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08b Sexually Transmitted Diseases in Pregnancy OBSTETRICS


Diana Bolisay-Bongala, MD, MSPH, FPOGS LE 3
26 November 2020 (Thu) TRANS 8b

OUTLINE Fluorescent Treponemal Antibody


FTA-ABS
Absorption
I. Overview 1 VI. Human Papillomavirus
II. Syphilis 2 (HPV) 8 HAART Highly Active Antiretroviral Therapy
A. Epidemiology 2 A. HPV Vaccination 8 HIV Human Immunodeficiency Virus
B. Etiopathogenesis 2 B. Management 8
C. Pregnancy Outcome 2 C. Neonatal Infection 8 HPV Human Papillomavirus
D. Stages 3 VII. Vaginitis: Bacterial HSV Herpes Simplex Virus
E. Diagnosis 3 Vaginosis 8
F. Treatment 4 A. Pregnancy Outcomes 9 Microhemagglutination Assay For
MHA-TP
III. Gonorrhea 4 B. Treatment of BV in Antibodies to T. pallidum
A. Screening and Pregnancy 9 NAAT Nucleic Acid AmplificationTest
Diagnosis 5 VIII. Vaginitis: Trichomoniasis 9
B. Treatment 5 A. Diagnosis 9 PCN Penicillin
IV. Chlamydia 5 B. Management 9 RPR Rapid Plasma Reagin
A. Pregnancy Outcome 5 C. Neonatal Outcomes 9
B. Screening IX. Vaginitis: Candidiasis 9 Treponema pallidum Passive Particle
TP-PA
Recommendations 5 X. Human Immunodeficiency Agglutination
C. Screening and Virus (HIV) 9 USG Ultrasound
Diagnosis 5 A. Statistics 10
D. Treatment 5 B. Transmission 10 VDRL Venereal Disease Research Laboratory
E. Screening after C. Clinical Manifestations 10
I. OVERVIEW
Treatment 6 D. HIV & AIDS 10
F. Lymphogranuloma E. HIV & Pregnancy 11 ● Because of the location of these infections, it has a propensity to
Venereum 6 F. HIV & Neonates 11 affect the pregnancy and it also has the ability to produce
V. Herpes Simplex Virus 6 G. Screening 11 congenital defects in some instances. ☊
A. Adult HSV Disease 6 H. Management 11 ● Ideally, a healthy pregnancy starts even before pregnancy. If
B. Genital Herpes Simplex XI. Conclusion 12 you are thinking of conceiving, wellness preparation for pregnancy
Virus 6 References 13 will include testing for sexually transmitted infections like HIV,
C. Manifestation 6 Review Questions 13 syphilis, HPV, and hepatitis B. ☊
D. Neonatal Transmission 6 Summary 14
E. Clinical Manifestation 6 Appendix 17 Sexually Transmitted Infections
F. HSV And Pregnancy 7 ● Syphilis
G. Screening and ○ Gonorrhea
Diagnosis 7 ○ Chlamydia
H. Treatment 7 ○ Herpes simplex virus
○ Hepatitis B
■ Sexually transmitted; may be prevented by vaccination
LEGEND
○ Human papillomavirus (HPV)
Important Recording Book/Article Previous Trans
■ May be prevented by vaccination
☜ ☊ (Author (ed), pp.) (Year & Section)
○ Vaginitis
■ Bacterial vaginosis
Lecture Objectives ■ Candidiasis
At the end of the lecture, the student should be able to: ■ Trichomoniasis
1. Diagnose the different types of STI based on history and PE ○ Human immunodeficiency virus (HIV)
2. Screen for and diagnose STDs using appropriate laboratory
Concerns of STI in Pregnancy
tests
3. Interpret screening tests and request appropriate confirmatory ● Vertical transmission from the mother to her fetus of an infectious
tests agent through the placenta during labor, delivery, or
4. Correctly manage STIs during pregnancy breastfeeding
5. Counsel pregnant women and their partners regarding effect of ● Treatment of most STDs associated with improved pregnancy
STIs on their fetus outcome and prevention of perinatal morbidity
6. Educate patients on prevention through avoidance of risky ● Essential components of prenatal care:
behaviors ○ Education
○ Prevention
WORD BANK ○ Screening
○ Treatment
Word/Abbreviation Meaning
ART Antiretroviral Therapy
BV Bacterial Vaginosis
EPT Expedited Partner Treatment

TRANS (14) Macariola, Magalong, Magbuhat (2022B) CORE Landig, Lee (2022B)
Magno Gaspar 1 of 18
3.08b Sexually Transmitted Diseases in Pregnancy
II. SYPHILIS ■ Identifying the basic ethical principles that should underlie
the conduct of biomedical and behavioral research involving
A. EPIDEMIOLOGY human subjects
● Syphilis is a very old disease, it has been there since the time of ■ Developing guidelines to assure that such research is
Christ and during the Romans as well. In the ruins of Rome, there conducted in accordance with those principles
● From 1932, it took 40 years for the study to be completed and after
were places where patients with syphilis were confined. ☊
which the Commission was created ☊
● Published by the Commission after 4 years of monthly discussions
● Considered as one of the leading works concerning ethics and
health care research
● Three Principles:
○ Beneficence
○ Justice
○ Respect for persons
B. ETIOPATHOGENESIS
● Causative agent: Treponema pallidum spirochete ☜
● Portal of entry: abrasions on vaginal mucosa ☜
● Cervical eversion
○ Columnar epithelium is more exposed compared to the
Figure 1. Syphilis prevalence among key populations in selected cities in the
Philippines (2015) squamous epithelium ☊
● Among the selected population, yellow represents men and ○ Increases the probability of having syphilis infection ☊
transexual men (M/TSM), green are freelance female sexual ○ Cervix appears hyperemic and friabie
workers (FSWs), blue are persons with disabilities who are still ● Incubation period
affected with syphilis, pink are transgender women and gray are ○ Averages 3 weeks
men who have exclusive sex with women (MEWs) who are the ○ Ranges from 3 - 90 days after the last sexual contact
least vulnerable population. Even if they do not consult, M/TSM are ● Vertical transmission
the ones with the highest risk in a lot of cities and also the FSWs in ○ Maternal syphilis can cause fetal infection through:
Cebu. ☊
■ Transplacental route (most common) ☜
■ Contact with spirochetes through lesions during delivery or
● From 2001-2015, the primary and secondary syphilis rates have
across the placental membranes
risen almost yearly (CDC Prevention, 2016c)
○ Fetal infection develops in: (Fiumara, 1975; Hollier, 2001)
○ Combined rate for both of these among women in the US
(2015) was 1.8 cases per 100,000 persons (de Voux, 2017)
■ Untreated early syphilis: >50% ☜
■ Late latent disease: 10%
● Congenital Syphilis
○ After 2012, has risen yearly to reach 12.4 cases per 100,000
live births in 2015
○ Higher congenital syphilis rates are linked to: (Su, 2016)
■ Inadequate prenatal care
■ Black or Hispanic race
■ Lack of treatment
○ Many countries reporting high numbers of new infections (Newman,
2015; WHO, 2012)

Tuskegee Trial (1932)


● “Tuskegee Study of Untreated Syphilis in the Negro Male”
● The reason why we have a lot of information about syphilis and its
different stages ☊ Figure 2. Dark field immunofluorescence of Treponema pallidum
● An unethical study which involved studies of 300+ males with
C. PREGNANCY OUTCOME
syphilis and 201 males without syphilis ☊
● The males did not have any consent, they did not know that they ● Antepartum syphilis can cause preterm labor, fetal death, and
were not being given any medications, and their disease was neonatal infection
allowed to progress despite the availability of Penicillin at that time ● Any stage may result in fetal infection ☜
☊ ○ Rate is much lower for the late disease ☊
● Belmont Report was then created because of this unethical study ● Risk related to maternal spirochete load
☊ D. STAGES
● Basis of some of the most important ethical principles for research
● Early stages of syphilis

○ Divided into primary, secondary, and early latent
● In 1997, President Clinton issues an apology to the people who
○ Associated with high spirochete loads, and partner
were involved in the study
transmission rates from 30-60% (Garnett, 1997; Singh, 1999)
Belmont Report ● Late-stage disease
● Written by the National Commission for the Protection of ○ Transmission rates decline because of smaller inoculum
Human Subjects of Biomedical and Behavioral Research sizes
○ Created as a result of the National Research Act of 1974 Primary Syphilis
○ Tasked with:
● Diagnosed by its chancre which develops at inoculation site
○ A chancre will usually resolve spontaneously in 2 to 8 weeks,
even if untreated

