TORCH Infections.pptx

Pedatrics

1. TORCH Infections Congenital infections 31/05/2022 1 by Yonas

2. What Is TORCH Infection ? Common or rare? Prevention methods ( ANC,cook,C / S,safe sexual practice,immunization ) 31/05/2022 2 by Yonas

3. Cont Agents that infect the mother during labor and delivery or pregnancy may infect the fetus These infections can cause fetal death , early neonatal loss,multi organ dysfunction or injury to the developing brain. The most common infecting agents include CMV, Toxoplasma gondi,Treponema pallidem , HSV, and rubella viruse 31/05/2022 3 by Yonas

4. What Is TORCH Infection? acronym for a cluster of congenital infections that the baby acquires from the mother. The infections pass from the mother to the baby, while the baby is still in the uterus or during the childbirth process. Although the condition is rare, TORCH poses more risk to the fetus than to the mother. The risk is higher if the fetus acquires the infection early on during pregnancy 31/05/2022 4 by Yonas

5. TORCH Infections T=toxoplasmosis O=other (syphilis) R=rubella C=cytomegalovirus (CMV) H=herpes simplex (HSV) 31/05/2022 5 by Yonas

6. The cause for each of these infections may vary, but their symptoms could be similar. The baby may not show the symptoms of the infections immediately after birth but may develop after some years 31/05/2022 6 by Yonas

7. 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 31/05/2022 7 by Yonas

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 Acute infection usually asymptomatic(immunity) 1/3 risk of fetal infection with primary maternal infection in pregnancy Infection rate higher with 3 rd trimester Fetal death higher with in 1 st trimester 31/05/2022 8 by Yonas

9. Clinical Manifestations Most (70-90%) are asymptomatic at birth Classic triad of symptoms: Chorioretinitis Hydrocephalus Intracranial calcifications Other symptoms fever, rash, HSM, microcephaly , seizures, jaundice, thrombocytopenia, LAP Asymptomatic infants are at high risk of developing abnormalities, especially chorioretinitis 31/05/2022 9 by Yonas

10. Chorioretinitis of congenital toxo 31/05/2022 10 by Yonas

11. Diagnosis Maternal IgG testing indicates past infection Can be isolated in culture from placenta, umbilical cord, infant serum PCR testing on WBC, CSF, placenta Not standardized Newborn serologies with IgM/ IgA 31/05/2022 11 by Yonas

12. Toxo Screening Neonatal screening with IgM testing implemented in some areas Identifies infected asymptomatic infants who may benefit from therapy 31/05/2022 12 by Yonas

13. Prevention and Treatment Pregnant mothers diagnosed with acute toxo Spiramycin daily Reduces transmission (up to 50%) If infant diagnosed prenatally, treat mom Spiramycin,or pyrimethamine & sulfadiazine Leucovorin Symptomatic infants Pyrimethamine and sulfadiazine plus leucovorine Treatment for 12 months total Asymptomatic infants Course of same medications Improved neurologic and developmental outcome 31/05/2022 13 by Yonas

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17. Syphilis Caused by T. palladium Transmitted via sexual contact Placental transmission as early as 6wks gestation Typically occurs during second half Primary or 2 nd syphilis more likely to transmit than latent disease 31/05/2022 17 by Yonas

18. 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 31/05/2022 18 by Yonas

19. Clinical Manifestations Fetal: Stillbirth Neonatal death Hydrops fetalis Intrauterine death in 25% Perinatal mortality in 25-30% if untreated 31/05/2022 19 by Yonas

20. Clinical Manifestations……. Early congenital (typically 1 st 5 weeks): Cutaneous lesions (palms/soles) HSM Jaundice Anemia Snuffles Periostitis and metaphysial dystrophy Funisitis (umbilical cord vasculitis ) 31/05/2022 20 by Yonas

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23. Periostitis of long bones seen in neonatal syphilis 31/05/2022 23 by Yonas

24. Clinical Manifestations…… Late congenital: Frontal bossing Short maxilla High palatal arch Hutchinson teeth 8 th nerve deafness Saddle nose Perioral fissures Can be prevented with appropriate treatment 31/05/2022 24 by Yonas

