L9 Infection and Immunity Sexually transmitted infections

Overview

This lecture covers the three classic bacterial STIs, chlamydia, gonorrhoea and syphilis, tracking each from organism biology through clinical presentation, diagnosis and current treatment, framed by rising notification rates in the US, Europe and New Zealand. A shared theme across all three is that infection, especially in women, is frequently asymptomatic, which drives silent transmission and delayed complications such as pelvic inflammatory disease (PID), infertility and neonatal infection.

Epidemiology

• STI notifications have been rising in the US, Europe and NZ. US 2019 CDC data: >2.5 million combined cases of chlamydia, gonorrhoea and syphilis, an all-time high for the 6th consecutive year (chlamydia 1.8 million, up 19% since 2015; gonorrhoea 616,392, up 56%; syphilis 129,813, up 74%; congenital syphilis 1,870, up 279%).
• 2021 US data (separate source): 1.6 million chlamydia cases, 710,151 gonorrhoea cases, 176,713 syphilis cases, 2,855 congenital syphilis cases.
• NZ rolling 12-month trends (2019Q1-2022Q4): syphilis case counts peaked around 2019, fell to a low near 2022Q2, then rose again; gonorrhoea rate fluctuated 110-155 per 100,000; chlamydia rate declined from ~620 to ~430 per 100,000 then rose slightly.
• NZ region ranking data (by syphilis case number, gonorrhoea rate, chlamydia rate) shows Auckland consistently high-ranked across all three; Nelson Marlborough, West Coast and South Canterbury consistently low-ranked.
• NZ term note: NZ uses “STIs” (Sexually Transmitted Infections) rather than “STDs” (Sexually Transmitted Diseases).

Chlamydia

Biology

• Chlamydia trachomatis is an obligate intracellular bacterium, weakly Gram-negative, ovoid and non-motile, non-spore-forming.
• Infectious cycle: the elementary body (EB) acts spore-like when released and infects a new cell; after about 8 hours it transforms into a reticulate body (RB), which multiplies inside an isolated compartment called an inclusion. [The detailed developmental-cycle diagram (binding/invasion, inclusion formation, RB replication, aberrant body/persistence, transition back to EB, host cell exit by lysis or extrusion) was marked explicitly non-examinable on the slide.]

Symptoms

• Acute symptoms appear 7-21 days after infection.
• Men: painful ejaculation, penile discharge (non-gonococcal urethritis with mucoid discharge), testicular swelling (epididymitis).
• Women: painful intercourse, vaginal discharge, bleeding between periods, cervicitis (inflamed, friable cervix).
• Most infections in both sexes are asymptomatic; about 7 in 10 infected women have no symptoms.
• Chronic complication: Pelvic Inflammatory Disease (PID), from repeated inflammation and scarring of the fallopian tubes, causing infertility (responsible for 25% of infertility in the US) and ectopic pregnancy.

Diagnosis

• Nucleic acid amplification tests (NAATs, e.g. PCR, DNA probes, ligase chain reaction, or automated systems such as Panther or BD Viper) are the most sensitive and most commonly used tests.
• Specimens: first-pass urine or swabs (vaginal, urethral, endocervical, rectal). Males are better detected from urine; females better detected from genital swabs.
• Other methods: tissue culture (e.g. McCoy cells, no longer routine); Giemsa/iodine/fluorescent-antibody staining of inclusion bodies; antibody detection (fluorescent or ELISA) targeting LPS/MOMP.

Treatment

• Azithromycin 1 g orally as a single dose, or doxycycline 100 mg orally twice daily for 7 days.

Gonorrhoea

Biology

• Neisseria gonorrhoeae is a Gram-negative, facultative intracellular diplococcus, transmitted sexually to genitals or pharynx.
• Pathogenesis (5 phases): (1) entry via sexual contact and attachment to microvilli; (2) endocytosis into the epithelial cell; (3) intracellular trafficking toward the nucleus; (4) transit across the basement membrane with release of LPS and enzymes causing cell damage, uptake by macrophages (bacterial killing) and TNF release; (5) polymorphonuclear (PMN) response producing infectious exudate.

