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Chancroid - UpToDate
Chancroid - UpToDate
Chancroid
AUTHOR: Charles B Hicks, MD
SECTION EDITOR: Jeanne Marrazzo, MD, MPH, FACP, FIDSA
DEPUTY EDITOR: Jennifer Mitty, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
INTRODUCTION
Chancroid is a rare infection in the United States and most other developed countries.
However, the true incidence of chancroid remains uncertain because a definitive diagnosis
requires detection of the causative organism, Haemophilus ducreyi, and few laboratories have
the capability of proper microbiologic diagnosis (eg, culture or nucleic acid amplification
testing [NAAT]) [1,2]. In addition, many clinicians do not attempt to diagnose genital ulcer
disease caused by pathogens other than Treponema pallidum or herpes simplex virus (HSV).
This topic will review the clinical manifestations, diagnosis, and treatment of chancroid. Topic
reviews that discuss the approach to patients with genital ulcer disease, syphilis, and genital
herpes are found elsewhere. (See "Approach to the patient with genital ulcers" and "Syphilis:
Epidemiology, pathophysiology, and clinical manifestations in patients without HIV" and
"Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus
infection".)
MICROBIOLOGY
H. ducreyi is a small, fastidious, gram-negative rod that requires an enriched growth medium
containing hemin and usually serum for successful cultivation [3]. Cultures must be delivered
expeditiously to the laboratory and incubated at 33° to 35°C in high humidity with CO2
enrichment. Small, heterogeneous colonies appear on culture medium after 48 to 72 hours.
The gray to tan translucent colonies slide intact across the agar plate when pushed.
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When examined by Gram stain, organisms from culture often clump in long parallel strands,
producing a so-called "school of fish" or "railroad track" appearance. This morphology can
occasionally be seen in gram-stained smears from clinical specimens, but it is not a
consistent or reliable clinical finding.
PATHOGENESIS
H. ducreyi is a highly infectious bacterium. The likelihood that inoculation will lead to papule
formation appears to be mainly influenced by inoculum dose and host factors [8]. Data from
a human model of experimental infection demonstrates that inoculation of a single colony
forming unit (cfu) results in papule formation in 50 percent of cases; inoculation of 100 cfu
leads to papule formation in 90 percent of cases [9].
The initiation of infection requires attachment of bacteria to susceptible cells, a process that
appears to involve the interaction of a protein mediator (probably pili) and
lipooligosaccharide with fibronectin contained in the extracellular matrix [10]. Bacterial
adherence to cells then occurs via the elaboration of a heat shock protein (GroEL), which may
also contribute to the bacterial chaining described above [11]. (See 'Microbiology' above.)
A cytotoxin secreted by H. ducreyi may then play an important role in epithelial cell injury and
subsequent development of an ulcer [12,13]. This cytotoxin, present in the majority of
strains, has been found to be similar to cytolethal distending toxins (CDTs) from other
bacterial species, including Escherichia coli, Shigella, Campylobacter, and Aggregatibacter
actinomycetemcomitans [14]. Similar to other CDTs, this toxin causes distension of cultured
epithelial cells and fibroblasts, leading to irreversible cell-cycle arrest in the G2 phase of cell
growth.
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EPIDEMIOLOGY
Chancroid is a rare infection in the United States and most other developed countries,
although it can occur in localized outbreaks while remaining endemically absent in most
areas. In such settings, there can also be occasional imported cases, which were acquired in
endemic areas. However, the true incidence of chancroid remains unclear because of the
difficulty isolating H. ducreyi in the laboratory. In addition, most facilities do not test for this
organism.
In the United States, chancroid has been diagnosed primarily in certain racial and ethnic
groups (African Americans and Hispanic individuals), in heterosexuals, and among female
sex workers and their clients [1,3,19]. Cases are more commonly reported in men, at least in
part because chancroid is more easily diagnosed in males [20], and uncircumcised men have
the highest incidence of infection. Crack cocaine and the exchange of sex for drugs have
been implicated in several outbreaks.