25. Hutchinson teeth – late result of congenital syphilis 31/05/2022 25 by Yonas

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28. Diagnosing Syphilis RPR/VDRL : nontreponemal test Sensitive but NOT specific Quantitative, so can follow to determine disease activity and treatment response FTA-ABS : specific treponemal test Used for confirmatory testing Qualitative, once positive always positive RPR/VDRL screen in ALL pregnant women 31/05/2022 28 by Yonas

29. 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 31/05/2022 29 by Yonas

30. Diagnosing Congenital Syphilis IgG can represent maternal antibody, not infant infection 31/05/2022 30 by Yonas

31. 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 ) 31/05/2022 31 by Yonas

32. Rubella(MMR) Single-stranded RNA virus Vaccine-preventable disease Mild , self-limiting illness Infection earlier in pregnancy has a higher probability of affected infant 31/05/2022 32 by Yonas

33. Copyright ©2006 American Academy of Pediatrics Meissner, H. C. et al. Pediatrics 2006;117:933-935 Reported rubella and CRS before & after MMR 31/05/2022 33 by Yonas

34. 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 31/05/2022 34 by Yonas

35. “Blueberry muffin” spots representing extramedullary hematopoesis 31/05/2022 35 by Yonas

36. 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 31/05/2022 36 by Yonas

37. Treatment Prevention…immunize, immunize, immunize! Supportive care only with parent education 31/05/2022 37 by Yonas

38. Cytomegalovirus (CMV) Most common congenital viral infection Mild , self limiting illness Transmission can occur with primary infection or reactivation of virus 40% risk of transmission in primary infection Increased risk of transmission later in pregnancy Severe sequalae associated with 1 st trimister 31/05/2022 38 by Yonas

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40. Clinical Manifestations 31/05/2022 40 by Yonas

41. Clinical Manifestations 90% are asymptomatic at birth! Symptomatic infection SGA, HSM, petechiae, jaundice, chorioretinitis, periventricular calcifications, neurological deficits >80% develop long term complications Hearing loss, vision impairment, developmental delay 31/05/2022 41 by Yonas

42. Ventriculomegaly and calcifications of congenital CMV 31/05/2022 42 by Yonas

43. Diagnosis Maternal IgG shows only past infection – useless Viral isolation from urine or saliva in 1 st 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 treated patient 31/05/2022 43 by Yonas

44. Treatment Ganciclovir for 6wks 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 31/05/2022 44 by Yonas

45. 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 31/05/2022 45 by Yonas

46. Clinical Manifestations Most are asymptomatic at birth 3 patterns of 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 31/05/2022 46 by Yonas

47. Presentations of congenital HSV 31/05/2022 47 by Yonas

48. 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 31/05/2022 48 by Yonas

49. Treatment High dose acyclovir X21days for disseminated, CNS disease X14days for SEM Ocular involvement requires topical therapy as well 31/05/2022 49 by Yonas

50. TORCH infections Several maternal infections during pregnancy may have permanent or long-lasting effects in the foetus The outcome following such intrauterine infections may depend on the maturity of the foetus when the infection is contracted The commonest congenital infections of significance constitute the TORCH’ infections—namely, Toxoplasmosis Other (particularly syphilis) Rubella Cytomegalovirus and Herpes simplex. 31/05/2022 50 by Yonas

51. Toxoplasmosis Infection with Toxoplasma gondii results in toxoplasmosis one of the commonest infections in the world The incidence of toxoplasmosis during pregnancy varies from 3–6 per 1000 to 1–2 per 1000 in low-risk countries (such as the UK and the USA) The mother can be infected by an infected cat, or by eating raw or inadequately cooked meat or contaminated vegetables Most individuals will have either no or minimal signs of acute infection The risk of foetal infection increases from the first trimester to the third trimester, while the risk of serious infection in the foetus decreases from 75% in the first trimester to being negligible in the third trimester Congenital toxoplasmosis with clinical manifestation of disease in the newborn occurs when the foetus is infected before 26 weeks’ gestation The incidence of congenital toxoplasmosis in the UK is approximately 1:10000 Approximately 60% of all infants born to infected mothers escape infection, 25% have subclinical infection without sequelae, and only 5–10% develop clinical infection The classic tetrad of congenital toxoplasmosis comprises chorioretinitis, intracranial calcification, epilepsy, and hydrocephalus Affected infants may also be growth restricted and present with petechiae, jaundice, and hepatosplenomegaly Diagnosis is based on serological tests for toxoplasmosis, particularly of the CSF. Antenatal diagnosis is possible Treatment with spiramycin , pyrimethamine , and sulphonamides may improve foetal outcome for mothers who seroconvert during pregnancy infected neonates receive a year’s therapy with spiramycin , sulphadiazine , and pyrimethamine . Prognosis for mild or subclinical cases is good, but 25% of those with neonatal symptoms die. Infection in the first 20 weeks of pregnancy may be an indication for termination. 31/05/2022 51 by Yonas

