Tuesday, 26 October 2010

Gonorrhoea

Gonococcal urethritis (Gonorrhoea). Gonorrhoea owes its name to the Greek physician Galen in the second century AD, as it was then thought that the discharge of urethral pus was seminal fluid-hence being misnamed “gonorrhoea” (Greek, flow of seed). Thus from the very earliest times it was characterised as being “a male disease” and little attention was given to its manifestations in females.


As the concept developed that gonorrhoea resulted from coitus (venery), steps were taken for its control and it is said that in the Middle Ages prostitutes of Paris were quartered in domiciles in the Les Clapiers (les clapiers meaning rabbit hutches, the slang name for brothels in Paris during the Middle Ages) district there, hence the term clap, which is still commonly used to refer to this disease.


Extragenital infections include rectal, pharyngeal and conjunctival infections. 

Gonorrhoea has a high infectivity and is easily transmitted before symptoms appear (during the incubation period - the incubation period ranges from 1 to 14 days or even longer in men). In males, the usual presentation is with acute anterior urethritis. There may be slight tender enlargement of the superficial inguinal lymph nodes. Urethritis in men may be divided into gonococcal (gonorrhoea) or non-gonococcal urethritis (NGU); there is considerable overlap and differentiation on clinical grounds alone is not advised. More than 50% of females are asymptomatic (seen as contacts on examination). Symptoms if present (e.g. lower abdominal pain, dysuria, and vaginal discharge) appear within 10 days of infection.

NGU occurring soon after curative therapy for urethral gonorrhoea is called postgonococcal urethritis. NGU can be further classified into Chlamydia trachomatis-positive and Chlamydia trachomatis -negative NGU. There is a proportion of cases of NGU that are not sexually transmitted.

The gonococcus (Neisseria gonorrhoeae)  has a predilection for columnar epithelium which is readily available after the organism has gained entrance to the urethra, rectum, pharynx and conjunctiva in both sexes and endocervix and Bartholin’s ducts in females. The infection can spread to other structures lined with susceptible epithelium such as Littré’s glands, Cowper’s glands, prostate gland, seminal vesicles and epididymes in the male and Skene’s glands and Fallopian tubes in the female. The gonococci, with the help of pili and other surface proteins, attach themselves to the epithelial cells. This attachment protects them from being dislodged by the normal flow of urine or mucous secretions. They may also become embedded within the epithelial cells. However, once phagocytosed by neutrophils (microphages), the gonococci may undergo lysis, especially after appropriate antibiotic treatment.


In contrast to female adults, in prepubertal girls the nonoestrogenized alkaline thin immature vaginal mucosa may be infected and colonised with N. gonorrhoeae. A clinician who is examining a prepubertal female for a gonococcal infection should be aware that contrary to female adults, it is not necessary to obtain a specimen from the cervical canal; a specimen from the vaginal canal suffices.


Gonococcal urethritis in boys, vulvo-vaginitis in girls and pharyngeal and rectal infection in both sexes are almost always the result of sexual abuse.


Complications in males include infection of the median raphe, Tysonitis, meatal paraurethral gland abscess, inflammation of Littré’s glands and periurethral cellulitis and abscess, urethral strictures and fistulae, Cowperitis and abscess formation, prostatitis and seminal vesiculitis and epididymitis.

Complications in females include inflammation of the paraurethral (Skene’s) glands, Bartholinitis with abscess formation, and pelvic inflammatory disease (PID). In pregnancy, genital infection is less likely to be complicated by PID (because of thickening of cervical mucus) but other adverse outcomes include e.g. premature rupture of membranes, and postpartum/intrapartum or postabortal endometritis.

Systemic complications include perihepatitis and disseminated gonococcal infection (DGI) (In DGI factors include e.g. serogroup IA-1 & 2/ auxotype AHU [arginine, hypoxanthine, and uracil] dependent). In DGI, the preceding genital infection tends to be asymptomatic and the patient usually presents with mild fever, gonococcal dermatitis especially at extremities, and arthralgia +/- arthritis.  AHU/IA-1 & 2 strains accumulate in the population because of their ability to cause asymptomatic infection in men. AHU/IA-1 & 2 strains are particularly susceptible to the penicillins but this varies over time and penicillin resistant strains now play a significant role.


