Infectious Disease in

Pregnancy

Mulyanusa A Ritonga
@mulyaritonga
Reading List !!!

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 Outline
• MATERNAL AND FETAL IMMUNOLOGY
• VIRAL INFECTIONS : Varicella-Zoster Virus, Influenza,
Rubeola (measles), Rubella (German Measles),
Hantavirus, Enterovirus, Coxsackievirus, Poliovirus,
Parvovirus, Cytomegalovirus
• BACTERIAL INFECTIONS : Group B Streptococcus,
MRSA, Listeriosis, Salmonella and Shigella, Hansen
disease, Lyme Diseases, Tuberculosis
• PROTOZOAL INFECTIONS : Toxoplasmosis, Malaria,
Amebiasis
• MYCOTIC INFECTIONS
• EMERGING INFECTIONS : West Nile Virus, Severe Acute
Respiratory Syndrome (SARS)

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 Fetal and Neonatal Infections
Viruses: VZV, Coxsackie, human
parvovirus B19, rubella, CMV, HIV
Transplacental
Bacteria: listeria, syphilis, Borrelia

Intrauterine Protozoa: toxoplasmosis, malaria

Bacteria: GBS, coliforms

Ascending infection
Viruses: herpes simplex
Bacteria: GO, chlamydia, GBS, TBC,
mycoplasmas
Maternal exposure
Viruses: HSV, HPV, HIV, hep B, hep C
Intrapartum
Bacteria: staphylococcus, coliforms
External contamination
Viruses: herpes simplex, VZV

Human transmission: staphylococcus, HSV

Neonatal
Respirators & catheters: staphylococcus, coliforms 4
MATERNAL AND FETAL IMMUNOLOGY

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VIRAL INFECTIONS :
Varicella-Zoster Virus
Herpes virus family, DNA virus.
If infection occurs in first trimester 4.9%
risk of congenital varicella .
Congenital Syndrome
• Limb hypoplasia
• Ocular abnormalities
• CNS abnormalities ( convulsive
disorders ).
• Dermatomal scarring

If infections aquired in the last 10 days of

pregnancy result in variably sever fetal
infections with neonatal mortality as high
as 34% .
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• Perinatal period (neonatal varicella)
• Chicken pox
• Encephalitis
• 20-40% risk of (neonatal varicella) infection if mother
develops varicella in peripartum period.
• Serology (IgG and IgM).
• Screening: Routine screening generally not recommended.

• Prevention: If pregnant
woman (with no history
of previous chickenpox)
is exposed, perform STAT
Varicella IgG.
• Exposed neonate should
receive VZIG prophylaxis.

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VIRAL INFECTIONS :
Rubeola (measles)

• Paramyxovirus
• Incubation - 10-14 days
• Respiratory droplet inoculation
• Fever, rash, cough, rhinorrhea,
conjunctivitis and Koplik’s
spots
• Pneumonia (2nd bacterial)
main cause of death
• Encephalomyolitis, SSPE,
Hepatitis
• No increased maternal or fetal
deaths
• Risk of preterm delivery

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VIRAL INFECTIONS :
Rubella (German Measles)
• 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

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 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)

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 Rubella
• Vaccination (95% seroconversion)
@ 15 months and early adulthood
• Immune status checking in teenagers, pre-
college and pre-pregnancy
• Antenatal testing
• Serology testing for presumed exposures
(paired Sera)
• No in-utero therapy

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VIRAL INFECTIONS :
Parvovirus

• Human parvovirus B19 (DNA virus)

- erythema infectiosum in childhood
- chronic arthropathy
- chronic bone marrow failure (immunodefic)
- aplastic crisis (Sickle disaease)
• Incubation 4-14 days
• Respiratory droplet spread
• High fever
• “Slapped cheek syndrome’
non specific rash, no symptoms

