Transcript Obstetric and perinatal infections

Obstetric and perinatal
infections
During pregnancy,
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tissues potentially susceptible to infection
-the placenta
The placenta
- effective barrier:
- protects the fetus from most circulating
microorganisms
- the fetal membranes shield the fetus from
microorganisms in the genital tract.
- Perforation of the amniotic sac, for instance,
at a late stage of pregnancy, often results in
fetal infection.
During pregnancy,
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certain infections in the mother can be
more severe than usual
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latent viruses can reactivate and infect the
fetus
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after delivery the raw uterine tissue is
susceptible to pathogens, causing
puerperal sepsis.
During pregnancy,
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certain infections in the mother can be
more severe than usual :
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Malaria
Hepatitis
Influenza
UTI..
The fetus
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once infected via the placenta, is highly susceptible,
but may survive certain pathogens and
develop congenital abnormalities;
examples include: Rubella, CMV, Toxoplasma gondii and
Treponema pallidum.
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Maternal genital HSV infection can cause more serious
neonatal disease and is underreported.
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TORCH: -Toxoplasma
-Rubella
-CMV(Cytomegalovirus)
-Herpes
-Others (Sy:Syphilis)
The fetus
Bacteria from the vagina, such as
-group B streptococci, can cause neonatal septicemia,
meningitis and death, and
 a birth canal infected with
-Neisseria gonorrhoeae or Chlamydia trachomatis inoculates
the infant to cause neonatal conjunctivitis.
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Maternal HIV infection :
◦ abortion
◦ prematurity
◦ low birth weight
◦ If no prophylaxis is applied up to 40%
of infants are infected(In resourcepoor countries or where maternal
infection is undiagnosed)
-about one-third in utero
-two-thirds perinatally:
- from maternal blood
- milk
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Maternal blood:
◦ hepatitis B (HBV)
◦ hepatitis C(HCV)
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milk can be a source of HTLV-1 (human T-cell
lymphotropic virus type 1)
INFECTIONS OCCURRING IN
PREGNANCY
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Immune and hormonal changes during pregnancy
worsen or reactivate certain infections
The fetus may be considered as an immunologically
incompatible transplant that must not be rejected by
the mother. Reasons for the failure to reject the fetus
include:
the absence or low density of major histocompatibility
complex (MHC) antigens on placental cells
a covering of antigens with blocking antibody
subtle defects in the maternal immune responses.
INFECTIONS OCCURRING IN
PREGNANCY
 The picture is further complicated when
there is malnutrition, which in itself impairs
host defenses by weakening immune
responses, decreasing metabolic reserves
and interfering with the integrity of
epithelial surfaces.
The fetus has poor immune defenses
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Once the fetus is infected, it is exquisitely susceptible
because:
IgM and IgA antibodies are not produced in significant
amounts until the second half of pregnancy
There is no IgG antibody synthesis
Cell-meditated immune responses are poorly developed
or absent, with inadequate production of the necessary
cytokines.
 Most microorganisms have sufficient
destructive activity to kill the fetus once it
is infected, leading to spontaneous
abortion, or stillbirth.
 They can interfere with fetal development
or cause lesions so that a live but damaged
baby is born.
CONGENITAL INFECTIONS
Intrauterine infection may result in
-death of the fetus or
-congenital malformations
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After primary infection during
pregnancy
certain microorganisms enter the blood,
establish infection in the placenta, and then
invade the fetus.
The fetus sometimes dies, leading to abortion,
but when the infection is less severe, as in the
case of a relatively non-cytopathic virus, or
when it is partially controlled by the maternal
IgG response, the fetus survives.
 It may then be born with a congenital infection,
often showing malformations or other
pathologic changes.
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After primary infection during
pregnancy
The infant is generally small and fails to
thrive.
 It produces specific antibodies, but often, for
instance with CMV, fails to generate an
adequate virus-specific cell-mediated
immune response, remaining infected for a
long period.
 Hence, the lesions may even progress after
birth. It is a striking feature of these
infections that they are generally mild or
unnoticed by the mother.
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Important causes of congenital
infections
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Viruses that induce fetal malformations (i.e. act as
teratogens) share certain characteristics with other
teratogens such as drugs or radiation .
