Transcript What are we to make of claims for treatment of congenital

Tom Rand MD PhD
St. Luke’s Children’s Infections
and Immune Deficiency Clinic
February 20, 2015
Herpes simplex virus
Cytomegalovirus
Hepatitis B virus
West Nile virus
Ebolavirus
Lyme disease (Borrelia burgdorferi)
Syphilis (Treponema pallidum)
“some minor pathogens”
Molecular diagnosis
Acyclovir dose for all neonatal management of HSV
60 mg/kg/day divided q 8 hr IV
*10 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,
2013
*14 days IV acyclovir therapy for HSV
disease confined to skin, eye, mucus
membranes (SEM)
*21 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 PCR
After completion of IV acyclovir therapy for
neonatal HSV disease, continue suppressive
oral acyclovir 300 mg/m2/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, 2011
*Lesion 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 CBC
*Primary maternal infection
*Reactivated maternal infection
*New infection with different
strain than primary infection
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.
*We screen for hearing loss present in
newborns
*An unknown proportion of congenital
CMV infections develop hearing loss
beyond newborn period
*No screening for congenital CMV per se
*Antiviral 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.
Must test greater than month after final
hep B vaccine (approximately 9 months):
•HBsAg
•Anti-HBs
*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
mother to infant
transmission 2) HBV DNA 3) hepatic issues
1)
*Be 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.
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 testing
*West Nile virus
*Ebolavirus
*Lyme disease (Borrelia
burgdorferi)
Only a couple publications but consistent
features of fetal infection with
chorioretinitis and cerebral white matter
disease
Transmission by breastfeeding reported
Viral hemorrhagic fevers have exceedingly poor
outcome during pregnancy.
Most fetuses spontaneously aborted
Obstetrical 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
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 78:505615, 2012.
Lyme disease is geographically
restricted by tick vector
* Ixodes pacificus
*
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, 7th ed, 2011, pp 564-576
Mylonas, Vector-borne and zoonotic diseases, 11:891-898,
2011
*Syphilis
*Leptospirosis
*Relapsing fever borreliosis
*90% 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)
Most Lyme disease is treated during
symptoms of erythema migrans
*No 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 causes
*Pregnancies 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
incidence
There is no reason to think
that a burden of
neurodevelopmental
problems in children has
resulted from undiagnosed
congenital Lyme disease.