Congenital infections Congenital Infections - PowerPoint Presentation

Slide1

Congenital infections

Slide2

Congenital Infections

an infection acquired

transplacentally

during gestation is a

congenital infection

. Numerous pathogens that produce mild or subclinical disease in older infants and children can cause severe disease in neonates who acquire such infections prenatally or

perinatally

.

Slide3

Congenital infections include a well-known group of fungal, bacterial, and viral pathogens: toxoplasmosis, rubella, CMV, HSV, varicella-zoster virus, congenital syphilis, parvovirus, HIV, hepatitis B,

Neisseria

gonorrhoeae

, Chlamydia,

and

Mycobacterium tuberculosis

.

Slide4

Many of the

clinical manifestations

of

congenital infections are similar, including IUGR, nonimmune hydrops, anemia, thrombocytopenia, jaundice, hepatosplenomegaly,

chorioretinitis

, and congenital malformations

Slide5

Evaluation of patients thought to have a congenital infection should include attempts to isolate the organism by culture (for rubella, CMV, HSV, gonorrhea, and

M. tuberculosis

), to identify the antigen of the pathogen (for hepatitis B and

C.

trachomatis

), to identify the pathogen's genome with PCR, and to identify specific fetal production of antibodies (

IgM

or increasing titer of

IgG

for

Toxoplasma

,

syphilis, parvovirus, HIV, or

Borrelia

).

Slide6

Treatment

is not always available, specific, or effective. Nonetheless, some encouraging results have been reported for preventing the disease and for specifically treating the infant when the correct diagnosis is made .

TOXOPLASMOSIS….

Vertical transmission of

Toxoplasma

gondii

occurs by

transplacental

transfer of the organism from the mother to the fetus after an acute maternal infection.

Slide7

Fetal infection rarely can occur after reactivation of disease in an

immunocompromised

pregnant mother. Transmission from an acutely infected mother to her fetus occurs in about 30% to 40% of cases, but the rate varies directly with gestational age. Transmission rates and the timing of fetal infection correlate directly with placental blood flow; the risk of infection increases throughout gestation to 90% or greater near term.

Slide8

The severity of fetal disease varies inversely with the gestational age at which maternal infection occurs. Most infants have subclinical infection with no overt disease at birth; however, specific ophthalmologic and CNS evaluations may reveal abnormalities.

The classic findings of hydrocephalus,

chorioretinitis

, and intra-cerebral calcifications suggest the diagnosis of congenital toxoplasmosis.

Slide9

Affected infants tend to be SGA, develop early-onset jaundice, have hepatosplenomegaly, and present with a generalized

maculopapular

rash. Seizures are common,

and skull films may reveal diffuse cortical calcifications in contrast to the

peri

-ventricular pattern observed with CMV

.

Slide10

IgG

-specific antibodies achieve a peak concentration 1 to 2 months after infection and remain positive indefinitely. For infants with seroconversion or a fourfold increase in IgG titers, specific IgM antibody determinations should be performed in patients to confirm disease.

Slide11

For symptomatic and asymptomatic congenital infection, initial therapy should include

pyrimethamine

(supplemented with folic acid) combined with sulfadiazine. Duration of therapy is often prolonged even up to 1 year.

RUBELLA.

With the widespread use of vaccination, congenital rubella is rare. Acquired in

utero

during early gestation, rubella can cause severe neonatal consequences.

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The occurrence of congenital defects approaches 85% if infection is acquired during the first 4 weeks of gestation; close to 40% spontaneously abort or are stillborn. If infection occurs during weeks 13 to 16, 35% of infants can have abnormalities

. Infection after 4 months' gestation does not seem to cause disease

.

Slide15

The most common characteristic abnormalities associated with congenital rubella include

ophthalmologic

(cataracts, retinopathy, and glaucoma),

cardiac

(PDA and peripheral pulmonary artery stenosis),

auditory

(sensorineural hearing loss), and

neurologic

(behavioral disorders, meningoencephalitis, and mental retardation

). purpuric

skin lesions ("blueberry muffin" appearance from dermal erythropoiesis).

Slide16

CYTOMEGALOVIRUS

CMV is the most common congenital infection and the leading cause of

sensorineural

hearing loss, mental retardation, retinal disease, and cerebral palsy. Congenital CMV occurs in about 0.5% to 1.5% of births. When primary infection occurs in mothers during a pregnancy, the virus is transmitted to the fetus in approximately 35% of

cases.

