15. Congenital infections of the newborn. Flashcards
what are the three group of infections for newborn ?
INTRAUTERINE/ congenital infections - the signs and symptoms are present at birth
PERINATAL - infection can be acquired during birth and signs and symptoms present after birth and first 48hrs
POSTNATAL - signs and symptoms start 48 hrs after birth
what are the most common causative agents for intrauterine/ congenital infection
TORCH
t - toxoplasmosis O- other syphillus (trepanoma palladium , varicella zoster , parvovirus ) R - rubella C - cytomegalovirus H- herpes simplex virus
and congenital listeriosis
in which trimester is it most dangerous to acquire intrauterine infections ?
1st trimester - greater risk for fetus
especially because the infection with the mother can be asymptomatic
how can TORCH infections be avoided ?
immunisation of rubella and VZV before pregnancy or in childhood
and some infections such as syphilus treated with benzylpenicillin
what are the most common routes of intrauterine infections ?
hematologically - esp viruses
ascending infection from the vagina - bacteria and Herpes simplex virus type 2
what is the source of transmission in toxoplasma gondii ?
cat feces , raw or insufficiency cooked meat , unpasteurised milk
what are the clinical features in toxoplasmosis gondii ?
when the mother gets the infection in first trim
triad symptoms very severe
TRIAD:
chorioretinitis
DIFFUSE INTRACRANIAL calcifications
hydrocephalus / cerebral ventricular dilation
affected may die in utero or a few days after birth
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Term newborns usually present with a milder form of the disease with symptoms such as hepatosplenomegaly and lymphadenopathy.
no apparent clinical manifestations at birth OR
intellectual disability
Recurring chorioretinitis resulting in vision loss
Motor delays
Learning disorders
Intellectual disability
SENORINEURAL HEARING LOSS
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In comparison, preterm newborns exhibit severe symptoms
micro or macrocephaly
hydrocephalus
meningoencephalitis
nystagmus
petechia and purpura - blueberry muffin rash
lymphadenopathy
epilepsy / seizures
retinal scars
microphthalmia
retinochoroiditis
what is the diagnosis of toxoplasmosis ?
suggestive sonographic findings
fetus - amniocenteisis and do PCR
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for NEWBORN
CT or MRI - intracranial periventricular calcifications , hydrocephalus , ring enhancing lesions
IgM Toxoplasma specific antibodies (concern for false positives due to maternal contamination of fetal blood during labor, repeat serological testing should be done 10 days after birth ; half-life of Toxoplasma IgM and IgA antibodies is 5 and 10 days)
Negative IgM and IgA antibodies do not exclude the infection. If the mother is affected later in her pregnancy, there is a delay in the production of antibodies in the newborn. When an infection is suspected, the antibodies should be repeated every 2 to 4 weeks until at least 3 months of age
Positive IgG is indicative of prior or current maternal infection. In the presence of other suggestive features but negative IgM and IgA antibodies, toxoplasma IgG testing requires repetition every 4 to 6 weeks until complete disappearance
PCR for T gondii DNA
positive Toxoplasma IgM or Ig A antibodies in the CSF
ophthalmological evaluation
what is the treatmnet of congenital toxoplasmosis ?
mother 1st trimester - immediate spiramycin to prevent fetal toxoplasmosis
3grams a day
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after 18th week up to birth
pyrimethamine 100mg/day first two days and maintenance dose of 50mg/day
sulfadiazine - 75mg/kg/day
folinic acid - 15mg every 3 day
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newborn - pyrimethamine , sulfadiazine and folinic acid
12 months
pyrimethamine
For Neonate
1 mg/kg twice daily for 2 days, then 1 mg/kg once daily for 6 months,
then 1 mg/kg 3 times a week for 6 months
sulfadiazine
50 mg/kg twice daily for 12 months
Folinic acid (leucovorin): 10 mg, 3 times per week
higher doses and longer duration (2 years) are the recommended approach when the presentation is severe, with over three intracerebral calcifications and/or more than one ocular sign or severe abnormalities at birth.
Asymptomatic infants with positive serology or newborn screening receive treatment for 3 months. Some experts recommend adding steroids to this regimen when the CSF protein is high or severe chorioretinitis affecting vision. Steroid therapy continues until the disappearance of protein in CSF or resolution of chorioretinitis
prevention of toxoplasmosis gondii is very important to be to taught to mother what are the preventive methods ?
avoid raw undercooked meat
avoid contact with CAT LITTER
how is trepanoma palladium transmitted ?
sexual transmission
or perinatal transmission during birth
what are the clinical features of syphillus ?
inutero
miscarriage , stillbirth , hydrocephalic fetus
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neonates born with CS are asymptomatic at birth
early congenital syphilus usually appear by three months, <2years old onset
- hepatomegaly and jaundice
- rhinorrhea - Copious, persistent white discharge is noted, which contains spirochetes that can be visualized under darkfield microscopy.