Fewer than 20 cases of chancroid per year have been reported in the United States since
2011. A total of 36 cases were reported from 2015 to 2019 [21]; in 2021, only three cases
were reported, but the CDC qualified this data by noting that chancroid is not a reportable
condition in all jurisdictions. In a report from a sexually transmitted disease (STD) clinic in
Paris, France, only 8 of 278 cases of genital ulcer disease evaluated between 1995 and 2005
were diagnosed as being caused by H. ducreyi, and no cases of chancroid were diagnosed
after 2002 [22]. However, during recognized outbreaks, chancroid has accounted for up to 20
percent of patients presenting to public STD clinics with genital ulcer disease [19,20,23,24].
While the absence of reported cases of chancroid most likely represents the rarity of this
infection, it is important to note that lack of testing may contribute to the apparent
disappearance of chancroid [20,23-27]. Limited data suggest that very few patients evaluated
in STD facilities are tested for chancroid. As an example, in 1996, a survey of 405 STD
treatment facilities in the United States found that only 32 (8 percent) tested patients for
chancroid [25]. It is unlikely that this proportion has increased in recent years.
The potential significance of this lack of testing was demonstrated in a study conducted from
1988 to 1990 in New York, where H. ducreyi caused 27 of 65 cases (42 percent) of genital ulcer
disease when a microbiologic diagnosis was established [26]. Similar findings were noted in
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a report of 299 men with nonsyphilitic genital ulcer disease from New Orleans [19]; cultures
revealed H. ducreyi in 39 percent and herpes simplex virus (HSV) in 19 percent; culture were
negative in 41 percent. These data exemplify the episodic nature of chancroid outbreaks.
Use of nucleic acid amplification testing (NAAT) also suggests that chancroid may be more
common than previously believed [20,23,24]. In 1996, data obtained using a multiplex
polymerase chain reaction (PCR) test demonstrated that H. ducreyi tended to occur in
epidemiologic clusters and accounted for a substantial proportion of genital ulcer cases
when present [20]. As an example, cases of chancroid were identified in Memphis and
Chicago and accounted for 20 and 12 percent of all cases of genital ulcers in these cities,
respectively. In Memphis, the diagnosis of chancroid was not made in any of the patients
when clinical criteria were used, and only two of these patients were prescribed an antibiotic
regimen that would treat chancroid. However, there are no molecular diagnostic assays for
chancroid approved for use by the United States Food and Drug Administration [21]. (See
'Nucleic acid amplification tests' below.)
Nonsexually transmitted cutaneous ulcer disease caused by H. ducreyi has been identified in
children and young adults (and in some visitors) from islands in the South Pacific, including
Papua New Guinea, Samoa, and Vanuatu, where the cutaneous ulcer disease yaws is
endemic [6,40-42]. Identification of the pathogen occurred as part of mass drug
administration programs for yaws and trachoma, where azithromycin was given and nucleic
acid amplification diagnostic tools were used to assess the etiology of cutaneous ulcers in
the treated population [4].
CLINICAL MANIFESTATIONS
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At presentation, a typical chancroid ulcer is about 1 to 2 cm in diameter ( picture 1), but the
size is variable and there may be more than one ulcer present, especially in patients with HIV.
The ulcer is painful and has an erythematous base; the borders are clearly demarcated and
sometimes undermined. The base of the ulcer is usually covered with a gray or yellow
purulent exudate and bleeds when scraped.
As predicted by the pathogenesis of H. ducreyi infections, the most common sites for
chancroid are those that are typically subject to friction during sex. In men, most lesions
involve the prepuce, corona, or glans penis. In women, the labia, vaginal introitus, and
perianal areas are most commonly affected. Some cases of chancroid may go undiagnosed,
especially in asymptomatic women with vaginal or cervical lesions.
Compared with the lesions of yaws, cutaneous ulcers caused by H. ducreyi are less circular in
shape and are less likely to have central granulating tissue indurated edges. In addition,
most lesions are on the limbs rather than the torso. The cutaneous manifestations of yaws
are described elsewhere.
DIAGNOSIS
However, the sensitivity and specificity of using clinical criteria to make a probable diagnosis
of chancroid is variable, and the accuracy of a clinical diagnosis ranges from 33 to 80 percent
[19,28,29,44]. Thus, if a diagnosis of chancroid is being considered, patients should also be
evaluated for other causes of genital ulcer disease, such as T. pallidum and herpes simplex
virus (HSV), which are more likely to occur. In addition, coinfection with H. ducreyi and other
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sexually transmitted infections have been reported [15,26]. (See "Approach to the patient
with genital ulcers".)
