Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study

Background Buruli ulcer, caused by Mycobacterium ulcerans, was identifi ed as a neglected emerging infectious disease by WHO in 1998. Although Buruli ulcer is the third most common mycobacterial disease worldwide, understanding of the disease is incomplete. We analysed a large cohort of laboratory-confi rmed cases of Buruli ulcer from Pobè, Benin, to provide a comprehensive description of the clinical presentation of the disease, its variation with age and sex, and its eff ect on the occurrence of permanent functional sequelae. Methods Between Jan 1, 2005, and Dec 31, 2011, we prospectively collected clinical and laboratory data from all patients with Buruli ulcer diagnosed at the Centre de Dépistage et de Traitement de l’Ulcère de Buruli in Pobè, Benin. We followed up patients to assess the frequency of permanent functional sequelae. All analyses were done on cases that were laboratory confi rmed. Findings 1227 cases of laboratory-confi rmed Buruli ulcer were included in the analysis. Typically, patients with Buruli ulcer were children (median age at diagnosis 12 years) presenting with a unique (1172 [96%]) large (≥15 cm, 444 [36%]) ulcerative (805 [66%]) lesion of the lower limb (733 [60%]). Atypical clinical presentation of Buruli ulcer included Buruli ulcer osteomyelitis with no identifi able present or past Buruli ulcer skin lesions, which was recorded in at least 14 patients. The sex ratio of Buruli ulcer widely varied with age, with male patients accounting for 57% (n=427) of patients aged 15 years and younger, but only 33% (n=158) of those older than 15 years (odds ratio [OR] 2·59, 95% CI 2·04–3·30). Clinical presentation of Buruli ulcer was signifi cantly dependent on age and sex. 54 (9%) male patients had Buruli ulcer osteomyelitis, whereas only 28 (4%) of female patients did (OR 2·21, 95% CI 1·39–3·59). 1 year after treatment, 229 (22% of 1043 with follow-up information) patients presented with permanent functional sequelae. Presentation with oedema, osteomyelitis, or large (≥15 cm in diameter), or multifocal lesions was signifi cantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29–11·31) and operationally defi nes severe Buruli ulcer. Interpretation Our fi ndings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specifi c aspect in areas endemic for Buruli ulcer; and specifi c disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our fi ndings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer

Contribution of the community health volunteers in the control of buruli ulcer in Bénin

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually BU begins as a painless nodule, plaque or edema, ultimately developing into an ulcer. The high number of patients presenting with ulcers in an advanced stage is striking. Such late presentation will complicate treatment and have long-term disabilities as a consequence. The disease is mainly endemic in West Africa. The primary strategy for control of this disease is early detection using community village volunteers.In this retrospective, observational study, information regarding Buruli ulcer patients that reported to one of the four BU centers in Bénin between January 2008 and December 2010 was collected using the WHO/BU01 forms. Information used from these forms included general characteristics of the patient, the results of diagnostic tests, the presence of functional limitations at start of treatment, lesion size, patient delay and the referral system. The role of the different referral systems on the stage of disease at presentation in the hospital was analyzed by a logistic regression analysis. About a quarter of the patients (26.5%) were referred to the hospital by the community health volunteers. In our data set, patients referred to the hospital by community health volunteers appeared to be in an earlier stage of disease than patients referred by other methods, but after adjustment by the regression analysis for the health center, this effect could no longer be seen. The Polymerase Chain Reaction (PCR) for IS2404 positivity rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems.This study clarifies the role played by community health volunteers in Bénin, and shows that they play an important role in the control of BU

Logistic regression analysis (enter method) on pre-hospital delay.

<p>Logistic regression analysis (enter method) on pre-hospital delay.</p

Multilevel model with level 1 and level 2 variables.

*<p>Wald statistic used to test the significance of the coefficients.</p

Model with level 1 and 2 factors potentially related to pre-hospital delay.

<p>Model with level 1 and 2 factors potentially related to pre-hospital delay.</p

Sample characteristics.

<p>Sample characteristics.</p

A multistage sampling procedure.

<p>A multistage sampling procedure.</p

Skin pictures (WHO) shown to respondents to estimate pre-hospital delay.

