Abstract
Chancroid is a sexually acquired disease caused by Haemophilus ducreyi. The infection is characterized by one or more genital ulcers, which are soft and painful, and regional lymphadenitis which may develop into buboes. The infection may easily be misidentified due to its rare occurrence in Europe and difficulties in detecting the causative pathogen. H. ducreyi is difficult to culture. Polymerase chain reaction (PCR) can demonstrate the bacterium in suspected cases. Antibiotics will usually be efficient for curing chancroid.
Epidemiology
Chancroid is a sexually transmitted infection (STI) caused by the small Gram-negative bacterium Haemophilus ducreyi. Recommendations for the diagnosis and management of chancroid have been given by a number of different institutions, including Centers for Disease Control and Prevention (CDC), 1 British Association for Sexual Health and HIV (BASHH), 2 and Public Health Agency of Canada. 3
In contrast to genital herpes, the number of cases of chancroid is decreasing overall, and the eradication of chancroid is considered a realistic objective. 4 However, chancroid is still a cause of genital ulcers in resource poor countries, especially in south east Asia and Africa (e.g. Botswana 5 ), where outbreaks have been occurring among sex workers in the cities, including capitals such as Nairobi, Kenya. 6 In India, a change from syphilis, chancroid and gonorrhoea to viral infections and chlamydia has been observed since 1980. 7
Europeans may contract the disease while staying in these areas.
As a number of people travel from high-risk areas to work in the sex industry in Europe, the possibility of contracting chancroid in European countries should be considered. Using an improved culture medium, Hafiz et al. 8 found a higher number of chancroid cases than expected in Sheffield, and also demonstrated that many of the patients had concurrent infections with other sexually transmitted infections (STIs), especially herpes simplex infections. However, there was some debate questioning whether the Sheffield data were accurate. Overall, chancroid accounted for eight cases (3%) of genital ulcers in an STI clinic in Paris from 1995–2005. 9 In the UK, the Health Protection Agency reported a total of 450 cases of chancroid, lymphogranuloma venereum and donovanosis diagnosed in genitourinary (GU) medicine clinics in the years 1995–2000. 10 Local outbreaks have been reported from various parts of Europe, including Rotterdam with 53 cases in 1977–1978 11 and Greenland, where 1463 cases were reported in a total population of 49,000 during 1977 and 1978. 12 In 1979 chancroid was eradicated, and has not been reported in Greenland since.
Non-sexual transmission has been reported.13,14 H. ducreyi has been demonstrated in asymptomatic individuals. 15 Male circumcision is associated with reduced risk of contracting chancroid. 16
Clinical Features
The incubation period for chancroid is short. Tender erythematous papules develop three to seven days after sexual intercourse with an infected person, most often on the prepuce and frenulum in men and on the vulva, cervix and perianal area in women. The papules quickly progress into pustules, which rupture after a few days and develop into superficial ulcers with ragged and undermined edges. The bases of the ulcers are granulomatous with purulent exudates. The ulcers are soft and painful and may persist for months if left untreated. Secondary superinfections may cause induration. Autoinoculation from primary lesions on apposing skin surfaces may result in so-called ‘kissing ulcers’.
Inguinal lymphadenitis, usually unilateral and painful, develops in approximately half of the patients, and may further progress into buboes. Fluctuant buboes may rupture spontaneously.
Extra-anogenital chancroid has been reported in children and adults.13,14 and may represent a diagnostic challenge, as clinical suspicion of chancroid may be low.
According to CDC, 1 a probable diagnosis of chancroid, for both clinical and surveillance purposes, could be made if all of the following criteria are met: (1) the patient has one or more painful genital ulcers; (2) the patient has no evidence of Treponema pallidum infection by darkfield examination of ulcer exudate or by a serological test for syphilis performed at least seven days after the onset of ulcers; (3) the clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid; and (4) a test for herpes simplex virus (HSV) performed on the ulcer exudates is negative (IV, C). However, as neither specificity nor sensitivity of microscopy, serology and antigen detection tests are comparable to nucleic acid detection, the latter is preferable for the diagnosis of genital ulcers including chancroid and such diagnostic tests are available in many European countries.