Diagnostic criteria — The United States Centers for Disease Control and Prevention (CDC)
has developed a case definition for definite and probable chancroid to be used for reporting
purposes, and often as a guide for initiation of therapy [45,46]:
● Probable – A "probable" diagnosis is made if all four of the following criteria are met:
• HSV-1 or HSV-2 NAAT or HSV culture performed on the ulcer exudate or fluid is
negative
The CDC surveillance case definition does not include NAAT testing for H. ducreyi, even if
using a Clinical Laboratory Improvement Amendments (CLIA)-verified test. However, if such a
test is clinically available, we would report cases diagnosed in this way as confirmed. (See
'Nucleic acid amplification tests' below.)
Tests to identify the organism — Both culture and NAAT testing are available to identify H.
ducreyi. However, these tests are not able to provide rapid results and are not always
available. Thus, in most instances, clinicians are unable to base treatment decisions on the
results of microbiologic testing and empiric therapy is administered. (See 'Approach to
diagnosis' above and 'Antimicrobial therapy' below.)
Gram stain — Gram stain of the exudate from an ulcer can show typical small gram-
negative rods in a chain, the so-called "school of fish." However, the sensitivity of the Gram
stain is poor [47,48]. (See 'Microbiology' above.)
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availability of NAAT testing for many pathogens, including H. ducreyi, has further diminished
the value of culture for the diagnosis of chancroid.
Nucleic acid amplification tests — Nonculture methods for the diagnosis of H. ducreyi (eg,
PCR) may lead to improvements in the diagnosis of chancroid and H. ducreyi-associated
cutaneous ulcer disease [29,49]. Although no United States Food and Drug Administration-
cleared nucleic acid amplification tests (NAATs) for H. ducreyi are available in the United
States, testing can be performed by commercial laboratories that have developed their own
PCR or other NAAT, if the performance of the test has been verified with a CLIA validation
study [46]. However, NAAT testing outside of clinical research settings is generally not
available in many areas of the world where H. ducreyi cutaneous ulcer disease is found. (See
'Resource-limited settings' above.)
An investigational multiplex PCR assay, which tests for H. ducreyi, T. pallidum, and HSV, was
evaluated in 105 patients attending a genitourinary medicine clinic in Lesotho, and was
determined to have a sensitivity for H. ducreyi of 95 percent [29]. A similar study, which
evaluated 298 genital ulcer swab specimens collected in New Orleans, reported a sensitivity
of PCR for H. ducreyi of 98.4 percent and a specificity of 99.6 percent [49].
Despite the potential benefits, PCR or other NAATs may not be a practical diagnostic tool for
most publically-funded STD clinics because of the cost and complexity of the test. In addition,
NAAT technology for H. ducreyi has not to date been adapted to provide rapid results.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of genital ulcer disease in sexually active persons is broad and is
influenced by the geographic location where the infection was acquired ( table 1). In the
United States (and increasingly worldwide), most cases are due to herpes simplex virus (HSV)
or syphilis. Chancroid remains exceedingly rare, particularly in developed countries.
Noninfectious causes include drug eruptions and Behçet syndrome. (See "Approach to the
patient with genital ulcers", section on 'Etiologies'.)
A diagnosis based on history and physical examination alone is often inaccurate since
findings such as pain, inguinal lymphadenitis, and multiple ulcers are not specific for any one
diagnosis. Nonetheless, some findings are more common in certain infections [43]. A
detailed discussion of how to evaluate patients with genital ulcers is found elsewhere and
summarized below (see "Approach to the patient with genital ulcers"):
● The classic genital presentation of chancroid is with a deep, undermined, purulent ulcer
that may be associated with painful inguinal lymphadenitis.
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● The classic presentation of genital herpes is with multiple, shallow, tender ulcers that
may be vesicular. In addition, only HSV is associated with recurrent disease. (See
"Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus
infection".)
● The classic genital presentation of primary syphilis is with a painless, indurated, clean-
based ulcer called a chancre. (See "Syphilis: Epidemiology, pathophysiology, and clinical
manifestations in patients without HIV", section on 'Clinical manifestations'.)