maculopapular rash on palms and soles ,back, buttocks, posterior thigh
skeletal abnormalities
and generalised lymphadenopathy
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late congenital syphilus (onset >2 years of age)
saddle nose
frontal bossing
short maxilla
hutchinson teeth - hypoplastic notched and widely spaced teeth upper central incisors
SABER SHINS
sensorineural hearing loss
perioral fissures
Skin and mucous membrane gummas
cranial nerve palsy - nerve 8 causing deafness
Eye- interstitial keratitis
Intellectual disability
Sensorineural hearing loss
Hutchinson triad (Hutchinson teeth, interstitial keratitis, and sensorineural hearing loss)
what is the diagnosis for congenital syphillus ?
newborn and mother
Maternal screening for syphilis in early pregnancy important
All neonates born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on the neonate’s serum!
because umbilical cord blood can become contaminated with maternal blood and yield a false-positive result,
and Wharton’s jelly within the umbilical cord can yield a false-negative result
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Non-treponemal tests
RPR -Rapid Plasma Reagin test
detects nonspecific anti-cardiolipin antibodies
is sensitive but not specific
or
VDRL Detects nonspecific anti-cardiolipin antibodies - is sensitive, but not specific
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Specific treponemal tests:
Conducting a treponemal test on neonatal serum is not recommended because it is difficult to interpret
Fluorescent treponemal antibody absorption (FTA-ABS) and/or micro hemagglutination test for antibodies to T.Pallidum (MHA-TP) testing
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CSF abnormalities including reactive CSF VDRL, CSF pleocytosis, elevated CSF protein
CSF PCR for detection of treponemal DNA
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Long bone radiographs that may show findings of pathologic fractures, metaphyseal serration, localized demineralization, and osseous destruction.
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always confirmatory test - dark field microscopy or PCR of suspicious lesion or bodily fluid (bullous rash and nasal discharge)
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in FETUS - repeated US examinations for plaentomegaly , hepatomegaly ascitis or hydrocephalus
what is the treatment for congenital syphilus ?
Infants up to 4 weeks of age: Aqueous crystalline penicillin G, 50,000 -75,000 units/kg intravenously every 12 hours in the first seven days of life. After 7 days of life, 50,000 units/kg per dose intravenously (IV) every 8 hours for 10 to 14 days. Alternatively, procaine penicillin G, 50,000 units/kg/day intramuscularly for 10 to 14 days.
Infants older than 4 weeks and older children: Aqueous penicillin G, 50,000 units/kg every 6 hours intravenously for 10 to 14 days.
how is listeria transmitted?
RAW milk products such as soft cheese -feta, brie, and camembert cheeses
or fish ,
meat
Do not eat refrigerated pâtés or meat spreads
or
direct contact with infected vaginal secretion or blood during delivery
what are the clinical features of listeria ?
Listeriosis of pregnancy :
- premature birth and spontaneous abortion
- Early-onset syndrome: granulomatosis infantiseptica - evere disseminated form of disease characterized by widespread microabscesses and granulomas
respiratory distress
Pustular erythematous lesion
fever
meningitis
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premature delivery with amnionitis
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Neonatal listeriosis
may be apparent within hours or days of birth (early onset) - frequentlylow birth weight, associated obstetric complications, show evidence of neonatal sepsis soon after birth with circulatory or respiratory insufficiency or both
Infants with late-onset listeriosis are generally full term, healthy at birth
source of listerial infection in this group is not known, but is possibly the mother’s alimentary tract or the environment, as the organism is rarely isolated from the mother’s genital tract
Late-onset syndrome (5 days to 3 weeks after birth): Listeria meningitis/encephalitis
diagnosis of listeriosis ?
can only be made by culturing,
from a sterile site such as blood, amniotic fluid, or spinal fluid or CSF sample for pleocytosis.
Vaginal or stool cultures not helpful because some women carriers but no clinical disease
Laboratory confirmation of the organism involves biochemical testing and observation of motility using a slide test or showing motility in semisolid media
what is the treatmnet of listeriosis ?
for mother
IV ampicillin and penicillin , amoxicillin
(Some in vitro studies suggest a synergistic effect when gentamicin is added to treatment regimens; however, animal models do not reliably show a synergistic effect. Given the toxicities of gentamicin some clinicians have questioned the value of adding it to the treatment regimen)
antibiotic must bind to the penicillin-binding protein 3 (PBP3) of Listeria, which causes cell death, these drugs block several PBP
Whichever antibiotic is chosen, dosage is critical
6 g or more per day of ampicillin during pregnancy (2 g every 6 to 8 hours) in IV duration of one to two weeks - if fetus survives continue
second line is erythromycin 4g/d iv - same time frame as ampicillin
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neonate
infants less than 7 days and less than 2kg
= ampicillin 100mg/kg/day IV (divided bid)
gentamicin - 2.5mg/kg/ every 12hr IV
two weeks course usually satisfactory (21 days for meningitis)
but the optimal duration is unknown
infants 8 days to 1 month and more than 2kg:
200mg/kg/day IV divided qid
2.5mg/kg/day IV very 8 hours
what is the transmission of varicella zoster virus (chicken pox) ?
