Infectious diseases in pregnancy

Introduction



In pregnant women, most infections are no more

serious than in non-pregnant women of similar age.



However, some infections can be transmitted to the

fetus in utero or to the infant during or immediately

after delivery, with potentially serious sequelae.



Uncommonly, serious infectious illness in the

mother can have non-specific fetal or obstetric

effects and lead to miscarriage, premature labour

or fetal death; these infections must be treated as

any other serious illness.



Much more common and a source of anxiety is mild

illness or suggestive laboratory findings in the

absence of symptoms.

Pregnancy represents a relatively
immunocompromised state, with hormonal
and immunological changes. Various
hormones made by the trophoblast have
been shown to interfere with the induction
of the immune response. These include

progeserone

and

oestradiol

,which inhibit

cytotoxic T-cells and natural killer cells.
These physiological alterations in
immunoregulation may help support the
feto-placental allographt, but may expose
the mother to increased susceptibility to
various pathogens.

Route of transmission

Vertical transmission: Spread of infection from a mother to

her fetus or newborn infant by a route dependent on their

unique relationship (eg, postnatal HIV transmission from breast

milk is vertical, whereas transmission of herpes simplex virus

from a maternal oral lesion is horizontal):



Intrauterine transmission: Occurs via the transplacental

(haematogenous) route any time during pregnancy. Ascending

transmission from the genital tract usually occurs late in

pregnancy or at delivery and is classified here in "perinatal"

transmission.



Perinatal transmission: Occurs shortly before onset of labour

or during delivery via the haematogenous or genital route.



Postnatal transmission: Breastfeeding is the only vertical

route.

Pathogen (disease) Usual route of

transmission

Intrauterine Perinatal
Postnatal



Rubella virus ++ – +



Treponema pallidum (syphilis) ++ - -



Toxoplasma gondii ++ - -



Cytomegalovirus ++ ++ (G,H) +



Parvovirus ++ – –



Varicella zoster virus (chickenpox)+ ++ (H) –



Human immunodeficiency virus ± ++(H) +



Hepatitis B virus ± ++ (H) +



Hepatitis C virus ± ++ (H) –



Herpes simplex virus ± ++ (G,H) –



Chlamydia trachomatis – ++ (G) –



Neisseria gonorrhoeae – ++ (G) –



Listeria monocytogenes + ++ (G,H) –



Group B streptococci +/- ++(G,H) –

G = genital H = haematogenous

TORCH



oxoplasmosis



thers – VZV, Parvovirus, Syphilis,

HIV



ubella



ytomegalovirus



erpes simplex virus

TORCH



The TORCH complex is a group of similar

malformations induced by microbial teratogens. These

microbes affect 1-5% of all live births and are among

the leading causes of neonatal morbidity and

mortality.



General symptoms include premature birth, growth

retardation, neurological abnormalities, damage of the

eye, liver, heart and ear as well as bone lesions.

Microcephaly, hydrocephaly, seizures and

psychomotor retardation accompany these

malformations.

Cytomegalovirus infection



Cytomegalovirus is the most common cause of

congenital infection and non-hereditary

deafness

Currently, there is no vaccine or treatment that can

be given during pregnancy.



CMV infection is transmitted by contact with

saliva,

urine or genital secretions

and often causes mild

hepatitis, atypical lymphocytosis and non-specific

symptoms during the self-limiting primary

infection. The virus then becomes latent, but is

reactivated periodically during episodes of mild

immunosuppression caused by intercurrent

infection, pregnancy or stress. Reactivation is

asymptomatic, except in severely

immunocompromised individuals.

Cytomegalovirus infection



Primary maternal infection

occurs in about 1,5-3,5% of

pregnancies and results in fetal infection in about 40%

of cases; fetal damage is most likely early in

pregnancy. Most congenitally infected infants are

apparently normal at birth, but

long-term sequelae

most commonly deafness and mild intellectual

impairment, occur in up to 40% (10%–15% of all

infants of women with primary infection during

pregnancy). Symptomatic multisystem disease,

characterised by growth retardation, microcephaly,

intracranial calcification, thrombocytopenia and

hepatitis, is uncommon.



Reactivation of maternal infection

during pregnancy

can also cause fetal or perinatal infection (about 1% of

infants), but sequelae are uncommon and usually mild.

