STIs in pregnancy

Ameeta Singh, BMBS(UK), MSc, FRCPC

ameeta@ualberta.ca

Early ID AHD

November 19, 2024

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Objectives

• To provide an approach to the diagnosis, management and follow up of syphilis, gonorrhea, chlamydia and HSV in non pregnant and pregnant women

Case # 1

• 21 year old woman, pregnant 26 weeks gestation
• Syphilis EIA positive, RPR NR
• Married x 1 year, 2 SPs prior to husband
• Canadian born, was on “mission to Jamaica”
• “likes” Percocet and Tramacet

Case # 1: Discussion

• What is going on here?
• Any additional questions?
• Any additional information required

Case # 1: Discussion responses

• What is going on here?
• Any additional questions?
• ? Any symptoms

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• Any additional information required
• WHAT IS TPPA RESULT?
• REPEAT EIA/RPR/TPPA
• Husband’s test results

Case # 1 cont’

Case # 2

• 35 year old woman
• Routine prenatal screen at 10 weeks:
• Syphilis EIA positive, RPR R 64 dilutions, TPPA reactive, HIV negative
• I am told no symptoms or signs of syphilis
• Comes into clinic with 8 month old baby
• Baby “sick” diagnosed with JMML at 3 months of age (hepatosplenomegaly, anemia, rash)
• Syphilis screen 1^st trimester of last pregnancy negative

Case # 2: Mother

• ? Stage
• Review of sexual history
• New sexual partner in last 2 months of previous pregnancy

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• Examination of mother

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Case # 2: Mother

Syphilis staging: importance of detailed physical examination

Secondary syphilis: rash common but variable presentation

Rash classically involves palms/soles

Secondary syphilis

• Concurrent symptoms – fever, malaise not uncommon
• Neurologic (including eye and ear involvement can occur during this stage)

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Syphilis - Latent stage

15-40% of untreated patients develop tertiary syphilis

• Neurosyphilis – most common tertiary stage

Cardiovascular

Gumma

Cooper R, IDSA, 2004: Review of tertiary syphilis in

Alberta 1974-2004: 77 cases-

96% neurosyphilis, 4% CV

Case # 2: 8 month old baby

• Diagnosed with JMML at 3 months (hepato-splenomegaly, rash, anemia)
• Sent to Stollery: RPR R 4096 dils
• Treated with 10 days of iv penicillin

Case # 2: what about follow up of current fetus?

Impact of congenital syphilis

• Risk of transmission of syphilis in pregnancy:
• 70-100% with primary
• 40% with early latent syphilis
• 10% for late latent syphilis

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• Transmission can occur as early as 9 weeks but risk of transmission increases with increasing gestational age – highest risk in last 4 weeks of pregnancy

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• Risk of HIV transmission(No treatment or C-section) = ~25% and hepatitis B ~ 33%

Overview of management of pregnant woman and infant

• < 20 weeks gestation with infectious syphilis
• Treat with 2 doses of Bicillin
• Usual serologic follow up plus at delivery
• Extremely low/negligible risk of transmission to infant – clinical assessment at birth

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ARE 2 DOSES NECESSARY DURING PREGNANCY?

“Certain evidence indicates that additional therapy is beneficial for pregnant

women to prevent congenital syphilis. For women who have primary,

secondary, or early latent syphilis, a second dose of benzathine penicillin

G 2.4 million units IM can be administered 1 week after the initial dose”

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https://www.cdc.gov/std/treatment-guidelines/syphilis-pregnancy.htm

Overview of management of pregnant woman and infant [previous recommendations]

• > 20 weeks gestation with infectious syphilis
• Detailed perinatal ultrasound
• Increased risk of Jarisch-Herxheimer reaction especially if fetal abnormalities – may precipitate labour
• Consider hospitalization for fetal monitoring and treatment
• ? Iv penicillin if fetal abnormalities
• Newborn needs detailed assessment at birth +/- treatment –dependent on time of maternal treatment – increased risk of congenital syphilis if Rx in last 4 weeks of pregnancy

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N=39 women

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2 mild J-H reactions (5.1%);

• no intervention required and no immediate maternal or fetal adverse events

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63% of infants required NICU care and 31% had probable or confirmed congenital syphilis

• preterm birth rate of 17% and a stillbirth rate of 5%, both markedly higher than local background risk of 8.1% and 0.7% respectively

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Our study does not support the routine practice of admission for the treatment of infectious syphilis in late pregnancy.

