Infection in Pregnancy

Jessica Octaviani
 TORCH
T: TOXOPLASMA
O: Other infections(go, sifilis,etc)
R: Rubella Viral Infection
C: Cytomegaloviral
H: Herpes Simplex
 TOXOPLASMOSIS
 Toxoplasmosis is an infection that can threaten the health of an unborn
child
 Toxoplasma gondii is a sporazoan of the subclass Coccidia. The only
species is Gondii.
 It exists in three forms : tachyzoites (trophozoites), tissue cysts (bradizoit
in latent infection), and oocytes (sporozoit).
 It is a common intracellular protozoan, which infects most species of
warm-blooded animals, They span many vertebrates from rodents to
domestic farm animals (including birds) to humans throughout the world.
 A Zoonotic Infection of Humans
 Normal cycle in cats (lions, tigers and puddy tat)
 enteroepithelial (EE) cycle in definitive host
 asexual and sexual division is intracellular in MEC
 oocytes become infective after passage in feces (Oocytes do not become infectious until they
sporulate. Depending on conditions such as temperature, sporulation occurs 2 to 21 days after
the oocyte is excreted in the feces )
 tissue cycle in intermediate/carrier hosts
 all vertebrates are potential hosts (mice, birds,, ?)
 motile, disease producing phase = tachyzoites
 non-motile “slow” phase in pseudocyst = bradyzoites
Pathogenesis
 Sources of Infection
 Source of all oocytes ...
 Domestic (cats, dogs) and wild (zoo) cats
 (Cats are the only known full-life-cycle host of the protozoan) parasite
 Rodents : rats
 Persist in environment (soil) if moist
 reservoir of infective oocytes
 Many intermediate hosts
 reservoir of infective tissue cysts( farm animals—cattle,sheep,rabbit)
 Cycle in humans (an accidental host)
 Infected
 by ingesting infective oocytes (in >4 day old cat feces)
 by ingesting tachyzoites or bradyzoites in rare meat
 by receiving blood or tissues with “-zoites”
 CONGENITALLY by transplacental tachyzoites
 Proliferative stages in humans
 tachyzoites result from all infective stages
 bradyzoites predominate within pseudocysts as IgG
 TOXOPLASMOSIS IN pregnancy
Primary Infection in pregnan womanCongenital
toxoplasmosis develops from the transplacental passage
of tachyzoites to a fetus.
The risk of congenital toxoplasmosis infection from a
mother with primary toxoplasmosis increases during
pregnancy
0% to 9% in the 1st trimester
15-40% of fetuse become infected , when mother are
infected in the 2nd trimester
35% to 59% in the third trimester.
 CLINICAL MANIFESTATION
 Toxoplasma gondii can cause a wide spectrum of disease after infecting a new host, including
acute, latent, and reactivated disease as well as congenital disease
 Congenital tox
 Maternal tox
 + inapparent—subclinical--usually is asymptomatic —most of cases
 +apparent ( 10-20 %)—not specific
 =generalised tox—flue like illness- fever,fatigue,weakness,malaise
 = lymphatic tox---fever,generalised lymphadenopathy(retroperitoneal,
mesentric{abdominal pain},lumbar,occiptal), liver and spleen enlargement
The lymphadenitis may wax and wane for months and finally resolve spontaneously. It is
commonly mistaken with infectious mononucleosis).
 =neurological tox---encephalopathy,chorioretinitis
 =exanthematous tox---generalised maculopapular erythramatous patches
 = Ocular tox--- eye pain, Photophobia, blurred vision, scotoma ("blind spot"),
chorioretinitis, Retinitis, blindness
 =The acute acquired form however, can be a fulminating disease with an erythematous
rash, fever, malaise, myositis, dyspnea, acute myocarditis,and encephalitis. Outcome can be
fatal, but this form of toxoplasmosis is rare
 Sayogo (1978) dari 288 wanita hamil yg dtg ke RSCM,
angka kejadian seropositif 14,25%, dan terjadi 4 persalinan
prematur dan 1 kasus kel. Kongenital.
 Incidens toxoplasmosis kongenital varians from 0,8 per
10.000 delivery in USA to 10 per 10.000 di Prancis. (Dubey,
2000).
 Toxo Diagnosis
 Morphologic
 tachyzoites in circulating WBC,
bone marrow, lung, spleen, brain ?
 histopathologic examination
 Culture or animal inoculation (rare) Isolation of parasites from
blood or other body fluids, by intraperitoneal inoculation into
mice or tissue culture. The mice should be tested for the
presence of Toxoplasma organisms in the peritoneal fluid 6 to
10 days post inoculation; if no organisms are found, serology
can be performed on the animals 4 to 6 weeks post
inoculation.
 Serologic (mainly)
 Detection of parasite genetic material by PCR, especially in
detecting congenital infections in utero.
 unreliable in immunodeficient (AIDS) pts
 normally IgM and IgG rise simultaneously
 IgG - persists for years
 IgM - undetectable after “cure”
 elevated IgM titer is diagnostic of recent infection in persons with normal
immunity
 disseminated infection may exist in AIDS pts without demonstrable titer
 A negative IgG or IgM test excludes Diagnosis
 both should be + if acutely infected
 If IgG screening is + then do IgM test
 a + IgM test confirms acute toxoplasmosis or current Toxoplasma infection
(measure IgM antibodies, have low specificity and the reported results are
frequently misinterpreted. In addition, IgM antibodies can persist for months
to more than one year)
 Submit IgG positive sera to CDC for IgM testing for diagnosis of acute Toxo
IgG levels begin to rise 1 or 2 weeks after infection.
Peak levels are reached in 6 to 8 weeks, then
gradually decline over a period of months or even
years. Low levels of IgG are generally detectable for
life.
Detectable levels of IgM antibody appear
immediately before or soon after the onset of
symptoms. IgM levels normally decline within 4 to 6
months, but may persist at low levels for up to a year
immunocompromised individuals may not produce
any IgM. Antibody levels do not correlate with
severity of illness
 prevention
 Previous exposure prevents congenital

