• Abortion/stillbirth
• Congenital Malformation
• IUGR
• Prematurity
• Acute neonatal disease/delayed neonatal disease
• Asymptomatic
• Persistent infection with late sequelae

• Timing (which trimester)

• IUGR
• Microcephalus/hydrocephalus
• Intracranial calcifications
• Chorioretinitis
• Cataracts
• Myocarditis
• Pneumonia
• HSM
• Direct hyperbilirubinemia
• Anemia/thrombocytopenia
• Seizures/SNHL/blindness
• Skin

• Dermal erythropoiesis
• CMV
• Rubella
• Parvo
• Congenital Leukemia
• Rh hemolytic disease

• HIV
• Syphilis
• HBsAg
• C trachomatis
• N gonorrhhoeae if at risk
• GBS (35-37 w)

Toxoplasma gondii human infection:
• Undercooked meat (oocysts)
• Contact with contaminated materials
(sandbox) (oocysts)
• Organ/BM transplantation (tachyzoite/cyst)
• IU (maternal infection during pregnancy)

• Mononucleosis like (fever, myalgia, rash, lymphadenopathy, hepatitis, meningitis, encephalitis, pericarditis, unilateral chorioretinitis, myo/pericarditis)

Congenital or acquired
30-40% of chorioretinitis in USA and western
Europe

• AIDS, malignancy, cytotoxic therapy, organ transplants, stem cell transplant (Tox+→Tox-)
• CNS 50%, also heart, lung, GI
• Toxoplasmic encephalitis 25 to 50% untreated
HIV

• 1 st trimester 17% severe infection
• 3 rd trimester 65% mild infection
• Susceptibility (HLA DQ3 etc)
• Wide range of presentation
• 50% of infected are asymptomatic at birth almost all of them will develop ocular involvement
• 10% severe CNS & systemic
• Untreated that presents later in the first 1yr 80% IQ<70
• IUGR, lymphadenopathy, HSM, pneumonitis, nephrotis syndrome, metaphyseal lucency
• SIADH, hypothyroidism, hypopit

• Hydrocephalus
• Seizures
• Microcephalus, developmental delay
• CSF abnormal in 30% (sometimes protein
>1gr)
• Calcifications more in caudate nucleus and basal ganglia
• SNHL static or progressive?

• Cultures (mice peritoneal fluid or tissue cultures 6-10 days for tachyzoites, if mouse survives and seroconverts at 6 weeks brain cysts)
• Serology:
Sabin-Feldman dye test
Specific, sensitive, difficult

• IgG indirect fluorescent antibody
1-2wk after infection, peaks at 6-8 wk, persist fo life at low titers, not standardised
• IgM IFA for older children, only 25% of congenital
• IGM ELISA more sensitive and specific (50-75%)
• ISAGA (immunosorbent agglutination assay) combines IGA, IGE and IGA, no FP is the best fot congenital infection
• Differential agglutination (HS/AC) (useful for pregnant women)
“recent antigen” “late antigen”

• Avidity (12 vs 16 wk)
• Body fluid coefficient
• Enzyme-linked immunofiltration assay ELIFA
85% sensitivity for congenital Toxo
• PCR in amniotic fluid 17-21 gest week 95% sensitive, PCR from WBC of neonate
• Ocular = characteristic lesion with positive serology

• General, ophtalmologic, neurologic ex
• Head CT
• Toxo PCR from peripheral blood buffy coat
• Toxo specific and total IGG,
IGM, IGE, IGA
• CSF for Toxo PCR (+general CSF )
• Mice inoculation

• Pyrimethamine & Sulfadiazine
Contraindicated in first trimester
DHFR inhibitor, bone marrow↓
Rash, hematuria, crystalluria
Hypersensitivity, especially with HIV
• Folinic acid (leukovorin) !!!
• During pregnancy Spiramycin

• Acquired (if at all…) 4-6 wk
• Ocular untill sharp borders usually 2-4 wks + steroids
• AIDS for life or until CD4>200 for more than 6 mts and no lesions
• Congenital for 1 year

• If infection during the 6 mo prior to conception treat as described for the pregnant
• Spiramycin for prevention if motherdevelops acute toxo until 24 w
• If fetus is infected P&S&FA after 1 st trimester
• Acute toxo after 24 w = P&S&A
• Amniotic fluid PCR 17-21 wk
• Prevention!!!

Specific antiviral therapy
Nonspecific antiviral therapy
Passive immunization
Active immunization

• Primary
• Non-primary first infection
• Recurrent symptomatic and asymptomatic

• Only in humans
• Direct mucocutaneous contact
• Any anatomic site
• Predisposition

Incidence of Neonatal HSV Infection and Other Congenital Infections in North America.
Corey L, Wald A. N Engl J Med 2009;361:1376-1385.

• Herpes Gingivostomatitis
• Herpes Labialis
• Herpes gladiatorum/scrumpox
• Whitlow
• Eczema Herpeticum
• Genital Herpes (15% aseptic meningitis)
• Ocular Herpes

• CNS infection:
HSV1 encephalitis, Mollaret meningitis (HSV2)
• Immunocompromised: mucositis, esophagitis, tracheobronchitis, pneumonitis, sepsis-like

Pathogenesis of Neonatal Herpes Simplex Virus (HSV) Infection.
Corey L, Wald A. N Engl J Med 2009;361:1376-1385.