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 Parvovirus and fetus
• Hydrops
(anaemia, myocarditis)
• Adults 60% sero-positive
• 1/3 fetuses affected in
acute infection
• Fetal loss rare with
appropriate treatment
• Assess serology - IgG, IgM,
paired serology
• Serial ultrasound,
intrauterine transfusion
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VIRAL INFECTIONS :
Cytomegalovirus
• DNA virus
• Congenital infection -
1%
• 5-10% of those infected
show clinical illness at
birth
• Neonatal MR - 20-30%
• 90% of survivors get
late complications
• 5-15% with no
demonstrable disease
at birth get some
abnormality (deafness)
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 CMV Congenital Infection
• Hepatomegaly TORCH Syndrome
• Spleenomegaly
• Jaundice
• Thrombocytopenia
• Petechiae
• Microcephaly
• Intrauterine growth
retardation

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 CMV Congenital Infection (Late)
• Venticulomegaly
• Cerebral atrophy
• Mental retardation
• Psychomotor delay
• Seizures
• Learning difficulties and language delay
• Chorioretinitis / Optic atrophy
• Intracranial calcifications
• Long bone radiolucencies, dental abnormalities
• Pneumonitis

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 CMV Congenital Infection
• Prolonged virus shedding

• No vaccine

• No treatment

• Risk group advice

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BACTERIAL INFECTIONS : Group B Streptococcus

• 25% women are carriers

• 50% of babies born will be
colonized
• 1-2% will have Grp B Strep
infection
• 1:1000 babies
• Pneumonia (early),
Meninigitis (Late)
• Screening v Risk factor
prophylaxis
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What does group B Strep do?
• Colonisation
– Asymptomatic and intermittent
– Intestinal (<30% of adults)
– Vaginal (<25% of women)

• Infection
– Newborn babies
– Adults: the elderly, pregnant/postpartum
women, others with underlying disease

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 Group B Strep infection
• “Early onset” 0-6 days (~75% cases)
– 90% show within 12 hours
– Usually septicaemia and pneumonia
– 11% mortality, 7% morbidity
– 90% preventable IV Penicillin

• “Late onset” 7-90 days (~25% cases)

– Usually meningitis and septicaemia
– 8% mortality, 21% morbidity (up to 50% with meningitis)
– No current prevention: good hygiene/education
– Vaccine: future hope for both late & early onset

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Known risk factors for EOGBS
infection
• Previous GBS baby 10 x
• GBS bacteriuria current pregnancy 4x
• GBS found current pregnancy 3x
• Maternal intrapartum fever (>380C) 3x
• PROM >18 hours before birth 3x
• Preterm labour 3x

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Typical signs of early-onset
GBS infection
• grunting;
• lethargy;
• irritability;
• poor feeding;
• very high or low heart rate;
• low blood pressure;
• low blood sugar;
• abnormal (high or low) temperature; and
• abnormal (fast or slow) breathing rates with
blueness of the skin due to lack of oxygen
(cyanosis).

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Typical signs of late onset
GBS infection
• fever;
• poor feeding and/or vomiting;
• impaired consciousness;
• fever, which may include the hands and feet feeling cold,
and/or diarrhoea;
• refusing feeds or vomiting;
• shrill or moaning cry or whimpering;
• dislike of being handled, fretful;
• tense or bulging fontanelle (soft spot on the head);
• involuntary body stiffening or jerking movements;
• floppy body;
• blank, staring or trance-like expression;
• abnormally drowsy, difficult to wake or withdrawn;
• altered breathing patterns;
• turns away from bright lights; and
• pale and/or blotchy skin.
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BACTERIAL INFECTIONS : MRSA

• Localized infections: • The infection is related to shaving

• Symptoms are more severe than
expected given the host
Furuncles, wound infection,
adenitis, abscesses, and
breast abscesses.
• Invasive infections:
Pneumonia, endocarditis,
• The wound is necrotic
osteomyelitis, arthritis • Infection is in a high-risk host

•
• Infection is in the axilla or groin
Septicemia - rare
if blood culture positive-
search for primary focus
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 Risk Factors for CA-MRSA
• Persons with prior CA-MRSA skin and soft tissue infection1
• AND their household contacts
• Children < 2 years of age2
• AND their day-care contacts3
• Men who have sex with men4
• Military recruits5
• Persons in correctional facilities5
• Athletes, especially those involved in contact sports6
• Native Americans7
• Pacific Islanders8
• Intravenous drug users9

