Haemophilus ducreyi is a Gram-negative bacterium best known for causing chancroid, a sexually transmitted infection marked by painful genital ulcers. Over the past decade, though, it has gained a second identity: a surprisingly common cause of chronic skin ulcers in children across the tropics, transmitted not through sex but likely through environmental contact and possibly insects. That dual role makes H. ducreyi one of the more peculiar pathogens in infectious disease, and one that public health programs are still figuring out how to handle.
The Bacterium Itself
Under the microscope, H. ducreyi appears as small Gram-negative rods (coccobacilli) that tend to cluster in short chains, clumps, or parallel arrangements sometimes described as “railroad tracks.” It is fastidious, meaning it has strict growth requirements and dies quickly outside a host.1PubMed Central. The laboratory diagnosis of Haemophilus ducreyi In the lab, it grows on gonococcal agar or Mueller-Hinton agar at around 34°C in a high-humidity, low-oxygen environment. Colonies are smooth, dome-shaped, and buff-yellow to grey, roughly 2 mm across, and can be pushed intact across the agar surface. The organism requires hemin (X factor) but not NAD (V factor), is catalase-negative, and produces beta-lactamase.2PubMed. Isolation and identification of Haemophilus ducreyi in a clinical laboratory That beta-lactamase production is clinically relevant because it means the bacterium is inherently resistant to simple penicillins.
Chancroid, the Classic Disease
Chancroid is the sexually transmitted form of H. ducreyi infection. It produces necrotizing genital ulcers that are typically painful and soft-edged, sometimes accompanied by swollen, tender inguinal lymph nodes that can develop into large abscesses called buboes.3Sexually Transmitted Infections. Chancroid: clinical manifestations, diagnosis, and management The ulcers look angry and ragged, with a purulent base, distinguishing them from the painless, clean-edged ulcers of primary syphilis, though in practice the two can be difficult to tell apart clinically.
Chancroid was once widespread in sub-Saharan Africa, Southeast Asia, and parts of Latin America, but reported cases have declined sharply in recent decades, partly because of syndromic management of genital ulcers and partly because of improved access to antibiotics. The disease has never been common in high-income countries and is now rare even in many endemic regions. That decline may be somewhat deceptive, however, since diagnostic confirmation is hard to get in the settings where the infection still circulates.
A key public health concern with chancroid is its relationship with HIV. Genital ulcers caused by H. ducreyi break the mucosal barrier and recruit immune cells to the ulcer site, creating an environment that facilitates both transmission and acquisition of HIV.4PubMed. Update on chancroid: an important cause of genital ulcer disease 5Hunter’s Tropical Medicine and Emerging Infectious Diseases. Chancroid During the early years of the HIV epidemic in Africa, chancroid was considered a significant amplifier of HIV spread. Even as chancroid has become less common, that biological interaction remains a concern wherever the two infections overlap.
How H. ducreyi Outwits the Immune System
For a fragile organism that dies quickly on surfaces, H. ducreyi is remarkably good at surviving inside the human body once it gains a foothold. It uses several strategies to dodge or suppress the host immune response.
One important weapon is a toxin called cytolethal distending toxin (CDT). This toxin causes host cells to stall in their growth cycle, effectively freezing them and preventing the tissue from repairing itself. Researchers believe CDT plays a role both in generating the characteristic ulcers and in keeping them from healing.6PubMed Central. The cytolethal distending toxin from the chancroid bacterium Haemophilus ducreyi induces cell-cycle arrest in the G2 phase
Another key trick involves the LspA proteins, which directly interfere with phagocytosis. Immune cells like macrophages normally engulf and destroy invading bacteria, but LspA proteins hijack a signaling enzyme called C-terminal Src kinase, activating it in a way that suppresses the machinery the immune cell needs to carry out phagocytosis.7PubMed Central. The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase The result is that immune cells arrive at the infection site but cannot efficiently clear the bacteria.