Slide17

The risk for transmission of CMV to the fetus is independent of gestational age at the time of maternal infection

The earlier in gestation that the primary maternal infection occurs, the more symptomatic the infant will be at birth. The most common sources of CMV for primary infections occurring in mothers during pregnancy are sexual contacts and contact with young

children.

Slide18

More

than 90% of infants who have congenital CMV infection exhibit no clinical evidence of disease at birth. Approximately 10% of infected infants have symptoms at birth. Findings include SGA, microcephaly, thrombocytopenia, hepatosplenomegaly, hepatitis, intracranial calcifications,

chorioretinitis

, and hearing abnormalities.

Slide19

Skull films may reveal periventricular calcifications. An additional 10% of infected infants may not present until later in infancy or early childhood, when they are found to have

sensorineural

hearing loss and developmental delays.

Mortality is 10% to 15% among symptomatic newborns

.

Slide20

CMV is diagnosed by detection of virus in the urine or saliva. Detection is often accomplished by traditional virus culture methods, but can take several weeks to obtain a result.

PCR

also can be used to detect small amounts of CMV DNA in the urine. Detection of CMV within the first 3 weeks after birth is considered proof of congenital CMV infection.

Slide21

Treatment

A randomized controlled study with

ganciclovir

(6 mg/kg/dose every 12 hr IV for the 1st 6 wk of life) concluded that treatment both prevents hearing deterioration and improves or maintains normal hearing function at 6 mo of age, and may prevent hearing deterioration that occurs after 1 yr of age.

Slide22

Prevention

Pregnant women who are CMV

seropositive

are at low risk of delivering a symptomatic newborn. If possible, pregnant women should undergo CMV serologic testing, especially if they provide care for young children who are potential CMV

excreters

.

Slide23

HIV

Slide24

ETIOLOGY

The cause of AIDS is HIV, a single-stranded RNA virus of the retrovirus family that produces a reverse transcriptase enabling the viral RNA to act as a template for DNA transcription and integration into the host genome. HIV-1 causes 99% of all human cases. HIV-2, which is less virulent, causes 1% to 9% of cases

.

Slide25

HIV infects human helper T cells (CD4 cells) and cells of monocyte-macrophage lineage via interaction of viral protein gp120 with the CD4 molecule and chemokines that serve as

coreceptors

, permitting membrane fusion and cell entry. Other cells bearing CD4, such as microglia, astrocytes, oligodendroglia, and placental tissues, also may be infected with HIV.

Slide26

Horizontal transmission

of HIV is by unprotected heterosexual or homosexual contact and IV drug use. Transmission by contaminated blood and blood products has been eliminated in developed countries, but still occurs in developing countries.

Vertical transmission

of HIV from mother to infant may occur

transplacentally

in

utero

, during birth, or by breast-feeding.

.

Slide27

Risk factors for perinatal transmission

prematurity, rupture of membranes more than 4 hours, and high maternal circulating levels of HIV at delivery.

Perinatal transmission can be decreased from approximately

25%

to less than

8%

with antiretroviral treatment of the mother before and during delivery and postnatal treatment of the infant

Slide28

In untreated infants, the mean incubation interval for development of an AIDS-defining condition after vertical transmission is 5 months (range 1 to 24 months) compared with an incubation period after horizontal transmission of generally 7 to 10 years.

Slide29

CLINICAL MANIFESTATIONS

Initial symptoms with vertical transmission vary and may include failure to thrive, neurodevelopmental delay, lymphadenopathy, hepatosplenomegaly, chronic or recurrent diarrhea, interstitial pneumonia, or oral thrush.

These findings may be subtle and remarkable only by their persistence.

Slide30

Manifestations that are more common in children than adults with HIV infection include recurrent bacterial infections, lymphoid hyperplasia, chronic parotid swelling, lymphocytic interstitial

pneumonitis

, and earlier onset of progressive neurologic deterioration.

Slide31

Pulmonary manifestations of HIV infection are common and include

P.

jirovecii

(

carinii

) pneumonia, which can present early in infancy as a primary pneumonia characterized by hypoxia, tachypnea, retractions, elevated serum lactate dehydrogenase, and fever. Infants born to HIV-infected mothers receive prophylaxis and are prospectively tested for infection.

Slide32

LABORATORY AND IMAGING STUDIES….

HIV infection can be diagnosed definitively by 1 month of age and in virtually all infected infants by 6 months of age using viral diagnostic assays (RNA PCR, DNA PCR, or virus culture). Maternal antibodies may be detectable until 12 to 15 months of age, and a positive serologic test is not considered diagnostic until 18 months of age.

