27th June 2023

Bacterial STIs

Chlamydia

Presentation

Chlamydia is a very common STI, caused by Chlamydia trachomatis. Transmission can be via vaginal, anal, and oral sex, or through vertical transmission from an infected mother to the infant during childbirth. Chlamydia is commonly asymptomatic, resulting in the rapid spread of the infection between individuals. If symptoms are present, these can include vaginal or penile discharge, dysuria (due to urethritis), and testicular swelling. Chlamydia infection can be a cause of sexually acquired reactive arthritis (SARA), which in some cases may result in the classic triad of arthritis, urethritis, and conjunctivitis.

Diagnosis is now mostly by nucleic acid amplification tests (NAATs) on vulvovaginal or endocervical swabs in females or first catch urine (recommended choice in males) or urethral swabs in males.

Treatment

Treatment of chlamydia is with antibiotics; the current first line treatment is seven days of oral doxycycline 100mg twice daily. It has an excellent cure rate, and it is advised that all sexual contacts within the past 60 days should be informed of the risk of infection and seek investigation and treatment if required.

Untreated, there is an increased risk of spread of infection in women causing pelvic inflammatory disease, which can result in infertility or ectopic pregnancy, or Fitz-Hugh-Curtis syndrome, a form of infectious perihepatitis. In men, complications include epididymitis, which can rarely lead to sterility if untreated.

Gonorrhoea

Presentation

Gonorrhoea is another common STI, caused by Neisseria gonorrhoeae. Transmission can be via vaginal, anal or oral sex, or through vertical transmission from mother to child during childbirth. Infection can commonly involve the genitals, rectum, or pharynx but may be asymptomatic. Symptoms, if present, include vaginal discharge, dysuria, dyspareunia, and pelvic pain (in females) and dysuria, penile discharge, or testicular pain (in males). A sore throat may occur if the pharynx is the affected site; however, infection here is commonly asymptomatic. Infants born to women with gonorrhoea may develop gonococcal ophthalmia neonatorum, a form of neonatal conjunctivitis which can lead to blindness if left untreated.

Diagnosis is with NAATs on vulvovaginal, endocervical, rectal or pharyngeal swabs or first catch urine samples. In NAAT positive cases, culture should be performed to determine antibiotic sensitivities, as high rates of antimicrobial resistance against gonorrhoea infection are reported. Microscopy of Gram-stained genital samples at the time of examination in clinic may show direct visualisation of N. gonorrhoeae as Gram-negative diplococci within polymorphonuclear leucocytes. This facilitates immediate presumptive diagnosis and treatment in these patients.

Microscopy of gonococcal urethritis, as evidenced by Gram-negative diplococci inside polymorphonuclear neutrophils.

Image Source: Wikimedia Commons (2014). Gonococcal urethritis PHIL 4085 lores, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Gonococcal_urethritis_PHIL_4085_lores.jpg (Accessed on: 11 January 2023).

Treatment

Treatment should be guided by local antibiotic guidelines. Uncomplicated infection is usually treated with a single intramuscular dose of ceftriaxone; however other treatment options exist depending on local susceptibility. Recent sexual partners within the past three months should also be tested and treated.

Untreated, gonorrhoea can lead to infertility or ectopic pregnancy due to pelvic inflammatory disease in females, and epididymitis in males. It can also cause disseminated infection, leading to skin pustules, septic arthritis, meningitis, endocarditis, or perihepatic abscess formation.

Chancroid

Chancroid is uncommon in the UK but is more prevalent in resource-poor countries. It is an STI caused by Haemophilus ducreyi and typically presents with a painful genital ulcer with associated painful inguinal lymphadenitis in some cases. The tender, enlarged inguinal lymph nodes can progress to draining abscesses, known as buboes.

Diagnosis is through Gram stain and culture of Haemophilus ducreyi from ulcer swabs or bubo aspirates, or with PCR testing. HIV should also be tested for, as chancroid is an important cofactor in HIV transmission. Sexual contacts within ten days of symptom onset should be treated, regardless of symptoms.

Treatment is with antibiotics; the first line choice is intramuscular ceftriaxone or oral azithromycin, however, the choice may vary depending on the HIV status of the patient. Lymph node aspiration or incision and drainage may be required in select cases.

Mycoplasma genitalium

Mycoplasma genitalium is the smallest known self-replicating bacterium and was not isolated until 1981. The majority of those infected are asymptomatic; however, symptoms in males include urethral discharge, dysuria, and recurrent urethritis, and in females, include dysuria, post-coital or intermenstrual bleeding.

Complications of infection include reactive arthritis, epididymitis (in males), and pelvic inflammatory disease (in females).

