MOD5-OB2-T10-Genital Tract Infections Affecting Pregnancy.pdf

OB2 OBSTETRICS 2 Genital Tract Infections Affecting Pregnancy TRANS 10...

OB2 OBSTETRICS 2 Genital Tract Infections Affecting Pregnancy TRANS 10 MODULE 5 Raizza Lezzette Peña-Cruz, MD, DPOGS, FPIDSOG September 5, 2024 LECTURE OUTLINE 3. Clinical Manifestations 4. Screening for Gonorrhea during Pregnancy I Vulvitis 5. Diagnosis A. Bartholinitis 6. Treatment 1. Pathophysiology 7. Prevention 2. Treatment 3. Differential Diagnosis V Group B Streptococcal Infection (GBS) B. Human Papillomavirus (HPV) A. Risk Factors for GBS Neonatal Sepsis 1. Etiology B. Clinical Manifestations 2. Transmission 1. Early-onset Disease 3. Risk Factors 2. Late-onset Disease 4. Epidemiology C. Diagnosis 5. Pathogenesis 1. Culture 6. Condyloma Acuminata 2. NAAT 7. Diagnosis D. Prophylaxis for Perinatal Infections 8. Treatment E. Culture-based Prevention 9. Neonatal Infection F. Risk-based Prevention 10. Labor and Delivery G. Treatment 🧠 Must Know 📖 Book 📝 Previous Trans 11. Prevention II Vulvar Ulcers A. Herpes Simplex Virus 1. Epidemiology I. VULVITIS 2. Transmission A. BARTHOLINITIS 3. Clinical Manifestation 4. Syndromes of Genital Herpes CASE A 25-year-old, G1P0, 32 weeks AOG, consulted due to 5. HSV and Pregnancy 1 vulvar pain 6. Diagnosis 7. Treatment Inspection B. Syphilis (+) 4x5 cm tender, erythematous, fluctuant mass on the left 1. Pathogenesis vulvovaginal area 2. Transmission 3. Diagnosis of Maternal Infection 4. Stages of Syphilis 5. Congenital Syphilis 6. Recommendations during Pregnancy 7. Recommendations for Neurosyphilis 8. Treatment 9. Monitoring Response to Treatment III Abnormal Vaginal Discharge A. Bacterial Vaginosis 1. Risk Factors 2. Diagnosis 3. Adverse Effects in Pregnancy Figure 1. Clinical presentation of bartholinitis Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 4. Treatment B. Trichomoniasis 1. Trichomonas vaginalis BARTHOLIN’S GLANDS 2. Signs and Symptoms Also known as the greater vestibular glands 3. Diagnosis Vulvovaginal glands that are located immediately beneath the 4. Adverse Effects in Pregnancy fascia at about 5 and 7 o’clock on the posterolateral aspect of the 5. Treatment vaginal orifice. C. Vulvovaginal Candidiasis Each lobulated, racemose gland is around the size of a pea 1. Effects of Pregnancy Histologically, the gland is composed of cuboidal epithelium 2. Adverse Pregnancy Outcome: Congenital Candidiasis ○ The duct of each gland is lined by transitional epithelium, is 3. Signs and Symptoms approximately 2 cm in length, and opens into a groove 4. Risk Factors between the hymen and the labia minora. 5. Diagnosis Homologous to Cowper’s gland in males 6. Uncomplicated vs Complicated VVC Produces a mucinous secretion that provides moisture to the 7. Treatment epithelium of the vestibules IV Cervicitis A. Chlamydia (Chlamydia trachomatis) 1. Risk Factors 2. Adverse Pregnancy Outcome 3. Diagnosis 4. Treatment B. Gonorrhea (Neisseria gonorrhoeae) 1. Risk Factors 2. Pathogenesis Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 1 of 22  Word Catheter Insertion ○ Short catheter with an inflatable foley balloon ○ Create a stab incision across the abscess for drainage. ○ One end of the catheter — inserted into the gland and the balloon is inflated ○ Other end of the catheter— tucked into the vagina to allow cyst to drain freely ○ Catheter is left in place for 4-6 weeks. Figure 2. Diagram showing the location of Bartholin’s gland and their ducts Excision of Bartholin Duct and Gland Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 ○ For persistent deep infection, multiple recurrences of abscesses, recurrent 1. PATHOPHYSIOLOGY enlargement of the gland in women ≥ 40 BARTHOLIN DUCT CYST years old Most women are actually asymptomatic while 2% of adult women ○ Infection is quiescent develop enlargement of one or both glands. ○ Complete removal of the gland ○ Following trauma or infection, either duct may swell and ○ Bartholin’s Gland Carcinoma is obstruct to form a cyst, or if infected, cause an abscess exceedingly rare hence routine ○ The most common cause is cystic dilation of the Bartholin recommendation for excision in women duct, typically caused by distal obstruction secondary to older than 40 with persistent enlargement nonspecific inflammation or trauma with subsequent continued may not be merited; drainage and biopsy may be sufficient 📝 glandular fluid secretion resulting in cystic dilation. Cysts may vary in size and are usually unilocular, unilateral, No < 40 yrs old tense, and non-painful 3 Treatment Asymptomatic cysts ○ Chronic or recurrent cysts may have multiple compartments Incision and Problem: tendency for cysts to recur 4 Drainage Figure 4. Marsupialization. Figure 3. Diagram showing a typical Bartholin gland cyst Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 BARTHOLIN DUCT ABSCESS Bartholin duct abscesses may develop rapidly over 2-4 days, with significant acute pain and tenderness. ○ Signs of an abscess: erythema, acute tenderness, edema, cellulitis of the surrounding subcutaneous tissue ○ Without therapy, it may rupture spontaneously by the 3rd or 4th Figure 5. Word Catheter Insertion. day. Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 ○ Usually polymicrobial, reflecting the normal flora of the vagina, and is rarely caused by a sexually transmitted illness Doctor’s Notes Bartholin Duct Abscess TREATMENT ○ Broad-spectrum antibiotics: Amoxiclav, Ampicillin-Sulbactam ○ If clindamycin is given for clearance of gram positive organisms, aminoglycoside can be added 2. TREATMENT Figure 6. Excision of Bartholin Duct and Gland. Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 Antibiotic Therapy 1 Observation ○ Broad Spectrum e.g. Co-amoxiclav, Doctor’s Notes Ampicillin-Sulbactam MANAGEMENT Marsupialization ○ The same whether the patient is pregnant or not ○ Surgical treatment of choice ○ Antibiotics given should not be contraindicated in pregnancy ○ < 40 years old ○ Co-amoxiclav may be given in the 1st and 2nd trimester ONLY → not advised in the 3rd trimester; may cause 📝Surgical ○ Low recurrence rate — 5-10% 2 ○ Small incision across the cyst — fistulous necrotizing enterocolitis in the newborn tract from dilated tract to the vestibule ○ Ampicillin-Sulbactam may also be used→ can be given ○ The cyst is drained and sides are stitched across all trimesters to the surrounding skin, leaving it open. 3. 📝 DIFFERENTIAL DIAGNOSIS 1 Mesonephric cysts of the vagina (more anterior and cephalad in the vagina) 2 Epithelial Inclusion Cysts - more superficial 3 Lipoma 4 Fibroma Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 2 of 22  5 Hernia Therapy via debulking symptomatic warts yet minimizing treatment toxicity for both the mother and the fetus. 6 Vulvar Varicosity 7 Hydrocoele HIGH ONCOGENIC TYPE More bothersome B. HUMAN PAPILLOMAVIRUS (HPV) 16 & 18 most often associated with lower reproductive tract dysplasia CASE A 32-year old housewife, G2P1 (1001) at 30 weeks AOG, ○ Frequently detected in women with high-grade squamous intraepithelial neoplasia and invasive cancers. 2 complained of vaginal pruritus and multiple palpable labial and peri-anal masses as seen below. Inspection 2. 📝TRANSMISSION Table 2. Transmission of HPV. Primary route Through contact with infected genital skin, mucous membranes, or body fluids from a sex partner with clinical or subclinical HPV SEXUAL infection TRANSMISSION Highest risk groups: sexually active adolescents and young adults Highly contagious with approximately 76% of sex partners becoming infected PERINATAL Especially of HPV 6 & 11 Figure 7. Genital warts seen on patient’s labial folds TRANSMISSION Rare Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 Source: Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 1. ETIOLOGY Double-stranded DNA virus from the family papovavirus 3. 📝RISK FACTORS May result in either clinically apparent, grossly visible disease 1 Early onset of sexual activity (genital warts) or subclinical disease (more common) Genital warts frequently increase in number and size during 2 Multiple sexual partners pregnancy ○ Reason is unknown 3 Increased frequency of intercourse Acceleration of viral replication by the physiologic changes of 4 Exposure to partner with genital warts pregnancy might explain perineal lesion growth and progression of some to cervical neoplasm 5 Failure to use condoms 6 Cigarette smoking Table 1. HPV Types Smoking, oral contraceptive use and new male partner were 6, 11, 12, 42, 43, 44 predictive of new HPV infection LOW ONCOGENIC 6 & 11 - mucocutaneous genital warts, Pregnancy is associated with an increased prevalence of HPV TYPES (condyloma acuminata) infection and genital warts Immunosuppressive states result in increased viral titers of HPV 16, 18, 20, 31, 45, 54, 55, 56, 64, 68 HIGH ONCOGENIC and more rapid progression of HPV disease-associated cervical 16 & 18 - lower reproductive tract dysplasia TYPES intraepithelial neoplasia (CIN) More bothersome Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting 4. EPIDEMIOLOGY Pregnancy Part 1 Sexual transmission is the primary route. Highest risk groups for infection are sexually active adolescents and young adults. Highly contagious with approximately 65% of sex partners becoming infected Although rare, perinatal transmission, especially of HPV 6 & 11 can occur RISK FACTORS OF ACQUIRING HPV 1 Early onset of sexual activity 2 Multiple sexual partners 3 Increased frequency of intercourse 4 Exposure to a sex partner with genital warts Figure 8. Grading cervical intraepithelial neoplasia 5 Failure to use condoms Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 6 Cigarette smoking LOW ONCOGENIC TYPE 7 Smoking, oral contraceptives, & new male partner were Associated primarily with mucocutaneous genital warts predictive of new HPV infection (condyloma accuminata) from strains 6 and 11. 8 Pregnancy is associated with increased prevalence of HPV and ○ Grows in number and size during pregnancy genital warts ○ BUT, may undergo apoptosis and spontaneous resolution postpartum even without treatment 9 Immunosuppressive states result in increased viral titers of ○ Rarely, lesions fill the vagina or cover the perineum, causing HPV & more rapid progression of HPV disease-associated CIN vaginal delivery or episiotomy to be difficult — eradication is unnecessary unless patient is symptomatic Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 3 of 22 5. PATHOGENESIS during sexual intercourse and this predisposes them to infection with HPV. ACUTE HPV INFECTION ○ More prone to develop CIN and later on invasive carcinoma of Occurs when microtrauma secondary to sexual intercourse allows the cervix virus to enter skin or mucosa of genital tract The immature columnar epithelial cells in the broad transformation The postpubertal adolescent cervix is characterized by a large zone are particularly susceptible to HPV transformation zone which is more susceptible to minor trauma during sexual intercourse. The immature columnar epithelial cells in the broad transformation zone are particularly susceptible to HPV. The virus enters cells in the basal layer of the epithelium and matures as it passes through the parabasal, spinous, and granular Figure 11. Diagram of disease progression from normal epithelium of the cervix layers of the epithelium. progressing to an invasive carcinoma. Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 6. 