1) Dietrich et al. Pediatrics 2004; 113(4): e347-e352 6) Kazakova et al. NEJM 2005; 352: 468-75.
2) Fridkin et al. NEJM 2005; 352: 1436-44. 7) Groom et al. JAMA 2001; 286: 1201-5.
3) Adcock et al. JID 1998; 178:577-80. 8) Castrodale et al. Alaska Med 2004; 46: 88-91
4) Lee et al. CID 2005; 40: 1529-34. 9) Young et al. Arch Surg 2004; 139: 947-53.
5) Aiello et al. Lancet Infect Dis 2006; 6: 335-41 26
 S. AUREUS - PHAGE GROUP II
• Expanded scalded skin syndrome:
bullous impetigo, toxic epidermal necrolysis,
Ritter’s disease, and non-streptococcal
scarlatina.
• Primary sites of infection may be umbilicus,
conjunctiva, circumcision site
• Skin lesions caused by exfolatin or epidermolytic
toxin (Nikolsky’s sign).
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 Neonatal MRSA
Pregnant
Children at home
Family with skin infections

Birth Health care system

Vertical transmission
Neonate

Postpartum
Hospital outbreaks
Skin infections
Mastitis – Breast Milk
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 S. aureus Neonatal Colonization

44% colonized in nares1

27% colonized at neck1

59% colonized at umbilicus1

55% colonized at groin1

• Risk factors for MRSA2

– Premature ( 28 wks)
– Low birth weight ( 1500 g)
1. Cimolai et al. Am J Perinatol 2003; 20(3): 125-36.
2. Huang et al. Pediatrics 2006; 118(2): 469-74
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S. AUREUS - CONTROL MEASURES
• ROUTINE:
Hand washing; Cord care
No hexachlorophene bathing - adverse CNS effects.
• DURING EPIDEMICS:
Hand washing, avoid overcrowding &understaffing.
Contact precautions
Cohort- infants and staff
Admit new infants to clean room

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 Neonatal MRSA via Breast Milk
Gastelum et al. Pediatrics 2007

• Infected Mother 
• 35yo woman with postpartum mastitis
• Premature quadruplets by caesarian section
– Infants were fed breast milk via nasogastric tube
– One infant died of MRSA sepsis on day 15
• Post-infection
– All other infants and mother were MRSA-colonized
– Breast milk was MRSA-positive
• 2yo child at home had “pimples” one month ago

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 Therapeutic Options
For Mild CA-MRSA Infections
• Clindamycin
– Good penetration into skin, lung, & bone
– Inducible resistance in vitro
– Associated with Clostridium difficile infection
– Effectiveness is dependent on local resistance rates

• Tetracyclines
– Limited data
– Cannot be used in pregnancy or in children (tooth discoloration)

• Trimethoprim-sulfamethoxazole
– Requires higher doses
– Risk of allergic reaction
– Cannot be used in pregnancy or in neonates

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 Therapeutic Options
For Severe CA-MRSA Infections
• Vancomycin
– Still the drug of choice for invasive infections
– Increasing resistance

• Linezolid
– May be more effective than vancomycin for SSTI and pneumonia
– High cost
– Associated with thrombocytopenia & peripheral neuropathy

• Daptomycin
Quinupristin-dalfopristin
Tigecycline
– Restricted indications for use

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BACTERIAL INFECTIONS : Listeriosis
• Gram positive coccobacilli, readily decolorized; mistaken for gram
negatives, diphtheroids, etc.
• Maternal infection- cheese, milk, shellfish,
uncooked vegetables fertilized with sheep manure
• Pathogenic strains are Ia , Ib, IV b
• May cause recurrent abortions
• 20% infants infected in-utero are stillborn

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 LISTERIA MONOCYTOGENES
• EARLY ONSET DISEASE:
Flu like symptoms in mother
Diminished fetal
movements
Fetal distress, chorio,
meconium staining
Respiratory distress, fever,
Disseminated infection