52. Rubella The risk of foetal infection decreases with advancing gestation In 90% of cases, maternal rubella infection in the first 8–10 weeks of pregnancy results in serious foetal infection and damage, whereas by 16 weeks the risk declines to 10–20%, and thereafter foetal damage is rare The clinical features of extended CRS include petechiae, jaundice, hepatosplenomegaly, eye and bone anomalies, a murmur, and, in 33%, birth weight below the third percentile Multiple foetal defects are common: eyes (cataract, glaucoma, and microphthalmia), CNS (microcephaly, mental retardation, and cerebral palsy), deafness (bilateral and sensorineural), cardiovascular (PDA and peripheral pulmonary artery stenosis), liver (hepatitis and prolonged jaundice), bone (osteitis), and haematological (anaemia and thrombocytopenia) Diagnosis is by culturing the virus from a throat swab or urine and demonstrating rubella-specific IgM in the infant’s blood Antiviral treatment is not available, and infants remain very infectious during the first months of life (hazard to female staff) Glaucoma and cataracts require ophthalmological intervention, and hearing should be formally assessed 31/05/2022 52 by Yonas

53. Cytomegalovirus (CMV) congenital CMV is the commonest disease of newborns with a significant morbidity Both primary and recurrent maternal infections during pregnancy can result in foetal infection, but the rate of foetal transmission is higher (24–75%) with a primary maternal infection than with a reactivation of infection (<1%). Approximately 90% of congenitally infected infants born to mothers who had their primary infection during pregnancy are asymptomatic at birth, but they are more likely to develop adverse sequelae than those infants born to mothers with reactivation of infection The characteristic features include petechiae, hepatosplenomegaly, sensorineural hearing impairment, microcephaly, intracranial calcification, chorioretinitis, jaundice, growth restriction, and thrombocytopenia The standard diagnostic test is viral culture (the most sensitive and specific test) of urine, saliva, or other bodily secretions/tissues obtained within the first three weeks of life, so as to distinguish congenital from perinatal and postnatal infection Other tests include serology for CMV-specific IgM antibody, detection of CMV DNA by PCR, and urine electron microscopy for viral particles These infants shed the virus for long periods (hazard to female staff) Therapy with ganciclovir and CMV immunoglobulin should be considered in severe disease, though efficacy has not been proven. Prognosis is generally good, with most infants developing normally Approximately 10% of asymptomatic neonates develop deafness in later life Of those with CNS signs in the neonatal period, 73% develop long-term sequelae, while 30% will have neurological sequelae in the absence of signs in the neonatal period 31/05/2022 53 by Yonas

54. Herpes simplex virus (HSV) HSV exists in two forms, types 1 and 2 (HSV-1 and HSV-2, respectively) HSV-2 causes about 85% of genital herpes, while HSV-1 causes mainly ophthalmic, orolabial , and CNS disease HSV-2 accounts for 60–70% of neonatal HSV infection Most HSV infection in neonates occurs intrapartum , but true congenital infection occurs in about 5% of cases as a result of both primary infection and (rarely) recurrent maternal infection. Congenital HSV is defined as the presence of vesicles or scarring at birth, abnormal brain CT scan within the first week of life, microcephaly, microphthalmia, or chorioretinitis Congenital HSV has a different presentation from intrapartum HSV The major clinical findings are cutaneous lesions (94%), CNS lesions (79%) (microcephaly, hydranencephaly , cerebral atrophy, and intracranial calcification), prematurity (59%), ocular lesions (42%) (chorioretinitis and microphthalmia), and organomegaly (hepatitis). HSV-2 causes >90% of congenital infection The congenitally infected infant may be mildly affected with eye involvement only, or severely affected with skin lesions, chorioretinitis, and microcephaly (or hydranencephaly ) Diagnosis is by virus culture (urine, stool, blood, CSF, vesicle fluid, conjunctival scrapings, and swabs of the eye, throat, and rectum), light microscopy ( intranuclear inclusions) or electron microscopy of conjunctival scrapings, and PCR to detect HSV DNA (as in CSF and serum) EEG may show localising signs of highvoltage , low-frequency activity, and CT or MRI scans may show temporal lobe necrosis or haemorrhage. Treatment is with aciclovir (30–60 mg/kg per day IV) with full intensive care support Mortality is 15% with CNS involvement, and 57% with disseminated disease. Rarely, infants with congenital HSV develop normally. 31/05/2022 54 by Yonas

