neonatal infectious diseases categories.pptx

Neonatology

1. PERINATAL INFECTIONS

2. INTRODUCTION Important cause of still births and morbidity Many diseases go undiagnosed Appropriate treatment can prevent morbidity/mortality 1971: Andres Nahmias proposed acronym ToRCH 1975: Harold Fuerst added Syphilis to the acronym

3. ACRONYM: TORCHES CLAP T o xopla s mosis O ther (Syphilis,Varicella Zoster, ParvovirusB- 19, HEP B) C hickenpox L yme disease A IDS P arvovirus B19 R ubella C MV H erpes simplex E nterovirus S yphilis Latest addition: Zika virus

4. Toxoplasma Toxoplasmosis is a disease caused by an intracellular parasite TOXOPLASMAGONDII. Human acquisition of the infection occurs by: Oocyst contaminated soil,salads,vegetables. Ingestion of raw or undercooked meat containing tissue cysts (Sheep,pigs and rabbits are the most common meat sources). Out breaks of toxoplasmosis have also been linked to the consumption of unfiltered wate

5. Primary maternal infection in pregnancy– Infection rate higher with infection in 3r d trimester. Fetal death higher with infection in 1s t trimester

6. Signs and sympoms Infected Pregnant women : usually no clinical manifestation. Although some may have a mild mononucleosis-like syndrome, regional lymphadenopathy, or occasionally chorioretinitis. Similarly, infected neonates are usually asymptomatic at birth.

7. The classic triad of findings : chorioretinitis, hydrocephalus, and intracranial calcifications

8. Diagnosis Serial IgG measurement (for maternal infection Amniotic fluid PCR (for fetal infection) Serologic testing, brain imaging, CSF analysis and ophthalmologic evaluation (for neonatal infection), and PCR testing of various body fluids or tissues

9. Treatment •In PREGNANT WOMEN with an established recent infection, SPIRAMYCIN (3g daily in divided doses) should be given. In neonates : Pyrimethamine: 50mg twice daily for 2 days then 50mg daily. PLUS Sulfadiazine: 75mg/kg/daily in two divided doses for 2 days then 50mg/kg/twice daily PLUS Folinic Acid: 10-20mg daily

10. Prevention- counselling Avoid raw/undercooked meat wash hands after gardening wash raw vegetables minimise contact with young kittens and their litter

11. RUBELLA

12. It is caused by rubella virus,Rubivirus genus and familyTogaviridae. Intrauterine infection with rubella virus is referred to as congenital rubella infection (CRI) or syndrome. Infection with rubella earlier in pregnancy(1st trimester ) cause worse prognosis and neonatal complications . The virus can be transmitted to the fetus through the placenta and is capable of causing serious congenital defects, abortions, and stillbirth

13. In the baby Infection in weeks 8-10 of pregnancy results in damage in up to 90% of surviving infants. Multiple defects are then common. The risk of damage reduces to 10- 20% if the infection is in weeks 11-16 of pregnancy. Fetal damage is rare over 18 weeks of gestation.

14. Transmission to the fetus occurs via maternal hematogenous spread to the placenta. It typically occurs 5-7 days after maternal inoculation. After the virus invades the placental barrier, it spreads throughout the fetus via their vascular system. The congenital defects that result from infection is secondary to the cytopathical damage ensued to the blood vessels. This in turn results in ischemia of the affected organs

15. Clinical features T ra n sie n t : Intrauterine growth restriction. Thrombocytopenic purpura (25% - 'blueberry skin'). Haemolytic anaemia. H epato s ple n o m e g a l y . Jaundice (common). Radiolucent bone disease (20%). Meningoencephalitis (25%) +/- neurological sequelae Developmental : Sensorineural deafness 80% . General learning disability (55%). Insulin-dependent diabetes (20%,) 'Late-onset' disease at 3-12 months with rash, diarrhoea, pneumonitis and high mortality. Perma n e n t : Congenital heart disease (commonly patent ductus arteriosus or pulmon ary artery stenosis). Eye defects ( cataracts, congenital glaucoma, pigmentary retinopathyand called 'salt and pepper'), severe myopia, m icropht h al m ia. Microcephaly.