More than one pathogen may be present, further complicating the diagnosis. Nucleic acid
amplification testing (NAAT) has shown that this phenomenon may be more common than is
evident with culture-based methods used in the past (17 versus 4 percent with culture in one
series) [29].
TREATMENT
Empiric treatment is reasonable if the clinical manifestations and epidemiology are strongly
suggestive of the diagnosis, especially for patients who are unlikely to follow up after their
initial evaluation. A detailed discussion of the epidemiology and clinical manifestations of
chancroid are found above. (See 'Epidemiology' above and 'Clinical manifestations' above.)
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The duration of infectivity after initiation of treatment is uncertain. Thus, patients with
chancroid should abstain from sex until the ulcer has healed, and condom use should be
stressed. (See 'Sex partners' below.)
Most of the evidence for the efficacy of these regimens comes from uncontrolled
observational studies that have shown high cure rates. As examples:
● Azithromycin given as a single 1 gram dose was evaluated as treatment for chancroid in
two study sites in Africa. At the first site in Kenya, 127 culture-positive patients were
treated with either azithromycin or erythromycin. Cure rates were approximately 90
percent with both drugs. Treatment failure in both groups was significantly associated
with HIV infection or being uncircumcised [54]. At the second study site in South Africa,
patients were treated in a noncomparative trial [55]. Azithromycin cured 89 percent of
patients with culture-positive H. ducreyi infection.
● Ceftriaxone given as a single 250 mg intramuscular injection has been associated with
cure rates as high as 98 percent [56]. However, limited data suggest that this regimen
may not be as effective in Kenya where failure rates as high as 35 percent have been
described [57]. Failure was more common among persons coinfected with HIV. (See
'Patients with HIV' below.)
Alternative regimens — A multiple dose regimen of ciprofloxacin (500 mg orally twice daily
for three days) is an alternative for patients who cannot take azithromycin or ceftriaxone
[46]. Erythromycin base 500 mg orally three times daily for seven days is also effective, but
patient adherence to the regimen may be challenging. Both ciprofloxacin and erythromycin
have been associated with cure rates above 90 percent [50,59].
As noted, the requirement for multiple doses makes these alternative regimens less
desirable. In addition, with erythromycin, there is an appreciable incidence of
gastrointestinal side effects, as well as a risk of sudden cardiac death due to QT interval
prolongation (especially when other drugs metabolized by CYP3A4 are taken concurrently).
(See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)
Special populations
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Patients with HIV — As with other sexually transmitted diseases (STDs), the presence
of HIV infection may result in atypical manifestations of chancroid. Such patients may
present with numerous lesions, extragenital involvement, and delayed resolution after
treatment [47,60]. However, there are no large case series of chancroid in persons with HIV
to determine the true incidence or predominant clinical features.
We administer the same antimicrobial regimens to patients with HIV as those described
above ( table 2). Some experts recommend multiple dose regimens with ciprofloxacin or
erythromycin for initial treatment of patients with HIV, based upon a small number of
reported treatment failures with single-dose regimens [35]. However, this approach has not
been studied prospectively, and we prefer single-dose regimens for patients with HIV,
especially those with well-controlled HIV and reasonable immune function [1]. In either case,
close follow-up is essential.
Pregnant women — Both azithromycin and ceftriaxone can be used for the treatment
of pregnant women with chancroid. The safety of these drugs has been well established
based upon studies and clinical experience with the use of azithromycin to treat C.
trachomatis and ceftriaxone to treat Neisseria gonorrhoeae in pregnant women [46]. (See
"Treatment of uncomplicated gonorrhea (Neisseria gonorrhoeae infection) in adults and
adolescents", section on 'Pregnant women' and "Treatment of Chlamydia trachomatis
infection", section on 'Pregnant individuals'.)
Drainage can be performed by needle aspiration through normal skin ( picture 2), or
through incision and drainage [35,46]. In a small study performed during a chancroid
epidemic in New Orleans, 27 patients with inguinal buboes were randomly assigned to either
needle aspiration or incision and drainage [62]. Both groups ultimately did well without any
adverse events during the period of follow-up. The patients managed with needle aspiration
often required repeated aspirations, but these were well tolerated.
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● The patient was not adherent with medications (if a multiple-dose regimen was
prescribed)
For patients who are considered treatment failures, more prolonged treatment with
ceftriaxone or a fluoroquinolone may be effective, but there are no definitive data to support
this strategy.
