Treatment Outcome of Patients with Buruli Ulcer Disease in Togo

Background Following introduction of antimycobacterial treatment of Buruli ulcer disease (BUD),several clinical studies evaluated treatment outcomes of BUD patients, in particular healing times, secondary lesions and functional limitations. Whereas recurrences were rarely observed, paradoxical reactions and functional limitations frequently occurred. Although systematic BUD control in Togo was established as early as 2007, treatment outcome has not been reviewed to date. Therefore, a pilot project on post-treatment follow-up of BUD patients in Togo aimed to evaluate treatment outcomes and to provide recommendations for optimization of treatment success. Methodology/Principal Findings Out of 199 laboratory confirmed BUD patients, 129 could be enrolled in the study. The lesions of 109 patients (84.5%) were completely healed without any complications, 5 patients (3.9%) had secondary lesions and 15 patients (11.6%) had functional limitations. Edema, category III ulcers >15cm, healing times >180 days and a limitation of movement at time of discharge constituted the main risk factors significantly associated with BUD related functional limitations (P180 days and limitation of movement at discharge constituted the main risk factors for functional limitations in Togolese BUD patients. Standardized treatment plans, patient assessment and follow-up, as well as improved management of medical records are recommended to allow for intensified monitoring of disease progression and healing process, to facilitate implementation of therapeutic measures and to optimize treatment success

Implementation of a National Reference Laboratory for Buruli Ulcer Disease in Togo

Background: In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Methodology: Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime'' and "Central,'' standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. Principal Findings: The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. Conclusions: High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory

Représentativité et réactivité du système de surveillance de la Fièvre Jaune au Togo, 2004-2014: Representativeness and responsiveness of the Yellow Fever surveillance system in Togo, 2004-2014

Introduction: Peu d’informations sont disponibles sur le système de surveillance de la fièvre jaune au Togo. L’objectif est d’évaluer la simplicité, la représentativité et la réactivité de ce système. Méthodes: Une étude transversale descriptive a été menée de 2015 à 2016 à l’Institut Na-tional d’Hygiène (INH) qui est le Laboratoire National de Référence (LNR) pour les maladies à po-tentiel épidémique du Togo. La base de données de 2004-2014 de la fièvre jaune- rougeole -rubéole du LNR et le guide de surveillance intégrée des maladies et riposte, le guide d’évaluation des systèmes de surveillance de Centers for Disease Control and Prevention (CDC) ont été utilisés. Les médianes, intervalles interquartiles et les proportions ont été calculés avec Epi Info 7 et Excel 2003. Résultats: Un cas suspect de fièvre jaune nécessite une confirmation biologique qui se fait à plusieurs niveaux. Le système est représentatif de tous les districts, toutes les années et de toutes les populations du Togo. Un total de 3054 de cas suspects a été notifié dont 32 cas probables et 12 cas confirmés, par-mi lesquels, 8 étaient des hommes. Environs 93,01 % (2833) des cas suspects ont été prélevés dans les 14 jours suivants le début des symp-tômes, 28,39% (866) des échantillons ont été acheminés dans les 72 heures et 77,95% des résultats rendus dans les 7 jours rendant le système peu réactif. Conclusion: Le système de surveillance de la fièvre jaune au Togo est représentatif, complexe et peu réactif. Il s’avère nécessaire de mettre en place un système de convoyage rapide des échantillons. Introduction: Little information is available on yellow fever surveillance system in Togo. The simplicity, representativeness and responsiveness of this system were assessed. Material and Methods: It was a descriptive cross-sectional study conducted from October 2015 to February 2016 at the Institut National d’Hygiène, the National Reference Laboratory (NRL) for epidemic prone diseases of Togo. We used the yellow fever-measles-rubella database, the integrated dis-ease surveillance and response guideline and the Centers for Disease Control and Prevention (CDC) guidelines for surveillance system evaluation. Medians, interquartile intervals and proportions were calculated and presented in tables and figures with Excel 2003 and Epi Info 7. Results: A yellow fever case must be confirmed at several reference levels making yellow fever surveillance complex. This surveillance system is representative of all districts, all years and all populations of Togo. A total of 3054 suspected cases were reported, including 32 probable cases and 12 confirmed cases. Of the confirmed cases, 08 were men. About 93.01% (2833) of the suspected cases samples were taken within 14 days after the symptoms onset, 28,39% (866) of samples were transported within 72 hours and 77, 95% of the results were available within 7 days, making the system unresponsive. Conclusion: The yellow fever surveillance system in Togo is representative, complex, and unresponsive due to the long delay in transporting samples to the NRL. A rapid sample conveying system is recommende