seronegative patients risk of acquiring VZV during pregnancy
airborne droplets
vesicle fluid contact from shingles
or reactivation in immunocompromised individuals
{ responsible for chickenpox (primary VZV infection) and herpes zoster (or shingles) reactivation of latent infection in the dorsal root ganglia}
what are the clinical features of VZV?
first and second trim :
congenital varicella syndrome
hypertrophic cictrical skin lesions
limb defects - hypoplasia / atrophy / malformation
cataracts / chorioretintis / nystagmus
CNS : microcephaly,
cortical atrophy,
seizures,
mental retardation.
Autonomic nervous system : neurogenic bladder, hydronephrosis,
esophageal dilation, gastrointestinal reflux
what is the diagnosis of VZV ?
Prenatal ultrasounds may be used to identify severe manifestations of intrauterine VZV infection
newborn and mother
skin lesions
DFA (Direct immunofluorescent antibody technique) or PCR of blisters or CSF
Viral cultures can also be obtained but often take up to 1 week to yield results
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fetus - amniocentsis PCR
what is the treatment of VZV ?
antiviral therapy in the newborn not expected to have much impact
However, if the infant develops clinical signs of active infection, acyclovir should be administered intravenously - 10mg/kg
therapy duration is determined based on active VZV replication with either cessation of new skin lesion formation or with negative VZV PCR testing.
If mother develops chickenpox infection during the high-risk time period for neonatal varicella infection (5 days before through 2 days after delivery), infants should receive Varicella-zoster immune globulin (VZIG) immediately after birth or as soon after the maternal symptoms appear in the two days after delivery
Cesarean delivery if lesions are present at the delivery
prevention of VZV?
Immunization of seronegative women before pregnancy
VZIG in pregnant women without immunity within 10 days of exposure
what is the transmission of rubella ?
airborne droplets
is after 20 weeks of gestation the mother is contracted with rubella there is no documented cases
what are the clinical features of rubella ?
intrauterine - miscarriage , preterm and fetal growth restrictions
==== congenital infection is high in first and last weeks of pregnancy (birth defects high in late esp first 12 weeks) ======
congenital rubella syndrome - triad :
- cardiac defect -patent ductus arteriosus or pulmonary artery stenosis , ventricular and atrial septal defect
- cataracts (leading to salt and pepper retinopathy)
- cochlear defect - bilateral senorinueral hearing loss
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early features : -hepatospelanomegaly , jaundice - blueberry muffin rash - hemolytic anemia -thrombocytopenia micropthalmia cerebral calcifications meningoencephalitis radiolucent bones - celery stalk of long bone metaphases
late features : microcephaly intellectual diabsility skeletal abnormalities chorioretinits delayed onset of insulin dependent diabetes and thyroid diseases
diagnosis of rubella ?
maternal screening
PCR for RNA
serology - RV-IgG and IgM
Viral culture (nasopharynx, blood)
prenatal fetal
igM antibody serology
PCR for rubella RNA through amniocentesis
postnatal
RV-IgG antibodies in neonatal serum using ELISA
Confirmation of infection virus in nasopharyngeal swabs, urine and oral fluid using PCR
what is the treatmnet for rubella ?
<16 weeks = counsel to terminate pregnancy
> 16 weeks - reassurance
how can we prevent rubella ?
immunisation before pregnancy
Children with congenital rubella syndrome should be considered contagious until at least one year of age
how does the transmission of cytomegalovirus occur?
humans are the main reservoir
Important risk factor for primary infection during pregnancy is prolonged exposure to young children.CMV infected children under 2 years of age secrete the virus in their urine and saliva for about 24 months.
mother contaminated via CMV-contaminated blood, urine, saliva, and genital secretions
Sexual transmission
Transplant-transmitted infection
postnatal via breastmilk from infected mother
clinical features of cytomegalovirus ?