Neonatal gonococcal infection occurs because of exposure in birth canal during labour and includes gonococcal ophthalmia neonatorum, gonococcal arthritis, anogenital infection, pharyngeal infection and other infections such as scalp abscess following trauma to scalp e.g. with intrauterine foetal monitoring.

Five or more polymorphonuclear leucocytes per high power field (in at least five x 1000 oil immersion microscopic fields) in the Gram-stained urethral smear will confirm urethritis and the presence of Gram-negative intracellular diplococci (red kidney bean-shaped organisms) within polymorphonuclear leucocytes (microphages) would enable the physician to make a presumptive diagnosis of gonococcal urethritis. Confirmation is by culture of the organism (also allows sensitivity testing) and differentiation from other Neisseria species by antigenic (monoclonal antibody test) or biochemical testing (gonococcus utilises glucose only). The culture medium is examined at 24 and 48 hours for growth. Growth is optimal at 35–37 °C in a 5% CO2 atmosphere, at a pH of about 6.5–7.5. For urethral specimens from symptomatic men, cultures on selective “antibiotic-containing” (e.g. modified Thayer-Martin medium) and nonselective media are equally sensitive, because the concentration of gonococci in the urethra usually exceeds that of other flora. In contrast, selective media are preferred for culturing the endocervix, rectum, and pharynx, where other, less fastidious bacteria often outnumber N. gonorrhoeae. Test of cure by culture should be delayed for at least 72 after treatment.




Nucleic acid amplification tests (NAATs) are extremely sensitive and will detect very small amounts of DNA or rRNA. Detection does not necessarily indicate that the organism is viable [the test of cure should be delayed for at least 2 weeks after treatment to avoid false positive results]. Using NAATs that exhibit little cross-reactivity reduces false positive results. NAATs are more sensitive than culture and can also be used as diagnostic/screening tests on non-invasively collected specimens (urine in men and self-taken vulvovaginal swabs). NAATs allow dual detection of N. gonorrhoeae and Chlamydia trachomatis too. Urine is a suitable sample in NAAT screening for Chlamydia trachomatis and so may be tested additionally for N. gonorrhoeae in both men and women, but NAATs sensitivity to detect N. gonorrhoeae in women is higher if a self-taken vulvovaginal swab is used. Confirmation of NAAT reactivity by culture is necessary (urine is not considered a suitable sample for culturing of N. gonorrhoeae or Chlamydia trachomatis) and allows antimicrobial sensitivity testing and thus resistant strains can be identified. Resistance may be due to plasmids (circular DNA fragments independent of chromosome) or chromosome mutations.


Gonorrhoea is known to facilitate the transmission of HIV (increase in detectable HIV in urethral/cervical secretions when infection is present). The impact of untreatable gonorrhoea (given the lack of new anti-gonococcal drugs on the horizon, gonorrhoea may eventually become untreatable) on HIV transmission could be enormous in countries with a high HIV prevalence*.

Uncomplicated gonorrhoea responds to a single dose of suitable antimicrobial (in view of the global increase in multidrug-resistant gonorrhoea, the wisdom of continued single-dose treatment may be challenged and extended treatment may be required), the choice of dose and drug depending on antimicrobial sensitivity.

Currently, 
dual treatment with ceftriaxone plus azithromycin is generally advised for the treatment of uncomplicated gonorrhoea (irrespective of the results of chlamydia testing) in order to mitigate against the selection of gonococci with reduced susceptibility to cephalosporins. The rationale is that it is difficult for an organism to develop simultaneous resistance to two different antimicrobial classes, meaning that dual treatment creates a pharmacological barrier to the emergence of isolates exhibiting resistance to one component of the recommended therapy. There is no good evidence for any antimicrobial synergy between ceftriaxone and azithromycin and this is NOT the reason for recommending dual therapy.


