17.TORCH infections notes for medical students.ppt

TORCH infections
TORCH infections

TORCH infections
TORCH infections
T – Toxoplasmosis
O – Other T. pallidum, Varicella- zoster virus
(VZV), Parvovirus B19
R – Rubellavirus
C – Cytomagalovirus (CMV)
H – Herpes Simplex Virus (HSV)

Toxoplasmosis
Toxoplasmosis
Epidemiology
Epidemiology
Toxoplasma gondii-intracellular parasite that exists in three forms
◦ Oocysts: form in the intestine of the cat and are excreted in large numbers in the stool. To
become infectious cysts must undergo sporulation-a process that takes 2-3 days in temperate
climates and no longer in cold climates-the risk of infection is minimized if cat litter boxes are
cleaned daily.
◦ Tachyzoites: flagellated proliferative forms released from the oocyst. They invade and
replicate within cells, and are responsible for tissue destruction. Tachyzoites divide rapidly and
their multiplication continues until either cyst formation or host cell destruction occurs. After cell
death, the free tachyzoites invade other cells and resume rapid multiplication. Tachyzoites
invade all organs, especially the muscles (including heart), liver, spleen, lymph nodes
and CNS.
◦ Bradyzoites: are slowly multiplying organisms contained in tissue cysts during latent infection,
usually localized to muscle (skeletal and cardiac) and brain. They live in their host cells for months
or years. Once ingested, gastric enzymes degrade the cyst wall, liberating viable bradyzoites.

Toxoplasmosis
Toxoplasmosis
Epidemiology
Epidemiology
Sporulated and unsporulated oocyst
The tachyzoites are elongate and crescent-shaped.
The cyst with many bradyzoites.
Prior to the development of host immunity, the trachyzoites
replicate within the vacuole leading to rupture of the cell
and infection of adjacent cells.
After the host immunity developed, the parasite
forms the tissue cyst within the vacuole, that
despite on occasion being quite large doesn’t lead
to rupture of the cell.

Pathways for Toxoplasma gondii infection. The feline intestinal tract is the only source for
the production of T. gondii oocysts. Transmission to humans usually occurs through the
ingestion of oocysts from contaminated sources (e.g., soil, cat litter, garden vegetables, water)
or the ingestion of tissue cysts in undercooked meat from infected animals. Although fetal
infection most often occurs after acute T. gondii infection in a pregnant woman, it also can
occur after the reactivation of latent infection in an immunocompromised pregnant women.

Toxoplasmosis
Toxoplasmosis
Incidence
Incidence
 Neonatal infection occurs in approximately 1-2/1000 births.
 Likelihood of infection and severity of symptoms depends on when in gestation the
mom is infected.
◦ The overall risk of congenital infection from acute T. gondii infection during pregnancy ranges
from approximately 20% to 50%
◦ The risk of congenital disease is lowest (10%-25%) when maternal infection occurs during the
first trimester
◦ The later in pregnancy the mom is infected, the greater the likelihood that the placenta and
fetus will be infected. If infection of mother occurs in the last month of pregnancy,
almost 90% of the placentas will have demonstrable infection
◦ However, congenital disease is more severe when infection is acquired in the first
trimester.

Toxoplasmosis
Toxoplasmosis
Presentations
Presentations
 Primary infection in an otherwise healthy pregnant women is asymptomatic
in 60% of cases.
◦ If symptoms are present in the mother, they are usually limited to lyphadenopathy
and fatigue without fever.
 Greater than 75% neonates are asymptomatic in early infancy
• The classic triad of congenital toxoplasmosis
◦ Chorioretinitis
◦ Hydrocephalus
◦ Intracranial calcifications (CHI)
◦ Neonatal disease- systemic illness in neonate
◦ Early disease- well infant, symptoms during first few months of life
◦ Subclinical disease- well infant, subclinical infection, symptoms later in childhood

