Congenital Infections Flashcards
1
Q
Congenital Infections
Definitions
A
- Congenital = born with it
- Prenatal = before birth
- Perinatal = around the time of birth (24-48 hrs before and after)
- Postnatal = after birth
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Neonatal = during the first 28 days of life
- Most at risk time of life for spontaneous acquisition and invasion of microorganisms
- Immune system immature
- Unable to localize infection ⇒ dissemination more common (ex. HSV)
- Most at risk time of life for spontaneous acquisition and invasion of microorganisms
-
Intrauterine = while in the womb
- Most common route of transmission
2
Q
Congenital Infections
Routes of Transmission
A
-
Transplacental: bacteremia, viremia, parasitemia
- Most common
- Ascending from cervix: esp. after rupture membranes, amnionitis
- During delivery: cervical secretions, blood
- Postnatal: contact, airborne, fecal-oral, breastmilk
3
Q
Congenital Infection
Vulnerability
A
- Maternal exposure: pregnant women frequently live w/ children
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Maternal immune suppression: pregnancy itself
- ↓ Maternal response to fetal Ag
-
Maternal primary infection: highest risk for fetus
- No maternal adaptive immune defense
-
Immunologic immaturity: fetus > neonate > 1 mo. Old
- IgM used to dx congenital infections
- Gestational age at congenital infection: early ⇒ worst
- Age at postnatal infection: < 2 wks ⇒ worst
4
Q
Congenital Infection
Clinical Manifestations
A
- Most congenital infections are asymptomatic/inapparent at birth
-
Possible signs of congenital infection include:
- Fetal death/premature birth
- Intrauterine growth retardation: small for gestational age
- Abnormal brain growth: microcephaly, hydrocephalus, intracranial calcifications
- Ocular abnormalities: chorioretinitis, cataracts, microphthalmia
- Hepatosplenomegaly
- Bone abnormalities: lytic lesions, celery stalking
- Hematologic abnormalities: anemia, thrombocytopenia
- Skin lesions: petechiae, extramedullary hematopoiesis
5
Q
Major Congenital Infections
A
- Toxoplasma
- Cytomegalovirus
- Rubella
- Treponema pallidum
- Zika virus
6
Q
Major Perinatal Infections
A
7
Q
Toxoplasma Gondii
Lifecycle
A
8
Q
Toxoplasma Gondii
Congenital Disease
A
-
Pregnant woman acquires 1° infection w/ T. gondii
- Cats are the definitive hosts
- Humans become infected via ingestion of oocysts from cat feces or contaminated animal meat
- If during 1st trimester ⇒ usu. spontaneous abortion or stillbirth
- > 70% of congenitally acquired toxoplasmosis is unapparent at birth, but will manifest months to yrs later
- Clinical manifestations include:
- Intellectual disability / Learning disabilities
- Intracranial calcifications and hydrocephalus
- Visual impairment & chorioretinitis
- Hearing loss
- Hepatosplenomegaly
- Thrombocytopenia
9
Q
Chorioretinitis
Appearance
A
10
Q
Toxoplasma Gondii
Diagnosis
A
Congenital Infection or Symptomatic Primary Infection
- Acute active infection dx by serology
- High seropositivity in general pop. (20–50% in US)
- Pay attention to ↑ IgG titers (4-fold) and presence of specific IgM
11
Q
Rubella
General Characteristics
A
-
Rubella virus
-
Togavirus
- Same characteristics as Arboviruses except is not transmitted by arthropod vector
- ⊕-sense ssRNA
- Replicates in the cytoplasm & buds off cytoplasmic membrane
-
Togavirus
-
Rubella (“little red” or German measles, or 3-day measles)
- 1 of the 5 childhood exanthems (also measles, rubeola, fifth disease and chickenpox)
- Only one serotype of virus
12
Q
Rubella
Transmission and Epidemiology
A
- Occurs via respiratory route, or transmitted vertically during first 20 wks of pregnancy from nonimmune mother → fetus
- Humans are the only host for the virus
- Peak incidence: late winter and early spring
- Epidemics occur every 6-9 yrs
13
Q
Rubella
Pathogenesis and Clinical Disease
A
1° infection w/ postnatal rubella virus
- Starts in the upper respiratory tract
- Virus replicates in lymphoid tissue
- Ass. w/ the prodromal phase (1-2 wks) ⇒ lymphadenopathy and flu-like symptoms
- Viremia → dissemination
-
Ab vs virus appears → onset of mild erythematous maculopapular rash and arthralgias (adolescents and adults)
- Probably immune complex mediated
- Rash lasts ~ 3 days
- Virus shed for ~ 1 wk after onset of rash and from 7-14 days prior to the rash
- 25-50% of infections are asymptomatic
14
Q
Rubella
Congenital Infection
A
- Vertical transmission during first 20 wks of pregnancy from nonimmune mother → fetus
- Virus replicates in the placenta and travels via blood in the fetus
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Occurrence of congenital defects
- > 50% if infection occurs in 1st month of gestation
- 20-30% in the 2nd month
- 5% in the 3rd or 4th month
- Most common anomalies are ophthalmologic, cardiac, auditory and neurologic
- Triad is deafness, PDA and cataracts
- Almost all will have intellectual disability and chorioretinitis
- Frequently growth retarded
- Small # of infants may shed virus from nasopharynx or urine for ≤ 1 year
15
Q
Rubella
Diagnosis
A
- In congenitally infected infants, virus can be isolated from nasal specimens, blood, urine and CSF (PCR)
