● TOXOPLASMAA, RUBELLA, CMC and HSV Infection

● SCREENING & DIAGNOSIS

DR.AMIN NUROKHIM, SpOG

PURWOKERTO 2017
Toxoplasma
 Toxoplasmosis
Prevalency
• 30% and 65% of all Country Prevalency
people worldwide France 88%
are infected with
Toxoplasmosis Germany 80%
• Prevalensi Netherlands 80%
toksoplasma di Brazils 67%
Indonesia berkisar
20-30 persen
Britain 22%
seropositif pada South Korea 4.3%
sejumlah populasi
yang di survei
•
Data Penapisan
Toxoplasma

Rachimhadhi T, disampaikan pada :

The VI National Congress of the Perinasia and International Symposium, 1997
Life Cycle

Ultrastructure of T. gondii
tachyzoit
 Risk Factors
• Infants born to mothers who became
infected with Toxoplasma for the first time
during or just before pregnancy.
• Persons with severely weakened immune
systems, such as those with AIDS. Illness
may result from an acute Toxoplasma
infection or reactivation of an infection
that occurred earlier in life.

http://en.wikipedia.org/wiki/Toxoplasmosis
 Risk Factors for T, gondii
infection in 131 mothers of infants
with congenital toxoplasmosis
Summary epidemiologic factors of maternal exposure and illness history
Factor %
Any exposure to cats 65
Any exposure to undercooked or uncooked meat 50
Any exposure to cat undercooked or uncooked meat 75
Specific exposure to cat litter or undercooked meat 39
Underexplained febrile illnes or lymphadenopathy-
during pregnancy 48
Exposure to cat litter, uncooked meat or toxoplasmosis-
like illness during pregnancy

Boyer K et. al Am J Obstet Gynecol. 2005 Feb, 192(2): 564-71

 Risk Factors

• Primary maternal infection with

Toxoplasma gondii during
pregnancy is not associated with
maternal symptoms.
• Transplacental transmission the risk
to the fetus is determined by the
gestational age at the time of
infection
 Hubungan Insidens dan derajat
keparahan
Toxoplasmosis Kongenital dengan
waktu
terjadinya infeksi pada ibu hamil
 Pregnancy precautions
• Treatment is very important for
recently infected pregnant women,
to prevent infection of the fetus
• Pregnant women who become ill
with acute toxoplasmosis should be
treated with spiramycin.
Toxoplasmosis During Pregnancy

• The vast majority of women who

acquire this infection during
pregnancy do not exhibit any
symptoms
• Diagnosis must be solely based on
serological screening
 Serological Testing
• Anti-Toxoplasma IgA*
• Anti-Toxoplasma IgM
• Anti-Toxoplasma IgG
• Aviditas Anti-Toxoplasma IgG
• Anti-Toxoplasma IgE*
Serologic tests are the primary
means of diagnosis, but results must
be interpreted carefully
Anti-Toxoplasma IgA
• IgA antibodies may be detected in sera
of acutely infected adults,
immunosuppressed indivuduals with or
without active infection, and congenitally
infected infants using ELISA, ISAGA or
other assays
• The IgA antibodies may persist for many
months to more than one year after acute
infection.
Anti-Toxoplasma IgM
• The lack of T gondii-specific IgM antibodies
indicates infection more than 6 months ago.
• The presence of T gondii-specific IgM antibodies
can indicate recent infection or can result from a
false-positive reaction
• Immunoglobulin M-specific antibodies can be
detected 2 weeks after infection, achieve peak
concentrations in 1 month, decrease thereafter,
and usually become undetectable within 6 to 9
months but uncommonly persist for as long as 2
years
Anti-Toxoplasma IgG
• Demonstration of seroconversion or
a significant rise in IgG Toxoplasma
antibodies usually establishes
recently acquired infection
•
Aviditas Anti-Toxoplasma IgG

• The utility of the avidity test is based

on the observation that toxoplasma
IgG antibodies from patients with a
recently acquired T. gondii infection
bind antigens weakly (i.e., have low
avidity), whereas IgG antibodies
from chronically infected patients
have stronger binding capacity
(high avidity)
Aviditas Anti-Toxoplasma IgG