Toxoplasmosis
Toxoplasmosis
Clinical Manifestations
Neonatal disease
◦ Onset at birth
◦ Hepatosplenomegaly with jaundice and hepatitis
◦ CNS involvement in almost all
 Microcephaly
 Necrosis and inflammation of basal ganglia and periventricular region. Cyst
formation with calcification occurs.
 Periaqueductal and periventricular vasculitis with sloughing of cells, increase
CSF protein, with obstruction of aqueduct and hydrocephalus
◦ Eye involvement
 Chorioretinitis with secondary iridocyclitis
 Cataracts
 Microphthalmia

Toxoplasmosis
Toxoplasmosis
Neonatal disease
◦ Congenital deafness
◦ Myocarditis and pneumonitis
◦ Lymphadenopathy
◦ Anemia, thrombocytopenia
◦ Cutaneous lesions
 Blueberry muffin lesions due to dermal erythropoiesis typically within first
few days of life
◦ 12% mortality rate
◦ Over 85% of survivors will have some degree of impairment
with blindness, deafness and mental retardation

Toxoplasmosis
Toxoplasmosis
Clinical Manifestations``
Clinical Manifestations``
Early disease
◦ Usually with onset in the first months of life
◦ In term infants the course is usually milder, with hepatosplenomegaly and
lymphadenopathy in the first two months of life
◦ Premature infants may develop severe CNS and ocular disease in the first three
months of life.
Subclinical disease or infants with late onset symptoms in infancy or
childhood
◦ Most of these patients will develop some evidence of chorioretinitis
◦ Although mental retardation, microcephaly, and deafness have been reported, these
are not seen as commonly as chorioretinitis

Computed tomography of the brain in a neonate
with toxoplasmosis demonstrating many
intraparenchymal and periventricular
calcifications.
Interstitial pneumonitis in the medial
aspects of the lung bases, as well as
hepatosplenomegaly in an infant with
generalized T. gondii infection.
Congenital toxoplasmosis

Toxoplasma chorioretinitis
Congenital toxoplasmosis
Cerebral hemispheres are almost
completely destroyed except for the
temporal lobes

Intracranial calcifications in congenital toxoplasmosis.
(A) Posterior-anterior
(B) lateral views of the skull showing scattered bilateral calcific
flecks, nodules and linear streaks in frontal and parietal lobes
of an infected infant

Congenital toxoplasmosis with intracranial hyrocephalus.
The grossly dilated lateral ventricles are outlined with air on (A) AP and (B) lateral
radiographs after pneumoencephalography. There is spreading of the cranial sutures due
to increased intracranial pressure. There is extensive calcification lining the walls of the
dilated lateral ventricles, mimicking exactly the intracranial calcifications seen in
cytomegaloviral infections.

Toxoplasmosis
Toxoplasmosis
Diagnostic Tests
Diagnostic Tests
Screening:
.
◦ Screening may have equivocal or false positive results that could
lead to inappropriate treatment or the termination of
pregnancy-because of the low incidence in the US the risk to
the fetus would be greater from routine screening than from no
screening.
 ACOG recommends toxoplasmosis screening only in high-risk
persons (owning a cat, cleaning a cat litter box, eating raw or
undercooked meat) or those in whom routine ultrasound
examination shows findings such as hydrocephalus, intracranial
calcifications, microcephaly, fetal growth retardation, ascites or
hepatosplenomegaly.
 Women with HIV infection should always be screened for
toxoplasmosis because of the risk of T. gondii reactivation and
toxoplasmic encephalitis.

Toxoplasmosis
Toxoplasmosis
Diagnostic Tests
Diagnostic Tests
Pregnant women:
◦ IgG specific antibodies indicate that infection has occurred, but does
not distinguish between recent infection and infection acquired in the
distant past
 achieve a peak concentration 1 to 2 months after infection and remain
positive indefinitely
◦ IgM T. gondii specific antibodies may indicate acute or recent infection
 Can be detected 2 weeks after infection, achieve peak concentrations in 1
month, decrease thereafter, and usually become undetectable within 6 to 9
months
◦ IgA and IgE antibodies
 Decrease to undetectable concentrations sooner than IgM antibodies
 Useful in pregnant women for whom more precise information about the
duration of infection is needed

