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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 Download Presentation

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congenital disease hsv lyme disease congenital lyme hsv infection therapy pregnancy cmv acyclovir neonatal hearing management hepatitis loss recommendations

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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.

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