Oxford Handbook of Genitourinary Medicine, HIV, and Sexual
Health (2 edn)
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Introduction
Gonorrhoea—literally ‘flow of seed’ as named by Galen, Greek physician, in the 2nd century AD—has probably been known to be sexually transmitted for several millennia as shown by references in the Old Testament (Leviticus 15) and attribution of ‘strangury’ to ‘pleasures of Venus’ by Hippocrates.
Aetiology: Neisseria gonorrhoeae
Gram-negative kidney-shaped coccus about 1μm in diameter; appear in pairs (diplococci) with concave aspects facing each other, typically inside polymorphonuclear leucocytes (PMNLs). Fastidious growth requirements: temperature 35–37°C, pH 6.5–7.5, atmosphere containing 5–7% carbon dioxide, and selective and enriched culture media (e.g. Thayer–Martin or Modified New York City) supplemented with iron, essential amino acids, glucose, and antimicrobials to inhibit other organisms
Humans are the only natural host. Primarily infects the columnar epithelium of lower genital tract, rectum, pharynx, and conjunctiva with transluminal spread to epididymis and prostate in ♂ and endometrium and pelvic organs in ♀ with occasional haematogenous dissemination.
Epidemiology and transmission
WHO estimates 62 million cases annually worldwide. In the UK the incidence peaked in the late 1960s and early 1970s. This was followed by a marked fall between 1985 and 1995 coinciding with the AIDS awareness campaign. However, since 1997 there has been a steady upward trend.
Highest incidence in the following: young people, urban dwellers, socio-economically deprived persons, migrants, and certain ethnic minorities. Rates of gonorrhoea are regarded as surrogate markers of unsafe sexual behaviour. An episode of gonorrhoea does not confer immunity as outer membrane proteins vary. Reinfection is common.
Closely associated with other STIs, especially Chlamydia trachomatis (up to 40% of ♀ and 25% of ♂ with gonorrhoea).
Sexual and non-sexual transmission
Anogenital and pharyngeal infections
Almost exclusively sexually transmitted. Although recoverable from laboratory, suspensions left on surfaces, such as toilet seats for up to 24 hours; loses viability on drying and evidence of transmission from toilet seats is contentious. Fomite transmission is very unusual but anecdotal cases have been reported following the shared use of a portable male urinal and inflatable sex doll.
Adult conjunctivitis
Often associated with anogenital infection due to autoinoculation but non-sexual transmission is possible as reported in sporadic epidemics and isolated cases attributed to poor hygiene, accidental inoculation, or irrigation with urine (folk remedy). Flies have been implicated as vectors responsible for an outbreak in Australia.
Neonatal infection
Vertical transmission due to exposure in birth canal following rupture of membranes.
♂ to ♀ infection after one episode of sex: 60–80%. Risk reduced by about 40% by use of condom.
♀ to ♂ infection after one episode of sex: 20%. Risk reduced by up to 75% by use of condom.
Pharynx to urethra: 26% of partners.
Vertical transmission: up to 30%.
Pharyngeal infection: almost 100% in 12 weeks.
Anogenital and conjunctival infections: no data available.
Clinical features
Sites of infection
Commonly identifiable at several different sites (Table 7.1).
| Heterosexual ♂ (%) | MSM* (%) | ♀ (%) | |
|---|---|---|---|
Urethra | >90 | 60–70 | 65–75 |
Cervix | – | – | 80–90 |
Pharynx ± other site(s) | 3–10 | 10–30 | 5–15 |
Pharynx only | <5 | 10–15 | <5 |
Rectum ± other site(s) | – | 25–50 | 25–40 |
Rectum only | – | 20–40 | 5 |
| Heterosexual ♂ (%) | MSM* (%) | ♀ (%) | |
|---|---|---|---|
Urethra | >90 | 60–70 | 65–75 |
Cervix | – | – | 80–90 |
Pharynx ± other site(s) | 3–10 | 10–30 | 5–15 |
Pharynx only | <5 | 10–15 | <5 |
Rectum ± other site(s) | – | 25–50 | 25–40 |
Rectum only | – | 20–40 | 5 |
MSM = ♂ who have sex with ♂
Male genital infection
Symptoms
Incubation period: 5–8 days, range 1–14.
