Varicella Infection (Chickenpox) in Pregnancy

Immunology Assignment

Name : Innas Tiara Ardhiani

NIM : 011614153001

Program Studi Ilmu Kedokteran Dasar

Fakultas Kedokteran Universitas Airlangga
2016

Contents

1. Introduction........................................................................................................3
2. Varicella Infection in Pregnancy: Maternal.....................................................5
3. Varicella Infection in Pregnancy: Fetal............................................................5
4. Prevention of Maternal Complication..............................................................6
5. Prevention of Intrauterine Infection.................................................................7
Reference List...........................................................................................................8

1.

1. Introduction
Varicella zoster virus is a highly contagious DNA virus of the herpes
family. It

is transmitted by respiratory droplets and by direct personal

contact with vesicular luid. The primary infection is characterized by fever,

malaise, and a pruritic rash that develops into crops of maculopapules,
which become vesicular and crust over before healing. The incubation
period lasts 10 to 21 days, and the disease is infectious 48 hours
before the rash appears and continues to be infectious until the vesicles
crust over. (Tyring, 1992)
VZV is known to utilize a variety of binding sites and receptors to gain
access to cells and to spread from an infected cell to an uninfected
neighbor. Cell-free VZV binds to heparin sulfate proteoglycan, while the
large cation-independent mannose 6-phosphate (Man 6-P) receptor (MPR)
evidently binds to Man 6-P moieties on glycoproteins of the viral envelope
and is required for viral entry (1114). Heparin and Man 6-P, therefore, are
able to compete with cell-free VZV in vitro and protect cells from infection.
In contrast, neither heparin nor mannose 6-phosphate interferes with the
cell-to-cell spread of cell-associated VZV. That process requires the insulindegrading enzyme (IDE), which is cytosolic but is expressed near cell
surfaces and can interact with IgE. (Anne & Michael Gerson, 2013)

The memory cell responses that develop during varicella or after vaccination
contribute to protection following re-exposure to VZV. These responses are
subsequently boosted either by endogenous re-exposure (silent reactivation of latent
virus) or exogenous re-exposure (environmental). VZV-specific T cell-mediated
immunity is also necessary to maintain latent VZV in a subclinical state in sensory
ganglia. When these responses decline, as occurs with aging or iatrogenic immune
suppression, reactivation of VZV leads to herpes zoster. Similarly, the magnitude of
these responses early after the onset of herpes zoster correlates with the extent of
zoster-associated pain. These essential immune responses are boosted by the VZV
vaccine developed to prevent herpes zoster. (Weinberg, 2010)
The primary infection with VZV is varicella (chickenpox), and its secondary
infection is zoster (shingles). During varicella, latent infection with VZV develops
due to infection of neurons from the skin vesicles (Chen J, et al., 2003) Weeks to
years later, in the setting of a decrease in the cell-mediated immune (CMI) response to
VZV, reactivation of the virus may occur, resulting in clinical zoster. CMI to VZV
may be compromised by ageing and/or illness and treatment, for example after cancer
3

chemotherapy or transplantation. In places where varicella vaccine is not commonly

used, varicella is usually a disease of children, and zoster a disease of adults. (Oxman
MN, et al., 2006)
The initial resistance that innate immunity provides has been postulated to slow
viral multiplication, thereby providing time for the development of adaptive
immunity, which nally controls multiplication of the virus (Arvin et al., 2010). The
ability of innate immunity to slow the spread of VZV backs up the diversion of VZV
to late endosomes during envelopment in infected cells, which ensures slow cell-tocell transmission, and thus provides a fail-safemechanismto prevent VZV
fromoverwhelming its host. Thesemechanisms, which promote host survival, thus
confer an evolutionary advantage to the virus (Chen JJ et al., 2004)
Primary varicella-zoster virus (VZV) infection (varicella) induces VZV-specific
antibody and VZV-specific T cell-mediated immunity. T cell-mediated immunity,
which is detected within 12 weeks after appearance of rash, and consists of both
CD4 and CD8 effector and memory T cells, is essential for recovery from varicella.
Administration of a varicella vaccine also generates VZV-specific humoral and
cellular immune responses. (Weinberg, 2010)
During lytic infection, each of the 72 genes (open reading frames [ORFs])
ofVZVis expressed in a relatively orderly cascade. These include immediate early
(regulatory), early, and late (structural) genes. At least 9 glycoproteins (gps) are
encoded in the VZV genome.Major gps include gE,which forms a complexwith gI,
the gH/gL complex, gB, and gC.Most of these gps play a role in infectivity of the
virus, enabling the agent to spread from an infected cell to a naive one. The gps also
stimulate immune responses in an infected host. Although the precise natures of
protective humoral and cellular immune responses are unclear, gE is likely to be an
important antigen because it is the major gp that VZV expresses. (Anne & Michael
Gerson, 2013)
Because of

this high frequency of

immunity, contact with chickenpox

among pregnant women rarely results in primary maternal VZV infection, which is
estimated to complicate up to 2 to 3 of every 1000 pregnancies. (Enders et al., 1994)
Being born and raised in a country, living there for more than a year, and years
lived abroad, were associated with lower im-munity. Age, siblings with varicella
history, subject/sibling attending nursery, having a child who attendednursery,
household exposure to varicella (as an adult),previous/current employment, health of
children atwork were associated with increased immunity. (Talukder et al., 2007)
4

