TORCH

Jessica Santoso
Moderator: dr. Maimun ZA, M.Kes, Sp.PK
TORCH is an acronym for Toxoplasmosis, Others
(Syphilis, Varicella-zoster virus, HIV, Parvovirus
B19), Rubella, Cytomegalovirus, and herpes
simplex.
It is also a medical acronym for a set of vertically
transmitted infections (i.e infections that are
passed from a pregnant woman to her fetus).
The TORCH infections can lead to severe fetal
anomalies or even fetal loss.
Toxoplasmosis is reserved for the disease
process in which symptoms and signs are
present, because of Toxoplasma infection.
The etiologic cause is a parasite called
Toxoplasma gondii.
Characteristics :
Sporozoon living intracellularly, forming large
tissues cysts. Natural host is cat, where parasite has
enteric cycle, producing oocysts in feces. In human
organisms can invade many tissues.
Transmissions :
Swallowing oocyts passed by cats; ingestion of
tissue cysts in raw or undercooked meat;
transplacental.
The parasite exists in several forms:
The tachyzoite
The oocyst that contains sporozoites
The tissue cyst that contains bradyzoites and
Macrogametes and microgametes.
The tachyzoite is the rapidly proliferating form
of the parasite responsible for the clinical
manifestations of toxoplasmosis observed in the
setting of the acute infection or reactivation of a
latent infection.
The tachyzoite, requires an intracellular habitat
for its survival, and multiplies every 6 to 8 hours
until rosette formation occurs and cell
disruption inevitably follows.
The tissue cyst (contain bradyzoites) is the
slower metabolic form of the parasite
responsible for chronic infection and for its
transmission through meat consumption in
humans and animals.
Tissue cysts persist in tissues for the life of the
host and cannot be eradicated by drugs.
The central nervous system (CNS), eye, and skeletal,
smooth, and heart muscles appear to be the most
common sites of tissue cyst formation (i.e., latent
infection).
Oocysts are shed by domestic & feral animals
belonging to the Felidae family, & are responsible for
the spread of the parasite.
Oocysts may remain viable for as long as 18 months in
moist soil; this results in an environmental reservoir
from which incidental hosts may be infected.
Transmissions :
Swallowing oocyts passed by
cats; ingestion of tissue cysts
in raw or undercooked meat;
transplacental.
Clinical categories Clinical manifestations & syndromes
Primary infection Most are asympthomatic
Immunocompetent individuals and Sympthoms: fever, lymphadenopathy, headache,
pregnant women myalgias, arthralgias, sore throat, stiff neck, nausea,
abdominal pain, anorexia, rash, confusion, ear ache, eye
pain, general malaise, fatigue, Chorioretinitis
Congenital toxoplasmosis
Fetus Fetal death
Newborn Can be normal, have a nonspesific illness, or have
abnormal physical examination (strabismus, blindness,
seizures etc)
Children & adults Children can continue to suffer the chronic sequelae of
the congenital disease.
Chronic infection Asymptomatic
Reactivation of chronic infection in Multiple brain abscesses, diffuse encephalitis,
immunocompromised patients chorioretinitis, fever of unknown origin, pneumonia,
myocarditis, hepatosplenomegaly,
lymphadenopathy, rash
Serologic tests
Polymerase chain reaction (PCR)
Direct visualization of the parasite
Method Clinical Interpretation
Serologic tests
IgG A positive test result establishes that the patient has been infected
with T. gondii. However, a negative test result can be seen in patients
infected within 4 weeks before serum sampling or in patients unable
to produce IgG (e.g., immunocompromised hosts).
IgM A positive test result suggests but is not necessarily diagnostic of an
acute infection.
Sera with positive IgM test results should be sent to a reference
laboratory for confirmatory testing. Positive IgM test results can be
seen in chronically infected patients because of persistence of the IgM
response.
Confirmatory IgG avidity test; a high IgG avidity test result indicates that the patient
testing for has been infected for more than 4 months (avidity). The window of
positive IgM test exclusion for acute infection varies for different avidity kits (usually
results between 3 and 5 months)
Method
Polymerase chain reaction (PCR)
Clinical interpretation
•B1 and AF487550 genes are the most commonly
used targets for amplification.