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3.08b Sexually Transmitted Diseases in Pregnancy
● Solitary, painless lesion with a raised, firm border and a red, ○ Anemia with thrombocytopenia
smooth ulcerated base without significant pus ○ Ascites
● Non-suppurative lymphadenopathy may develop ○ Hydrops
● Multiple lesions, if found, are predominantly in HIV-1 co-infected ■ Congenital syphilis is one of the more frequent causes of
women hydrops fetalis ☊
○ Jaundice with petechiae or purpuric skin lesions
○ Rhinitis
○ Pneumonia
○ Myocarditis
○ Lymphadenopathy
○ Nephrosis
○ Long-bone involvement
■ Manifest as moth-eaten appearance of femur on radiography
Placenta of Patients with Syphilis
Figure 3. Primary syphilis. Tongue lesion (left); Vaginal chancre (right)
● Upon examination, placenta may appear grossly large and pale
Secondary Syphilis which have lost their characteristic arborization and the villi
● From dissemination of spirochetes to affect multiple organ systems have become thicker and clubbed
● Manifests 4-10 weeks after the chancre appears ☜ ● Sheffield and colleagues (2002c) described these villi in more than
● Manifests as dermatological abnormalities in up to 90% of women 60% of syphilitic placentas:
○ Diffuse macular rash ○ Blood vessels markedly diminished in number
○ Plantar and palmar target-like lesions ○ In advanced cases, almost entirely disappear as a result of
○ Patchy alopecia endarteritis and stromal cell proliferation.
○ Mucous patches ● Lucas and coworkers (1991):
● Condylomata lata ○ Demonstrated increased vascular resistance in uterine and
○ Characteristic lesions seen in secondary syphilis ☜ umbilical arteries of infected pregnancies
○ Flesh-colored papules and nodules found on perineum and ○ Umbilical arteries on USG and on delivery
perianal area ● Schwartz and associates (1995):
○ Biopsy of these lesions will show spirochetes and are highly ○ Reported that necrotizing funisitis is present in 30% of 25
infectious untreated women
● Other conditions which may develop in secondary syphilis include: E. DIAGNOSIS
○ Hepatitis
○ Nephropathy Screening
○ Ocular changes ● Ideally performed during first prenatal visit for all pregnant
○ Anterior uveitis patients ☜
○ Periostitis ● In populations with a high prevalence of syphilis (even if
negative), screening may be repeated in the 3rd trimester and
again just before delivery (Workowski, 2015)
● Serological Testing
○ Screening is non-treponemal testing
○ Screening for asymptomatic patients:
○ Includes:
■ Venereal Disease Research Laboratory (VDRL)
■ Rapid plasma reagin (RPR)
○ Both tests measure patient IgM and IgG
○ Antibodies formed against cardiolipin that is from damaged host
cells and possibly also from treponemes
○ False positive antibodies can also be produced in response to:
(Larsen, 1995)
Figure 4. Secondary syphilis
■ Recent vaccination
Latent Syphilis ■ Febrile illness
● Result of untreated primary or secondary syphilis ■ Pregnancy
● Early latent: <12 months after primary of secondary infection ■ Chronic conditions (such as intravenous drug abuse, SLE,
● Late latent syphilis or tertiary syphilis aging, leprosy, or cancer)
○ Slowly progressive disease affecting all organ systems
Definitive Diagnosis
○ Produce slow organ damage ☊
● Dark field examination
Congenital Syphilis ○ Visualization of the spirochetes ☊
● Without screening and treatment, approximately 70% of infected ● Direct fluorescent antibody testing
women will have an adverse pregnancy outcome (Hawkes, 2011)
● Maternal infection can lead to: (Gomez, 2013) Confirmatory Tests
○ Preterm labor ● Fluorescent treponemal antibody absorption (FTA-ABS)
○ Fetal death ● Microhemagglutination assay for antibodies to T. pallidum
○ Fetal-growth restriction (MHA-TP)
○ Fetal infection ● Treponema pallidum passive particle agglutination (TP-PA)
● Rare for those mothers affected <18 weeks AOG VDRL and RPR
● Stillbirths have been noted
● Newborns manifest with:

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3.08b Sexually Transmitted Diseases in Pregnancy
● In screening, VDRL or RPR is used for qualitative examination. If a
Primary, secondary, or early latent syphilis of <1 year duration
the result is positive, we now go to quantitative VDRL and RPR. b
Latent syphilis of unknown or more than 1-year duration, tertiary
☊ syphilis, missed doses are not acceptable for pregnant women, and
● Positive non-treponemal test results those who miss any dose of therapy must repeat the full course of
● Findings are quantified and expressed as titers therapy
● Titers are expected to increase during early syphilis and often c
Some recommend benzathine penicillin, 2-4 million units IM after
exceed levels of 1:32 in secondary syphilis completion of the neurosyphilis treatment regimens
● Used to follow up treatment of primary and secondary syphilis ☊
● Serological testing (Rac, 2014a) Congenital Syphilis
○ Done at 3-6 months following treatment ● Congenital syphilis may be noted despite treatment of mother in
○ A 4-fold drop in VDRL or RPR titers usually confirms that the 1.8% of pregnancies (usually if treated after 26 weeks) (Alexander, 1999)
treatment is effective
● Consistent use of the same test for surveillance is recommended;
● High maternal titers are expected to increase preterm delivery ☜
● Delivery after therapy increases risk of treatment failure (Sheffield, 2002)
you cannot mix and match the two examinations ☊ ☜
Prenatal Diagnosis Management during Pregnancy
● Ultrasound (USG) ● Must be continued until the 3 doses are given in latent syphilis, if 1
○ Sometimes, USG examination precedes the qualitative or dose is missed, treatment will be started again ☜
quantitative results ☊ ● No other alternative to penicillin (PCN) therapy ☜
○ Present as: ○ If the patient has a penicillin allergy, penicillin is still given, and
■ Hydrops fetalis the patient will undergo a desensitization protocol
■ Ascites ● Proposed medications include: ceftriaxone, azithromycin,
■ Hepatomegaly tetracycline and doxycycline
■ Placental thickening ○ However, doxycycline is not recommended for pregnant women
■ Hydramnios ● Erythromycin and Azithromycin
● Amniocentesis ○ May be curative for the mother
○ PCR to detect T. Pallidum in amniotic fluid ○ Have limited transplacental passage, therefore these do not
○ Dark field examination of amniotic fluid prevent all congenital disease (Berman, 2004; Wendel, 1988; Zhou, 2007)
● Macrolide-resistant strains of T. pallidum
○ Prevalent in several countries (Stamm, 2015)
○ Cephalosporins may prove useful but data are limited (Liang, 2016)
○ Tetracyclines (including doxycycline) are effective but
generally not recommended during pregnancy, because of the
risk for deciduous-teeth discoloration.

CONCEPT CHECKPOINT:
1. What is the characteristic lesion seen in secondary syphilis
described as flesh-colored papules and nodules?
2. False positive results in serologic testing may be produced by?

ANSWERS:
1. Condyloma lata
2. Recent vaccination, febrile illness, pregnancy, and chronic conditions (such as
intravenous drug abuse, SLE, aging, leprosy, or cancer)

III. GONORRHEA
● Caused by Neisseria gonorrhoea
○ Sexually transmitted infection that causes cervicitis
Figure 5. Percentage of patients who will test positive using the different tests like
Epidemiology
IgM, FTA-ABS, and TPHA. It is also reflective of the response of the patient to
treatment. These values are taken during specific weeks after primary infection has ● 124 cases per 100,000 persons (2015)
been noted. ☊ ● Prevalence in pregnant women 0.6% (Blatt et al)
F. TREATMENT ● Concomitant chlamydial infection is found in 40% of cases

Table 1. Treatment of syphilis (Data from Worlowski, 2015; CDC, 010b) ☜ Pregnancy Outcomes
Category Treatment ● Gonococcal cervicitis is associated with increased incidence of
septic abortion
Benzathine penicillin G, 2.4 million units as a ● In the most pregnant women: infection of cervix, urethra, and
Early syphilisa single injection (some recommend a second periurethral and vestibular glands
dose 1 week later) ● Acute salpingitis is rare in pregnancy because there are blocked
More than 1 year Benzathine penicillin G, 2.4 million units IM tubes, and one would probably be unable to conceive in these
durationb weekly for 3 doses cases ☊.
● Preterm delivery, premature rupture of membranes,
Aqueous crystalline penicillin G, 3-4 million units chorioamnionitis, and postpartum infection may occur if gonorrhea
IV every 4 hours for 10-14 days present during delivery
OR
Neurosyphilisc Untreated Gonococcal Cervicitis Pregnancy Outcome
Aqueous procaine penicillin, 2-4 million units IM
daily + Probenecid 500 mg orally 4 times daily, ● Untreated gonococcal cervicitis is associated with:
both for 10-14 days ○ Septic abortion