• The IgG avidity test results were

interpreted according to the
manufacturer’s instructions as high
(0.300), equivocal (0.200 to 0.300), or
low (0.200).
•
 Hasil Evaluasi Vidas Toxo IgG Avidity
Menggunakan 939 Sera yang diketahui
saat
infeksi terjadi (> atau < 4 bulan)
 Sample Collection Performed
During
The First 3 Months of Pregnancy
VIDAS TOXO IgG
Avidity
Cut-off : 0.300 (index)
0.750 = high
avidity
High avidity excludes recent infection
(< 4 months) from diagnosis
and indicates that IgM are residual
(result to be confirmed using a 2nd sample
collection)
Anti-Toxoplasma IgE
• The duration of IgE seropositivity is
less than that of IgM or IgA
antibodies.
• In combination with other
serological tests IgE antibodies
appear not useful as an additional
confirmation assay during recently
acquired infections
 Guidelines for serodiagnosis of
toxoplasmosis before pregnancy or
infertility treatment and consequences for
conception.
 Guidelines for the timing of a primary
Toxoplasma-infection during the first trimenon and
recommendations for treatment
(Spiramycin)

Ingrid Reiter-Owona, J Lab Med 2005;29(6):439–445

Diagnosis Congenital
Toxoplasmosis (1)
• If the diagnosis for an infant is unclear at
the time of delivery, Toxoplasma-specific
laboratory tests for IgG, IgM, IgA, and IgE
on newborn and maternal serum samples
should be performed.
• Peripheral blood white blood cells, CSF,
and amniotic fluid specimens should be
assayed for T gondii by polymerase chain
reaction assay in a reference laboratory.
• Evaluation of the infant should include
ophthalmologic, auditory, and neurologic
examinations; lumbar puncture; and
computed tomography of the head.
Diagnosis Congenital
Toxoplasmosis (2)
• Congenital infection is confirmed
serologically by persistently positive IgG
titers beyond the first 12 months of life.
Before 12 months of age, a persistently
positive or increasing IgG antibody
concentration in the infant compared with
the mother, and/or a positive
Toxoplasma-specific IgM or IgA assay
indicate congenital infection
 Clinical
manifestations-Congenital
Toxoplasmosis

Toxoplasma gondii Infections

Toxoplasma gondii (Toxoplasmosis). Infant girl with
Infections congenital toxoplasmosis with
(Toxoplasmosis). A 12 day hepatosplenomegaly.
old white male with
congenital toxoplasmosis
with marked
hepatosplenomegaly
RUBELLA
 Rubella
• Togavirus (RNA virus)
• Incubation - 14-21 days
• Respiratory droplet inoculation
– only modestly contagious
• Fever, rash (3 days), cough, arthralgias,
post auricular and suboccipital
lymphadenopathy
• Usually mild, overt clinical symptoms
50-75% of cases
• Encephalitis, bleeding diathesis & arthritis
are rare complications
•
•
 Rubella Infection During
Pregnancy
• Diagnosis of rubella virus (RUB) infection is
essential after potential exposure of a
woman in the first trimester of pregnancy
• It is necessary for confirmation of
potential cases of congenital rubella
syndrome in newborns (12), and is
important in the surveillance component
of rubella vaccination programs
 Rubella and the Fetus
• Purpura, Splenomegaly, jaundice,
meningoencephalitis, thrombocytopenia
are transient
• Congenital cataracts, Glaucoma, heart
disease, deafness, microcephaly and
mental retardation are permanent
abnormalities
• Diabetes, thyroid abnormalities,
precocious puberty & Progressive
panencephalitis (late)
Risiko Transmisi Infeksi dan
Kecacatan pada Janin
 Rubella Clinical Features
• Incubation period 14 days (range 12-23
days)

• Prodrome of low grade fever

• Lymphadenopathy in second week

• Maculopapular rash 14-17 days after

exposure
Congenital Rubella Syndrome
• Infection may affect all organs
• May lead to fetal death or
premature delivery
• Severity of damage to fetus depends
on gestational age
• Up to 85% of infants affected if
infected during first trimester
Congenital Rubella Syndrome
• Deafness
• Cataracts
• Heart defects
• Microcephaly
• Mental retardation
• Bone alterations
• Liver and spleen damage
 Diagnosis Rubella Infection