Toxoplasmosis
Toxoplasmosis
Diagnostic Tests
Diagnostic Tests
Prenatal
 A definite diagnosis of congenital toxoplasmosis can be made prenatally
by:
◦ detecting the parasite in fetal blood, umbilical cord blood, amniotic fluid or
placenta
◦ documenting the presence of T.gondii IgM or IgA antibodies in fetal blood
◦ detection of T.gondii DNA in amniotic fluid by PCR assay-safe and accurate
method- most common method
 Ultrasonographic examinations- ventricular dilatation, ascites,
hepatomegaly, intracranial calcifications

Toxoplasmosis
Toxoplasmosis
Diagnostic Tests
Diagnostic Tests
Postnatal
 If the diagnosis for an infant is unclear at the time of delivery, evaluation of the
infant should include
◦ ophthalmologic, auditory, and neurologic examinations
◦ lumbar puncture
◦ CT of the head
 Peripheral blood, CSF and amniotic fluid specimens should by assayed for T.gondii
by PCR in a reference laboratory.
 Congenital infection is serologically confirmed on the basis of positive IgM or IgA
assay within the first 6 months of life or persistently positive IgG titers beyond the
first 12 months of life.
 In an uninfected infant, a continues decrease in IgG titer without IgM or IgA will
occur. Transplacentally transmitted IgG antibody usually will become undetectable
by 6 to 12 months of age.

Toxoplasmosis
Toxoplasmosis
Treatment
Treatment
 If mother infected
◦ Treat with Spiramycin (Rovamycine) during pregnancy to attempt to
decrease transmission rate
◦ This treatment appears to reduce the likelihood of congenital
transmission to the fetus by as much as 50%
◦ Does not appear to treat established disease in the fetus

Toxoplasmosis
Toxoplasmosis
Treatment
Treatment
 If mother and fetus infected
◦ Treat with Pyrimethamine and Sulfadiazine to attempt to decrease fetal
effects
◦ Folinic acid (Leucovorin) must be taken with this treatment to prevent
neutropenia from Pyrimethamine
 If symptomatic or asymptomatic infected neonate
◦ Treatment in newborns is complicated and prolonged, requiring up to a
year of Pyrimethamine, Sulfadiazine and Folinic acid.
◦ Monitor with: ophthalmologic exams, head imaging, CBC and diff, UA,
creatinine, toxo IgG and IgM levels
◦ Consider consultation with infectious disease specialist

Toxoplasmosis
Toxoplasmosis
Prognosis
Prognosis
 Normal development in 70% of
treated infants despite initial
neurological symptoms
 Poor outcome if delayed
diagnosis and/or delayed
treatment

Syphilis
Syphilis
Epidemiology
Epidemiology
 Congenital syphilis occurs when the spirochete Treponema pallidum is
transmitted from a pregnant women to her fetus.
 Incidence in U.S. increased during 1980’s and 1990’s (in 1991 107 cases per
100,000 live births), and declined by 90.5% to 10 cases/per 100,000 live
births in 2002.
 Untreated infection can result in stillbirth (among women with
untreated early syphilis 40% of pregnancies result in spontaneous
abortion), hydrops fetalis, or prematurity and associated long-term
morbidity.
 Most congenital cases are due to lack of prenatal care, but a negative test in
the first trimester of pregnancy that was not repeated later in pregnancy as well as
inadequate maternal treatment are also important contributing factors.