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3.08b Sexually Transmitted Diseases in Pregnancy
○ Infection after voluntary abortion (Burkman, 1976) ○ Untreated cervical infection increases the risk of preterm
● Vertical transmission is due to fetal contact with vaginal secretions delivery, preterm PROM, low birth weight, or perinatal mortality
during delivery ☊
(Andrew, 2000, 2006; Blas, 2007; Johnson, 2011; Moodley, 2017; Silva, 2011)

○ Transmission rates approximate 40% (Laga, 1986) ● Reports of delayed postpartum metritis (2-3 weeks postpartum)
(Hoyme, 1986)
○ Predominant sequela is gonococcal ophthalmia neonatorum
■ Corneal scarring, ocular perforation, and blindness ● Vertical transmission is 8-44% from neonates delivered vaginally
■ Ocular prophylaxis is provided to newborns (Mabry-Hernandez, 2010) ● Perinatal transmission:
○ Ophthalmia neonatorum conjunctivitis (most common)
A. SCREENING AND DIAGNOSIS ○ Pneumonia
● Culture or nucleic acid amplification tests (NAATS) B. SCREENING RECOMMENDATIONS
○ Gonorrhea PCR (GeneXpert)
● U.S. Preventive Services Task Force (LeFevre, 2014; AAP & ACOG, 2017)
○ Screening for symptomatic cases
○ Chlamydia screening for all women at 1st prenatal visit
● Vaginal or cervical samples are preferred, as urine collection
● ACOG suggests testing in the 3rd trimester for those:
may detect up to 10% fewer infections (Papp, 2014)
○ Treated in the 1st trimester
○ Initial urine stream, not midstream is collected
○ All women aged ≤ 25 years
● NAATS are also recommended for diagnosis of:
○ Aged ≥ 25 years with behavioral factors, which mirror those for
○ Rectal or pharyngeal disease
women at risk for gonorrhea
○ Laboratories must be CLIA (Clinical Laboratory Improvement
Amendments) compliant C. SCREENING AND DIAGNOSIS
● Repeat testing is recommended in the following: ☜ ● Diagnosis:
○ Any woman treated for gonorrhea in the 1st trimester who is on ○ Culture or NAAT (PCR using GeneXpert)
her 3rd trimester of pregnancy ○ Vaginal or cervical samples are preferred
○ Any uninfected woman who is at high risk for gonococcal ■ Because urine collection may detect up to 10% fewer
infection (American Academy of Pediatrics, 2017) infections (Papp, 2014; Wiesenfeld, 2017)
B. TREATMENT ○ However, Roberts and associates (2011) evaluated NAAT of
urine specimens compared with cervical secretions in more
● Ceftriaxone 250 mg IM than 2000 pregnant women and found them to be equivalent
● Plus 1 gram of azithromycin (orally) (Workowski,2015) ○ The initial urine stream is collected instead of the midstream
○ Another drug with a different mechanism of action against N.
urine ☊
gonorrhoeae
○ Treats chlamydial co-infections ☜ D. TREATMENT
● Patients must abstain from sexual intercourse for 7 days after they Oral Treatment of Chlamydia trachomatis Infections During
and their sexual partners have completed treatment Pregnancy (Workowski, 2015)
Alternative Regimen ● Preferred
● A single, 400 mg oral dose of cefixime + 1 gram of azithromycin ○ Azithromycin 1 gram as a single dose
● Should be reserved for situations that preclude IM ceftriaxone ● Alternative
treatment ○ Amoxicillin 500 mg TID for 7 days or
○ Erythromycin base, 500 mg QID for 7 days or
With Cephalosporin Allergy ○ Erythromycin ethylsuccinate 800 mg QID for 7 days or
● Gentamicin 240 mg IM + 2 grams oral azithromycin dose ○ Erythromycin base, 250 mg QID for 14 days or
○ Erythromycin ethylsuccinate 400 mg QID for 14 days
Antimicrobial Resistance
● Gonorrhea treatment has evolved during the past decades due to Expedited Partner Treatment
ability of N. gonorrhoeae to rapidly develop antimicrobial resistance
(CDCP, 2011b,c; Dionne-Odom, 2011; Ram, 2012; Unemo, 2011)
● Guidelines for EPT by the CDCP (2006a) and endorsed by the
ACOG (2015)
● Rapid development of fluoroquinolone resistance resulted in the
● Prescription is provided to the diagnosed patient for their partner
CDC removal of this therapeutic class from its treatment guidelines
● Delivered by the patient to their partner without medical
in 2007
assessment of the partner or professional counselling
● The Gonococcal Isolate Surveillance Project has reported
● Does not replace traditional strategies, such as standard patient
decreasing susceptibility to cephalosporins
referral with screening for other STDs
IV. CHLAMYDIA
Chlamydia
● Causative agent: Chlamydia trachomatis ● Acceptable for treatment of sexual contacts with chlamydial
○ Obligate intracellular bacterium infection
○ Attaches to the columnar or transitional epithelium and causes
cervical infection Gonorrhea
● Cause cervical infection and cervicitis ● Is less desirable unless the partner will otherwise not seek
● Most common reportable STD in the US and the overall chlamydial treatment (CDCP, 2016a)
infection rate among woman was 646 cases per 100,000 females Trichomoniasis
in 2015 (CDCP, 2016c)
● Fewer date are available to assess this strategy (Kissenger, 2006; Schwebke,
● Most pregnant women asymptomatic 2010)
● 30% present with urethral syndrome urethritis or bartholin’s gland
infections Syphilis
● Not usually seen in pregnancy are endometritis, salpingitis, ● EPT is not recommended (Workowski, 2015)
reactive arthritis, and Reiter syndrome
A. PREGNANCY OUTCOME
● Effects on pregnancy

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3.08b Sexually Transmitted Diseases in Pregnancy
E. SCREENING AFTER TREATMENT → mucocutaneous infection → virus moves retrogradely along
sensory nerves → remains latent in cranial nerves or dorsal spinal
● Advised because a review of repeat chlamydial infections among ganglia, which is why recurrences are common
women revealed a reinfection rate of 14% (Hosenfeld, 2009)
● Most recurred within the first 8 to 10 months (Hosenfeld, 2009) D. NEONATAL TRANSMISSION
● Intrauterine - 5%
F. LYMPHOGRANULOMA VENEREUM
● Peripartum - 85%
● Caused by Chlamydia trachomatis ● Postnatal - 10%
● Primary infection characterized by transient, inguinal adenitis, or ● HSV-1 and 2 both infect neonates
suppurations ● Risk of neonatal infection correlated with:
● Lymphatic sclerosis, fibrosis, vulvar elephantiasis ○ Presence of HSV in genital tract
● Treatment during pregnancy ○ Invasive OB procedures (ex. intrapartal fetal scalp monitoring
○ Erythromycin 500 mg QID for 21 days (CDC, 2006; Workowski, 2015) or ☊)
○ Azithromycin 1 gram orally weekly for 3 weeks ○ Stage of maternal infection (Brown, 2007)
CONCEPT CHECKPOINT:
3. What is the treatment for Gonorrheal infection?
4. What is the treatment for Lymphogranuloma Venereum?

ANSWERS:
3. Ceftriaxone 250mg IM + 1 gram of azithromycin orally
4. Erythromycin 500mg 4 times a day for 21 days or Azithromycin 1 gram orally
weekly for 3 weeks

