Diagnostic Value of Histological Analysis of Punch Biopsies in Suspected Cutaneous Buruli Ulcer: A Study on 32 Cases of Confirmed Buruli Ulcer in Cameroon.

BACKGROUND: Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. In this prospective study, we aim to clarify the main histopathological features of cutaneous BU based on 4-mm skin punch biopsies and to evaluate the diagnostic value of this method. METHODS: Between 2011 and 2013, a prospective study was conducted in Cameroon. Dry swabs from ulcerative lesions and fine-needle aspirates of nonulcerative lesions were examined for Ziehl-Neelsen (ZN) staining, followed by PCR targeting IS2404 and culture. Two 4-mm punch biopsies were performed in the center and in the periphery of each lesion. RESULTS: The 364 patients included in the study had 422 lesions (381 were ulcerative and 357 lesions were biopsied). Among the 99 ulcerated lesions with a final diagnosis of BU, histological features for BU were fulfilled in 32 lesions. 32/32 showed subcutaneous necrosis with a neutrophilic inflammatory infiltrate. 26/32 presented alcohol-resistant bacilli confirmed by ZN stain on histology. CONCLUSION: Punch biopsies help in establishing the correct diagnosis of BU and also in the differential diagnosis of chronic ulcers. The main histological feature for BU is diffuse coagulative necrosis of subcutaneous tissue, with acid-fast bacilli detected by ZN stain.

Performance of a brief geriatric evaluation compared to a comprehensive geriatric assessment for detection of geriatric syndromes in family medicine: a prospective diagnostic study.

BACKGROUND: Geriatric syndromes are rarely detected in family medicine. Within the AGE program (active geriatric evaluation), a brief assessment tool (BAT) designed for family physicians (FP) was developed and its diagnostic performance estimated by comparison to a comprehensive geriatric assessment. METHODS: This prospective diagnostic study was conducted in four primary care sites in Switzerland. Participants were aged at least 70 years and attending a routine appointment with their physician, without previous documented geriatric assessment. Participants were assessed by their family physicians using the BAT, and by a geriatriciant who performed a comprehensive geriatric assessment within the following two-month period (reference standard). Both the BAT and the full assessment targeted eight geriatric syndromes: cognitive impairment, mood impairment, urinary incontinence, visual impairment, hearing loss, undernutrition, osteoporosis and gait and balance impairment. Diagnostic accuracy of the BAT was estimated in terms of sensitivity, specificity, and predictive values; secondary outcomes were measures of feasibility, in terms of added consultation time and comprehensiveness in applying the BAT items. RESULTS: Prevalence of the geriatric syndromes in participants (N=85, 46 (54.1%) women, mean age 78 years (SD 6))ranged from 30.0% (malnutrition and cognitive impairment) to 71.0% (visual impairment), with a median number of 3 syndromes (IQR 2 to 4) per participant. Sensitivity of the BAT ranged from 25.0% for undernutrition (95%CI 9.8% - 46.7%) to 82.1% for hearing impairment (95%CI 66.5% - 92.5%), while specificity ranged from 45.8% for visual impairment (95%CI 25.6-67.2) to 87.7% for undernutrition (76.3% to 94.9%). Finally, most negative predictive values (NPV) were between 73.5% and 84.1%, excluding visual impairment with a NPV of 50.0%. Family physicians reported BAT use as per instructions for 76.7% of the syndromes assessed. CONCLUSIONS: Although the BAT does not replace a comprehensive geriatric assessment, it is a useful and appropriate tool for the FP to screen elderly patients for most geriatric syndromes. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov on February 20, 2013 ( NCT01816087 ).

Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon.

BACKGROUND: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. METHOD: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. RESULTS/ DISCUSSION: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). CONCLUSION: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status.

The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon.

BACKGROUND: Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. METHODODOLOGY/PRINCIPAL FINDINGS: Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82-0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0-98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2-84.7). Patients with intermediate BU probability needed to be tested by PCR. CONCLUSIONS/SIGNIFICANCE: We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use.

Clinical epidemiology, diagnosis and treatment of visceral leishmaniasis in the Pokot endemic area of Uganda and Kenya.

Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.