Syphilis
Syphilis
Epidemiology
Epidemiology
Transmission
 Transplacental route in majority
◦ T. pallidum readily crosses the placenta; vertical
transmission can occur at any time during pregnancy (as
early as six weeks of gestation) or at birth
◦ Can be transferred and infect the fetus at any stage of the
disease; risk to fetus 70-100% if untreated primary syphilis,
40% if early latent infection
◦ The greater the gestational age, greater risk of fetal
infection
 Can be acquired by contact with active lesion at delivery

Syphilis
Syphilis
 30-40% infected fetuses are stillborn
 Increased risk of nonimmune hydrops fetalis and IUGR
 Clinical manifestations after birth are divided into:
◦ Early CS (≤2 years of age)
◦ Late CS (>2 years of age)
 Early CS (≤2 years of age)
◦ 2/3 infants asymptomatic at birth; 1/3 symptomatic at birth
◦ May have unexplained large placenta
◦ Hepatosplenomegaly and/or generalized lymphadenopathy and/or
desquamating maculopapular rash (often involving palms and soles)

Syphilis
Syphilis
Early Congenital Syphilis
 Systems review:
◦ Respiratory: pneumonitis, persistent rhinitis “snuffles” (typically 1 week to 3
months of age)
◦ Dermatologic: cutaneous bullous eruptions, pigmented macules, desquamating
maculopapular rash
◦ Hematologic: hyperbilirubinemia, hemolytic anemia, thrombocytopenia,
leukopenia or leukocytosis
◦ Renal: nephrotic syndrome
◦ Ophthalmologic: chorioretinitis, uveitis
◦ Orthopedic: osteochondritis (Wimberger sign= bilateral destruction of proximal
medial metaphysis – tibia> humerus), periostitis
◦ Neurologic: Erb’s palsy, leptomeningitis

Syphilis
Syphilis
The earliest sign of CS is nasal discharge (snuffles) that occurs 1-2
weeks before the onset of the rash. Treponemes abound in the
discharge, providing a definitive means of diagnosis.

Syphilis
Syphilis
The vesiculobullous eruption, known as pemphigus syphiliticus, is
highly distinctive when present. When the bullae rupture, they
leave a macerated, dusky red surface that readily dries and
crusts.

Syphilis
Syphilis
Other stigmata seen before the age of 2 years include
maculopapular rash, hepatosplenomegaly and jaundice.

Syphilis
Syphilis
Diagnostic Tests
Diagnostic Tests
 Definitive diagnosis
◦ Made by identifying spirochetes by microscopic darkfield examination or direct
fluorescent antibody test of lesion exudates or tissue, such as placenta or
umbilical cord.
 Non-treponemal tests: VDRL and RPR
◦ Detect a cell membrane cardiolipin nonspecific IgG Ab, which is a sign of response to host tissue
damage
◦ Both are reported as titers; titers correlate with disease activity
◦ Used for screening, to evaluate therapy success, reinfection and relapse (RPR not appropriate for
CSF)
◦ Reactive in 75% adults with primary syphilis within 1-2 months of infection and reactive in all
with secondary infection
◦ Become negative 2 years following treatment
◦ Neonate has positive test if titer 4-fold higher than maternal titer

Syphilis
Syphilis
Diagnostic Tests
Diagnostic Tests
 Non-treponemal tests: VDRL and RPR
◦ False positive if connective tissue disease, autoimmune disorders,
TB, Ebstain-Barr virus, endocardiatis, passively transferred
maternal IgG antibody to neonate
◦ May be falsely negative = prozone phenomenon; secondary to excess
antibody in test sera which prevents antibody-antigen complex necessary
for reactive test; occurs in 1-2% of secondary syphilis; avoid by diluting
sera.
 Treponemal tests: fluorescent treponemal antibody absorption
(FTA-ABS)
◦ Confirmatory test that detects specific Ab (IgG or IgM) to Treponema
pallidum
◦ Positive for life even after therapy
◦ Does not correlate with disease activity
◦ False positive tests occur in patients with other spirochetal diseases
(Lyme disease) or if antinuclear antibody present (SLE)

Syphilis
Syphilis
Evaluation of Newborn Infant
 TEST ALL PREGNANT WOMEN FOR SYPHILIS
◦ Because of neonatal morbidity, great emphasis has been placed on routine
syphilis screening of all pregnant women.
 Evaluation of following neonates:
◦ Infant born to seropositive mother with untreated syphilis
◦ Mother treated for syphilis during pregnancy treated with
nonpenicillin regimen
◦ Treatment less than 30 days prior to delivery (since treatment failures
can occur)
◦ Mother treated appropriately during pregnancy without an appropriate
serologic response (≥4-fold decrease in titers)
◦ Mother treated appropriately before pregnancy but had insufficient
serological follow-up
◦ Symptomatic neonate

