Download Pediatric Infections

Microbiology: Perinatal and Pediatric Infections (Freji)
CYTOMEGALOVIRUS (CMV):
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General:
Structure: enveloped, dsDNA virus
Persists after primary infection: in low-grade chronic or latent states with periodic reactivations
Transmission: spread of infected oropharyngeal secretions, sexual intercourse, blood transfusions or mother to
fetus spread (transplacental)
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Maternal CMV Infection:
Many adults in the population have Abs to CMV, however, pregnant women can have a primary infection
Pregnant women can shed CMV from cervix, urinary tract, throat, and in breast milk post-partum
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Primary CMV Infection in Pregnancy:
Most are asymptomatic (~90%)
Symptomatic cases present with many symptoms, including:
o Infectious mononucleosis
o Hepatitis
o Thrombocytopenia
o Myocarditis
Transmission of CMV to fetus occurs ~50% of the time in mothers infected for the first time during pregnancy
Diagnosis:
o Isolate virus from urine, buffy coat or cervical secretions
o Measure anti-CMV IgM antibodies (indicates primary infection)
o Rapid diagnosis using PCR (can perform on any tissue- urine, blood, CSF etc.)
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Congenital CMV:
~1% of live births: however, only a small amount of these are symptomatic at birth
Diagnosis: isolation of CMV from urine or saliva within the first 2 weeks of life
Symptomatic Congenital CMV:
o Mortality Rate: 15-30%; most survivors have long-term sequelae
o Common Findings: petechiae, jaundice, hepato- and splenomegaly, thrombocytopenia, conjugated
hyperbilirubinemia
o Neurologic abnormalities: microcephaly, seizures, hypotonia, intracranial calcifications
o Sensorineuronal hearing loss: most common cause of non-genetic congenital hearing loss
o Eye abnormalities: chororetinitis most frequently; also optic atrophy, micopthalmia and cloudy cornea
o Dental defects
o Urinary CMV shedding: continues for months or years
o Treatment: Ganciclovir in symptomatic CMV infection
Asymptomatic Congenital CMV:
o Can follow primary or reactivate CMV infection in the mother
o Urinary CMV shedding: continues for months or years
o Sensorineural hearing loss: found less often than in symptomatic CMV
o Mental or behavioral problems: seen in some cases
o Antiviral therapy NOT recommended
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Perinatal CMV:
CMV is acquired during passage through infected birth canal or by ingestions of CMV-positive breast milk
Most cases are asymptomatic
Most common clinical illness: self-limited infantile pneumonitis (can be severe in premature infants)
No long-term hearing or neurologic deficits
HERPES SIMPLEX VIRUS:
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Maternal HSV Infection During Pregnancy:
Only 1/3 of women infected with HSV during pregnancy will have symptoms
If infection occurs shortly before delivery, ~50% of newborns will get infected (not enough Ab to pass on yet)
Asymptomatic shedding: can occur in pregnant women at or near term (most common type of shedding)
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Neonatal HSV:
Transmission: intrapartum is usual route; can also occur via transplacental spread as well
Risk of Transmission: much higher for mothers with primary HSV infection than those with recurrent infection
Risk Factors:
o Cervical HSV infection
o Multiple genital lesions
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o Prematurity
o Prolonged rupture of maternal membranes
o Intrauterine instrumentation
o Low/absent titers of maternal neutralizing Ab (which normally blocks virus action)
Intrauterine HSV Infections: baby born already sick; only small percentage of neonatal cases
Hallmarks: vesicular rash present at birth/appears shortly after
Associated Abnormalities: microcephly, chorioretinitis, microphthalmia, intracranial calcifications, seizures
High Mortality Rate: ~50%; survivors have long-term complications
Clinical Manifestations of Neonatal HSV:
Asymptomatic Infection: very rare
Three Presentations:
1. Skin/Eyes/Mucous Membranes (SEM):
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Cutaneous Lesions: discrete vesicles, large bullae, or denuded skin (10-11 days old)
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Eye Disease: keratoconjunctivitis and chorioretinitis
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Mouth: ulcerative lesions
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Neurological Abnormalities: can develop in some, although CNS involvement was not
evident during acute illness
2. Localized CNS Involvement (Encephalitis):
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Symptoms: focal or generalized seizures, lethargy, or apnea
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Skin lesions often absent: makes it hard to diagnose
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CSF: mononuclear pleocystosis and elevated protein
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Mortality Rate: fairly high; survivors have long-term sequelae (a small number have a CNS
relapse within one month of completing therapy)
3. Disseminated Disease:
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Presentation: similar to sepsis patient (around age 9-11 days)
