3. Case scenario
• You are taking care of a term newborn male with
birth weight/length <10th
%ile. Physical exam is
normal except for a slightly enlarged liver span.
A CBC is significant for low platelets.
• What, if anything, do you worry about?
4. Index of Suspicion
• When do you think of TORCH infections?
▫ IUGR infants
▫ HSM
▫ Thrombocytopenia
▫ Unusual rash
▫ Concerning maternal history
▫ “Classic” findings of any specific infection
5. Diagnosing TORCH Infection
• Good maternal/prenatal history
▫ Remember most infections of concern are mild
illnesses often unrecognized
• Thorough exam of infant
• Directed labs/studies based on most likely
diagnosis.
7. Toxoplasmosis
• Caused by protozoan – Toxoplasma gondii.
• Much higher prevalence of infection in European
countries (ie France, Greece).
• Incidence 1- 10 per 10000 live births.
8.
9. Toxoplasmosis
• Domestic cat is the definitive host with
infections via:
▫ Ingestion of cysts (meats, garden products)
▫ Contact with oocysts in feces
• Acute infection in adults usually asymptomatic
(90%)
• 1/3 risk of fetal infection with primary maternal
infection in pregnancy
▫ Infection rate higher with infxn in 3rd
trimester
▫ Fetal death higher with infxn in 1st
trimester
10. Pnemonic – R C T
• RUBELLA - 1 ST TRIMESTER
• CYTOMEGALOVIRUS - 2 ND TRIMESTER
• TOXOPLASMOSIS - 3 RD TRIMESTER
11. Clinical Manifestations
• Most (70-90%) are asymptomatic at birth
• Classic triad of symptoms: {HCC}
▫ Hydrocephalus
▫ Chorioretinitis
▫ Intracranial calcifications
• Other symptoms include fever, rash, HSM,
microcephaly, seizures, jaundice, thrombocytopenia,
lymphadenopathy
• Initially asymptomatic infants are still at high risk of
developing abnormalities, especially chorioretinitis
14. Diagnosis – A REAL CHALLENGE
• Maternal IgG testing indicates past infection.
• Congenital toxo. Diagnosis in newborn based on
CLINICAL SUSPICION + SEROLOGY
• Most cases ( 70 -90%) ASYMPTOMATIC.
Missed if SCREENING TESTS not done.
• Can be isolated in culture from placenta,
umbilical cord, infant serum – NOT READILY
AVAILABLE.
• PCR testing on blood,CSF, placenta
▫ Not standardized
• Newborn serologies with IgM/IgA
15. Toxo Screening
• Neonatal screening with IgM testing
implemented in some areas
▫ Identifies infected asymptomatic infants who may
benefit from therapy
16. Prevention and Treatment
• Treatment for pregnant mothers diagnosed with acute toxo
▫ Spiramycin daily
Macrolide antibiotic
▫ Small studies have shown this reduces likelihood of congenital
transmission (up to 50%)
• If infant diagnosed prenatally, treat mother
▫ Spiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase
inhib), and sulfadiazine (sulfa antibiotic)
▫ Leucovorin rescue with pyrimethamine
• Symptomatic infants
▫ Pyrimethamine (with leucovorin rescue) and sulfadiazine
▫ Treatment for 12 months total
• Asymptomatic infants
▫ Course of same medications
▫ Improved neurologic and developmental outcomes demonstrated
(compared to untreated pts or those treated for only one month)
18. RUBELLA
• Single-stranded RNA virus
• Vaccine-preventable disease
• Mild, self-limiting illness
• Infection earlier in pregnancy has a higher
probability of affected infant
• { R C T remember??????)
21. Clinical Manifestations
• Sensorineural hearing loss (50-75%) GREG
• Cataracts and Retinopathy(20-50%) SYN.
• Cardiac malformations (20-50%)
• Neurologic (10-20%) – MR,Language
delay,microcephaly.
• Others include growth retardation, bone disease,
HSM, thrombocytopenia.
22. Diagnosis
• Maternal IgG may represent immunization or
past infection.
• Can isolate virus from nasal secretions
▫ Less frequently from throat, blood, urine, CSF
• Serologic testing
▫ IgM = recent postnatal or congenital infection
▫ Rising monthly IgG titers suggest congenital infection
• Diagnosis after 1 year of age difficult to establish.
25. CYTOMEGALOVIRUS (CMV)
• Most common congenital viral infection
▫ ~40,000 infants per year in the U.S.
• Mild, self limiting illness
• Transmission can occur with primary infection
or reactivation of virus
▫ 40% risk of transmission in primary infection
• Studies suggest increased risk of transmission in
2 nd trimester of pregnancy { Remember R C T}
▫ However, more severe sequelae associated with earlier
acquisition
26. Clinical Manifestations
• 90% are asymptomatic at birth!