Urethral discharge in 80% (typically profuse and yellow/green/white) and/or dysuria in 50%. May be scanty and mucoid initially but becomes profuse and purulent within 24 hours. Asymptomatic in 5–10%.
Signs
Mucopurulent or purulent urethral discharge, typically profuse but if scanty can be elicited by urethral massage.
Erythema of the urethral meatus sometimes with oedema.
Urine ‘threads’—plugs of pus from urethral (Littré’s) glands in first passed 20mL urine indicating anterior urethritis.
Female genital infection
Symptoms
Asymptomatic in 50–70% (>50% are usually seen as contacts).
Symptoms, when present, appear within 10 days of infection.
↑ vaginal discharge in up to 50% (often related to co-infection).
Lower abdominal pain in up to 25%.
Dysuria without frequency ~12%.
Intermenstrual bleeding or menorrhagia (unusual).
Signs
Commonly no abnormal findings.
Cervix: mucopurulent discharge and easily induced bleeding (<50%).
Pelvic/lower abdominal tenderness (<5%).
Extragenital infections in ♂ and ♀
Rectal infection
In MSM
In the UK ↓ between 1985 and 1995 (following AIDS awareness campaign) but has since ↑. Usually asymptomatic (~90%) but may cause anal discharge, pain, discomfort, or pruritus, and less frequently rectal bleeding, tenesmus, and constipation. Proctoscopy may show mucoid or purulent discharge, erythema, oedema, and friability.
In ♀
An estimated 10% (possibly more) may be due to anal sexual intercourse. The positive correlation with duration of cervical infection suggests tracking of infected material into the anal canal as the main cause. Usually asymptomatic but symptoms and signs as in ♂.
Pharyngeal infection
Asymptomatic in >90%. Occasional mild pharyngitis and/or cervical lymphadenopathy. Almost 100% spontaneous clearance within 12 weeks but significant association with disseminated gonococcal infection.
Conjunctival infection
Adult infection, which is uncommon, presents with purulent discharge and inflammation affecting one or both eyes. If untreated, complications such as keratitis and pan-ophthalmitis, can lead to blindness.
Prepubertal children
In girls the vulval and vaginal epithelium are vulnerable to infection. Although theoretically infection may be acquired accidentally from infected secretions, especially with poor sanitation and hygiene, gonorrhoea is a strong indicator of sexual abuse. It usually presents as a purulent oedematous vulvovaginitis.
Gonococcal urethritis in boys, or pharyngeal and rectal infection in both sexes, is almost always the result of sexual abuse.
Complications
In ♂
Infection of the median raphe: linear erythematous swelling.
Tysonitis: painful swelling of parafrenal gland.
Meatal para-urethral gland abscess.
Peri-urethral cellulitis and abscess: inflammation of Littré’s glands with duct obstruction produces small cysts and abscesses causing tender swelling in fossa navicularis or bulb. Urine flow may be restricted. Painful erections ± ventral angulation if corpus spongiosum is affected.
Urethral strictures and fistulae: sequelae of peri-urethral abscess in untreated infection.
Cowperitis and abscess: Cowper’s (bulbo-urethral) glands at the base of the prostate are affected, causing fever, pain in perineum, particularly on defecation, and urinary frequency or retention. Abscesses usually point to one side of the perineum or are palpable rectally.
Prostatitis and seminal vesiculitis: acute features include: fever, malaise, perineal discomfort, tenesmus, suprapubic pain, urgency of micturition or retention, haematuria, and painful erections. A tender swollen prostate on rectal examination. Chronic prostatitis may develop.
Chapter In ♀
Inflammation of para-urethral (Skene’s) glands.
Bartholinitis ± Bartholin’s abscess: single or bilateral. Vulval pain and erythema with tender cystic swelling of the posterior half of the labium majora. Pus may be seen or expressed from the duct orifice.
Systemic
Perihepatitis (Fitz-Hugh–Curtis syndrome)
Disseminated gonococcal infection (DGI)
Occurs in <1% with mucosal infection.
