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STIs in Pregnancy

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Title: STIs in Pregnancy


1
STIs in Pregnancy
  • Lisa M. Hollier, MD, MPH
  • University of Texas
  • Houston Medical School

2
Conflicts of Interest
  • According to ACCME policy, the speakers must
    disclose all associations with proprietary
    entities that may have a direct relationship to
    the subject matter of this lecture. They must
    also disclose any discussion of unlabeled or
    unapproved uses of products.

3
Conflicts of Interest
  • I have no such financial relationships
  • I will not discuss unlabeled or unapproved uses
    of products.

4
Educational Objectives
  • This lecture should enable you to
  • Be familiar with the epidemiology of STIs in
    pregnancy
  • Know who and how to screen for infection
  • Compare and contrast various treatment options

5
Sexually Transmitted Infections
  • STIs are a major public health challenge in the
    United States
  • CDC estimates that 19 million new infections
    occur each year, almost half of them among young
    people ages 15 to 24
  • Direct medical costs associated with STDs in the
    US are estimated at up to 14.1 billion annually

6
STI Screening
Pathogen ACOG CDC
Chlamydia Women at risk at first visit All women at first visit, 3rd trimester rescreen age lt25 other women at risk
Gonorrhea Women at risk at first visit Women at risk at first visit, 3rd trimester rescreen women at risk
Hepatitis B All women All women
Hepatitis C Women at risk Women at risk
Herpes Not recommended Insufficient info
Syphilis All women All women
7
Chlamydia
8
Chlamydia Epidemiology
9
Chlamydia in Pregnancy
  • About 10 of patients screen positive
  • Complications controversial
  • preterm delivery
  • premature rupture of membranes
  • postpartum infection

10
Chlamydia in Pregnancy
Author Gest Age N Adverse Outcome Adverse Outcome
CT pos CT neg
Martin lt 19 wks 268 33 8
Thompson Tri 1 or 2 433 14 12
Harrison Tri 1,2,3 1185 14 8
Sweet Tri 1,2,3 540 19 8
Gravett Tri 2 or 3 534 36 12
Berman lt24 wks 781 9 6
Polk 23-30 wks 803 OR 1.6, (1.01-2.50) OR 1.6, (1.01-2.50)
Andrews 24-28 wks 190 RR 2.3 (1.01-5.03) RR 2.3 (1.01-5.03)
Andrews 16-23 wks 2356 9 8
11
Chlamydia in Pregnancy
  • Neonatal infections
  • Pneumonia
  • Conjunctivitis
  • 60-70 of exposed infants become infected

12
Diagnosis
  • Non-amplified tests
  • Nucleic Acid Hybridization (NA Probe), e.g.
    Gen-Probe Pace-2
  • sensitivities ranging from 75 to 100
    specificities greater than 95
  • detects chlamydial ribosomal RNA
  • able to detect gonorrhea and chlamydia from one
    swab
  • need for large amounts of sample DNA

13
Diagnosis
  • DNA amplification assays (NAATs)
  • polymerase chain reaction (PCR)
  • ligase chain reaction (LCR)
  • transcription-mediated amplification (TMA)
  • strand displacement amplification (SDA)
  • Sensitivities with PCR and LCR 95 and 85-98
    respectively specificity approaches 100

14
Diagnosis
  • PCR testing of self-collected samples from the
    vaginal introitus yielded sensitivities/specificit
    ies similar to physician-collected samples

Ostergaard L. BMJ 1996313(7066)1186-9
15
Treatment
  • Recommended regimens
  • Azithromycin 1 gm single dose
  • or
  • Amoxicillin 500mg po TID x 7 days

16
Treatment
  • Alternative regimens
  • Erythromycin base 500 mg qid for 7d
  • Erythromycin base 250 mg qid for 14d
  • Erythromycin ethylsuccinate 800 mg qid for 7 days
  • Erythromycin ethylsuccinate 800 mg qid for 14
    days

17
Test of Cure
  • Recommended for all pregnant women
  • Repeat testing (preferably by NAAT) 3 weeks after
    completion of therapy to ensure therapeutic cure
  • Important sequelae might occur in the mother and
    neonate if the infection persists

18
Partner Mgmt
  • Instruct patients to refer their sex partners for
    evaluation, testing, and treatment
  • Most recent partner
  • Any partner within last 60 days
  • If partner evaluation/treatment unlikely
  • Consider delivery of antibiotic therapy by
    patients to their partner
  • Limited studies demonstrate trend toward a
    decrease in persistent or recurrent chlamydia