<p>^a From The Lancet, 354, Tjip S Van der Werf, Winette TA Van der Graaf, Jordan W Tappero, Kingsley Asiedu, Mycobacterium ulcerans infection, 1013–1018, 1999 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002014#pntd.0002014-vanderWerf1" target="_blank">[39]</a>.</p

Decrease in Mycobacterium ulcerans disease (Buruli ulcer) in the Lalo District of Bénin (West Africa)

Abstract Background Buruli ulcer (BU) is a chronic, necrotizing infectious skin disease caused by Mycobacterium ulcerans. In recent years, there has been a decrease in the number of new cases detected. This study aimed to show the evolution of its distribution in the Lalo District in Bénin from 2006 to 2017. Methods The database of the BU Detection and Treatment Center of Lalo allowed us to identify 1017 new cases in the Lalo District from 2006 to 2017. The annual prevalence was calculated with subdistricts and villages. The trends of the demographic variables and those related to the clinical and treatment features were analysed using Microsoft Excel® 2007 and Epi Info® 7. Arc View version® 3.4 was used for mapping. Results From 2006 to 2017, the case prevalence of BU in the Lalo District decreased by 95%. The spatial distribution of BU cases confirmed the foci of the distribution, as described in the literature. The most endemic subdistricts were Ahomadégbé, Adoukandji, Gnizounmè and Tchito, with a cumulative prevalence of 315, 225, 215 and 213 cases per 10,000 inhabitants, respectively. The least endemic subdistricts were Zalli, Banigbé, Lalo-Centre and Lokogba, with 16, 16, 10, and 5 cases per 10,000 inhabitants, respectively. A significant decrease in the number of patients with ulcerative lesions (p = 0.002), as well as those with category 3 lesions (p < 0.001) and those treated surgically (p < 0.001), was observed. The patients confirmed by PCR increased (from 40.42% in 2006 to 84.62% in 2017), and joint limitation decreased (from 13.41% in 2006 to 0.0% in 2017). Conclusion This study confirmed the general decrease in BU prevalence rates in Lalo District at the subdistrict and village levels, as also observed at the country level. This decrease is a result of the success of the BU control strategies implemented in Bénin, especially in the Lalo District

Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study

Background: Buruli ulcer, caused by Mycobacterium ulcerans, was identified as a neglected emerging infectious disease by WHO in 1998. Although Buruli ulcer is the third most common mycobacterial disease worldwide, understanding of the disease is incomplete. We analysed a large cohort of laboratory-confirmed cases of Buruli ulcer from Pobè, Benin, to provide a comprehensive description of the clinical presentation of the disease, its variation with age and sex, and its effect on the occurrence of permanent functional sequelae. Methods: Between Jan 1, 2005, and Dec 31, 2011, we prospectively collected clinical and laboratory data from all patients with Buruli ulcer diagnosed at the Centre de Dépistage et de Traitement de l'Ulcère de Buruli in Pobè, Benin. We followed up patients to assess the frequency of permanent functional sequelae. All analyses were done on cases that were laboratory confirmed. Findings: 1227 cases of laboratory-confirmed Buruli ulcer were included in the analysis. Typically, patients with Buruli ulcer were children (median age at diagnosis 12 years) presenting with a unique (1172 [96%]) large (≥15 cm, 444 [36%]) ulcerative (805 [66%]) lesion of the lower limb (733 [60%]). Atypical clinical presentation of Buruli ulcer included Buruli ulcer osteomyelitis with no identifiable present or past Buruli ulcer skin lesions, which was recorded in at least 14 patients. The sex ratio of Buruli ulcer widely varied with age, with male patients accounting for 57% (n=427) of patients aged 15 years and younger, but only 33% (n=158) of those older than 15 years (odds ratio [OR] 2·59, 95% CI 2·04–3·30). Clinical presentation of Buruli ulcer was significantly dependent on age and sex. 54 (9%) male patients had Buruli ulcer osteomyelitis, whereas only 28 (4%) of female patients did (OR 2·21, 95% CI 1·39–3·59). 1 year after treatment, 229 (22% of 1043 with follow-up information) patients presented with permanent functional sequelae. Presentation with oedema, osteomyelitis, or large (≥15 cm in diameter), or multifocal lesions was significantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29–11·31) and operationally defines severe Buruli ulcer. Interpretation: Our findings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specific aspect in areas endemic for Buruli ulcer; and specific disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our findings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer. Funding: Agence Nationale de la Recherche (ANR), Fondation Raoul Follereau, Fondation pour la Recherche Médicale (FRM), and Institut des Maladies Génétiques (IMAGINE)