Reconstructive surgery for sequellae of Mycobacterium ulcerans infection (Buruli ulcer) of the upper limb.

INTRODUCTION: Infection by Mycobacterium ulcerans constitutes a neglected tropical disease whose prevalence seems to have overrun those of cutaneous tuberculosis and leprosy. Its aggressivity depends on a mycolactone toxin. Lesions may involve skin, tendon and bone with a large spectrum of manifestations: non-ulcerative (papules, nodules, plaques), ulcerative and oedematous presentations as well as osteomyelitis with muscular contraction and ankylosis. Upper limbs account for more than two thirds of the infection sites. Surgical treatment may involve tendon transpositions, partial and total skin grafts. Amputation is relegated to extreme cases. MATERIAL AND METHODS: Selected iconography from patients during the last 15 years is presented. At least 1500 cases had partial skin grafts (anterior thigh). Total skin grafts (inguinal region) were used in about 200 cases. Complex lesions involved 9 ilioinguinal flaps (5 boys, 4 girls, mean age 11.2 years, range 2-16 years), 5 tendon transfers (4 boys, one girl, mean age 15.4 years, range 12-19 years) and 3 resections of the first carpal row (2 girls, 1 boy, mean age 8 years, range 4-15 years). RESULTS AND DISCUSSION: Out of 9 ilioinguinal flaps mild, marginal necrosis was the only complication in 2 patients without flap loss. Mean hospital stay was 26.44 days (range, 18-41 days), with return to full weight-bearing after a mean of 12 weeks (range 9-25 weeks) after discharge. Functional thumb opposition to allow pencil prehension was achieved in all three cases of resection of first carpal row resection without postoperative complications.

Buruli ulcer: Evaluation of its medical and surgical management at the Allada (Benin) Screening and Treatment Center, 2010-2014.

The objective of our study was to evaluate the medico-surgical management of Buruli ulcer (BU) in the BU Screening and Treatment Center (CDTUB) of Allada in Benin. This retrospective and descriptive study retrospectively reviewed records of patients seen from 2010 to 2014 at the CDTUB of Allada. It included patients diagnosed with BU according to WHO epidemiological and clinical criteria as well as laboratory results and who were treated according to WHO medical and surgical recommendations. In all, 274 patients were diagnosed and treated, 57.7% of them children younger than 15 years. Ulcerative lesions (189, 69%) and WHO category II lesions (144, 52.5%) predominated. All patients received dual antibiotic therapy and 43.4% (119) underwent surgery as well. Category III lesions and multifocal lesions required more surgery, whereas most category I lesions healed under medical treatment. The overall rate of healing was 92%: 53.3% for patients who received only antibiotic therapy and 38.7% for those who also had surgery. The median healing time was 13 weeks and ranged from 4 to 56 weeks. In the CDTUB of Allada, between 2010 and 2014, most patients were treated with antibiotic therapy alone, but a significant number still received surgery.

Buruli ulcer treatment: Rate of surgical intervention differs highly between treatment centers in West Africa.

BACKGROUND: Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic. METHODS: A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders. RESULTS: A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. CONCLUSION: The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU.

Mycobacterium ulcerans disease management in Australian patients: the re-emergence of surgery as an important treatment modality.

With the demonstration of the effectiveness of antibiotic treatment, the management of Mycobacterium ulcerans disease has changed from a predominantly surgically to a predominantly medically treated disease. However, research among Australian patients has revealed that antibiotic treatment alone is associated with prolonged wound healing times, high rates of treatment toxicity, and the potential for significant tissue destruction associated with severe paradoxical reactions. We present the current state of M. ulcerans management in Barwon Health, Australia, where a close working relationship exists between the Plastic Surgical and Infectious Diseases units. Here treatment has evolved based on nearly 20 years of experience gained from managing more around 600 patients from a M. ulcerans epidemic on the nearby Bellarine and Mornington Peninsulas. In our experience, surgery has re-emerged to play an important role in the treatment of M. ulcerans in improving the rate of wound healing, minimizing antibiotic associated toxicity and preventing further tissue loss associated with severe paradoxical reactions. For selected small lesions surgery without antibiotics may also be an effective treatment option, however aggressive surgical resection of lesions with wide margins through uninvolved tissue should no longer be performed. Furthermore, extensive excisional surgery that will require the use of split skin grafts and vascularized tissue flaps to repair skin defects should be avoided if possible.

Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease).

BACKGROUND: Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery. OBJECTIVES: To summarize the evidence of drug treatments for treating Buruli ulcer. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.Rifampicin combined with streptomycinWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).An additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.Rifampicin combined with clarithromycinTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phaseOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).Novel combination therapyTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%. AUTHORS' CONCLUSIONS: While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.

Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial.

BACKGROUND: Surgical intervention was once the mainstay of treatment for Buruli ulcer disease, a neglected tropical disease caused by Mycobacterium ulcerans. Since the introduction of streptomycin and rifampicin for 8 weeks as standard care, surgery has persisted as an adjunct therapy, but its role is uncertain. We investigated the effect of delaying the decision to operate to 14 weeks on rates of healing without surgery. METHODS: In this randomised controlled trial, we enrolled patients aged 3 years or older with confirmed disease at one hospital in Lalo, Benin. Patients were randomly assigned (1:1) to groups assessing the need for excision surgery 8 weeks (standard care) or 14 weeks after initiation of antimicrobial treatment. The primary endpoint was the number of patients healed without the need for surgery (not including skin grafting), assessed in all patients in follow-up at 50 weeks (or last observation for those healed for >10 weeks). A doctor masked to treatment assignment checked the indications for surgery according to predefined criteria. This study is registered with ClinicalTrials.gov, number NCT01432925. FINDINGS: Between July 1, 2011, and Jan 15, 2015, 119 patients were enrolled, with two patients per group lost to follow-up. 55 (96%) of 57 participants in the delayed-decision group and 52 (90%) of 58 participants in the standard-care group had healed lesions 1 year after start of antimicrobial treatment (relative risk [RR] 1·08, 95% CI 0·97-1·19). 37 (67%) of 55 patients in the delayed-decision group had their lesions healed without surgical intervention, as did 25 (48%) of 52 in the standard-care group (RR 1·40, 95% CI 1·00-1·96). The time to heal and residual functional limitations did not differ between the two groups (median time to heal 21 weeks [IQR 10-27] in the delayed-decision group and 21 weeks [10-39] in the standard-care group; functional limitations in six [11%] of 57 and three [5%] of 58 patients; p=0·32). Postponing the decision to operate resulted in reduced median duration of hospitalisation (5 days [IQR 0-187] vs 131 days [0-224]; p=0·024) and wound care (153 days [IQR 56-224] vs 182 days [94-307]; p=0·036). INTERPRETATION: In our study, patients treated for Buruli ulcer benefited from delaying the decision to operate. Even large ulcers can heal with antibiotics alone, without delaying healing rate and without an increase in residual functional limitations. FUNDING: NWO-VENI grant 241500, BUG Foundation, and UBS OPTIMUS.

Surgical Management of Chronic Wounds in a Buruli Ulcer Endemic Area in Central Africa.

BACKGROUND: Chronic wounds, especially Buruli ulcers (BU) are emerging public health threat in West and Central Africa. Akonolinga in Cameroon is one of the four health districts affected by BU. Since 2002, Médécins Sans Frontières has established a specialized wound carecenter to actively diagnose and provide treatment of chronic wounds that is accessible and affordable for all patients. Our objectives were to report the surgical activities in Akonolinga, to provide description of the types of chronic wounds and elements of anticipation of treatment needs in a public health perspective. METHOD: We carried out a retrospective cohort and descriptive study from January 2012 to June 2014 (30 months) on a series of consecutive patients with chronic wounds, managed surgically in Akonolinga, Centre Region, Cameroon. Among BU patients only those with necessity of surgery were included and the others followed only their 8 weeks medical treatment with antibiotics. RESULTS: A total of 148 patients were recorded. 101 cases of BU and related disability and 47 cases of non-Buruli chronic wounds. Patients had a mean age of 34 years. Most of the procedures used were debridement 40 %, skin graft 29 %, stripping 5 %, plastic procedures 7 %, and amputation 4 %. The mean number of procedures was 2 for each patient in this series. CONCLUSION: Chronic wounds occur worldwide and may be caused by specific health conditions. Medical and paramedical education should provide both the theoretical knowledge and practical skills to help health care personnel to face this problem in their communities.