The recommended choice of test for diagnosis is a NAATs of first catch urine in men and vulvovaginal swab in women. M. genitalium is very slow-growing; therefore, culture is not useful for diagnosis. All M. genitalium-positive specimens should be tested for macrolide resistance mediating mutations.

Treatment is with doxycycline for seven days, followed by a short course of azithromycin, if the organism is known to be macrolide-sensitive, or moxifloxacin for ten days, if the organism is known to be macrolide-resistant.

Syphilis

Syphilis is caused by the spirochaete Treponema pallidum. It is transmitted through direct contact with an infectious lesion (usually during sexual activity), via infected blood products/needle-sharing, or by vertical transmission during pregnancy (transplacentally) or childbirth, leading to congenital syphilis. Risk factors include sexual intercourse with an infected person, men who have sex with men (particularly if HIV co-infection), commercial sex workers, and co-infection with other STIs.

Syphilis can present variably depending on the stage of infection: primary, secondary, latent, or tertiary.

Primary syphilis

Primary syphilis infection typically presents with a painless ulcer, called a chancre, in the anogenital region. In 40% of cases, multiple chancres may be present. There may be extragenital ulcers in some cases and associated regional lymphadenopathy. The primary lesion lasts several weeks before healing over, however, syphilis will progress to the secondary infection stage if left untreated.

Primary syphilitic chancre on the penis.

Image Source: Wikimedia Commons (2005). Penis syphilis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Penis_syphilis.png (Accessed on: 20 February 2023).

Secondary syphilis

Dissemination of the infection to cause multisystem symptoms usually occurs within two years of primary infection if untreated. Features of secondary syphilis include:

• Rash – this is a non-itchy, macular, papular or maculopapular rash affecting the trunk, extremities, palms, and soles. It is usually symmetrical.
• Condylomata lata – these are wart-like lesions which may be seen in moist areas such as the groin, vulva, or anus.
• Mucus membrane lesions may affect the mouth, vagina, and anus. These can coalesce.
• Lymphadenopathy – can be localised to the inguinal region or more generalised.
• Constitutional symptoms such as fever, malaise, weight loss, myalgia and arthralgia may be present.
• Less common symptoms include anterior uveitis, hepatitis, glomerulonephritis, meningitis, cranial nerve palsies, and alopecia.

Latent syphilis

The latent phase of syphilis can span many years and represents an asymptomatic phase of the disease; however, syphilis infection remains within the body unless treated, and therefore serology for Treponema Pallidum remains positive. Latent syphilis within two years of syphilis infection is called early latent disease; latent syphilis after two years of infection is called late latent syphilis.

Late (tertiary) syphilis

Approximately a third of patients with untreated syphilis may go on to develop late (tertiary) syphilis, sometimes decades following initial infection.

Presentation of tertiary syphilis is varied due to its ability to affect multiple organ systems, however, patients are not infectious during this phase. The main forms of tertiary syphilis include neurosyphilis, cardiovascular syphilis, and gummatous syphilis.

Neurosyphilis may result in damage to the dorsal columns of the spinal cord, leading to ‘tabes dorsalis’. Clinical features of this include ataxia, loss of vibration and proprioception, areflexia, and loss of control of the bladder and anal sphincter. Neurosyphilis can also present as generalised paresis. There may be more generalised brain or meningovascular involvement, which can lead to non-specific symptoms such as confusion, cognitive impairment, altered mood, altered personality, or seizures. Argyll-Robertson pupils (small, irregular pupils which do not constrict on light reflex, but accommodation reflex is preserved) are a frequent pupillary abnormality associated with tertiary syphilis.

Cardiovascular syphilis typically occurs 10-30 years after infection and causes an aortitis, which may result in aortic regurgitation, or aortic aneurysm formation.

Gummatous syphilis is a rare form of tertiary syphilis characterised by gumma lesions (granulomatous, rubbery lesions with a necrotic centre) affecting skin and viscera, which can lead to organomegaly. They are destructive granulomatous nodular lesions formed due to reactivation of residual treponemes and are not contagious.

Congenital syphilis

Congenital syphilis occurs when syphilis is transmitted transplacentally. Early congenital syphilis occurs in the first two years of life, whilst late congenital syphilis is detected after the age of two. It can result in a large range of symptoms and complications, including rash, hepatosplenomegaly, glomerulonephritis, neurosyphilis, and bone deformities such as ‘saber shins’ (malformation of the tibia), ‘Hutchinson’s teeth’ (smaller, widely spaced teeth), and ‘Mulberry molars’ (small molars with globular enamel growths). There is an associated risk of miscarriage, stillbirth, and neonatal death in early congenital syphilis.