It is usually difficult to distinguish asymptomatic

primary maternal infection from reactivation or to

determine precisely when infection occurred.

Cytomegalovirus infection

Symptoms of CMV infection in fetus:



Low birthweight



Hepatosplenomegaly



Intracranial calcifications



Hemolytic anaemia



Thrombocytopenic purpura



Chorioretinitis



Microophtalmia



Jaundice



Deafness



Mental and motor retardation

Cytomegalovirus infection



If primary maternal CMV infection is suspected

because of close contact or a compatible illness,

serological and liver function tests will usually

confirm the diagnosis.



More often, primary CMV infection is suspected

because of a positive CMV IgM result in routine

antenatal screening. False positive CMV IgM results

are common, because of cross-reactions, viral

reactivation or persistent low-level IgM after past

primary infection.



IgG avidity testing will help distinguish recent from

long-past infection. Ideally, women who believe they

are at risk of CMV infection, such as childcare

workers, should be tested for IgG before conceiving.

Cytomegalovirus infection



If recent CMV infection is likely or cannot be excluded,

especially in the first trimester, amniocentesis should

be considered to determine whether the fetus is

infected. It should be done at least six weeks after the

likely time of infection. CMV isolation or positive

nucleic acid test results from amniotic fluid indicate

fetal infection, but not necessarily morbidity, while

negative results indicate that severe fetal morbidity is

extremely unlikely.



If fetal infection is confirmed, the stage of pregnancy

at which it occurred, viral load in the amniotic fluid

and evidence of fetal abnormality or growth

retardation on ultrasound examination may aid in

considering termination of pregnancy.

Toxoplasmosis



Toxoplasma gondi is an intracellular protosoan parasite.



Like CMV infection, toxoplasmosis is usually asymptomatic

or has mild, non-specific symptoms. Primary infection

during pregnancy can cause serious fetal effects. However,

unlike CMV infection, toxoplasmosis during pregnancy can

be treated, potentially reducing the fetal effects.



Asymptomatic women with perceived risk (eg, contact with

cats) are often tested for toxoplasma IgG. There is no

clearly defined group of women at increased risk, about

80% of women are susceptible and seroconversion during

pregnancy is uncommon. False positive toxoplasma IgM

results are not uncommon, and low levels of IgM may

persist for many months or years after primary infection.

Like CMV, toxoplasma infection remains latent for life, but

clinical reactivation is confined to severely

immunosuppressed individuals. Infants of women who are

seropositive before conception are not at risk.

Toxoplasmosis



Toxoplasmosis is acquired through eating

raw

or undercooked meat

or ingesting

soil

contaminated with toxoplasma oocysts, which

are excreted in the faeces of infected cats.



Pregnant women should be specifically

advised to avoid these exposures. Frequent

hand washing is advised. Direct contact with

cats is rarely a source of infection (they are

usually infected as kittens and excrete

oocysts for a relatively short time).

Toxoplasmosis



Investigation of suspected acute toxoplasmosis is

similar to that of suspected CMV infection.



Serological testing can demonstrate antibodies to

Toxoplasma gondi, IgM antibody or significant

changes in the IgG antibody titre, indicating recent

infection.



For maternal infection in the first trimester, it is

particularly important to determine whether the

fetus is infected, as likelihood of fetal infection is low

(about 15%), but, if it occurs, fetal damage is likely

to be severe.

Later in pregnancy, infection is more

likely, but fetal damage is less likely and, if it occurs,

less severe.

Congenital toxoplasmosis



Chorioretinitis



Intracranial calcifications



Hydrocephalus



Hepatosplenomegaly



Icterus



Anemia



75% of infected infants at birth have no symptoms

but long-term sequelae occur in up to 40%:



Intellectual impairment



Mental and motor retardation

Toxoplasmosis

Laboratory tests in pregnant
woman

Before pregnancy



Women with (+) IgG– recent infection in the past;

there is no risk of infection for fetus.



Women with low level of (+)IgG – check IgM and

repeat IgG after 3 weeks
if (-) IgM and IgG is stabile – recent infection

In pregnant women



If high level of IgG or IgM – active infection –

repeat tests systematically



If (-)IgG – there is no infection – repeat IgG every

1-2 months

When toxoplasmosis in pregnancy is
diagnosed...



