congenital infection

Congenital infection

INTRODUCTION• Congenital infections account for 2% - 3% of birth defects which

arise form a spectrum of organisms.

• Mostly viral

• Congenital infections in the newborn are either transmitted via

1. the placenta during pregnancy or 2. acquired from the birth canal at the time of labour.

• The first trimester is usually the most dangerous time for fetus being affected.

• mostly viral• T=toxoplasmosis• O=other (syphilis, varicella-zoster, parvovirus B19)• R=rubella• C=cytomegalovirus (CMV)• H=herpes simplex (HSV)• The term TORCH is now obsolete as other agents

are important ( e.g. HIV)• Malaria• TB

CONGENITAL INFECTION

?????• we are taking care of a term newborn male with

birth weight/length <10th %. Physical exam is normal except for a slightly enlarged liver span. A CBC is significant for low platelets.

1. What, if anything, do we worry about?

2. How do we proceed with a work-up?

Index of Suspicion• When do you think of congenital infections?

–IUGR infants–HSM–Thrombocytopenia–Unusual rash–Concerning maternal history–Microcephaly–“Classic” findings of any specific infection

Diagnosing TORCH Infection

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

Diagnosing TORCH Infection

• Good maternal/prenatal history– most infections of cause mild illnesses often

unrecognized• Thorough exam of infant• Directed labs/studies based on most likely

diagnosis…– Again, DO NOT USE TORCH TITERS!

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

• 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.

• Of 603 patients undergoing serologic tests for Toxoplasma, syphilis, rubella, cytomegalovirus, and herpes simplex (TORCH tests) during a 4-year period,

• 381 (63%) were infants younger than 6 months and 110 (18%) were either the mothers of those infants or pregnant women.

• The remaining 112 (19%) were older infants and children, male adults, or nonpregnant female adults.

• Of 381 infants less than 6 months of age who were tested, 323 (85%) had only a single TORCH test.

• Of 35 (9%) infants who had follow-up titers, 16 (46%) had a specific titer requested whereas in 19 (54%) the entire TORCH battery was repeated. Follow-up titers were infrequently (25%) requested when initial titers were elevated.

• Infection with a TORCH agent was not confirmed serologically in any of the 603 patients. The pattern of TORCH test use has a poor diagnostic return.

Toxoplasmosis

Toxoplasmosis• Caused by protozoan – Toxoplasma gondii• T. Gondi is a coccidian protozoan that

multiplies only in living cells• Domestic cat is the definitive host with• Birds, mammals, human are intermediate

host• infections via:

– Ingestion of tissue cysts (meats, garden products)

– Contact with oocysts in feces

• Most often, maternal infection is asymptomatic or without specific symptoms or signs.

• As with other adults with acute toxoplasmosis,lymphadenopathy is the most common symptom.

• Risk of fetal infection: First Trimester - 15 % ( less incidence of fetal infection but

serious disease is most common ).

Second Trimester - 25 % .

Third Trimester - 65 % ( but almost 90% of newborns are without clinical signs of disease ).

– Infection rate higher with infxn in 3rd trimester– Fetal death higher with infxn in 1st trimester

Clinical Manifestations• Most (70-90%) are asymptomatic at birth

1. More than 50% of congenitally infected infants are considered normal in the perinatal period, but almost all such children develop ocular involvement later in life if they are not treated during infancy.

2. Almost all congenitally infected individuals who are not treated manifest signs or symptoms of infection, such as chorioretinitis, by adolescence.

3. Initially asymptomatic infants are still at high risk of developing abnormalities, especially chorioretinitis

• Classic triad of symptoms:– Chorioretinitis– Hydrocephalus– Intracranial calcifications

• Other symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathy

SIGNS AND SYMPTOMS OCCURRING DURING THE COURSE OF

UNTREATED ACUTE CONGENITAL TOXOPLASMOSIS IN 152 INFANTS

Diagnosis• Either persistent or rising titers of IgG in the dye

test or IFA test.

• positive IgM-ELISA or IgM-ISAGA (immunosorbent agglutination assay (ISAGA) result is diagnostic of congenital toxoplasmosis.

Toxo Screening

• Neonatal screening with IgM testing implemented in some areas– Identifies infected asymptomatic infants who may

benefit from therapy

Prevention and Treatment• Treatment for pregnant mother

– Spiramycin (1 g every 8 hr PO without food) is recommended for prevention of fetal infection if the mother develops acute toxoplasmosis during pregnancy.

– Small studies have shown this reduces likelihood of congenital transmission (up to 50%)

• Pyrimethamine (50 mg once daily PO), sulfadiazine (1.5-2 g bid PO), and leukovorin (10 mg once daily PO) are recommended for treatment of the pregnant woman whose fetus has confirmed or probable fetal infection except in the 1st trimeste– pyrimethamine (anti-malarial, dihydrofolate reductase

inhib), and sulfadiazine (sulfa antibiotic)– Leucovorin rescue with pyrimethamine

• Treatment of the mother of an infected fetus with pyrimethamine and sulfadiazine reduces infection in the placenta and the severity of disease in the newborn.