The response of chancroid-associated lymphadenitis may occur more slowly. In one study,
for example, 8 of 35 patients with inguinal lymphadenitis developed fluctuance that required
needle aspiration despite successful treatment of the genital ulcer with erythromycin [64]. In
advanced cases, scarring may result despite eradication of infection [46].
SEX PARTNERS
The duration of infectivity after initiation of treatment is uncertain. Thus, patients with
chancroid should abstain from sex until the ulcer has dried/resolved, and condom use
should be stressed.
Sex partners of patients with chancroid should be treated if they have had sexual contact
with the patient within 10 days of symptom presentation [46]. Treatment does not depend
upon the presence of symptoms or signs of the disease in the exposed partner. The
treatment for exposed partners is the same as for persons with diagnosed infections
( table 2), and a single-dose regimen should be administered whenever possible. (See
'Antimicrobial therapy' above.)
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Sexually transmitted
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infections".)
● Chancroid is very rare in the United States and most other developed countries.
However, the true incidence of chancroid in most areas remains unclear because of the
difficulty identifying H. ducreyi in the laboratory. (See 'Epidemiology' above.)
● The diagnosis of chancroid is challenging because testing for H. ducreyi is not routinely
available. As such, most providers rely on clinical criteria to make a diagnosis of
chancroid in patients with signs and symptoms consistent with infection. In addition,
testing for herpes simplex virus (HSV) and syphilis should also be performed. (See
'Diagnosis' above.)
● Fluctuant inguinal lymph nodes should be drained, usually by needle aspiration. (See
'Management of buboes' above.)
● Clinical improvement usually occurs promptly after treatment is initiated. Relief of pain
is noted by most patients within two to three days, and objective improvement in the
ulcers is usually apparent within a week. (See 'Patient monitoring' above.)
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● The duration of infectivity after initiation of treatment is uncertain. Thus, patients with
chancroid should abstain from sex until the ulcer has dried/resolved, and condom use
should be stressed. In addition, sex partners of patients with chancroid should be
treated if they have had sexual contact with the patient within 10 days of symptom
presentation. (See 'Sex partners' above.)
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buboes in the emergency department during an epidemic of chancroid. Sex Transm Dis
1995; 22:217.
63. Schmid GP. The treatment of chancroid. JAMA 1986; 255:1757.
64. Plummer FA, D'Costa LJ, Nsanze H, et al. Antimicrobial therapy of chancroid:
effectiveness of erythromycin. J Infect Dis 1983; 148:726.
Topic 7582 Version 27.0
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GRAPHICS
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HSV HSV-1 and HSV-2 Multiple small 2 to 7 days Usually Reactive painf
grouped ulcers; painful; nodes commo
erythematous can be
base. painless
Occasionally, or
single pruritic
lesions/fissures
can be seen
Heals Regional
spontaneously
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Rapid Unilateral or o
spontaneous bilateral
healing
Large painful
fluctuant "bub
Painful groove
sign
Sinus tracts
common
Granulation-like
tissue
Rolled edges
GUD: genital ulcer disease; HSV: herpes simplex virus; LGV: lymphogranuloma venereum.
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Drugs of choice
Alternatives
Ciprofloxacin* 500 mg orally twice daily for three days OR
Erythromycin ¶ base 500 mg orally three times daily for seven days
IM: intramuscular.
¶ Erythromycin is rarely used given gastrointestinal toxicity. Erythromycin ethylsuccinate 800 mg may
be substituted for erythromycin base 500 mg.
Adapted from: Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment
guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
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Aspiration of purulent fluid (seen in the syringe) from a fluctuant bubo in a patient with chancroid.
Repeated needle aspirations may be necessary, even after effective antimicrobial therapy.
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Contributor Disclosures
Charles B Hicks, MD No relevant financial relationship(s) with ineligible companies to
disclose. Jeanne Marrazzo, MD, MPH, FACP, FIDSA Grant/Research/Clinical Trial Support: BD
Diagnostics [Vaginal infections, STI]; GSK [Vaccines]. Consultant/Advisory Boards: Merck [HIV]. All of the
relevant financial relationships listed have been mitigated. Jennifer Mitty, MD, MPH No relevant
financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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