•PCR test can be performed in any body fluid,
including peripheral blood, cerebrospinal fluid,
bronchoalveolar lavage fluid, vitreous fluid,
aqueous humor, peritoneal fluid, pleural fluid, and
ascitic fluid. PCR can also be performed in any tissue.
•A positive test result in any body fluid establishes
that the patient has either primary or reactivated
toxoplasmosis. However, a positive PCR test result in
tissue is more difficult to interpret because it does
not differentiate toxoplasmosis from a latent
infection.
Method
Direct visualization of the parasite
Tachyzoites with Wright-Giemsa stain
Clinical interpretation
Identification of tachyzoites in any body fluid or
tissue is diagnostic of toxoplasmosis due to
primary infection or reactivation of a chronic
infection. Tachyzoites can be identified by
hematoxylin and eosin or cytologic studies but
are better visualized with Wright-Giemsa and
immunoperoxidase stains.
Oocysts isolated from cats feces
 SYPHILIS
 VARICELLA-ZOSTER VIRUS
 HUMAN IMMUNODEFICIENCY VIRUS (HIV)
 PARVOVIRUS B19
Is a chronic infectious disease caused by the
bacterium Treponema pallidum
Usually acquired by sexual contact with another
infected individual.
T. pallidum is a thin, helical bacterium
approximately 0.15 μm wide and 6-15 μm long.
The organism has 6 to 14 spirals and is tapered
on either end.
The T. pallidum outer membrane composed of
predominantly phospholipids, with few surface-
exposed proteins.
It can be visualized in wet mounts by dark-field
microscopy or in fixed specimens by silver stain
or fluorescent antibody methods.
 T. pallidum may penetrate through normal mucosal membranes
and minor abrasions on epithelial surfaces.
Clinical manifestations
Primary syphilis Typical lesion: the chancre (painless, clean-based, ulcer) mostly in
anogenital. Regional adenopathy unilateral / bilateral (+).
Secondary syphilis Occur between 4-8 weeks after primary chancre, such as malaise,
fever, headache, sore throat & other systemic complaints.

Relapsing syphilis Recurrence lesions after resolution of the primary or secondary

lesions.
Latent syphilis Is the stage at which there are no clinical signs of syphilis and the
CSF is normal. Latency begins shen the first attack of the
secondary syphilis has passed and may last for a lifetime.
Late syphilis Slowly progressive, certain neurologic syndrome may have a
sudden onset because of endarteritis & CNS thrombosis. It is not
infectious through sexual contact.
Results from the transplacental, hematogenous spread
of syphilis from the mother to the fetus.
The risk for fetal infection is greatest in the early stages
of untreated maternal syphilis and declines slowly
thereafter.
Early congenital syphilis are often seen in the perinatal
period.
The child often has rhinitis, hepatosplenomegaly,
hemolytic anemia, jaundice, and pseudoparalysis (i.e.,
immobility of one or more extremities) as a result of
painful osteochondritis.
Late congenital syphilis is defined as congenital syphilis
diagnosed more than 2 years after birth.
The disease may remain latent, with no manifestations
of late damage.
Neurologic manifestations are common and may
include eighth cranial nerve deafness and interstitial
keratitis.
Periostitis, Hutchinson’s teeth.
Dark-Field Examination
Positive : typical morphology and motil spirochetes.
Serologic tests :
Nontreponemal tests that detect antibodies
reactive with diphosphatidylglycero (cardiolipin),
which is a normal component of many tissues
Tests that detect antibodies to specific treponemal
antigens.
Primary infection with varicella-zoster virus (VZV)
results in the rash of varicella (chickenpox).
The virus establishes a latent infection in the nervous
system and can reactivate later in life to cause zoster
(shingles).
Previous infection with varicella is believed to confer
lifelong immunity to varicella.
Zoster occurs in the presence of neutralizing antibody
to varicella.
VZV is a member of the alpha herpesvirus family
and has a DNA core surrounded by a
nucleocapsid, which is in turn surrounded by a
viral envelope that is studded with
glycoproteins.
The virus encodes a thymidine kinase, which
phosphorylates acyclovir, which in turn inhibits
viral DNA replication by inhibiting the VZV DNA
polymerase.
Varicella
Incubation period for varicella is 2 weeks
(10 - 21 days)
The lesions begin as papules that
become vesicles, followed by pustules
and then crusts.
