1. Ashley M. Maranich, MD CPT/USA/MC Pediatric Infectious Disease Fellow
TORCH Infections
Ashley M. Maranich, MD
CPT/USA/MC
Pediatric Infectious Disease Fellow

2. TORCH Infections T=toxoplasmosis O=other (syphilis) R=rubella
C=cytomegalovirus (CMV)
H=herpes simplex (HSV)

3. 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?
How do you proceed with a work-up?

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
!!!!!!DO NOT USE TORCH TITERS!!!!!!

6. 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…
Again, DO NOT USE TORCH TITERS!

7. Screening TORCH Infections
Retrospective study of 75/182 infants with IUGR who were screened for TORCH infections
1/75 with clinical findings, 11/75 with abnl lab findings
All patients screened:
TORCH titers, urine CMV culture, head US
Only 3 diagnosed with infection
NONE by TORCH titer!!
Overall cost of all tests = $51,715
“Shotgun” screening approach NOT cost effective nor particularly useful
Diagnostic work-up should be logical and directed by history/exam findings
Khan, NA, Kazzi, SN. Yield and costs of screening growth-retarded infants for torch infections. Am J Perinatol 2000; 17:131.

8. Toxoplasmosis Caused by protozoan – Toxoplasma gondii
Domestic cat is the definitive host with infections via:
Ingestion of cysts (meats, garden products)
Contact with oocysts in feces
Much higher prevalence of infection in European countries (ie France, Greece)
Acute infection usually asymptomatic
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

9. Clinical Manifestations
Most (70-90%) are asymptomatic at birth
Classic triad of symptoms:
Chorioretinitis
Hydrocephalus
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

10. Chorioretinitis of congenital toxo

11. Diagnosis Maternal IgG testing indicates past infection (but when…?)
Can be isolated in culture from placenta, umbilical cord, infant serum
PCR testing on WBC, CSF, placenta
Not standardized
Newborn serologies with IgM/IgA

12. Toxo Screening
Prenatal testing with varied sensitivity not useful for screening
Neonatal screening with IgM testing implemented in some areas
Identifies infected asymptomatic infants who may benefit from therapy

13. 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 mom
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)

14. Syphilis Treponema pallidum (spirochete)
Transmitted via sexual contact
Placental transmission as early as 6wks gestation
Typically occurs during second half
Mom 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

15. From MMWR – Aug 2004

16. From MMWR – Aug 2004

17. 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

18. Clinical Manifestations
Fetal:
Stillbirth
Neonatal death
Hydrops fetalis
Intrauterine death in 25%
Perinatal mortality in 25-30% if untreated

19. Clinical Manifestations
Early congenital (typically 1st 5 weeks):
Cutaneous lesions (palms/soles)
HSM
Jaundice
Anemia
Snuffles
Periostitis and metaphysial dystrophy
Funisitis (umbilical cord vasculitis)

20. Periostitis of long bones seen in neonatal syphilis

21. Clinical Manifestations
Late congenital:
Frontal bossing
Short maxilla
High palatal arch
Hutchinson teeth
8th nerve deafness
Saddle nose
Perioral fissures
Can be prevented with appropriate treatment

22. Hutchinson teeth – late result of congenital syphilis

23. 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!!

24. 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
Funisitis (“barber shop pole” umbilical cord)
RPR/VDRL >4 times maternal test
Positive IgM antibody

25. Diagnosing Congenital Syphilis
IgG can represent maternal antibody, not infant infection
This is VERY intricate and often confusing
Consult your RedBook (or peds ID folks) when faced with this situation

26. 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
Mom was treated <4wks before delivery
Mom treated with non-PCN med
Maternal titers do not show adequate response (less than 4-fold decline)

27. Rubella Single-stranded RNA virus Vaccine-preventable disease
No longer considered endemic in the U.S.
Mild, self-limiting illness
Infection earlier in pregnancy has a higher probability of affected infant

28. Reported rubella and CRS: United States, 1966-2004
Meissner, H. C. et al. Pediatrics 2006;117:
Copyright ©2006 American Academy of Pediatrics

29. Clinical Manifestations
Sensorineural hearing loss (50-75%)
Cataracts and glaucoma (20-50%)
Cardiac malformations (20-50%)
Neurologic (10-20%)
Others to include growth retardation, bone disease, HSM, thrombocytopenia, “blueberry muffin” lesions

30. “Blueberry muffin” spots representing extramedullary hematopoesis

31. Diagnosis
Maternal IgG may represent immunization or past infection - Useless!
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

32. Treatment Prevention…immunize, immunize, immunize!
Supportive care only with parent education

33. 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 infxn
Studies suggest increased risk of transmission later in pregnancy
However, more severe sequalae associated with earlier acquisition

34. Clinical Manifestations
90% are asymptomatic at birth!
Up to 15% develop symptoms later, notably sensorineural hearing loss
Symptomatic infection
SGA, HSM, petechiae, jaundice, chorioretinitis, periventricular calcifications, neurological deficits
>80% develop long term complications
Hearing loss, vision impairment, developmental delay

35. Ventriculomegaly and calcifications of congenital CMV

36. Diagnosis Maternal IgG shows only past infection
Infection common – this is useless
Viral isolation from urine or saliva in 1st 3weeks of life
Afterwards may represent post-natal infection
Viral load and DNA copies can be assessed by PCR
Less useful for diagnosis, but helps in following viral activity in patient
Serologies not helpful given high antibody in population

37. 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
Area of active research to include use of valgancyclovir, treating asx patients, etc.

38. 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

39. 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

40. Presentations of congenital HSV

41. 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

42. Treatment High dose acyclovir 60mg/kg/day divided q8hrs
X21days for disseminated, CNS disease
X14days for SEM
Ocular involvement requires topical therapy as well

44. Which TORCH Infection Presents With…
Snuffles?
syphilis
Chorioretinitis, hydrocephalus, and intracranial calcifications?
toxo
Blueberry muffin lesions?
rubella
Periventricular calcifications?
CMV
No symptoms?
All of them

45. Which TORCH Infections Can Absolutely Be Prevented?
Rubella
Syphilis

46. When Are TORCH Titers Helpful in Diagnosing Congenital Infection?
NEVER!

47. Questions?