USG (calcification, microcephalus,

hydrocephalus, hepatomegaly, NIHF-non-

immunlogic hydrops fetalis)



Cordocentesis at about 20 weeks’gestation
IgM - sensitivity 47%, IgA – 38%
Specificity – 97%



LDH, leukocytes, eozynophiles, platels, GGTP



Amniotic fluid – PCR - sensitivity – 81%,

specificity – 96%

Toxoplasmosis

Treatment



If maternal infection is confirmed or
cannot be excluded, antibiotic
treatment appears to reduce the risk
of fetal infection and sequelae.



<20 w’g – spiramycin



>20 w’g – pirymethamine +
sulphonamides

Rubella



Rubella is an acute child-age disease and is caused by

Rubella virus –RNA virus



The incubation period – 2-3 weeks



Infectivity – from 7 days before rash till 14 days after

the onset of rash



Spread is via respiratory droplets or in-utero

transmission



In children : fever, malaise, rash, conjunctivitis,

lymphadenopathy



In adults : bronchitis, pneumonia, encephalitis, hepatitis

Rubella



Although rubella is generally preventable

by vaccination, congenital rubella still

occurs. Up to 10% of women of child-

bearing age are susceptible, as they have

not been vaccinated, vaccination has

failed, or vaccine-induced immunity has

waned.



If infection occurs in the first trimester of

pregnancy, the risk of fetal infection and

damage is high (about 90% in the first two

months of pregnancy, and 50% in the

third), and termination of pregnancy is

usually recommended.

Congenital rubella
syndrome:



Eye defects including cataracts and congenital glaucoma.



Heart disease, including patent ductus arteriosus and

peripheral pulmonary artery stenosis



Sensorineural deafness-the most common single defect



Central nervous system defects, including microcephaly,

developmental delay, mental retardation, and

meningoencephalitis



Pigmentary retinopathy



Purpura



Hepatosplenomegaly and joundice



Radiolucent bone disease



Risk of fetal damage falls steeply after the first trimester

and is negligible after 16 weeks; between 12 and 16 weeks,

deafness has been reported.

Rubella



If a pregnant woman has close contact with or

develops rubella-like illness, her IgG and IgM titres

should be measured, even if she was previously

positive for rubella IgG — rarely, women with

apparently adequate immunity can be reinfected

(although the risk of fetal abnormality is probably

less than 5%, even in the first trimester).



If contact is in the second or third trimester and

rubella IgG was detected in the first trimester,

further investigation is not necessary. Women who

remain susceptible to rubella should receive MMR

vaccine post partum, unless two previous attempts

at immunisation have failed.

Rubella

Before pregnancy



All susceptible women who are receiving

healthcare should ideally have their

serological state tested.



If immunity to rubella is not confirmed, the

vaccine should be offered. It is recommended,

that pregnancy should be avoided for 1

month after the vaccine is administered.

Rubella

During pegnancy



If not immune, the patient should be

councelled about avoidance of any affected

person.



All pregnant women, presenting with a non-

vesicular rash compatibile with a viral

infection should be investigated for rubella

and parvovirus B19 infection, irrespective of a

prior history of rubella vaccination or previous

positive rubella anibody tests.

Herpes simplex virus



This virus is classified into types 1 and 2.
HSV-1 – the orofacial infections and encephalitis
HSV-2 – the genital manifestation



The incubation period < 1 week



A first attack of genital herpes is usually more severe

and symptomatic, presenting with multiple painful

genital ulcers. In 80-90% of cases primary genital

herpes involves the vulva and cervix. All the skin

lesions start with erythema, proglessing to vesicles,

then ulcers and finishing with crusting (up to 2

weeks)

Herpes simplex virus



Herpes simplex virus (HSV) causes spontanous

abortion, stillbirth, IUGR, preterm labour, neonatal

HSV sepsis syndrome and encephalitis, which are

often fatal or produce long-term sequelae.



The risk of vertical transmission of HSV (types 1

and 2) is greatest during primary maternal

infection, which is often associated with viraemia.

Primary genital herpes (usually type 2) may be

clinically severe, with heavy and prolonged viral

excretion, and higher risk of transmission to the

infant during vaginal delivery than recurrent

disease.



If primary genitaly herpes occurs during

pregnancy, acyclovir should be administered.

