title: Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.
abstract: BACKGROUND
  Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands-Haemophilus ducreyi-as causes of skin ulceration in a yaws-endemic region. Additionally, we identified specific signs and symptoms associated with these causative agents of cutaneous ulcers and compared these findings with laboratory-based diagnoses.
  
  
  METHODS
  We did a prospective cohort study of five yaws-endemic villages (total population 3117 people) during a yaws elimination campaign in Papua New Guinea in April, 2013. We enrolled all consenting patients with chronic moist or exudative skin ulcers. We undertook a detailed dermatological assessment, syphilis serology, and PCR on lesional swabs to detect the presence of T pallidum pertenue and H ducreyi. Patients with PCR-confirmed bacterial infections were included in a comparative analysis of demographics and clinical features.
  
  
  RESULTS
  Full outcome data were available for 90 people with skin ulcers. Of these patients, 17 (19%) had negative results in all molecular tests and were therefore excluded from the comparative analyses. A bacterial cause was identified in 73 (81%) participants-either H ducreyi (n=42), T pallidum pertenue (yaws; n=19), or coinfection with both organisms (dual infection; n=12). The demographic characteristics of the patients infected with yaws and with H ducreyi were similar. Skin lesions in patients with yaws and in those with dual infection were larger than those in patients infected with H ducreyi (p=0·071). The lesions in patients with yaws and dual infection were more circular in shape (79% and 67%) than in those infected with H ducreyi (21%; p<0·0001); more likely to have central granulating tissue (90% and 67% vs 14%; p<0·0001); and more likely to have indurated edges (74% and 83% vs 31%; p=0·0003). The prevalence of reactive combined serology (positive T pallidum haemagglutination test and rapid plasmin reagin titre of ≥1:8) was higher in cases of yaws (63%) and dual infections (92%) than in H ducreyi infections (29%; p<0·0001).
  
  
  CONCLUSIONS
  In 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.
  
  
  BACKGROUND
  Newcrest Mining Company.
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain; Lihir Medical Centre - International SOS, Newcrest Mining, Lihir Island, Papua New Guinea. Electronic address: oriolmitja@hotmail.com.
authors.forename: Oriol
authors.initials: O
authors.lastname: Mitjà
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Lukehart
authors.affiliation: Lihir Medical Centre - International SOS, Newcrest Mining, Lihir Island, Papua New Guinea.
authors.forename: Gideon
authors.initials: G
authors.lastname: Pokowas
authors.affiliation: Lihir Medical Centre - International SOS, Newcrest Mining, Lihir Island, Papua New Guinea.
authors.forename: Penias
authors.initials: P
authors.lastname: Moses
authors.affiliation: Lihir Medical Centre - International SOS, Newcrest Mining, Lihir Island, Papua New Guinea.
authors.forename: August
authors.initials: A
authors.lastname: Kapa
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Charmie
authors.initials: C
authors.lastname: Godornes
authors.affiliation: Department of Microbiology, Sullivan Nicolaides Pathology, Brisbane, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robson
authors.affiliation: Department of Microbiology, Sullivan Nicolaides Pathology, Brisbane, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cherian
authors.affiliation: Disease Control Branch, National Department of Health, Port Moresby, Papua New Guinea.
authors.forename: Wendy
authors.initials: W
authors.lastname: Houinei
authors.affiliation: World Health Organization, Office of the WHO Representative, Boroko NCD, Port Moresby, Papua New Guinea.
authors.forename: Walter
authors.initials: W
authors.lastname: Kazadi
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka, Eastern Highland Province, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: de Lazzari
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
mesh_terms: D000293:Adolescent; D002602:Chancroid / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection; D019353:Endemic Diseases; D005260:Female; D006191:Haemophilus ducreyi; D006386:Hemagglutination Tests; D006801:Humans; D008297:Male; D010219:Papua New Guinea / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011446:Prospective Studies; D012883:Skin Ulcer / Q000175:diagnosis / Q000209:etiology / Q000382:microbiology*; D013587:Syphilis / Q000175:diagnosis / Q000382:microbiology*; D013588:Syphilis Serodiagnosis; D014210:Treponema pallidum; D014456:Ulcer / Q000209:etiology / Q000382:microbiology; D015001:Yaws / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology*