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1
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2
Perinatal Transmission Of Infectious Disease
Oormila P. Kovilam, M.D. University of
Cincinnati Department of Obstetrics
Gynecology Cincinnati STD/HIV Prevention Training
Center
3
World wide prevalence

• 39 million ww, 50 women.

• gt 10 million
• gt 50 ?
• 25 unaware
• 300 newborns/yr.
• No decline in rate

4
HIV Pregnancy

• Initial 5 cases of PCP in men (1981)
• 25 yrs. later, AIDS in ? 7 ? 27
• 7 10,000 babies born/yr. to ve ?
• 2 3,000 will be ve
• Can ? to lt 500 by universal screening

5

• ? testing/
• 3 phase therapy
• ? to 2

6
MAGNITUDE OF MTCT

• Trend is rising
• Most tragic consequence of HIV epidemic
• 650,000 infected/day ww.
• 75 MTCT
• Detrimental tochild survival program

7
WHY DOES PERINATAL TRANSMISSION STILL OCCUR?

• 25 unaware
• 78 AIDS in women of color
• 1/9 no prenatal care
• No care until labor
• Test ? Treatment delay
• Compliance/Resistance

8
Prevalence of DZ screened for in newborns

• MSU 1 175,000
• Homocystinuria 1100,000
• Galactosemia 1 60,000
• PKU 114,000
• Tyrosinemia 1 300,000
• Hypothyroidism 14000
• Perinatal HIV 11500

9
WHY A NEW INITIATIVE

• HIV at its highest
• Availability of a simple, rapid HIV test
• 40 of infected newborn born to unaware pregnant
  women
• 95 AZT/ 01 combination Rx
• 03 no child to be born with unknown status

LD a 48 hr Window
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SCREENING

• CDC screening
• Prenatal opt out
• LD rapid testing
• Post-natal Rapid testing to status unknown

11
Rapid testing

• Point of care test Rx ? time of
  unawareness to awareness
• 100 vs. 84notification
• Critical in ICU, surgical obstetric setting
• UNO WHO recommend rapid testing instant
  notification of result

12
Turn around Time

• Point of care 45 mts 0 .5-2.5 hrs (LD)
• Laboratory 210 mts 1.6-16 hrs
• Mmwr 5236 2003

13
RAPID TEST
Mother infant rapid intervention at delivery
(MIRIAD) 70 to ? - 5 hrs to Rx
14
FDA APPROVED RAPID TESTS

• Sensitivity Specificity
• (95 C.I.) (95 C.I.)
• OraQuick Advance
• whole blood 99.6
  100
• oral fluid 99.3
  99.8
• Uni-Gold Recombigen
• whole blood 100
  99.7
• serum/plasma 100
  99.8
• Reveal g2
• Multispot HIV-1/ HIV2

15
Rapid Protocol Team

• Obstetrician Epidemiologist
  Laboratory
• Pediatrician
• Health educator

• Infectious disease
• Social worker
• Public Health Nursing

16
Third Trimester Testing

• Before 36 wks.
• History of STD
• Multiple partners
• Illicit drugs
• Symptoms/ signs of seroconversion

17
TRANSMISSION - TIMING

• In utero 25 - 40 of cases
• Intrapartum 60 - 75 of cases
• Addition risk with breastfeeding
• 14 ? risk with established infection
• 29 ? risk with primary infection
• most transmission during intrapartum period

18
DETERMINANTS OF TRANSMISSION

• Maternal disease stage
• Advanced stage higher transmission
• AIDS
• Lower CD4 counts
• Maternal p24 antigenemia
• High plasma RNA levels

• Obstetrical Factors
• Length of PROM
• Infection
• Vaginal delivery
• Invasive procedures
• Infant Factors
• Prematurity
• Susceptibility

19
Vertical Transmission

• In Utero lt 10
• Peripartum 40 70
• Breast feeding 0.5 /m risk
• Most important factor Viral load

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Chorio in utero
22
Chorio Placenta
23
Acute Chorioamnionitis
24
ABRUPTIO PLACENTA

• Perinatal Transmission not all related to viral
  load

25
HSV - FEMALE
26
Trichomonas Vaginalis
27
Cervical Intraepithelial Neoplasia
28
TWIN GESTATION
29
MULTIPLE GESTATION
Most vulnerable closest to cervix
30
Short Cervix with funneling
31
Chemical structure of Zidovudine
AZT (Zidovudine)
32
ACTG 076