V. HERPES SIMPLEX VIRUS


● Characterized by ulcerations
● One of the most common sexually transmitted diseases
● Causes more danger to the neonate than the mother ☜
● There are several strategies that are being done to curb vertical
transmission
● Most women unaware they are infected or asymptomatic and
transmit the disease Figure 6. Vulvar lesions and Lesions on the baby
● 0.5-2% of pregnant women acquire HSV-1 or HSV-2 during
pregnancy (Brown et al., 1997)
A. ADULT HSV DISEASE
● Caused by HSV-1 and HSV-2
● Two types with significant DNA homology
● Type 1
○ Most non-genital
○ But cause more than half of new cases of genital herpes in
adolescents
● Type 2
○ Almost all from genital tract and transmitted by sexual contact
○ Most recurrences are from HSV-2
Figure 7. Baby infected by the mother close to the time of delivery. Maculopustular
B. GENITAL HERPES SIMPLEX VIRUS rashes are seen in the baby.
● HSV near time of delivery has a 30-50% risk of infection
● Affects an estimated 50 million adolescents and adults in the
● Recurrent HSV
United States (Workowski, 2015)
○ Documented to have occurred in less than 1% of neonates
● Most women are unaware of their infection and unknowingly
○ Mostly HSV-2
transmit the virus
● HSV-2 Seroprevalence E. CLINICAL MANIFESTATION
○ Differs among populations ● Viral replication at point of entry moves retrogradely along sensory
○ Non-Hispanic white females in the United States: 15.3 from nerves where it remains latent
2007 to 2010 (Fanfair 2014; Schulte, 2014) ● Primary infection: HSV-1 or 2 without antibodies
○ Black females: 53% (Fanfair 2014; Schulte, 2014) ○ Incubation period 2-10 days from contact ☊
● 16,000 pregnant women from 2000 to 2010, the overall ○ Papular eruptions with itching or tingling sensation
seroprevalence (Delaney, 2014) ■ Painful and vesicular; multiple vulvar and perineal lesions
○ HSV-2: 16% may coalesce
○ HSV-1: 66% ○ Flu-like symptoms, hepatitis, encephalitis, or pneumonia
● Seronegative pregnant women ● First episode non-primary infection HSV
○ Have a 4-5 % risk of acquiring HSV-1 or HSV-2 during ○ Diagnosis considered when one HSV type is isolated from a
pregnancy (Brown, 1997; Kulhanjian, 1992) lesion in a woman who has only the other serological
● HSV-1 seropositive(Brown, 1997) HSV-type antibody present (Williams (25th ed) p. 2781)
○ Acquisition risk for HSV-2 approximates 2% ○ Fewer lesions with fewer systemic manifestations, less pain,
○ Acquisition of HSV-1 protects patients against HSV-2 shorter duration of lesions and viral shedding
C. MANIFESTATION ○ Due to cross reacting antibodies
● Once transmitted by contact through abrasions in the vaginal or ○ May also be considered as a primary infection if the patient has
reproductive tract mucosa → HSV-1 or 2 replicates at the entry site been infected previously with other HSV type

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Herpes Simplex Virus Reactivation HSV Treatment in Pregnancy
● Isolation of HSV-1 or 2 in those with antibodies of same type ● Acyclovir - for first-episode genital herpes
○ Occurs during latency periods ○ Safe in pregnant women
○ Recur at same sites ■ Through 1999, the manufacturers of acyclovir and
○ Common during 1st year after infection valacyclovir maintained a registry of outcomes following
○ Recurrences are more frequently seen in HSV-2 exposure to the drugs during pregnancy
○ Lesions fewer, less tender, and viral shedding last for 2-5 days ■ More than 700 neonates exposed during the 1st trimester
were evaluated, and there were no adverse effects attributed
Herpes Simplex Viral Shedding
to acyclovir (Stone, 2004)
● May be seen in asymptomatic individuals ○ Used for peripartum shedding prophylaxis at 36 weeks AOG
○ HSV shedding without signs or symptoms ● Oral or parenteral preparations attenuate clinical infection and
● Most HSV transmission to other sexual partners occurs during this viral shedding duration
time ☜ ● Suppressive therapy is also used to limit recurrent infections and
● Neonatal transmission has not been fully studied for patients who to reduce heterosexual transmission (Corey, 2004)
shed the virus and are asymptomatic ● At this time, data are insufficient regarding famciclovir exposure,
F. HSV AND PREGNANCY although a pregnancy registry is being maintained
(1-888-669-6682)
● Most primary and 1st episodes in early pregnancy have no effect
on abortion or stillbirth rates (Eskild et al, 2002) Table 2. Oral Antiviral Medications for Herpes Virus Infection in Pregnancya
● Newborn infections presents as Indication Pregnancy Recommendation
○ Eye or oral lesions in 35% of cases Acyclovir, 400 mg TID for 7-10 days
○ Disseminated disease/major organs (25%) Primary or first
or
● Disseminated infection mortality rate is almost 30% episode infection
Valacyclovir, 1 g BID for 7-10 days
G. SCREENING AND DIAGNOSIS Acyclovir, 40 0mg TID for 5 days or
Acyclovir, 800 mgBID for 5 days
Screening Symptomatic or
● Several organizations recommend against routine serological recurrent Acyclovir, 800 mg TID for 2 days
HSV screening in asymptomatic gravidas (ACOG 2016b; Workowski, 2015; infection or
U.S Preventive Services Task Force, 2016) (episodic therapy) Valacyclovir, 500 mg BID for 3 days
● Diagnosis should be confirmed by laboratory testing if there is a or
clinically suspicious lesion Valacyclovir, 1 g OD for 5 days
● HSV tests: virological or type-specific serological tests Acyclovir, 400 mg TID from 36 weeks until delivery
or
Diagnosis of HSV Daily suppression
Valacyclovir, 500 mg BID from 36 weeks until
● Direct virological tests performed on a specimen from delivery
mucocutaneous lesion a
○ PCR Famcyclovir not preferred during pregnancy due to fewer safety data
■ More sensitive
Mode of Delivery and HSV
■ Results are generally available in 1-2 days
■ Easier specimen handling ● To diminish vertical transmission risks, cesarean delivery is
○ Viral Culture indicated for women with active genital lesions or prodromal
■ Sensitivity of HSV isolation is relatively low symptoms (ACOG, 2016b)
■ Results are sometimes not available until 7-14 days after ● Several studies have shown that:
(Strick 2006) ○ Acyclovir or valacyclovir suppression initiated at 36 weeks AOG
■ A negative culture or PCR result does not exclude infection for gravidas with recurrences during pregnancy lowers the
☜ number of HSV outbreaks at term
■ Viral load of the woman was decreased, and outcome of the
○ HSV viral types should be differentiated (LeGoff, 2014.)
neonates were better ☊
Type Specific Antibody Responses to HSV-1 and HSV-2 ● Goal: To decrease the need for cesarean delivery (Hollier, 2008)
● Help in documenting infection ☊ ● This suppressive therapy will also decrease viral shedding (Scott, 2002;
Sheffield, 2006; Watts, 2003)
● IgG antibodies develop 1-2 weeks after primary infection and then
persist ● One systematic review evaluated acyclovir prophylaxis given from
● Confirmation of clinical infection and identification of asymptomatic 36 weeks to delivery to women with HSV recurrence during
carriers may be done through this technique ☊Request pregnancy. (Sheffield)
type-specific glycoprotein G-based assays when serology is ● Cesarean delivery is not recommended for women with HSV but
being performed with no genital disease.
○ Sensitivity: 90-100% ● Lesions in non-genital area: occlusive dressing then NSD
○ Specificity: 99-100% (Wald, 2002) Premature Rupture of Membranes (PROM)
● IgM antibody detection is not a useful test because it is only
● Preterm PROM: no evidence suggests that external lesions cause
present for a short time
ascending fetal infection
H. TREATMENT ● Expectant management of preterm PROM in 29 women at
gestational ages <31 weeks.(Major et al, 2003)
HSV Treatment in Non-Pregnant Women ○ There were no cases of neonatal HSV
● Acyclovir ○ Maximum infection risk was calculated to be 10%
● Famciclovir ○ Antiviral treatment is recommended
● Valacyclovir

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3.08b Sexually Transmitted Diseases in Pregnancy
● For women with clinical recurrence at delivery, there is not an
absolute duration of membrane rupture beyond which the fetus
would not benefit from CS delivery (ACOG, 2016d)
○ In PROM with active genital lesions, CS is still beneficial for the
neonate as it will help decrease the probability of a neonatal
infection ☊
Breastfeeding and Concurrent Treatment of HSV
● Women with active HSV may breastfeed if there are no active
breast lesions
● Strict hand washing is essential
● Valacyclovir and acyclovir may be used for symptomatic
maternal lesions during breastfeeding, as drug concentrations in
breast milk are low.
○ Acyclovir concentration to be only 2% of that used for
therapeutic dosing of the neonate (Sheffield, 2022)
VI. HUMAN PAPILLOMAVIRUS (HPV) Figure 8. Vulvar Papillomatosis

● 40 serotypes C. NEONATAL INFECTION


● High risk HPV 16 and 18 are associated with dysplasia and
cervical cancer
● Genital warts caused by HPV 6 and 11
● Prevalence is highest in younger women and some of this
seroprevalence now reflects HPV vaccination in this age group
(Brouwer, 2015)