Syphilis
Syphilis
Evaluation includes:
◦ Physical examination; ophthalmologic exam
◦ Nontreponemal and treponemal serologic test for syphilis on infant’s serum sample
◦ Anti-treponemal IgM
◦ CSF VDRL, analysis of CSF
 Increased cell count, elevated CSF protein, positive VDRL
◦ Long bone x-rays
 Especially femur and humerus
◦ CBC, LFTs, direct bilirubin, UA

Syphilis
Syphilis
Treatment
Treatment
Penicillin is the gold standard for therapy: 10-14 day
treatment courses
Follow-up evaluation
◦ Non-treponemal antibody serologic testing should be
checked at 1, 3, 6, 12 and 24 months following treatment.
◦ Titers should decrease four-fold by 6 months post
therapy and become nonreactive by 12 to 24 months.
◦ Titers that show four-fold rise or do not decrease
suggests either treatment failure or re-infection.

Rubella
Rubella
Epidemiology
Epidemiology
 Known as a German measles, usually results in a mild illness in adults and
children but can have serious consequences when fetus is infected
 Reported cases of rubella have decreased dramatically since a vaccine (MMR)
became available in 1969 (the annual number of reported rubella and CRS cases in
the US decreased by 99.6% and 97.4 %, respectively)
 Only 4 cases of CRS were reported in the US during 2001 to 2004. In the
fall 2005 Centers for Disease Control and Prevention concluded that
rubella and CRS are no longer endemic in the US
 However, cases continue to occur among infants born to women who emigrated
from countries without, or only recently implemented rubella control programs.

Rubella
Rubella
Epidemiology
Epidemiology
 Risk of fetal infection is possible throughout pregnancy, but the risk of
infection and the manifestations depend on the time in gestation when
maternal infection occurs
 Risk of infection is highest in the first trimester, and lowest in the
second trimester, rising again in the third trimester
 Risk of congenital defects may be as high as 85% for those infected in
the period of time from 1 month before conception through the first 8
weeks of gestation. The risk of any congenital defects from
infection is low after 20 weeks of gestation

Rubella
Rubella
The rate of fetal infection in relation to gestational age
The rate of fetal infection in relation to gestational age

Congenital Rubella Syndrome
 In utero – hydrops
 General
◦ Infants usually born at term; ~ 60% IUGR, poor growth postnatally
 Hearing loss-the most common isolated sequela (65-75%)
◦ Occurs if maternal infection < 20 weeks gestation
 Heart defects (50%)
◦ If infection <8 weeks gestation
◦ PDA; peripheral pulmonic stenosis; aortic stenosis; valve abnormalities; TOF; myocarditis
 Cataracts
◦ Additional ocular findings are: pigmentary retinopathy (salt and pepper chorioretinitis), microphthalmia and strabismus
 Skin lesions-”blueberry muffin” rash
◦ Represent extramedullary hematopoesis within the skin
 Hematologic
◦ Thrombocytopenia, hemolytic anemia
 Neurologic
◦ Microcephaly (5%); meningoencephalitis; hypotonia; behavioral disorders and mental retardation
 Other
◦ Radiolucent bone disease- “celery stalking” of long bone metaphyses
◦ Interstitial pneumonia, myositis
◦ Hepatosplenomegaly, hepatitis

Congenital Rubella Syndrome Clinical
Clinical
Manifestations
Manifestations
The classic triad:
Deafness
Cataracts
Congenital heart disease