Symptoms

• Acute symptoms occur 1-14 days post infection. [flag: slide text describing the discharge was garbled, likely intended as “Purulent discharge: yellow/white, sometimes greenish”]
• Men: greenish-yellow or whitish penile discharge; burning on urination; burning in throat and swollen throat glands (from oral sex); painful or swollen testicles.
• Women: greenish-yellow or whitish vaginal discharge; lower abdominal/pelvic pain; burning on urination; conjunctivitis; bleeding between periods; spotting after intercourse; vulvitis; burning in throat (from oral sex).
• Disease progression follows incubation, prodromal, illness (with a possible death branch if untreated) and convalescent stages.

Sex differences

• Infection risk after a single exposure: 50% in females vs 20% in males.
• Females are frequently asymptomatic and undiagnosed and are the major reservoir of infection; 95% of males are initially symptomatic (acute).
• Female primary site is the cervix (cervicitis), though vagina, urethra and rectum can be colonised; male infection is generally restricted to the urethra (urethritis) with purulent discharge and dysuria.
• Ascending infection occurs in 10-20% of females (salpingitis, tubo-ovarian abscesses, PID, chronic infection can cause sterility); male complications (epididymitis, prostatitis, periurethral abscess) are rare.
• Disseminated infection (septicaemia, skin and joint infection) occurs in 1-3% of females and is very rare in males.
• Females can transmit infection to the infant at delivery, causing conjunctivitis/ophthalmia neonatorum; disseminated disease in males is more common in men who have sex with men than in heterosexual men.
• As with chlamydia, gonorrhoea in women is usually asymptomatic, with downstream risk of PID, infertility, and neonatal infection.

Diagnosis and treatment

• Preferred diagnosis: NAAT (especially PCR), requiring a first-pass urine sample of about 20 mL.
• Culture is acceptable only in limited circumstances, mainly to test for drug resistance, from pharyngeal, urethral (men), or endocervical/vaginal (women) specimens; requires enriched selective medium (e.g. Thayer-Martin), moist conditions, 5% CO2, 48 hours.
• Microscopy shows intracellular Gram-negative diplococci; presumptive identification is Gram-negative, oxidase-positive diplococci, confirmed by monoclonal antibodies, biochemical tests, or MALDI-TOF.
• DNA testing (e.g. Panther, BD Viper) has higher sensitivity but lower specificity than culture.
• Treatment: single dose of intramuscular ceftriaxone 250 mg plus oral azithromycin 1 g; completing the full prescribed course is important for cure.
• Antimicrobial resistance in NZ (2017-2021): azithromycin resistance rose from ~1.5% (2017) to a peak of ~9.2% (2020) before falling to ~5.4% (2021), with an intermediate dip to ~3.3% (2019); ceftriaxone reduced susceptibility stayed low throughout (~0.4-1.5%). [flag: the resistance data table referenced alongside this graph was cut off on the slide and its contents are not available]
• The pharynx is highlighted as a “silent reservoir” for gonorrhoea. Evidence for transmission by kissing (including French kissing) is not strong, per a Lancet Infectious Diseases personal view (Hook & Bernstein, 2019).

Neonatal infection

• Chlamydia trachomatis causes disease in about 50% of exposed neonates, most commonly inclusion conjunctivitis, with pneumonia in 5-10%.
• Gonorrhoea causes ophthalmia neonatorum (neonatal conjunctivitis with eye swelling and discharge) in exposed infants.

Syphilis

Biology

• Treponema pallidum subspecies pallidum, discovered in 1905 by Fritz Schaudinn and Erich Hoffmann, is a slender spirochaete.
• It does not Gram stain and cannot be cultured; it has endoflagella between the inner and outer cell membranes; it does not survive well outside the body and is sensitive to drying, heat and disinfectants.
• Transmitted sexually, entering through minute abrasions; it can cross the placenta.
• Recent NZ data show a sharp rise in syphilis cases from 2013 to a peak of over 210 cases in 2019 Q1 (dominated by men who have sex with men, MSM), fluctuating between 100-175 cases through 2019-2022, with an increasing share of cases in heterosexual women (WSM) over time. [flag: an outbreak-warning news article referenced on this topic had its text cut off at the bottom of the slide, so the full detail of the DHB’s handling of the 2018 Auckland syphilis outbreak is not available beyond: it was repeatedly warned of “out of control” rates before cutting sexual health positions, and there were stillbirths from mother-to-child transmission]

Stages and course (if untreated)