2. Varicella Infection in Pregnancy: Maternal

During VZV viremia, which may last for some days, VZV-infected immune cells,
which home to the skin, carry infection to keratinocytes. This viremia may also infect
other cells and tissues in the body. Innate immunity, involving production of alpha
interferon, transiently controls themultiplication of VZV in the skin, but eventually
innate resistance in skin is overcome, resulting in the development of cutaneous
lesions. (Ku CC et al., 2005)
The mortality rate for chickenpox increases with age. Thus in early adulthood it is
associated with mortality rate that is 1,5 times higher than the childhood mortality
rate. (Rouse et al., 1996)
Mortality rates are higher in pregnant women than in non-pregnant adults, and
death usually results from respiratory disease. It is estimated that 5% to 10% of
pregnant women with varicella infection develop pneumonitis.(Paryani & Arvin,
1986)
Most of the complications of adult chickenpox, such as pneumonitis occur on
day 4 or later. (Grose, 1999) In one prospective study, 12 out 21 pregnant patients
who were diagnosed with varicella pneumonitis and treated with acyclovir in the
second or third trimester of

pregnancy required intubation and mechanical

ventilation. The strongest correlate with maternal death was onset of disease in the
third trimester, with no deaths among the second-trimester subjects (Smego &
Aperilla, 1991)
3. Varicella Infection in Pregnancy: Fetal
Maternal varicella during the irst half of pregnancy may cause congenital
malformations or deformations by transplacental infection. Some of

these

manifestations include chorioretinitis, cerebral cortical atrophy, hydronephrosis, and

cutaneous and bony leg defects, often presenting as a partial limb reduction.
(Andrews, 2004)
Findings

that

can

be

seen

on

ultrasound

include musculoskeletal

abnormalities seen as asymmetric limb shortening or malformations, chest wall

malformations, intestinal and hepatic echogenic foci, intrauterine growth restriction,
polyhydramnios, fetal hydrops, or fetal demise. Cerebral anomalies documented with
ultrasound

include ventriculomegaly,

hydrocephalus,

microcephaly

with
5

polymicrogyria, and porencephaly. Congenital cataract and microphthalmos are the

most common ocular lesions but are not readily visible on ultrasound. (Degani,
2006)
A congenital varicella syndrome occurs in about 2% of the offspring
ofwomenwho develop varicella between the 8th and the 26th weeks of pregnancy
(58). Affected infants manifest a variety of problems, including scarring of the skin,
severe damage to the central and autonomic nervous systems, eye involvement, and
limb abnormalities. Children born with the congenital varicella syndrome often do not
survive infancy, and if they do, they are highly likely to develop HZ early in life.
(Anne & Michael Gerson, 2013)
IgG antibody was present at birth in all babies born more than 7 days after the
onset of maternal chickenpox. When the mother's rash appeared 7-3 days before
delivery progressively fewer babies were born with antibody, and no infant born less
than 3 days after the onset had antibody at birth. (Miller Elizabeth et al., 1989) When
the virus is most likely to damage the developing neural tissues anatomic locakle and
possibly before the production of fetal IgM antibodies specific for virus. (Anne et al.,
1994)
4. Prevention of Maternal Complication
In one study, oral acyclovir was shown to be more effective than placebo in
reducing the duration of

fever and symptoms of

varicella

infection

in

immunocompromised children and immunocompetent adults if commenced within

24 hours of development of the rash. As a result it is generally recommended that
children at high risk and adults with a substantive varicella infection (> 100 lesions)
and/or respiratory co-factors should be treated with oral antivirals. Pregnant
women with varicella pneumonitis should deinitely be treated with oral antivirals
and, if level of illness warrants, with IV antivirals. (SGOC, 2012)
A VZV-induced vasculopathy, which may accompany HZ or occur without a
rash,mimics giant cell arteritis of cerebral arteries (70). This is a serious condition that
may present as a cerebrovas cular accident, disturbed vision or blindness, and/or
transient ischemic attacks. Diagnosis can be made if the temporal artery is biopsied;
VZV DNA can be detected, and immunocytochemistry can reveal viral proteins if the
condition is due to VZV.Measurement of antibodies to VZV, including calculation of

serum/cerebrospinal uid (CSF) specic IgG ratios, may also be used to implicate
VZV in this neurologic disease. (Anne & Michael Gerson, 2013)
5. Prevention of Intrauterine Infection
Direct contact exposure is defined as direct contact that lasts an hour or
longer with an infectious person while indoors. Substantial exposure for hospital
contacts consists of sharing the same hospital room with an infectious patient
or prolonged, direct, face-to-face contact with an infectious person (e.g., health
care workers). Brief contacts with an infectious person (e.g., contact with X-ray
technicians or housekeeping personnel) are less likely than more prolonged
contacts to result in VZV transmission. Persons with continuous exposure to
household members who have varicella are at greatest risk for infection. (SGOC,
2012)
The introduction of the routine use of varicella vaccine in theUnited States has
caused this syndrome to become extremely rare in the United States. Because of the
resistance to vaccination in other countries and the absence of herd immunity to VZV
in those locations, the congenital varicella syndrome has not totally vanished; itmight
also be imported as a result of international travel. (Anne & Michael Gerson, 2013)

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