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CNS involvement: only in about 2/3s of cases
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Other severely infected organs: adrenal glands, GI tract, liver, pancreas, heart, and kidneys
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High mortality rate: over 50% even with therapy; majority of survivors have severe
neurologic impairment
Treatment: acyclovir (almost always) or vidarabine
Prevention:
C-section for women with signs and symptoms suggestive of genital HSV at onset of labor (as long as membrane
rupture is not greater than 4-6 hours)
Oral acyclovir or valcyclovir given late in pregnancy for women with frequent genital recurrences (in practice,
many more than just this receive this therapy)
Diagnosis:
Isolate virus from vesicular lesions or CSF
PCR: detects HSV DNA in CSF, blood and skin lesions (very sensitive and test of choice)
VARICELLA ZOSTER (CHICKENPOX AND SHINGLES):
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Varicella:
General Comments:
o Highly communicable and usually benign disease of childhood
o Most women have Abs to VZV
Typical Illness: fever, malaise, pruritic rash
o Truncal rash characterized by crops of maculopapules that evolve in to vesicles, which eventually crust
over (presence of lesion in various stages of evolution)
Complications: bacterial superinfection (most common), pneumonia, arthritis, encephalitis, bleeding diathesis
o Adults are more likely to have complications
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Zoster (General):
Rash: unilateral, usually follows distribution of one or more sensory nerve roots (shingles)
o Follows same evolutionary pattern as varicella
o Painful in adults; not so much in kids
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Diagnosis: usually done clinically with laboratory confirmation rarely being needed
Laboratory confirmation possible via:
o Recovery of virus from vesicle fluid or detection of VZV Ags from base of fresh vesicles
o PCR detecting VZV DNA (most common now)
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Fetal Varicella Syndrome:
Cause: occurs after maternal chicken pox during the first 20 weeks of pregnancy (although risk of transmission is
small)
Clinical Findings:
o Cutaneous scars, denuded skin
o Limb hypoplasia: usually unilateral; most commonly leg
o Shingles during infancy
o CNS abnormalities: microcephaly, seizures, focal brain calcifications
o Ocular abnormalities
o Autonomic dysfunction: dysphagia, loss of urinary or bowel sphincter control
Neonatal Varicella Syndrome:
Cause: most often due to maternal chickenpox during the last 3 weeks of pregnancy (no Abs transferred to help)
Illness:
o Infection within 5 days of delivery: may be mild but can become severe (fever, hemorrhagic rash,
generalized visceral involvement)
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Mortality high for severe infection: ~30%; usually due to pneumonia
o Infection 5-21 days before delivery: illness usually mild
Treatment: acyclovir
Prevention: infants born to mothers who develop varicella 5 days before or 2 days after delivery should receive
125 units of varicella zoster immune globulin ASAP
PARVOVIRUS B19 INFECTION:
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Maternal B19 Infection:
Source: infected respiratory secretions or blood transfusions (uncommon)
Higher rates of infections in some women: school teachers, healthcare workers, homemakers
Clinical Manifestations:
o Asymptomatic: ~20%
o Symptomatic:
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Erythema infectiosum (slapped cheek appearance; most common, usually seen in kids)
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Influenza-like illness and symmetric polyarthropathy (in adults)
o Chronic Condition:
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Anemia
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Transient aplastic crisis
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Hemophagocytic syndrome
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Fetal B19 Infection:
Serious infection that can result in death:
o Hydrops fetalis, spontaneous abortion, or stillbirth possible after maternal infection during pregnancy
o Chronic anemia (B19 suppresses fetal bone marrow RBC production)
o Cardiac dysfunction (direct infection of fetal heart muscles possible)
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Diagnosis:
B19 specific IgM (seen by day 3; can persist for up 2 4 months)
B19 specific IgG (by the end of the first week; persists for life)
B19 DNA detected in serum/tissues using PCR
TOXOPLASMOSIS GONDII:
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General:
Obligate intracellular protozoan
3 forms: tachyzoite, tissue cyst or oocyst
Hosts: cats and other felines
Infect: humans and other warm blood animals
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Transmission
Primary:
o Ingestion of oocyst contaminated food or water
o Consumption of cyst-containing raw/undercooked meat
o Oocysts from cat litter box material, dust or soil
Other Methods: eating raw infected eggs, blood transfusion, organ transplants from positive donors
Intrauterine Transmission: from mother to fetus
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Maternal Toxoplasmosis:
