Sexually Transmitted Infections: Gonorrhea, Syphilis
1. Sanket Gawai
Thangam Karthika
2. Aidarbek K. A.
(1. Students, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Teacher, Department of Microbiology and Infectious Diseases, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic)
ABSTRACT
Sexually transmitted infections (STIs) remain a major global public health challenge, disproportionately affecting adolescents, young adults, and key populations at risk. Among the classical bacterial STIs, gonorrhea and syphilis are of particular importance because of their high incidence, severe long‑term sequelae, effect on pregnancy outcomes, and role in facilitating HIV transmission. Gonorrhea, caused by Neisseria gonorrhoeae, primarily affects mucosal surfaces of the urethra, endocervix, rectum, pharynx, and conjunctiva and is characterized by purulent genital discharge and dysuria. Untreated infection can lead to pelvic inflammatory disease (PID), infertility, chronic pelvic pain, and disseminated gonococcal infection. A major contemporary challenge is the rapid emergence of multidrug‑resistant strains, threatening the effectiveness of current first‑line regimens.
Syphilis, caused by Treponema pallidum subsp. pallidum, is a chronic systemic infection that progresses through distinct clinical stages—primary, secondary, latent, and tertiary—and can involve virtually any organ system. Vertical transmission results in congenital syphilis, a preventable but still common cause of stillbirth, neonatal death, and long‑term disability. Although syphilis is readily curable with penicillin, late diagnosis, inadequate treatment, and reinfection are frequent, particularly in resource‑limited settings.
This review provides an organized, clinically oriented overview of gonorrhea and syphilis, highlighting microbiology, epidemiology, pathogenesis, clinical manifestations, diagnostic strategies, management principles, complications, and prevention. Emphasis is placed on syndromic approaches used in low‑resource settings, evidence‑based antibiotic regimens, partner management, and integration of STI control with HIV prevention and reproductive health services. Early recognition and effective treatment of these infections are critical to reducing individual morbidity, interrupting chains of transmission, and achieving global STI control targets.
Keywords: sexually transmitted infections, gonorrhea, syphilis, Neisseria gonorrhoeae, Treponema pallidum, pelvic inflammatory disease, congenital syphilis, antimicrobial resistance, syndromic management, HIV co‑infection.
I. INTRODUCTION
Sexually transmitted infections (STIs) are infections primarily transmitted through sexual contact (vaginal, anal, or oral), and in some cases via blood products, needle sharing, or vertical transmission from mother to child. The World Health Organization (WHO) estimates more than 374 million new infections each year with four curable STIs—chlamydia, gonorrhea, syphilis, and trichomoniasis—representing a substantial burden on health systems worldwide.
Gonorrhea and syphilis, two long‑recognized bacterial STIs, continue to re‑emerge despite the availability of effective antibiotics. Their importance lies in:
- High incidence and prevalence, particularly among young sexually active populations.
- Potential for serious reproductive and systemic complications if untreated.
- Significant role in facilitating acquisition and transmission of HIV.
- Impact on pregnancy outcomes, including miscarriage, stillbirth, preterm birth, neonatal infection, and congenital anomalies.
- Challenges related to antimicrobial resistance (gonorrhea) and persistent reservoirs of infection (syphilis).
From a clinical and public health perspective, understanding the pathophysiology, risk factors, modes of presentation, and evidence‑based management strategies for gonorrhea and syphilis is crucial for medical practitioners at all levels of care.
This article focuses on two major bacterial STIs:
- Gonorrhea (Neisseria gonorrhoeae infection)
- Syphilis (Treponema pallidum infection)
GENERAL CONSIDERATIONS IN SEXUALLY TRANSMITTED INFECTIONS
1. Definition and Significance
Sexually transmitted infections are infections in which sexual contact plays a central role in transmission. Many STIs are asymptomatic, yet they can cause long‑term sequelae and ongoing transmission.
Public health significance:
- Contribute substantially to infertility, ectopic pregnancy, chronic pelvic pain, and adverse pregnancy outcomes.
- Increase susceptibility to and infectiousness of HIV by disrupting mucosal barriers and promoting inflammatory cell recruitment.