• In diagnosing rubella, clinicians should

consider:
• Including both rubella and measles in the
differential diagnosis of patients presenting
with an acute generalized rash and fever.
• Ordering serology tests only if the clinical case
definition is met; otherwise, false positive
results may be detected.
• Collecting specimens for both culture and
serology.
•
• Minnesota Department of Health,
www.health.state.mn.us/immunize 2006
Diagnosis Rubella Infection
• Acute rubella infection is lab
confirmed by the presence of one or
more of the following:
• a positive rubella-specific IgM
antibody,
• a significant rise in IgG antibody from
paired acute and convalescent sera,
• a positive viral culture for rubella,
•
•
 Exposure to Rubella during
pregnancy
• If a pregnant woman is exposed to rubella and
her immune status is unknown, test a blood
specimen for rubella IgG antibody to determine
immunity.
• If not detectable, collect a second specimen 2
to 3 weeks later and run concurrently with the
first (paired sera).
• If negative, collect a third specimen 6 weeks
after exposure and test concurrently with the first
specimen. Negative tests indicate that no
infection occurred.
 Vaccination and
Pregnancy
• Women who are pregnant or intend
to become pregnant within 4 weeks
should not receive rubella vaccine.
• If a pregnant woman is inadvertently
vaccinated or if she becomes
pregnant within 4 weeks after
vaccination, counsel her about the
concern for the fetus
Diagnosis of and Screening for
Cytomegalovirus Infection in
Pregnant Women
 CMV infection

• Human cytomegalovirus (CMV) is the

most common cause of congenital
malformation resulting from viral
intrauterine infection in developed
countries
• Primary CMV infection occurs in 0.15 to
2.0% of all pregnancies and may be
transmitted to the fetus in up to 40% of
cases
 CMV Infection

• Up to 15% of intrauterine CMV infections

result in symptomatic congenital disease
at birth, and 10 to 15% of those born with
asymptomatic congenital CMV will
develop significant clinical sequelae in
infancy
• The clinical sequelae of congenital CMV
is usually more severe if transmission
occurs early in gestation

S. C. Munro, Journal Of Clinical Microbiology, Sept. 2005,

 Anti-CMV IgM
• The presence of CMV-specific
immunoglobulin M (IgM) may not be
indicative of primary infection, since it is
also produced during reactivation and
re-infection
• CMV IgM peak during the first 1 to 3
months after primary infection in pregnant
women and then persist at a low level for
18 to 39 weeks, with detection depending
upon both the individual patient and the
sensitivity of the IgM assay used
 Aviditas Anti-CMV IgG
• IgG antigen avidity has been used to
clarify primary or nonprimary infections
by measuring the binding affinity of IgG
antibodies.
• IgG of low avidity are produced at the
onset of infections, and subsequent
maturation of the antibody increases its
avidity over time.
 Aviditas Anti-CMV IgG

• CMV IgG avidity has been shown to

distinguish primary CMV infections from
reactivated infections in pregnant
women, and the maturation rate and
duration of the antibody has been shown
to correlate with patient viremia
• Low-avidity IgG in pregnant women
persists for approximately 17 weeks, with
full maturation of the antibody occurring
approximately 25 weeks after onset of
symptoms
Women Seropositive For CMV
Before Conception
• Fowler et al.6 reported a 1.2% and
12.9% transmission rate in
seropositive and seronegative
women, respectively, indicating that
preconceptional maternal immunity
is protective against congenital
CMV infection, decreasing the risk of
infection by 90%.
S. C. Munro, Journal Of Clinical Microbiology, Sept. 2005
HSV
 HSV
• Herpes simplex virus in the virus family
Herpesviridae, subfamily Alphaherpesvirinae
• Reservoir : Humans.
• Transmission of HSV-2 is usually by sexual
contact
• Transmission to the neonate usually occurs via
the infected birth canal, but less commonly
occurs in utero or postpartum
• Incubation Period: From 2-12 days.
 HSV

• Screening for HSV-1 and –2 infection in

the general population is not indicated
• There are two etiologic agents, herpes
simplex virus (HSV) types 1 and 2:
• HSV-1 causes about 2% of acute
pharyngotonsillitis, usually as a primary
infection.
• HSV-2, occurs mainly in adults and is
sexually transmitted
 Risk Factors for Genital
Herpes Infection (HSV 2)
•
• Advent of sexual activity at or before 17 years of
age
• History of sexually transmitted diseases
• History of undiagnosed genital lesions or
discharge
• Human immunodeficiency virus infection
• Multiple sex partners
• Multiple lifetime sex partners
• Partner diagnosed with genital HSV infection
•
 High Risk of Vertical
Transmission of HSV
• Highest risk among women experiencing
true primary genital HSV infection
• No maternal HSV antibodies before
delivery
• Shedding HSV-1 at delivery (primary or
recurrentdisease)
• Use of fetal scalp monitors in
HSV-seropositive women or women with a
history of genital herpes
•
HSV Infection During Pregnancy
• Approximately 22% of pregnant women
are infected with herpes simplex virus
(HSV)-2, and 2% of women will acquire
HSV during pregnancy
• Maternal acquisition of HSV in the third
trimester of pregnancy carries the highest
risk of neonatal transmission.
•