Lesions appear on the head → spread to
the trunk → to the extremities; the
mucosa can also be involved.
In primary infection, neurons in cranial
nerve ganglia and dorsal root ganglia
become latently infected with the virus.
If VZV-specific cellular immunity
declines, the virus reactivates from a
ganglion, travel down the axon,and
replicate in epithelial cells to cause
dermatomal zoster.
Zoster
Zoster, presents with localized pain and increased
sensation for 1 to 3 days before the development
of a dermatomal vesicular rash that does not cross
the midline.
Zoster most frequently presents in the dermatomes
innervated by trigeminal or thoracic ganglia.
The rash is usually accompanied by itching, tingling,
or pain.
The lesions evolve from vesicles to pustules, and
crusting is usually complete by 10 days.
Women who develop varicella during pregnancy
may experienced spontaneous abortion, fetal
demise & congenital anomalies.
Congenital anomalies usually resulted from
maternal infection in the first 20 weeks of
pregnancy.
Most cases of varicella and zoster are diagnosed on the
basis of their clinical presentation.
Laboratory test:
Serology test (IgM or IgG antibody)
Definitive confirmation : polymerase chain reaction (PCR)
for VZV from vesicular fluid (most sensitive & spesific)
HIV is a retrovirus, a member of
the Lentivirus genus
Women with HIV are more susceptible to direct
or obstetric causes of maternal mortality such
as post-partum hemorrhage, puerperal sepsis,
and complications of caesarean section.
More prone for opportunistic infection such as
tuberculosis.
 Types of Test Function
CD4 T-cell enumeration To evaluate the degree of immune suppression
in HIV-infected patients for several years
Antibody detection screening tests, whose goal is to detect all
infected persons,
confirmatory tests, performed on samples giving
a positive result on a screening test
Antigen detection P24 antigen testing : Levels of this antigen in
the circulation are thought to correlate with the
amount of HIV replication
Testing for viral nucleic acid (viral to determine the amount of virus present in
load tests) patients and to determine whether and what
type of drug resistance has developed.
Parvoviruses are the simplest DNA animal
viruses
Because of the small coding capacity of their
genome, viral replication is dependent on
functions supplied by replicating host cells or by
coinfecting helper viruses.
The only known parvovirus pathogenic for
humans, B19, has a tropism for erythroid
progenitor cells.
Transmission is presumably by the respiratory route.
The virus can be transmitted parenterally by blood
transfusions or by infected blood products (clotting
and immunoglobulin concentrates) and vertically from
mother to fetus
Immature cells in the erythroid lineage are principal
targets for human B19 parvovirus
The major sites of virus replication in patients are
assumed to be the adult marrow, some blood cells, and
the fetal liver
Viral replication causes cell death, interrupting red cell
production
In cases of fetal death, chronic infections may have
caused severe anemia in the fetus.
Types of clinical findings
Fifth Disease
Most B19 parvovirus infections are asymptomatic. The most common manifestation
of infection is erythema infectiosum, or fifth disease, a rash illness of childhood
characterized by a “slapped cheek” appearance
B19 Arthropathy
An acute parvovirus infection in adults, particularly middle-aged women. Characterize
by symmetrical joint involvement of the hands, ankles, knees, and wrists. B19
arthropathy usually resolves within a few weeks; joint destruction
does not occur.
Transient Aplastic Crisis
anemic crises in persons with underlying hemolysis or a high demand for production
of circulating erythrocyte caused by B19 parvovirus infection. Transient aplastic crisis is
associated with a pathognomonic bone marrow appearance, absence of maturing
erythroid precursors, and the presence of “giant pronormoblasts” that represent the
cytopathic effect of parvovirus infection
Types of clinical findings
Persistent Infection
B19 parvovirus persists in the absence of an appropriate host antibody
Response causes a hematologic syndrome of pure red cell aplasia. The anemia is severe
& requires transfusion; reticulocytes are absent from blood, as are the erythroid
presursors from marrow. There is no antibody to parvovirus in the blood, but the virus
can be detected in the circulation, often at extremely high levels (>1012 genome copies
per milliliter). These occurs in patients with congenital immunodeficiency.