Studies using a human challenge model, where volunteers are deliberately infected on the upper arm, have painted a detailed picture of what happens at the tissue level. The immune response is a messy mix of pro-inflammatory and anti-inflammatory signals. The host tissue shows signs of oxidative stress and metabolic rewiring, creating what appears to be a nutrient-limited, hostile environment for the bacterium. Yet H. ducreyi persists, suggesting it has adapted to survive under those harsh conditions.8PubMed Central. Haemophilus ducreyi Infection Induces Oxidative Stress, Central Metabolic Changes, and a Mixed Pro- and Anti-inflammatory Environment in the Human Host Advanced imaging and single-cell analyses of these experimental infections have helped map the immune and tissue cell populations involved, providing insights that are difficult to get from natural infections in low-resource settings.9PubMed Central. A high-resolution view of the immune and stromal cell response to Haemophilus ducreyi infection in human volunteers
A Second Life as a Tropical Skin Pathogen
The bigger surprise in H. ducreyi research over the past decade has been the discovery that this supposedly sex-transmitted bacterium is a major cause of chronic skin ulcers in children living in tropical communities. These ulcers appear on the legs, arms, and other non-genital sites and have nothing to do with sexual contact.
The discovery came about almost by accident. During surveys for yaws, a chronic skin infection caused by a subspecies of the syphilis spirochete, researchers in the Solomon Islands tested ulcer swabs from 41 children by PCR. About a third of them turned out to be infected with H. ducreyi rather than the yaws bacterium, and the ulcers looked identical to yaws lesions on clinical examination alone.10PubMed Central. Haemophilus ducreyi associated with skin ulcers among children, Solomon Islands A larger prospective study in Papua New Guinea found even more striking numbers: among 90 ulcer cases where a bacterial cause could be identified, H. ducreyi alone accounted for about 58%, the yaws bacterium alone for about 26%, and co-infection with both for 16%.11The Lancet. Haemophilus ducreyi as a cause of skin ulcers in children in a yaws-endemic area of Papua New Guinea: a prospective cohort study Most affected individuals were children and young adults, with a median age of 10.
Studies in Cameroon added to the picture. In a community survey covering thousands of people, roughly 1% had cutaneous ulcers, and H. ducreyi was identified in about 30% of those ulcers. The bacterium was also detected on the skin of nearly 9% of asymptomatic people, hinting at a reservoir of carriers who might spread the infection without showing symptoms themselves.12PLOS Neglected Tropical Diseases. Prevalence and risk factors associated with Haemophilus ducreyi cutaneous ulcers in Cameroon
This was a paradigm shift. H. ducreyi had been pigeonholed as a sexually transmitted pathogen for over a century, and suddenly it was responsible for a substantial chunk of non-genital skin disease in tropical children. The finding also had immediate implications for the World Health Organization’s yaws eradication program, which relies on identifying and treating yaws-like ulcers with antibiotics. If a large portion of those ulcers are actually caused by H. ducreyi, the clinical diagnostic approach used in the field becomes unreliable.13BMJ Open. LAMP4yaws: Treponema pallidum, Haemophilus ducreyi loop mediated isothermal amplification − protocol for a cross-sectional, observational, diagnostic accuracy study
Genital Strains Versus Skin Strains
A natural question is whether the strains causing skin ulcers in children are genetically distinct from those causing genital chancroid. The answer is nuanced. Whole-genome sequencing has shown that H. ducreyi genital ulcer strains fall into two distinct lineages, called class I and class II. The first cutaneous ulcer strains to be sequenced were nearly identical to class I genital strains, differing only by scattered single nucleotide changes and carrying no additional genes.14PubMed Central. Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains
As more strains from places like Vanuatu, Samoa, and Ghana were sequenced, the picture grew more complex. Most cutaneous ulcer strains clustered near the class I genital lineage, but a few unexpectedly grouped with class II strains, and the cutaneous strains from different geographic regions formed distinct subgroups.15PLOS Neglected Tropical Diseases. Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies This means the cutaneous ulcer strains are not a single clone that jumped from genital to skin disease. Different lineages appear to have independently acquired the ability to cause non-genital ulcers, or perhaps it was always there and simply never noticed. Either way, the genomic closeness between genital and cutaneous strains means there is no obvious genetic signature that explains why the same species causes two very different diseases in two very different patient populations.