19
Infant Treatment
  • Infants born to mothers who have untreated
    Chlamydial infection
  • high risk for infection
  • prophylatic antibiotic treatment is not indicated
  • infants should be monitored to ensure appropriate
    treatment if symptoms develop

20
Controversies
  • When to screen
  • Who to screen

21
Gonorrhea
22
Gonorrhea Epidemiology
23
Gonorrhea in Pregnancy
  • Complications more common in women with infection
  • septic spontaneous ab postabortal infection
  • preterm delivery
  • premature rupture of membranes
  • chorioamnionitis
  • postpartum infection

24
Gonorrhea in Pregnancy
  • Neonatal infections
  • ophthalmia neonatorum
  • scalp abscess
  • disseminated disease

25
Disseminated Infection
  • Gonococcal bacteremia
  • may lead to petechial or pustular skin lesions,
    arthralgias, septic arthritis, or tenosynovitis
  • Pregnant women may account for disproportionate
    number of cases
  • may include fatal endocarditis

26
Diagnosis
  • Non-amplified DNA probe tests
  • Nucleic acid amplification tests
  • PCR, TMA
  • High false positive rate for Amplicor
    PCRconsider repeating positive tests with
    different assay
  • If culture is done use dacron or rayon swab with
    modified Thayer-Martin media

27
Diagnosis
  • Use of NAAT for rectal and oropharyngeal
    specimens is being evaluated
  • Traditional culture may be used in these
    situations

28
Treatment
  • Recommended regimens
  • Ceftriaxone 125mg IM
  • or
  • Cefixime 400mg po
  • Alternative regimen
  • Spectinomycin 2gm IM

29
Syphilis
30
Syphilis
  • Rates in US fell until 2000 lt 8,000 cases
  • Cases are rising in men over the last 3 years
  • Incidence highly concentrated
  • Half of all US cases in 22 cities and counties
  • mostly in the South, among poor blacks and
    Hispanics

31
Syphilis
  • Total rate of primary and secondary syphilis
    3.8 per 100,000 population
  • Congenital syphilis 10.5 per 100,000 live births

32
Syphilis in Pregnancy
  • Complications
  • spontaneous abortion
  • preterm birth
  • fetal death
  • congenital infection by transplacental or
    perinatal transmission

33
Primary Syphilis
34
Secondary syphilis
  • Rash is usually symmetric and dry
  • Flaky nodular lesions are most common

Source Tania Lee, MD
35
Secondary Syphilis
Condylomata Lata Smooth, raised areas that are
teaming with spirochetes
Source Tania Lee, MD
36
Diagnosis
  • Screening with nonspecific test
  • Rapid plasma reagin (RPR)
  • Venereal Disease Research Laboratory (VDRL)
  • Automated Reagin Tests
  • Generally quantitative
  • Very sensitive

37
Diagnosis
  • Confirmation with a Treponemal specific test
  • Fluorescent treponemal antibody absorbed
    (FTA-ABS)
  • Treponema pallidum particle agglutination test
    (TP-PA)

38
Treatment
  • Obtain treatment history from health department
  • Benzathine Penicillin G 2.4 million units IM
  • One injection for primary syphilis
  • One or two injections for secondary and early
    latent
  • Three injections one week apart for late latent
    or unknown duration
  • Desensitize if PCN-allergic

39
Efficacy of Syphilotherapy by Stage
40
Treatment
  • Because of reports of treatment failure with
    azithromycin, penicillin is the preferred
    therapy.
  • 2-gram dose of azithromycin may be considered for
    penicillin-allergic patients, but only with close
    follow-up because treatment efficacy is not well
    documented and has not been studied in persons
    with HIV infection

41
Treatment
  • Some experts recommend ultrasound prior to
    syphilotherapy in pregnancy

CDC. Sexually Transmitted Diseases Treatment
Guidelines. MMWR 200655(No. RR-11)
42
Congenital Syphilis
43
Congenital Syphilis
  • Ultrasound findings
  • Hepatomegaly
  • Polyhydramnios
  • Placentomegaly
  • Ascites
  • Hydrops

44
Follow-up
  • Notify health department of treatment
  • Serofast
  • RPR each trimester
  • Primary or Secondary
  • At least every trimester (?monthly)
  • Latent syphilis
  • At least every trimester

45
Controversies
  • Testing with EIA
  • Penicillin allergy testing
  • Use of MCA doppler for fetal assessment

46
Hepatitis B
47
Hepatitis B
  • 350 million chronically infected patients
    worldwide
  • Perinatal transmission accounts for 35-50 of
    hepatitis B carriers
  • 70-90 of infants born to positive women will be
    chronically infected
  • Risk of perinatal transmission closely related to
    HBeAg status

48
Hepatitis B in Pregnancy
  • Approximately 25 of the frequent sexual contacts
    of infected individuals will themselves become
    infected
  • Serologic testing and possible vaccination of
    sexual partner and household contacts should be
    discussed

49
Hepatitis B in Pregnancy
  • Serologic testing
  • HepBsAg positive
  • Confirm chronic infection
  • Presence of Heb B core IgG
  • Absence of Hep B core IgM
  • Liver function tests
  • HIV
  • HepBeAg, if available

50
Hepatitis B in Pregnancy
  • Risk of hepatitis B infection through
    amniocentesis is low
  • Knowledge of hepatitis Be antigen status may be
    valuable in counseling about risks

51
Hepatitis B in Pregnancy
  • Referral to a physician experienced in the
    management of chronic liver disease
  • opportunity to receive appropriate subspecialty
    care for counseling and targeted treatment,
    usually after delivery
  • All HBsAg-positive results should be reported to
    state or local health department

52
Management
  • Limit use of invasive monitors
  • Infants of all Hepatitis B s Ag positive patients
    should receive
  • Immune globulin (HBIG)
  • Vaccination for Hep B
  • Vertical transmission rates are very low with
    immunoprophylaxis

53
Management
  • Breast feeding does not appear to increase the
    risk of transmission of Hepatitis B to infants
  • 0/101 (0) breast fed and 9/268 (3) formula fed

54
Prevention of Hep B
  • Pregnant women at risk for HBV infection during
    pregnancy should be vaccinated
  • having more than one sex partner during the
    previous 6 months
  • evaluated or treated for STD
  • recent or current injection-drug use,
  • HBsAg-positive sex partner

55
Hepatitis C
56
Hepatitis C
  • Routine screening of pregnant women not
    recommended
  • Risk factors
  • IVDA
  • blood transfusion or solid organ transplant
    before 7/92
  • received clotting factor concentrates before 1987
  • long-term dialysis
  • signs and symptoms of liver disease
  • HIV positive

57
Hepatitis C in Pregnancy
  • Transmission increased in women who are HCV-RNA
    positive at delivery
  • Average rate of infection 6
  • Higher (17) with HIV co-infection
  • Role of viral titer unclear
  • No association with delivery method or
    breastfeeding
  • Infected infants do well
  • Severe hepatitis is rare

58
HCV Testing for Diagnosis of Asymptomatic Persons
STOP
Negative
Screening Test for Anti-HCV
Positive
OR
Negative
NAT for HCV RNA
RIBA for Anti-HCV
Negative
Positive
Indeterminate
Positive
STOP
Additional Laboratory Evaluation (e.g. PCR, ALT)
Medical Evaluation
Negative PCR, Normal ALT
Positive PCR, Abnormal ALT
MMWR 199847 (No. RR 19)
59
Genital Herpes
60
HSV-2 Epidemiology
Level II-c
61
HSV Epidemiology
  • Approximately 17-30 of the US population is
    infected with herpes simplex type 2
  • 15-50 of genital infection is HSV-1
  • HSV-2 is virtually exclusively a genital pathogen

62
Acquisition of Herpes in Pregnancy
  • 2 become seropositive during pregnancy
  • About 1/3 are symptomatic
  • About 1/3 in each trimester
  • Risk of HSV 2 acquisition among susceptible women
    is higher

Level II-b
Brown ZA et al. NEJM 1997337(8)509-15 Gardella
C et al. AJOG 2005193(6)1891-9
63
Herpes in Pregnancy
  • Complications

64
Transmission
  • Rate of transmission depends on clinical
    characteristics of maternal disease
  • Symptomatic first episode 50
  • Asymptomatic first episode 33
  • Symptomatic recurrent 3
  • Asymptomatic recurrent 0.02

65
Patient with genital ulceration or suspicious
lesion
Viral Detection Technique
positive
negative
Infection NOT ruled out
Genital Herpes infection

Serologic Screening
negative
Positive for HSV-2
Genital Herpes infection
Repeat Screening in 6-8 weeks
66
Diagnosis
  • Viral Identification Techniques
  • Culture
  • Direct Fluorescent Antibody tests
  • Polymerase chain reaction
  • Detection of Antibody
  • Laboratory based assays
  • Point of care testing

67
Diagnosis
  • Viral Culture
  • Virus grown in tissue culture
  • Can be differentiated by type
  • Sensitivity limited by duration of viral shedding
  • Negative results do not rule out herpes

