TORCH infections and HIV/AIDS in newborn

- ddiagnostic, treatment and prophylaxis.iagnostic, treatment and prophylaxis.

Prof. Pavlyshyn H.A. Prof. Pavlyshyn H.A.

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

• IUGR infantsIUGR infants• HSMHSM• ThrombocytopeniaThrombocytopenia• Unusual rashUnusual rash• Concerning maternal Concerning maternal historyhistory• ““Classic” findings of any specific Classic” findings of any specific

infectioninfection

TORCH InfectionsTORCH Infections

T=toxoplasmosisT=toxoplasmosisO=other (syphilis)O=other (syphilis)R=rubellaR=rubellaC=cytomegalovirus (CMV)C=cytomegalovirus (CMV)H=herpes simplex (HSV)H=herpes simplex (HSV)

ToxoplasmosisToxoplasmosis• Caused by protozoan – Toxoplasma gondiiCaused by protozoan – Toxoplasma gondii• Domestic cat is the definitive host with infections via:Domestic cat is the definitive host with infections via:

• Ingestion of cysts (meats, garden products)Ingestion of cysts (meats, garden products)• Contact with oocysts in fecesContact with oocysts in feces

• Much higher prevalence of infection in European Much higher prevalence of infection in European countries (ie France, Greece)countries (ie France, Greece)

• Acute infection usually asymptomaticAcute infection usually asymptomatic• 1/3 risk of fetal infection with primary maternal 1/3 risk of fetal infection with primary maternal

infection in pregnancyinfection in pregnancy• Infection rate higher with infxn in 3Infection rate higher with infxn in 3 rdrd trimester trimester• Fetal death higher with infxn in 1Fetal death higher with infxn in 1stst trimester trimester

Clinical ManifestationsClinical Manifestations

• Most (70-90%) are asymptomatic at birthMost (70-90%) are asymptomatic at birth• Classic triad of symptoms:Classic triad of symptoms:

• ChorioretinitisChorioretinitis• HydrocephalusHydrocephalus• Intracranial calcificationsIntracranial calcifications

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

• Initially asymptomatic infants are still at high risk of Initially asymptomatic infants are still at high risk of developing abnormalities, especially chorioretinitisdeveloping abnormalities, especially chorioretinitis

TreatmentTreatment

• Symptomatic infantsSymptomatic infants• Pyrimethamine (with leucovorin rescue) Pyrimethamine (with leucovorin rescue)

and sulfadiazineand sulfadiazine• Treatment for 12 months totalTreatment for 12 months total

• Asymptomatic infantsAsymptomatic infants• Course of same medicationsCourse of same medications• Improved neurologic and developmental Improved neurologic and developmental

outcomes demonstrated (compared to outcomes demonstrated (compared to untreated pts or those treated for only one untreated pts or those treated for only one month)month)

Syphilis Syphilis Clinical ManifestationsClinical Manifestations

Early congenital (typically 1st 5 weeks):• Cutaneous lesions (palms/soles)Cutaneous lesions (palms/soles)• HSMHSM• JaundiceJaundice• AnemiaAnemia• SnufflesSnuffles• Periostitis and metaphysial dystrophyPeriostitis and metaphysial dystrophy• Funisitis (umbilical cord vasculitis) Funisitis (umbilical cord vasculitis)

Late congenital:• Frontal bossingFrontal bossing• Short maxillaShort maxilla• High palatal archHigh palatal arch• Hutchinson teethHutchinson teeth• 88thth nerve deafness nerve deafness• Saddle nose Saddle nose • Perioral fissuresPerioral fissures

• Can be prevented with appropriate treatmentCan be prevented with appropriate treatment

TreatmentTreatment

• Penicillin G is THE drug of choice for ALL Penicillin G is THE drug of choice for ALL syphilis infectionssyphilis infections

• Maternal treatment during pregnancy very Maternal treatment during pregnancy very effective (overall 98% success)effective (overall 98% success)

