St Lukes Childrens Infections and Immune Deficiency Clinic February 20 2015 Perinatal infections Some things you never knew and important changes in recommendations Will touch upon ID: 532761
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Slide1
Tom Rand MD PhDSt. Luke’s Children’s Infections and Immune Deficiency ClinicFebruary 20, 2015
Perinatal infections:
Some things you never knew, and important changes in recommendationsSlide2
Will touch upon …Herpes simplex virus
Cytomegalovirus
Hepatitis B virus
West Nile virus
Ebolavirus
Lyme disease (
Borrelia
burgdorferi
)
Syphilis (
Treponema
pallidum
)
“some minor pathogens”
Molecular diagnosisSlide3
Acyclovir dose for all neonatal management of HSV 60 mg/kg/day divided q 8 hr IV
Recommendations for management of neonatal HSV have become more aggressive over timeSlide4
Recommendations for management of neonatal HSV has become more aggressive over time10 days acyclovir therapy reserved for newborns diagnosed by surveillance cultures after exposure and before disease (“preemptive therapy”)Kimberlin
et al. “Guidance on management of asymptomatic neonates born to women with active genital herpes lesions”
Pediatrics
131:e635-646, 2013Slide5
Recommendations for management of neonatal HSV has become more aggressive over time14 days IV acyclovir therapy for HSV disease confined to skin, eye, mucus membranes (SEM)Slide6
Recommendations for management of neonatal HSV has become more aggressive over time21 days of IV acyclovir therapy for CNS or disseminated HSV disease
For positive CSF PCR, repeat LP before end of therapy and treat additional week until negative CSF PCRSlide7
Recommendations for management of neonatal HSV has become more aggressive over timeAfter completion of IV acyclovir therapy for neonatal HSV disease, continue suppressive oral acyclovir 300 mg/m
2
/dose TID for 6 months
Kimberlin
et al. “Oral acyclovir suppression and neurodevelopmental outcome after neonatal herpes”
New England Journal of Medicine
365:1284-1292, 2011Slide8
Testing before IV acyclovir so you know you can stop treating for HSVLesion HSV culture
Pooled conjunctivae and pharynx swabs for HSV culture
Genital or rectal swab for HSV culture
CSF PCR, and routine CSF studies
Blood PCR
Hepatic chemistries and CBCSlide9
Source of CMV infection resulting in congenital CMVPrimary maternal infection
Reactivated maternal infection
New infection with different strain than primary infectionSlide10
Failed newborn hearing screen with confirmation of sensorineural hearing loss of any degree prompts testing urine CMV culture.This is the responsibility of primary care provider to order testing and should not be deferred for specialty evaluation. Slide11
How we are missing hearing loss due to congenital CMVWe screen for hearing loss present in newbornsAn unknown proportion of congenital CMV infections develop hearing loss beyond newborn period
No screening for congenital CMV per seSlide12
Decisions around therapy for congenital CMV are complexAntiviral therapy for congenital CMV can prevent progressive hearing loss, but standard 6 weeks IV ganciclovir is too short to have an impact.
Hearing loss may progress in an infant that is not otherwise symptomatic from congenital CMV.
“Asymptomatic” congenital CMV does not have recommendation to treat with IV ganciclovir.
Duration of oral
valganciclovir
therapy and selection of candidates for therapy are currently subjected to clinical trials.Slide13
5% of babies receiving HBIG and hep B vaccine for perinatal prophylaxis develop hepatitis B infection
Must test greater than month after final
hep
B vaccine (approximately 9 months):
HBsAg
Anti-HBsSlide14
You are going to see more use of antivirals during pregnancy for HBeAg+, HBV DNA >10
5
copies/ml, and elevated ALT/SGPT
Tenofovir
, lamivudine, and
telbivudine
current options
If taking
adefovir
or
entecavir
, then change
Each drug has specific safety concerns, but actual experience in pregnancy is encouraging
Flare of hepatitis at end of pregnancy is common and can be controlled by antivirals
Demonstrated reduction of
1)
mother to infant transmission
2)
HBV DNA
3)
hepatic issuesSlide15
Hepatitis follow-up after pregnancyBe sure women with chronic viral hepatitis B and C infection have a provider identified to continue to counsel and monitor liver disease.Changes in therapies for hepatitis B and C have expanded options. Individuals that were previously discouraged from therapy have become promising candidates for newer therapies.Slide16
Please include hep B vaccine in standing orders for newborn.
No one has a “low-risk population”!
Important failsafe for all human and med record failures in prenatal
HBsAg
testingSlide17
What do you know about the outcome of the following infections during pregnancy?West Nile virusEbolavirus
Lyme disease (
Borrelia
burgdorferi
)Slide18
West Nile virus infection during pregnancyOnly a couple publications but consistent features of fetal infection with chorioretinitis
and cerebral white matter disease
Transmission by breastfeeding reportedSlide19
Viral hemorrhagic fevers have exceedingly poor outcome during pregnancy.Most fetuses spontaneously abortedObstetrical emergencies responsible for substantial transmission of ebolavirus to healthcare workers
Death rate of
ebolavirus
-infected mothers 95%
Mupapa
et al.
Journal of Infectious Diseases
179:S11012, 1999
Are we to expect congenital infection from
ebolavirus
in pregnancy?Slide20
What are we to make of claims for treatment of congenital Lyme disease in children with neurodevelopmental disorders?For example, publications such as:
Kuhn, Grave,
Bransfield
, and Harris. “Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and Autism Spectrum Disorder”
Medical Hypotheses
78:505-615, 2012.Slide21
Vector of Lyme disease and anaplasmosis not found in IdahoIxodes pacificus
Lyme disease is geographically restricted by tick vectorSlide22
Is there an entity of congenital Lyme disease?Occasional reports of infection of fetus
No consistent consequences of congenital infection
No inflammation associated with spirochetes in tissues in the fetuses or babies reported
Shapiro and Gerber, In
Reminton
& Klein Infectious Diseases of the Fetus and Newborn Infant, 7
th
ed
, 2011, pp 564-576
Mylonas
,
Vector-borne and zoonotic diseases,
11:891-898, 2011Slide23
Congenital syndromes important for other spirochete diseasesSyphilis
Leptospirosis
Relapsing fever
borreliosisSlide24
Lyme disease is readily treatable at any stage diagnosed90% are diagnosed during erythema migrans
Disseminated manifestations are reversible with treatment, including carditis, cranial nerve palsies, meningitis
Arthritis may take months to resolve clinically after treatment
Existence of chronic Lyme disease has been refuted (for example
Feder
et al.
New England Journal of Medicine 357:1422-1430, 2007)Slide25
Most Lyme disease is treated during symptoms of erythema
migransSlide26
4 case reports of spontaneous abortion or newborn death testing positive for Lyme diseaseNo relationship of the clinical problems leading to fatal outcome to the tissues where spirochetes were found
Appeared to be incidentally found in variety of adverse outcomes due to other causesSlide27
Large studies of pregnancy outcome after Lyme diseasePregnancies treated for acute symptomatic Lyme disease (erythema migrans or other) no consequences
Seroconversions
during pregnancy or
seropositives
at end of pregnancy no consequences
Birth defects no pattern or increased incidenceSlide28
There is no reason to think that a burden of neurodevelopmental problems in children has resulted from undiagnosed congenital Lyme disease.