📝CONDYLOMA ACUMINATA Frequently grow in number and size with pregnancy Commonly undergo apoptosis and resolution postpartum Rarely, lesions fill the vagina or cover the perineum and make vaginal delivery or episiotomy difficult Eradication during pregnancy is usually unnecessary unless symptomatic Therapy is directed toward debulking symptomatic wats yet minimizing treatment toxicity to the mother and fetus TRANSMISSION Through CONTACT with infected genital skin, mucous membranes or body fluids from a sex partner with clinical or subclinical HPV infection Doctor’s Notes REMEMBER: Having condyloma acuminata during pregnancy is Figure 9. Progression of cervical disease after HPV infection. not an indication to perform cesarean section, except when: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 ○ Lesions are obstructing the outlet ○ If the mass/ lesions are bleeding LATENT VIRAL INFECTION Occurs when the HPV genome is stabilized as a non integrated 7. DIAGNOSIS episome and remains in the host cells without causing clinical or morphological changes in the squamous epithelium of the genital tract 1 Visual 📝For genital warts use of HPV nucleic acid tests is not recommended in the routine diagnosis and Latency can lead to sustained remission, which is the case in most inspection HPV infections. management of visible genital warts Active infection may occur depending on the type of HPV present. Required only in the ff circumstances: Diagnosis is uncertain LOW-RISK HPV TYPES Lesions do not respond to standard Especially 6 & 11, cause proliferation of squamous epithelial cells therapy with resultant formation of genital warts 2 Biopsy Disease worsens during therapy Patient is immunocompromised Warts are pigmented, indurated, fixed, bleeding, or ulcerated Identification of viral nucleic acid (DNA or RNA) or capsid protein Digene Hybrid Capture 2 (HC 2) High Risk HPV DNA Test Only one approved by the FDA for clinical use Uses liquid nucleic acid hybridization to detect 13 high-risk HPV types Does not report type-specific results The specimen is identified as positive or negative for high-risk HPV only Test has been approved for triage of women who have Pap test results Figure 10. Genital warts that are presented in various forms. Left: genital warts Asymptomatic in a 9 yr old child who was sexually assaulted. Right: genital warts seen in a 3 showing atypical squamous cells of HPV Infection commercial sex worker which initially started as a very small lesion and undetermined significance (ASC US) and eventually grew. in combination with the Pap test for Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 cervical cancer screening in women older than 30 years of age HIGH-RISK ONCOGENIC HPV Cytologic evidence of HPV (koilocytosis) May become integrated into the host genome resulting in cervical Colposcopy intraepithelial neoplasia (CIN) Biopsy CIN may progress to precancerous lesions (CIN 2 & CIN 3) and to Acetic acid application invasive cervical cancer. PCR assays targeting genetically CIN may also resolve spontaneously, especially CIN 1 and to a conserved regions of the L1 gene and lesser extent CIN 2. HPV serologic assays to detect The postpubertal adolescent cervix is characterized by a large antibodies to the L1 viral protein (used in transformation zone which is more susceptible to minor trauma research only) Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 4 of 22 When we are presented with a pregnant Px who has condyloma acuminata, is it mandatory to treat or can we just observe? Dra. Peña-Cruz 8. TREATMENT There may be incomplete response to treatment during pregnancy, but lesions Figure 13. Juvenile-onset Recurrent Respiratory Papillomatosis commonly improve or regress rapidly Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 1 Observation following delivery. Even without treatment, if lesions are VERY 10. LABOR AND DELIVERY SMALL or very insignificant, these lesions will regress spontaneously post-partum The risk of HPV during labor and delivery is when there’s prolonged rupture of membranes. Wart Usually not necessary during pregnancy ○ Associated with a 2-fold increased risk, BUT not associated 2 Eradication with any delivery mode Directed toward minimizing treatment toxicity Long-term follow-up studies are consistent with a very LOW to the mother and fetus and debulking vertical transmission risk Goal of 3 symptomatic genital warts Therapy CESAREAN DELIVERY Therapy should be limited to patients who have multiple, confluent lesions Its benefit to decrease transmission is unknown Not recommended to solely prevent transmission Only considered if: 1. Obstruction of pelvic inlet is likely. 2. Vaginal delivery would cause massive bleeding due to multiple confluent lesions. Otherwise, the patient should undergo a trial of labor and vaginal delivery. 11. PREVENTION 1 Sexual abstinence 2 Long-term mutual monogamy with a single partner 3 Limiting the number of sexual partners 4 Limiting sexual contacts to men who have been abstinent for a longer period of time Figure 12. Recommended Regimens for External Anogenital Warts. Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 5 Having a circumcised partner 6 Using latex condoms TREATMENT OPTIONS DURING PREGNANCY 7 Receiving the HPV vaccines Safe treatment options to be used if a decision to treat condyloma acuminata during pregnancy is made: HPV VACCINES Trichloroacetic Acid (TCA) 80%–90% solution applied 1 Quadrivalent vaccine or Bichloroacetic Acid (BCA) topically once a week 1 Gardasil 4 Covers HPV types 6,11,16 &18 2 Cryotherapy Nonavalent vaccine 3 Laser Ablation 2 Gardasil 9 HPV types 6,11,16 & 18, + 31, 33, 45, 52, 58 4 Surgical Excision Bivalent vaccine 3 Cervarix HPV 16 & 18 Doctor’s Notes All are three-dose series and licensed for both females and males. TCA is safe and may be applied even if the patient is pregnant Not recommended for pregnant women If inadvertently given in a pregnant patient, no adverse 9. NEONATAL INFECTION pregnancy outcomes associated with the vaccine. Women who are breastfeeding may receive the vaccine. JUVENILE-ONSET RECURRENT RESPIRATORY If a woman is found pregnant after starting the vaccination series, PAPILLOMATOSIS (JoRRP) the remaining dose should be delayed until after delivery. Very rare, benign neoplasm of the larynx Can cause hoarseness and respiratory distress secondary to II. VULVAR ULCERS 📝 obstruction Risks for infection are maternal genital HPV infection and longer labors 1 Herpes Simplex Virus 2 Syphilis Often due to HPV Types 6 or 11 Recurrence after treatment is common. CASE A 30-year old, G3P2 (2-0-0-2) patient at 39 3/7 weeks 3 AOG, consulted at the ER due to severe dysuria. She also tells you that she has been having regular uterine contraction. On a physical exam you noted multiple, shallow vesicles and superficial ulcers over a large area of the vulva which are tender on palpation. Internal examination revealed a 5 cm dilated cervix, 50% effaced, with an intact bag of waters. The fetus is in cephalic presentation. All her previous pregnancies were delivered vaginally. Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 5 of 22 A. HERPES SIMPLEX VIRUS 📝 FIRST EPISODE, PRIMARY INFECTION Chorionic, life-long viral illness Clinical presentation in patients without antibodies to either HSV-1 ○ Once you acquire it, it will stay with you the rest of your life. or HSV-2. Typical lesions are painful vesicular or ulcerative involving only Clinical manifestation include severe local symptoms, with lesions the skin and mucous membranes. lasting 3-6 weeks, regional adenopathy, constitutional symptoms, and in a small percentage of cases, viral meningitis 1. EPIDEMIOLOGY Vesicular lesions → Ulcerative → Crusting HSV-1 or -2 is isolated from the genital secretions in the absence Table 2. HSV Types of HSV-1 or -2 antibodies Responsible for most non-genital infections. The typical incubation period of 6-8 days which may be followed More than half of the new cases of genital by a “classic presentation” TYPE 1 herpes in adolescents and young adults are ○ Characterized by a papular eruption with itching or tingling caused by HSV -1 infection probably due to an sensation which then becomes painful and vesicular increase in oral-gential practices. ○ Multiple vulvar and perineal lesions may coalesce and inguinal adenopathy may be severe Recovered almost exclusively from the genital Transient systemic influenza-like symptoms are common and are tract and is usually transmitted by sexual presumably caused by viremia TYPE 2 contact. ○ Lasts 3-6 weeks Most recurrences (>90%) are secondary to In 2-4 weeks, all signs and symptoms disappear even without HSV-2 treatment. Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Incidence of asymptomatic primary infections may be as high Pregnancy Part 1 as 80%. Whitlow: distal site inoculation NOTE: The disease is NOT more severe or more protracted in pregnancy. 2. TRANSMISSION Primarily transmitted through sexual contact Pathway of infection: ○ HSV-1 or HSV-2 replicates at the entry site. ○ Following mucocutaneous infection, the virus moves retrograde along sensory nerves. ○ Remains latent in the cranial nerves or dorsal spinal ganglia. Figure 15. First Episode/ Primary Infection in Genital Herpes. Figure 14. Pathway of a Herpes Infection. Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 1 Vesicular lesions → Ulcerative → Crusting 📝 NEONATAL TRANSMISSION FIRST EPISODE, NON-PRIMARY INFECTION The fetus becomes infected by the virus shed from the cervix or Initial clinical episode with either HSV-1 or HSV-2 in a patient who lower genital tract It either invades the uterus following membrane rupture or is transmitted by contact with the fetus at delivery 📝 has antibodies to the other serotype Diagnosed when HSV is isolated in women who have only the other serum HSV-type antibody present Neonatal herpes is caused by both HSV-1 &-2 although HSV-2 Characterized by: infection predominates ○ Fewer lesions Most infected infants are born to mothers with no reported history ○ Fewer systemic manifestations of HSV infection The risk of neonatal infection correlates with the presence of HSV in the genital tract, the HSV type, invasive obstetrical procedures, ○ Less pain ○ Briefer duration of lesions and viral shedding ( immunity from cross-reacting antibodies) 📝 due to some and stage of maternal infection Presentation is more similar to recurrent episodes than to first Infants born to women who acquire genital HSV near the time of episode primary genital herpes delivery have a 30-50% risk of infection Women with recurrent HSV have 5/mm3) or protein 5 Thickened placenta concentration (>5 mg/dl) e. Reactive test for FTA-ABS-19S-IgM 6. RECOMMENDATIONS DURING PREGNANCY antibody 📝 All pregnant women should be tested at their initial prenatal Presumptive 📝 T. pallidum can cross the placenta and infect visit. Case the fetus as early as the 6th gestational week ○ Screen universally at first prenatal check up Anatomic abnormalities in the fetus are NOT ○ Request for an RPR or a VDRL. If it turns out to be positive, apparent until after 16 weeks of gestation when request for a confirmatory test. fetal immunocompetence develops High-risk patients should be rescreened at 28 weeks of 📝 Congenital infection is uncommon before 18 gestation. weeks ○ If with high-risk factors, retest at 28-32 weeks AOG and at 📝 The risk to the fetus is present throughout delivery pregnancy ○ Any mother who delivers a newborn a stillborn after 20 The degree of risk is related to the quantity of weeks AOG should be screened for