Rubella
Rubella
Diagnosis
Diagnosis
Evaluation of newborn with clinical findings suggestive of CRS:
 Maternal history (evidence of rubella immunity)
 Physical stigmata consistent with the syndrome
◦ more than 60% infants show at least three manifestations
 Viral diagnosis
◦ Rubella virus is readily cultured from the oro/nasopharynx in the first several weeks of life
◦ Virus can be also isolated from blood, urine, CSF
 Serology
◦ Elevated cord blood specific IgM titers, infant’s serum IgM levels and serial IgG levels
 Cardiac evaluation
 CBC and PLT count; Lumbar puncture
 Radiographs of long bones; Head imaging (ultrasound or CT)
 Audiologic evaluation
 Ophthalmologic evaluation

Rubella
Rubella
Management
Management
 The best therapy for CRS is prevention
◦ Every pregnant women should be tested for rubella immunity
◦ All girls should be vaccinated against rubella before entering the childbearing
years
 In women with confirmed rubella infection in pregnancy, management principally
consist counseling about the risk and types of congenital anomalies
◦ The classic findings of CRS in the newborn are most prominent when the
onset of maternal infection occurs during the first 8 weeks of gestation
 Only 36% of these pregnancies result in a normal live birth
 39% in abortion or stillbirth
 25% in significant congenital defects
 Congenital defects have been estimated to occur in 61% when maternal
infection develops in the first 4 weeks of gestation; 26% in weeks 5 through
8; and 8% in weeks 9 through 12.

Rubella
Rubella
Management
Management
 Rubella vaccination of NI pregnant women is not recommended
◦ Inadvertent administration of vaccine- risk of subclinical fetal infection is 1.6%, but
no congenital defects have been reported from first trimester vaccine
 Rubella vaccine is recommended to be given after delivery for seronegative women,
even if these women are breastfeeding
 No contraindication to breast-feeding if mother with rubella infection
 Neonate with congenital rubella infection
◦ Currently no available medical therapy; treatment of newborn is supportive
◦ Isolate neonate from other newborns
◦ May be contagious for 1 year unless repeat urine and blood cultures are negative
 Congenital rubella is a chronic infection with viral shedding for months after
delivery

Cytomegalovirus
Cytomegalovirus

CMV
CMV
Epidemiology
Epidemiology
 Member of the herpes virus family and has the largest DNA genome of any known
viruses; intracellular and cytoplasmic inclusions
 CMV is endemic and infects almost all humans at some point in their lives, ~ 2-2.5%
seroconvert during pregnancy
 CMV infection at any age is usually asymptomatic
 After a period of active replication, the virus usually becomes latent but retains the
capability of reactivation under special circumstances – such reactivation occurs
commonly during pregnancy
◦ shedding in urine and other secretions occurs for a period of months to years before the virus
enters a latent phase
 Most common congenital viral infection in developed countries; perinatal or postnatal
infection is also common but rarely results in symptomatic infection

CMV
CMV
Incidence
Incidence
 The most common intrauterine infection worldwide
 If maternal primary CMV- transpalcentally 30-40% fetuses infected with
only 10% symptomatic at birth
◦ If symptomatic: 20-30% mortality; 90% with sequelae
◦ If asymptomatic at birth: minimal mortality; 5-15% with sequelae
 If maternal secondary CMV/recurrent CMV
◦ 1% fetuses infected
◦ Almost all asymptomatic at birth
◦ Less morbidity to neonate than if exposure to primary maternal CMV infection
 If maternal infection is during first ½ of pregnancy, greater risk of neonatal
disease and greater severity of neonatal illness

CMV
CMV
Transmission
Transmission
 Secretions (requires close contact)
 Sexual intercourse
 Blood products
 Transplacental (all trimesters)
 Intrapartum
 CMV can also be transmitted via human milk
◦ uncommon due to passively transferred maternal antibodies
◦ decreased risk if pasteurization or freezing
◦ Increased risk if premature infant