Exploration of a standard treatment for Buruli ulcer through a comprehensive analysis of all cases diagnosed in Japan.

Buruli ulcer (BU) is a refractory skin ulcer caused by Mycobacterium ulcerans or M. ulcerans ssp. shinshuense, a subspecies thought to have originated in Japan or elsewhere in Asia. Although BU occurs most frequently in tropical and subtropical areas such as Africa and Australia, the occurrence in Japan has gradually increased in recent years. The World Health Organization recommends multidrug therapy consisting of a combination of oral rifampicin (RFP) and i.m. streptomycin (SM) for the treatment of BU. However, surgical interventions are often required when chemotherapy alone is ineffective. As a first step in developing a standardized regimen for BU treatment in Japan, we analyzed detailed records of treatments and prognoses in 40 of the 44 BU cases that have been diagnosed in Japan. We found that a combination of RFP (450 mg/day), levofloxacin (LVFX; 500 mg/day) and clarithromycin (CAM; at a dose of 800 mg/day instead of 400 mg/day) was superior to other chemotherapies performed in Japan. This simple treatment with oral medication increases the probability of patient adherence, and may often eliminate the need for surgery.

Mycobacterium ulcerans treatment--can antibiotic duration be reduced in selected patients?

INTRODUCTION: Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. METHODOLOGY / PRINCIPAL FINDINGS: A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21-41 days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14-27 days and 100% for 28-55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14-27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. CONCLUSION: In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes.

[Paradoxical reactions and responses during antibiotic treatment for Mycobacterium ulcerans infection (Buruli ulcer). Four cases from French Guiana]. / Réponses et réactions paradoxales au cours du traitement médicamenteux de l'infection à Mycobacterium ulcerans (ulcère de Buruli). Quatre observations en Guyane française.

BACKGROUND: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin. PATIENTS AND METHODS: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years. DISCUSSION: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics.

Wound care in Buruli ulcer disease in Ghana and Benin.

Buruli ulcer (BU) is a disease affecting the skin, subcutaneous fat, and bone tissues. Wound care is important in the prevention of disabilities. Awareness of current wound care practices in BU-endemic regions is necessary for future wound care interventions. Thirty-one health care workers in Ghana and Benin were interviewed with a semi-structured interview, complemented by structural observations. Quantitative data were analyzed through t tests and one-way analysis of variance, and qualitative data through descriptive statistics. There appeared to be a general understanding of wound assessment. A large variety of different topical antiseptics was reported to be used, pressure irrigation was never reported. Gauze was the main dressing type and a moist environment was preferred, but could not be maintained. Bleeding and pain were observed frequently. Standard of wound care differed importantly between health care personnel and between institutions and adherence to World Health Organization guidelines was low.

Treatment and prevention of Mycobacterium ulcerans infection (Buruli ulcer) in Australia: guideline update.

• Guidelines reflecting contemporary clinical practice in the management of Buruli ulcer (Mycobacterium ulcerans infection) in Australia were published in 2007. • Management has continued to evolve, as new evidence has become available from randomised trials, case series and increasing clinical experience with oral antibiotic therapy. • Therefore, guidelines on the diagnosis, treatment and prevention of Buruli ulcer in Australia have been updated. They include guidance on the new role of antibiotics as first-line therapy; the shortened duration of antibiotic treatment and the use of all-oral antibiotic regimens; the continued importance, timing and role of surgery; the recognition and management of paradoxical reactions during antibiotic treatment; and updates on the prevention of disease.

Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort.

