Haemophilus ducreyi: Chancroid, Soft vs Hard Chancre, and Lab Diagnosis

A young adult presents with a painful ulcer on the genitals that appeared a few days ago, along with a tender, swollen lymph node in the groin. The single most useful question at this moment is not which antibiotic to give, but which organism this is, because the answer is usually written in one feature: the pain. A painful ulcer points toward chancroid, caused by Haemophilus ducreyi. A painless one points toward the hard chancre of early syphilis. This distinction, painful versus painless, is where the diagnosis of genital ulcer disease begins, and it is what makes H. ducreyi worth knowing well.

Haemophilus ducreyi is a fastidious Gram-negative bacterium and the cause of chancroid, a sexually transmitted genital ulcer disease. It is one of the classic causes of genital ulcer, alongside syphilis and genital herpes, and it is distinguished from them chiefly by producing a painful (soft) ulcer.

What is Haemophilus ducreyi?

Haemophilus ducreyi is a member of the genus Haemophilus, but unlike H. influenzae it is not a respiratory pathogen. It is a strict human pathogen transmitted by sexual contact, and it causes a single important disease: chancroid, an acute genital ulcer with painful, tender regional lymph node swelling.

It is most common in parts of Africa, Asia, and the Caribbean, and it has become uncommon in high-income countries, though it remains a recognized cause of genital ulcer worldwide and a facilitator of HIV transmission.

General characteristics

• Gram stain: small Gram-negative coccobacillus
• Characteristic arrangement: in smears from the ulcer, the organisms often line up in parallel chains and clusters described as a "school of fish," a "shoal of fish," or a "railroad track" pattern. This appearance is a classic clue, though it is not seen reliably enough to diagnose chancroid on smear alone.
• Fastidious: requires enriched media and does not grow on ordinary agar
• Growth factor requirement: requires X factor (hemin) only. It does not require V factor (NAD). This separates it from H. influenzae (needs both X and V) and H. parainfluenzae (needs V only).
• Oxidase: positive (reduces nitrate)
• Catalase: negative or only weakly positive, in contrast to H. influenzae, which is catalase-positive
• Culture: slow and difficult; grows best at about 33°C (lower than most pathogens), in a humid atmosphere with added CO₂, on specially enriched media
• Strict human pathogen: no animal or environmental reservoir; transmitted only by sexual contact

Chancroid: the disease

Chancroid is an acute, localized genital ulcer disease. After sexual exposure and a short incubation (usually 4 to 7 days, occasionally longer), a tender papule appears at the site of contact, breaks down into a pustule, and then ulcerates. The disease stays local; unlike syphilis, H. ducreyi does not disseminate through the body.

The ulcer itself, the soft chancre, has a set of features that are worth learning as a group because together they define the disease:

• Painful. This is the single most important feature and the first thing that separates it from syphilis. The chancroid ulcer hurts.
• Soft, non-indurated base. Unlike the firm, rubbery hard chancre of syphilis, the base of a chancroid ulcer is soft, which is the origin of the name "soft chancre."
• Ragged, undermined, sharply demarcated edges, often with a grey-yellow purulent base.
• Often multiple. Autoinoculation to adjacent skin can produce several ulcers ("kissing ulcers"), whereas the syphilitic chancre is classically single.
• Painful, tender inguinal lymphadenopathy (buboes). The regional nodes enlarge, become tender, and can suppurate and rupture, discharging pus. This tender, fluctuant bubo is characteristic and again contrasts with the non-tender, rubbery nodes of syphilis.

Why it matters beyond the ulcer: genital ulcers of any cause, chancroid included, disrupt the mucosal barrier and recruit inflammatory cells, and chancroid is well recognized as a facilitator of HIV transmission. A patient with chancroid should be evaluated for co-existing sexually transmitted infections, including HIV and syphilis.

Soft chancre vs hard chancre vs herpes

The genital ulcer a clinician sees is most often one of three organisms, and telling them apart is the core of this topic. The table compares the three classic causes. For the two that are not H. ducreyi, follow the links to their own detailed articles.

The one-line version students remember: the soft chancre is soft and sore; the hard chancre is hard and painless. Herpes is painful like chancroid, but it begins as grouped vesicles and recurs, which chancroid does not.

Two other organisms cause genital ulcer less commonly, lymphogranuloma venereum (Chlamydia trachomatis L serovars) and granuloma inguinale/donovanosis (Klebsiella granulomatis). They are outside the classic triad above; see the overview of major sexually transmitted diseases for where they fit.