• Primary: chancre, appearing 10-90 days after infection (typically around 3 weeks); may be inconspicuous/subtle.
• Secondary: eruptions occurring 6 weeks to 6 months after infection (5-8 weeks after primary resolves; typically 2-12 weeks post-primary). Rash is initially maculopapular, then papulosquamous; starts on the trunk and spreads outward, may involve palms and soles, and can resemble pityriasis rosea. An uncommon secondary manifestation is condylomata lata: broad, moist, highly infectious wart-like plaques in intertriginous folds, especially genital/anal, which can become hypertrophic mushroom-like masses 1-3 cm across.
• From secondary disease, 25-60% progress to early neurosyphilis, and 25% relapse back into secondary disease. Primary and secondary stages together form the “active disease/infectious” phase.
• Latency: early latent lasts 12-24 months; late latent lasts 1-46 years; this marks the boundary between infectious and non-infectious disease. Overall latency can last up to 20 years.
• Tertiary: occurs 10-30 years after primary infection in about one-third of untreated patients. Extensive tissue damage from cell-mediated immunity (CMI), producing “gumma” lesions in soft tissue and bone; can progress to insanity and death. Tertiary disease branches into gummatous and neurologic forms, both of which can lead to cardiovascular disease.
• Congenital syphilis is separately classified as early (<2 years old) or late (≥2 years old).

Diagnosis

• Combination of treponemal and non-treponemal tests interpreted alongside history and clinical findings:
  • CLIA or EIA: screening treponemal test.
  • TPPA: confirmatory treponemal test.
  • RPR: non-treponemal test used to monitor treatment response.
• Interpretation patterns: all three negative/not done indicates no syphilis or early seroconversion; indeterminate/negative/non-reactive suggests likely no syphilis, ruling out early seroconversion with a repeat test in 2-4 weeks; all three reactive indicates syphilis of any stage, previously treated disease, or another treponemal infection; various indeterminate/reactive combinations indicate syphilis of any stage except secondary, early seroconversion, previous treatment, or another treponemal infection; a reactive CLIA/EIA with non-reactive TPPA is usually a biologic false positive, requiring repeat testing.

Treatment (2015 CDC guidance)

• Primary, secondary, or early latent syphilis: Benzathine penicillin G 2.4 million units intramuscularly as a single dose.
• Late latent syphilis or latent syphilis of unknown duration: Benzathine penicillin G 7.2 million units total, given as 3 weekly intramuscular doses of 2.4 million units.
• Neurosyphilis or ocular syphilis: Aqueous crystalline penicillin G 18-24 million units per day, given as 3-4 million units IV every 4 hours (or continuous infusion), for 10-14 days.

Self-test

1. Describe the elementary body to reticulate body transition in Chlamydia trachomatis, including where replication occurs.
2. List the acute symptoms of chlamydia in men and in women.
3. What proportion of infected women with chlamydia are asymptomatic, and why is this clinically significant?
4. Describe the mechanism by which chlamydia and gonorrhoea lead to infertility.
5. What is the first-line NAAT-based diagnostic approach for chlamydia, and how does optimal specimen type differ between men and women?
6. State the two recommended chlamydia treatment regimens.
7. Describe the five phases of Neisseria gonorrhoeae pathogenesis from entry to exudate formation.
8. Distinguish the clinical course of gonorrhoea in men from that in women, including risk of infection per exposure and disseminated disease rate.
9. Explain why women are described as the “major reservoir” for gonorrhoea.
10. Describe the recommended treatment regimen for gonorrhoea and why both drugs are given together.
11. Describe the trend in azithromycin resistance in Neisseria gonorrhoeae in New Zealand from 2017 to 2021, and how it compares with ceftriaxone.
12. What neonatal complications can result from maternal chlamydia and gonorrhoea infection respectively?
13. Distinguish Treponema pallidum from Chlamydia trachomatis and Neisseria gonorrhoeae in terms of Gram staining and culturability.
14. Describe the four stages of untreated syphilis in order, with approximate timing for each.
15. What is condylomata lata, and at what stage of syphilis does it occur?
16. A patient has reactive CLIA/EIA, reactive TPPA and reactive RPR. What does this combination indicate?
17. A patient has reactive CLIA/EIA but non-reactive TPPA. What is the likely interpretation and next step?
18. State the syphilis treatment regimen for primary/secondary/early latent disease versus neurosyphilis.
19. Explain why chlamydia and gonorrhoea are both described as often “silent” infections, and what downstream consequence this shares across all three STIs covered in this lecture.