- Impose high economic costs through loss of productivity, health‑care expenditures, and need for long‑term care of complications such as neurosyphilis or congenital syphilis.
2. Modes of Transmission
- Sexual: vaginal, anal, and oral intercourse.
- Vertical: transplacental (syphilis), during passage through the birth canal (gonococcal conjunctivitis, syphilis), and through breastfeeding in certain STIs (not typical for gonorrhea or syphilis).
- Parenteral: blood transfusion (rare with modern screening), needle sharing among people who inject drugs.
- Occupational: accidental inoculation with infectious material (e.g., healthcare workers).
3. Common Risk Factors
- Multiple sexual partners or new sexual partner.
- Inconsistent or incorrect condom use.
- Early onset of sexual activity.
- Men who have sex with men (MSM).
- Sex work or transactional sex.
- History of previous STIs or HIV.
- Substance abuse, including alcohol, which impairs judgment.
- Limited access to sexual health services, stigma, and lack of comprehensive sexuality education.
4. Clinical Approach to Suspected STI
The approach to a patient with suspected STI must combine clinical evaluation, counseling, diagnosis, and treatment while ensuring confidentiality and respect.
Key steps:
- Detailed history: sexual practices, partners, contraception, previous STIs, HIV status, pregnancy status, allergies.
- Focused physical examination: inspection of external genitalia, urethral meatus, perianal region, oropharynx, skin, and in women, speculum and bimanual examination when indicated and feasible.
- Syndromic assessment: urethral discharge, vaginal discharge, genital ulcer, lower abdominal pain, scrotal swelling, and inguinal bubo are common syndromes used in low‑resource settings.
- Laboratory testing: where available, etiologic diagnosis using microscopy, culture, nucleic acid amplification tests (NAATs), and serology.
- HIV and other STI screening: offer testing for HIV, syphilis, chlamydia, hepatitis B, and C as per local guidelines.
- Partner notification and treatment: critical to prevent reinfection and further transmission.
- Counseling: risk‑reduction strategies, condom use, adherence to therapy, and follow‑up.
5. Public Health Principles
- Surveillance: monitoring incidence, prevalence, and antimicrobial resistance patterns.
- Screening programs: particularly for high‑risk groups and pregnant women (e.g., syphilis screening in early pregnancy).
- Vaccination: although not available for gonorrhea or syphilis, HPV and hepatitis B vaccines are integral parts of STI prevention programs.
- Education and stigma reduction: essential to improve health‑seeking behavior.
II. GONORRHEA
Definition and Etiology
Gonorrhea is an STI caused by Neisseria gonorrhoeae, a gram‑negative, kidney‑shaped diplococcus that primarily infects columnar or cuboidal epithelium of the urogenital tract, rectum, pharynx, and conjunctiva. It is characterized by purulent exudate and intense local inflammation.
Epidemiology
- Global burden: WHO estimates tens of millions of new cases annually, with highest incidence in sub‑Saharan Africa, Southeast Asia, and parts of the Americas.
- Age and sex distribution: predominantly affects adolescents and young adults (15–29 years). Reported rates are often higher in men, partly due to symptomatic urethritis leading to care‑seeking.
- High‑risk populations: MSM, sex workers, individuals with multiple concurrent partners, and those with prior STIs.
- Antimicrobial resistance: N. gonorrhoeae has progressively developed resistance to sulfonamides, penicillins, tetracyclines, fluoroquinolones, and increasingly to third‑generation cephalosporins and macrolides, prompting classification by WHO as a “priority pathogen.”
Pathogenesis and Pathophysiology
- Attachment: Pili and outer membrane proteins (e.g., Opa proteins) mediate adherence to epithelial cells.
- Invasion: Bacteria are endocytosed and traverse the epithelium to the submucosa, where they multiply.
- Evasion of host defenses: Antigenic and phase variation of surface structures, production of IgA protease, and resistance to complement‑mediated killing.
- Inflammation: Intense neutrophilic response produces characteristic purulent discharge; damage to mucosa predisposes to ascending infection in women.