Primary infection cannot clinically be distinguished from Epstein Barr virus (EBV) : fever, malaise, headache, pharyngitis, lymphadenopathy, hepatosplenomegaly, arthralgia
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Fetal infection
IUGR
Microcephaly
Sensorineural hearing loss - hallmark
Chorioretinitis, optic atrophy and cataracts
Petechiae, purpura -(blueberry muffin rash)
Hepatosplenomegaly, jaundice
Small for gestational age (SGA)
Seizures
hydrocephalus, ventriculomegaly
periventricular calcifications, or
intraventricular hemorrhage
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most infected newborns are asymptomatic
diagnosis of cmv ?
mother
CMV IgM antibodies
IgM antibodies can persist for several months. More sophisticated testing such as IgG antibody avidity testing is necessary for sorting out the timing of infection. With recent infections, the avidity is low (antibodies bind less tightly with their protein); thus the presence of IgM levels along with a low IgG avidity index is highly suggestive of a recent primary infection
Viral culture or PCR for CMV DNA (urine, saliva)
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Fetus
via amniocentesis for amniotic fluid PCR with or without viral culture
Replication of the virus in the fetal kidney, leading to shedding in the urine, occurs at least 5 to 7 weeks after infection. Thus, the optimal time for performing this test is after 21 weeks gestation and 7 weeks after maternal infection
treatment for cmv ?
Fetus
termination of the pregnancy
Severe anemia: intrauterine blood transfusions
Thrombocytopenia: platelet transfusions
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Newborn
first line
with symptomatic CCMV should receive oral valganciclovir for 6 months 16 mg/kg/dose twice daily. This therapy has been shown to preserve normal hearing or prevent the progression of hearing loss
Alternative:
• Ganciclovir IV 6 mg/kg/dose twice daily
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Mother:
valacyclovir - only therapy approved during pregnancy
what type of causative agent is HERPES simplex virus ?
genital herpes HSV 2 (type 1 - oral rare)
what is the transmission of HSV2?
ontact with contaminated oral secretions via small skin lesions
Reactivation: usually in immunocompromised individuals
transmission through vaginal delivery
what is the clinical features of HSV2
Intrauterine HSV infection (∼ 5% of cases)
Fetal demise, preterm birth, very low birth weight Microphthalmia and chorioretinitis Vesicular skin lesions
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Perinatal and postnatal transmission
persistent fever and negative bacterial cultures
SKIN EYE AND MOUTH DISEASE :
1) Vesicular skin lesions
2) Keratoconjunctivitis leading to cataracts, chorioretinitis
CNS DISEASE
1) Meningoencephalitis - Seizures
2) vesicular skin lesions
DISSEMINTAED DISEASE
prominently liver and lungs
(fever or hypothermia, irritability, lethargy, respiratory distress, apnea, abdominal distension, hepatomegaly, ascites)
Thrombocytopenia
2) Vesicular skin lesions
When skin lesions are not present, it can be challenging to diagnose neonatal HSV infection
what is the diagnosis of HSV2?
neonates
Swab specimens from the mouth, nasopharynx, conjunctivae, and anus (“surface cultures”) for HSV culture and, if desired, for HSV PCR assay;
Specimens of skin vesicles for HSV culture and, if desired, for PCR assay;
CSF sample for HSV PCR assay;
Whole blood sample for HSV PCR assay; and
Whole blood sample for measuring alanine aminotransferase (ALT).
Positive cultures obtained from any of the surface sites more than 12 to 24 hours after birth indicate viral replication and are, therefore, suggestive of infant infection rather than merely contamination
treatmnet of HSV2
IV acyclovir
60 mg/kg per day in 3 divided doses
or 14 days in SEM disease
Given intravenously for a minimum of 21 days in CNS disease or disseminated disease
repeat lumbar puncture performed near the end of therapy to document that the CSF is negative for HSV DNA on PCR assay
prevention of HSV2?
Antiviral therapy (acyclovir) beginning at 36 weeks of gestation for individuals with a known history of HSV lesions
Cesarean delivery in women with active genital lesions or prodromal symptoms (e.g., burning pain)
if the mother is infected with HIV what’s the chance the baby having it ?
there is a 25 percent chance the fetus being affected
depending on : high viremia , AIDS or low CD4+ CELL COUNT
HOW is HIV passed from mother to fetus ?
late in pregnancy through haematological route , and highest during delivery
what are the clinical manifestations of HIV in fetes ?
fever hepatomegaly splenomegaly lyphadenectomy freq opportunistic infection - such as oral thrush
usually do not have symptoms until opportunistic infections occur
diagnosis of hiv in children and adults
Diagnosis in infants: if < 18 months, diagnosis is confirmed via PCR, not ELISA
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detect both HIV antigen (p24 capsid protein) and anti-HIV antibodies (IgG antibodies against HIV-1/HIV-2) through ELISA → a negative result essentially rules out HIV infection (almost 100% sensitivity)
Not recommended for suspected neonatal HIV infection (results may be false-positive due to maternally transferred anti-HIV antibodies)
Confirmatory tests
HIV-1/HIV-2 antibody differentiation immunoassay
