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Lecture 38

TORCH Infection in Pregnant Women

Dr. dr. I.B.G. Fajar Manuaba, Sp.OG, MARS
Department Obstetric and Gynaecology of Medical Faculty
Udayana University

Infections have historically been a major cause of maternal and fetal morbidity and
mortality worldwide, and they remain so in the 21st century. The unique maternal-fetal
vascular connection in some cases serves to protect the fetus from infectious agents,
whereas in other instances it provides a conduit for their transmission to the fetus.
TORCH infections include infections associated with Toxoplasma, Other organisms
(Parvovirus, human immunodeficiency virus, Epstein-Barr virus, herpesviruses 6 and
8, varicella, syphilis, enteroviruses), Rubella, Cytomegalovirus (CMV), and Hepatitis.
Despite the recent emphasis in the screening, antibiotic prophylaxis, and management
of early-onset many neonates and children yearly experience the consequences of
classic perinatal infections

Infections have historically been a major cause of maternal and fetal morbidity and
mortality worldwide, and they remain so in the 21st century. The unique maternal-fetal
vascular connection in some cases serves to protect the fetus from infectious agents,
whereas in other instances it provides a conduit for their transmission to the fetus.
Maternal serological status, gestational age at the time infection is acquired, the mode
of acquisition, and the immunological status of both the mother and her fetus all
influence disease outcome.

TORCH is an acronym for a group of congenitally acquired infections that may cause
significant morbidity and mortality in neonates. TORCH infections include infections
associated with Toxoplasma, Other organisms (Parvovirus, human immunodeficiency
virus, Epstein-Barr virus, herpesviruses 6 and 8, varicella, syphilis, enteroviruses),
Rubella, Cytomegalovirus (CMV), and Hepatitis. Despite the recent emphasis in the
screening, antibiotic prophylaxis, and management of early-onset many neonates and
children yearly experience the consequences of classic perinatal infections.

The obligate intracellular parasite Toxoplasma gondii has a life cycle with two distinct
stages. The feline stage takes place in the catthe definitive hostand its prey.
Unsporulated oocysts are secreted in feces. In the non-feline stage, tissue cysts
containing bradyzoites or oocysts are ingested by the intermediate host, including
humans. Human infection is acquired by eating raw or undercooked meat infected with
tissue cysts or by contact with oocysts from cat feces in contaminated litter, soil, or
water. Prior infection is confirmed by serological testing, and its prevalence depends
on geographic locale and parasite genotype.

Most acute maternal infections are subclinical and are detected only by prenatal or
newborn serological screening. In some cases, maternal symptoms may include
fatigue, fever, headache, muscle pain, and sometimes a maculopapular rash and

posterior cervical lymphadenopathy. The incidence and severity of fetal toxoplasmosis
infection depend on gestational age at the time of maternal infection. Risks for fetal
infection increase with pregnancy duration A metaanalysis estimated the risk to be 15
percent at 13 weeks, 44 percent at 26 weeks, and 71 percent at 36 weeks. Conversely,
the severity of fetal infection is much greater in early pregnancy, and these fetuses are
much more likely to have clinical findings of infection.

Pregnant women suspected of having toxoplasmosis should be tested. The parasite

is rarely detected in tissue or body fluids. Anti-toxoplasma IgG develops within 2 to 3
weeks after infection, peaks at 1 to 2 months, and usually persists for lifesometimes
in high titers. Although IgM antibodies appear by 10 days after infection and usually
become negative within 3 to 4 months, they may remain detectable for years. Thus,
IgM antibodies should not be used alone to diagnose acute toxoplasmosis. IgA and
IgE antibodies are also useful in diagnosing acute infection. Toxoplasma IgG avidity
increases with time. Thus, if a high-avidity IgG result is found, infection in the preceding
3 to 5 months is excluded. Multiple commercial avidity tests are now available that
provide a 100-percent positive predictive value of high avidity confirming latent

No randomized clinical trials have been performed to assess the benefit and efficacy
of treatment to decrease the risk for congenital infection. A systematic review of data
from 1.438 treated pregnancies found weak evidence for early treatment to reduce
congenital toxoplasmosis risks. Treatment has been associated with a reduction in
rates of serious neurological sequelae and neonatal demise.