• Early ARV Rx
• 94 ACTG 076 AZT ? MTCT
• HIV CD4 gt 200 (N477)
• N180 N185

ZDV 100mg x 5/day Placebo 2 mg/kg loading
IV 1 mg/kg till delivery 2 mg/kg q 6 hr.
infant thru 6 wks. HIV 13 HIV 40
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Results of ACTG
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Perinatal Transmission through the years

• Without ARV 16 25 (WITS 93)
• Newborn ve
• A2T 7.6 (ACTG 076 94)
• A2T C/S 2 (06)
• HAART C/S 1 (06)

MTCT
35
VL in Genital Secretions MTCT (Thailand)
Chuachoowong et al. JID 2000(181) p. 105
36
PREGNANCY CONCERNS

• Physiological changes
• Less aggressive use of therapy
• Treatment to ? MTCT resistant strains
• Less compliance

37
Unique pharmacokinetics

• Placenta with increase flow
• Transport of drugs
• Compartmentalization of drugs
• Biotransformation of drugs by fetus placenta
• Elimination of drugs by fetus

38
Effect of drugs of fetus/newborn

• Teratogenicity
• Mutagenicity
• Carcinogenicity
• Hemolytic anemia
• PK toxicity of transplacental drugs
• Barkers Hypothesis

39
Perinatal Guidelines

• 94 in response to ACTG 076
• Working group established inDecember 99

40
Care guidelines

• Define HIV stage/CD4, viral load
• Concurrent Risk factors
• Plan care for pregnancy, delivery infant
• Comprehensive care HAART
• Compliance/Risk for resistance

41
Anti retroviral therapy

• Site of action
• lt insert picturegt

42
HAART in pregnancy

• NRTI - Nucleoside RTI
• NNRTI - Non Nucleoside RTI
• PI - Protease Inhibitors

43
Counsel Woman

• Importance of adherence to care
• Important to take every pill every day
• Seek care of experienced OBS/ID team
• Obtain all laboratory tests on schedule
• Immediate follow up for new symptoms

44
Changing ART during Pregnancy

• Poor CD4 response
• Drugs with potential teratogenicity
• Poor viral load response
• Poor adherence to regimen
• Evidence of viral resistance

45
PRENATAL DIAGNOSIS
46
INTRAPARTUM

• 1991 European Collaborative study
• 1993 Le Zuriages et al
• 1994 McIntosh et al
• 1994 McIntosh
• 1995 Duliege I of twin effected more
• 1995 Minkoff increase with PROM

47
PERINATAL TRANSMISSION
Confidence Interval
48
Comparison of Regimens
49
HIV transmission Mode of Delivery
50
ROLE OF C/S

• Amsley,Momif 1974 Protective effect of
  HIV
• Lee 1988 Decrease Hep B
• Shah 1986 Decrease HIV
• Fr Perinatal 1998 Elective (.8)
  (n87)
• Emergency
  (11.4)
• Vaginal (6.6)
  P0.02
• Kind 1998 Swiss
  neonatal HIV study
• Gibbs 2000 Decrease Hep C
  transmission
• 4-hour rule guiding timing of delivery

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Cesarean section (C-section)

• Women with HIV RNA levels gt1,000 copies/ml
  C-section delivery
• Discuss risks associated with C-section delivery.
  Risks balanced with the potential benefits
  expected for the neonate
• Scheduled C-section delivery should be performed
  at 38 weeks gestation (rather than at 39)

52
Counseling regarding scheduled cesarean section
(C-section)

• Plasma HIV-1 RNA levels most recent value used
  when counseling a woman regarding mode of
  delivery
• HIV RNA levels lt1,000 copies/ml, No evidence to
  reduce transmission
• Unknown HIV RNA levels not on ARV or only on ZDV
  for prophylaxis, C-section reduces perinatal
  transmission

53
Budding virus from immune cell

• Tr. with undetectable viral load can occur
• ZDV ? VL at all levels
• ZDV should be given to all women in labor

54
MORBIDITY FROM CESAREAN SECTION

• International perinatal HIV group - no ?
• Marcollett 2002 -?morbidity cesarean 1.85
  elective Vs 4.17 emergency C/S
• Crubert 2002 ? postop. complications
  with ? immune status

55
Obstetric Intervention

• Avoid scalp electrode
• AROM
• Instrumental delivery
• Episiotomy
• Prolonged Induction
• External tocodynamometry

56
UNCLEAR ISSUES

• Role of PPROM and cesarean section
• Interval from PPROM to cesarean section
• Longer interval ? transmission short PPROM high
  load ? cesarean section

57
Other options

• Vaginal disinfection no ? in MTCT
• Vitamin A therapy
• Maternal baths
• Infant baths