The fetus tends to show similar responses (e.g.
hepatosplenomegaly, encephalitis, eye lesions, low birth
weight) to different infectious agents, and the diagnosis
is difficult on purely clinical grounds.
Most of these infections, HSV, rubella, CMV and syphilis,
can also, at times, kill the fetus.
They generally follow primary infection of the mother
during pregnancy, so their incidence depends upon the
proportion of non-immune females of childbearing age.
Routine antenatal screening
rubella antibody,
 treponemal antibody (which includes syphilis, yaws, pinta
or bejel, which cannot be identified individually by
serology),
 hepatitis B surface antigen and
 HIV antibody
 These tests help identify women who are infected with
hepatitis B or HIV, infected or have been exposed in the
past to treponemal infections, the most important of
which is syphilis in this setting, or are susceptible to
rubella.
 Toxoplasma antibody
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Routine antenatal screening
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rubella antibody: ELISA Rubella IgG /IgM
If positive:
avidity test
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treponemal antibody:RPR/TP-PA
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hepatitis B surface antigen
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HIV antibody
Routine screening programs lead to
clinical management issues for both the
mother and child.
For example, HIV diagnosis will lead to
consideration of
-antiretroviral therapy for the mother and,
immediately on birth,
-the child, offering a caesarean section delivery, and
-advising against breast-feeding to reduce the risk of
vertical transmission.
In addition, the child will then be followed-up for at
least 12 months using sensitive tests to determine
whether HIV has been transmitted vertically.
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Routine screening programs lead to
clinical management issues for both
the mother and child.
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Diagnosis of chronic hepatitis B infection will
result in determination of the maternal level of
infectivity, and
subsequently offering an accelerated course of
hepatitis B vaccine alone or,
if the mother is highly infectious, vaccine and
HBV-specific immunoglobulin (HBIG) to the
baby.
In addition, there are antiviral drugs for chronic
hepatitis B that might be offered, together with
long term follow-up, to the mother.
Routine screening programs lead to
clinical management issues for both
the mother and child.
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Rubella susceptible women are offered rubella
immunization postnatally.
Women found to have been exposed to treponemal
infection in pregnancy are offered antibiotic
treatment and the baby is followed-up for the first
year using serology to identify active infection, as
congenital syphilis can result from earlier untreated
infection of the mother
In the case of CMV, which is not part of routine
antenatal screening, a primary infection, re-infection
or reactivation of the latent virus during pregnancy,
can lead to fetal infection .
The likelihood of fetal infection
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is increased when the mother develops a
poor immune response, when the
concentration of infectious agents in her
blood is high (primary or secondary
syphilis, e antigen positive hepatitis B
carrier, HIV), or in a primary infection.
 Maternal mumps, influenza or poliovirus infection during
pregnancy:
 no good evidence for harmful effects in the fetus
 Human parvovirus:
 fetal damage or death in 5-10% of cases
following maternal infection in early
pregnancy.
 severe anemia with ascites and
hepatosplenomegaly (hydrops fetalis)
 the virus infects progenitor erythroid stem
cells.
 Intrauterine exchange blood transfusion is
used to manage hydrops fetalis.
Congenital rubella
The fetus is particularly susceptible to
rubella infection when maternal
infection occurs during the first 3
months of pregnancy
 At this time, the heart, brain, eyes and
ears are being formed and the infecting
virus interferes with their development.
 If the fetus survives, it may show certain
abnormalities
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Organ involvement and effects in
congenital rubella
Congenital rubella
 Not all fetuses are affected
 detectable congenital defects were seen:
 15.3% in the first month
 24.6% in the 2nd month
 17.5% in the 3rd month
 6.5% in the 4th month.
Congenital rubella can affect the
eye, heart, brain and ear
 Fetal rubella IgM is found in cord
and infant blood
 Congenital rubella is completely
preventable by vaccination
RUBELLA Vaccination
 live
attenuated virus vaccine :
MMR (mumps, measles and
rubella)
 Contraindication: Pregnancy to
vaccination,
 Safe
time during reproductive
life is the immediate postpartum
period.