Management of sexually transmitted urethritis includes, screening for other STIs, contact tracing and sexual partner(s) notification, education/counselling, examination, investigation and treatment

*Lewis DAThe Gonococcus fights back: is this time a knock out? Sex Transm Infect 20108641521.

5 comments:

  1. Note that:

    1) When Gram-stained smear of urethral discharge shows polymorphonuclear leucocytes (microphages), and within the cytoplasm (it is considered equivocal if only extracellular gram-negative diplococci are seen), there are Gram-negative diplococci (red kidney bean-shaped organisms), the most likely diagnosis then is gonorrhoea, but as other species of Neisseriae, for example, N. meningitidis (meningococci), can colonize the genital tract and are indistinguishable microscopically, culture with the appropriate confirmation of the identity of the isolate is essential. The pathogenicity of anogenital meningococcal infection and the frequency with which it produces clinical disease are unclear. Non-pathogenic Neisseriae are generally not cell associated.

    2) Since secretory IgA [sIgA] is the main arm of antibody-mediated defence at mucosal surfaces (human responses at genital surfaces appear to be made up of 50% sIgA1 and 50% sIgA2), the Neisseria IgA1 protease may help evade specific immune responses on mucosal surfaces (sIgA2 lacks the hinge structures required for cleavage by the gonococcal IgA1 protease, and thus is protease resistant). The terminal lacto-N-neotetraose (LNnT) moiety on gonococcal LOS (lipooligosaccharide) is similar to the structure of certain human glycosphingolipids, which seems to help immune evasion. Repeated reinfection of the same patient by the same strain highly suggests that gonococci are able to change surface antigens frequently and/or to escape local immune mechanisms.

    ReplyDelete
  2. Note that:

    The diagnosis of urethritis is confirmed by demonstrating abnormal number of polymorphonuclear leucocytes in the anterior urethra through:

    (i) A Gram stained urethral smear containing five or more polymorphonuclear leucocytes per high power field (in at least five x 1000 oil immersion microscopic fields).

    and/or

    (ii) A Gram stained preparation from a centrifuged sample of a first passed urine (FPU) specimen (first 10 mL – 20 mL of urinary stream, in practice, the first void is normally made directly into a urine container with a maximum volume of approximately 20 ml), containing ten or more polymorphonuclear leucocytes per high power field (in at least five x 1000 oil immersion microscopic fields).

    Either test can be used. Both tests will identify cases missed by the other test though.

    The sensitivity of the smear test, but probably not the FPU is affected by the period since last passing urine. The optimum time is not known (2 - 4 hours is conventional). Symptomatic patients, in whom no discharge or urethritis is detected, are retested having held their urine overnight.

    ReplyDelete
  3. Note that:

    Modern microengineered nanotechnologies may provide the basis for rapid or point-of-care susceptibility testing for gonorrhoea in the near future*.

    * Sadiq ST, Dave J, Butcher PD. Point-of-care antibiotic susceptibility testing for gonorrhoea: improving therapeutic options and sparing the use of cephalosporins. Sex Transm Infect 2010; 86: 445-46.

    ReplyDelete
  4. Note that:

    Trichomonads readily phagocytose N. gonorrhoeae, C. trachomatis, and M. hominis.

    In the case of N. gonorrhoeae, and C. Trachomatis the phagocytosed bacteria are efficiently killed by the protozoan thus it does not seem to play a role in the transmission (or persistence) of gonococcal or chlamydial infections.

    In the case of M. hominis, survival and replication of it within T. vaginalis suggests that the protozoan can play a role in the transmission of M. hominis.

    ReplyDelete
  5. Note that:

    A test of cure is recommended for ALL cases of gonorrhoea (culture should be delayed for at least 72 hours and NAAT at least 2 weeks after treatment).

    ReplyDelete

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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Ackerman's Resolving Quandaries in Dermatology, Pathology and Dermatopathology
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
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  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
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  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
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