Host factors:
4-fold ↑ in ♀ (especially during or just after menstruation or in pregnancy particularly with pharyngeal infection)
complement deficiency predisposing to recurrent episodes in <10% with DGI.
Bacterial factors:
serogroup IA-1(WI)
auxotype AHU− (arginine, hypoxanthine, and uracil dependent)
complement resistance.
penicillin sensitivity and vancomycin susceptibility but these vary over time and penicillin-resistant strains now play a significant role.
Clinical features
The preceding mucosal infection tends to be asymptomatic. Usual presentation: mild fever, skin rash, and arthralgia ± arthritis.
Skin (gonococcal dermatitis) in 67%: initial macules develop into papules, vesicles with petechiae, and then typical necrotic pustules surrounded by erythema. Usually at extremities (especially hands).
Skeletal: tenosynovitis (in ~33%) producing migratory arthralgia mostly in wrists, fingers, toes, and ankles. Arthritis (single joint), in ~50%, with effusion typically involving the knee, wrist, or metacarpo-phalangeal joints.
Other sites (rare):
heart: endocarditis in 1–3% leading to aortic incompetence and cardiac failure; also pericarditis and myocarditis.
hepatitis
meningitis, similar to meningococcal (very rare).
Pregnancy and the neonate
In pregnancy the proportion of pharyngeal infection is ↑ by 15–35%, presumably due to ↑ in oral sex. Genital infection is less likely to be complicated by PID (because of thickening of cervical mucus) but cases of salpingitis have been reported in the 1st trimester.
Adverse pregnancy outcomes
Infection of chorio-amnion can cause septic abortion but there is no consistent evidence for ↑ risk.
Preterm delivery and low birth weight ↑ 3- to 6-fold.
Premature rupture of membrane (PROM) is more frequent.
Postpartum/intrapartum or postabortal endometritis and pyrexia illness are ↑ (3-fold) and occur in ~42% with gonorrhoea.
Some studies suggest that risk of DGI is ↑, reflecting ↑ pharyngeal infection.
Screening in pregnancy advisable in PROM, septic abortion, intra/postpartum fever, or those considered to be at risk.
Neonatal gonococcal infection
Occurs because of exposure in birth canal during labour.
Gonococcal ophthalmia neonatorum
A notifiable disease in the UK, defined as conjunctivitis with a purulent discharge in an infant arising within 21 days of birth. Occurs in 30–40% of those exposed with ↑ risk if PROM or preterm delivery. Typically develops within 2–5 days of delivery and presents with oedema of the conjunctiva and eyelids with profuse discharge. Without treatment infection may extend to sub-conjunctival connective tissue and the cornea leading to ulceration. If ulcers perforate, anterior synechiae formation or panophthalmitis may follow, which can result in blindness.
The rate of infection in at-risk infants is ↓ to 2–5% by prophylaxis (1% silver nitrate solution (‘Crede prophylaxis’), 1% tetracycline, or 0.5% erythromycin ointment) applied to the eyes soon after birth.
Gonococcal arthritis
Associated with vulvovaginitis, proctitis, or ophthalmia neonatorum. Usually polyarticular, presenting as pseudoparalysis. Rarely progressive. Skin lesions not usual.
Scalp abscess
Follows trauma to scalp, e.g. with intra-uterine fetal monitoring.
Other neonatal gonococcal infection
Pharyngeal infection in ~33% with ophthalmia neonatorum. Rhinitis may be associated.
Vaginitis, urethritis, and anorectal infection.
Neonatal sepsis without arthritis particularly in preterm infants. N.gonorrhoeae is recoverable from nasogastric aspirate or blood. Rarely complicated by meningitis.
In ♂ urethral symptoms usually appear within 10 days of exposure to gonorrhoea, although 5–10% are asymptomatic when diagnosed. Symptoms are much less common with rectal and throat infection. Up to 70% of ♀ diagnosed with gonorrhoea are asymptomatic. Therefore, although most people are probably diagnosed shortly after being infected, it is possible that it may have been present for weeks or months.