Antirubella IgG antibodies
should be quantitative and
 ≥10IU/ml shows immunity
CMV
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Primary maternal infection during pregnancy:
◦ 40% of fetuses are infected
◦ 5% of these show signs at birth.
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CMV reactivation during pregnancy in women with
previous CMV exposure,:
◦ Fetal damage is then uncommon.
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As many as 1-2% of infants born in the USA are
infected, and up to about 10% of these are symptomatic,
with up to 1 million infectious doses of virus present
per ml of urine.
However, the incidence of congenital CMV infection is
likely to be an underestimate worldwide.
Congenital cytomegalovirus infection
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Microcephaly with associated severe
psychomotor retardation and
hepatosplenomegaly
 Clinical features of congenital CMV include
mental retardation, spasticity, eye abnormalities,
hearing defects, hepatosplenomegaly,
thrombocytopenic purpura and anemia
 Deafness and mental retardation may not be
detectable until later in childhood.
 Diagnosis:
 CMV-specific IgM antibodies in infant blood
(within 2-3 weeks of delivery)
 CMV DNA in the blood or urine during this
period.
Congenital syphilis
As a result of routine serologic screening for
syphilis in antenatal clinics and treatment with
penicillin,
 congenital syphilis is now rare,
 but is more common in resource-poor
countries.
 Clinical features in the infant include rhinitis
(snuffles), skin and mucosal lesions,
hepatosplenomegaly, lymphadenopathy, and
abnormalities of bones, teeth and cartilage
(saddle-shaped nose).
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Congenital syphilis
Pregnancy often masks the early signs of
syphilis, but the mother will have
serological evidence of treponemal
infection, and treponemal IgM will be
detected in the fetal blood.
 Vertical transmission most commonly
takes place after 4 months of gestation,
therefore treatment of the mother before
the 4th month of pregnancy should
prevent fetal infection.
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Diagnosis of congenital sy in the
baby
enzyme-linked immunosorbent assays:
 SY IgM and IgG
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 Congenital syphilis is completely
preventable if women are screened
serologically early in pregnancy (<3
months) and those who are positive are
treated with penicillin.
Congenital toxoplasmosis
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Acute asymptomatic infection by Toxoplasma gondii
during pregnancy can cause fetal malformation
Approximately 35% of healthy adults have serological
evidence of previous Toxoplasma gondii infection.
Clinical features of congenital toxoplasmosis in the
infant include convulsions, microcephaly, chorioretinitis,
hepatosplenomegaly and jaundice, with later
hydrocephaly, mental retardation and defective vision
There are often no detectable abnormalities at birth,
but signs (e.g. chorioretinitis; generally appear within a
few years.
Congenital toxoplasmosis
Toxoplasma IgM
Toxoplasma IGG
Avidity test if IgG/IgM is positive
PCR (in amniotic fluid)
Avidity
A test carried out with spesific positive
IgG test
 The strength the antibodies bind with
their antigen and shown against being
separated.
 As the antibody matures the avidity
increases:
 Recent infection:Low avidity
 Past infection(more than 3 months
ago): High avidity
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Congenital HIV infection
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Most infections take place during late pregnancy or during delivery,
transmission rates are reduced by
lowering the HIV load by offering
antiretroviral drugs during
pregnancy, especially during the last
trimester or during labor,
◦ carrying out an elective caesarean
section
◦ avoiding breast-feeding.
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Congenital HIV infection
 IgG antibodies present in the neonatal blood sample
may be maternal in origin and can persist for at least 1
year.
 The mainstay of laboratory diagnosis therefore involves
detection of HIV-1 proviral DNA or HIV-1 RNA by
polymerase chain reaction (PCR), although these tests
may not be positive until several months after birth,
Congenital and neonatal listeriosis
Listeria monocytogenes
 small Gram-positive rod
 beta-hemolytic
 worldwide
 a great variety of animals including cattle, pigs, rodents
and birds, and the bacteria occur in plants and in soil
 can grow at regular refrigeration temperatures (e.g. 34°C)
 Transmission to humans is by:
 contact with infected animals and their feces
 consumption of unpasteurized milk or soft cheeses or
contaminated vegetables.
