk Grove Village, IL: American Academy of Pediatrics. Beneson, A. S. (1995). Control of communicable diseases manual. Washington, DC: American Public Health Association. Brody, M. B., & Moyer, D. Varicella-zoster virus infection. Postgraduate Medicine, Temple University Series, 102, 187. Centers for Disease Control and Prevention (1996). Prevention of varicella: Recommendations of the Advisory Committee on Immunizations (ACIP). Morbidity and Mortality Weekly Report, 45, 26-27. Donowitz, L.G. (1996). Infection control in the child care center and preschool. (3rd Ed.). Baltimore: Williams & Wilkins. Enders, G., Miller, E., Cradock-Watson, J., Bolley, I., & Ridehalgh, M. (1994). Consequences of varicella and herpes zoster in pregnancy: prospective study of 1,739 cases. Lancet, 343, 1548-1551. Facts and Comparisons Publishing Group. (1998). 2998 drug facts and comparisons pocket book (2nd Ed.). St. Louis: Facts and Comparisons. Frederick, I. B., White, R. J., Braddock, S. W. (1986). Excretion of varicella herpes zoster in breast milk. American Journal of Obstetrics and Gynecology, 154, 116-1 17. Grant, A. (1996). Varicella infection and toxoplasmosis in pregnancy. Journal of Perinatal and Neonatal Nursing, 2(10), 17-24. Jones, K.L., Johnson, K.A., & Chambers, C.D. (1994). Offspring of women infected with varicella during pregnancy: A prospective study. Teratology, 49, 29-32. Katz, V.L., Kuller, J.A., McMahon, M.J., Warren, M.A. & Wells, S.R. (1995). Varicella during pregnancy: Maternal and fetal effects. Western Journal of Medicine, 163, 446-450. Lawrence, R.A. (1994). Breastfeeding: A guide for the medical profession (4th ed.) St. Louis: Mosby. McIntosh, D. & Isaacs, D. (1993). Varicella zoster virus infection in pregnancy. Archives of Disease in Childhood, 68, 1-2. Merck & Co. (1997). Varivax product information. West Point, PA: Merck & Co., Circular No. 7999905. Paulman, P., & McLellan, R. (1990). Varicella during pregnancy: The timing of effective treatment. Journal of the American Board of Family Practice, 2, 121-123. Seward, J., Reef, S., Meyer, P., Kilgore, P., & Wharton, M. (1997). Varicella. [Online] Available: http://www.cdc.gov/nip/manuai/varicell/varicell/htm ( 1997, September 12). Wharton, M. (1996). The epidemiology of varicella-zoster virus infections. Infectious Disease Clinics of North America, 10, 571-581. Whitley, R. J. (1995) Varicella-zoster virus. In G. L. Mandell, J. E. Bennett, & R. Dolins (Eds.) Principles and practice of infectious diseases (4th Ed). (pp. 1534-1351). New York: Churchill Livingstone. Yoshida, M., Yamagami, N., Tezuka, T., & Hondo, R. (1992). Case report. Detection of varicella virus DNA in maternal breast milk. Journal of Medical Virology, 38, 108-1 10. Zimmerman, R.K. (1996). Varicella vaccine: Rationale and indications for use. American Family Physician, 53, 647-651.