Haemophilus ducreyi: a newly recognised cause of chronic skin ulceration
Authors: Sally A Roberts, Susan L Taylor
Journal: The Lancet Global Health (2014)

Haemophilus ducreyi, a fastidious Gram negative bacillus first described by Augusto Ducrey in 1889, is the causative agent of chancroid, a genital ulcer disease common in developing countries. It is a strict human pathogen and there are no known animal or environmental reservoirs. In addition to causing chancroid there is increasing evidence to support its previously unrecognised role as a causative agent of chronic skin ulceration in children from developing countries, in particular South Pacific Island Countries and Territories (PICT). The study by Oriol Mitjà and colleagues1Mitjà O Lukehart SA Pokowas G et al.Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.Lancet Glob Health. 2014; 2: 236-242Google Scholar in this issue provides further support for H ducreyi as a cause of non-sexually acquired chronic skin ulceration. Earlier evidence was provided by case reports describing cutaneous skin infections in individuals from PICT.2Ussher JE Wilson E Campanella S Taylor SL Roberts SA Haemophilus ducreyi causing chronic skin ulceration in children visiting Samoa.Clin Infect Dis. 2007; 44: e85-e87Crossref PubMed Scopus (49) Google Scholar, 3McBride WJH Hannah RCS Le Cornec GM Bletchly C Cutaneous chancroid in a visitor from Vanuatu.Australas J Dermatol. 2008; 49: 98-99Crossref PubMed Scopus (37) Google Scholar, 4Pell TN Bhatti D De Boer JC Stratov I Spelman DW Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection.Med J Aust. 2010; 192: 348-350PubMed Google Scholar These individuals, three children and three adults, were residents of Australia, New Zealand, or a PICT, who reported the onset of the lesion while spending periods of time in a PICT. All, irrespective of age, presented with painful non-healing chronic skin ulcers on their legs. Mitjà and colleagues1Mitjà O Lukehart SA Pokowas G et al.Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.Lancet Glob Health. 2014; 2: 236-242Google Scholar did a prospective cohort study of five yaws-endemic villages in Papua New Guinea during a yaws elimination campaign. The characteristics of the skin lesions, occurring in predominantly children, were described in detail. Several non-culture-based investigations were used to determine the causative organism including treponemal serology and PCR on lesional exudate using gene targets to detect Treponema pallidum and H ducreyi DNA. A bacterial cause was identified in 81% of individuals. Surprisingly, H ducreyi was the most common pathogen, with H ducreyi DNA found in 54 of the 73 individuals, either alone (n=42) or in conjunction with T pallidum subsp pertenue DNA (n=12). There is limited data describing the causative agents of infected chronic skin lesions in children and adults in PICT. Lesions typically occur on the legs and are more common in children. A study from the 1980s looking at the bacterial cause of infected skin lesions in children in Papua New Guinea reported "Vincent's organisms" (Fusobacterium fusiforme and Borrelia vincentii) in almost three-quarters of Gram stains of exudative material collected from tropical ulcers.5Montgomery J The aerobic bacteriology of infected skin lesions in children of the Eastern Highlands Province.Papua New Guinea Med J. 1985; 28: 93-103PubMed Google Scholar Other pathogens such as Staphylococcus aureus, Streptococcus pyogenes, and Corynebacterium diphtheriae were also present. However, culture for fastidious pathogens such as anaerobes or H ducreyi was not undertaken. H ducreyi is a fastidious organism requiring specific nutritional, atmospheric, and temperature requirements for growth. For this reason culture capability might only be available in limited PICT microbiology laboratories. The use of multiplex PCR targeting common pathogens associated with genital ulceration—T pallidum, H ducreyi, and herpes simplex virus—has increased the diagnostic yield.6Bong CTH Bauer ME Spinola SM Haemophilus ducreyi: clinical features, epidemiology, and prospects for disease control.Microbes Infect. 2002; 4: 1141-1148Crossref PubMed Scopus (52) Google Scholar PCR for H ducreyi DNA has better sensitivity than culture because it is not affected by the loss of viability of organisms associated with collection at sites distant from the processing laboratory. The study by Mitjà and colleagues1Mitjà O Lukehart SA Pokowas G et al.Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.Lancet Glob Health. 2014; 2: 236-242Google Scholar used PCR for these very reasons. However, although PCR alone allows for the detection of the organism, it does not allow for susceptibility testing and molecular characterisation.7Trees DL Morse SA Chancroid and Haemophilus ducreyi: an update.Clin Microbiol Rev. 1995; 8: 357-375Crossref PubMed Google Scholar Future studies will need to attempt culture of H ducreyi in addition to detection by PCR. Yaws is a contagious non-venereal endemic treponemal infection caused by T pallidum subsp pertenue. It affects mostly children in rural communities in developing countries and infection occurs after direct person-to-person contact. Ulcerative skin lesions occur early in the disease. The lesions differ from those caused by H ducreyi; most importantly they are usually painless, as shown in this recent study.1Mitjà O Lukehart SA Pokowas G et al.Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.Lancet Glob Health. 2014; 2: 236-242Google Scholar In endemic regions, such as Papua New Guinea, the presence of characteristic lesions is adequate for diagnosis. The yaws eradication programmes of the 1950s have not succeeded in eliminating this infection; newer strategies to eradicate yaws have recently been proposed.8Mitjà O Hays R Rinaldi AC McDermot R Bassat Q New treatment schemes for yaws: the path towards eradiction.Clin Infect Dis. 2012; 55: 406-412Crossref PubMed Scopus (15) Google Scholar Increasing antimicrobial resistance in H ducreyi strains has been reported, leading to a shift away from benzylpenicillin as the treatment of choice. Strains containing TEM-1 β-lactamase plasmid were recognised in the 1970s and resistance to multiple other antibiotics is also widely reported.7Trees DL Morse SA Chancroid and Haemophilus ducreyi: an update.Clin Microbiol Rev. 1995; 8: 357-375Crossref PubMed Google Scholar Of note, the isolates from New Zealand were all penicillin susceptible, with penicillin minimum inhibitory concentrations of 0·25 mg/L, and were negative for TEM β-lactamase by PCR. Newer yaws eradication strategies propose the use of a single oral dose of azithromycin.8Mitjà O Hays R Rinaldi AC McDermot R Bassat Q New treatment schemes for yaws: the path towards eradiction.Clin Infect Dis. 2012; 55: 406-412Crossref PubMed Scopus (15) Google Scholar This strategy would also be effective against lesions caused by H ducreyi; however, active surveillance would need to be undertaken to monitor for the development of resistance to macrolides. There remains a number of unanswered questions. First, have these two clinical entities always existed in parallel or has there been a more recent shift to non-genital-site infections? Human infection studies have shown infection of abraded upper arm skin with low infecting doses, supporting infection occurring at non-genital sites.9Spinola SM Wild LM Apicella MA Gaspari AA Campagnari AA Experimental human infection with Haemophilus ducreyi.J Iinfect Dis. 1994; 169: 1146-1150Crossref PubMed Scopus (113) Google Scholar Second, infection confers only partial immunity, allowing for reinfection; presumably these might present at different sites.6Bong CTH Bauer ME Spinola SM Haemophilus ducreyi: clinical features, epidemiology, and prospects for disease control.Microbes Infect. 2002; 4: 1141-1148Crossref PubMed Scopus (52) Google Scholar, 10Janowicz DM Li W Bauer ME Host-pathogen interplay of Haemophilus ducreyi.Curr Opin Infect Dis. 2010; 23: 64-69Crossref PubMed Scopus (21) Google Scholar Additional work is needed to better understand the role of H ducreyi in chronic skin ulceration. We declare that we have no competing interests. Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort studyIn this yaws-endemic community, H ducreyi is an important and previously unrecognised cause of chronic skin ulceration. Reactive syphilis serology caused by latent yaws can occur in ulcers with the presence of H ducreyi alone. The introduction of PCR for ulcer surveillance could improve the accuracy of diagnosis in countries with yaws eradication campaigns. Full-Text PDF Open Access