Clinical Manifestations :-
A. Urogenital Gonorrhea
1. In Men
- Incubation period: typically 2–7 days after exposure.
- Urethritis:
- Symptoms: dysuria (burning micturition), purulent urethral discharge (often yellow‑green), urethral pruritus.
- Signs: erythema at the meatus, profuse discharge on milking the urethra.
- Asymptomatic infection: up to 10% of men may have minimal or no symptoms, especially with pharyngeal or rectal infection.
2. In Women
- Incubation period: usually 7–14 days, but highly variable.
- Cervicitis:
- Symptoms: increased or altered vaginal discharge, intermenstrual or post‑coital bleeding, dysuria, lower abdominal discomfort; many women are asymptomatic.
- Signs: mucopurulent endocervical discharge, easily induced endocervical bleeding (“friable cervix”).
- Urethritis: dysuria, frequency, and urethral tenderness may occur.
- Bartholin’s gland infection: unilateral painful vulvar swelling and abscess formation.
B. Extragenital Gonorrhea:-
- Rectal infection: common in MSM and women engaging in receptive anal intercourse; presents with pruritus, discharge, tenesmus, or may be asymptomatic.
- Pharyngeal infection: acquired via oral sex; usually asymptomatic or presents with sore throat and mild pharyngitis.
- Conjunctival infection: particularly in neonates (ophthalmia neonatorum) but can also occur in adults via autoinoculation; manifests as profuse purulent conjunctivitis that can rapidly lead to corneal ulceration and blindness if untreated.
C. Complications: -
3. In Women
- Pelvic inflammatory disease (PID): ascending infection of the uterus, fallopian tubes, and adjacent structures.
- Clinical features: lower abdominal pain, adnexal tenderness, cervical motion tenderness, fever, purulent discharge.
- Sequelae: tubal factor infertility, ectopic pregnancy, chronic pelvic pain, perihepatitis (Fitz‑Hugh–Curtis syndrome).
2. In Men
- Epididymitis and epididymo‑orchitis: unilateral testicular pain, swelling, and tenderness.
- Urethral stricture: due to chronic inflammation and scarring (now less common with appropriate therapy).
3. Disseminated Gonococcal Infection (DGI)
- Occurs when bacteria invade the bloodstream.
- Two classic presentations:
- Arthritis‑dermatitis syndrome: migratory polyarthralgia, tenosynovitis, and sparse pustular or hemorrhagic skin lesions.
- Purulent septic arthritis without skin lesions.
- Rare complications: endocarditis, meningitis.
Diagnosis: -
1. Specimen Collection
- Men: first‑void urine or urethral swab.
- Women: endocervical or vaginal swabs; first‑void urine for NAAT.
- Extragenital sites: rectal and pharyngeal swabs in at‑risk individuals; conjunctival swabs for suspected ophthalmia.
2. Laboratory Tests
- Nucleic Acid Amplification Tests (NAATs):
- Gold standard in many settings due to high sensitivity and specificity.
- Can be performed on urine or swab specimens.
- Facilitate simultaneous testing for Chlamydia trachomatis.
- Microscopy:
- Gram‑stained smear of urethral discharge in symptomatic men showing intracellular gram‑negative diplococci within polymorphonuclear leukocytes is highly predictive.
- Less sensitive in women and for extragenital sites.
- Culture:
- Requires selective media (e.g., Thayer–Martin agar) and CO₂‑enriched environment.
- Essential for antimicrobial susceptibility testing, especially in the context of treatment failure or suspected resistance.
Management
Principles:
- Provide effective antibiotic treatment using current guidelines and local resistance data.
- Treat sexual partners empirically (“partner treatment”) to prevent reinfection and onward transmission.
- Screen for coexisting STIs, particularly chlamydia, syphilis, and HIV.
- Counsel on safe sex and need for test‑of‑cure when recommended.
Example regimens (adapt to local guidelines and resistance patterns):
- Uncomplicated urogenital, rectal, or pharyngeal gonorrhea in adults:
- A single dose of a third‑generation cephalosporin (e.g., ceftriaxone intramuscularly) plus empiric coverage for chlamydia (e.g., doxycycline), unless chlamydia has been excluded.