Acute Infection: most often asymptomatic
If Symptomatic: lymphadenopathy (head and neck region) is the most common illness; causes a small number of
infectious mononucleosis cases
Possible Complications: hepatitis, pneumonia, myocarditis, encephalitis, deafness
Transplacental Spread:
o Infection Early in Pregnancy: risk of transmission is the lowest, but transmission during this time
causes the most severe disease
o Infection Late in Pregnancy: risk of transmission is highest, but disease not as severe
Treatment:
o Spiramycin sometimes give to reduce risk of fetal infection
o If fetal infection occurs, mother treated with pyrimethamine and sulfadiazine (folic acid antagonists)
Congenital Toxoplasmosis:
Most are asymptomatic at birth: but still affected by disease
Symptomatic disease at birth: can be mild, moderate or severe
o Often born premature
o Only a small number are born with severe disease (survivors have major neurologic sequelae)
Symptoms:
o CNS Symptoms: vasculitis, thrombosis, infarction of brain tissue, hydrocephalus, intracranial
caclifications, hypotonia, microcephaly, seizures
o Eye Symptoms: chorioretinitis, chorioretinal scars (important), iritis, optic atrophy, cataracts
o Sensorineural hearing loss: not as common as in congenital CMV
o Other Symptoms: hepatosplenomegaly, jaundice, petechiae, purpura, anemia, thrombocytopenia
Diagnosis:
o Isolation of parasite from placenta or blood
o PCR to detect DNA in urine, CSF or serum
o Specific IgM Abs
o Specific IgG Abs (transferred from mother to fetus; typically drop by ~50% per month- if levels do not
fall, suspect congenital infection)
Treatment:
o Pyrimethamine, sulfadiazine and leucovorin for one year
o Steroids to treat chorioretinitis or high CSF protein levels
o Need a lot of monitoring during therapy (platelet count, neutrophil count etc.)
Prognosis:
o Regardless of treatment, most will develop chorioretinitis or chorioretinal scars by age 10-20;
treatment reduces the severity and frequency of these adverse sequelae
o Recurrences of ocular toxoplasmosis occur even if treated infants (although less often than untreated)
o Neurologic problems (hydrocephalus, seizures) can occur even with treatment
SEPSIS NEONATORUM:
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General: disease of infants who are less than 1 month of age, are clinically ill, and have positive blood cultures
Early Onset: first week of life (often caused by Group B Streptococci and E.coli)
Late Onset: after first week of life (often caused by Coagulase-negative Staph picked up in the NICU)
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Risk Factors:
Premature labor
Prolonged rupture of fetal membranes
Chorioamnionitis
Maternal fever
Use of arterial and venous umbilical catheters, central venous catheters, or endotracheal tubes
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Clinical Manifestations:
Symptoms (Non-Specific): temperature instability (hyper- or hypothermia), lethargy, apnea, poor feeding,
tacynpnea, vomiting, diarrhea, abdominal distention
Lab Abornomalities: abnormal WBC count, unexplained metabolic acidosis, hyperglycemia
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Group B Streptococcal Sepsis:
Vertical Transmission of GBS: occurs often, but does not always result in infant colonization
Prevention of Transmission: intrapartum antibiotic (usually penicillin) as prophylaxis in women who are carriers
of GBS
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Early Onset GBS Sepsis: ~around 20 hours old
o Most often in premature infants
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Other risk factors: low birth weight, early membrane rupture, intrapartum fever, maternal
GBS rectovaginal colonization, race (African American), young maternal age (<20) , GBS
bacteriuria during pregnancy, previous stillbirth/abortion, previous child with GBS infection
o Sudden onset and can be fulminant (life-threatening)
o Primary focus of inflammation occurs in the lung (meningitis can also occur)
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Respiratory distress, apnea, hypotension, DIC
o Can be treated so mortality rate not very high (but is inversely related to birth weight)
Late Onset GBS Sepsis: ~2-4 weeks of age
o Symptoms: insidious onset (poor feeding and fever most common signs)
o Presentation: bacteremia without specific focus, follow by meningitis
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Neurologic deficits: may occur ~1/2 the time after GBS meningitis
o Relapse/Reingection: possible but uncommon
EPSTEIN-BARR VIRUS:
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General:
Transmission: only found in humans and spread by intimate contact
Most common clinical outcome: NOTHING (most often asymptomatic)
Other clinical manifestations: infectious mononucleosis (most common if symptomatic), Burkitt’s lymphoma,
nasopharyngeal lymphoma, B-cell lymphoma in immunodeficient children
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Infectious Mononucleosis:
Classic Disease: fever, exudative pharyngitis, lymphadenopathy, hepatosplenomegaly, atypical lymphocytes
Complications: aseptic meningitis, encephalitis, rupture of spleen (avoid sports), hemolytic anemia, myocarditis,
thrombocytopenia
Diagnosis:
o Heterophile Abs (non-specific; can be done quickly)