BACKGROUND: Mycobacterium ulcerans (MU) is responsible for disfiguring skin lesions and is endemic on the Bellarine peninsula of southeastern Australia. Antibiotics have been shown to be highly effective in sterilizing lesions and preventing disease recurrences when used alone or in combination with surgery. Our practice has evolved to using primarily oral medical therapy. METHODS: From a prospective cohort of MU patients managed at Barwon Health, we describe those treated with primary medical therapy defined as treatment of a M. ulcerans lesion with antimicrobials either alone or in conjunction with limited surgical debridement. RESULTS: From 1/10/2010 through 31/12/11, 43 patients were treated with exclusive medical therapy, of which 5 (12%) also underwent limited surgical debridement. The median patient age was 50.2 years, and 86% had WHO category 1 and 91% ulcerative lesions. Rifampicin was combined with ciprofloxacin in 30 (70%) and clarithromycin in 12 (28%) patients. The median duration of antibiotic therapy was 56 days, with 7 (16%) receiving less than 56 days. Medication side effects requiring cessation of one or more antibiotics occurred in 7 (16%) patients. Forty-two (98%) patients healed without recurrence within 12 months, and 1 patient (2%) experienced a relapse 4 months after completion of 8 weeks of antimicrobial therapy. CONCLUSION: Our experience demonstrates the efficacy and safety of primary oral medical management of MU infection with oral rifampicin-based regimens. Further research is required to determine the optimal and minimum durations of antibiotic therapy, and the most effective antibiotic dosages and formulations for young children.

Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort.

OBJECTIVE: To describe risk factors for recurrence after exclusive surgical treatment of Mycobacterium ulcerans infection. DESIGN, SETTING AND PARTICIPANTS: Prospective observational cohort study of all M. ulcerans cases managed with surgery alone at Barwon Health, a tertiary referral hospital, from 1 January 1998 to 31 December 2011. A random-effects Poisson regression model was used to assess rates and associations of treatment failure. MAIN OUTCOME MEASURES: Rates of treatment failure and rate ratios (RRs) for factors associated with treatment failure. RESULTS: Of 192 patients with M. ulcerans infection, 50 (26%) had exclusive surgical treatment. Median age was 65.0 2013s (interquartile range [IQR], 45.5-77.7 2013s), and median duration of symptoms was 46 days (IQR, 26-90 days). There were 20 recurrences in 16 patients. For first lesions, the recurrence incidence rate was 41.8 (95% CI, 25.6-68.2) per 100 person-2013s, and median time to recurrence was 50 days (IQR, 30-171 days). Recurrence occurred ≤ 3 cm from the original lesion in 13 cases, and > 3 cm in nine. On univariable analysis, age ≥ 60 2013s (RR 13.84; 95% CI, 2.21-86.68; P < 0.01), distal lesions (RR, 20.43; 95% CI, 1.97-212.22; P < 0.01), positive histological margins (RR, 21.02; 95% CI, 5.51-80.26; P < 0.001), immunosuppression (RR, 17.97; 95% CI, 4.17-77.47; P < 0.01) and duration of symptoms > 75 days (RR, 10.13; 95% CI, 1.76-58.23; P = 0.02) were associated with treatment failure. On multivariable analysis, positive margins (RR, 7.72; 95% CI, 2.71-22.01; P < 0.001) and immunosuppression (RR, 6.45; 95% CI, 2.42-17.20; P = 0.01) remained associated with treatment failure. CONCLUSIONS: Recurrence rates after exclusive surgical treatment of M. ulcerans disease in an Australian cohort are high, with increased rates associated with immunosuppression or positive histological margins.

Perceptions on the effectiveness of treatment and the timeline of Buruli ulcer influence pre-hospital delay reported by healthy individuals.

BACKGROUND: Delay in seeking treatment at the hospital is a major challenge in current Buruli ulcer control; it is associated with severe sequelae and functional limitations. Choosing alternative treatment and psychological, social and practical factors appear to influence delay. Objectives were to determine potential predictors for pre-hospital delay with Leventhal's commonsense model of illness representations, and to explore whether the type of available dominant treatment modality influenced individuals' perceptions about BU, and therefore, influenced pre-hospital delay. METHODOLOGY: 130 healthy individuals aged >18 years, living in BU-endemic areas in Benin without any history of BU were included in this cross-sectional study. Sixty four participants from areas where surgery was the dominant treatment and sixty six participants from areas where antibiotic treatment was the dominant treatment modality were recruited. Using a semi-structured interview we measured illness perceptions (IPQ-R), knowledge about BU, background variables and estimated pre-hospital delay. PRINCIPAL FINDINGS: The individual characteristics 'effectiveness of treatment' and 'timeline acute-chronic' showed the strongest association with pre-hospital delay. No differences were found between regions where surgery was the dominant treatment and regions where antibiotics were the dominant treatment modality. CONCLUSIONS: Individual characteristics, not anticipated treatment modality appeared predictors of pre-hospital delay.