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BUT small study which may have precluded the ability to determine if a subset of women are at risk for more serious complications

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Similar to findings in recent Manitoba study (Dhaliwal, 2022)

Revised recommendations for the management of infectious syphilis in pregnancy > 20 weeks gestation

• Low risk of Jarisch-Herxheimer [J-H] reaction which can cause premature onset of labour
• New Alberta and Manitoba STI guidelines now recommend proceeding with treatment and advise woman to seek urgent medical care if sustained contractions
• Detailed perinatal ultrasound and referral to OBGYN also recommended
• Infant should be assessed at birth in consultation with Pediatric Infectious Diseases

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Government of Alberta. Alberta Treatment Guidelines for STIs, 2018 https://open.alberta.ca/dataset/93a97f17-5210-487d-a9ae-a074c66ad678/resource/bc78159b-9cc4-454e-8dcd-cc85e0fcc435/download/sti-treatment-guidelines-alberta-2018.pdf

Manitoba Communicable Disease Management Protocol: Syphilis, 2023. https://www.gov.mb.ca/health/publichealth/cdc/protocol/syphilis.pdf

Serologic follow up of the infant

• Maternal antibody transfer:
• Infant RPR titres will decline by three months of age and be nonreactive by six months of age in the absence of congenital syphilis
• Treponemal test results, such as EIA usually revert to non-reactive by 12 months of age and always by 18 months of age
• Persistently positive treponemal tests at 18 months = congenital syphilis

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Case # 3

• 30 year old black woman
• Immigrant from Somalia to Canada in 2000
• Immigration medical exam (Nairobi) negative syphilis in 2000
• Prenatal screen at 12 weeks:
• Syphilis EIA positive, RPR NR, syphilis TPPA reactive, HIV negative

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Case # 3: Discussion points

What is diagnosis?

What is management?

Case #3 cont

• Repeat syphilis serology 1 month later: unchanged
• Husband negative syphilis EIA
• Diagnosis: late latent syphilis or non venereal trepanematosis
• Management of mother: Bicillin weekly x 3 doses, no serologic follow up as baseline RPR NR
• Management of infant: no follow up required; if wish to ensure clearance of passively transferred antibodies, then syphilis serology at birth, > 6 months and if not all negative then again at 15-18 months
• Consider testing other children

Alternates to penicillin for the treatment of syphilis in pregnancy

Pregnant

• There is no good alternate to penicillin; attempt oral desensitization
• Needs admission; fetal monitoring

Expected serologic decline in RPR

No follow up blood tests required if RPR non reactive at baseline or if low titre in late stage syphilis

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Treponemal tests (EIA and TPPA) usually remain reactive for life

Case # 4

• 31 year old female, married for 2 years
• First episode of painful sores in the genital area x 48 hours, dysuria, tender left sided inguinal lymphadenopathy, no other symptoms
• 3 male lifetime partners before husband

Case #4: Discussion points

• Has her husband been cheating on her?
• Has she had a relationship outside of her marriage?
• Did she get it from a toilet seat?
• What is her risk of recurrent infection?
• What is her risk of transmitting HSV to future babies?
• Should she and her husband use condoms?

HSV Epidemiology

• Approximately 20% of the US population has HSV-2 infection - 30% increase since

the 1970s

• In a BC study, age-adjusted seroprevalence of HSV-2 in pregnant women was 17.3%
• In Alberta, seroprevalence in patients who attended two STI clinics was:

- HSV-1: 56%

- HSV-2: 19%

Corey L, Handsfield HH. JAMA 2000;283(6):791-794

Fleming DT, et al. N Engl J Med 1997;337(16):1105-1111

Patrick DM, et al. Sex Transm Dis 2001;28(7):424-428

Singh A, et al. Sex Transm Dis 2005

Transmission of HSV During Asymptomatic Viral Shedding

Mertz GJ, et al. Ann Intern Med 1992;116(3):197-202

ASYMPTOMATIC VIRAL

SHEDDING IS THE

MAIN METHOD OF

TRANSMISSION

- higher with HSV 2

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Tip of the Iceberg

9.2%

90.8%

Unrecognized�or asymptomatic

infection

Recognized

infection

Iceberg represents persons

with HSV-2 antibody

Fleming DT, et al. N Engl J Med 1997;337(16):1105-1111

Wald A, et al. N Engl J Med 2000;342(12):844-850

Current criteria for HSV Serology in Alberta

• Pregnant women with first episode of genital herpes
• Discordant couple when male has history of GH and woman has no history and pregnancy is planned
• Discordant couple when one partner has known history of GH
• Confirming diagnosis of GH when other tests negative
• Atypical presentations of mucosal lesions when other diagnoses have been ruled out

Provincial Lab for Public Health (Alberta), 2005

Interpretation of HSV Type specific serology

1 - / 2 - 1 + / 2 - 1 - / 2 + 1 + / 2 +��

�Non infected but repeat GH cannot be excluded GH confirmed GH & labial herpes the test if recent contact but less probable if �(< 8-12 sem) history of labial herpes�

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Results of Type specific serology

GENITAL HERPES�Management

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• Counselling
• Discuss antiviral therapy
• Shortens duration and severity of infection or reduces frequency of outbreaks
• Suppressive therapy (taken continuously) reduces viral shedding and therefore transmission
• NOT curative

GENITAL HERPES�Counselling

Explain natural history

• potential for recurrences
• asymptomatic shedding
• sexual transmission

Advise abstinence from sex while lesions present

• inform sex partner(s) that they have GH
• use condoms (↓ risk of transmission by 50%)

Discuss risk of neonatal infection

GH increases risk of HIV two fold

NEONATAL HERPES 1

• Intrauterine infection is rare
• Neonatal herpes most often acquired during delivery
• Mortality rate of 70% if untreated
• Transmission increased with invasive procedures

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NEONATAL HERPES 2

• RISK OF TRANSMISSION:
• maternal 1° infection : 30 - 50%
• maternal recurrent infection : 3%
• Most cases (70%) of children with neonatal herpes are born to women with no history of genital herpes

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Herpes: Treatment in pregnancy

Suppressive therapy in pregnancy

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• Acyclovir 200 mg qid OR 400 mg tid
• Valacyclovir 500 mg po BID
• All regimens require initiation of at 36 weeks, until delivery

Case #4: Discussion points

• Has her husband been cheating on her?
• Has she had a relationship outside of her marriage?
• Did she get it from a toilet seat?
• What is her risk of recurrent infection?
• What is her risk of transmitting HSV to future babies?
• Should she and her husband use condoms?

Case 5

• 33 year old female
• Pregnant, 14 weeks gestation

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Urine test positive for gonorrhea negative for chlamydia

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Case 5: Management

Case 5: Follow up

Case 5: Follow up of mother and infant

Mother [positive GC at delivery] :

• Re-treat with cefixime 800 mg po SD plus azi 1 gm po SD
• Review treatment of partners
• Notification – presumed re-infection

Infant:

• Treat with Ceftriaxone 50 mg/kg IM up to 250 mg IM SD

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Case 5: Follow up

Manifestations of gonorrhea in neonates

Ocular prophylaxis in neonates: controversial

• CDC: Neonatal ocular prophylaxis with erythromycin, the only agent available in the United States, is required by law in most states and is recommended because of safety, low cost, and ease of administration. It can contribute to preventing gonococcal blindness because not all pregnant women are screened for gonorrhea. The USPSTF recommends ocular prophylaxis with erythromycin ointment for all newborns <24 hours after birth.
• In addition to continuing routine ocular prophylaxis, prevention should focus on prenatal screening for N. gonorrhoeae

https://www.cdc.gov/std/treatment-guidelines/gonorrhea-neonates.htm

Canadian Pediatric Society statement on ocular prophylaxis, 2015

https://cps.ca/en/documents/position/ophthalmia-neonatorum

Case 5: Follow up of mother

Mother (positive chlamydia at delivery):

• Re-treat azithromycin 1 gm po SD
• Review treatment of partners
• Notification – presumed re-infection

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Manifestations of chlamydia in neonates

• Initial C. trachomatis neonatal infection involves the mucous membranes of the eye, oropharynx, urogenital tract, and rectum, although infection might be asymptomatic in these locations
• C. trachomatis infection among neonates is most frequently recognized by conjunctivitis that develops 5–12 days after birth.
• C. trachomatis also can cause a subacute, afebrile pneumonia with onset at ages 1–3 months. 

Case 5: Follow up of infant (mother positive for chlamydia at delivery)

• Topical therapy alone for conjunctivitis is NOT adequate and is unnecessary when systemic treatment is used
• Neonates born to infected mothers need to be tested for C. trachomatis. Neonates should be treated if their test results are positive. They should be closely monitored for signs of chlamydial infection (e.g., conjunctivitis, pneumonitis).Prophylaxis is not recommended unless follow-up cannot be guaranteed.
• If treated, should be treated with oral erythromycin (or azithromycin in consultation with Pediatric ID; the use of erythromycin in infants under 6 weeks of age has been associated with infantile hypertrophic pyloric stenosis (IHPS).
• Test of cure should be performed 3-4 weeks after the completion of treatment in all prepubertal children.

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References

• Holmes KK et al. Sexually Transmitted Diseases, 3rd Ed. New York, McGraw-Hill, 1998

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• Canadian Guidelines on Sexually Transmitted Infections: https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines.html

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• Alberta STI Treatment Guidelines, https://open.alberta.ca/publications/treatment-guidelines-for-sti-2018

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• CDC STI Treatment Guidelines, 2021. https://www.cdc.gov/std/treatment-guidelines/default.htm

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