o EBV specific Abs (ie. to viral capsid Ag, early Ag, nuclear Ag; reserved for more severe cases due to
increased accuracy)
Treatment: bed rest in acute phase and avoid sports until spleen not palpable
o Steroids: used to control tonsilar swelling, splenomegaly, hemolytic anemia and hemophagocytic
syndrome
HUMAN HERPESVIRUS-6 (HHV-6):
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General:
Most cases are asymptomatic
Transmission: infected respiratory secretions
Symptomatic cases: most commonly show up as roseola infantum (exanthema subitum)
o Reactivation of virus infection can also occur in immunosuppressed patients (BM suppression,
hepatitis, pneumonia)
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Roseola (Exanthem Subitum):
Basics: acute febrile illness of infants and young children (6 months-3 years)
Fever: abrupt and high spiking, lasts 3-7 days
Rash: follows fever; erythematous macular/popular rash that lasts for 2 days, beginning on trunk and spreading
outward
Complications: febrile seizures most common; others include hemiplegia, encephalopathy, thrombocytopenia
purpura
STAPHYLOCOCCAL SCALDED SKIN SYNDROME:
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General:
Cause: exotoxin of S.aureus
Diagnosis: clinical grounds alone (organism can be isolated from skin or nose but often not needed)
Therapy: oral or parenteral Abx; no topical Abx or steroids
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Symptoms:
Children often febrile and uncomfortable
Severe Form:
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Bullous desquamation of large areas of the skin
o Tender erythroderma (baby will cry if you hold them in attempt to soothe)
o Positive Nikolsky sign (separate epidermis from dermis when you drag your finger over the skin)
Mild Form:
o Diffuse scarlantiform erythroderma with sandpaper texture (skin is also tender, but not as extreme)
o Cracks appear around the eyes and mouth
KAWASAKI DISEASE:
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General: disease resulting from blood vessel inflammation (medium size arteries most severely affected- coronary
and renal arteries are examples)
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Diagnostic Criteria:
Fever lasting at least 5 days (high spiking and remittent; will persist for weeks without treatment)
o Treatment: immunoglobulin IV + high dose aspirin
Plus, 4 of the following 5 signs:
o Bilateral conjunctival injection without exudates (begins after fever; resolves easily with therapy)
o Changes of the oral mucosa
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Lips: erythema, dryness, fissuring, peeling, bleeding
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Oral/Pharyngeal mucosa: erythema
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Strawberry tongue
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Note: if oral ulcers, Koplik spots or exudates present it is NOT Kawasaki
o Changes of the hands and feet
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Palms/Soles: erythema
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Swelling: of hands and feet
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Periungual desquamation: of fingers and toes
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Beau’s Lines: transverse grooves across nails (1-2 months after onset of disease)
o Rash (often a diffuse maculopapular erythematous rash; vesicles and bullae not seen)
o Cervical lympadenopathy (must be >1.5cm)
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Least common finding of all (ie. if one is missing, it is probably this one)
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Node must be nonfluctuent and nonpurulent
Disease not explained by any other process
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Clinical Phases: without treatment (therefore, not seen anymore because usually treated)
Acute Febrile Phase: 1-2 weeks
Subacute Phase: begins when fever, rash and lymphadenopathy resolve (risk of sudden death the highest)
o Aneurysms: usually develop at this stage
Convalescent Phase: usually 6-8 weeks after onset of fever
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Laboratory Features:
Can have normal or elevated WBC counts
Elevation of ESR and other acute phase reactants
Normocytic anemia
Thrombocytopenia (uncommon; associated with severe coronary disease and MI)
Thrombocytosis
Sterile pyruia (urine containing pus)
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Epidemiology:
Most cases in children under 4 years of age (rare <3 months), but can occur in older children and adults
Occurs around the word but Asians are at highest risk
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Cardivascular Manifestations:
Many untreated patients develop coronary abnormalities (ie. diffuse dilation or aneursyms)
o Aneurysms: ~50% resolve, but the rest have persistent aneurysm (can lead I increased risk of MI and
stenosis)
o Other Abnormalities: myocarditis, vavulitis, pericardial effusion, MI
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Management:
Therapy in Acute Phase: should be started in first 10 days of illness to reduce risk of coronary artery disease
o IGIV high dose (often 2 doses needed) + high dose aspirin for the fever
Management: follow up echocardiograms, aspirin for life with those with aneurysms
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