CMV
CMV
Congenital CMV (transplacental transmission)
• Usually due to primary maternal infection at time of conception
• Most (90%) asymptomatic at birth
• Jaundice (62%); Hepatosplenomegaly (50%)
• Thrombocytopenia/Petechiae (58%);
• IUGR (33%); Preterm (25%)
• Microcephaly (21%); periventricular calcifications
• High likelihood long-term neurological sequelae (45%)
• Mental deficiency, seizures
• Hearing loss
• correlates with presence of periventricular calcifications
• sensorineural, often bilateral; moderate to profound
• often progressive and may not be detected until > 1 year of age
• Increased risk of cavities due to abnormal tooth enamel
• Chorioretinitis (20%)
• Dermal hematopoesis (blueberry muffin rash)
• Inguinal hernias
• DIC, liver failure, sepsis, possible death

CMV
CMV
Perinatal
◦ If infants are infected by this route, it is almost always due to maternal
shedding as a result of reactivation of a latent viral infection
◦ Breast feeding infants have a 30-70% risk of becoming infected if mother is
excreting virus in her breast milk
◦ Contact with infected secretions in the vagina during delivery results in
infection in 30-50% of infants
Acquired
◦ Transfusion associated, can be prevented through the use of CMV
seronegative donors
◦ Preterm infants < 1500 gm appear to be at greatest risk; mortality of~20% -
the result of a severe pneumonitis

CMV
CMV
Perinatal and Acquired
 Incubation period 4-12 weeks
 Can lead to pneumonitis
 Possible sepsis
 Hepatosplenomegaly
 Thrombocytopenia
 Microcephaly
 Hearing loss

CMV
CMV
Diagnosis
Diagnosis
 The definitive diagnosis
◦ Viral culture from urine or other body fluids (results in 2-6 weeks)
◦ Spin-enhanced culture or shell virus (results in 1-2 days)
 Less definitive test
◦ Increase in IgG titers by 4-fold and positive IgM anti-CMV
Prenatal evidence of fetal infection
 US
◦ Microcephaly, ventricular dilatation, periventricular calcifications
◦ IUGR, hydrops
◦ Hepatic lesions, echogenic abdominal foci
 Amniocentesis
◦ Amniotic fluid culture, PCR
 Cordocentesis
◦ IgM anti-CMV, PCR

CMV
CMV
Management
Management
 If congenital infection
◦ Head CT or MRI
◦ Ophthalmologic exam
◦ Hearing screen
◦ PLT count, LFTs, CSF evaluation
 Gancyclovir
◦ Little experience in neonates and given toxicity of gancyclovir
caution is warranted
◦ Used especially to treat chorioretinitis and neurological
abnormalities
◦ Can lead to thrombocytopenia, anemia
◦ Increase relapse after discontinue gancyclovir

CMV neonatal hepatitis
Notice an area of necrosis with nuclear
inclusions in hepatocytes and not
much inflammatory reaction.
CMV
CMV inclusion body
Hepatocyte with a large
intranuclear inclusion body.
Surrounded by a clear halo. Dark
punctiform inclusions are seen also
in the cytoplasm.

Cytomegalovirus (CMV) Retinitis
Mixture of cotton wool spots, infiltrates, and hemorrhages.
The virus gets into the vascular endothelium, closes off blood
vessels, and spreads through tissue. The entire retina can be
destroyed within weeks.
"Pizza pie" Retinopathy

Congenital CMV
Microcephaly and smooth cortex.
Congenital CMV
Cortical atrophy and calcifications.
CMV

HSV
HSV
Epidemiology
Epidemiology
 HSV type 1 (oral) or HSV type 2 (genital)
 Belongs to a group of double-stranded herpes DNA (CMV, EBV, varicella-
zoster virus)
 After acute infection virus establishes latency in the CNS
 Intrauterine and intrapartum infection is usually with type 2
 Postnatal infection is usually with type 1
 Recurrent genital herpes occurs at some point in ~1% of pregnancies
 Primary infection in moms before 20 weeks has been associated with
spontaneous abortion

HSV
HSV
Incidence
Incidence
 Neonatal infection occurs 1 in 2000 to 5000 deliveries per year
 Less common than CMV or toxo, similar incidence as syphilis
 Mother with primary genital lesion during delivery  40-50% of neonates
will become infected due to high viral titer and neonate without protective
antibodies
 Mother with secondary genital lesion during delivery  < 5% of exposed
neonates will become infected (low % probably due to maternally
transmitted antibodies)
 However, since secondary lesions are more common, ~50% of neonates with HSV
are born to mother with secondary HSV
 60-80% of women with neonates who develop HSV are asymptomatic or
without a history of HSV