Diagnosis
Microscopy
H. ducreyi appear as small Gram-negative rods. Microscopy may be done on ulcer swabs. Due to low sensitivity and specificity microscopy is, however, not recommended.
Culture
H. ducreyi is a very fastidious bacterium, and selective, enriched culture media are required for its isolation. A combination of at least two media may be used for optimal recovery rates as the ability to grow on different media may vary between strains.17,18
Samples should be taken with a cotton-tipped swab from the base at the undermined edge of a lesion after cleansing by flushing with sterile saline. H. ducreyi will survive only a few hours on the swab, and bedside inoculation of culture plates followed by immediate incubation can help to reduce the loss of viable bacteria during transportation. However, bedside plating is often not possible, and the swab should then be sent to the laboratory in an appropriate transport medium, e.g. Amies or Stuart's medium. 19 Minimizing transport time and keeping the specimen at 4°C during transit will increase the chance of a positive culture of H. ducreyi. Inoculated culture plates should be incubated at 33°C in a humid atmosphere containing 5% CO2 for more than three days. Culture of material from buboes obtained by puncture and aspiration is less sensitive than culture from ulcers. Culture of H. ducreyi ensures a definite diagnosis of chancroid, but it does not rule out other concomitant infections. Culture is particularly important when further characterization of the bacterium such as antimicrobial susceptibility is needed, e.g. in cases of therapeutic failure.
A definitive diagnosis of chancroid requires the identification of H. ducreyi on culture media; however, the advent of more sensitive DNA amplification techniques has demonstrated that the sensitivity of culture for H. ducreyi reaches only 75% at best20–22 (III, B).
Nucleic acid amplification tests
Nucleic acid amplification tests (NAATs) are excellent for demonstrating H. ducreyi in clinical sample material. Individual strain-specific growth requirements do not influence the outcome of NAATs, and NAATs show higher positivity rates than culture. As these methods do not depend on live bacteria, samples may be analysed in laboratories placed remotely from the patient, which is relevant in Europe as only a few laboratories have established NAATs for H. ducreyi due to its rare occurrence. Specimens should be obtained as described for culture; no specific transport medium is required unless special procedures related to individual NAATs indicate otherwise. Specimens used for culture may be used for NAATs after inoculation on culture plates.
Various different in-house polymerase chain reaction (PCR) methods have been described, some of which have the advantage of simultaneously testing for other relevant pathogens, in particular T. pallidum and HSV23–27 (III, B).
Serology
Detection of antibodies against H. ducreyi is not appropriate for the individual diagnosis of acute chancroid as demonstrated by experimental inoculation of the bacterium into volunteers. 28
Management
Information, explanation and advice for the patient
Patients should be informed that chancroid is a bacterial infection that is sexually transmitted but curable with antibiotics and that it is a co-factor for HIV transmission, as are genital herpes and syphilis (IV, C).
Symptoms should resolve within 1–2 weeks of commencing antibiotic therapy (III, B).
Patients should abstain from any sexual contact until they and their partner(s) have completed therapy (IV, C).
Testing for syphilis and HSV should always be done in patients suspected to suffer from chancroid, both because the three diseases may clinically be difficult to distinguish from each other and because co-infections occur (IV, C). As mentioned above, tests based on nucleic acid detection are preferable if accessible.
Therapy
Successful treatment for chancroid cures the infection and resolves the clinical symptoms. In advanced cases, scarring can result, despite successful therapy.
The World Health Organization (WHO) has proposed syndromic approaches for the treatment of genital ulcers to be used in settings where appropriate laboratory diagnosis is not available. 29 The antibiotic treatment used should be based on the local epidemiology of ulcer disease and antibiotic susceptibility patterns.
Several antibiotic regimens have been recommended for confirmed cases of chancroid:
First line: ceftriaxone can be administered as a single intramuscular injection of 250 mg (Ib, A). The response is generally good although failures, especially in HIV-positive individuals, have been reported. Alternatively, azithromycin, as single 1 g oral dose, seems clinically at least as efficient as ceftriaxone (Ib, A); Second line: ciprofloxacin can be used as a three-day course of 500 mg orally twice a day (Ib, B), or erythromycin may be used orally as 500 mg three or four times a day for seven days (Ib, B).
