Three Common Neonatal Infections: 2013
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Transcript of Three Common Neonatal Infections: 2013
Three Common Neonatal Infections: 2013
Roger G. Faix, M.D.The University of Utah
Primary Children’s Medical CenterIntermountain Medical Center
Importance of Cytomegalovirus(CMV)
Frequent pathogen in all human populations 70-80% of US adults are seropositive Up to 100% in the developing world
Importance Transmission usually involves prolonged
intimate contact with infected body fluid Infection ≠ Disease – usually asymptomatic
in immunocompetent subjects Among immunocompromised, CMV is a
leading cause of morbidity and mortality
Cytomegalovirus CPE In Vivo
CMV One of at least 8 human herpesviruses
DNA genetic material Latency – lifelong potential dormancy Persistence – may shed virus for years Reactivation- latent virus may become
actively shed again
Importance Congenital infection (acquired in utero,
present at birth): 0.5 – 2.5% of liveborns, (10,000-50,000/year in US)
Natal infection (acquired during passage through infected birth canal): 10-35% of liveborns; detectable after 3 weeks
Post-natal infection (acquired after birth): up to 100% in some populations; breast milk, day care, contact with infected fluid
Importance Natal and postnatal infections usually
are asymptomatic in newborns, but VLBWs may develop sepsis-like
condition and other syndromes May cause significant disease if subject
later immunocompromised May serve as a source for transmission to
high risk individuals
Importance of Congenital CMV Major cause of morbidity and death for
embryo, fetus, and neonate Wide array of potential responsible
agents for congenital infection - important to identify which responsible
CMV most common cause of congenital infection in US by far
Congenital CMV Infection
Congenital CMV Infection
Congenital CMV Infection Potential for intervention Limitations of therapy
Effective therapy may arrest further injury, BUT
May not reverse injury that already occurred
May not immediately stop injury
Congenital Cytomegalovirus (CMV) Mother usually asymptomatic Transmission from mother to fetus
hematogenous or transamniotic Father may be source of infection or
multiple other sources DNA analysis useful for epidemiologic
investigations
Congenital Cytomegalovirus (CMV)
With congenital CMV infection, symptomatic disease occurs in 5-10%
With symptomatic presentation, 90+% will have severe neurodevelopmental sequelae (100% if microcephaly or intracranial destructive lesions)
Symptomatic Presentation Abnormal head size CNS lesions Calcifications Organomegaly Adenopathy Petechiae ‘Blueberry muffin’
Symmetric IUGR Hydrops Anemia Bony/dental lesions Deafness Chorioretinitis Numerous others
Congenital CMV
Congenital CMV
Congenital Cytomegalovirus (CMV)
With congenital CMV infection, 90%+ are usually asymptomatic at birth 10-15% of these may develop later
sequelae, usually relatively mild• Hearing loss (SNHL)• Enamel hypoplasia• Seizure disorders• Learning disorders
Congenital CMV: Hearing Loss >20 dB (Fowler et al, 1999)
05
1015
2025
3035
40
0 6 12 18 24 30 36 42 48 54 60 66 72
Months since birth
Hear
ing
loss
,%
Symptomatic Asymptomatic
What Determines Presentation?