Loop-Mediated Isothermal Amplification for Laboratory Confirmation of Buruli Ulcer Disease-Towards a Point-of-Care Test

Background As the major burden of Buruli ulcer disease (BUD) occurs in remote rural areas, development of point-of-care (POC) tests is considered a research priority to bring diagnostic services closer to the patients. Loop-mediated isothermal amplification (LAMP),a simple, robust and cost-effective technology, has been selected as a promising POC test candidate. Three BUD-specific LAMP assays are available to date, but various technical challenges still hamper decentralized application. To overcome the requirement of cold-chains for transport and storage of reagents, the aim of this study was to establish a dry-reagent-based LAMP assay (DRB-LAMP) employing lyophilized reagents. Methodology/Principal Findings Following the design of an IS2404 based conventional LAMP (cLAMP) assay suitable to apply lyophilized reagents, a lyophylization protocol for the DRB-LAMP format was developed. Clinical performance of cLAMP was validated through testing of 140 clinical samples from 91 suspected BUD cases by routine assays, i.e. IS2404 dry-reagent-based (DRB) PCR, conventional IS2404 PCR (cPCR),IS2404 qPCR, compared to cLAMP. Whereas qPCR rendered an additional 10% of confirmed cases and samples respectively, case confirmation and positivity rates of DRB-PCR or cPCR (64.84% and 56.43%;100% concordant results in both assays) and cLAMP (62.64% and 52.86%) were comparable and there was no significant difference between the sensitivity of the assays (DRB PCR and cPCR, 86.76%;cLAMP, 83.82%). Likewise, sensitivity of cLAMP (95.83%) and DRB-LAMP (91.67%) were comparable as determined on a set of 24 samples tested positive in all routine assays. Conclusions/Significance Both LAMP formats constitute equivalent alternatives to conventional PCR techniques. Provided the envisaged availability of field friendly DNA extraction formats, both assays are suitable for decentralized laboratory confirmation of BUD, whereby DRB-LAMP scores with the additional advantage of not requiring cold-chains. As validation of the assays was conducted in a third-level laboratory environment, field based evaluation trials are necessary to determine the clinical performance at peripheral health care level

Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

Background: The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guerin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology: The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings: After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31),sex (p = 0.24),age (p = 0.96),and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions: In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD

Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

Background: The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guerin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology: The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings: After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31),sex (p = 0.24),age (p = 0.96),and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions: In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD

Emergence of Epidemic Neisseria meningitidis Serogroup X Meningitis in Togo and Burkina Faso

Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006–2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006–2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007–2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March–April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine

Risk factors for Mycobacterium ulcerans infection (Buruli Ulcer) in Togo ─ a case-control study in Zio and Yoto districts of the maritime region

Abstract Background Buruli ulcer (BU) is a neglected mycobacterial skin infection caused by Mycobacterium ulcerans. This disease mostly affects poor rural populations, especially in areas with low hygiene standards and sanitation coverage. The objective of this study was to identify these risk factors in the districts of Zio and Yoto of the Maritime Region in Togo. Methods We conducted a case-control study in Zio and Yoto, two districts proved BU endemic from November 2014 to May 2015. BU cases were diagnosed according to the WHO clinical case definition at the Centre Hospitalier Régional de Tsévié (CHR Tsévié) and confirmed by Ziehl-Neelsen (ZN) microscopy and IS2404 polymerase chain reaction (PCR). For each case, up to two controls matched by sex and place of residence were recruited. Socio-demographic, environmental or behavioral data were collected and conditional logistic regression analysis was used to identify and compare risk factors between BU cases and controls. Results A total of 83 cases and 128 controls were enrolled. The median age was 15 years (range 3–65 years). Multivariate conditional logistic regression analysis after adjustment for potential confounders identified age (< 10 years (OR =11.48, 95% CI = 3.72–35.43) and 10–14 years (OR = 3.63, 95% CI = 1.22–10.83)), receiving insect bites near a river (OR = 7.8, 95% CI = 1.48–41.21) and bathing with water from open borehole (OR = 5.77, (1.11–29.27)) as independent predictors of acquiring BU infection. Conclusions This study identified age, bathing with water from open borehole and receiving insect bites near a river as potential risk of acquiring BU infection in Zio and Yoto districts of the Maritime Region in south Togo

Additional file 1: Questionnaire form S1. of Risk factors for Mycobacterium ulcerans infection (Buruli Ulcer) in Togo ─ a case-control study in Zio and Yoto districts of the maritime region

Questionnaire form used to collect data during the survey on risk factor for Mycobacterium ulcerans infection in Zio and Yoto districts of Maritime Region, Togo, May 19–30, 2017. (DOC 84 kb