Azithromycin and ceftriaxone offer the advantage of single-dose therapy. Children, and pregnant and lactating women can be treated with ceftriaxone but not ciprofloxacin.
An unblinded, prospective study designed to determine the efficacy of single-dose azithromycin for the treatment of chancroid was done in 133 patients who were randomized to receive 250 mg of ceftriaxone intramuscular or 1 g of azithromycin orally, both given as a single dose. 30 Azithromycin and ceftriaxone were equally effective in healing ulcers in which cultures were negative, and azithromycin was as effective as ceftriaxone 23 days after treatment for chancroid (Ib, A).
An open-label prospective study to examine the efficacy of a single 2 g dose of spectinomycin for treatment of chancroid resulted in a 98% cure rate 14 days after treatment 31 (III, B). The results of another study with 5.0 g of granulated thiamphenicol, orally, in a single dose, indicated a high cure rate with a low incidence of side-effects 32 (IIb, B). In clinical trials, fleroxacin has been evaluated in the treatment of chancroid (single oral doses of 200 or 400 mg) with bacteriological cure rates around 80% 33 (III, B).
Adjunctive therapy
All patients, and in particular those co-infected with HIV and other immunosuppressive conditions, should be carefully followed up with clinical examination
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(IV, C); Patients with fluctuant buboes will experience symptomatic relief if these are drained. Needle aspiration is effective but may need to be repeated. Incision and drainage is an alternative
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but some authorities believe that it may lead to sinus formation. Antibiotic cover is recommended if this is done (IV C).
Partner notification
Sexual partners of patients who have chancroid should be examined and treated, regardless of whether symptoms of the disease are present, if they had sexual contact with the patient during the 10 days preceding the onset of symptoms 2 (IV C).
Follow-up
All patients diagnosed with chancroid should be followed up after treatment:
To ensure resolution of symptoms and signs of infection; successful treatment should improve symptoms within three to seven days. A test of cure is not necessary; To evaluate healing that might be slower for some HIV-infected patients and uncircumcised men; To document treatment failure consider antibiotic resistance, re-infection, other causes of anogenital ulcers, or an underlying immunodeficiency; To check that adequate partner notification has been completed; To address any patient concerns; To arrange suitable testing for syphilis and HIV.
Prevention/health promotion
Patients diagnosed with chancroid should be counselled regarding the prevention of other STIs:
Offer regular sexual health screening; Patients should be re-tested for syphilis and HIV three months after the diagnosis of chancroid, if the initial test results were negative; Condom use should be demonstrated and promoted.
Auditable outcome measures
All cases of suspected chancroid should undergo laboratory investigation. Target 100%; Sexual contacts within three months should be traced, tested and treated; HIV and syphilis serological testing should be offered, as well as screening for concomitant STIs; Suspected or confirmed cases of chancroid should be reported and relevant surveillance data collected according to local and national guidelines.
Footnotes
Acknowledgement
IUSTI/WHO European STD guidelines Editorial Board: Keith Radcliffe – Editor-in-Chief, Karen Babayan, Marco Cusini, Simon Barton, Mikhail Gomberg, Michel Janier, Jorgen Skov Jensen, Lali Khotenashvili, Marita van de Laar, Willem van der Meijden, Harald Moi, Martino Neumann, Raj Patel, Angela Robinson, Jonathan Ross, Jackie Sherrard and Magnus Unemo.
Search Strategy
The previous European IUSTI guideline titled ‘European Guideline for the Management of Tropical Genito-ulcerative diseases’ from October 2001 was used as a basis for the current guideline, as it was ‘The 2007 National Guideline for the Management of Chancroid’ produced by the British Association for Sexual Health and HIV (www.bashh.org). MEDLINE and PubMed searches were performed from 2007 to December 2009 using the MeSH heading ‘chancroid’ including all documents and subheadings. A Cochrane search showed 61 clinical trials published between 1951–1999 but no systematic reviews on chancroid.