Maternal infection – primary or recurrent Gestational timing of infection Maternal organism load Other factors to be determined
Congenital Cytomegalovirus (CMV)
N o rm a l1 0%
S eq u e lae9 0 % (se ve re )
S ym p to m a tic5 -1 5%
S eq u e lae5 -1 5%
m ild -m od
N o rm a l8 5 -9 5%
A sym pto m a tic8 5 -9 5%
C o ng e n ita l in fec tion4 0%
P rim a ry in fe c tion1 -4 % o f se ro n eg
Effect of GA at primary CMV infection on transmission and disease
Outcome 4-22 wk GA 16-27 wk GA 23-40 wk GA Total
Maternal primary CMV
33 10 26 69
Fetal infection 17 (51%) 6 (60%) 12 (46%) 35 (51%)
Symptomatic congenital
2 (12%) 1 (16%) 0 (0%) 3/37* (8%)
Severe sequelae 5 (29%) 0 (0%) 0 (0%) 5/37* (13%)
*32 of original 69 were terminated or otherwise lost before birth
Congenital CMV Much lower risk in mother who is
seropositive at start of pregnancy, BUT absolute number of those who are seropositive is so much greater that absolute number of resultant infants with symptomatic CMV is significant
Up to 40% of those with symptomatic congenital CMV result from mothers who were seropositive at start of pregnancy
Diagnosis of Congenital CMV Many other pathogens may cause
congenital disease that mimic CMV It is important to determine the
presence/absence of these organisms Some are amenable to specific therapy Many are associated with very different
sequelae and care needs
Diagnosis of Congenital CMV
Viral culture (urine, saliva) up to age 3 weeks – congenital detected more quickly due to high viral load
PCR up to 3 weeks of age OR blood spot from newborn screen
Diagnosis of Congenital CMV
TORCH titers - very limited utility IgG- specific usually transplacental IgM-specific antibody – diagnostic if + in
first 3 weeks; does not exclude if negative
Treatment of Congenital CMV Treat signs/symptoms as detected Longitudinal assessment for SNHL Ganciclovir (GCV)
IV 6 weeks; CVC requirement 50% thrombocytopenia, neutropenia Does ↓frequency and severity of SNHL Sparse data re: other CMV issues Chorioretinitis usually treated
Quantity of CMV in urine with 42 days of GCV (Whitley, 1997)
0
1
2
3
4
5
6
0 7 14 21 28 35 42 49
Study days
pfu
log1
0
8 mg/kg 12 mg/kg
Treatment of Congenital CMV Valganciclovir – oral prodrug
converted to GCV upon absorption; sparse neonatal data, but what there is appears promising
Problems with all Not eradicate latency Viral infection recurs once stop Not reverse established injury
Utah State Law – 2013 Session
All newborn infants who fail hearing screen must undergo testing for congenital CMV
Parents of all infants found to be positive, must be offered counseling re: treatment, consequences
Prevention of Congenital CMV Infection control and universal
precautions remain critical At home, school, hospital, all settings High potential (not always avoidable) for
contacting infected fluids of asymptomatic, actively shedding individuals
Early-onset GBS (EOGBS) in the Era of Intrapartum
Antibiotic Prophylaxis IAP)
GBS
Although dramatic decreases in frequency since adoption of universal screening and IAP, still #1 cause of early-onset sepsis in term infants in US
Frequent cause of mortality (5-10% of affected) and morbidity
EOGBS and ECMO
Suspicion aroused, if no IAP and…
No antenatal culture Culture obtained, but results unavailable History GBS UTI History maternal chorioamnionitis History prior infant with EOGBS Unexplained POL ROM >18 hours
Suspicion aroused, if IAP given but…
Negative culture may be false-negative IAP with erythromycin or clindamycin may
be ineffective IAP with penicillin or cefazolin may be
ineffective if given <4 hrs prior to delivery
EOGBS – Presenting Signs
Temp Instability Respiratory distress Neutropenia Thrombocytopenia Hypoperfusion Hypoglycemia
Pneumonia PPHN Focal erythema Arthritis Meningitis Others
Treatment for EOGBS Supportive Culture
Blood CSF Focal areas
Empirical treatment Ampicillin and Gentamicin If +, covert to PCN G – 400,000U/kg/d
Treatment for EOGBS
Follow-up culture to assure sterilization Duration
7-10 after sterilization, if + blood only 14-21 after sterilization, if CSF+ 14+ after resolution of sequestered focus
RSV
Respiratory syncytial virus (RSV) Paramyxovirus: RNA, many strains Mother or other contacts (family,
healthcare staff) symptomatic or mild URI
Spread by contact with respiratory droplets, not aerosol
RSV and ECMO
Respiratory syncytial virus (RSV) Neonatal signs: rhinorrhea, wheezing,
pneumonia, lethargy, irritability, apnea; in preterms, absent or minimal respiratory signs is not unusual
Diagnosis culture/PCR IFA or EIA of NP swab (only 80-90% sensitive)
Respiratory syncytial virus (RSV) Prevention: RSVIg (IM or IV)
Controversial based on cost-benefit analyses, lack of data re: mortality and need for vent
Nonetheless recommended by AAP in select circumstances and widely used, including SLC
Respiratory syncytial virus (RSV) Infection control:
Careful attention to handwashing Minimizing hand-eye contact Barrier precautions Discouraging visiting by infected family, work
by infected staff
Respiratory syncytial virus (RSV) Treatment
Supportive Careful attention to upper airway toilet Bronchodilators controversial (racemic epi-,
albuterol, DXM) Ribavirin very controversial