Prenatal treatment is based on two regimensspiramycin alone or a pyrimethamine

sulfonamide combination with folinic acid. These two regimens have also been used
consecutively. Little evidence supports the use of a specific regimen. That said, most
experts will use spiramycin in women with acute infection early in pregnancy.
Pyrimethaminesulfadiazine with folinic acid is selected for maternal infection after 18
weeks or if fetal infection is suspected.

Human parvovirus B19 causes erythema infectiosum, or fifth disease. The B19 virus
is a small, single-stranded DNA virus that replicates in rapidly proliferating cells such
as erythroblast precursors. This can lead to anemia, which is its primary fetal effect.
Only individuals with the erythrocyte globoside membrane P antigen are susceptible.
In women with severe hemolytic anemiafor example, sickle-cell disease
parvovirus infection may cause an aplastic crisis.

In 20 to 30 percent of adults, infection is asymptomatic. Fever, headache, and flu-like

symptoms may begin in the last few days of the viremic phase. Several days later, a
bright red rash with erythroderma affects the face and gives a

slappedcheekappearance. The rash becomes lacelike and spreads to the trunk and
extremities. Adults often have milder rashes and develop symmetrical polyarthralgia
that may persist several weeks.

There is vertical transmission to the fetus in up to a third of maternal parvovirus

infections Fetal infection has been associated with abortion, nonimmune hydrops, and
stillbirth. In a review of 1089 cases of maternal B19 infection from nine studies, Crane
(2002) reported an overall fetal loss rate of 10 percent. It was 15 percent for infections
before 20 weeks but was only 2.3 percent after 20 weeks.

Depending on gestational age, fetal transfusion for hydrops may improve outcome in
some cases. Mortality rates as high as 30 percent have been reported in hydropic
fetuses without transfusions. With transfusion, 94 percent of hydrops cases resolve
within 6 to 12 weeks, and the overall mortality rate is < 10 percent. Most fetuses require
only one transfusion because hemopoiesis resumes as infection resolves.

There is currently no approved vaccine for human parvovirus B19, and there is no
evidence that antiviral treatment prevents maternal or fetal infection. Decisions to
avoid higher-risk work settings are complex and require assessment of exposure risks.
Pregnant women should be counseled that risks for infection approximate 5 percent
for casual, infrequent contact; 20 percent for intense, prolonged work exposure such
as for teachers; and 50 percent for close, frequent interaction such as in the home.
Workers at day-care centers and schools need not avoid infected children because
infectivity is greatest before clinical illness. Finally, infected children do not require

RubellaGerman Measles
This RNA togavirus typically causes infections of minor importance in the absence of
pregnancy. Rubella infection in the first trimester, however, poses significant risk for
abortion and severe congenital malformations. Transmission occurs via
nasopharyngeal secretions, and the transmission rate is 80 percent to susceptible
individuals. The peak incidence is late winter and spring.

Maternal rubella infection is usually a mild, febrile illness with a generalized

maculopapular rash beginning on the face and spreading to the trunk and extremities.

Other symptoms may include arthralgias or arthritis, head and neck
lymphadenopathy,and conjunctivitis. The incubation period is 12 to 23 days. Viremia
usually precedes clinical signs by about a week, and adults are infectious during
viremia and through 5 to 7 days of the rash. Up to half of maternal infections are
subclinical despite viremia that may cause devastating fetal infection.

Rubella may be isolated from the urine, blood, nasopharynx, and cerebrospinal fluid
for up to 2 weeks after rash onset. The diagnosis is usually made, however, with
serological analysis. Specific IgM antibody can be detected using enzyme-linked
immunoassay from 4 to 5 days after onset of clinical disease, but it can persist for up
to 6 weeks after appearance of the rash. Importantly, rubella reinfection can give rise
to transient low levels of IgM. Serum IgG antibody titers peak 1 to 2 weeks after rash
onset. This rapid antibody response may complicate serodiagnosis unless samples
are initially collected within a few days after the onset of the rash. If, for example, the
first specimen was obtained 10 days after the rash, detection of IgG antibodies would
fail to differentiate between very recent disease and preexisting immunity to rubella.
IgG avidity testing is performed concomitant with the serological tests above. High-
avidity IgG antibodies indicate an infection at least 2 months in the past.