Hydrops Fetalis
Transplacental transmission to the fetus in infected pregnant woman. Hydrops is the
result of severe anemia, contributing to congestive heart failure. Infection during the
second trimester poses the greatest risk for birth of a hydropic infant.
Because of the difficulty in propagating B19 parvovirus in
standard tissue culture, laboratory diagnosis relies on :
Serologic test (IgM, IgG antibody to parvovirus B19)
DNA tests (PCR)
Is an acute viral illness that usually presents with a
generalized maculopapular rash of 1 to 3 days’
duration, low grade or no fever, and associated clinical
symptoms such as lymphadenopathy, arthropathy, and
conjunctivitis.
However, about 20 to 50% of persons infected with
rubella may present without a rash or other symptoms.
It is the mild in children and adults, but can cause
devastating problems if it infects the fetus, especially if
infection is in the first few weeks of pregnancy.
Rubella virus is the only member of
the Rubivirus genus of the Togavirus
family.
Unlike most Togaviruses it is NOT
arthropod-borne, but is acquired via
the respiratory route.
It is an enveloped (toga=cloak), non-
segmented, RNA virus and replicates
in the cytoplasm.
Its nucleocapsid has icosahedral
symmetry.
There is only one major antigenic
type.
Postnatally Acquired Rubella
Acquired rubella, which occurs in 50 to 80% of
persons infected with rubella virus, is
characterized by a generalized maculopapular
rash that usually persists for 1 to 3 days.
The rash usually starts on the face and neck and
progresses downward. The rash is fainter than
the rash of measles and does not coalesce.
The rash might be difficult to detect in persons
with darker skin.
Children usually have few or no prodromal symptoms,
so the rash is usually the first sign of illness.
However, in older children and adults, a 1- to 5-day
prodrome of low-grade fever, malaise, and upper
respiratory symptoms often precedes the rash.
Lymphadenopathy, particularly occipital and
postauricular, may be noted during the second week
after exposure.
Arthralgia and arthritis are commonly observed in
infected adults, particularly in postpubertal girls.
Rash of rubella on the
skin of a child’s back
Congenital Rubella Syndrome
The most serious consequences occur when a woman
becomes infected during pregnancy, particularly during the
first trimester.
Complications can include miscarriage, fetal death, or a live
birth with a constellation of congenital defects.
The most common defects of congenital rubella syndrome
affect the eyes (e.g., cataracts, pigmentary retinopathy,
microphthalmos, congenital glaucoma), the ears (e.g.,
hearing impairment), and the heart (e.g., patent ductus
arteriosus, pulmonary arterial stenosis).
Other clinical manifestations of congenital rubella
syndrome may include microcephaly, developmental delay
Postnatally Acquired Rubella
Serologic testing:
IgM antibody: detectable for up to 6 weeks after the
onset of the rash.
Diagnosis also can be made on the basis of a significant
rise in the IgG antibody titer in paired acute and
convalescent specimens.
The acute serum specimen should be collected within
7 to 10 days after the onset of the rash, and the
convalescent serum specimen should be collected 14
to 21 days after the first specimen.
Isolation and Identification of Virus
Nasopharyngeal or throat swabs taken 6 days before
and after onset of rash are a good source of rubella
virus.
During the first 4 days after the onset of the rash,
rubella RNA detection by reverse transcription–
polymerase chain reaction (RT-PCR) is more sensitive
than rubella IgM testing.
For viral cultures, specimens should be obtained during
the time of maximum virus secretion—up to 4 days
after the onset of rash.
Diagnosis in Pregnant Women
In the United States, all pregnant women should be
screened for rubella IgG antibodies as part of routine
prenatal care.
Pregnant women who have a positive serologic test
result for IgG antibody to rubella virus are considered
to be immune if they do not have a recent history of
exposure to rubella virus.
Pregnant women exposed to rubella virus should be
evaluated for evidence of acute infection by testing for
presence of IgM antibodies in sera or a significant rise
of IgG antibodies in acute and convalescent sera.
Congenital Rubella
Can be confirmed by either serologic or virologic
methods.
Serum IgM antibodies may be present in an infant with
congenital rubella syndrome for up to a year after
birth; however, IgM antibody may not be detectable
during the first month of life.
Documentation of a persistent rubella serum IgG titer
beyond the time expected from passive transfer of
maternal IgG antibody can confirm congenital rubella.