55. Other infections Syphilis Infected newborn infants may appear normal or be severely affected with extensive skin eruptions through to marked hydrops fetalis. All pregnant mothers should be screened (VDRL, TPHA, or ELISA test) for syphilis False-positives may occur after Treponema pertenue infection (yaws) Maternal infection leads to intrauterine infection in up to half of all pregnancies, with increased foetal loss from abortions or still-births Clinical features infant initially appearing normal, with signs only appearing weeks to months later extensive mucocutaneous lesions in the absence of systemic disturbance but with hepatosplenomegaly and lymphadenopathy severe systemic disturbance but without the typical skin rashes cutaneous manifestations (maculopapular rash with circinate lesions involving palms and soles of feet) rhinitis followed by mucopurulent, blood-stained nasal discharge destruction of nasal cartilage and bone producing flattened nasal bridge and saddle nose fissures and bleeding from lesions at mucocutaneous junctions rhagades Infection 31/05/2022 55 by Yonas

56. condylomata around anus and female genitalia osteochondritis , especially wrists, elbows, and knees periostitis , especially in limb bones and skull meningitis and hydrocephalus. Investigations FBC liver function tests syphilis serology (VDRL, TPHA, or ELISA test with rising or persistently high titres) dark-field microscopy of fluid from skin lesions and nasal discharge radiography of long bones ( periostitis and osteochondritis ) CSF examination (lymphocytosis, raised protein, normal glucose level, and syphilis serology positive). Management Take precautions as skin lesions are infectious Procaine penicillin 30 mg/kg per day i.m . for ten days or single i.m . injection of long-acting benzathine penicillin 60mg/kg. Treat mother and partner(s)! 31/05/2022 56 by Yonas

57. Varicella-zoster Varicella -zoster virus (VZV) infection during pregnancy (incidence ~0.7 in 1000), particularly during the first 20 weeks, may result in foetal loss or the congenital varicellazoster syndrome with cutaneous lesions (scars) (70%), ocular abnormalities (chorioretinitis, microphthalmia, cataracts, and Horner’s syndrome), CNS lesions (50%) (cortical atrophy, calcifications, and mental retardation), and abnormal limb development (hypoplasia, and abnormal or absent digits). Administration of varicella-zoster immune globulin (VZIG) after exposure may prevent foetal infection, and aciclovir therapy during pregnancy may be safe. 31/05/2022 57 by Yonas

58. Parvovirus B19 Parvovirus B19, the causative agent of erythema infectiosum (fifth disease), has a predilection for bone-marrow erythroid precursors. Lysis of the erythroid precursors is responsible for the decreased red cell production. The incidence of B19 infection is reported as 3.7%, with a vertical transmission of 16% during the first 20 weeks and 35% after 20 weeks’ gestation. Infection-related foetal loss is low at 0.6 per 1000 women. The commonest symptomatic presentation of prenatal infection is nonimmune hydrops secondary to severe foetal anaemia, but this only occurs in about 1% of infected infants. Most infants with prenatal B19 infection are normal. No studies support a correlation between maternal infection and an increased risk of birth defects. Diagnosis is by electron microscopy of virions in tissue specimens, detection of viral DNA by PCR, or serology (IgM and IgG antibodies). Negative IgM assay at birth does not rule out congenital 31/05/2022 58 by Yonas

59. HIV infection From 8% to 24–50% of the total HIV vertical transmission is estimated to occur in utero. Vertical transmission is reduced by prenatal, perinatal, and early neonatal anti-retroviral therapy. No HIV-associated dysmorphic syndrome exists. (see ‘HIV and AIDS’ chapter.) 31/05/2022 59 by Yonas