- Disseminated gonococcal infection:
- Hospitalization, intravenous or intramuscular ceftriaxone for several days followed by oral therapy to complete at least 7 days.
- Ophthalmia neonatorum:
- Systemic ceftriaxone and saline eye irrigation; evaluate for co‑infection with Chlamydia.
Emerging Antimicrobial Resistance
- Surveillance programs (e.g., WHO GASP, CDC GISP) track resistance to ceftriaxone and azithromycin.
- Treatment failures should prompt culture and susceptibility testing and reporting to public health authorities.
- Research into novel antibiotics and potential vaccines is ongoing but not yet implemented in routine practice.
Prevention and Control
- Consistent and correct condom use.
- Screening of sexually active individuals in high‑prevalence settings, especially MSM and sex workers.
- Routine screening of pregnant women to prevent neonatal gonorrhea.
- Prompt treatment of cases and partners, with adherence support.
- Education on risk reduction, including limiting number of partners and avoiding anonymous partners.
III. SYPHILIS
Definition and Etiology: -
Syphilis is a systemic, multistage STI caused by the spirochete Treponema pallidum subsp. pallidum. It is characterized by periods of active clinical disease interspersed with latent phases. Without treatment, it may progress to serious cardiovascular, neurologic, and gummatous complications years after initial infection. Transplacental transmission can occur at any stage, resulting in congenital syphilis.
Epidemiology
- Global resurgence: Increased incidence has been observed in many high‑income and low‑middle income countries, especially among MSM and individuals living with HIV.
- Congenital syphilis: Despite availability of cheap and effective penicillin, thousands of cases of congenital syphilis occur yearly, reflecting gaps in antenatal screening and treatment.
- High‑risk populations: MSM, sex workers, individuals with multiple partners, people who inject drugs, and sexual partners of persons with known syphilis.
Morphology and Biology of Treponema pallidum
- Thin, tightly coiled, motile spirochete.
- Cannot be cultured on artificial media; maintained only in animal models.
- Highly sensitive to environmental conditions; transmission requires close mucocutaneous contact with infectious lesions or transplacental passage.
Pathogenesis
- Entry: Through microscopic abrasions in skin or mucosa during sexual contact with an infectious lesion (chancre, mucous patch, condylomata lata).
- Dissemination: Rapidly disseminates via lymphatics and bloodstream within days to weeks, explaining systemic manifestations of secondary syphilis and involvement of fetus in congenital infection.
- Immune response: Cell‑mediated and humoral responses partly control infection but do not completely eradicate it, leading to latent stages.
Clinical Stages
A. Primary Syphilis
- Incubation period: Usually 10–90 days (average ~3 weeks).
- Primary lesion (chancre):
- Painless, indurated ulcer with clean base, most often on genitalia, but may occur in mouth, anus, or other exposed sites.
- Typically solitary, with associated painless, firm, non‑suppurative regional lymphadenopathy.
- Heals spontaneously within 3–6 weeks, even without treatment, leaving a scar or pigmentary change.
- Infectivity: Highly infectious stage.
B. Secondary Syphilis
- Occurs 4–10 weeks after appearance of chancre, due to systemic dissemination.
- General symptoms: Low‑grade fever, malaise, headache, sore throat, weight loss, generalized lymphadenopathy.
- Mucocutaneous lesions:
- Symmetric, non‑pruritic maculopapular rash involving trunk and extremities; classically involves palms and soles.
- Condylomata lata: broad, moist, highly infectious anogenital or intertriginous papules.
- Mucous patches: grey‑white plaques on oral or genital mucosa.
- Other manifestations: Patchy “moth‑eaten” alopecia, hepatitis, nephrotic syndrome, ocular or neurologic involvement.
- Secondary lesions resolve spontaneously over weeks to months but may recur.
C. Latent Syphilis
- Asymptomatic stage with seroreactivity on serologic testing.
- Early latent: within first year after infection; still considered infectious due to potential relapses.