● Most reproductive-aged women become infected within a few


years of becoming sexually active, and most infections are
asymptomatic and transient
● There is an increase in number of warts and size during
pregnancy
○ Eradication of warts during pregnancy is not always needed
A. HPV VACCINATION
● HPV is a vaccine-preventable sexually transmitted infection. Figure 9. Laryngeal papillomatosis
● Three types of vaccines available in the market: ● Juvenile onset respiratory papillomatosis is a rare, benign
○ Quadrivalent vaccine (Gardasil 4) - against HPV types 6, 11, neoplasm of the larynx. It can cause hoarseness and respiratory
16, and 18 distress in children usually caused by HPV 6 and 11.
○ Nonavalent vaccine (Gardasil 9) - against HPV types 6, 11, 16, ● Cesarean delivery is not recommended.
18, 31, 33, 45, 52, and 58 ○ The benefit of CS delivery to decrease transmission risk is
■ Only HPV 6 and 11 are the low risk types, the rest are unknown. Thus, it is currently not recommended solely to
cancer-causing HPV types ☊ prevent HPV transmission.(Workowski, 2015)
○ Bivalent vaccine (Cervarix) - against HPV types 16 and 18 ● HPV vaccination may ultimately decrease JoRRP rates in the
● Vaccines are licensed for females aged 9 to 26 or 44 years, and future.(Matys, 2012)
the target age is 11 to 12 years but may be given off label to
different age groups CONCEPT CHECKPOINT:
● Three dose series on a schedule of 0, 1-2, and 6 months for those 1. Dysplasia and cervical cancer are associated with what type of
aged 15 to 26 years old. HPV?
● A two-dose regimen has been started and is being given at 0 and 2. Nonavalent vaccine (Gardasil 9) protects the body against what
again at 6 to 12 months for those who start their vaccination at 9 to types of HPV?
14 years of age.
● The vaccines are not recommended for pregnant women, ANSWERS:
1. HPV 16 & 18
however, inadvertent exposures do occur. 2. HPV 6, 11, 16, 18, 31, 33, 45, 52, & 58
● No adverse pregnancy outcomes are associated with the vaccines.
● If a woman is found to be pregnant after starting vaccination VII. VAGINITIS: BACTERIAL VAGINOSIS (BV)
series, remaining doses are delayed and given after delivery.
● Causative agent: Gardnerella vaginalis, Bacteroides sp.
● Safe to give in breastfeeding women.
○ The decreased lactobacilli that may be seen during pregnancy
B. MANAGEMENT may increase the risk of having this infection.
● Prevalence: 30% of non-pregnant women
● Management during pregnancy may or may not be necessary but it
● BV has not really been classified as sexually transmitted
would depend on the size and location of the lesion and the
infection, however, it has been classified as related to sexual
preference of the mother ☊
activity ☊
● Management includes:
● Associated with preterm birth
○ Tricholoacetic acid 80-90% solution applied once a week
● Symptomatic women with fishy-smelling vaginal discharge
○ Cryotherapy, surgical excision, or laser ablation
should be treated with:
○ Podophyllin, podofilox 0.5%, or Imiquimod 5% cream not
○ Metronidazole 500 mg BID for 7 days
recommended in pregnancy
○ Metronidazole gel
○ Clindamycin cream 2%

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3.08b Sexually Transmitted Diseases in Pregnancy
● Treatment does not reduce preterm birth (ACOG, 2001) A. DIAGNOSIS
Amsel Criteria 1983 ● Wet Smear: parasites seen microscopically moving briskly in a
● For clinical diagnosis of BV, three of the four criteria are present: sample mixed on a slide with saline
○ Vaginal pH > 4.5 ● Prompt inspection of vaginal secretions should be done because
○ Thin, milky, noninflammatory, vaginal discharge trichomonads move very slowly with cooling.
○ > 20% clue cells seen microscopically ● May be found incidentally on a Pap smear
○ Fishy odor after addition of 10% KOH to vaginal secretion ● Both have low diagnostic sensitivity that approximates only
samples (positive “whiff test”) 60%(Krieger, 1988; Wiese, 2000)
● Pap test positive warrant wet-prep microscopy or other diagnostic
confirmation
B. MANAGEMENT
● Metronidazole a single 2 gram dose per orem
○ For those with concurrent HIV infection: Metronidazole 500
mg orally BID for 7 days
● High rate of reinfection even after treatment so retesting for T.
vaginalis is recommended for all sexually active women within 3
months following initial treatment
Metronidazole Safety During Pregnancy
● Metronidazole, an FDA category B drug, is not teratogenic or
fetotoxic, but has some tumorigenicity in animal studies(Briggs, 2015;
Czeizel, 1988)

● Manufacturer recommends against its use during the 1st trimester


Figure 10. Clue Cells

A. PREGNANCY OUTCOMES C. NEONATAL OUTCOMES

● Preterm birth, premature rupture of membranes, and postpartum ● Perinatal transmission of trichomoniasis by direct contact in the
endometritis (Hillier, 1995; Leitich, 2003; Watts, 1990) birth canal is rare but may lead to:
● Increased susceptibility to STDs, including HIV (Atashili, 2008; Brotman, 2010) ○ Neonatal respiratory or genital infection(Bruins, 2013; Trintis, 2010)
● For women at low risk for preterm birth, however, treatment of BV ○ Preterm birth, preterm PROM, and SGA newborns (Silver, 2014)
does not reduce preterm birth rates (Brocklehurst, 2013; Carey, 2000) ● Klebanoff and colleagues (2001) RCT
● For high-risk women (those with previous preterm delivery), ○ Treatment did not lower preterm birth rates
evidence is conflicting IX. VAGINITIS: CANDIDIASIS
● ACOG (2016c), CDC, and US Preventive Services Task Force do
not recommend routine BV screening of asymptomatic ● Causative agent: Candida albicans
gravidas—at either high or low risk for preterm delivery—to prevent ● Affects 25% of pregnant women
preterm birth. ● Causes an extremely profuse, irritating discharge associated with
pruritic, tender, edematous vulva (2021)
B. TREATMENT OF BV IN PREGNANCY ● Treatment for symptomatic patients for 7 days:
● For symptomatic women only ○ Clotrimazole 1% cream
● Preferred drugs are: ○ Miconazole 2% cream
○ Metronidazole 500 mg BID orally for 7 days ○ Terconazole 0.4-0.8% cream
○ Metronidazole 0.75% gel, one applicator vaginally, daily for 5 ● Oral Fluconazole has been found in new studies to probably be
days teratogenic, hence it is avoided during pregnancy ☊
○ Clindamycin 2% cream, one applicator intravaginally nightly for X. HUMAN IMMUNODEFICIENCY VIRUS (HIV)
7 days
● Alternatives: ● One of the most dreaded infections worldwide ☊ ☜
○ Clindamycin 300 mg orally BID for 7 days ● Prevalence: 35 million with HIV/AIDS
○ Clindamycin ovules, 100 mg placed intravaginally nightly for 3 ● Perinatal transmission decreased from 30% to 2%
days ○ Due to prenatal HIV testing and antiviral therapy to the pregnant
● Treatment of male partners does not appear to lower recurrence woman and to her neonate
rates of BV. ● Caused by RNA retroviruses HIV-1 and 2
● Transmission is through blood, sexual intercourse, and vertical
VIII. VAGINITIS: TRICHOMONIASIS
transmission
● Causative agent: Trichomonas vaginalis ● Profound immunosuppression, opportunistic infections, and
● Affects 20% of women neoplasms
● Presentation: Foamy leukorrhea with pruritus and irritation
A. STATISTICS
● Demonstration of trichomonads, flagellated pear-shaped motile
organisms ● US, the CDC (2016c) estimated more than 1.2 million individuals
● Enters fetal circulation but there is no increased frequency of birth were infected in 2013
defects ○ New cases numbered more than 39,000
● Treatment: Metronidazole 2 gram dose ● Approximately 8,500 women with HIV deliver annually in the US
● Association with preterm birth is still unclear and treatment of ● Perinatally acquired HIV cases have decreased and perinatal
trichomonas does not seem to decrease the risk of preterm births transmission rate in 2013 was 1.8% (CDCP, 2016b, 2017)
○ This is predominantly due to:
■ Prenatal HIV testing

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3.08b Sexually Transmitted Diseases in Pregnancy
■ Antiretroviral therapy (ART) for the woman and then her
neonate
● 36.7 million people living with HIV globally
○ Africa: 25.6 million
○ American: 3.3 million
○ South-East Asia: 3.5 million
○ Europe: 2.4 million
○ Eastern Mediterranean: 360,000
○ Western Pacific: 1.5 million
● Epidemiology of people who have been diagnosed with HIV/AIDS