58
Effect of Pregnancy on HIV

• No progression of disease
• Lowers CD4 count in all females

59
Obstetric outcome

• HAART therapy - no ? in PTD/IUGR
• No difference in outcome (US studies) (Minkoff
  90)
• Disparity noted in women from countries with
  inadequate treatment
• Anemia
• Low birth weight Chamiso 1996
• Leroy 1996

60
ACUTE FATTY LIVER
NORMAL
61
CLINICAL SCENARIOS
62
BEWARE OF POSTPARTUM

• Lactic acidosis
• Pancreatitis
• Mitochondrial fatty oxidation in fetus
• Follow LFT every 3-4 weeks last trimester
• Neonatal mitochondrial dysfunction
• ZDV Lamivudine

63
Breastfeeding and HIV Infection

• Breast feeding not recommended
• All Women considering breastfeeding should know
  their HIV status

64
Post-delivery recommendation

• Refer for specialty HIV care
• Possible changes in therapy
• Discontinue ZDV if given only to prevent
  perinatal transmission
• Start on combination ARV regimen or
• No ARV (if viral/immune parameters dont warrant
  therapy)

65
In Utero Exposure
66
Mitochondrial toxicity

• Affinity for mitochondrial DNA polymerase
• Depletion dysfunction
• Acute fatty liver
• Inability to oxidize fatty acids
• Genetic susceptibility to exposed infants

67
Antiretroviral Pregnancy Registry

• Collaborative project managed by PharmaResearch
  (OB/GYN, ID, teratology, epidemiology, CDC NIH)
  sponsored by
• Abbott Laboratories, Agouron Pharmaceuticals,
  Inc., Boehringer Ingelheim Company, Bristol-Myers
  Squibb, Co., Gilead Sciences, Inc.,
  GlaxoSmithKline, F. Hoffmann-LaRoche Ltd., Merck
  Co., Inc. and PharmaResearch.
• To assess safety of ARVs in pregnancy
• [phone] Fax [phone]
  http//www.apregistry.com

68
Until all pregnant women have access to therapy,
the promise of ACTG 076 cannot be realized!
69
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70
Syphilis

• Treponema Pallidum
• Readily cross placenta
• Perinatal transmission
• Primary/secondary syphilis 50
• Early latent 40
• Late latent 10
• Tertiary 10

71
Clinical Phase Transmission
Primary Chancre 2-6 wks Infectious Secondary
Bacteremia gt 6 wk Infectious Latent Exacerbations
lt 1 yr from I Infectious Late Latent gt 1
yr Transplacental infn Tertiary CVS Not by
sex CNS Gummas MSK
72

• Primary Syphilis
• 3 6 wk of infections
• Secondary Syphilis
• Disseminated d z
• 6 wk 6 mo
• Latent syphilis
• Subclinical with or without relapse

73

• Congenital Syphilis
• 1.5/100,000 in Non-hispanics whites
• Declined by 21 from 2000- 2002
• Parallel with 35 decline of incidence of
  primary syphilis

74
Cong. Syphilis

• 80 occur due to inadequate meds
• Transplacental panape as early as 6 wks
• CF not seen until 16 wks
• Intrapartum, lesion from skin lesions

75
Perinatal Pathology

• Hydrops placentalis
• Villitis (plasmacell infiltrate)
• Villous proliferation around vessels (onion skin
  vessels)
• Funisitis
• Chrono ammionitis
• Plasma cell deciduitis

76
Fetus

• Depend on stage of development
• Abnormal liver function
• Hepatomegaly
• Low platelets
• Anemia
• Ascites

77
Infant Clinical Stigma
78
Maternal Screening

• Universal screening
• First visit
• III trimester delivery in high risk population
• Any still birth

79
Therapy

• Treat all women with positive titre unless
  adequate treatment history, clearly documented
  and decline in antibody titre documented

80
Treatment

• Primary, secondary early latent (lt1yr)
• Benzathine penicillin G, 2.4 m units IM x 1
• Late latent (gt1yr)
• 3 doses at 1 wk interval
• Penicillin allergic
• Confirm allergy desensitize

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Gonorrhea

• Incidence 0.5-7
• Transmission from infected male to female 50-90
• Incubation period 3 days
• Early bacteremic phase
• Septic arthritis phase, endocervicitis

83
Perinatal Complications

• Premature Rupture of Membrane
• Preterm Labor
• Chorioamnionitis
• Neonatal conjunctivitis (3-4 d)
• Corneal ulceration, scarring, blindness

84
Prevention

• Early diagnosis I visit
• Consider alternate site sampling
• Gram stain positive 60 only
• Amplified DNA probes (PACE 2 system)
• 20-50 co-existing chlamydia
• Reculture TOC (high risk)