- Late latent: beyond one year; less infectious sexually, but vertical transmission to fetus can still occur.
D. Tertiary (Late) Syphilis
Develops years to decades after initial infection in a subset of untreated individuals.
Major forms:
1. Gummatous Syphilis
- Granulomatous lesions (gummas) in skin, mucosa, bones, or viscera.
- May lead to destructive lesions of palate, nasal septum, or long bones.
2. Cardiovascular Syphilis
- Aortitis involving the ascending aorta and aortic root.
- Complications: aortic aneurysm, aortic valve insufficiency, coronary ostial stenosis.
3. Late Neurosyphilis
- Classified as meningeal, meningovascular, general paresis, or tabes dorsalis.
- Clinical features: stroke in young adults, progressive dementia, psychiatric symptoms, ataxia, lightning pains, Argyll Robertson pupil.
Neurosyphilis can also occur earlier in the course, particularly in people with HIV.
Congenital Syphilis
- Transmission: Hematogenous spread from mother to fetus, mainly after the first trimester. Risk correlates with stage and bacterial load in maternal infection.
- Outcomes: Miscarriage, stillbirth, preterm birth, low birth weight, neonatal death, or symptomatic disease.
- Early congenital syphilis (within first 2 years of life): hepatosplenomegaly, jaundice, snuffles (mucopurulent rhinitis), rash, lymphadenopathy, bone changes, anemia, and failure to thrive.
- Late congenital syphilis: interstitial keratitis, Hutchinson teeth, saddle nose, Clutton joints, sensorineural deafness, and neurologic impairment.
Diagnosis
1. Direct Detection
- Dark‑field microscopy or direct fluorescent antibody tests: used on exudate from chancres or mucous patches where available; enables visualization of motile spirochetes.
2. Serologic Tests
Serology forms the cornerstone of diagnosis and follow‑up.
a) Nontreponemal Tests
- Examples: Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR).
- Measure antibodies to cardiolipin‑cholesterol‑lecithin antigens.
- Reported as titers (e.g., 1:8, 1:32).
- Useful for: screening, assessing disease activity, and monitoring response to therapy—titers should decline after effective treatment.
- Limitations: false positives (e.g., in pregnancy, autoimmune diseases, infections) and false negatives in early primary or late syphilis (“prozone phenomenon”).
b) Treponemal Tests
- Examples: FTA‑ABS (fluorescent treponemal antibody‑absorbed), TPPA (Treponema pallidum particle agglutination), EIA/CIA (enzyme or chemiluminescent immunoassays).
- Detect antibodies specific to T. pallidum.
- Usually remain positive for life, even after successful treatment.
- Used to confirm diagnosis after a positive nontreponemal test or as initial screening in some algorithms.
3. Diagnosis of Neurosyphilis
- Requires evaluation of cerebrospinal fluid (CSF): cell count, protein, and VDRL.
- CSF VDRL is highly specific but less sensitive; negative test does not fully exclude neurosyphilis.
4. Diagnosis in Pregnancy and Newborn
- All pregnant women should be screened at first antenatal visit and again in the third trimester in high‑prevalence areas.
- For infants, diagnosis is based on maternal history, physical findings, and comparison of maternal and neonatal nontreponemal titers, supplemented by treponemal tests and clinical evaluation.
Management
Penicillin remains the drug of choice for all stages of syphilis and for congenital infection. Regimens may vary by national guidelines; examples include:
- Primary, secondary, and early latent syphilis:
- Single intramuscular dose of long‑acting benzathine penicillin G.
- Late latent syphilis or syphilis of unknown duration:
- Weekly intramuscular benzathine penicillin G for three doses.
- Neurosyphilis, ocular syphilis:
- Intravenous aqueous crystalline penicillin G for 10–14 days.
- Congenital syphilis:
- Intravenous or intramuscular penicillin for 10 days, with regimen depending on clinical and serologic findings.
Penicillin Allergy :-
- Non‑pregnant adults may receive alternative antibiotics (e.g., doxycycline) when penicillin cannot be used, provided adherence and follow‑up are assured.