Herpes simplex virus



Caesarean section is recommended for all women presenting

with first-episode genital herpes at the time of delivery.



If the first episode is whithin 6 weeks of the due date,

elective caesarean section should be considered.



There is no agreement on the use of caesarean section in the

management of patients with a history of reccurent HSV.



If a patient presents in early labour with a visible herpetic

lesion, c.s. is recommended.



If a patient has frequent symptomatic recurrences during

pregnancy, the use of acyclovir from 36 weeks is

recommended, and vaginal delivery is not contraindicated.

Varicella (chickenpox)



Varicella Zoster Virus (VZV) has two distinct

diseases : Varicella (chickenpox) and herpes zoster

(shingles)



The diagnosis of chickenpox is usually obvious. The

disease is more likely to be severe in adults than in

children and may be complicated by pneumonia,

especially in smokers and in the latter half of

pregnancy, and is occasionally fatal.

Varicella



Fetal infection occurs in 10%–15% of cases of varicella

(chickenpox) in pregnant women but is usually

transient and asymptomatic.



The most common clinical manifestation, if any occurs,

is shingles in the first year of life.



2%–3% of infants of women who have chickenpox in

the first half of pregnancy develop

fetal varicella

syndrome

, with potentially severe defects, including

skin scarring in a dermatomal distribution, ipsilateral

limb hypoplasia, visceral, neurological and eye lesions.



Maternal varicella within a few days before or after

delivery can result in potentially severe varicella in the

infant, who should be given zoster immune globulin

(ZIG) as soon as possible after birth.

Varicella



Use of aciclovir is not recommended during

pregnancy, but evidence is accumulating that it has

no adverse fetal effects. Given during the incubation

period or within 24 hours of rash onset, it can reduce

risk of infection or illness duration and severity.



Its use should be considered during the incubation

period for women who have not received ZIG, or

soon after rash onset, especially in women with risk

factors for severe disease, such as chronic lung

disease, smoking or impaired immunity, or in the

latter half of pregnancy.



If disease progresses, admission to hospital and

intravenous aciclovir are indicated.

Varicella



More than 90% of women of child-bearing age are

immune to varicella virus, with a history of infection

providing reliable evidence of immunity.



If in doubt when contact occurs, pregnant women

should be tested for varicella IgG as soon as possible

(including those who have been vaccinated, if

seroconversion has not been confirmed).



If seronegative, they should be offered

ZIG

preferably

within 48 hours

of contact (maximum, 72

hours). ZIG may not prevent infection but reduces

illness severity. It is not effective after rash onset

Syphilis



Syphilis is caused by Treponema pallidum



Untreated maternal syphilis results in fetal infection 75-90%

of the time. Several hundred children are born each year

with syphilis; 75% of them are asymptomatic at birth.



Early infection most often results in spontaneous abortion.

Some newborns do survive but are small for gestational

age, anemic with spleen and liver malformations, have skin

lesions and nasal discharge and bone and joint pain.



Gestationally late infections often present in children over 2

years of age. They have nerve deafness, dental and bony

abnormalities, cardiovascular defects and skin lesions.

Syphilis

Serological diagnosis



A suitable serological screening test such as the Veneral

Disease Research Laboratory (VDRL) slide test or rapid

plasma reagin (RPR) test should be performed at the first

prenatal visit.



Serological tests yield positive in many women with

primary syphilis and in all of those with secondary and

latent syphilis.



Because such reagin tests lack specificity, a

trepomnema test is used to confirm a positive result.

These include : FTA – ABS, MHA – TP, TP – PA.

Syphilis

Treatment



Syphilis therapy during pregnancy is given to

eradicate maternal infection and to prevent

congenital syphilis.



Penicillin is the treatment of choice



Erythromycin can be curative for the mother, but it

does not prevent all congenital syphilis. Infants born

to mothers treated with erythromycin or a non-

penicillin regimen for syphilis during pregnancy should

be retreated as though they have congenital syphilis.

Parvovirus B19 infection



Parvovirus B19 causes erythema infectiosum, or fifth

disease, which occurs in epidemic waves lasting two

to three years, mainly among primary-school-aged

children. Infection is often asymptomatic, but can

cause rash and arthralgia or arthritis, particularly in

adults.