Answers

Reveal answers

1. The elementary body (EB) is released from an infected cell and acts spore-like, allowing it to survive and infect a new host cell. After about 8 hours inside the new cell, the EB transforms into a reticulate body (RB), which multiplies within an isolated compartment called an inclusion. [The full developmental cycle diagram beyond this was marked non-examinable.]
2. Men: painful ejaculation, penile discharge, testicular swelling. Women: painful intercourse, vaginal discharge, bleeding between periods.
3. About 7 in 10 infected women are asymptomatic. This is clinically significant because it allows silent ongoing transmission and delays diagnosis, increasing risk of chronic complications such as PID.
4. Repeated inflammation from infection causes scarring of the fallopian tubes (PID), which can obstruct normal transport of eggs/embryos, leading to infertility (25% of US infertility is attributed to PID) and ectopic pregnancy.
5. Nucleic acid amplification tests (NAATs, e.g. PCR) are the most sensitive and most commonly used, run on first-pass urine or swabs. Men are better detected from urine; women are better detected from genital swabs.
6. Azithromycin 1 g orally as a single dose, or doxycycline 100 mg orally twice daily for 7 days.
7. (1) Entry via sexual contact with attachment to microvilli; (2) endocytosis into the epithelial cell; (3) intracellular trafficking toward the nucleus; (4) transit across the basement membrane, release of LPS and enzymes damaging cells, macrophage uptake/killing and TNF release; (5) PMN response producing infectious exudate.
8. Women have a 50% infection risk per exposure vs 20% in men, and are frequently asymptomatic (major reservoir) vs 95% of men being acutely symptomatic. Women’s primary site is the cervix with possible ascending infection (10-20%, salpingitis, tubo-ovarian abscess, PID, sterility) and disseminated infection in 1-3%; men’s infection is generally restricted to the urethra, with rare complications (epididymitis, prostatitis) and very rare dissemination.
9. Because infection in women is frequently asymptomatic and undiagnosed, women act as the main ongoing source of transmission in the population without being identified or treated.
10. Single intramuscular dose of ceftriaxone 250 mg plus a single oral dose of azithromycin 1 g; dual therapy is used to ensure cure and address resistance, and the patient must take the full prescribed course.
11. Azithromycin resistance rose from about 1.5% (2017) to a peak of about 9.2% (2020), with an intermediate dip to about 3.3% in 2019, then fell to about 5.4% by 2021, an overall increasing and fluctuating trend. Ceftriaxone reduced susceptibility stayed consistently low across the same period (roughly 0.4-1.5%), showing far less resistance development.
12. Chlamydia: about 50% of exposed neonates develop disease, mostly inclusion conjunctivitis, with pneumonia in 5-10%. Gonorrhoea: causes ophthalmia neonatorum (neonatal conjunctivitis).
13. T. pallidum does not Gram stain and cannot be cultured at all, unlike C. trachomatis (weakly Gram-negative, can be grown in tissue culture such as McCoy cells, though not routinely) and N. gonorrhoeae (Gram-negative, grown on enriched selective culture media such as Thayer-Martin).
14. Primary: chancre, 10-90 days after infection. Secondary: eruptions, 6 weeks to 6 months after infection. Latency: asymptomatic period, up to about 20 years. Tertiary: 10-30 years after primary infection, in about one-third of untreated patients.
15. Condylomata lata are broad, moist, highly infectious wart-like plaques that form in intertriginous folds (especially genital/anal areas), which can become hypertrophic mushroom-like masses. They occur as a relatively uncommon manifestation of secondary syphilis.
16. All three reactive indicates syphilis at any stage, which may be a previously treated infection, or another treponemal infection.
17. This pattern (reactive screening test, non-reactive confirmatory test) usually represents a biologic false positive; the recommended next step is to repeat testing, and re-evaluate if results change.
18. Primary/secondary/early latent: Benzathine penicillin G 2.4 million units IM as a single dose. Neurosyphilis/ocular syphilis: Aqueous crystalline penicillin G 18-24 million units per day IV (3-4 million units every 4 hours or continuous infusion) for 10-14 days.
19. Most chlamydia and gonorrhoea infections, especially in women, cause no symptoms, allowing infection to persist and spread undetected. Across all three STIs in this lecture, this silent transmission (or, for syphilis, a long latent period) enables progression to serious downstream complications, PID and infertility for chlamydia/gonorrhoea, and neonatal infection or tertiary organ damage for syphilis, before the infection is diagnosed and treated.