• Treat newborn if:Treat newborn if:• They meet CDC diagnostic criteriaThey meet CDC diagnostic criteria• Mom was treated <4wks before deliveryMom was treated <4wks before delivery• Mom treated with non-PCN medMom treated with non-PCN med• Maternal titers do not show adequate response Maternal titers do not show adequate response

(less than 4-fold decline)(less than 4-fold decline)

Rubella Rubella Clinical ManifestationsClinical Manifestations• Sensorineural hearing loss (50-Sensorineural hearing loss (50-

75%)75%)• Cataracts and glaucoma (20-50%)Cataracts and glaucoma (20-50%)• Cardiac malformations (20-50%)Cardiac malformations (20-50%)• Neurologic (10-20%)Neurologic (10-20%)• Others to include growth Others to include growth

retardation, bone disease, HSM, retardation, bone disease, HSM, thrombocytopenia, thrombocytopenia, “blueberry “blueberry muffin” lesionsmuffin” lesions

““Blueberry muffin” spots representingBlueberry muffin” spots representing

extramedullary hematopoesisextramedullary hematopoesis

DiagnosisDiagnosis• Maternal IgG may represent immunization or past Maternal IgG may represent immunization or past

infection - Useless!infection - Useless!• Can isolate virus from nasal secretionsCan isolate virus from nasal secretions

• Less frequently from throat, blood, urine, CSFLess frequently from throat, blood, urine, CSF

• Serologic testingSerologic testing• IgM = recent postnatal or congenital infectionIgM = recent postnatal or congenital infection• Rising monthly IgG titers suggest congenital infectionRising monthly IgG titers suggest congenital infection

• Diagnosis after 1 year of age difficult to establishDiagnosis after 1 year of age difficult to establish

TreatmentTreatment• Prevention…immunize, immunize, Prevention…immunize, immunize,

immunize!immunize!

• Supportive care only with parent educationSupportive care only with parent education

Cytomegalovirus (CMV)Cytomegalovirus (CMV)• 90% are asymptomatic at birth!90% are asymptomatic at birth!

• Up to 15% develop symptoms later, notably sensorineural Up to 15% develop symptoms later, notably sensorineural hearing losshearing loss

• Symptomatic infectionSymptomatic infection• SGA, HSM, petechiae, SGA, HSM, petechiae, • jaundice, chorioretinitis, jaundice, chorioretinitis, • periventricular calcificationsperiventricular calcifications, , • neurological deficitsneurological deficits• >80% develop long term >80% develop long term complicationscomplications

• Hearing loss, Hearing loss, • vision impairment, vision impairment, • developmental delaydevelopmental delay

Ventriculomegaly and Ventriculomegaly and calcifications of calcifications of congenital CMVcongenital CMV

DiagnosisDiagnosis• Maternal IgG shows only past infectionMaternal IgG shows only past infection

• Infection common – this is uselessInfection common – this is useless

• Viral isolation from urine or saliva in 1Viral isolation from urine or saliva in 1stst 3weeks of life3weeks of life• Afterwards may represent post-natal infectionAfterwards may represent post-natal infection

• Viral load and DNA copies can be assessed Viral load and DNA copies can be assessed by PCRby PCR• Less useful for diagnosis, but helps in following Less useful for diagnosis, but helps in following

viral activity in patientviral activity in patient

• Serologies not helpful given high antibody in Serologies not helpful given high antibody in populationpopulation

PCR diagnostic

PCR diagnostic

TreatmentTreatment

• Ganciclovir x6wks in symptomatic infantsGanciclovir x6wks in symptomatic infants• Studies show improvement or no progression of Studies show improvement or no progression of

hearing loss at 6moshearing loss at 6mos• No other outcomes evaluated (development, etc.)No other outcomes evaluated (development, etc.)• Neutropenia often leads to cessation of therapyNeutropenia often leads to cessation of therapy

• Treatment currently not recommended in Treatment currently not recommended in asymptomatic infants due to side effectsasymptomatic infants due to side effects