- Pregnant women and infants with penicillin allergy must undergo desensitization as penicillin is the only recommended therapy for preventing congenital syphilis.
Jarisch–Herxheimer Reaction :-
- Acute febrile reaction within 24 hours after initiation of therapy, especially in early syphilis and during pregnancy.
- Features: fever, chills, myalgia, headache, exacerbation of skin lesions; may cause transient fetal distress.
- Management: symptomatic treatment with antipyretics; usually self‑limiting.
Follow‑Up:-
- Clinical and serologic follow‑up is mandatory to document treatment response and detect reinfection.
- Nontreponemal titers are repeated at 3, 6, 12 months, and annually thereafter as indicated. Four‑fold decline in titer (e.g., from 1:32 to 1:8) within 6–12 months typically indicates adequate response in early syphilis.
Prevention and Control of Syphilis: -
- Routine screening of at‑risk populations and all pregnant women.
- Early treatment of infected individuals and sexual partners.
- Education on safer sex and condom use.
- Integration of syphilis testing with HIV and antenatal services.
- Strengthening surveillance for congenital syphilis and improving access to penicillin.
IV. INTEGRATED APPROACH TO GONORRHEA AND SYPHILIS CONTROL
1. Syndromic Management
In resource‑limited settings where laboratory facilities are restricted, syndromic algorithms guide empirical treatment based on presenting symptoms and signs (e.g., genital ulcer disease or urethral discharge). Algorithms typically include coverage for both gonorrhea and syphilis when clinically appropriate.
Advantages:
- Rapid treatment at first contact.
- No dependence on laboratory infrastructure.
Limitations:
- Overtreatment or undertreatment due to poor specificity.
- Inability to detect asymptomatic infections, which are common.
2. Laboratory‑Based Etiologic Diagnosis
Where possible, etiologic diagnosis is preferred to:
- Tailor therapy based on specific pathogens and resistance patterns.
- Enable accurate surveillance and partner management.
3. Partner Notification and Expedited Partner Therapy
- All sexual partners of infected individuals within a defined look‑back period should be traced, counseled, tested, and treated.
- Some settings utilize expedited partner therapy (providing medication or prescriptions to the index patient for partners who may not present for care).
4. Integration with HIV and Reproductive Health Services
- Offering HIV testing and counseling to all patients presenting with STIs.
- Incorporating STI prevention into family planning, antenatal care, and youth‑friendly services.
- Use of pre‑exposure prophylaxis (PrEP) for HIV in high‑risk groups often coincides with intensified STI screening.
5. Vaccines and Future Directions
- There is currently no licensed vaccine for gonorrhea or syphilis. However, cross‑protection observed with some meningococcal B vaccines against gonorrhea in observational studies has renewed interest in vaccine development.
- Improved point‑of‑care tests, molecular assays for resistance detection, and microbicide research are additional promising areas.
CONCLUSION
Gonorrhea and syphilis remain central challenges in the control of sexually transmitted infections worldwide. Gonorrhea, driven by high transmission dynamics and rapidly evolving antimicrobial resistance, threatens to become untreatable in some regions without coordinated stewardship and development of new therapies. Syphilis, although readily curable with penicillin, continues to cause significant morbidity, mortality, and adverse pregnancy outcomes due to missed opportunities for diagnosis and treatment, especially among vulnerable populations.
For clinicians and public health practitioners, effective management of these infections requires a comprehensive approach that integrates:
- Detailed understanding of clinical presentations across different stages and anatomical sites.
- Appropriate utilization of laboratory tests, including NAATs for gonorrhea and treponemal/nontreponemal serology for syphilis.
- Adherence to up‑to‑date treatment guidelines, with special attention to antibiotic resistance, neurosyphilis, and pregnancy.
- Systematic partner notification, health education, and promotion of safer sexual practices.
- Strengthening of screening programs, particularly in antenatal care, HIV clinics, and among high‑risk groups.
By combining individual patient care with robust public health strategies, it is possible to substantially reduce the burden of gonorrhea and syphilis, prevent complications such as infertility and congenital infection, and move closer to global goals for STI elimination.
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