Neely: Obstetric and Perinatal Infections

Question 1

Obstetric and Perinatal Infections

DEFINITION:

Answer 1

Infections acquired in utero, during delivery, or shortly after delivery.

Question 2

PERIOD OF HIGH SUSCEPTIBILITY

Time period:
Why?

Answer 2

Birth through 1st 4 weeks of life

Fetus had previously been living in a germ free environment; Now exposed to a whole zoo of pathogens that can infect them

Question 3

PERIOD OF HIGH SUSCEPTIBILITY

Risk of infection and the types of pathogens encountered depends on several factors: (5)

Answer 3

o State of maternal health
o Maternal susceptibility to certain agents
o Nutrition (both before and during pregnancy)
o Integrity of fetal membranes
o Degree of maturity at birth

Question 4

PERIOD OF HIGH SUSCEPTIBILITY

Special Defenses: (4)

Answer 4

Fetal membranes: physical barrier to infection

Placenta/Maternal Immunity: protect against bloodborne pathogens

Transplacental IgG: present weeks to months after birth

Breast-fed infants: IgA provides some protection against pathogens invading GI tract

Question 5

Special Susceptibility

When is the competent state of immunity reached?
What is decreased in fetal immunity? (2)

Answer 5

Fetal immune system is immature:
o Competent state not reached until age 2
o Decreased phagocytic activity
o Decreased levels of complement

Question 6

Special Susceptibility

What happens to mother’s immunity?
What rates are highest at this time?

Answer 6

Mother’s immune system also suppressed: protects mother and fetus from activation of immune response, preventing immunological rejection of the fetus

Cell growth and organ differentiation rates are highest at this time: especially susceptible to permanent damage.

Question 7

Congenital (In Utero)
Definition:

What agents? (2)

Answer 7

Congenital (In Utero): across placenta

L.monocytogenes
T.gondii

Question 8

Perinatal
Definition:

What agents? (3)

Answer 8

Perinatal: from maternal bloodstream or during passage down the birth canal

o E. coli
o L.monocytogenes
o S.agalactiae

Question 9

Post-natal
Definition:

What agents? (3)

Answer 9

Post-natal: milk, blood, saliva, contact

o E. coli
o L.monocytogenes
o S.agalactiae

Question 10

Streptococcus agalactiae (Group B Strep)

G +/-?
Shape:
Cat +/-?
Type of hemolysis:

Answer 10

Basic ID: Gram positive, diplococci or short chain in liquid media

Lab Test ID: catalase negative, beta-hemolytic

Question 11

Streptococcus agalactiae (Group B Strep)

Normal flora of where?

Answer 11

Normal flora: of GI tact and female genitourinary tract (~40% of females colonized in vagina); opportunistic pathogens.

Question 12

What is the leading cause of bacterial meningitis in newborns?

Answer 12

Streptococcus agalactiae (Group B Strep)

Question 13

Streptococcus agalactiae (Group B Strep)
Infection occurs by exposure to organism

Ascending route in utero via:
Contamination during:

Answer 13

Ascending route in utero through ruptured membranes

Contamination during passage through birth canal

Question 14

Streptococcus agalactiae (Group B Strep)

Where does the infant become infected? How?
How does the colonization of the maternal vaginal tract relate?

Answer 14

Infant becomes infected in mucus membranes (oropharynx, GI tract): via inhalation of amniotic fluid or maternal vaginal secretions; organism then penetrates into the bloodstream.

The heavier the colonization of the maternal vaginal tract, the higher the risk to the newborn.

Question 15

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Age:

Answer 15

<7 days

Usually withing 24 hours of birth

Question 16

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Risk Factors: (4)

Answer 16

1. Heavily colonized mother without specific Ab
2. Premature rupture of membranes
3. Pre-term delivery and low birth weight
4. Prolonged labor, obstetric complications such as intrapartum fever

Question 17

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Type of Disease:

Answer 17

Bacteremia, pneumonia, meningitis

Question 18

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Serotype:
Meningitis mainly due to:

Answer 18

All serotypes

Meningitis mainly due to type III

Question 19

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Outcome:

Answer 19

~60% fatal; serious sequelae in survivors

Question 20

Streptococcus agalactiae (Group B Strep)
Early Onset Disease (EOD)

Prevention:

Answer 20

Antibiotic treatment does not reliably abolish carriage in mother

“Blind” treatment of sick baby who has risk factors (treat on suspicion)

Question 21

Streptococcus agalactiae (Group B Strep)
Late Onset Disease (LOD)

Age:

Answer 21

1 week to 3 months

Question 22

Streptococcus agalactiae (Group B Strep)
Late Onset Disease (LOD)

Risk Factors: (3)

Answer 22

1. Lack of maternal Ab
2. Exposure to cross infection from heavily colonized babies
3. Poor hygiene in the nursery

Question 23

Streptococcus agalactiae (Group B Strep)
Late Onset Disease (LOD)

Type of Disease:

Answer 23

Predominantly meningitis

Question 24

Streptococcus agalactiae (Group B Strep)
Late Onset Disease (LOD)

Serotype:

Answer 24

90% due to type III

Question 25

``` Streptococcus agalactiae (Group B Strep) Late Onset Disease (LOD) ``` Outcome:

Answer 25

~20% fatal

Question 26

``` Streptococcus agalactiae (Group B Strep) Late Onset Disease (LOD) ``` Prevention:

Answer 26

Good hygiene practices in the nursery | Do not allow mothers to handle other babies

Question 27

Streptococcus agalactiae (Group B Strep) Virulence Factors Adherence:

Answer 27

Initial event in colonization and invasion

Question 28

``` Streptococcus agalactiae (Group B Strep) Virulence Factors Polysaccharide capsule ``` How many serotypes? What is on the terminal sugar? What does it limit the deposition of on the surface? What does this lead to? What happens during invasion?

Answer 28

9 different serotypes Sialic acid moiety on terminal sugar Limits C3b deposition on surface (decreased phagocytosis) Note: will turn off capsule during invasion

Question 29

Streptococcus agalactiae (Group B Strep) Virulence Factors Invasion

Answer 29

Ability to invade respiratory epithelium and BBB (lack of capsule promotes invasion)

Question 30

Streptococcus agalactiae (Group B Strep) Virulence Factors Beta-hemolysis is cytolytic for what? What is promoted?

Answer 30

Cytolytic for lung epithelial cells and human brain endothelial cells (promotes BBB invasion)

Question 31

What is the most important virulence factor for Streptococcus agalactiae (Group B Strep)?

Answer 31

Polysaccharide capsule

Question 32

Streptococcus agalactiae (Group B Strep) Diagnosis EOD presents as: LOD: Lab diagnosis:

Answer 32

EOD – first 5 days after birth – presents as septicemia, pneumonia or meningitis LOD – 3 to 8 weeks after birth Lab diagnosis of cerebrospinal fluid or blood. Commercial kits can detect the group B antigen

Question 33

``` Streptococcus agalactiae (Group B Strep) Treatment ``` What is intrapartum prophylaxis? When do you treat?

Answer 33

Intrapartum prophylaxis: administer antibiotic course during delivery (most important prevention) TREAT ON SUSPICION: do NOT wait for lab results to get back

Question 34

E.Coli K1 G +/-? Shape: Normal flora of what? Another common cause of what?

Answer 34

Basic ID: Gram negative bacillus Normal Flora: major inhabitant of large intestine Another common cause of neonatal meningitis

Question 35

E.Coli K1 How does vaginal E.Coli colonize the infant? Mortality Rate:

Answer 35

Ruptured amniotic membranes, OR During delivery High mortality rate (40-80%): survivors have neurological or developmental abnormalities

Question 36

E.Coli K1 | Risk Factors:

Answer 36

Prematurity Low birth weight Prolong rupture of membranes

Question 37

E.Coli K1 When does septicemia present? When does meningitis present?

Answer 37

Septicemia: at birth or within 2 days after birth Meningitis: infection in infants more than 2 days old