Zane A. Brown, Obstetrics & Gynecology 2005;106:845-856

 Clinical Criteria for Diagnosis
• A condition characterized by visible,
painful genital or anal lesions. 
• The clinical diagnosis of herpes is
both insensitive and non-specific
Laboratory Criteria for Diagnosis

• Since the distinction between HSV

serotypes influence prognosis and
counseling, HSV should  be
confirmed by laboratory testing :
• Isolation of HSV in cell culture
• HSV antigen detection
• PCR (polymerase chain reaction)
assays
•
 Neonatal Infection
• Neonatal infections are most frequently due to
HSV-2
• Risk to the infant depends on two important
maternal factors: stage of pregnancy at which
the mother excretes HSV whether the infection is
primary or secondary.
• Only excretion at the time of delivery is
dangerous to the newborn, with the rare
exception of intrauterine infections.
• Primary infection in the third trimester in the
mother raises the risk of infection from 3% to over
30%, presumably because earlier maternal
immunity confers a degree of protection.
 Serologic testing
• HSV antibodies form during the first
several weeks after infection and remain
indefinitely.
• Fifty to 90 percent of adults have
antibodies to HSV, but only about 30
percent have antibodies specific to HSV-2
• HSV-2 infection is almost exclusively
sexually acquired, HSV-2 antibodies are
consistent with an anogenital infection
Several types of genital herpes infection
may occur during pregnancy:

• Reactivated infection or recurrence

• Primary infection, where the woman has
not been previously infected by either
HSV-1 or HSV-2
• Nonprimary first episode, where
antibodies to the heterologous HSV
already exist and convey some
protection, making the primary infection
less severe
•
Outcomes From Mothers Who
Shed HSV at Delivery
 How Neonatal Herpes
Infections are Acquired
• At delivery—Up to 90% of all neonatal herpes
infections result from exposure to infected
secretions from an active maternal genital
infection at the time of delivery
• Congenital—Approximately 5% of neonatal
herpes infections are acquired in utero,
so-called true congenital HSV infection
• Nonmaternal source—Around 5% of cases are
contracted from a nonmaternal source, such as
a grandparent, a nurse, or the father
Neonates Acquired HSV
 Reference
• Ingrid Reiter-Owona, Laboratory Diagnosis of Toxoplasmosis-possibilities and
limitations. J Lab Med 2005;29(6):439–445
• Jones J, Lopez and Wilson. Congenital Toxoplasmosis. Am Fam Physician
2003;67:2131-8,2145-6.
• Press C, Montoya JG and Remington JS. Use of single serum sample for diagnosis
of acute toxoplasmosis in pregnant women and other adults. J Clin Microbiol 2005;
43(7): 3481-3483
• Janitschke K. Laboratory diagnosis of toxoplasmoxix-possibilities and limitations. J
Lab Med 2005; 29(6): 439-445
• Brown ZA, Gardella C, Wald A, Morrow RA and Corey, L. Genital Herpes
Complicating Pregnancy. Obstetrics & Gynecology 2005;106:845-856
• Munro SC, Hall B. Whybin Leader R, Robertson, Main GT and Rawlinson WD.
Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women.
Journal Of Clinical Microbiology, Sept. 2005, p. 4713–4718
• Beauman, Genital Herpes: A Review. Am Fam Physician 2005;72:1527-34, 1541-2
• Toxoplasma gondii Infections (Toxoplasmosis) -- 2006 (1) 666 -- Red Book.htm
• Wen-pin Tzeng, Journal Of Clinical Microbiology, Feb. 2005
• Boyer K et. al Am J Obstet Gynecol. 2005 Feb, 192(2): 564-71
• http://www.doh.wa.gov/Notify/guidelines/herpes.htm
• http://www.herpes-foundation.org/download/monitorvol4no1.pdf
• Minnesota Department of Health, www.health.state.mn.us/immunize 2006
• http://en.wikipedia.org/wiki/Toxoplasmosis
•
•
•