Rubella virus in infants with congenital rubella
syndrome also can be detected by RT-PCR with use of
the same specimens as for viral isolation.
Cytomegalovirus (CMV) is a member of the
herpesvirus family and shares,with the other
members, the ability to establish a long-lived
latent infection.
Most of the clinical disease caused by this virus
results from reactivation of latent virus in
immune-impaired patients, although
The name for the classic cytomegalic inclusion
disease derives from the propensity for massive
enlargement of cytomegalovirus-infected cells.
Cytomegalovirus has the largest genetic content
of the human herpesviruses.
Its DNA genome (240 kbp) is significantly larger
than that of HSV.
One, a cell surface glycoprotein, acts as an Fc
receptor that can nonspecifically bind the Fc
portion of immunoglobulins.
This may help infected cells evade immune
elimination by providing a protective coating of
irrelevant host immunoglobulins.
Cytomegalovirus produces a characteristic
cytopathic effect.
Perinuclear cytoplasmic inclusions form in
addition to the intranuclear inclusions typical of
herpesviruses.
Multinucleated cells are seen. Many affected
cells become greatly enlarged. Inclusion-bearing
cytomegalic cells can be found in samples from
infected individuals.
CMV may be transmitted person-to-person in several
different ways, all requiring close contact with virus-
bearing material.
There is a 4- to 8-week incubation period in normal
older children and adults after viral exposure.
The virus causes a systemic infection; it has been
isolated from lung, liver, esophagus, colon, kidneys,
monocytes, and T and B lymphocytes.
The CMV envelope glycoproteins that participate in
viral entry are gB, gH/gL, and gCII.
The immune response involves both the
humoral and cell-mediated arms, but the CD8+
cytotoxic T-cell response appears to be the most
important.
Cytomegalovirus establishes lifelong latent
infections.
It is thought that monocytes and bone marrow
progenitor cells are sites of human CMV latency.
Reactivation from the latent state has classically
been associated with immunosuppression.
Congenital & Neonatal Infection
Clinical evidence of congenital disease, such as
microcephaly, intracerebral calcification,
hepatosplenomegaly, and rash.
90% of these clinically infected newborns will
survive, but most will have unilateral or bilateral
hearing loss or mental retardation (or both).
Infection in Immunocompetent Persons
Usually are asymptomatic, but some resemble
infectious mononucleosis like syndrome but with
minimal pharyngitis and lymphadenopathy.
Infection in Patients with AIDS
Retinitis occurred in approximately a third of patients
with AIDS, most often in those with CD4 counts below
50/mm3. It usually begins unilaterally with visual
blurring, floaters, decreased acuity, and loss of visual
fields and progresses to blindness if it is untreated.
Serology
Seroconversion is an excellent marker for
primary CMV infection, but rises in IgG titers,
even four-fold or greater, are not diagnostic of
newly acquired infection.
CMV-specific IgM antibody develops during
primary infection but may reappear during
reactivation of latent CMV.
The presence of IgG antibody is a sensitive
marker of past infection and is used to screen
transplant recipients and donors as well as
certain blood product recipients and donors.
CMV Antigen or Nucleic Acid Detection
Monoclonal antibodies can detect and count
CMV antigens directly in peripheral
bloodleukocytes (antigenemia) ( with a high
sensitivity. Assays of viral
DNA by polymerase chain reaction or hybrid
capture are also more sensitive than culture and
at least comparable to antigenemia assays.
Culture
Historically, culture has been regarded as the
“gold standard” for detection of CMV infection,
but false-negative culture results do occur.
CMV may require at least 4 to 6 weeks for
detection.
More rapid culture results may be achieved by
centrifuging specimens in a shell vial seeded
with diploid fibroblast cells and examining them
after 1 to 2 days of incubation by
immunofluorescence.
Is a member of the family Herpesviridae, based on the
structure of virion.
There are two distinct herpes simplex viruses: type 1
and type 2 (HSV-1, HSV-2)
HSV contains double-stranded DNA at its central core,
has a molecular weight of approximately 100 million,
and encodes at least 80 polypeptides.
The DNA core is surrounded by a capsid that consists
of 162 capsomers arranged in icosapentahedral
symmetry. The capsid is 100 to 110 nm in diameter.