Question 38

``` E.Coli K1 Virulence Factors (4): ```

Answer 38

K1 Polysialic Capsule Invasins (IbeA and IbeB) Type O Antigen on LPS S.fimbriae

Question 39

K1 Polysialic Capsule What percent of E.coli isolates from neonates have this capsule? Resists killing by what? How does it affect BBB crossing?

Answer 39

80% of E.coli isolates from neonates have this capsule Resistance to killing by neutrophils and normal serum (aids in survival in the blood and CSF) However, not necessary for invasion across BBB

Question 40

E.Coli K1 What do invasins do? What is Type O Antigen important for? What is S.fimbriae important for?

Answer 40

Invasins (IbeA and IbeB): contribute to crossing the BBB Type O Antigen on LPS: important for establishing infection S.fimbriae: important for establishing infection

Question 41

E.Coli K1 Diagnosis Symptoms: (3) Cultures (2): When do you treat?

Answer 41

Symptoms Variable: respiratory distress, fever, poor feeding, abdominal distention (can all be subtle) Cultures: CSF and blood TREAT ON SUSPICION: do NOT wait for lab results to return

Question 42

Listeria Monocytogenes G +/-? Shape: Growth temperature: Found where?

Answer 42

Basic ID: Gram positive rod Growth: grows at temperatures between 4-41 degrees C (can grow in the refrigerator) Ubiquitous in the environment: ~5% of people asymptomatic fecal carriers

Question 43

Listeria Monocytogenes Can cause all of the following (4): Where is listeriosis contracted during delivery localized to?

Answer 43

Congenital (transplacental) infections Perinatal (ascending) infections Listeriosis contracted during delivery is localized to the CNS (usually meningitis) Post-natal infections

Question 44

Listeria Monocytogenes Transmission: At Risk Populations:

Answer 44

Transmission: primarily food-borne (contaminated foods eaten by the mother transferred to the fetus) At Risk Populations: immnocompromised (AIDS, chemotherapy, transplant patients, pregnant women, neonates)

Question 45

Listeria Monocytogenes Primarily what type of immunity? What are first line defense? What does later defense depend on?

Answer 45

Primarily cell-mediated Macrophages are first line (non-specific defense) Later immunity dependent upon CD8+ T cells

Question 46

Listeria Monocytogenes Tropism for: What can infections in utero lead to? In live-birth, when does septecemia begin?

Answer 46

Tropism: for the fetus and placenta Infections in utero can lead to spontaneous abortion, premature birth, stillbirth, or death within a short time after birth If infant is born alive, septicemia begins within hours

Question 47

Listeria Monocytogenes Virulence Factors (4): How does it evade the immune system? How does it invade cells? What helps it escape from host vacuoles? What helps it recruit host cell-derived actin filament? What does this allow?

Answer 47

Intracellular lifestyle: infects many types of cells; evades immune system Internalins: cell invasion Listeriolysin O: escape from host vacuoles (Hemolysin) ActA: recruits host cell-derived actin filaments for cell-to-cell spread (allows it to evade Ab mediated host responses)

Question 48

Listeria Monocytogenes Diagnosis Samples: Commercial Kits: PCR:

Answer 48

Samples: blood, CSF, amniotic fluid and genital tract secretions Commercial kits: detection using specific Abs PCR: for specific genes

Question 49

Toxoplasma gondii What type of parasite? What are the 2 phases of the life cycle? Where does each one take place?

Answer 49

Obligate intracellular parasites Life cycle has 2 phases: - Sexual phase (takes place only in cats) - Asexual phase (takes place in any warm-blooded animal)

Question 50

Toxoplasma gondii What are the 3 morphological forms?

Answer 50

Oocyst Tachyzoites (Trophozoites) Tissue Cysts/Bradyzoites

Question 51

Toxoplasma gondii Oocyst Shape: Produced where? Spreads via what route? What happens within 1-5 days in the environment? How long can it survive in the environment?

Answer 51

Ovoid with thick protective wall Produced in cats and responsible for spread to other animals via fecal oral route Sporulates into sporocysts within 1-5 days in the environment (infective) (Natalja's notes) Can survive in the environment for long periods of time

Question 52

Toxoplasma gondii Tachyzoites (Trophozoites) When does it form from the oocyst? What form invades host cells and replicates? Where is it localized?

Answer 52

Form from the oocyst AFTER ingestion Asexual proliferation form (invade host cells, rapidly replicate- burst cells released) Localize in neural and muscle tissue

Question 53

Toxoplasma gondii Tissue Cysts/Bradyzoites When is the more slowly growing form elicited? How can it persist? Present where? What happens during immunosuppression?

Answer 53

More slowly growing form elicited once an immune response is generated Can persist for the life of the host in cyst-like structures present in the brain and other tissues During immunosuppression, the parasite can resume rapid replication as a tachyzoite

Question 54

Toxoplasma gondii | Transmission (4):

Answer 54

Transmission: humans can become infected several ways 1. Eating undercooked meat of animals with tissue cysts 2. Consuming food or water contaminated with cat feces or by contaminated environmental samples 3. Blood transfusion or organ transplantation 4. Transplacentally from mother to fetus

Question 55

Toxoplasma gondii Formation of tissue cysts: Where in the host? (4) Once ingested, what happens?

Answer 55

Occurs in the human host in the following tissues and can remain throughout life of the host - Skeletal muscle - Myocardium - Brain - Eyes Once ingested: sporozites enter macrophages and parasite is then transported to all organ systems n the macrophages

Question 56

Toxoplasma gondii Congenital Infection What affects the seriousness of the infection? What can it result in? What may live-born children demonstrate? What can happen to healthy children?

Answer 56

Congenital Infection: the earlier the infection is acquired, the more severe the consequences Can result in spontaneous abortion and stillbirth Live-born children may demonstrate microcephaly, hydrocephaly, psychomotor disturbances, and convulsion Children may also appear healthy at birth, but can develop epilepsy or retardation months to years later

Question 57

Toxoplasma gondii When does it occur? What happens in subsequent pregnancies?

Answer 57

Only occurs when the mother was infected for the first time during the pregnancy. If it was not her first time being infected, she would have immunity to it Therefore, no subsequent pregnancies will result in transplacental infection

Question 58

Toxoplasma gondii | Most common manifestation:

Answer 58

Chorioretinitis (bouts of eye pain and loss of visual acuity)

Question 59

Toxoplasma gondii Virulence Factors Where does the parasite acquire its actin? What does T.gondii do to the host cell vacuole? What is prevented?

Answer 59

Actin-based motor: parasite has its own actin; used for invasion Modification of host cell vacuole: secretes proteins into the vacuole membrane that prevents fusion with lysosomes

Question 60

Toxoplasma gondii Diagnosis Symptoms similar to: What does acute infection result in? In which specimens? When must acute specimen be collected? IgG titers:

Answer 60

Symptoms similar to the flu: swollen LNs, fever, headache, anemia Acute infection: a four-fold rise in IgG antibody titer between acute and convalescent serum specimens. Acute specimen must be collected early in the course of the illness Very high IgG titers (greater than 1:1000)

Question 61

Toxoplasma gondii | Prevention:

Answer 61

Have someone else change the litter box during pregnancy Avoid uncooked or lightly cooked meat during pregnancy Wash hands well after handling raw meat during pregnancy