Rubella is one of the most complete teratogens, and sequelae of fetal infection are
worst during organogenesis. Pregnant women with rubella infection and a rash during
the first 12 weeks of gestation have a fetus with congenital infection in up to 90 percent
of cases
At 13 to 14 weeks gestation, this incidence was 54 percent, and by the end of the
second trimester, it was 25 percent. Defects are rare after 20 weeks.

There is no specific treatment for rubella. Droplet precautions for 7 days after the onset
of the rash are recommended. Primary prevention relies on comprehensive
vaccination programs. To eradicate rubella and prevent congenital rubella syndrome
completely, a comprehensive approach is recommended for immunizing the adult
population. MMR vaccine should be offered to nonpregnant women of childbearing
age who do not have evidence of immunity whenever they make contact with the
health-care system. Vaccination of all susceptible hospital personnel who might be
exposed to patients with rubella or who might have contact with pregnant women is
important. Rubella vaccination should be avoided 1 month before or during pregnancy
because the vaccine contains attenuated live virus. Although there is a small overall
theoretical risk of up to 2.6 percent, there is no observed evidence that the vaccine
induces malformations. MMR vaccination is not an indication for pregnancy
termination. Prenatal serological screening for rubella is indicated for all pregnant
women. Women found to be nonimmune should be offered the MMR vaccine

This ubiquitous DNA herpes virus eventually infects most humans. Cytomegalovirus
(CMV) is the most common perinatal infection in the developed world. Specifically,
some evidence of fetal infection is found in 0.2 to 2.5 percent of all neonates. The virus
is secreted into all body fluids, and person-to-person contact with viral-laden saliva,
semen, urine, blood, and nasopharyngeal and cervical secretions can transmit
infection. The fetus may become infected by transplacental viremia, or the neonate is
infected at delivery or during breast feeding.

Primary maternal CMV infection is transmitted to the fetus in approximately 40 percent

of cases and can cause severe morbidity. In contrast, recurrent maternal infection
infects the fetus in only 0.15 to 1 percent of cases. A review of nine studies of CMV
vertical transmission rates reported first-trimester transmission in 36 percent, second-
trimester in 40 percent, and third-trimester in 65 percent. Naturally acquired immunity
during pregnancy results in a 70-percent risk reduction of congenital CMV infection in
future pregnancies. However, as noted earlier, maternal immunity does not prevent
recurrences, and maternal antibodies do not prevent fetal infection. Also, some
seropositive women can be reinfected with a different viral strain that can cause fetal
infection and symptomatic congenital disease.
Routine prenatal CMV serological screening is currently not recommended. Pregnant
women should be tested for CMV if they present with a mononucleosis-like illness or
if congenital infection is suspected based on abnormal sonographic findings. Primary
infection is diagnosed using CMV-specific IgG testing of paired acute and
convalescent sera. CMV IgM does not accurately reflect timing of seroconversion
because IgM antibody levels may be elevated for more than a year. Moreover, CMV
IgM may be found with reactivation disease or reinfection with a new strain. Thus,
specific CMV IgG avidity testing is valuable in confirming primary CMV infection. High
anti-CMV IgG avidity indicates primary maternal infection > 6 months before testing.
Finally, viral culture may be useful, although a minimum of 21 days is required before
culture findings are considered negative.

Several fetal abnormalities associated with CMV infection may be seen with
sonography, computed tomography, or magnetic resonance imaging. In some cases,
they are found at the time of routine prenatal sonographic screening, but in others they
are part of a specific evaluation in women with CMV infection. Findings include
microcephaly, ventriculomegaly, and cerebral calcifications; ascites, hepatomegaly,
splenomegaly, and hyperechoic bowel; hydrops; and oligohydramnios.