How Cutaneous Ulcers Spread
If skin ulcers in children are not sexually transmitted, then how does H. ducreyi get from one person to another? The answer is still being worked out, but one leading hypothesis involves flies.
In Papua New Guinea, researchers collected flies and environmental samples in villages with high rates of skin ulcers. A substantial fraction of flies carried detectable H. ducreyi DNA, and some also carried DNA from the yaws bacterium.16PubMed Central. Transmission of viable Haemophilus ducreyi by Musca domestica A study in Cameroon found H. ducreyi DNA in about 15% of lysis buffers from fly traps and nearly 28% of whole flies collected in endemic villages, supporting the idea that flies in these communities routinely contact the pathogen.17PLOS Neglected Tropical Diseases. Detection of Haemophilus ducreyi from environmental and animal samples in Cameroon
A laboratory study went a step further, using common houseflies (Musca domestica) in a controlled setting. After exposure to H. ducreyi, over 86% of flies transmitted viable bacteria, though the organisms became undetectable within about an hour of initial exposure, suggesting that transmission would need to happen quickly and over short distances.18PubMed Central. Transmission of viable Haemophilus ducreyi by Musca domestica That fits with a scenario common in tropical villages: a fly lands on a child’s open wound, picks up bacteria, and deposits them on a scratch or insect bite on another child within minutes.
Direct skin-to-skin contact, shared bedding, and contaminated fomites are also plausible routes, and the detection of H. ducreyi on the skin of asymptomatic children supports the notion that the bacterium can be carried without causing disease, at least temporarily.19PLOS Neglected Tropical Diseases. Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea The full transmission cycle remains incomplete, but the evidence strongly points to a non-sexual environmental pathway driven by poor sanitation, high fly density, and frequent minor skin trauma in barefoot children.
Why Diagnosis Is Difficult
A recurring theme in H. ducreyi research is how hard the bacterium is to diagnose. Culture, the traditional gold standard for identifying bacteria, works poorly because the organism is so fragile. It dies rapidly outside the human body, and even under optimal lab conditions, culture sensitivity for H. ducreyi from genital ulcers has been reported around 74%.20PubMed Central. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers In the field settings where skin ulcers are common, culture is essentially impractical.
PCR-based testing is far more sensitive, reaching about 98% for H. ducreyi in head-to-head comparisons with culture.21PubMed Central. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers Multiplex PCR assays can simultaneously test for H. ducreyi, the syphilis and yaws spirochetes, and herpes simplex virus from a single swab, which is valuable because genital and skin ulcers often look alike regardless of cause. However, PCR requires laboratory infrastructure and trained personnel that are scarce in the rural tropical communities where cutaneous H. ducreyi is most common. Efforts are underway to develop simpler point-of-care molecular tests, such as loop-mediated isothermal amplification (LAMP) assays, that could be used in the field.22BMJ Open. LAMP4yaws: Treponema pallidum, Haemophilus ducreyi loop mediated isothermal amplification − protocol for a cross-sectional, observational, diagnostic accuracy study
Without reliable point-of-care diagnostics, many H. ducreyi infections go unrecognized. In yaws-endemic communities, children with skin ulcers are typically assumed to have yaws and treated accordingly. If they actually have H. ducreyi, they may still improve on azithromycin (which treats both infections), but the epidemiological data become unreliable. Programs tracking yaws elimination cannot accurately measure their progress if a third or more of the ulcers they are counting as yaws are caused by a different pathogen entirely.
Treatment and the Mass Drug Administration Problem
Individual chancroid cases respond well to several antibiotics. Single-dose azithromycin, ceftriaxone, or short courses of ciprofloxacin or erythromycin are all effective. For cutaneous ulcers in children, azithromycin is the practical first-line choice, especially since the WHO yaws eradication strategy already calls for mass distribution of azithromycin to affected communities.