▫ Up to 15% develop symptoms later, notably
sensorineural hearing loss
{MC CAUSE OF SN. HEARING LOSS IN
CHILDREN}
• Symptomatic infection
▫ SGA, HSM, petechiae, jaundice, chorioretinitis,
periventricular calcifications, neurological
deficits
▫ >80% develop long term complications
Hearing loss, vision impairment, developmental
delay
30. Diagnosis
• Maternal IgG shows only past infection
▫ Infection common – this is useless
• Viral isolation from urine or saliva in 1st
3weeks
of life – CULTURE – GOLD STANDARD.
▫ Afterwards may represent post-natal infection
• Viral load and DNA copies can be assessed by
PCR > 3 WKS
▫ Less useful for diagnosis, but helps in following viral
activity in patient
• Serologies not helpful given high antibody in
population !!!!!!!!!
31. Treatment
• Ganciclovir x6wks in symptomatic infants
▫ Studies show improvement or no progression of
hearing loss at 6mos
▫ No other outcomes evaluated (development, etc.)
▫ Neutropenia often leads to cessation of therapy
• Treatment currently not recommended in
asymptomatic infants due to side effects
33. Herpes Simplex (HSV)
• HSV1 or HSV2
• Primarily transmitted through infected maternal
genital tract
▫ Rationale for C-section delivery prior to
membrane rupture
• Primary infection with greater transmission risk
than reactivation
34. Clinical Manifestations
• Most are asymptomatic at birth
• 3 patterns of ~ equal frequency with symptoms
between birth and 4wks:
▫ Skin, eyes, mouth (SEM)
▫ CNS disease
▫ Disseminated disease (present earliest)
• Initial manifestations very nonspecific with skin
lesions NOT necessarily present
36. Diagnosis
• Culture of maternal lesions if present at delivery
• Cultures in infant:
▫ Skin lesions, oro/nasopharynx, eyes, urine, blood,
rectum/stool, CSF
• CSF PCR
• Serologies again not helpful given high
prevalence of HSV antibodies in population
37. Treatment
• High dose acyclovir 60mg/kg/day divided q8hrs
▫ X 21days for disseminated, CNS disease
▫ X 14days for SEM
39. SYPHILIS
• Treponema pallidum (spirochete)
• Transmitted via sexual contact
• Placental transmission as early as 6wks gestation
▫ Typically occurs during second half
▫ Mother with primary or secondary syphilis more likely
to transmit than latent disease
• Large decrease in congenital syphilis since late
1990s
▫ In 2002, only 11.2 cases/100,000 live births reported
41. Congenital Syphilis
• 2/3 of affected live-born infants are
asymptomatic at birth
• Clinical symptoms split into early or late (2 years
is cutoff)
• 3 major classifications:
▫ Fetal effects
▫ Early effects
▫ Late effects
42. Clinical Manifestations
• Fetal:
▫ Stillbirth
▫ Neonatal death
▫ Hydrops fetalis
• Intrauterine death in 25%
• Perinatal mortality in 25-30% if untreated
48. Diagnosing Syphilis
(Not in Newborns)
• Available serologic testing
▫ RPR/VDRL: nontreponemal test
Sensitive but NOT specific
Quantitative, so can follow to determine disease activity and
treatment response
▫ MHA-TP/FTA-ABS: specific treponemal test
Used for confirmatory testing
Qualitative, once positive always positive
• RPR/VDRL screen in ALL pregnant women
early in pregnancy and at time of birth
▫ This is easily treated!!
49. CDC Definition of Congenital Syphilis
• Confirmed if T. pallidum identified in skin
lesions, placenta, umbilical cord, or at
autopsy
• Presumptive diagnosis if any of:
▫ Physical exam findings
▫ CSF findings (positive VDRL)
▫ Osteitis on long bone x-rays
▫ RPR/VDRL >4 times maternal test
▫ Positive IgM antibody
50. Treatment
• Penicillin G is THE drug of choice for ALL
syphilis infections
• Maternal treatment during pregnancy very
effective (overall 98% success)
• Treat newborn if:
▫ They meet CDC diagnostic criteria
▫ Mother was treated <4wks before delivery
▫ Mother treated with non-PCN med
▫ Maternal titers do not show adequate response (less
than 4-fold decline)
51. Which TORCH Infection Presents
With…
• Snuffles?
▫ syphilis
• Hydrocephalus,Chorioretinitis,and
intracranial calcifications {HCC} ?
▫ toxo
• Blueberry muffin lesions?
▫ CMV
• Periventricular calcifications?
▫ CMV
• No symptoms?
▫ All of them !!!!!!