○ 6% sex workers
○ 12% people who inject drugs
○ 17% men who have sex with men
○ 1% transgender
○ 18% clients of sex workers and sex partners of other key
populations
■ Clients of sex workers and sex partners of other key
population is the group that has increased significantly ☊
○ 46% remaining population
● 840 newly diagnosed HIV cases in the Philippines in April 2019
● Modes of transmission among newly diagnosed from January 2018
○ 61% men having sex with males only
○ 26% men having sex with males and females
○ 10% male-female sex
○ 2% injecting drug user Figure 12. Number of cases of HIV in the Philippines
○ <1% mother to child
○ 1% no data B. TRANSMISSION
● Primary determinant of transmission: Plasma HIV-1 viral load
● The viral HIV envelope binds to mucosal dendritic cells then
present the viral particle to specific T lymphocytes
○ Lymphocytes are defined phenotypically by their cluster of
differentiation 4 (CD4) glycoprotein surface antigens
○ CD4 site serves as a receptor for the virus
○ Once infected, CD4 T-lymphocytes may die
■ Immunodeficiency
● Sexual transmission
○ Mucosal dendritic cells bind to HIV envelope glycoprotein
○ Dendritic cells bring virus to the T-lymphocytes with CD4
glycoprotein surface antigen
○ CD4 site serves as receptor for virus
○ Co-receptors CCR5 and CXCR4 necessary for viral entry into
the cell
○ After infection T cells decrease
● Pregnancy
○ Has minimal effect on CD4+ T-cell counts
○ HIV RNA is higher
Figure 11. Number of new HIV infections according to UNAIDS, unicef, WHO, Asian
Development Bank C. CLINICAL MANIFESTATIONS
● Incubation period is days to weeks
● Acute HIV infection (< 10 days )
○ Fever, night sweats, fatigue, rash, headache, lymphadenopathy,
pharyngitis, myalgias, arthralgias, nausea, diarrhea
● Chronic viremia
● Viremia to AIDS median time: 10 years
● Factors affecting progression:
○ Route of infection
○ Viral load
○ Immunological status of host affect progression
D. HIV & AIDS
● Disease progression:
○ Generalized lymphadenopathy, oral hairy leukoplakia, aphthous
ulcers, and thrombocytopenia
● AIDS
○ Esophageal or pulmonary candidiasis, persistent HSV or zoster,
condyloma, PTB, CMV pneumonia
○ Definitive: CD4+ count <200 / mm ☜
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3.08b Sexually Transmitted Diseases in Pregnancy

E. HIV & PREGNANCY HIV-1 and 2

● Repeated pregnancy has shown no effect on clinical or


immunological course of viral infection
● Prenatal screening (1st and 3rd trimester if high risk)
● Screening: ELISA test
○ Sensitivity >99.5%
● Confirmatory: Western blot immunofluorescence assay (IFA)
● Transplacental HIV transmission occurs early
● Higher rate of transmission in preterm births and PROM
● Non-breastfeeding untreated HIV-infected mothers have infected
babies 15-40% of cases
○ 20% of fetal transmission occurs before 36 weeks
○ 50% in the days before delivery
○ 30% intrapartum
F. HIV & NEONATES
● Rate of neonatal infection varies ☊
● Viral burden and neonatal infection rates are directly related
Figure 14. HIV-1/ 2 antigen/antibody combination immunoassay screening
● In one cohort (Cooper, 2002)
○ Neonatal infection was 1% with <400 viral copies/mL H. MANAGEMENT
○ Increased to 23% when maternal viral RNA levels were
● Patients with HIV are jointly managed with infectious disease
>30,000 copies/mL ☊
● Preterm birth and fetal growth restriction: increased specialists ☊
● Maternal morbidity and mortality rates: not increased During Pregnancy
G. SCREENING ● Plasma HIV RNA quantification levels
● CD4 T-lymphocyte count
● Initial laboratory screening test for HIV ● Hepatic transaminase determination
● An antigen / antibody combination immunoassay that detects ● HSV-1 and 2 determination
antibodies against HIV-1 and HIV-2 and detects HIV-1 p24 antigen ● Chest X-Ray
(CDCP, 2014)
● Tuberculosis testing
○ The antibody can be detected in most patients within 1 month of ● Ultrasonography
infection, and thus, antibody sero-testing may not exclude early ● CMV, HSV, Hepatitis B Testing
infection ● Evaluate need for vaccination
● Getting tested for HIV is crucial
● Preventing one at-risk person from getting HIV only costs Php
● Management should begin with antiretroviral therapy ☊ ☜
○ Recommended for all HIV infected pregnant woman
3,200 per year, while treating one HIV-infected person can reach
● Treatment reduces risk of perinatal transmission regardless of
up to Php 33,000 annually
CD4+ T cell count or HIV RNA level
● So many people are getting tested but do not get treatment
● HAART
During Labor and Delivery
● Previous studies have recommended cesarean section, however
manual labor and delivery are still allowed ☊
● During labor, artificial membrane rupture, fetal scalp electrode
placement, episiotomy, and operative vaginal delivery are reserved
for clear obstetrical indications (Mandelbrot, 1996; Peters, 2016)
● Labor augmentation, if necessary, may be given to shorten the
interval to delivery to further lower the transmission risk
● Delayed cord clamping in preterm neonates is acceptable
● Neuraxial analgesia is suitable
○ Aka epidural anesthesia ☊
● Postpartum hemorrhage is best managed with oxytocin and
prostaglandin analogues
○ Methylergonovine (Methergine) and other ergot alkaloids
adversely interact with reverse transcriptase and protease
Figure 13. Home testing kit for rapid screening of HIV/AIDS inhibitors to cause severe vasoconstriction
P24 ■ Not recommended ☊
● For acute primary HIV infection Mode of Delivery
○ Identification of viral p24 core antigen or viral RNA
● Cesarean delivery done to decrease perinatal transmission to 50%
● Accurate for 11 days to 1 month after getting infected
● Antiretroviral therapy given with CS results to reduced perinatal
● Usually not used by itself to screen for HIV infection
transmission by 87%
● No further testing is required for specimens that are negative on
● In some cases, cesarean delivery lowers HIV prenatal transmission
the initial immunoassay unless a known exposure to HIV has (European Mode of Delivery Collaboration, 1999; International Perinatal HIV Group, 1999)
.
occurred
● The ACOG (2017b) recommends:
○ That scheduled cesarean delivery be discussed and
recommended for HIV-infected women with HIV-1 RNA loads
>1000 copies/mL

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3.08b Sexually Transmitted Diseases in Pregnancy
○ Scheduled delivery is recommended at 38 weeks AOG in these ● WHO (2016) recommends breastfeeding during the first 6-12
women to avert spontaneous labor months in nutritionally deprived countries, where infectious disease
■ Better for everyone because this is in a controlled and malnutrition are primary causes of infant death
environment ☊ ● The Panel on Treatment of HIV-Infected Pregnant Women and
● For women with HIV RNA levels ≤1000 copies/mL, data are Prevention of Perinatal Transmission (2016) strongly recommends
insufficient to predict similar benefits that:
○ Therefore, scheduled CS delivery is unlikely to confer ○ ART regimens not to be discontinued postpartum but continued
additional risk reduction for women already taking ART and lifelong for the advantages of viral suppression
achieving viral suppression (Briand, 2013; Jamieson, 2007; Read, 2005) XI. CONCLUSION
○ Vaginal delivery in this group may be considered at 39 weeks
after proper counselling ☊
ART in Pregnant Women

Figure 16. Number of STD cases in the US

Figure 17. STD Complications and Treatment


● If left untreated, STD can cause increased risk of giving or getting
Figure 15. Table shows the recommendation of taking ART during pregnancy ☊ HIV ☊
Table 3. Table summary of ART recommendations in certain condition☊ ● In the long term, there are pelvic and abdominal problems
associated with STD specifically your pelvic inflammatory disease.
Condition Recommendation

Currently taking ART + ● Inability to get pregnant or may have pregnancy complications are
Continue ART
pregnant sequelae also of STD ☊
ART naive, never been given ● Prevent STDs with three simple steps
Start ART ○ Very much with COVID advice, we would like to talk to these
ART + pregnant
patients, to educate them ☊
History of ART but currently
not in ART
Restart ART ○ We have to test them ☊
○ We have to treat them ☊
No ART and presented with ● They have to behave responsibly, protecting themselves, the
Give HIV ZDV
labor
others, and their babies. ☊
HIV RNA levels 500-1000
Do ART drug resistance testing CONCEPT CHECKPOINT:
copies/mL
3. What is the primary determinant of transmission in HIV?
Postpartum Care 4. What drug/s is/are not recommended during labor and delivery
● Vertical transmission increased by breastfeeding, and it of HIV patients?
generally is not recommended for HIV-positive women in the US,
ANSWERS:
where formula is readily available (Read, 2003) 3. Plasma HIV-1 viral load
4. Methylergonovine (Methergine) and other ergot alkaloids.