85
Therapy

• 10 penicillin resistent
• Ceftriaxone 125 mg IM x 1
• OR
• Cifixime 400 mg PO x 1
• Azithromycin 1 gm PO x 1
• Amoxycillin 500 mg tid x 7 days
• Prophylactic agent into newborn life
• Erythromycin 0.5

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87
Cytomegalovirus

• CMV
• Double stranded DNA virus
• Horizontal transmission via
• Infected organ or blood
• Sexual contact
• Secretions Saliva, urine, vaginal
• Vertical transmission to fetus
• Transplacental infection
• Contaminated genital tract secretion
• Breast feeding

88
CMV

• 1-4 uninfected seroconvert
• Primary Inf, 40-50 fetus affected
• 5-20 of babies symptomatic at birth
• 30 severely infected fetus die
• 80 survive with morbidity
• Ocular abnormality
• Sensory neural hearing loss
• IUGR, ? LFT, ? Platelets
• Recurrent or reactivation less likely trans. But
  long term follow-up 15 hearing loss

89
Diagnosis

• IgM or increasing 1gG titres
• Amniotic fluid PCR or culture UBS
• Umbilical blood sampling
• USG, wnl - range of anomalies
• Microcephaly
• Intra cerebral calcification
• Hydrops, IUGR, Oligo
• Heart block, echogenic bowel, anemia
• Isolated serous effusions

90
Intrapartum

• Genital tract secretions (10 ? shed virus)
• 20-60 fetus shed virus from pharynx
• Postpartum breast feeding

91
Prevention

• No vaccine or meds in pregnancy
• Education Health care, daycare, school teachers,
  young mothers
• Risk of sexual transmission
• CMV free blood products
• Universal precautions
• Antivirals

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93
HSV

• HSV 1 above waist
• HSV 2 below waist
• True only 90 time
• Sero prevalence 25
• Pregnant women 0.02-1
• Asymptomatic preg. women 0.6

94
Clinical Findings

• I episode local symptoms 2-3 wks
• 2/3 acquired asymptomatically!!
• Recurrent lesion viral shedding 3-5 d

95
Perinatal Infection

• Transplacental rare reported cases
• Current genital HSV, higher incidence
• 50 infected fetus may not have lesions
• Infn acquired from infected genital tract
• Previous antibody lesion risk 1-2
• Infected infants 50-90 mortality morbidity

96
Diagnostic Pitfalls

• 1/3 of women no typical lesions
• Pap not reliable
• Viral culture false
• Others ELISA, PCR

97
Management

• All pregnant women, history, screen
• Serial cultures not recommended
• Specimen PCR

98
Therapy

• Supportive
• Therapeutic dose antiviral for primary infection
• Prophylatic chronic suppressive dose 3-4 wks
  prior to delivery
• Acyclovir
• Valacyclovir
• Famciclovir

99
Labor Management

• Precaution to present early
• If lesion CD, if not normal
• If lesion SROM, CD may not completely prevent
  transmission
• Non-genital herpes
• Gown glove precaution
• Linen dressing till lesion encrust

100
HPV

• More than 100 types of HPV
• 1 million new cases annually
• Smoking, prolonged OCP use ? risk
• Asymptomatic dz ? risk
• 40 sexually active women HPV
• 65 infection rate, ICP 3-8 m

101
Perinatal Transmission

• Transplacental rare
• Vaginal, cervical lesions
• Postpartum newborn (nb) contact
• 151 female 74/PCR (20,34,36 wk)
• Only 4 nb were positive (Watts, et al.)
• Follow up of 11 nb ve pts
• 30 nb ve at 5 wks
• All were ve at 18 mo (Tent, et al.)
• Suggest contamination vs infection
• Routine CD not recommended
• CD for obstructive lesions

102
Medication during Pregnancy

• Trichloroacetic acid
• Cryotherapy
• Surgical excision

103
Questions?

• Cincinnati HIV/STD Prevention Training Center
  Website
• http//www.stdptc.uc.edu
• Consultation Line 1-800-459-2820
• Email std.traincenter_at_cincinnati-oh.gov

104
Thank You!
105
Reminder Get your CMEs

• After viewing this eLearning Seminar, please go
  to our website, www.stdptc.uc.edu
• Sign in, look for the title of this seminar
• Follow directions to register
• Complete the evaluation
• Print out your CEU certificate!

106
Perinatal Transmission Of Infectious Disease
Oormila P. Kovilam, M.D. University of
Cincinnati Department of Obstetrics
Gynecology Cincinnati STD/HIV Prevention Training
Center