About 95% of women of childbearing age in the United States have serologic evidence of past VZV infection. The proportion of seropositive women is smaller in those from tropical or semitropical countries (489).

Varicella is a highly communicable and usually benign disease of childhood. Its incubation period is usually 14 to 16 days, with a range of 10 to 21 days. Before licensure of the varicella vaccine in 1995, children younger than 15 years of age accounted for more than 90% of cases and fewer than 2% of reported cases occurred in those 20 years of age or older (490). Vaccination coverage rates were about 80% in U.S. children by the year 2000, but disease activity and hospitalizations had declined by 76% to 87% (491). Although the greatest decrease in incidence has been in children 1 to 4 years of age, cases declined in all age groups including infants and adults (492). The estimated incidence of gestational varicella before vaccine availability was 1 to 7 per 10,000 pregnancies, but there have been no revised estimates to date (493,494). Zoster results from reactivation of latent VZV and is encountered more frequently in elderly or immunosuppressed patients. Its incidence in pregnancy is unknown, but it is probably lower than that of varicella. One estimate placed the incidence at about 0.5 per 10,000 pregnancies (493).

Less than 5% of primary VZV infections are subclinical (495). The typical illness consists of fever, malaise, and a pruritic rash. The exanthem is mostly truncal in distribution and is characterized by crops of maculopapules that rapidly evolve into vesicles. The vesicles gradually crust over. New lesions continue to appear for 3 to 5 days, producing the distinctive finding of cutaneous lesions in various stages of evolution. Complications of varicella include pneumonia, encephalitis, arthritis, bacterial cellulitis, retinal vasculitis, and bleeding diathesis. The risk of incurring complications from varicella in otherwise normal adults may be up to 25-fold greater than that for normal children (490,496,497). Pregnancy is generally not considered a risk factor for maternal complications, but there may be an increased prevalence of varicella pneumonia in the third trimester (497). Immunity after varicella is usually long lasting, but recurrent VZV infections can occur in immunocompetent persons (498,499).

Zoster is characterized by pain localized to the area of distribution of one or more sensory nerve roots. The rash is unilateral in most patients and follows the same evolutionary pattern seen in varicella except for its restricted distribution.

Varicella and herpes zoster usually are diagnosed clinically, and laboratory confirmation is needed infrequently. The virus can be isolated from vesicular fluid by inoculating freshly collected specimens onto human diploid cell lines. The VZV-specific antigens can be detected in vesicular fluid by immunofluorescence staining of smears of cell scrapings collected from the base of fresh vesicles (500). VZV DNA can be detected in vesicle samples, including most crusted lesions, by PCR methodologies (501,502). PCR assays have also been used to detect VZV DNA in CSF, genital lesions, and other clinical specimens (503,504). Quantitative VZV DNA measurements in blood and skin lesions show that viral loads are higher in patients with varicella than in those with herpes zoster (505,506).

Several serologic assays are available for the detection of antibodies to VZV. These include complement fixation, neutralization, IHA, immune adherence hemagglutination, radioimmunoassay, immunoblot, latex agglutination,
fluorescent antibody against membrane antigen (FAMA), indirect fluorescent antibody (IFA), and ELISA. These tests can be used to diagnose VZV infections or to ascertain the susceptibility status of an individual (507).

Complement fixation antibodies develop within 10 days of onset of varicella and peak at 2 to 3 weeks. These antibodies appear earlier in herpes zoster. Complement fixation antibodies tend to disappear with time. By 1 year after infection, about two-thirds of persons do not have detectable complement fixation antibody titers. The complement fixation test is relatively insensitive compared with FAMA or ELISA, and it is now rarely used in clinical laboratories. The FAMA test is very sensitive and is considered to be the gold standard for VZV antibody measurements. However, FAMA is arduous to perform and is not readily available. The ELISA test is more frequently used for VZV antibody measurements. The IFA methods appear to be as sensitive as FAMA.

Two serum samples collected 1 to 2 weeks apart can provide a retrospective diagnosis of VZV infection if a fourfold or greater rise in antibody titer is demonstrated. If the first sample is collected late in the course of the illness, a single high titer indicates a recent primary or a reactivated VZV infection.

Measurement of VZV-specific IgM antibodies is useful for documenting a recent infection with this virus. VZV-specific IgM antibodies can be detected in serum for several weeks after varicella and may be transiently found after herpes zoster.

For uncomplicated varicella, symptomatic treatment with antipruritics and cleansing of lesions is adequate. Analgesics are needed for pain control in herpes zoster. Early therapy of varicella within the first day of illness with oral acyclovir (800 mg given orally five times per day for 7 days) or valacyclovir (1000 mg given orally three times daily for 5 days) hastens resolution of fever and shortens the time period to complete crusting of the lesions (508,509). Acyclovir and valacyclovir are not recommended for use during pregnancy, but can be given for the treatment of severe or life-threatening VZV complications such as pneumonia.

There have been several reports of pregnant women with varicella pneumonia who were treated with acyclovir (510,511,512,513,514,515,516,517). The drug was used at doses ranging from 5 to 18 mg/kg every 8 hours, and the treatment results generally have been favorable. It is currently recommended that women who need intravenous acyclovir therapy for varicella pneumonia should get 10 mg/kg every 8 hours for 5 days.

VZV transmission to the fetus occurs primarily through the transplacental route. Congenital malformations after maternal infection during the first half of pregnancy occur infrequently. VZV antigens and its DNA have been detected in fetal tissues from pregnancies complicated by varicella using immunohistochemical staining methods and PCR, respectively (518,519,520,521,522).

About one-fourth of newborns delivered to mothers who contract varicella during the last 3 weeks of pregnancy develop clinical infection (516). Paryani and Arvin (523) used several clinical and immunologic criteria to document intrauterine transmission of VZV in 43 pregnancies complicated by varicella and 14 others complicated by herpes zoster. These criteria included malformations consistent with the congenital varicella syndrome, acute varicella of the newborn, detection of VZV-specific IgM in the neonatal period, specific lymphocyte transformation to VZV antigen, persistence of anti-VZV IgG, and the occurrence of herpes zoster in infancy. The rate of intrauterine transmission was 24% after maternal varicella and 0% after maternal herpes zoster (523).

Varicella during pregnancy is not associated with an increased incidence of prematurity or fetal death (523- 525). Chromosomal abnormalities have occurred after VZV infections in experimentally infected human diploid fibroblasts and in the peripheral leukocytes of patients with acute varicella (526,527). Leukocyte chromosomal breaks were described in one child whose mother had gestational varicella (528). An increased risk of leukemia in the offspring of women with gestational varicella has been found by some investigators, but the numbers are too small to confirm the association (529).

Numerous case reports published over the past 58 years have described the occurrence of congenital malformations in the progeny of women who acquire chickenpox during pregnancy (521,522,523,524,530,531,532,533,534,535,536,537,538,539,540,541,542,543,544,545,546,547,548,549,550,551,552,553,554,555,556,557,558,559,560,561,562,563,564,565,566,567,568,569,570,571,572,573,574,575,576,577,578,579,580,581). With the exception of a few infants with congenital anomalies after maternal varicella at 24 to 32 weeks of gestation, these infections usually occurred during the first half of gestation, and mostly between weeks 8 and 20 of pregnancy (582,583,584,585). Abnormalities are primarily cutaneous, musculoskeletal, neurologic, and ocular (Table 48-5).