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3.08b Sexually Transmitted Diseases in Pregnancy
REFERENCES 3. Vertical transmission of gonorrhea occurs mainly during
which of the following stages?
Bongala, D. (2020). Sexually Transmitted Diseases in Pregnancy [lecture
a. Antepartum
powerpoint].
b. Early Labor
REVIEW QUESTIONS c. Parturition
No feedback was given for this LE. d. Postpartum
4. Infections with which of the following organisms is expedited
Poll Questions partner treatment considered acceptable by CDC ?
1. 32 year old G1P0 has reactive VDRL. Which of the following a. Trichomonas vaginalis
tests should be requested prior to treatment b. Treponema pallidum
a. Serum IgG c. Bacteroides fragilis
b. FTA ABS d. Chlamydia trachomatis
c. Rapid Plasma Reagin 5. Based on current evidence , presence of lesions and active
d. NAATS infection with which of the following sexually transmitted
2. Which of the following is best used to treat a 20 year old G1 diseases will warrant cesarean delivery ?
P0 who has painless ulcerations at the vulvar and vaginal a. Treponema pallidum
area and has reactive result to microhemagglutination test to b. Human papillomavirus
treponema ? c. Herpes simplex virus
a. PCN d. Chlamydia trachomatis
b. Ceftriaxone
Answers: (1) b, (2) a, (3) c, (4) d, (5) c
c. Erythromycin
d. Azithromycin

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3.08b Sexually Transmitted Diseases in Pregnancy

SUMMARY

OVERVIEW ■ Serological testing: Venereal Disease Research


● Essential components of prenatal care: Laboratory (VDRL) and Rapid Plasma Reagin (RPR)
○ Education ○ Definitive Diagnosis
○ Prevention ■ Dark field examination
○ Screening ■ Direct fluorescent antibody testing
○ Treatment ○ Confirmatory
SYPHILIS ■ FTA-ABS
● Tuskegee Trial (1932) ■ Microhemagglutination assay for antibodies to T. pallidum
○ “Tuskegee Study of Untreated Syphilis in the Negro Male” (MHA-TP)
○ An unethical study which involved studies of 300+ males with ■ Treponema pallidum passive particle agglutination
(TP-PA)
syphilis and 201 males without syphilis ☊
○ VDRL and RPR
○ Basis of some of the most important ethical principles for
■ Titers are expected to increase during early syphilis and
research ☊ often exceed levels of 1:32 in secondary syphilis
● Belmont Report ■ Done at 3-6 months following treatment
○ Written by the National Commission for the Protection of ■ A 4-fold drop in VDRL or RPR titers usually confirms that
Human Subjects of Biomedical and Behavioral Research the treatment is effective
■ Created as a result of the National Research Act of 1974 ○ Prenatal Diagnosis
○ One of the leading works concerning ethics and health care ■ Ultrasound (USG)
research ● Present as: hydrops fetalis, ascites, hepatomegaly,
○ Consists of 3 principles: beneficence, justice, and respect for placental thickening, hydramnios
persons ■ Amniocentesis
● Causative agent: Treponema pallidum spirochete ● PCR to detect T. Pallidum in amniotic fluid
● Portal of entry: abrasions on vaginal mucosa ● Dark field examination of amniotic fluid
● Incubation period: averages 3 weeks, range from 3-90 days ● TREATMENT:
after the last sexual contact Table 1. Treatment of syphilis (Data from Worlowski, 2015)
● Vertical transmission
Category Treatment
○ Transplacental route (most common)
○ Contact with spirochetes through lesions during delivery or Benzathine penicillin G, 2.4 million units as a
across the placental membranes Early syphilisa single injection (some recommend a second
● STAGES OF SYPHILIS: dose 1 week later)
○ Early syphilis
More than 1 year Benzathine penicillin G, 2.4 million units IM
■ Primary syphilis
durationb weekly for 3 doses
● Diagnosed by its chancre which develops at
inoculation site a
Primary, secondary, or early latent syphilis of <1 year duration
● Solitary, painless lesion with a raised, firm border and a b
Latent syphilis of unknown or more than 1-year duration, tertiary
red, smooth ulcerated base without significant pus syphilis, missed doses are not acceptable for pregnant women, and
■ Secondary syphilis those who miss any dose of therapy must repeat the full course of
● From dissemination of spirochetes to affect multiple therapy
organ system
● Manifests 4-10 weeks after the chancre appears ○ High maternal titers = increased preterm delivery
● Manifests as dermatological abnormalities in up to 90% ○ Delivery after therapy = increased risk of treatment failure
of women ○ No other alternative to PCN therapy
● Condylomata lata: flesh-colored papules and nodules GONORRHEA
found on perineum and perianal area ● Caused by Neisseria gonorrhoeae
■ Latent syphilis ○ Sexually transmitted infection that causes cervicitis
● Result of untreated primary or secondary syphilis ● Concomitant chlamydial infection is found in 40% of cases
● Early latent: <12 months after primary of secondary ● Gonococcal cervicitis is associated with increased incidence of
infection septic abortion
● Late latent syphilis or tertiary syphilis: slowly ● Acute salpingitis is rare in pregnancy because in acute
progressive disease affecting all organ systems salpingitis there is a blocked tube therefore unable to conceive
○ Late syphilis in these cases.
○ Congenital syphilis ● Preterm delivery, Premature rupture of membranes,
■ Maternal infection can lead to preterm labor, fetal death, chorioamnionitis and postpartum infection (if gonorrhea present
fetal-growth restriction, or fetal infection during delivery)
■ Rare for those mothers affected earlier than 18 wks AOG ● Vertical transmission is due to fetal contact with vaginal infection
○ Placenta of patients with syphilis: On examination, during deliver
placenta may appear grossly large and pale which have lost ○ Predominant sequela is gonococcal ophthalmia neonatorum
their characteristic arborization and the villi have become ■ Corneal scarring. ocular perforation and blindness
thicker and clubbed ○ Ocular prophylaxis is provided to newborns
● DIAGNOSIS: ● SCREENING AND DIAGNOSIS
○ Screening ○ Culture or nucleic acid amplification tests (NAATS)
■ Ideally performed during first prenatal visit for all pregnant ■ Gonorrhea PCR(Geneexpert)
patients ■ Screening for symptomatic cases

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3.08b Sexually Transmitted Diseases in Pregnancy
○ Vaginal or cervical samples are preferred, as urine collection ■ Erythromycin ethylsuccinate 800mg 4 times daily for 7
may detect up to 10% fewer infections (Papp, 2014) days or
■ Initial urine stream, not midstream is collected. ■ Erythromycin base, 250mg 4 times daily for 14 days or
○ Repeat testing is recommended in the following: ■ Erythromycin ethylsuccinate 400mg 4 times daily for 14
■ Any woman treated for gonorrhea in the 1st trimester who days
is on her 3rd trimester of pregnancy ● LYMPHOGRANULOMA VENEREUM
■ Any uninfected woman who is at high risk for gonococcal ○ Caused by Chlamydia Trachomatis
infection ○ Primary infection characterized by transient, inguinal adenitis
● TREATMENT or suppurations
○ Ceftriaxone 250mg (intramuscularly) ○ Lymphatic sclerosis, fibrosis, vulvar elephantiasis
○ Plus 1 gram of azithromycin (orally) ○ Treatment during pregnancy
■ Another drug with a different mechanism of action against ■ Erythromycin 500 mg 4 times a day for 21 days; or
N. gonorrhoeae ■ Azithromycin 1 gram orally weekly for 3 weeks
■ Treats chlamydial co-infections HERPES SIMPLEX VIRUS
○ Patients must abstain from sexual intercourse for 7 days ● Characterized by ulcerations
after they and their sexual partners have completed ● One of the most common sexually transmitted diseases
treatment ● Causes more danger to the neonate than the mother
○ Alternative Regimen ● Most women unaware they are infected or asymptomatic and
■ A single, 400-mg oral dose of cefixime transmit the disease
■ Plus 1 gram of azithromycin ● EFFECTS ON PREGNANCY
■ Should be reserved for situation that preclude ceftriaxone ○ Most primary and 1st episode in early pregnancy no effect on
treatment abortion or stillbirth rates (Eskild et al, 2002)
○ With Cephalosporin Allergy ○ Newborn infection presents as
■ Gentamicin 240-mg (intramuscularly) ■ Eye or oral lesions in 35% of cases
■ Plus 2 grams oral azithromycin dose ■ Disseminated disease/major organs (25%)
CHLAMYDIA ○ Disseminated infection mortality rate is almost 30%
● Cause cervical infection and cervicitis ● SCREENING
● Obligate intracellular bacterium ○ Several organizations recommend against routine serological
● Attach to columnar or transitional epithelium and cause cervical HSV screening in asymptomatic gravidas
infection ○ Diagnosis should be confirmed by laboratory testing if
● Most pregnant women asymptomatic there is a clinically suspicious lesion
● 30% present with urethral syndrome urethritis or bartholin’s ○ HSV tests: virological or type-specific serological tests
gland infection ● DIAGNOSIS
● Pregnancy Outcome ○ Direct virological tests performed on a specimen from
○ Untreated cervical infection increases the risk of preterm mucocutaneous lesion.
delivery, preterm PROM, low birth weight, or perinatal ■ PCR
mortality ● More sensitive
○ Reports of delayed postpartum metritis (2-3 weeks ● Results are generally available in 1 to 2 days
postpartum) ● Easier specimen handling
○ Vertical transmission is 8-44% from neonates delivered ● TREATMENT
vaginally ○ HSV Treatment in Non-pregnant Women
○ Perinatal transmission: ■ Acyclovir
■ Ophthalmia neonatorum conjunctivitis (most common) ■ Famciclovir
■ Pneumonia ■ Valacyclovir
● SCREENING ○ HSV Treatment in Pregnancy
○ Chlamydia screening for all women at 1st prenatal visit ■ Acyclovir - for first-episode genital herpes
○ ACOG suggests testing in the third trimester for those: ■ Oral or parenteral preparations attenuate clinical
■ Treated in the 1st trimester infection and viral shedding duration
■ All women aged ≤ 25 years ■ uppressive therapy is also used to limit recurrent
■ Those aged ≥ 25 years with behavioral factors, which infections and to reduce heterosexual transmission
mirror those for women at risk for gonorrhea ■ Peripartum shedding prophylaxis with acyclovir at 36
● DIAGNOSIS weeks
○ Culture or NAAT ■ Acyclovir is safe in pregnant women
■ Geneexpert HUMAN PAPILLOMAVIRUS (HPV)
○ Vaginal or cervical samples are preferred ● Prevalence is highest in younger women
○ Urine collection may detect up to 10% fewer infections ● HPV 16 & 18 - associated with dysplasia and cervical cancer
○ However, Roberts and associates (2011) evaluated NAAT of ● HPV 6 & 11 - genital warts
urine specimens compared with cervical secretions in more ● HPV VACCINATION
than 2000 pregnant women and found them to be equivalent ○ Quadrivalent vaccine (Gardasil 4) - against HPV types 6, 11,
○ The first portion of the urine stream is collected 16, and 18
● TREATMENT ○ Nonavalent vaccine (Gardasil 9) - against HPV types 6, 11,
○ Preferred 16, 18, 31, 33, 45, 52, and 58
■ Azithromycin 1 gram as a single dose ■ Only HPV 6 and 11 are the low risk types, the rest are
○ Alternative cancer-causing HPV types.
■ Amoxicillin 500mg 3 times daily for 7 days or ○ Bivalent vaccine (Cervarix) - against HPV types 16 and 18
■ Erythromycin base, 500mg 4 times daily for 7 days or