The management of the immunocompetent pregnant woman with primary or recurrent

CMV is limited to symptomatic treatment. If recent primary CMV infection is confirmed,
amnionic fluid analysis should be offered. Counseling regarding fetal outcome
depends on the gestation age during which primary infection is documented. Even
with the high infection rate with primary infection in the first half of pregnancy, most
fetuses develop normally.

There is no CMV vaccine. Prevention of congenital infection relies on avoiding

maternal primary infection, especially in early pregnancy. Basic measures such as
good hygiene and hand washing have been promoted, particularly for women with
toddlers in day-care settings. Although there may be sexual transmission from infected
partners, there are no data on the efficacy of preventive strategies.

Hepatitis B
Chronic hepatitis B virus (HBV) infection is estimated to affect >350 million people
worldwide and represents a significant cause of morbidity and mortality related to
cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV
remains an important source of incident cases of HBV. Current barriers to eradication
of incident HBV infections via MTCT include underutilization of immunoprophylaxis
with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions
as well as failure of immunoprophylaxis.

Hepatitis B perinatal transmission remains a common mode of viral transmission,

especially in highly endemic areas globally.The availability over the past decade of
effective oral agents that suppress viral replication has allowed the consideration of
thirdtrimester treatment to reduce the risk of this transmission. This is important,
particularly in pregnant women with very high viral levels (>108 copies/mL or 2 107
IU/mL), in whom the risk is highest, but transmission can occur even at levels >200
000 IU/mL. Treatment decisions necessitate careful discussion of risks and benefits
as emerging data suggest some possible effect on bone mineral concentration in
tenofovir-exposed pregnant women, which must be balanced by a nearly 10% risk of
chronic infection with an incurable virus. Pregnant women with HBV must be
monitored for clinical flares, with or without medications, and breastfeeding should be
allowed as well.

In the absence of HBV immunoprophylaxis, 10 to 20 percent of women positive for

HBsAg transmit viral infection to their infant. This rate increases to almost 90 percent
if the mother is HBsAg and HBeAg positive. Immunoprophylaxis and hepatitis B
vaccine given to infants born to HBV-infected mothers has decreased transmission
dramatically and prevented approximately 90 percent of infections.

Hepatitis C
Hepatitis C virus (HCV) is a well known cause of chronic liver disease in adults, but
the burden of HCV in pregnant women and children is underappreciated. The leading
route of HCV acquisition in children is vertical transmission.

Women with chronic HCV infection often have uneventful pregnancies without
worsening of liver disease or other maternal or infant adverse effects; some women
mayeven have improvement. For example, in a series of 266 pregnant women infected
with HCV, elevated serum alanine aminotransferase (ALT) levels were detected in
56% of women at the beginning of pregnancy but only 7% during the third trimester.
However, 55% of women returned to elevated ALT levels by 6 months postpartum.
Such changes may be due to the significant changes in the maternal immune system
during pregnancy.

Infants born to women infected with HCV were more likely to be low birth weight, small
for gestational age, and require neonatal intensive care and assisted ventilation. In the
same cohort, women infected with HCV had an increased risk for gestational diabetes
but only when combined with excessive gestational weight gain.

There is currently no licensed vaccine for HCV prevention. The chronic HCV infection
treatment has traditionally included alpha interferon (standard and pegylated), alone
or in combination with ribavirin. This regimen is contraindicated in pregnancy because
of the teratogenic potential of ribavirin in animals.

Learning task
1. What is IgG avidity ? Who important this result for the treatment scenario ?
2. Describe about indication, side effect, effective dose, contra indication of
spiramycin ?
3. How to protect pregnant women from Parvovirus infection ?
4. Describe about MMR vaccination ?
5. How to protect pregnant women from Cytomegalovirus infection ?

Self assement
1. Explain how to manage pregnant women with human immunodeficiency virus ?
2. Explain how to manage pregnant women with Epstein-Barr virus ?
3. Explain how to manage pregnant women with herpesviruses 6 and 8 ?
4. Explain how to manage pregnant women with varicella ?
5. Explain how to manage pregnant women with syphilis ?
6. Explain how to manage pregnant women with enteroviruses ?