Complications of parvovirus infection during

pregnancy are excess fetal loss in the first 20 weeks

(up to 10% excess) and hydrops (about 3%) if

maternal infection occurs between nine and 20

weeks' gestation. Hydrops is caused by severe fetal

anemia

and presents about five weeks after maternal

infection. About a third of cases resolve

spontaneously, and outcome is significantly improved

in the remainder by

intrauterine transfusion

Parvovirus B19 infection



About 50% of women of child-bearing age are

susceptible to parvovirus B19 and the annual

seroconversion rate varies from about 1%–2%

during non-epidemic years to 10%–15% during

epidemics.



Routine antenatal screening for parvovirus antibody

is not indicated, nor is it generally recommended

that susceptible pregnant women with occupational

exposure to the virus stay away from work.

Epidemics are protracted, infection is prevalent in

the community, and infectivity precedes rash onset.

If contact occurs during pregnancy, IgG tests should

be done to determine susceptibility and, if

seronegative, repeated two to three weeks later.

Parvovirus B19 infection



If infection is confirmed during pregnancy, the

fetus should be monitored for signs of hydrops by

ultrasound examination over the next six to 12

weeks, with appropriate specialist referral if it

occurs.



PCR examination of amniotic fluid is not

recommended after proven maternal parvovirus

infection, but it can be helpful during

investigation of non-immune hydrops of unknown

cause.

Listeriosis



Listeriosis is an uncommon foodborne illness caused by

Listeria monocytogenes



Pregnant women are particularly susceptible to the disease,

which can result in fetal death or chronic intrauterine and

congenital or perinatal infection.



Investigation of symptoms such as headache, myalgia and

fever associated with relatively inconspicuous

gastrointestinal symptoms in a pregnant woman should

include a recent dietary history and blood culture.



Congenital listeriosis:
1) early type – preterm labour, septic shock, pneumonitis
2) late type (7 days after labour)- meningitis, hydrocephalus



Treatment: ampicilin.

Group B streptococcus
(GBS)

Streptococus agalactiae



There is a spectrum of maternal and fetal GBS infections

ranging from asymptomatic colonization to sepsis.



S. Agalactiae has been implicated in adverse pregnancy

outcomes, including: preterm labour, PROM, clinical and

subclinical chorioamnionitis and fetal and neonates

infections.



The bacterium can also cause bacteriuria,

pyelonephritis, and postpartum: matritis, osteomyelitis,

mastitis.

Group B streptococcus



Vaginal GBS screening cultures at 35-37 weeks’gestation for all pregnant

women (unless patient had GBS bacteriuria during the current pregnancy or a

previous infant with invasive GBS disease)



Indications for intrapartum prophylaxis to prevent perinatal group B

streptococcal disease:
1. Previous infant with invasive GBS disease
2. GBS bacteriuria during pregnancy
3. Positive GBS screening culture during current pregnancy (unless a planned

caesarean delivery, in the absence of labour or amniotic membrane rupture, is

performed)
4. Unknown GBS status (culture not done, incomplete, or results unknown) and

any of the following:

- delivery at < 37 weeks’gestation
- amniotic membrane rupture >18 hours
- intrapartum temperature >38st.C

Human Immunodeficiency
Virus



HIV – positive pregnant women should

receive the same antiretroviral treatment

as non-pregnant women.



Antiretroviral treatment should not be

withheld unless clear maternal or fetal

contraindications to standard therapy exist.



For women diagnosed for HIV infection

during the first trimester, treatment should

be delayed until the second trimester.

Human Immunodeficiency
Virus



Zidovudine (ZDV) is the treatment of

choice.



ZDV needs to be taken

orally

from the

second trimester.It should be

administered by

intravenus infusion

the time of delivery and then taken by the

child during the first 4-6 weeks after birth.

Human Immunodeficiency
Virus



Delivery by caesarean section is

recommended.



A high serum viral load significantly

increases the likelihood of newborn

infection.



The avoidance of breastfeeding is

recommended.

Human Immunodeficiency
Virus

Increased mother-to-child transmision
occurs with:



A low maternal CD4 count



High maternal HIV RNA load



Invasive needling procedures in the

antenatal period



Invasive procedures during labour

(artificial rupture of membranes)



Prolonged interval between rupture of

membranes and delivery



Concurrent ascending bacterial infection



Vitamin A deficiency

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