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Congenital and neonatal listeriosis
 the pregnant woman:
 mild influenza-like illness
 Asymptomatic
 but there is a bacteremia:
 which leads to infection of the placenta and then
the fetus:
 abortion
 premature delivery
 neonatal septicemia
 The infant can also be infected shortly after
birth, for instance from other babies or from
hospital staff, and this may lead to a meningitic
illness.
VZV
 Primary
infection with varicellazoster virus (VZV)
 in the first 20 weeks of pregnancy
 can lead to limb deformities and
other severe lesions in the newborn
Fetal infection with herpes
simplex must be considered in a
baby who is acutely ill within a
few weeks of birth
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HSV
generalized infection and severe CNS involvement.
Approximately 80% of mothers with primary HSV
infection (only about 10% with recurrent HSV) have
cervical lesions and about a third of their infants are
infected. Babies <4 weeks of age may present with
neonatal HSV as acutely ill and 'septic' but classically
there are three well-defined clinical presentations.
Treatment could be started at the same time as
samples are collected for HSV DNA detection that
include swabs of the vesicles, if present, EDTA whole
blood samples and cerebrospinal fluid. Morbidity and
mortality rates are higher in those with encephalitis
and disseminated disease.
 Gonococci , chlamydia or staphylococci can infect
the eye to cause ophthalmia neonatorum. Infection
with group B streptococci generally occurs at this
time.
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Gonococcal ophthalmia
neonatorum
Signs appear 2-5 days after birth. The inflammation and edema are
more severe than with chlamydia infection
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In countries with high hepatitis B carrier rates, maternal
blood is a major source of infection during or shortly
after birth. More than 90% of infants from carrier
mothers become infected and then carry the virus. This
is preventable by giving the vaccine plus specific
immunoglobulin to the newborn. Hepatitis C, in
contrast, is not usually transmitted in this way, and <5%
of children with carrier mothers are infected.
Human milk may contain rubella virus, CMV, human Tcell lymphotropic virus (HTLV) and HIV.Virus titers are
generally low and, except in the case of HTLV and HIV,
milk is not thought to be an important source of
infection. However, it makes sense to pasteurize milk in
human milk banks, just as we pasteurize cows' milk.
Puerperal sepsis
 After
delivery (or abortion), a large
area of damaged vulnerable uterine
tissue is exposed to infection.
 Puerperal sepsis (childbed fever) was
a major cause of maternal death in
Europe in the 19th century.
Puerperal sepsis
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Group A beta-hemolytic streptococci
nose, throat or skin of hospital attendants
Other possible organisms include anaerobes
such as Clostridium perfringens or Bacteroides, E.
coli and group B streptococci and originate from
the mother's own fecal flora.
During the first 1-2 weeks of life
Staphylococci
 from the noses and fingers of adult carriers
 staphylococcal conjunctivitis or 'sticky eye‘ skin sepsis
in the neonate, and sometimes the staphylococcal
'scalded skin' syndrome due to a specific 'epidermolytic'
staphylococcal toxin.
 Handwashing
 aseptic techniques.
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Poor hygienic
in resource-poor countries
Clostridium tetani
usually because instruments used to cut
the cord are contaminated with bacterial
spores
 It can be prevented by immunizing
mothers with tetanus toxoid
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Tetanus. Risus sardonicus in a newborn
infant.
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During pregnancy, certain infections can be more severe than usual, and
there can be reactivation of certain persistent infections
A few infections are able to pass to the fetus via the placenta and cause
damage. These infections are generally mild or subclinical in the mother
(rubella, CMV, toxoplasmosis), but this is not always the case (syphilis)
Once infected, the fetus may die, but more importantly may survive and be
born with the infection (HIV, toxoplasmosis), often showing characteristic
malformations (rubella, syphilis)
Infection of the infant during birth or shortly afterwards can cause local
disease (conjunctivitis due to gonococci or chlamydia) or occasionally
severe life-threatening illness (E. coli meningitis, herpes simplex virus or
group B streptococcal infection)
Life-threatening bacterial infection of the mother via the postpartum
uterus (puerperal sepsis) used to be common but is now rare in resourcerich countries.