Risk factors for Buruli ulcer disease (Mycobacterium ulcerans infection):Results from a case-control study in Ghana

Background. Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection caused by Mycobacterium ulcerans, has been increasingly recognized in rural West Africa. The source and mode of transmission remain unknown. Methods. To identify BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin biopsy specimens. M. ulcerans infection was confirmed by at least I of the following diagnostic methods: histopathologic analysis, culture, polymerase chain reaction, and Ziehl-Neelsen staining of a lesion smear. We compared characteristics of case patients with confirmed BUD with those of age- and community-matched control subjects using conditional logistic regression analysis. Results. Among 121 case patients with confirmed BUD, leg lesions (49%) or arm lesions (36%) were common. Male case patients were significantly more likely than female case patients to have lesions on the trunk (25% vs. 6%; P = .009). Multivariable modeling among 116 matched case-control pairs identified wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence interval [Cl], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27; 95% Cl, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR, 0.36; 95% Cl, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95% Cl, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly associated with penetrating injuries (P = .14), insect bites near water bodies (P = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency virus infection (P = .99). Conclusions. BUD is an environmentally acquired infection strongly associated with exposure to river areas. Exposed skin may facilitate transmission. Until transmission is better defined, control strategies in BUD-endemic areas could include covering exposed skin

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana

ABSTRACT: BACKGROUND: Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. METHODS: Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents' narratives clarified illness experiences and meanings with reference to PC and PD variables. RESULTS: Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages CONCLUSIONS: Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healin is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiative

An Automated Phenotype-Driven Approach (GeneForce) for Refining Metabolic and Regulatory Models

Integrated constraint-based metabolic and regulatory models can accurately predict cellular growth phenotypes arising from genetic and environmental perturbations. Challenges in constructing such models involve the limited availability of information about transcription factor—gene target interactions and computational methods to quickly refine models based on additional datasets. In this study, we developed an algorithm, GeneForce, to identify incorrect regulatory rules and gene-protein-reaction associations in integrated metabolic and regulatory models. We applied the algorithm to refine integrated models of Escherichia coli and Salmonella typhimurium, and experimentally validated some of the algorithm's suggested refinements. The adjusted E. coli model showed improved accuracy (∼80.0%) for predicting growth phenotypes for 50,557 cases (knockout mutants tested for growth in different environmental conditions). In addition to identifying needed model corrections, the algorithm was used to identify native E. coli genes that, if over-expressed, would allow E. coli to grow in new environments. We envision that this approach will enable the rapid development and assessment of genome-scale metabolic and regulatory network models for less characterized organisms, as such models can be constructed from genome annotations and cis-regulatory network predictions

Risk Factors for Buruli Ulcer: A Case Control Study in Cameroon

Buruli ulcer (BU) is a neglected tropical infectious disease caused by Mycobacterium ulcerans. While BU is associated with areas where the water is slow-flowing or stagnant, the exact mechanism of transmission of the bacillus is unknown, impairing efficient control programs. Two hypotheses are proposed in the literature: previous trauma at the lesion site, and transmission through aquatic insect bites. Using results from a face-to-face questionnaire, our study compared characteristics from Cameroonian patients with Buruli ulcer to people without Buruli ulcer. This latter group of people was chosen within the community or within the family of case patients. The statistical analysis confirmed some well-known factors associated with the presence of BU, such as wearing short lower-body clothing while farming, but it showed that the use of bed nets and the treatment of wounds with leaves is less frequent in case patients. These newly identified factors may provide new insight into the mode of transmission of M. ulcerans. The implication of domestic or peridomestic insects, suggested by the influence of the use of bed nets, should be confirmed in specific studies

Distribution of Mycobacterium ulcerans in Buruli Ulcer Endemic and Non-Endemic Aquatic Sites in Ghana

Mycobacterium ulcerans, the causative agent of Buruli ulcer, is an emerging environmental bacterium in Australia and West Africa. The primary risk factor associated with Buruli ulcer is proximity to slow moving water. Environmental constraints for disease are shown by the absence of infection in arid regions of infected countries. A particularly mysterious aspect of Buruli ulcer is the fact that endemic and non-endemic villages may be only a few kilometers apart within the same watershed. Recent studies suggest that aquatic invertebrate species may serve as reservoirs for M. ulcerans, although transmission pathways remain unknown. Systematic studies of the distribution of M. ulcerans in the environment using standard ecological methods have not been reported. Here we present results from the first study based on random sampling of endemic and non-endemic sites. In this study PCR-based methods, along with biofilm collections, have been used to map the presence of M. ulcerans within 26 aquatic sites in Ghana. Results suggest that M. ulcerans is present in both endemic and non-endemic sites and that variable number tandem repeat (VNTR) profiling can be used to follow chains of transmission from the environment to humans. Our results suggesting that the distribution of M. ulcerans is far broader than the distribution of human disease is characteristic of environmental pathogens. These findings imply that focal demography, along with patterns of human water contact, may play a major role in transmission of Buruli ulcer

Mass Calibration of Optically Selected des Clusters Using a Measurement of CMB-cluster Lensing with SPTpol Data

We use cosmic microwave background (CMB) temperature maps from the 500 deg 2 SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel'dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz data sets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7σ(6.7σ) with the flux (volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be M 200m = (1.62 -0.25+0.32 [stat] ± 0.04 [sys.]) and (1.28 -0.18+0.14 [stat] ± 0.03[sys.])× 10 14 M ⊙ for the volume- and flux-limited samples, respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES

Ecology and Transmission of Buruli Ulcer Disease: A Systematic Review

Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis. Cases have been reported from at least 32 countries in Africa (mainly west), Australia, Southeast Asia, China, Central and South America, and the Western Pacific. Large lesions often result in scarring, contractual deformities, amputations, and disabilities, and in Africa, most cases of the disease occur in children between the ages of 4–15 years. This environmental mycobacterium, Mycobacterium ulcerans, is found in communities associated with rivers, swamps, wetlands, and human-linked changes in the aquatic environment, particularly those created as a result of environmental disturbance such as deforestation, dam construction, and agriculture. Buruli ulcer disease is often referred to as the “mysterious disease” because the mode of transmission remains unclear, although several hypotheses have been proposed. The above review reveals that various routes of transmission may occur, varying amongst epidemiological setting and geographic region, and that there may be some role for living agents as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult mosquitoes or other biting arthropods. We discuss traditional and non-traditional methods for indicting the roles of living agents as biologically significant reservoirs and/or vectors of pathogens, and suggest an intellectual framework for establishing criteria for transmission. The application of these criteria to the transmission of M. ulcerans presents a significant challenge

Consensus recommendation for mouse models of ocular hypertension to study aqueous humor outflow and its mechanisms

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

The evolving role of the IS planning executive: An empirical investigation

Recent and rapid developments in IS technology, greater competitiveness of business, and related factors have brought about major shifts in the orientation of organizational Information Systems (IS). Necessary adaptations in IS management techniques have to be made to cope effectively with these changes. One area which has been the focus of much attention in the context of the growing complexity of IS environments is IS planning. This study explores the nature of the changes in emphasis in the IS planning executive's role in the context of the changes in the orientation of the organizational IS. The data for the study consist of responses of IS executives to a survey questionnaire. Descriptions of the executive's role as it existed five years earlier are compared to descriptions at the time of responding to the survey instrument. Results suggest that there have been significant changes in the IS planning executive's role over this period, adding support to current thinking that IS management techniques should be suitably adapted to cope with the emergence of changing IS environments.IS planning IS management IS executive role strategic grid