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

Clinical ManifestationsClinical Manifestations

• Most are asymptomatic at birthMost are asymptomatic at birth• 3 patterns of ~ equal frequency with symptoms 3 patterns of ~ equal frequency with symptoms

between birth and 4wks:between birth and 4wks:• Skin, eyes, mouth (SEM)Skin, eyes, mouth (SEM)• CNS diseaseCNS disease• Disseminated disease (present earliest)Disseminated disease (present earliest)

• Initial manifestations very nonspecific with Initial manifestations very nonspecific with

skin lesions NOT necessarily presentskin lesions NOT necessarily present

Herpes Simplex (HSV)Herpes Simplex (HSV)

DiagnosisDiagnosis• Culture of maternal lesions if present at deliveryCulture of maternal lesions if present at delivery• Cultures in infant:Cultures in infant:

• Skin lesions, oro/nasopharynx, eyes, urine, blood, Skin lesions, oro/nasopharynx, eyes, urine, blood, rectum/stool, CSFrectum/stool, CSF

• CSF PCRCSF PCR• Serologies again not helpful given high prevalence of Serologies again not helpful given high prevalence of

HSV antibodies in populationHSV antibodies in population

Treatment•High dose acyclovir 60mg/kg/day divided q8hrsHigh dose acyclovir 60mg/kg/day divided q8hrs

X21days for disseminated, CNS diseaseX21days for disseminated, CNS disease X14days for SEMX14days for SEM

•Ocular involvement requires topical therapy as Ocular involvement requires topical therapy as wellwell

What is HIV?• Human immunodeficiency virus is the virus that causes AIDS. Human immunodeficiency virus is the virus that causes AIDS. • The human immunodeficiency virus (HIV) infects cells of the immune The human immunodeficiency virus (HIV) infects cells of the immune

systemsystem - (CD4+) T cells - (CD4+) T cells, destroying or impairing their function. , destroying or impairing their function. • Infection with the virus results in the progressive deterioration of the Infection with the virus results in the progressive deterioration of the

immune system, leading to "immune system, leading to "immune deficiency."immune deficiency." • Infections associated with severe immunodeficiency are known as Infections associated with severe immunodeficiency are known as

""opportunistic infectionsopportunistic infections", ", because they take advantage of a because they take advantage of a weakened immune system.weakened immune system.

Symptoms of HIV/AIDS in Children

CNSCNS – microcephaly– microcephaly- progressive neurological deterioration - progressive neurological deterioration or spastic encephalopathyor spastic encephalopathy- developmental delay/regression- developmental delay/regression- predisposition to CNS infections- predisposition to CNS infections

Respiratory SystemRespiratory System- Recurrent infections (pneumonia, sinusitis, otitis - Recurrent infections (pneumonia, sinusitis, otitis media)media)- Tuberculosis- Tuberculosis- Pneumocystis carinii pneumonia (PCP) or - Pneumocystis carinii pneumonia (PCP) or lymphoid interstitial pneumonitis (LIP)lymphoid interstitial pneumonitis (LIP)

Clinical Features

• CVSCVS – cardiomyopathy with congestive cardiac failure – cardiomyopathy with congestive cardiac failure

• GITGIT- AIDS enteropathy (malabsorption, infections with - AIDS enteropathy (malabsorption, infections with various pathogens) leads to chronic diarrhoea resulting in various pathogens) leads to chronic diarrhoea resulting in failure to thrivefailure to thrive

- Abdominal pains, dysphagia, chronic hepatitis, pancreatitis- Abdominal pains, dysphagia, chronic hepatitis, pancreatitis

• RenalRenal – AIDS nephropathy: the most common presentation – AIDS nephropathy: the most common presentation being nephrotic syndromebeing nephrotic syndrome

• Skin Skin – Eczema, seborrheic dermatitis, candida infections, – Eczema, seborrheic dermatitis, candida infections, molluscum contagiosum, anogenital wartsmolluscum contagiosum, anogenital warts