Diagnosis

Diagnosis is most commonly by serology testing, however, dark-field microscopy and PCR can be used in some settings. Serology can take up to 3 months from infection exposure to become positive.

Serology tests involve an initial treponemal test (specific) and, if positive, a subsequent non-treponemal test (non-specific).

The treponemal tests detect antibiotics specific for syphilis and include:

• Treponemal enzyme immunoassay (EIA)
• Treponema pallidum particle agglutination assay (TPPA)
• Treponema pallidum haemagglutination assay (TPHA)
• Fluorescent antibody absorption (FTA-ABS)
• Immunocapture assay (ICA)

Treponemal antibodies appear earlier than non-treponemal antibodies and remain detectable for life, even following successful treatment.

A non-treponemal test is performed following a positive treponemal test to confirm the diagnosis and assess whether infection is active. Non-treponemal tests include:

• RPR (rapid plasma reagin) test
• VDRL (venereal disease research laboratory) test

Non-treponemal tests detect antibody response to the release of cardiolipin during syphilis infection and can provide a quantitative measure of disease activity. They become non-reactive with effective treatment. False positives of non-treponemal tests can occur with pregnancy, vaccination, autoimmune or connective tissue diseases, lymphoma, and other infections.

Dark field microscopy is a form of microscopy in which the object is lit by oblique beams of light, causing the sample to appear bright against a dark background. It is not commonly available at many centres. PCR has limited availability at some services but can be used to detect T. Pallidum on an ulcer swab.

Neurosyphilis can be diagnosed on CSF analysis and typically shows a raised CSF white cell count >10 cells/mm3, raised CSF protein >50 mg/dL and a positive CSF VDRL test.

Treponema pallidum spirochaetes on dark field microscopy.

Image Source: Wikimedia Commons (2008). Treponema pallidum cropped, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Treponema_pallidum_cropped.png (Accessed on: 20 February 2023).

Treatment

Treatment of syphilis is typically with intramuscular benzathine benzylpenicillin or doxycycline. Duration of treatment is dependent on the stage of the disease. Jarisch-Herxheimer reaction is an acute reaction that can occur within 24 hours of treatment for syphilis. It occurs in response to the bacterial endotoxins and antigens released on destruction of spirochaetes following the initiation of antibiotic treatment. Most reactions are mild and self-limiting, consisting of acute fever, headache and myalgia; however, life-threatening reactions can occur if associated with significant hypotension, causing multi-organ failure.

Condoms provide an element of protection, however, skin lesions associated with primary and secondary syphilis, such as chancres or condylomata lata, can be highly infectious and may be exposed despite the use of a condom.

Bacterial vaginosis

Bacterial vaginosis (BV) is a result of an imbalance of normal vaginal flora (typically lactobacilli) with associated overgrowth of anaerobic bacteria. Normal vaginal flora creates a pH of 3.5-4.5, however, in BV, the anaerobic bacteria increase this to a pH >4.5. It is not usually directly sexually transmitted but it can be linked to increased sexual activity or new sexual partners. Another common risk factor for BV is the use of perfumed soaps around the vagina as this can alter the vaginal flora.

BV may be asymptomatic in approximately 50%, however, symptoms can include offensive, thin, grey, or white vaginal discharge, which may have a fishy odour, but usually without any itch or soreness unless co-existing with vulval candidiasis.

Since the make-up of vaginal flora is dynamic, BV can arise and resolve spontaneously in both sexually active and sexually inactive females. BV can be associated with complications in pregnancy, including late miscarriage, preterm rupture of membranes, or preterm birth, low birth weight, and postpartum or post-termination-of-pregnancy endometritis.

The Amsel criteria for diagnosis of BV state three of the following four criteria be fulfilled:

• Thin, white, homogenous discharge
• Clue cells on wet mount microscopy – these are vaginal epithelial cells coated in small Gram-variable bacilli.
• pH of vaginal fluid >4.5
• Positive amine test – release of fishy odour on adding alkali (10% potassium hydroxide); this is no longer widely used due to the caustic nature of potassium hydroxide.

The Hay-Ison criteria for diagnosis are based on the appearance of vaginal flora on Gram-stained smear:

• Grade 1 (normal flora): Lactobacillus morphotypes predominate
• Grade 2 (intermediate flora): Mixed flora with some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present.
• Grade 3 (BV flora): Predominantly Gardnerella and/or Mobiluncus morphotypes, with few or absent lactobacilli.

Management of BV includes education regarding avoidance of perfumed soap use around the vagina, including bubble baths, and avoidance of vaginal douching. Full STI screen should be offered as BV can co-exist with STIs. Treatment is typically with oral metronidazole, although intravaginal metronidazole or clindamycin creams exist as alternatives.