• LATE ONSET DISEASE:

MEAN AGE 14 DAY
Meningitis due to IVb most
common
CSF - no monocytes; CBC:
monocytes

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BACTERIAL INFECTIONS : Salmonella and Shigella

• 2 species Salmonella enterica

Salmonella bongori
• intestines of birds, reptiles and mammals

• most important in foodborne disease:

S. enterica subspecies enterica (cca 1500 serotypes)

• serotype Enteritidis abbreviated to S. Enteritidis

• serotype Typhimurium (≠ S. Typhi!)
• serotype Infantis
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 SALMONELLA - infective dose
• Infective dose vary widely:
105-106 cells
the young or the elderly: 10 - 100 cells

• Period of infectivity: during illness,

reconvalescence

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SALMONELLA - occurrence in foods
 Foods of animal origin (meat, poultry, eggs and raw
milk)
 Fresh produce
 Cooked ready-to-eat foods (cross contamination)
 Processed food

Examples:
 Confectionery, pastries (custard, egg white coating)
 Cooked ready to eat food containing eggs
 Bologna sausage, tripe sausage, meat loaf, liver paste
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 SALMONELLOSIS - symptoms
• non-typhoid salmonellae
– incubation period: 12 – 36 hours
– 1-7 days
– diarrhea, abdominal pains, nausea, vomiting, chills
– dehydration and headaches

– Susceptible individuals: more severe symptoms

– septicaemia, or chronic conditions (reactive arthritis)

• Salmonella Typhi
– Typhoid fever (≠ typhus - rickettsia)
– vaccination
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 SALMONELLOSIS - treatment
 Gastroenteric form:
oral fluids
severe diarrhea - rehydration with intravenous
fluids

 Typhoid form:
ATB (e.g. ampicillin, chloramphenicol)

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 SHIGELLOSIS
Shigella - a family of bacteria that causes diarrhea in humans

• Shigella sonnei (" Group D" Shigella) over 2/3 of shigellosis

in the US, in CR over 90 % of cases
• Shigella flexneri ("group B" Shigella) almost all the rest

• Other types, e.g. Shigella dysenteriae type 1 – developing

world

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 SHIGELLOSIS
• Highly infective disease, infective dose 200 cells
• Incubation period 1-3 days
• Duration: 5-7 days

SYMPTOMS:
• Diarrhea (distal part of colon) – with mucus and blood
• Fever
• Stomach cramps

risk of dehydration and perforation of colon

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 SHIGELLOSIS
• Sources of infection:
infected person (diarrheal stools – poor hygiene)
contaminated food
contaminated water

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PROTOZOAL INFECTIONS : Toxoplasmosis

protozoan parasite Toxoplazma gondii

• Foodborne transmission (undercooked, contaminated meat)

• Animal-to-human transmission (cat’s feces)
• Mother-to-child transmission
Mothers often without symptoms
Miscarriage, stillborn child
Congenitally infected infants - later in life: mental disability,
potential eye loss

• Incubation period: 5 – 23 days

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sporozoite

bradizoite

tachyzoite

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 Damage to Fetus
• A pregnant host has a 40-60% chance of
transmitting the infection to baby w/
serious damage
– 1st trimester=fetal death or severe impairment
– 1st or 2nd = eye abnormalities, hydrocephalus,
seizures
– 3rd = often no impairments

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• Infection in the pregnancy may result in:
(occur only if there is acute exacerbation during
pregnancy):
1.spontaneous abortion.
2.perinatal death.
3.abnormal growth.
4.characteristic triad of fetal anomalies:
a- Chorioretinitis .
b- Hydrocephaly or microcephaly.
c- Cerebral calcification .