syphilis spirochetes in the maternal bloodstream In areas with high rates of congenital syphilis, rescreening at Transmission may also occur intrapartum via admission in labor is recommended. contact with active genital lesions in the mother In populations in which prenatal care is less than optimal, Women with primary or secondary syphilis are RPR-card test is recommended at the time that pregnancy is more likely to transmit infection to their offspring diagnosed, with treatment of patients who have a reactive test. than are women with latent disease Any woman who delivers a stillborn infant after 20 weeks gestation The most severe adverse pregnancy outcomes should be screened for syphilis. occur with primary or secondary syphilis No infant should leave the hospital without maternal serostatus for The newborn may develop: syphilis having been assessed at some time in the pregnancy. ○ jaundice with petechiae or purpuric skin lesions Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 11 of 22  In pregnancy, it is best to consider all seropositive women as Primary, Secondary, and Benzathine penicillin G 2.4 MU infected unless an adequate treatment history is documented and 1 Early Latent Syphilis IM single dose sequential serologic antibody titers have declined. 📝RECOMMENDATIONS FOR NEUROSYPHILIS Benzathine penicillin G 2.4 MU 2 Late Latent Syphilis 7. IM q weekly x 3 doses Can occur at any stage Aqueous crystalline penicillin G Can occur even if no neurologic findings 3-4 MU IV q 4 hours or Unless clinical signs or symptoms of neurologic involvement are continuous infusion for 10-14 present, lumbar puncture is not recommended for routine 3 Neurosyphilis days OR evaluation in primary or secondary syphilis Procaine penicillin 2.4 MU IM In patients with latent syphilis, prompt CSF examination should daily + Probenecid 500 mg PO be performed if any of the following is present: QID for 10-14 days ○ Clinical evidence of neurologic involvement (cognitive dysfunction, motor or sensory deficits, ophthalmic or 4 Penicillin-Allergic If pregnant, desensitized patient auditory symptoms, cranial nerve palsies, symptoms or signs of meningitis) JARISCH-HEXHEIMER REACTION ○ Evidence of active tertiary syphilis (aortitis, gummas or iritis) Occurs more commonly during the treatment of early syphilis Treatment failure Fever, chills, myalgia, headache, hypotension, and transient HIV infection with latent syphilis or syphilis of unknown duration worsening of cutaneous lesions after being given penicillin. ○ Recently it has been suggested that only HIV-infected patients Commences within several hours after treatment and resolves by with neurologic manifestations or serum RPR result of 1:32 or 24-36 hours greater require a lumbar tap Among pregnant women, the most frequent findings are fever ○ A study showed that an RPR titer of 1:32 or greater increased (73%), uterine contractions (67%), decreased fetal movement the odds of neurosyphilis almost 11-fold in HIV-uninfected (67%) and transient late decelerations (30%) individuals and almost 6-fold among HIV-infected patients After a pregnant woman is given penicillin, she should stay in the hospital for observation. 📝DIAGNOSIS OF NEUROSYPHILIS 📝 PENICILLIN DESENSITIZATION 1 Reactive serologic tests Desensitization can be accomplished orally or intravenously 2 Abnormal CSF cell count ○ Oral desensitization is believed to be safer and easier to perform 3 Elevated protein levels Patients should be desensitized in a hospital setting because serious IgE mediated allergic reactions can occur 4 Reactive CSF VDRL Desensitization can be accomplished in approximately 4 hours 5 Increased levels of tau protein after which the 1st dose of penicillin is administered After desensitization, patients are maintained on penicillin continuously for the duration of the therapeutic course 8. TREATMENT 📝WHO SHOULD BE TREATED? ALTERNATIVE TREATMENT NOT RECOMMENDED for pregnant patients 1 All pregnant women who have a history of sexual contact with a person with documented syphilis Efficacy for treatment of syphilis in the Erythromycin and 1 fetus and for prevention of transmission is 2 Women with dark-field microscope confirmation or the presence Azithromycin inadequate of spirochetes or serologic evidence of syphilis documented by a specific treponemal test Not used in pregnancy due to concern Doxycycline and 2 about discoloration of the infant’s 3 Patients in whom the diagnosis cannot be ruled out with certainty Tetracycline deciduous teeth 4 Those who have been previously treated but now show evidence of reinfection such as dark-field microscope confirmation or a 9. MONITORING RESPONSE TO TREATMENT fourfold rise in the titer on a quantitative nontreponemal test VDRL titer should decrease and become negative or very low within 6-12 months in early syphilis and within 12-24 months in Drug of choice: Penicillin late syphilis ○ 📝 ○ Preferred treatment for all stages of syphilis. The preparation of penicillin used and length of treatment are determined by the stage and clinical manifestation of the Rising titer indicates the need for further diagnostic measures such as a lumbar puncture and appropriate treatment For primary and secondary syphilis, patients should be disease re-examined clinically and serologically at 3-6 months, 12 months Parenteral penicillin is the only therapy with documented efficacy and 24 months after treatment ○ 📝 for syphilis during pregnancy. In pregnancy, Penicillin G is effective for treating maternal infection, preventing transmission to the fetus and treating A response is defined as two-dilution (fourfold) decline in nontreponemal titer at 1 year after treatment. Patients with signs and symptoms that persist or recur and those established