Yes, gonorrhoea can be cured by antibiotics. When swabs are taken for gonorrhoea culture, the laboratory also tests for antibiotic sensitivities, so that the appropriate antibiotic is identified. It is recommended that, while awaiting these results, an antibiotic be used to which >95% of the local stains of N.gonorrhoeae are sensitive.
In ♀: PID may occur in 10–20% of untreated cases of gonorrhoea. Infertility may occur as a result of PID.
In ♂: urethral strictures and fistulae are sequelae of periurethral abscesses in untreated gonorrhoea and it may also cause epididymitis.
No. Although this was a recommended practice, audit studies have shown that it is unnecessary provided that the isolate is fully sensitive to the antibiotic administered, and the patient has taken all of their medication correctly and has not been re-exposed to the infection.
Not normally. However, in prepubertal girls the vulvovaginal skin is vulnerable to N.gonorrhoeae and a report has alleged acquisition of gonorrhoea from a dirty toilet seat in an aeroplane by an 8-year-old girl.
There is a risk of neonatal infection due to exposure in the birth canal during labour. Gonococcal ophthalmia neonatorum is acquired by 30–40% of infants exposed to N.gonorrhoeae.
Without treatment there are ↑ risks of preterm delivery, low birth weight, premature rupture of membranes, and postpartum/post-abortion endometritis.
Diagnosis
Screening
Genital: ♂ urethra, ♀ cervix and urethra. Vaginal or vulval if sensitive nucleic acid amplification test (NAAT) is used.
Pharynx: all MSM and heterosexuals with symptoms of gonorrhoea elsewhere or history of contact.
Rectum: all MSM (advised as ~20% with rectal infection deny receptive anal intercourse) and ♀ with symptoms, gonorrhoea elsewhere, or history of contact
► Sensitivity of cervical culture alone is 75–85%. A single set of tests from the urethra, cervix, rectum, and pharynx ↑ this to >95%.
Conjunctivitis: include potential 1 ° infection sites.
DGI:
from potential 1 ° infection sites
material from skin lesions and joint aspirate
blood culture.
Culture of joint fluid and skin lesions is insensitive; therefore NAAT is recommended.
Microscopy
Microscopy (1000×) of Gram-stained genital specimens shows N.gonorrhoeae as Gram-negative diplococci within PMNLs (Plate 6). Smear sensitivity (compared with culture):
in ♂—urethra 90–95% (symptomatic) and 50–75% (asymptomatic)
in ♀—cervix 23–65% and urethra 20%
rectum—blind swab 40%, using proctoscope 70–80%.
Microscopy is not appropriate for pharyngeal specimens as other neisserial commensals are commonly seen. Conjunctival specimens are suitable for Gram staining and microscopy.
Laboratory detection of N.gonorrhoeae
Culture—isolation and identification of N.gonorrhoeae
Dependent on good specimen collection and efficient transport to the laboratory. ► Caution with lubricants during examination, as they may inhibit the growth of N.gonorrhoeae.
Specimens for culture may be:
directly inoculated onto culture medium and incubated
transported in a non-nutrient medium (e.g. Amies, Stuart) or a CO2− producing culture medium.
Transport media should be kept at ≤4°C after inoculation (check product information or with local laboratory). Provided that the material in the transport medium is processed within 48 hours, there is only ~5% loss in sensitivity compared with direct inoculation.
The culture medium is examined for growth at 24 and 48 hours. Presumptive identification is by positive cytochrome oxidase reaction and microscopy. Definitive identification by a combination of further tests, e.g. carbohydrate utilization (N.gonorrhoeae utilizes glucose only), monoclonal antibody test (e.g. Phadebact), and enzyme substrate degradation.
Molecular detection
NAATs are ~100% sensitive for genital, rectal, and pharyngeal specimens compared directly with culture (75–85% endocervix, <60% rectum, <50% pharynx) but cannot identify antibiotic sensitivities. They are suitable for urine, vaginal (including self-collected), and vulval samples. They are unlicensed for rectal and pharyngeal specimens, although there are some data showing >90% sensitivity with NAAT (culture <60%). Transcription-mediated amplification and Strand displacement assay methods are more sensitive than polymerase chain reaction in women. False-positive reactions may ↓ positive predictive value to <90% with some reagents in low prevalence populations. Confirmation of NAAT reactivity by culture is recommended and allows antimicrobial sensitivity assay.