68
Diagnosis
  • Polymerase Chain Reaction (PCR)
  • Increased sensitivity because only small amounts
    of DNA are necessary
  • Viral typing is possible

69
Diagnosis
  • Serology
  • Many commercially available tests limited by lack
    of specificity for viral types
  • Useful if completely negative
  • Testing is available to identify type-specific
    antibodies
  • type specific must include detection of
    antibodies to glycoproteins gG-1 and gG-2

70
Serologic Tests
  • IgM testing is not clinically useful
  • IgM is absent in some primary infections
  • IgM is detected with recurrent infections

71
Serologic Tests
Tests Sensitivity Sensitivity Specificity Specificity
Tests HSV-1 HSV-2 HSV-1 HSV-2
HerpeSelect? gG-1 or gG-2 91-96 96-100 92-95 96-97
HerpeSelect? Immunoblot 99-100 97-100 93-95 94-98
Captia ELISA 90-100 90-100 90-99 90-99
72
Point of Care Tests
  • Membrane-based immunoassay for the qualitative
    determination of circulating IgG antibodies
    specific for herpes simplex virus type 2 (HSV-2)
  • Results available in 10 minutes

73
Rapid Serologic Tests
Tests Sensitivity Sensitivity Specificity Specificity
Tests HSV-1 HSV-2 HSV-1 HSV-2
Sure-Vue HSV-2 93-96 98
biokit HSV-2 Rapid test 93-96 98
Level II-c
74
Prophylaxis and Treatmentin Pregnancy
  • Women with symptomatic outbreaks can be treated
  • Can offer suppression to women with history of
    HSV and initial outbreaks of HSV

75
Treatment of Initial Episodes
Acyclovir Famcyclovir Valacyclovir
400 mg TID for 7-10 days 250 mg TID for 7-10 days 1 gram BID for 7-10 days
200 mg 5x/day for 7-10 days
CDC. Sexually Transmitted Diseases Treatment
Guidelines. MMWR 200655(No. RR-11)
76
Treatment of Recurrent Episodes
Acyclovir Famcyclovir Valacyclovir
400 mg TID for 5 days 125 mg BID for 5 days 500 mg BID for 3-5 days
200 mg 5x/day for 5 days (1 gm BID for 1 day) 1 gram once daily for 5 days
800 mg BID for 5 days (800 mg TID for 2 days)
CDC. Sexually Transmitted Diseases Treatment
Guidelines. MMWR 200655(No. RR-11)
77
Anti-viral Suppression in Pregnancy
Acyclovir Famcyclovir Valacyclovir
400 mg TID from 36 weeks until delivery 500 mg BID from 36 weeks until delivery
78
Suppression in Pregnancy
Recurrence at delivery
79
Suppression in Pregnancy
Cesarean delivery
80
Current ACOG Recommendations
  • Trial of labor is indicated in the absence of
    prodromal symptoms or a lesion
  • In the presence of active lesions or prodrome,
    Cesarean should be performed regardless of the
    duration of membrane rupture

Level III
81
Route of Delivery
  • Cesarean delivery should be considered for women
    with true primary infection with HSV, even in the
    absence of lesions

82
Controversies
  • Screening

83
Thank you
84
Obstetric Screening
Strategy Incidence of NH Cases averted per case averted per QALY gained
Screen/rx s 1456 640 194,837 18,680
Screen 1132 240 375,000
Screen/rx s 731 376 1,765,852 155,988
Screen/rx partner 1311 1071 363,000
Level III
Baker et al AJOG 2004 Rouse et al AJOG 2000
Thung et al AJOG 2005 Barnabas et al Sex Transm
Infect 2002
85
Conclusions
  • No clinical evidence to support routine screening
    of the obstetrical population

86
Clinical Scenarios
  • Viral -, serology - truly negative possible
    false negative, repeat serology in 6-12 weeks
  • Virus HSV1, serology - primary genital HSV1
  • Virus HSV2, serology - primary genital HSV2
  • Virus HSV1, serology HSV1 recurrent genital
    HSV1

87
Clinical Scenarios
  • Virus HSV2, serology HSV2 recurrent genital
    HSV2
  • Virus HSV2, serology HSV1, HSV2 - nonprimary
    genital HSV2
  • Virus -, serology HSV1 UNCERTAIN, counsel
    regarding symptoms, repeat serology in 6-12 weeks
  • Virus -, serology HSV2 recurrent genital HSV2,
    ?false positive, consider repeat testing with
    another serologic test
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