fetal infection with a sustained fourfold increase in the non-treponemal test titer 📝 ○ Pregnant patients with syphilis in ANY STAGE who are have probably failed treatment or become re-infected. allergic to penicillin should be desensitized and be given ○ For treatment failure, patients should be re-treated and 📝 penicillin. assessed for HIV infection and CNS infection ○ Additional dose is given 1 week after initial dose for pregnant ○ For re-treatment, weekly injections of Benzathine penicillin women with primary, secondary, or early latent syphilis G 2.4 MU IM for 3 weeks is recommended Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 12 of 22  FACTORS CONTRIBUTING TO FAILURE TO PREVENT CONGENITAL SYPHILIS 📝 TREATMENT FOR NEUROSYPHILIS Aqueous crystalline Penicillin G 18-24 MU/day administered as 3-4 MU IV Q4 or continuous infusion for 10-14 days 1 High maternal VDRL titer at the time of diagnosis Alternative treatment: 2 Unknown duration of infection ○ Procaine Penicillin 2.4 MU IM OD + Probenecid 500 mg OD PO QID for 10-14 days 3 Treatment within 4 weeks of delivery ○ Then Benzathine Penicillin G 2.4 MU IM q weekly for 3 doses 4 Signs of fetal syphilis on ultrasound (hepatomegaly, fetal after completion of neurosyphilis treatment hydrops, placentomegaly) FOLLOW-UP POST-TREATMENT 5 Preterm delivery If CSF has pleocytosis, repeat CSF analysis q 6 months until normal If not normal after 2 years, retreatment is warranted DO CSF EXAM IF WITH… Neurologic or ophthalmic signs and symptoms Evidence of active tertiary syphilis Serologic treatment failure ○ Titers increase fourfold ○ Initially high titer fails to decline at least fourfold within 12-24 months of therapy ○ Signs and symptoms attributable to syphilis develop Even if CSF is negative, retreatment for latent syphilis should be initiated Only acceptable alternatives for late latent syphilis or unknown duration: ○ Doxycycline 100 mg BID x 28 days ○ Tetracycline 500 mg QID x 28 days 📝 TREATMENT FOR SYPHILIS IN PREGNANCY Benzathine Penicillin G but give additional dose 1 week after usual Figure 28. Syphilis Treatment Algorithm. dose for non-pregnant patients Dr. Peña Cruz’s Handout on Genital Tract Infections Affecting Pregnancy Part 1 If allergic to syphilis, desensitize then immediately administer TREATMENT OF PARTNERS III. ABNORMAL VAGINAL DISCHARGE Screen and Treat if: 1 Bacterial Vaginosis 1 Partner has been exposed within 90 days preceding diagnosis of 2 Trichomoniasis primary, secondary or early latent syphilis 3 Vulvovaginal Candidiasis 2 Partner has been exposed >90 days before diagnosis and if serologic tests are not immediately available and follow up is uncertain A. BACTERIAL VAGINOSIS Not an infection in the ordinary sense 3 If unknown duration with high nontreponemal titers (>1:32) since Maldistribution of normal vaginal flora patient is assumed to have early syphilis Numbers of lactobacilli are decreased 4 Long-term sex partners who have latent syphilis should be Overrepresentation of anaerobic bacteria including Gardnerella evaluated and treated based on findings vaginalis, Mobilincus, and some Bacteroides spp. It is marked by a major shift in vaginal flora from the normal 📝 FOLLOW-UP predominance of lactobacilli to a predominance of anaerobes It is usually polymicrobial, and a replacement of the normal hydrogen peroxide-producing lactobacilli species occurs in the Repeat clinical and serological evaluation after 6, 12, and 24 months of treatment vagina with high concentrations of anaerobic bacteria, Gardnerella vaginalis, ureaplasma, mycoplasma FAILED TREATMENT CASE With signs and symptoms of syphilis that persists or recur or Bacterial Vaginosis sustained fourfold increase in non-treponemal test titers 5 Retreat with Benzathine Penicillin G 2/4 MU q weekly x 3 weeks Review of History 📝PENICILLIN ALLERGY A 25-year-old, G1P0, 28 weeks AOG consulted due to whitish vaginal discharge 1 Desensitize Speculum Examination 2 Doxycycline 100mg BID x 14 days Whitish-grayish vaginal discharge coming out from the cervix 3 Ceftriaxone 1g OD IM or IV x 10-14 days 4 Azithromycin 2g PO SD MISSED DOSE OF PENICILLIN G Currently unclear guideline (if patient is not pregnant) If interval of 10-14 days between doses, restart sequence of injections But if pregnant, REPEAT FULL COURSE Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 13 of 22  3 Low birth weight Microscopic Examination 4 Increased neonatal morbidity Presence of clue cells and decrease in lactobacilli 5 Chorioamnionitis 6 Endometritis 4. TREATMENT Bacterial Vaginosis in the absence of symptoms does not warrant treatment RECOMMENDED TREATMENT 1. RISK FACTORS Reserved for symptomatic women who usually complain of fishy-smelling discharge 1 Multiple male or female partners When the patient is pregnant treatment must be immediately initiated because bacterial vaginosis has adverse effects in 2 New sex partner pregnancy 3 Douching Both Metronidazole and Clindamycin may be given during pregnancy 4 Vitamin D deficiency Treatment includes: 5 Young age 1 Metronidazole 500 mg BID x 7 days 6 Smoking 2 Metronidazole Gel 0.75% (5g) intravaginal OD x 7 days 7 Black race 3 Clindamycin Cream 2% (5g) intravaginal x 7 days 2. DIAGNOSIS ALTERNATIVE TREATMENT 1 Amsel’s Criteria Tinidazole 2g PO OD x 2 days Tinidazole 1g PO x 5 days 2 Nugen’s Scoring (Gram Stain) Clindamycin 300 mg bID x 7 days 3 Pap Smear Clindamycin ovule intravaginal OD x 3 days Septidazole - has very little information regarding its use during pregnancy AMSEL’S CRITERIA ○ Its use during pregnancy may be limited The patient has to meet 3 out of 4 criteria to be diagnosed with bacterial vaginosis TREATMENT FOR RECURRENCES The patient may use a different or same treatment regimen if the Thin, homogenous, gray