• Fewer than 30% of mothers have history of herpes
• Primary (>30% risk) vs recurrent (<2%)
• Scalp electrodes
• Intrauterine: skin vesicles, microcephaly, keratononjuctivitis
• During delivery: SEM, encephalitis, disseminated

• 5-11 days few small vesicles
• If untreated may progress

• 8-17 days irritability, lethargy, poor feeding, poor tone, seizures
• Usually no fever
• Vesicles 60%
• If untreated 50% will die

• 5-11 days
• Sepsis
• Vesicles 75%
• If untreated 90% will die

• DNA PCR
• HSV IGM unreliable
• HSV IGG only for retrospect
• Cultures

• Acyclovir
• Valacyclovir
• Famciclovir (prodrug of penciclovir)
• Foscarnet, cidofovir
• Perinatal infection – high dose (60mg/kg/day)

Common Misperceptions about Neonatal Herpes.
Corey L, Wald A. N Engl J Med 2009;361:1376-1385.

Outcome of Neonatal Herpes.
Corey L, Wald A. N Engl J Med 2009;361:1376-1385.

• The most common cause of congenital infection
• Important opportunistic pathogen
• β-herpes group
• Large (200-300nm)

• Attachment gB, gH proteins (interact with cell surface heparan sulfate)
• Cytoplasmic inclusion typical (accumulation of nucleocapsids and tegument in the Golgi ap.)

• Mucosal (UR or genital)
• Viremia
• Leukocytes and endothelial cells infection
• CMV-encoded cell traffic machinery
• Different tissues tropism (PM healthy people
CMV was found in salivary, lung, kidney, liver, pancreas, gut, etc)
• Viral shedding 4-6 weeks after acquisition (saliva, urine, genital)

• Interfere with immune response
• Maintenance of viral genome in CD34+ cells, also kidney and salivary
• Severity of disease parallels the immunity impairment
• Antibodies modify cannot prevent infection
• Critical role of T-cell mediated (most severe infection after BMT recipients, AIDS (<100cd4) and solid organ after ATG treatment)

• Majority of congenital infections are benign
• Congenital symptomatic at birth CMV=
Microcephaly, IC calcifications, CSF protein↑↑, seizures, cochlear, vestibular defects (Mondini dysplasia), retinitis, hepatitis
• 40% of maternal primary are transmittes
• First trimester = 26% symptomatic (32%), third=6%(15%)

• At areas with high seropositivity >50% positive at 1 yr, >90% of first time mothers
• US overall prevalence is 59%
• Child care centers
• Second peak adolescents (sexual transmission)
• Vertical (10% of seropositive mothers shed
CMV at genital tract, 50% of neonates will be infected)

• Congenital CMV 0.2-2.2% live births
• Nosocomial: breast milk, blood products
(leukocytes!), organ T, BMT, BW<1250g
• Child care workers at risk, medical workers are considered not at risk

• Heterophil-negative mononucleosis (mean duration of fever 14 days)
• Peak ALT usually <300 IU/L
• The expected course is recovery without sequellae in healthy host

• DVT, uveitis, persistant trmbocytopenia, hemolytic anemia, myocarditis, GI ulcerations, transverse myelitis, Guillain-Barre, encephalitis

• >90% appear healthy at birth
• 7-10% petechiae, microcephaly, thrombocytopenia, conjugated hyperbilirubinemia, optic atrophy, seizures, poor sucking reflex etc etc
• 5% of asymptomatic at birth will have CNS seq
• 7-10% will have progressive SNHL

• 20y ago transfusion related syndrome in VLBW
• Rare today because of leukocytes filtration
• 59% of premature <1500 gr newborns of CMV positive mothers who were fed mother’s milk were infected, half of them symptomatic (?)
• Compared with term less maternal IGG
• Symptoms = sepsis like
• No consensus, controversial studies

• Solid organ:
Most common RN DP (majority will develop disease w/o treatment)
Can occur at RP also if profound immunosuppressed (5-
25%)
4-12 weeks after transplantation
Fever, malaise arthralgia, hepatitis, pancytopemia, deterioration of graft function
Pneumonitis is more common in lung or heart lung transplants
Antithmocyte globulin or anti Tlymph ab at risk

• Similar as SOT
• Pneumonia and GI disease!!!
• Prior to routine antiviral therapy 40% interstitial pneumonia (half of them CMV with
50% mortality)
• At risk DP RN, GVH, lymphopenia
• Due to ativiral therapy only 5% HSCT will develop CMV during first 120 d but late onset disease has become a problem

• Extremely low CD4 (<50)
• Usually retinitis, esophagitis or colitis
• Controversial in neurological AIDS syndromes
• Adults>children

• In the healthy IGG, IGM (unreliable during pregnancy), IGG avidity

• Detection of CMV in body fluids within first 3 weeks
• Culture, shell vial, PCR
• Quantification in blood – to assess risk of sequella

• Quantification of CMV DNA in blood (different techniques: whole blood, leukocytes, plasma)
• pp65 antigenemia (immunofluorescence staining)
• Lack of standartization

• Acquired healthy – not indicated
• Congenital symptomatic ganciclovir 12 mg/kg/day in two doses daily for 6 weeks
“deserve consideration”
• Congenital asymptomatic “no evidence to support” but…