Here is where things get frustrating. Mass drug administration of oral azithromycin has been effective at reducing yaws prevalence in many communities, but it has failed to eliminate H. ducreyi from those same communities.23International Journal of Infectious Diseases. Prevention of Haemophilus ducreyi infections: one organism, two stories In a pilot study in Ghana, for example, H. ducreyi was found in about 28% of children’s skin lesions sampled before mass treatment, a higher proportion than the yaws bacterium itself.24PubMed Central. Community-based mass treatment with azithromycin for the elimination of yaws in Ghana—Results of a pilot study Despite mass azithromycin rounds, H. ducreyi ulcers persisted. Several factors could explain this: the asymptomatic carriage reservoir, possible environmental persistence mediated by flies and fomites, and the difficulty of reaching every individual in a community with a single round of treatment. If even a small number of carriers are missed, the infection can re-establish itself quickly in communities with high fly density and poor wound hygiene.
This creates a practical dilemma for the yaws eradication campaign. Mass azithromycin is the centerpiece strategy, and it works against the yaws spirochete. But it leaves behind a reservoir of H. ducreyi that continues to cause clinically indistinguishable ulcers, undermining confidence that yaws is truly gone. Eliminating H. ducreyi may require a fundamentally different approach, one that addresses environmental transmission through insect control, improved sanitation, and wound care alongside antibiotics.
Research Models for Studying Infection
Studying H. ducreyi is made easier by the existence of two animal and human models that mimic natural disease. The human challenge model, in which volunteers are infected on the upper arm under controlled conditions, produces pustules that mirror the progression of natural chancroid.25PubMed Central. Interactions of the Skin Pathogen Haemophilus ducreyi With the Human Host This model has been essential for dissecting the immune response and identifying bacterial factors needed for infection, and it is one of the few examples in modern medicine where a sexually transmitted pathogen is deliberately given to healthy people for research.
For vaccine and drug testing, a swine model provides an alternative. Domestic pigs infected with H. ducreyi develop cutaneous ulcers that are histologically similar to human chancroid, complete with a progression from pustules to ulcers containing immune cells.26PubMed Central. Swine model of Haemophilus ducreyi infection The pig model has been used to test vaccine candidates that would be premature to try in humans.
Vaccine Development
There is currently no approved vaccine against H. ducreyi, but early-stage research has identified promising leads. One candidate that has reached animal testing is based on DsrA, a surface protein the bacterium uses to stick to host tissue and extracellular matrix proteins. In the swine model, pigs immunized with a recombinant form of DsrA’s functional domain cleared the infection entirely: no viable H. ducreyi was recovered from any vaccinated animal, while all control animals became infected. The vaccine triggered strong antibody responses, and the resulting antibodies partially blocked the bacterium from binding fibrinogen at its surface.27PubMed Central. The Haemophilus ducreyi trimeric autotransporter adhesin DsrA protects against an experimental infection in the swine model of chancroid
Computational approaches have also been applied to the problem. A genomic analysis of 28 H. ducreyi strains used reverse vaccinology, a method that screens entire bacterial genomes for surface-exposed proteins likely to provoke an immune response, and identified 13 candidate vaccine targets and three potential drug targets.28PubMed Central. Putative vaccine candidates and drug targets identified by reverse vaccinology and subtractive genomics approaches to control Haemophilus ducreyi, the causative agent of chancroid Several of these targets are located on pathogenicity islands, the stretches of DNA that encode virulence factors, which is encouraging because targeting virulence-associated proteins reduces the risk of also hitting similar proteins in the host.
Vaccine development for H. ducreyi faces a practical obstacle that has nothing to do with biology: there is little commercial incentive. Chancroid is declining globally, and cutaneous ulcers in tropical children attract minimal pharmaceutical investment. Any vaccine that does emerge will probably depend on public-sector funding and the infrastructure of tropical disease elimination programs. The timeline, realistically, is measured in decades rather than years.