or white discharge that smoothly coats patient has recurrence after the first occurrence a the vaginal walls The following are treatments for multiple recurrences for bacterial May have clue cells on smears, or squamous epithelial cells so vaginosis b ○ Although eradication is possible, treatment does not reduce heavily stippled with bacteria that their borders are obscured preterm birth rates. c pH >4.5 Routine Screening is also not recommended for asymptomatic Fishy order or amine-like odor accentuated upon addition of 10% patients. d Follow-ups are unnecessary if symptoms resolve. KOH or after coitus Some concepts DURING PREGNANCY: ○ Treatment is recommended for all symptomatic pregnant women Crosses the placenta, it may be given during pregnancy because there is not evidence of 1 Metronidazole teratogenicity or mutagenic effects among infants Figure 29. Bacterial Vaginosis 2 Tinidazole Should be avoided during pregnancy Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 2 3 Clindamycin Can be safely given Characteristic thick, homogenous, whitish discharge seen in bacterial vaginosis (left), clue cells; the borders of the epithelial cell is already obscured by bacteria Although, oral therapy has not been reported as superior to topical (middle), paucity of lactobacilli (right) therapy for treating symptomatic bacterial vaginosis in effecting cure or preventing adverse pregnancy outcomes. NUGENT’S SCORING (GRAM STAIN) Metronidazole is secreted in breast milk therefore some clinician Gold standard in diagnosing Bacterial Vaginosis recommend deferring breastfeeding for 12-24 hrs after maternal Scoring increase in numbers and kinds of bacteria and a reduction treatment which is single dose, 2g Metronidazole. in numbers of lactobacilli ○ However if we give Metronidazole at lower doses, this is You see less lactobacilli increase in the gram negative gram compatible with breastfeeding. variable rods and cocci and increase gram negative rods Table 5. Summary on the Treatment for Bacterial Vaginosis PAP SMEAR TREATMENT Not used for diagnosis of Bacterial Vaginosis Treatment includes: 3. ADVERSE EFFECTS IN PREGNANCY ○ Metronidazole 500 mg BID x 7 days RECOMMENDED ○ Metronidazole Gel 0.75% (5g) 1 Preterm delivery TREATMENT intravaginal OD x 7 days ○ Clindamycin Cream 2% (5g) 2 Early and late miscarriage intravaginal x 7 days Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 14 of 22  Tinidazole 2g PO OD x 2 days 3. DIAGNOSIS Tinidazole 1g PO x 5 days ALTERNATIVE TREATMENT Clindamycin 300 mg bID x 7 days Clindamycin ovule intravaginal OD x 3 days 1 Wet Saline Microscopy 🧠 Presence of trichomonads Most commonly used in clinical setting Presence of leukocytes and bacteria Septidazole - has very little information regarding its use during pregnancy 60-70% sensitivity TREATMENT FOR Metronidazole Gel 2x/week for 4-6 months Best method RECURRENCES Monthly Oral Metronidazole + Fluconazole Uses Diamond or Kupferberg Medium Examined daily for 5-7 days for Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy 2 Culture appearance of motile organisms Part 2 Results take too long making it less important in clinical setting B. TRICHOMONIASIS Unreliable (52-67% accuracy) Pap Test 3 Inflamed epithelial cells can be mistaken for CASE (Liquid Based) Trichomoniasis T vaginalis 6 4 ELISA Review of History 5 Latex Agglutination A 33-year-old, G3P1 (1011), 25-weeks AOG who consulted due to foul-smelling, greenish vaginal discharge associated with 6 PCR severe pruritus. Urine Look for the presence of trichomonads 7 Speculum Examination Sediment 🧠 Clinically, what is really used is just the Wet Mount (Wet Saline Microscopy) Dra. Pena-Cruz 4. ADVERSE EFFECTS IN PREGNANCY 1 Increased rate of PROM in term pregnancy 2 Low birth weight Strawberry cervix Greenish frothy vaginal discharge 3 Preterm delivery 4 Increased rates of HIV transmission 1. TRICHOMONAS VAGINALIS NOTE: Routine screening and treatment are NOT recommended. Flagellated, pear-shaped, motile organisms that are larger than leukocytes Patients will usually present with diffuse, malodorous, 5. TREATMENT yellow-green, frothy vaginal discharge with vulvar irritation. ○ Trichomonas reduces gas resulting in the foul-smelling odor. Table 7. Treatment for Trichomoniasis On speculum examination, you will appreciate a strawberry or flea bitten cervix and a punctate mucosal hemorrhages of the cervix. TREATMENT Flagellated protozoan moving under the microscope NON-PREGNANT WOMEN: Metronidazole Sexually-transmitted RECOMMENDED 500 mg BID x 7 days TREATMENT MEN: Metronidazole 2g PO single dose ALTERNATIVE Tinidazole 2g PO single dose TREATMENT Not given during pregnancy Rescreen 3 months after treatment FOLLOW UP There should be a documented resolution of Trichomoniasis TREATMENT Metronidazole or Tinidazole 2g OD x 7 days FAILURE Metronidazole: discontinue breastfeeding LACTATING during treatment and 12-24 hours after last PATIENT dose Figure 30. Trichomonas vaginalis as shown when samples are collected from Tinidazole: 3 days after last dose the vagina and put on a wet mount, seen under the microscope Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 2 HIV PATIENTS Metronidazole for 7 days Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy 2. SIGNS AND SYMPTOMS Part 2 Table 6. Signs and Symptoms of Trichomoniasis SIGNS SYMPTOMS Malodorous, yellow-green, frothy Intense pruritus discharge Strong odor Strawberry of flea-bitten cervix Dysuria (punctate lesions) Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy Part 2 Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 15 of 22 C. VULVOVAGINAL CANDIDIASIS (VVC) Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Usually caused by Candida albicans. Pregnancy Part 2 May become an opportunistic pathogen, especially if host defense mechanisms are compromised. 