• In the 1st trimester when there is definite infection, sulfadiazine alone is recommended because pyrimethamine is potentially teratogenic at that time.

Treatment of infant• All newborns infected with T. gondii should be treated

whether or not they have clinical manifestations of the infection because treatment may be effective in interrupting acute disease that damages vital organs.

Infants should be treated for 1 yr with :-• Pyrimethamine (2 mg/kg/day divided bid for 2 days )• then 1 mg/kg/day for 2 or 6 mo, and • then 1 mg/kg given on Monday, Wednesday, and Friday

PO), • sulfadiazine (100 mg/kg/day divided bid PO), and• leukovorin (5-10 mg given on Monday, Wednesday, and

Friday, or more often depending on neutrophil count

RUBELLA

Rubella• Rubella (German measles or 3-day measles) • Single-stranded RNA virus• Vaccine-preventable disease• mild, self-limiting often exanthematous disease of

infants and children.• In the pre vaccine era, rubella appeared to occur in

major epidemics every 6-9 yr, • with smaller peaks interspersed every 3-4 yr, • was most common in preschool and school-aged

children.

Rubella• Following introduction of the rubella vaccine, the

incidence fell by >99%.

• Its major clinical significance is trans placental infection and fetal damage as part of the congenital rubella syndrome (CRS).

• Infection earlier in pregnancy has a higher probability of affected infant.

• The most important risk factor for severe congenital defects is the stage of gestation at the time of infection.

• The risk for congenital defects has been estimated at 90% for maternal infection before 11 wk of gestation,

• 33% at 11-12 wk, • 11% at 13-14 wk, and • 24% at 15-16 wk.

• Defects occurring after 16 wk of gestation are uncommon, even if fetal infection occurs

• CLINICAL MANIFESTATIONS OF CONGENITAL RUBELLA SYNDROME IN 376 CHILDREN FOLLOWING MATERNAL RUBELLA

MANIFESTATION RATE (%)

Deafness 67Ocular 71 Cataracts 29 Retinopathy 39Heart disease[†] 48 Patent ductus arteriosus 78 Right pulmonary artery stenosis 70 Left pulmonary artery stenosis 56 Valvular pulmonic stenosis 40Low birthweight 60Psychomotor retardation 45Neonatal purpura 23Death 35

Table 193-1 Common Transient and Permanent Manifestations in Infants With Congenital Rubella SyndromeTransient Manifestations Permanent Manifestations

Hepatosplenomegaly Hearing impairment/deafnessInterstitial pneumonitis Congenital heart defects (patent

ductus arteriosus, pulmonary arterial stenosis)

Thrombocytopenia with purpura/petechiae (e.g., dermal erythropoiesis, or "blueberry muffin syndrome") Hemolytic anemiaBony radiolucencies

Eye defects (cataracts, cloudy cornea, microphthalmos, pigmentary retinopathy, congenital glaucoma)

Intrauterine growth retardation Microcephaly

Adenopathy Meningoencephalitis Central nervous system sequelae

(mental and motor delay, autism)

Clinical Manifestations• Sensorineural hearing loss (50-75%)• Cataracts and glaucoma (20-50%) Retinal findings

described as salt-and-pepper retinopathy are the most common ocular abnormality but have little early effect on vision.

• Unilateral or bilateral cataracts are the most serious eye finding, occurring in about a third of infants

• Cardiac malformations (20-50%)• Neurologic (10-20%)• Others to include growth retardation, bone disease,

HSM, thrombocytopenia, “blueberry muffin” lesions

“Blueberry muffin” spots representingextramedullary hematopoesis

Diagnosis• Diagnostic tests used to confirm CRS include serologic

assays and virus isolation.• Can isolate virus from nasal secretions

– Less frequently from throat, blood, urine, CSF – Infants with congenital rubella may excrete virus for up to

1 year

– Serologic testing– IgM capture assay = recent postnatal or congenital infection– serum IgM antibodies may be present for up to 1 year after birth– Rising monthly IgG titers suggest congenital infection

• Diagnosis after 1 year of age difficult to establish

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

• Management of children with CRS is more complex and requires pediatric, cardiac, audio logic, ophthalmologic, and neurologic evaluation and follow-up.

PREVENTION • Children with CRS may excrete the virus in

respiratory secretions up to 1 yr of age, so contact precautions should be maintained for them until then, unless repeated cultures of urine and pharyngeal secretions have negative results.

• Vaccination a 2-dose regimen at 12-15 mo and 4-6 yr of age

congenital infection

Healthcare