16. The risk of maternal-fetal transmission is the greatest in the first 10 days after gestation cardiac and eye defects typically resulting when maternal infection occurs prior to 8 week. Hearing loss is typically observed in infections up to 18 weeks of gestation

17. DIAGNOSIS Isolation of the rubella virus in culture Demonstration of rubella-specific IgM antibodies Demonstration of rubella-specific IgG antibodies that persist at a higher concentration or longer duration than expected from mere passive transfer of maternal antibodies Detection of rubella virus RNA by reverse- transcriptase polymerase chain reaction in nasopharyngeal swabs, urine, CSF, and blood at birth Avidity testing of IgG

18. Avidity: Strength with which IgG bi n ds to a n tigenic epitrop e s expressed by a specific protein. Gradually matures over months. IgG produced in first few months following primary infection Low avidity (Bind weakly to Ag) Therefore, LOW IgG avidity is a marker of RECENT PRIMARY infection. High avidity excludes primary infection in preceding 3 months .

19. Treatment Supportive care and surveillance is the only recommended option available at this time. Close monitoring within the first 6 to 12 months of life is recommended; particularly for the evaluation of hearing impairment . Prevention . Preventive measures include recommended immunizations, testing of pregnant women for rubella immunity and proper counseling regarding avoiding exposure

20. CYTOMEGALOVIRUS

21. CMV is a doubles stranded DNA herpes virus The most common congenital viral infection. The CMV seropositivity rate increases with age. Geographic location, socioeconomic class, and work exposure are other factors that influence the risk of infection. CMV infection requires intimate contact through saliva,urine, and/ or other body fluids. Possible routes of transmission include sexual contact, 2. organ transplantation, 3.transplacental transmission, 4. transmission via breastmilk,and 5.blood transfusion(rare)

22. Primary,reactivation,or recurrent CMV infection can occur in pregnancy and can lead to congenital CMV infection. Approximately 85 percent of newborns with congenital CMV infection can be asymptomatic at birth. 15 percent will develop progressive hearing loss and visual impairment as they age. Transplacental infection can result in : intrauterine growth restriction Sensorineural hearing loss, Intracranial calcifications Petichiae Jaudice microcephaly, hydrocephalus hepatosplenomegaly, Delayed psychomotor development, Thrombocytopenia and/ Chorioretinitis

23. Vertical transmission of CMV can occur at any stage of pregnancy. Severe sequelae are more common with infection in the 1st trimester . The overall risk of infection is greatest in the 3rd trimester . The risk of transmission to the fetus in primary infection is 30%-40%

24. Diagnosis : Virus culture from urine/saliva CMV-DNA PCR in urine, blood, saliva and CSF CMV IgM antibodies in blood before 3 weeks of age. IgG Avidity testing

25. T reatment Ganciclovir 5mg/kg IV every 12 hours for 14 days OR Valganciclovir 900mg PO daily for 3- 6 months OR CMV-specific hyperimmune globulin (200 units/kg of body weight) Foscarnet, Cidofovir for refractory CMV/ Ganciclovir resistance

26. HERPES SIMPLEX VIRUS

27. Herpes simplex virus (HSV) infection during pregnancy can pose a serious threat to the developing fetus and the newborn infant. Transmission typically occurs via direct contact between the neonate and an infected maternal genital tract. If the primary HSV infection was acquired during pregnancy, then the risk of transmission is greater as compared with reactivation of a previous infection. incidence of neonatal HSV infection ranges from 1 in 3200 to 1 in 10,000 births .

28. HSV is a member of the Herpes viridae family of viruses Enters the host through the inoculation of oral, genital, or conjunctival mucosa. Inoculation also can occur through breaks in the skin. Dissemination of the virus eventually allows the virus to reach the dorsal root ganglia, where it remains dormant for the rest of the host’s life. Antiviral drugs do not affect latent HSV infection and therefore infection is life-long Intrauterine HSV is a rare occurrence and most likely is caused by maternal viremia associated with primary infection during pregnancy.

29. Intrauterine infection is associated with hydropsfetalis and in-utero fetal demise. The characteristic triad noted at birth includes skin lesions consistent of vesicles, ulcerations or scarring , eye damage and CNS abnormalities, such as hydranencephaly and microcephaly. Clinical manifestation can arise any time during the first six weeks of life, but usually occurs within the first month of life

30. Diagnosis Isolation of HSV in culture Detection of DNA via PCR assays Detection of HSV specific antigens using rapid direct immunofluorescence or enzyme immunoassays. Classic CSF findings include : a mononuclear cell pleocytosis, normal or slightly low glucose concentration and moderately elevated protein level. Electroencephalogram (EEG) is often abnormal from early on in the disease and may show focal or multifocal periodic epileptic form discharges . Neuroimaging studies may show parenchymal brain edema, hemorrhage or destructive lesions in the temporal frontal, parietal or brainstem regions in the brain

31. After completion of parenteral therapy suppressive course of oral acyclovir for 6 months PREVENTION 85% neonatal HSV are acquired perinatally. True intrauterine infection 5% Careful speculum examination for active genital HSV Caesarean section reduces risk of HSV transmission

32. SYPHILIS

33. Infant usually infected in utero by transplacental passage of Treponema pallidum from infected mother at any time. Infection may also occur from contact with an infectious lesion during passage through the birth canal It remains unclear what factors determine which mothers, particularly those in the latent stage, will pass the disease to the fetuses. Also unclear why some infants, infected in utero, are born asymptomatic, but develop overt dz. In first few wks./mo.