 education
 avoiding exposure to the parasite, mostly by simple hygienic
measures.
 avoid exposure to oocytes
 no cats or cat feces !
 no raw meat for you or your kitty !
 keep house cats inside - avoid stray cats !
 let anyone empty the cat box !
 cover the kid’s sand box !
 wear gloves in the garden, wash your hands!
 wash all fruits and vegetables,
 wash hands carefully after handling raw meat, fruit, vegetables, and soil
 pregnant women should cook their meat until it is no longer pink and
the juices run clear
 TREATMENT
 Drugs of choice for pregnant women or immunocompromised persons:
      Spiramycin or Pyrimethamine plus Sulfadiazine

 Treatment
 pyrimethamine (Daraprim) 25 mg/days + sulfadiazine 1 g/days
side effects( skin rashes and leukopenia )are common in AIDS pts
 High-dose therapy is continued for 4-6 weeks, and lower dose
maintenance therapy is given thereafter. Maintenance therapy can be
discontinued in patients who have completed the course of initial
treatment and are without symptoms,
  Spiramycin 3g/ days given in 3 weeks,in aterm pregnancy it’s given
again between 2 weeks alone before 26 weeks
 pyrimethamine + clindamycin or dapsone( 1-2 mg/kgbw/days 2x/days)
 Clindamycin, a similar drug, is often substituted for sulfadiazine in
patients with sulfa allergy
 NB : Pyrimethamine can cause low blood counts in some people.  To
counter the possible effects of pyrimethamine on the bone marrow,
another drug called leucovorin (folinic acid) is given along with
pyrimethamine