The envelope consists of
polyamines, lipids, and
glycoproteins.
These glycoproteins
confer distinctive
properties to the virus
and provide unique
antigens to which the
host is capable of
responding.
HSV is transmitted from infected to susceptible
individuals during close personal contact, and the virus
must come in contact with mucosal surfaces or
abraded skin for infection to be initiated.
Acquisition of HSV-1 infection is related to
socioeconomic factors, presumably a consequence of
crowded living conditions that provide a greater
opportunity for direct contact with infected individuals.
Infections with HSV-2 are usually acquired through
sexual contact.
Localized, recurrent HSV-2 infection is the most
common form of HSV infection during gestation.
Transmission of infection to the fetus is most
frequently related to shedding of the virus at the time
of delivery.
The incidence of cervical shedding in pregnant women
with asymptomatic HSV infection is approximately 1%.
Most infants in whom neonatal disease develops are
born to women who are completely asymptomatic for
genital HSV infection at the time of delivery and who
have neither a past history of genital herpes nor a
sexual partner reporting a genital vesicular rash.
Cytopathology
Isolation & identification of virus
Polymerase chain reaction (PCR)
Serology
Methods & Clininal interpretation
Cytopathology
A rapid cytologic method is to stain scrapings obtained from the base of a vesicle (eg,
with Giemsa's stain); the presence of multinucleated giant cells indicates that
herpesvirus (HSV-1, HSV-2, or varicella-zoster) is present, distinguishing lesions from
those caused by coxsackieviruses and nonviral entities.
Isolation and Identification of Virus
Isolation and Identification of Virus. Virus may be isolated from herpetic lesions and
may also be found in throat washings, cerebrospinal fluid, and stool, both during
primary infection and during asymptomatic periods. Therefore, the isolation of HSV is
not in itself sufficient evidence to indicate that the virus is the causative agent of a
disease under investigation.
Inoculation of tissue cultures is used for viral isolation. The agent is then identified by Nt
test or immunofluorescence staining with specific antiserum. Typing of HSV isolates may
be done using monoclonal antibody or by restriction endonuclease analysis of viral DNA
Methods & clinical interpretations
Polymerase Chain Reaction (PCR)
PCR assays can be used to detect virus and are sensitive and specific. PCR amplification
of viral DNA from cerebrospinal fluid has replaced viral isolation from brain tissue
obtained by biopsy or at postmortem examination as the standard assay for specific
diagnosis of HSV infections of the central nervous system.
Serology
Antibodies appear in 4–7 days after infection and reach a peak in 2–4 weeks. They
persist with minor fluctuations for the life of the host.
The diagnostic value of serologic assays is limited by the multiple antigens shared by
HSV-1 and HSV-2. There may also be some heterotypic anamnestic responses to
varicella-zoster virus in persons infected with HSV, and vice versa.
Thank you…
The parasite has a sexual and an asexual life
cycle. The sexual life cycle in which
macrogametes and microgametes copulate to
form the fertilized gamete (gametogony) takes
place only in the enteroepithelium of cats and
other members of the Felidae family (the
definitive host).
An asexual life cycle (schizogony) also takes
place in the small intestine of these animals as
well as in the tissues of other animals and
humans (incidental hosts).
Unsporulated oocysts are formed within the
intestine of cats as a result of both cycles.
Sporulation is required for the oocysts to
become infectious, takes place outside the cat’s
intestine, and is more rapid at warm
temperatures (2 to 3 days at 24° C compared
with 14 to 21 days at 11° C).
Type
NONTREPONEMAL (ANTICARDIOLIPIN) ANTIBODIES
Nontreponemal (anticardiolipin) antibodies
VDRL (slide flocculation)
RPR (circle card) (agglutination)
SPECIFIC TREPONEMAL ANTIBODIES
FTA-ABS (immunofluorescence with
absorbed serum)
TP-PA (microhemagglutination)
EIA
Use
Screening, quantitation of response
to treatment
Screening, quantitation of response
to treatment
Confirmatory, diagnostic; not for routine
screening
Similar to FTA-ABS but can be
quantified and automated
Confirmatory and increasingly
used for screening; automated
Schematic diagram of replication of herpes simplex virus
Schematic diagram of primary herpes Schematic diagram of herpes simplex
simplex virus infection virus latency and reactivation