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• Maternal screening: not
recommended, if infection
suspected( toxoplasma
IgG, IgM, and repeat test
every 10 weeks through
pregnancy.
• Treatment: start
spiramycin in infected
mothers to reduce
transmission to the fetus.
• Prevention: wash hands
before eating, after
handling raw meat , after
contact with cat feces, &
soil & cook their meat
adequately.
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PROTOZOAL INFECTIONS : Malaria

• Caused by Plasmodium
parasites
• Spread by female Anopheles
mosquitoes infected with
parasites
• Anopheles mosquitoes
usually active at night
• Infected mosquito bites a
person
• Malaria parasites reproduce
in human blood
• Mosquito bites infected
person, and goes on to bite
and infect another person

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 Populations Most Affected by Malaria
• Children under 5 years of age
• Pregnant women
• Unborn babies
• Immigrants from low-transmission areas
• HIV-infected persons

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Effects of Malaria on Pregnant Women
• All pregnant women in malaria-endemic areas
are at risk
• Parasites attack and destroy red blood cells
• Malaria causes up to 15% of anemia in
pregnancy
• Can cause severe anemia
• In Africa, anemia due to malaria causes up to
10,000 maternal deaths per year
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 Effects on Unborn Babies
• Parasites hide in placenta
• Interferes with transfer of oxygen and
nutrients to the baby, increasing risk of:
– Spontaneous abortion
– Preterm birth
– Low birthweight—single greatest risk factor for
death during first month of life
– Stillbirth

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Intermittent Preventive Treatment

Based on the assumption that every pregnant

woman living in an area of high malaria
transmission has malaria parasites in her blood
or placenta, whether or not she has symptoms
of malaria

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Intermittent Preventive Treatment
Although a pregnant woman with malaria may
have no symptoms, malaria can still affect her
and her unborn child

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 Intermittent Preventive Treatment:
WHO Recommendation
• All pregnant women should receive at least two
doses of IPT after quickening, during routinely
scheduled ANC visits (WHO recommends a
schedule of four visits, three after quickening)
• Presently, the most effective drug for IPT is
sulfadoxine-pyrimethamine (SP)
• Women should receive at least two doses of IPT
with SP at ANC visits after quickening, but no
more frequently than monthly
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 Intermittent Preventive Treatment:
Dose and Timing
• A single dose is three tablets of sulfadoxine
500 mg + pyrimethamine 25 mg
• Healthcare provider should dispense dose and
directly observe client taking dose

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 Instructions for Giving Intermittent
Preventive Treatment
• Ensure woman is at least 16 weeks pregnant
and that quickening has occurred
• Inquire about use of SP in last 4 weeks
• Inquire about allergies to SP or other sulfa
drugs (especially severe rashes)
• Explain what you will do; address the
woman’s questions
• Provide cup and clean water
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 Instructions for Giving Intermittent
Preventive Treatment (cont’d.)
• Directly observe woman swallow three tablets
of SP
• Record SP dose on ANC and clinic card
• Advise the woman when to return:
– For her next scheduled visit
– If she has signs of malaria
– If she has other danger signs

Reinforce the importance of using ITNs

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 Intermittent Preventive Treatment:
Contraindications to Using SP
• Do NOT give during first trimester: Be sure quickening has
occurred and woman is at least 16 weeks pregnant
• Do NOT give to women with reported allergy to SP or other
sulfa drugs: Ask about sulfa drug allergies before giving SP
• Do NOT give to women taking co-trimoxazole, or other sulfa-
containing drugs: Ask about use of these medicines before
giving SP
• Do not give SP more frequently than monthly: Be sure at least
1 month has passed since the last dose of SP

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Chemoprophylaxis with Chloroquine: For
Women Allergic to Sulfa Drugs*

Dose Chloroquine Timing

150 mg
1 4 tablets First ANC visit after 16 weeks

2 4 tablets Second day after first dose

3 2 tablets Third day after first dose

Weekly 2 tablets Every week during pregnancy

*If chloroquine resistance rates in the country are high,

chemoprophylaxis with chloroquine is not recommended.

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 Summary of Health Education Points

• Pregnant women should sleep under ITNs every

night
• By preventing malaria, IPT reduces the incidence
of maternal anemia, spontaneous abortion,
preterm birth, stillbirth, and low birthweight
• IPT should be administered to pregnant women at
regularly scheduled ANC visits after quickening,
but not more often than monthly
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