Virulence and pathogenesis

H. ducreyi stays at the site of inoculation and causes a persistent, non-healing ulcer rather than spreading. A few factors explain how:

• Cytolethal distending toxin (CDT): the principal virulence factor. CDT damages host cell DNA and arrests the cell cycle, killing keratinocytes and immune cells and preventing the ulcer from healing. This is a direct reason the chancroid ulcer persists rather than closing over.
• Hemolysin and other cytotoxins: contribute to tissue damage and ulcer formation.
• Serum resistance: the organism resists killing by complement in serum, helping it survive locally.
• Its X-factor (hemin) requirement reflects an inability to synthesize heme, so it must scavenge it from the host, which is also why it needs hemin-enriched media to grow in the lab.

Putting it together: the organism attaches and stays local, resists complement, and uses CDT to kill the very cells that would repair the tissue, producing a painful ulcer that does not heal on its own.

Laboratory diagnosis

The central problem is that H. ducreyi is hard to grow. Culture is insensitive, so a negative culture does not rule out chancroid, and diagnosis often rests on the clinical picture supported by ruling out syphilis and herpes.

• Specimen: material from the base or undermined edge of the ulcer, or pus aspirated from a bubo. For collection and transport of genital specimens, see genital and STI specimen collection.
• Gram stain: may show small Gram-negative coccobacilli in the "school of fish" arrangement. Sensitivity is low and other organisms in the ulcer confuse the picture, so a smear supports but does not confirm the diagnosis.
• Culture: requires special enriched media containing hemin, incubation at about 33°C in a humid, CO₂-enriched atmosphere. Even under ideal conditions, recovery is poor, which is why culture is considered insensitive.
• PCR (nucleic acid amplification): the most sensitive method and the modern diagnostic standard where available. It also allows testing for H. ducreyi, T. pallidum, and HSV together from a single ulcer swab.
• Clinical diagnosis: because the lab tests are limited, a probable diagnosis of chancroid is often made when a patient has one or more painful genital ulcers, no evidence of syphilis (negative dark-field or serology) and a negative herpes test, and a clinical picture typical of chancroid.

Treatment

Chancroid is treated with antibiotics, and the organism is not one students need to memorize doses for. The drugs of choice are azithromycin or ceftriaxone; erythromycin and ciprofloxacin are alternatives. Sexual partners should be evaluated and treated, and the patient should be tested for co-existing sexually transmitted infections, particularly HIV and syphilis. Buboes that are large and fluctuant may need drainage. Ulcers usually improve within days of effective treatment; failure to improve should prompt reconsideration of the diagnosis, including co-infection.

How to remember

Ducreyi makes you cry. H. ducreyi causes the painful ulcer. Pain is the headline feature and the fastest way to separate chancroid from syphilis.

Soft and sore versus hard and painless. The soft chancre (chancroid) is soft-based and painful; the hard chancre (syphilis) is indurated and painless. The words "soft" and "hard" describe the base; the pain is the giveaway.

School of fish. In a smear from the ulcer, H. ducreyi lines up in parallel like a school of fish (also called railroad tracks). A memorable image for a Gram-negative coccobacillus in a genital ulcer.

X marks ducreyi. Among the medically important Haemophilus, H. ducreyi needs X factor only. A memory aid used on the H. influenzae page: ducreyi → d = das = ten = X in Roman numerals → X factor only.

Where students get confused

• Chancroid is painful; the syphilitic chancre is painless. This is the single most tested point and the one most often reversed. Soft chancre (chancroid) hurts; hard chancre (syphilis) does not. If you remember nothing else, remember the pain.
• A negative culture does not rule out chancroid. H. ducreyi is genuinely difficult to grow, and culture is insensitive. Diagnosis often rests on the clinical picture plus exclusion of syphilis and herpes, or on PCR where available.
• "Chancre" and "chancroid" are not the same word for the same thing. The chancre (hard chancre) is the painless ulcer of syphilis. Chancroid is the painful ulcer disease caused by H. ducreyi. The near-identical spelling causes constant confusion; the diseases are opposite in pain and caused by unrelated organisms.
• Catalase separates it from H. influenzae. H. ducreyi is catalase-negative or only weakly positive, while H. influenzae is catalase-positive. Both are fastidious Haemophilus, but they differ here and in growth-factor needs (ducreyi needs X only; influenzae needs X and V).

Key exam facts

References

1. Tille PM. Bailey and Scott's Diagnostic Microbiology. 15th ed. St. Louis: Elsevier; 2022.
2. Procop GW, Church DL, Hall GS, et al. Koneman's Color Atlas and Textbook of Diagnostic Microbiology. 7th ed. Philadelphia: Wolters Kluwer; 2017.
3. Lewis DA. Epidemiology, clinical features, diagnosis and treatment of Haemophilus ducreyi - a disappearing pathogen? Expert Rev Anti Infect Ther. 2014;12(6):687-696. https://doi.org/10.1586/14787210.2014.892414
4. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. https://doi.org/10.15585/mmwr.rr7004a1