34. Infection can be transmitted to fetus at any stage of disease. Rate of infection 60% - 100% during second stage. Transmission rates slowly decreases with increasing duration of the disease. Women, untreated early syphilis: 40% of pregnancies result in spontaneous abortion, stillbirth, or perinatal death.

35. Clinical Manifestations Damage to fetus depends on the stage of development at which infection has taken place and time elapsed before treatment. a. Early infection, untreated: miscarriage, stillbirth, neonatal death, IUGR, premature delivery. Survivors : Early congenital syphilis : clinical manifestations within first 2 years of life Late congenital syphilis : clinical manifestations after 2yo

36. EARLY CONGENITAL SYPHILIS Early manifestations are varied, with multi-system Involvement Hepatosplenomegaly- diffuse inflammation, scarring Jaundice – due to hepatitis Generalized lymphadenopathy – epitrochclear nodes Coombs – hemolytic anemia, thromobocytopenia, leukopenia, leukocytosis Hydrops fetalis Mucocutaneous: rhinitis (highly infectious) , “snuffles”, mucous patches Macuolpapular rash Desquamation Pemphigus syphiliticus (vesicular bullous eruptions of palms and soles ) Petechial lesions Bony lesions, osteochondritis, periostitis, pseudoparalysis Syphilitc leptomeningitis Chorioretinitis, salt and pepper fundus , glaucoma Pancreatitis

37. LATE CONGENITAL SYPHILIS Results primarily from chronic inflammation of bone, teeth, and CNS . Interstitial keratitis ( i n flamm a tor y ) Nerve deafness Clutton’s Joints ( synositis, restricted movement ) Hutchinson’s triad ( teeth, intersitial keratitis, 8 th nerve d e af n es s ) Mulberry molars Flaring scapulas Hydrocephalus Mental retardation Frontal bossing Saddle nose Protruding mandible ,High arched palate ,Perioral fissures Saber shins Anterior bowing of tibias Rhagades ( linear scars that become fissured or ulcerated ) Hutchinson’s teeth – peg shaped upper incisors Frontal Bossing Gumma: Thin atrophic scar

38. Diagnosis : Adequacy of maternal treatment Examination of placenta/umbilical cord for pathology Dark field microscopy of suspicious lesions/body fluid Clinical findings suggestive of syphilis: Non immune hydrops/ jaundice/hepatosplenomegaly/ rhinitis/ skin rash Quantitative Nontreponemal test: VDRL, RPR Quantitative results correlate with disease activity, therefore helpful in screening. Titers rise when disease is active, fall when treatment is adequate These tests become non- reactive within a few months of adequate treatment. Treponemal tests : TPI, FTA-ABS, MHA-TP

39. Infant Testing Reactive serology in neonate could be due to IgG passively transferred to newborn through placenta, and does not indicate active infection. If infant’s titer higher than mother’s congenital infection If decreasing titer in infant passive transfer of antibodies, should disappear by 3-4 months of age. Persistently reactive VDRL, with rising titer Active Infection

40. T reatment Aqueous crystalline Penicillin G 100,000-150,000U/kg/day (given q8- q12hrs) IV for 10 days OR Procaine Penicillin G 50,000 U/kg/day IM for 10days If >1 day of therapy missed, entire course should be restarted

41. V ARIC E LLA

42. Neonatal Varicella Infants whose mothers demonstrate varicella in the period from 5 days prior to delivery to 2 days afterward are at high risk for severe varicella. The infant acquires the infection transplacentally The infant's rash usually occurs toward the end of the 1st week to the early part of the 2nd week of life maternal immunoglobulin G (IgG) is able to cross the placenta if delivery occurs after 30 wk of gestation

43. Clinical manifestations 1.Congenital varicella syndrome. include cicatricial skin lesions, ocular defects,limb abnormalities, CNS abnormalities, IUGR, and fetal demise or early death. The syndrome most commonly occurs with maternal VZV infection between weeks 7 and 20 of gestation 2. Zoster. Zoster is uncommon in young infants but may occur as a consequence of in utero fetal infection with VZV. usually self-limiting, with only symptomatic therapy indicated in otherwise healthy children. 3.Postnatal varicella. mild disease likely due to the presence of maternal antibodies against the virus. Rarely, severe disseminated disease occurs in newborns exposed shortly after birth following an acute maternal infection.