- Rubella specific IgM usu. indicates congenital infection
- 4-fold increase of rubella specific IgG in serum over several months can also confirm dx
- Many states have implemented prenatal screening of pregnant women for anti-rubella titers to determine at risk women
17
Q
Cytomegalovirus
Adult Infection
A
18
Q
Cytomegalovirus
Congenital or Perinatal Infection
A
-
~1% of live births are infected in utero
- Usu. d/t 1° infection of the mother during pregnancy
- Transmission can also result from passage through the birth canal and postnatally by ingesting virus containing breast milk
- Most full-term infants who acquire infection during or after birth have asymptomatic infections
- Preterm infants at higher risk for interstitial pneumonia or hepatitis
-
Clinical manifestations:
- 10-20% dx w/ intellectual disability or deafness
- Microcephaly, chorioretinitis, hepatosplenomegaly, jaundice
- CMV likes to be periventricular in the brain ⇒ microcephaly, periventricular calcifications and hydrocephalus ex vacuo
- Extramedullary hematopoiesis ⇒ hepatosplenomegaly & Blueberry muffin lesions (palpable purpura)
19
Q
Congenital or Perinatal CMV
Manifestations
A
21
Q
Treponema pallidum
Congenital Infection
A
-
100% of pregnant mothers susceptible to new Syphilis infection
- No protection from prior infections
-
Unique clinical manifestations:
- Celery stalk osteomyelitis
- Dental and long bone deformities
- Keratitis ⇒ blindness
22
Q
Congenital Syphilis
Manifestations
A
Celery stalk osteomyelitis
Dental and long bone deformities
Keratitis ⇒ blindness
23
Q
Zika Virus
A
-
Maternal infection during pregnancy:
- 1st trimester (@ 7-13 wks, up to 18 wks gestation) ⇒ anomalies noted
- Risk of microcephaly is 1-13%
- Zika causes ↑ apoptosis in the fetal brain
- Between 6-32 wks gestation ⇒ fetal loss reported
- Avoid travel to or having sex w/ traveler from endemic area during/just before pregnancy
24
Q
Listeria monocytogenes
Morphology and General Characteristics
A
- Listeria are fairly widespread and cause a spectrum of disease in animals and humans
- Listeria monocytogenes ⇒ human disease
-
Normal bowel flora
- Also common among fowl and cattle
- Short, gram-⊕, non-spore forming rods
- May resemble diphtheroids
- Aerobe
- Grow at temperatures as low as 4°C
25
Q
Listeria monocytogenes
Transmission and Epidemiology
A
- Ubiquitous, found in soil, water, vegetation and a variety of animals
- Asymptomatic intestinal carriage in 2-12% of humans
-
Transmission:
- 1° by ingestion of contaminated food
- Dairy products, particularly unpasteurized milk, soft cheeses
- Prepared meats, such as hot dogs and cold cuts
- L. monocytogenes able to grow at 4__°__C ⇒ pathogenic inoculum sizes can be reached during refrigeration
- Elderly, pregnant women, immunocompromised ⇒ ↑ risk
- Incidence of listeriosis in AIDS pts significantly increasing
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If acquired by a pregnant woman, can be transferred across the placenta to the developing fetus
- Frequently results in miscarriage, stillbirth or severely ill newborn
- 1° by ingestion of contaminated food
26
Q
Listeria monocytogenes
Pathogenesis
A
- L. monocytogenes is a facultative intracellular pathogen
- Can replicate both within and outside of cells
- Invades cells of the GI tract: undifferentiated epithelial cells, M cells, intestinal crypt cells, and MΦ
- Invasion mediated by internalin
-
Once inside the cell, L. monocytogenes produces a pore-forming cytolysin, listeriolysin O (LLO)
- Aids escape from vacuole → host cytoplasm ⇒ avoids killing
- Resistance mediated by activated MΦ via inactivation of listeriolysin O by oxidative metabolites
- MΦ activation dependent on recruitment of inflammatory T cells (TH1) ⇒ secrete cytokines like IFN-γ
27
Q
Listeria monocytogenes
Clinical Syndromes
A
-
Early-onset disease in the neonate
- 1° infection of pregnant mother
- Asymptomatic vs flu-like sx or UTI
-
In utero fetal infection ⇒ granulomatosis infantiseptica
- Serious disease characterized by disseminated abscesses and granulomas in multiple organs
- 1° infection of pregnant mother
-
Late-onset disease in the neonate
- Perinatal infection from Listeria colonizing the vagina
- Disease is much less severe than early-onset disease & occurs less frequently
- Appears 2-3 wks after birth as meningitis and septicemia
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Meningitis
- Occurs in neonates and immunosuppressed adults
- Meningitis is the most common infection caused by Listeria in adults
- Most often occurs in pts w/ depressed CMI
-
Bacteremia and endocarditis
- Occur in pts w/ depressed CMI
28
Q
Listeria monocytogenes
Diagnosis
A
- Culture L. monocytogenes from blood, CSF or focal lesions
- Grow on blood agar ⇒ small zone of beta hemolysis around colonies
- Catalase ⊕
- CAMP ⊖
- Characteristic tumbling end-over-end motility at 25°C
- Serologic tests available
29
Q
Listeria monocytogenes
Treatment and Control
A
- Several abx including penicillin G, ampicillin, erythromycin and chloramphenicol
- Immunity ass. w/ CMI, esp. activation of MΦ by INF-γ
-
High risk individuals:
- Avoid eating raw, unpasteurized cheeses, processed meats (hotdogs, cold cuts) unless steaming hot
- Thoroughly wash raw vegetables