Typing
Serotyping, auxotyping, opa-typing, and plasmid analysis are not applicable to routine clinical practice but are useful in monitoring the epidemiology of the infection and the identification of transmission chains.
Antibiotic sensitivity
Identifies appropriate treatment. Sensitivity predicts success in >95% with intermediate sensitivity suggesting failure in 5–15% although ↑ dosage may be effective. Resistance may be due to plasmids (circular DNA fragments independent of chromosome) or chromosomal mutations.
Management
►Advise avoidance of sexual intercourse until the patient and partner(s) have completed treatment and resolution has been established. Screen for C.trachomatis using a sensitive assay (NAAT) or provide epidemiological treatment. Treatment before antibiotic sensitivity is known should be with an antibiotic to which >95% of local strains are sensitive.
Uncomplicated genital and rectal infections
(all single doses)
Recommended:
Ceftriaxone 250mg IM
Cefixime 400mg oral
Spectinomycin 2g IM.
Alternative (if regional prevalence of resistance <5%):
Ciprofloxacin 500mg oral
Ofloxacin 400mg oral
Ampicillin 2g or 3g plus probenecid 1g oral.
Complicated genital infection
Pharyngeal infection
(all single doses)
Ceftriaxone 250mg IM
Ciprofloxacin 500mg oral
Ofloxacin 400mg oral
Pregnancy and breastfeeding
(all single doses)
Quinolone and tetracycline antimicrobials are contraindicated.
Ceftriaxone 250mg IM
Cefotaxime 500mg IM
Ampicillin 2g or 3g plus probenecid 1g oral (provided that local prevalence of penicillin-resistant N.gonorrhoeae <5%)
Spectinomycin 2g IM
Adult gonococcal conjunctivitis
Ceftriaxone 1g IM as a single dose (limited evidence base).
Disseminated gonococcal infection
Hospital admission is recommended. Assess for endocarditis/meningitis.
A parenteral antibiotic is necessary initially, e.g.
ceftriaxone or cefotaxime or ceftizoxime 1g IM 8 hourly
ciprofloxacin or ofloxacin 400mg IV 12 hourly
spectinomycin 2g IM 12 hourly.
The parenteral antibiotic should be continued for 24–48 hours until improvement, and then replaced with oral cefixime 400mg, ciprofloxacin 500mg, or ofloxacin 400mg twice daily for 7 days.
Other situations
Gonococcal meningitis and endocarditis: IV antibiotic for at least 2 weeks and 4 weeks, respectively.
Ophthalmia neonatorum: single dose of ceftriaxone 25–50mg/kg up to a maximum of 125mg.
Neonatal sepsis, scalp abscess, meningitis, and arthritis: ceftriaxone 25–50mg/kg daily IV or IM for 7–14 days.
Neonatal prophylaxis: if mother is not treated before delivery a single dose of ceftriaxone 25–50mg/kg to a maximum of 125mg.
Prepubertal infection:
weight >45kg—adult regimens.
weight <45kg—ceftriaxone 125mg IM (single dose).
Partner notification
Partner notification is essential. Contact tracing period:
♂ symptomatic urethral infection—2 weeks prior to onset of symptoms or until last sexual partner, if longer.
Other—3 months prior to diagnosis or until the last sexual partner.
Epidemiological treatment and, ideally, screening should be offered to sexual partners. Similar principles should apply to the mother of a neonate with gonococcal infection and her sex partner(s).
Follow-up
Tests of cure are unnecessary provided that the isolate is sensitive to the antibiotic prescribed and the patient has adhered fully to the treatment and advice provided. If required, culture should be delayed for at least 72 hours and NAAT for at least 2 weeks after treatment.
HIV infection
Gonorrhoea facilitates HIV transmission, producing ↑ in detectable virus in genital secretions. This is reversed following antibiotic treatment.