Diagnostic viral testing should be performed by 48 hours of age, at 1 to 2 months of age, and at 3 to 6 months of age. An additional test at 14 days of age is often performed because the diagnostic sensitivity increases rapidly by 2 weeks of age.

Slide33

HIV DNA PCR is the preferred

virologic

method for diagnosing HIV infection during infancy

.HIV

infection of an exposed infant is confirmed if

virologic

tests are positive on two separate occasions.

Slide34

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of AIDS in infants includes primary immunodeficiency syndromes and intrauterine infection. Prominence of individual symptoms, such as diarrhea, may suggest other etiologies

.

Slide35

TREATMENT

Because the risk of HIV progression is fourfold to

sixfold

greater in infants and very young children, treatment recommendations for children are more aggressive than for adults. All age groups show rapid increases in risk as CD4 cell percentage declines to less than 15%.

Slide36

Initiation

of therapy is recommended for infants less than 12 months of age regardless of symptoms of HIV disease or HIV

RNA level

Initiation of therapy is recommended for all children 1 to 5 years of age with AIDS or significant HIV-related symptoms or CD4 below 25% regardless of symptoms or HIV RNA level.

Slide37

For

children older than 5 years with AIDS or significant HIV-related symptoms, CD4 count below 350/mm3 should be treated

.

Indications for treatment of adolescents and adults include CD4 cell count less than 200 to 350/mm3 or plasma HIV RNA levels above 55,000 copies/

mL.

Slide38

Combination therapy with

highly active antiretroviral therapy (HAART)

is recommended Antiretroviral drugs include nucleoside analogue or nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors(

ritonavir, nelfinavir, fosamprenavir, tipranavir, and lopinavir

), and fusion inhibitors(

enfuvirtide

).

Slide39

Combination therapy with dual nucleoside reverse transcriptase inhibitor combinations (zidovudine-lamivudine, zidovudine-

didanosine

, or

stavudine

-lamivudine) and a protease inhibitor is a common initial regimen for children

.

Routine immunizations are recommended to prevent vaccine-preventable infections, but may result in suboptimal immune responses

Slide40

In

addition to

heptavalent pneumococcal conjugate vaccine

,

23-valent pneumococcal polysaccharide

vaccine is recommended for HIV-infected children at 2 years of age and adolescents

.

children without severe immunosuppression should receive their first dose of

MMR at 12 months of age with the second dose of MMR 1 month later

.

MMR should not be administered to severely immunocompromised children

.

Slide41

VZV vaccine should be given only to asymptomatic,

nonimmunosuppressed

children beginning at 12 months of age as two doses of vaccine at least 3 months apart

. Inactivated split

influenza virus vaccine

should be administered annually to all HIV-infected children 6 months old or older.

Slide42

Complications

*prophylactic regimens are integral for the care of

hiv

-infected children. All infants between 4-6

wk

and 1

yr

of age who are proven to be

hiv

-infected should receive prophylaxis to prevent pneumocystis

jiroveci

infection regardless of the cd4 count or percentage.

Slide43

The best prophylactic regimen is 150 mg/m2/day of trimethoprim component of

tmp

/

smz

given as 1-2 daily doses 3 days per wk.

**P.

Jiroveci

pneumonia is treated with high-dose

tmp-smz

and corticosteroids. Oral and gastrointestinal candidiasis is common in children and usually responds to imidazole therapy.

Slide44

PROGNOSIS

The availability of HAART has improved the prognosis for HIV and AIDS dramatically. Risk of death is directly related to the degree of immunosuppression, viral load, and young age. Children less than 1 year of age with very low CD4 percentiles and high viral loads have the poorest prognosis.

Slide45

PREVENTION

The rate of vertical transmission is reduced to less than 8% by chemoprophylaxis with a regimen of

zidovudine

to the mother (100 mg five times/24 hr orally) started by 4 weeks' gestation and continued during delivery (2 mg/kg loading dose intravenously followed by 1 mg/kg/hr intravenously) and to the newborn for the first 6 weeks of life (2 mg/kg every 6 hours orally). Other regimens incorporating single-dose

nevirapine

.

Slide46

Preventing HIV infection in adults decreases the incidence of infection in children. Prevention of pediatric AIDS includes avoidance of pregnancy and breast-feeding (in developed countries) in high-risk women. Screening of blood donors has reduced markedly the risk of HIV transmission from blood products. HIV infection almost never is transmitted in a casual or nonsexual household setting.