4. RISK FACTORS 2nd most common cause of vaginitis after bacterial vaginosis. 1 Glycosuria CASE Vulvovaginal Candidiasis 2 Diabetes mellitus 7 3 Pregnancy Review of History 4 Obesity A 25-year-old, G3P2 (2002), presented with severe vulvo-vaginal pruritus associated with thick, whitish vaginal 5 Recent use of antibiotics discharge 6 Steroid use Speculum Examination 7 Immunosuppression Presenting with thick, whitish vaginal discharge 5. DIAGNOSIS Wet Prep (saline, 10% Demonstrates yeasts, hyphae, and 1 KOH) or Gram Stain of pseudohyphae Vaginal Discharge Identifies Candida species However, in the absence of signs 2 Culture and symptoms, this is not an indication for treatment. Microscopic Examination Wet mount examined under the microscope: presence of 6. UNCOMPLICATED VS COMPLICATED VVC pseudohyphae Table 9. Uncomplicated vs. Complicated VVC UNCOMPLICATED VVC COMPLICATED VVC Sporadic or infrequent Recurrent VVC Mild to moderate VVC Severe VVC Candida albicans Non-albicans Non-immunocompromised Women with uncontrolled DM, debilitation, or 1. EFFECTS OF PREGNANCY immunocompromised Asymptomatic VVC affects 15% of pregnant women. Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting The hormonal environment of pregnancy in which there are high Pregnancy Part 2 levels of estrogen produces an increased concentration of vagina glycogen accounting for increased frequency of symptomatic 7. TREATMENT infection in gravid patients. MAIN TREATMENT 2. ADVERSE PREGNANCY OUTCOME Butoconazole 2% Cream 5 g intravaginal for 3 days CONGENITAL CANDIDIASIS Clotrimazole 1% Cream 5 g intravaginal for 7-14 days Clotrimazole 2% Cream 5 g intravaginal for 3 days Manifests at birth or within the first 24 hours after birth. Miconazole 2% Cream 5 g intravaginal for 7 days Results from intrauterine infection or heavy maternal colonization Miconazole 4% Cream 5 g intravaginal for 3 days at the time of labor and delivery. Miconazole 100 mg vaginal suppository OD for 7 days Clinical manifestation ranges from superficial skin infection and Miconazole 200 mg vaginal suppository OD for 3 days oral infection to severe systemic disease with hemorrhage and Miconazole 1200 mg vaginal suppository SD necrosis of the heart, lungs, kidneys, and other organs. Tioconazole 6.5% Ointment 5 g intravaginal SD Oropharyngeal candidiasis of the neonate (thrush) is the most Fluconazole 150 mg tablet SD frequent manifestation of congenital infection. Most common route of infection is by direct contact during delivery through an infected vagina. TREATMENT FOR RECURRENT VVC Potential mechanisms for intrauterine candidiasis are similar to (4 or more episodes in 1 year) those of bacterial intra-amniotic infection, including hematogenous Fluconazole 100, 150, or 200 mg tablet every 3 days (day 1, 4, 7) spread from mother-fetus, invasion of intact membranes and Maintenance: Oral Fluconazole weekly for 6 months ascending infection after rupture of the membrane. VVC has not been associated with preterm birth, preterm labor, TREATMENT FOR SEVERE VVC low birth weight or PROM. Fluconazole 150 mg, two sequential doses Asymptomatic colonization requires NO treatment. 2nd dose to be given 72 hours after initial dose 3. SIGNS AND SYMPTOMS NOTE: Table 8. Signs and Symptoms of VVC Fluconazole is contraindicated in pregnancy. Only give Fluconazole to gynecologic patients. SIGNS SYMPTOMS VVC is NOT usually acquired through sexual intercourse, so Edema Pruritus treatment for sex partners is NOT recommended. FIssures Vaginal soreness / burning Treatment of partners should be considered for women who have Excoriations Dyspareunia recurrent VVC and for male sex partners with balanitis. Thick, curdy vaginal Dysuria discharge Abdominal Vaginal discharge Group 7A & 11A | Genital Tract Infections Affecting Pregnancy 16 of 22  FOLLOW-UP Erythromycin Base 500mg PO QID for 7 Return for follow-up visits only if symptoms persist or recur within days 2 months of onset of initial symptoms. ALTERNATIVE Erythromycin ethylsuccinate 800mg PO Otherwise, if the symptoms resolve, there is no need for follow-up. REGIMENS QID for 7 days Levofloxacin 500mg OD for 7 days IV. CERVICITIS Ofloxacin 300mg BID for 7 days Source: Dr. Peña Cruz’s Lecture on Genital Tract Infections Affecting Pregnancy 1 Chlamydia (Chlamydia trachomatis) Part 2 = 2 Gonorrhea (Neisseria gonorrhoeae) NOTE: Repeat testing, preferably by NAATs, is recommended for ALL A. CHLAMYDIA (Chlamydia trachomatis) PREGNANT women 3 weeks after completion of therapy to An obligate intracellular bacterium ensure cure Most commonly encountered strains are those that attach only to Sex partners should be referred for evaluation, testing and columnar or transitional cell epithelium and cause cervical treatment infection. Untreated chlamydial infection results in substantial adverse reproductive effects, including pelvic inflammatory disease (PID) A. GONORRHEA and its sequelae of tubal factor infertility, ectopic pregnancy, and Etiology: Neisseria gonorrhea (gram-negative diplococcus) chronic pelvic pain. Chlamydial infection during pregnancy is associated with adverse CASE Gonorrhea maternal outcomes including preterm delivery, premature rupture 8 of membranes (PROM), low birth weight, and neonatal death Untreated chlamydial infection may result in neonatal conjunctivitis Review of History or pneumonia or both A 20-year-old, G2P1 (1011), delivered vaginally to a baby with the following eye infection 1. RISK FACTORS Physical Examination Partners with non-gonococcal 1 Unmarried status 7 urethritis Presence of mucopurulent 2 Age younger than 25 8 endocervicitis Sterile pyuria (Acute Urethral 3 Multiple sex partners 9 Syndrome) New s