Tom Rand MD PhD

St. Luke’s Children’s Infections and Immune Deficiency Clinic

February 20, 2015

Perinatal infections:

Some things you never knew, and important

changes in recommendations

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 diagnosis

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 time

Recommendations for management of neonatal HSV has become more aggressive over time

*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

Recommendations for management of neonatal HSV has become more aggressive over time

*14 days IV acyclovir therapy for HSV disease confined to skin, eye, mucus membranes (SEM)

Recommendations for management of neonatal HSV has become more aggressive over time

*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

Recommendations for management of neonatal HSV has become more aggressive over time

After completion of IV acyclovir therapy for neonatal HSV disease, continue suppressive oral acyclovir 300 mg/m2/dose TID for 6 monthsKimberlin et al. “Oral acyclovir suppression and neurodevelopmental outcome after neonatal herpes” New England Journal of Medicine 365:1284-1292, 2011

Testing before IV acyclovir so you know you can stop treating for HSV

*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

Source of CMV infection resulting in congenital CMV*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.

How we are missing hearing loss due to congenital CMV

*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

Decisions around therapy for congenital CMV are complex

*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.

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-HBs

You are going to see more use of antivirals during pregnancy for HBeAg+, HBV DNA >105 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 issues

Hepatitis follow-up after pregnancy

*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

What do you know about the outcome of the following infections during pregnancy?

*West Nile virus

*Ebolavirus

*Lyme disease (Borrelia burgdorferi)

West Nile virus infection during pregnancy

Only a couple publications but consistent features of fetal infection with chorioretinitis and cerebral white matter diseaseTransmission by breastfeeding reported

Viral hemorrhagic fevers have exceedingly poor outcome during pregnancy.Most fetuses spontaneously abortedObstetrical emergencies responsible for substantial transmission of ebolavirus to healthcare workersDeath 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?

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.

*Vector of Lyme disease and anaplasmosis not found in Idaho

*Ixodes pacificus

Lyme disease is geographically restricted by tick vector

Is there an entity of congenital Lyme disease?

Occasional reports of infection of fetusNo consistent consequences of congenital infectionNo inflammation associated with spirochetes in tissues in the fetuses or babies reportedShapiro and Gerber, In Reminton & Klein Infectious Diseases of the Fetus and Newborn Infant, 7th ed, 2011, pp 564-576Mylonas, Vector-borne and zoonotic diseases, 11:891-898, 2011

Congenital syndromes important for other spirochete diseases

*Syphilis

*Leptospirosis

*Relapsing fever borreliosis

Lyme disease is readily treatable at any stage diagnosed

*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

4 case reports of spontaneous abortion or newborn death testing positive for Lyme disease

*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

Large studies of pregnancy outcome after Lyme disease*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.