 Prophylaxis –in the primary prevention of toxoplasmosis in persons with

HIV who have dormant or latent infection
 TMP-SMX - trimethoprim-sulfamethoxazole
 pyrimethamine plus folinic acid
 dapsone + pyrimethami
RUBELLA
 RUBELLA
 Togavirus
 RNA virus
 Rapidly inactivated by chemical agents, ultraviolet light,
low pH, and heat
 RUBELLA PATHOGENESIS
 Respiratory transmission of virus
 Replication in nasopharynx and regional lymph nodes
 Viremia 5-7 days after exposure with spread to tissues
 Placenta and fetus infected during viremia
CLINICAL MANIFESTATION
 Incubation period 14 days
 (range 12-23 days)
 Prodrome of low-grade fever
 Maculopapular rash 14-17 days after exposure
 Lymphadenopathy in second week
Congenital Rubella Syndrome
 Deafness
 Cataracts
 Heart defects
 Microcephaly
 Mental retardation
 Bone alterations
 Liver and spleen damage
 Rubella Laboratory Diagnosis
 Isolation of rubella virus from clinical specimen (e.g.,
nasopharynx, urine)
 Positive serologic test for rubella IgM antibody
 Significant rise in rubella IgG by any standard serologic
assay (e.g., enzyme immunoassay)
 A pregnant woman exposed to rubella should be tested
immediately for a rubella-specific antibody. The presence of
rubella-specific immunoglobulin G (IgG) is evidence that the
patient is immune.
 If the test result is negative, repeat the test again in 3-4 weeks,
and also repeat the test on the first specimen. If an antibody is
present in the second test and not in the first test, an infection
has occurred.
 If the second test result is negative, repeat the test in 6 weeks,
and, again, test it with the first specimen.
 A negative test result in both specimens means an infection
has not occurred, whereas if the last specimen is positive and
the first specimen is negative, then an infection has occurred
 prenatal diagnosis Tanemura (1996) finding RNA rubella
in vili chorion,amnion fluid, or blood of fetus in 23% to 34
in suspected case
 TREATMENT
 No specific treatment of rubella exists.
 Prevention
 Vaccine rubella before marriage
 CYTOMEGALOVIRUS
 CMV
EPIDEMIOLOGY
DNA virus
Humans are only host
May remain latent in host
cells
 CMV
EPIDEMIOLOGY
Horizontal transmission
Vertical transmission
In utero – greatest danger
During delivery – minimal risk
Breast feeding – minimal risk
Infeksi pada trimestes I atau awal trimester II
hidrosefalus, mikrosefalus, mifkroftalmia, hernia,
gangguan pendengaran, retardasi mental, dan
kalsifikasi serebral.
Infeksi pada bulan2 terakhir kehamilan 
hepatosplenomegali, trombositopeni, purpura,
korioretinitis, dan pneumonitis.
Infeksi setelah lahir  pneumonia,
hepatosplenomegali, dan sepsis
 CMV
CLINICAL MANIFESTATIONS
Malaise
Fever
Lymphadenopathy
Hepatosplenomegaly
 CONGENITAL CMV
DETERMINANTS OF FETAL RISK

THE GREATEST RISK IS ASSOCIATED WITH

PRIMARY MATERNAL INFECTION IN THE FIRST
HALF OF PREGNANCY
 CONGENITAL CMV
DETERMINANTS OF FETAL RISK

Recurrent maternal infection

poses much less risk to fetus
Infection acquired during
delivery or via breast feeding
poses negligible risk
RISK OF CONGENITAL CMV WITH PRIMARY
MATERNAL INFECTION
1 to 4 % of pregnant women
seroconvert
40 - 50 % of fetuses are infected
5 - 15 % of these fetuses will be
symptomatic at birth
MANIFESTATIONS OF SEVERE CONGENITAL
CMV INFECTION
Hepatosplenomegaly
Intracranial calcifications
Jaundice
Growth restriction
Chorioretinitis
Hearing loss
“ Blueberry Muffin Baby”
 Diagnosis
 ELISA
 Viral isolation in tissue
 Diagnosis prenatal  USG, CT Scan, MRI.
 Enders (2001)  abnormal USG with positive CMV +
amnion fluid 75% symtomatic congenital infection
 TREATMENT
  diberik obat anti virus.
 PREVENTION OF CONGENITAL CMV
INFECTION
Vaccine is not commercially available
Anti-viral drugs do not prevent fetal injury
Anti-CMV antibody may be effective
Key to prevention is “universal precautions”
HERPES INFECTION
 Virology
 Alpha herpes viruses:
Herpes simplex virus type 1 (HSV-1)

Herpes simplex virus type 2 (HSV-2) Varicella zoster virus

(VZV)
 Virology
 HSV-1
 HSV-2
 The incidence of antibodies specific for HSV-2 increases with
age.
 20% of women have antibody to type HSV-2 virus.
 The risk for type 2 antibody were greatest among blacks and
previously married women.
Clinical Infection
• Primary Infection

• Reccurent infection
 First episode infection:
 It is frequently symptomatic.
 Some first episodes are mild due to cross reacting antibody from
childhood acquired type 1 infection.
 Prior orolabial infection with type 1 virus may modify an initial
type 2 genital infection .
• Typical incubation period of 3-6 days.
• Popular eruption with tingling which then
become painful and vesicular.
• Painful perineal lesions that may coalesce.
• Inguinal adenopathy
• Influenza-like symptom
• Occasionally hepatitis ,encephalitis ,or
pneumonia
• Urinary retention due to sacral nerve
involvement
• Cervical involvement
 Recurrent infection
 Lesions are fewer in number, less tender ,shed virus for shorter
periods (2-5 days).
 Typically recur at same sites.
 Cervical involvement is less frequent.
 Sub clinical shedding often followed symptomatic recurrence.
• Tissue culture(95% sensitive) optimal for
clinically or asymptomatic recurrence .
• Cytological examination, specific for cervical
infection and sensitive for for genital ulcer
disease
• PCR(8 times higher detection rate)
• Antibodies
 Treatment: No effective treatment
• In first episode infections:
Acyclovir: -Topically
-Oral 400 mg orally
-Parenteral
Analgesics or topical anesthetics
Indwelling catheter in severe urinary retention .
In HIV patient ,increasing the dose of Acyclovir

• In recurrent infections:
Acyclovir :Reduce recurrence in pregnancy
Decrease rate of C/S due to recurrent herpes
200-400 mg TDS is well tolerated in late of pregnancy
• 0.2-0.3 pregnant women in early labor has HSV
infection, most of them are recurrent infection.
• Baschat AA, determined this prevalence in
asymptomatic patients . Forty-four (6.4%) amniotic
fluid samples were positive for viral genome . Viral
genome is commonly found in amniotic fluid with a
sonographically normal fetus, and the prevalence
follows a seasonal pattern .
(J Matern Fetal Neonatal Med. 2003 Jun;13(6):381-4).
• 80% of women with recently acquired HSV-2
genital infection will have an average of 2-4
symptomatic recurrence during pregnancy.
• Concomitant cervical shedding is identified in
about 15% of women with clinically evident
vulvular recurrence.
• 10% of recurrence in pregnancy will be
asymptomatic.
• Clinical recurrence appear to be slightly more
common in late pregnancy ,asymptomatic
cervical shedding of herpes virus is unaffected
by the duration of pregnancy.
• Vertically transmission:
Trans placental (in uteri transmission)
Retrograde (Ascending)
Immediate postnatal period (Breastfeeding)
• Prophylactic acyclovir beginning at 36 weeks'
gestation reduces the risk of clinical HSV
recurrence at delivery, cesarean delivery for
recurrent genital herpes, and the risk of HSV
viral shedding at delivery.
(Sheffield JS, Obstet Gynecol. 2003
Dec;102(6):1396-403).
 Significant experience has been gained with the use of
acyclovir in pregnancy and it is recommended for both
episodic and suppressive therapy in pregnant women. Its use
has been demonstrated to be cost-effective in suppressive
therapy, although issues regarding compliance and the
potential for neonatal neutropenia need to be addressed
 ((Sheffield JS, Obstet Gynecol. 2003 Dec;102(6):1396-403).
 Refrences
 Wiknjosastro H, Saifuddin AB, Rachimhadhi T. Ilmu
Kebidanan. Edisi 3. Jakarta: Yayasan Bina Pustaka Sarwono
Prawirohardjo.2007;551-4
 Cunningham FG et al. William Obstetrics. New York. Mc
Graw Hill. 2003.
 Sheffield JS, Obstet Gynecol. 2003 Dec;102(6):1396-403).