HSV
HSV
Transmission
Transmission
 Intrapartum (~95%)
◦ Most often acquired due to infection while passing through
an infected birth canal
 In utero (~5%)
◦ Ascending or transplacental
 Postnatal (rare)
◦ Can be transmitted from breast milk or contact with infected
skin lesion

HSV
HSV
Neonatal risks
Neonatal risks
 Primary maternal genital infection during pregnancy
◦ Greatest risk factor, 10-20 x higher risk compare with secondary/recurrent lesion due to
 High viral replication
 Longer excretion of virus from primary lesion (3 weeks if primary infection vs. 2-5 days shedding if
recurrent HSV)
 Lack of maternal antibodies to infant
 Prematurity
◦ Probably due to low transplacental IgG antibodies in premature infants
 Fetal scalp monitoring
◦ May break infant’s skin barrier and thus contraindicated if known HSV infection
 PROM
◦ > 4-6 hours; increases risk of ascending infection

HSV
HSV
Perinatal HSV (acquired at time of delivery or postnatally)

HSV
HSV
Congenital HSV (acquired in utero): rare
Triad:
1. Brain
 Microcephaly, hydranencephaly
 Intracranial calcifications
 Hypertonicity, seizures
2. Eyes
 Microphthalmia, blindness
 Chorioretinitis, cataracts
3. Skin
 Vesicles (often present at birth, unlike perinatal HSV)
 Scar, hypopigmented lesions
 Also with in utero growth restriction
 Elevated cord IgM levels

Cutaneous Herpes
Cutaneous Herpes

Oral Herpes and Ocular Herpes
Oral Herpes and Ocular Herpes

Disseminated yellowish white necrotic lesions in the
liver of a newborn infant
HSV

Neonatal HSV encephalitis.
Neonatal HSV encephalitis.
Diffuse hemorrhagic necrosis

HSV
HSV
Diagnosis
Diagnosis
 If low suspicion and not treating with acyclovir, obtain surface cultures of
conjunctivae, nasopharynx and rectum 24-48 hours post delivery
 If high index of suspicion (ill infant, vesicles present) and treating with acyclovir,
obtain surface cultures as well as CSF, urine and vesicular base cultures
◦ CBC/differential
◦ CSF
 Elevated protein
 Pleocytosis-especially mononuclear cells
 Increased RBCs
 Herpes PCR
◦ May have abnormal LFTs, elevated bilirubin, thrombocytopenia, coagulapathy
◦ CXR consistent with pneumonitis
◦ Diffusely abnormal EEG (typically spike and slow-wave activity in temporal region)
◦ Head imaging if high suspicion

HSV
HSV
Management
Management
 Prevention: Current recommendations are to deliver infants by c-
section if there is evidence of active lesions at the time of labor, and less
than 4-6 hours after ROM has occurred
 If mother with PROM and fetus is premature management
controversial, some recommend acyclovir IV to mother if delay labor
 Isolate infants with proven HSV
 Isolate infants born vaginally or by C/S to mother with ROM>6 hours and
active lesions

HSV
HSV
Management
Management
 Treat if
◦ Positive HSV culture
◦ Neonate with clinical symptoms consistent with HSV
◦ Neonate with nonspecific symptoms and exposure to primary HSV
 Acyclovir
◦ Inhibits viral DNA transcription; specifically is activated by thymidine kinase
◦ The dosage is 60 mg/kg/day in 3 divided doses, given IV for 14 days if disease
is limited to the skin, eye and mouth; and for 21 days if disease is disseminated
or involves the CNS
◦ Monitor urine output and creatinine to asses for renal toxicity
◦ Monitor CBC to assess for thrombocytopenia

17.TORCH infections notes for medical students.ppt

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17.TORCH infections notes for medical students.ppt