44. DIAGNO S IS clinical findings and maternal history culture of vesicular fluid, VZV antibody titer by the fluorescent antibody to membrane antigen assay or by ELISA; antigen detected from cells at the base of a vesicle By immunofluorescent antibody or PCR detection.

45. TRE A TMENT [phone] +1 +2 +4 Newborn will have protective antibodies Likelihood of severe disease is low Do not separate baby from mother Continue breast feeding No VZIG Acyclovir if baby develops rash Newborn will not have protective antibodies Likelihood of severe disease is high Separate baby from mother If baby devps rash stay with mother VZIG within 72 hours Acyclovir Newborn will not have protective antibodies But, likelihood of severe disease is low Separate baby from mother f baby devps rash stay with mother No VZIG Acyclovir if baby develops ras

46. HEPATITIS

47. HBV infection during late pregnancy or near the time of delivery, however,may result in up to 90% transmission rate in the absence of any prophylaxis and is most common in women who have both HBsAg and HBeAg detected in blood, indicating high plasma HBV DNA level.

48. Risk of vertical transmission mother HBsAG +VE BUT HBeAg –VE: 5-20% HBsAg +ve and HBeAg +ve: 70-90% No contraindication for breast feeding Hepatitis B vaccine : 90% active immunity HBIG: additional 5- 10% immunity 90% of infected infants become chronic cases

49. NEONATE BORN TO MOTHER WITH HEPATITIS B (prenatal testing of all pregnant womens for HBsAG is recommanded At birth : Hepatitis B vaccine with HBIG(200 IU IM) (Perferably within 12 hrs bt not after 48 to 72 hrs) FOLLOWUP: complete HBV immunization as per schedule 3 dose schedule I n fants<2 k g: do not c o u nt birth dose a nd g i v e 3 m ore d ose Infants>2kg:give total 3 doses FOLLOW UP TESTING DONE AT 9 TO 18 MONTHS OF AGE FOR ANTI-HBs and HbsAg

50. F O L L O W UP A T 9 T O 18 MONTHS Infants with a n ti-HB>/1 mIU/ml and HBsAG neg IMMUNE NO AC T I O N REQUIRED Infants with anti HB<10mIU/ml and HBsAG neg NO HBV INFECTION B U T F AIL T O RESPOND TO IMMUNIZ A T I O N RE V AC C IN A T I O N( 3 DOSES) Infants with Anti HBs neg And HBsAG positive HBV INFECTION FOLLOWUP

51. CONGENITAL MALARIA

52. Malaria during neonatal period occurs due to administration of infected blood. It appears that placenta act as barrier to malarial paracite and its transplacental transmission if futher blocked if mother is immune. Placental malaria is asymptomatic and it silently causes fetal wasting

53. Matarnal malaria causes severe anemianand adversly affect placental circulation interfering with nutrition and oxygenation--- Leading to abortion, still birth, prematurity , fetal growth retardation and neonatal deaths Fetal infection occures due to direct penetration of paracite through chorionic villi, premature separation of placenta, maternofetal transfusion during delivery Disease manifests around 2-8 weeks with Fever Jaundice Hemolytic anemia reticulocytosis throm b ocy t osis Hs megaly

54. TRE A TMENT Oral administration chloroquine 10mg/kg followed by 5mg/kg at 6,24 &48 hrs (IM injections is unsafe risk of seizures) Radical therapy with primaquine is unnessesary as congenital malaria is form of transfusion malaria and it has no exoerythrocytic phase Chloroquine resistant malaria oral quinine sulfate 25mg/kg 8 th hrly for 3-5 days

55. TUBERCULOS I S

56. Women with pulmonary TB do not pose any treat to fetus but may infect after birth Congenital TB may occur if mother having tubercular endometriosis, miliary TB, or placenta affected by tubercular bacilli. Infection may transmit to fetus through umbilical vein or by aspiration at time of birthInfant may born with active disease or symptoms may appear in first 8 weeks of life Present with HS megally Tachypnea Lethargic Skin papules Features of miliary TB LN pathy Fever Poor feeding Jaundice

57. Reassure the mother to breast feed the baby Separation of mother & baby required only if mother – is sick non adherent to treatment has MDR TB BCG vaccination after completion of INH course