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3.08b Sexually Transmitted Diseases in Pregnancy
● Vaccination Schedule: ○ primary determinant of transmission is the plasma HIV-1 viral
○ Three-dose series - 0, 1-2, and 6 months for those aged 15 load
to 26 years old. ○ CD4 site serves as a receptor for the virus
○ Two-dose regimen - 0 and again at 6 to 12 months for ● Clinical manifestations
those who start their vaccination at 9 to 14 years of age. ○ Incubation period is days to weeks
● Vaccines are not recommended for pregnant women ○ Acute HIV infection (< 10 days )
● Safe to give in breastfeeding women ■ Fever, night sweats, fatigue, rash, headache,
● MANAGEMENT lymphadenopathy, pharyngitis, myalgias, arthralgias,
○ Tricholoacetic acid 80-90% solution applied once a week nausea, diarrhea
○ Cryotherapy, surgical excision or laser ablation ○ Factors affecting progression:
○ Podophyllin, podofilox 0.5% or Imiquimod 5% cream not ■ Route of infection
recommended in pregnancy ■ Viral load
● NEONATAL INFECTION ■ Immunological status of host affect progression
○ Juvenile onset respiratory papillomatosis is a rare, benign ○ AIDS
neoplasm of the larynx. It can cause hoarseness and ■ Esophageal or pulmonary candidiasis, persistent HSV or
respiratory distress in children usually caused by HPV 6 and zoster, condyloma, PTB, CMV pneumonia
11. ■ Definitive: CD4+ count <200/mm
BACTERIAL VAGINOSIS ● Pregnancy
● Causative agent: Gardnerella vaginalis, bacteroides sp. ○ Prenatal screening (1st and 3rd trimester if high risk)
● Symptomatic women with fishy-smelling discharge should be ○ Screening: ELISA test
treated with: ○ Confirmatory: Western blot immunofluorescence assay (IFA)
○ Metronidazole 500mg BID for 7 days ○ Non-breastfeeding untreated HIV-infected mothers have
○ Metronidazole 0.75% gel, one applicator vaginally, daily infected babies 15-40%
for 5 days ● Neonate
○ Clindamycin cream 2% one applicator intravaginally ○ Preterm birth and fetal growth restriction: increased
nightly for 7 days ○ Maternal morbidity and mortality rates: not increased
○ AMSEL CRITERIA ● Screening
○ For clinical diagnosis of BV, three of the four criteria are ○ p24
present: ■ For acute primary HIV infection
■ Vaginal pH > 4.5 ■ Accurate for 11 days to 1 month after getting infected
■ Thin, milky, noninflammatory, vaginal discharge ■ Usually not used by itself to screen for HIV infection
■ > 20% clue cells seen microscopically ○ HIV 1 and 2
■ A fishy odor after addition of 10% KOH to vaginal ● Management
secretion samples (positive “whiff test”) ○ During pregnancy
TRICHOMONIASIS ■ Management should begin with antiretroviral therapy
● Causative agent: Trichomonas vaginalis ● Recommended for all HIV infected pregnant woman
● Presentation: Foamy leukorrhea with pruritus & irritation ○ During Labor and delivery
● Treatment: Metronidazole 2gm dose ■ Delayed cord clamping in preterm neonates is acceptable
● Diagnosis: ■ Neuraxial analgesia is suitable
○ Wet smear: parasites seen microscopically moving briskly in ■ Postpartum hemorrhage is best managed with oxytocin
a sample mixed on a slide with saline and prostaglandin analogues
● Management ● Methylergonovine (Methergine) and other ergot
○ For those with HIV infection: Metronidazole 500mg orally alkaloids adversely interact with reverse transcriptase
BID for 7 days and protease inhibitors to cause severe
● Neonatal Outcomes vasoconstriction: not recommended
○ Perinatal transmission of trichomoniasis by direct contact in ○ Mode of delivery
the birth canal is rare but may lead to: ■ Cesarean delivery done to decrease perinatal
■ Neonatal respiratory or genital infection transmission to 50%
■ Preterm birth, preterm PROM and SGA newborns ■ Antiretroviral therapy is given with CS perinatal
CANDIDIASIS transmission is decreased by 87%
● Causative agent: Candida albicans ■ Scheduled delivery is recommended at 38 weeks’
● Presentation: gestation in these women to avert spontaneous labor
○ Extremely profuse, irritating discharge associated with ■ Vaginal delivery in women with HIV RNA levels ≤1000
pruritic, tender, edematous vulva copies/mL may be considered at 39 weeks after proper
● Treatment for symptomatic patients for 7 days: counselling
○ Clotrimazole 1% ○ ART in Pregnant women
○ Miconazole 2% ■ Those who are taking ART and became pregnant: advised
○ Terconazole 0.4 - 0.8% to just continue ART
HIV ■ Those who are ART naive, never been given ART, and
● Statistics then became pregnant: ART may be started
○ More than 1.2 million individuals were infected in 2013 ■ Those with history of ART but are not in ART: ART is
○ 8,500 women with HIV deliver annually in the US again restarted
○ Perinatally acquired HIV cases has decreased due to: ■ Those with no ART and presented with labor: HIV ZDV is
■ Prenatal HIV testing given intrapartum
■ ART for the woman and neonate ■ Antepartum care would include ART therapy initiated asap
● Transmission ○ Postpartum Care

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3.08b Sexually Transmitted Diseases in Pregnancy
■ Vertical transmission increased by breastfeeding, and it ● Conclusion
generally is NOT recommended for HIV-positive women in ○ STP can be prevented in 3 steps:
the US, where formula is readily available ■ Talk
■ WHO (2016) recommends breastfeeding during the first 6 ■ Test
to 12 months in nutritionally deprived countries ■ Treat
■ ART regimens not to be discontinued postpartum but
continued lifelong for the advantages of viral suppression
APPENDIX

Figure 14. HIV 1/ 2 antigen/antibody combination immunoassay screening

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3.08b Sexually Transmitted Diseases in Pregnancy

Figure 15. Table shows the recommendation of taking ART during pregnancy ☊

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