Effectiveness of purified methylene blue in an experimental model of Mycobacterium ulcerans infection.

PubMed

Tian, Roger B D; Asmar, Shady; Napez, Claude; Lépidi, Hubert; Drancourt, Michel

2017-03-01

Mycobacterium ulcerans is responsible for Buruli ulcer, characterised by extensive, disabling ulcers. Standard treatment combining rifampicin and streptomycin exposes patients to toxicity and daily painful injections. In this study, the in vitro susceptibilities of 3 M. ulcerans strains, 1 Mycobacterium marinum strain and 18 strains representative of eleven other Mycobacterium species and subspecies to methylene blue were determined. Whilst growth of M. ulcerans was inhibited by 0.0125 g/L methylene blue, growth of all other tested strains was not inhibited by 1 g/L methylene blue. The effectiveness of methylene blue in a murine model of M. ulcerans infection was then tested. Topical treatment by brushing a methylene blue solution on the skin lesion, systemic treatment by intraperitoneal injection of methylene blue, and a combined treatment (topical and systemic) were tested. The three treatment groups exhibited a significantly lower clinical score compared with the non-treated control group (P <0.05). Moreover, subcutaneous nodules were significantly smaller in the systemic treatment group (excluding males) (3 ± 0.7 mm) compared with the other groups (P <0.05). The M. ulcerans insertion sequence IS2404 and the KR-B gene were detected in all challenged mice, but not in negative controls. The density of M. ulcerans (mycobacteria/cell) was significantly lower in the combined treatment group compared with the other groups. These data provide evidence for the effectiveness of purified methylene blue against the initial stage of Buruli ulcer. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

PubMed Central

Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

2015-01-01

Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model.

PubMed

Trigo, Gabriela; Martins, Teresa G; Fraga, Alexandra G; Longatto-Filho, Adhemar; Castro, António G; Azeredo, Joana; Pedrosa, Jorge

2013-01-01

Buruli Ulcer (BU) is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates. We used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN). We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ), both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile. Our observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

Multiple Introductions and Recent Spread of the Emerging Human Pathogen Mycobacterium ulcerans across Africa

PubMed Central

Meehan, Conor J.; Eddyani, Miriam; Affolabi, Dissou; Phanzu, Delphin Mavinga; Eyangoh, Sara; Jordaens, Kurt; Portaels, Françoise; Mangas, Kirstie; Seemann, Torsten; Marsollier, Laurent; Marion, Estelle; Chauty, Annick; Landier, Jordi; Fontanet, Arnaud; Leirs, Herwig; Stinear, Timothy P.; de Jong, Bouke C.

2017-01-01

Buruli ulcer (BU) is an insidious neglected tropical disease. Cases are reported around the world but the rural regions of West and Central Africa are most affected. How BU is transmitted and spreads has remained a mystery, even though the causative agent, Mycobacterium ulcerans, has been known for more than 70 years. Here, using the tools of population genomics, we reconstruct the evolutionary history of M. ulcerans by comparing 165 isolates spanning 48 years and representing 11 endemic countries across Africa. The genetic diversity of African M. ulcerans was found to be restricted due to the bacterium’s slow substitution rate coupled with its relatively recent origin. We identified two specific M. ulcerans lineages within the African continent, and inferred that M. ulcerans lineage Mu_A1 existed in Africa for several hundreds of years, unlike lineage Mu_A2, which was introduced much more recently, approximately during the 19th century. Additionally, we observed that specific M. ulcerans epidemic Mu_A1 clones were introduced during the same time period in the three hydrological basins that were well covered in our panel. The estimated time span of the introduction events coincides with the Neo-imperialism period, during which time the European colonial powers divided the African continent among themselves. Using this temporal association, and in the absence of a known BU reservoir or—vector on the continent, we postulate that the so-called "Scramble for Africa" played a significant role in the spread of the disease across the continent. PMID:28137745

The incubation period of Buruli ulcer (Mycobacterium ulcerans infection) in Victoria, Australia - Remains similar despite changing geographic distribution of disease.

PubMed

Loftus, Michael J; Trubiano, Jason A; Tay, Ee Laine; Lavender, Caroline J; Globan, Maria; Fyfe, Janet A M; Johnson, Paul D R

2018-03-01

Buruli ulcer (BU) is a geographically-restricted infection caused by Mycobacterium ulcerans; contact with an endemic region is the primary risk factor for disease acquisition. Globally, efforts to estimate the incubation period of BU are often hindered as most patients reside permanently in endemic areas. However, in the south-eastern Australian state of Victoria, a significant proportion of people who acquire BU are visitors to endemic regions. During a sustained outbreak of BU on the Bellarine peninsula we estimated a mean incubation period of 4.5 months. Since then cases on the Bellarine peninsula have declined but a new endemic area has developed centred on the Mornington peninsula. Retrospective review of 443 cases of BU notified in Victoria between 2013 and 2016. Telephone interviews were performed to identify all cases with a single visit to an endemic region, or multiple visits within a one month period. The incubation period was defined as the time between exposure to an endemic region and symptom onset. Data were subsequently combined with those from our earlier study incorporating cases from 2002 to 2012. Among the 20 new cases identified in short-term visitors, the mean incubation period was 143 days (4.8 months), very similar to the previous estimate of 135 days (4.5 months). This was despite the predominant exposure location shifting from the Bellarine peninsula to the Mornington peninsula. We found no association between incubation period and age, sex, location of exposure, duration of exposure to an endemic region or location of BU lesion. Our study confirms the mean incubation period of BU in Victoria to be between 4 and 5 months. This knowledge can guide clinicians and suggests that the mode of transmission of BU is similar in different geographic regions in Victoria.

Evolution of Mycobacterium ulcerans and Other Mycolactone-Producing Mycobacteria from a Common Mycobacterium marinum Progenitor▿ †

PubMed Central

Yip, Marcus J.; Porter, Jessica L.; Fyfe, Janet A. M.; Lavender, Caroline J.; Portaels, Françoise; Rhodes, Martha; Kator, Howard; Colorni, Angelo; Jenkin, Grant A.; Stinear, Tim

2007-01-01

It had been assumed that production of the cytotoxic polyketide mycolactone was strictly associated with Mycobacterium ulcerans, the causative agent of Buruli ulcer. However, a recent study has uncovered a broader distribution of mycolactone-producing mycobacteria (MPM) that includes mycobacteria cultured from diseased fish and frogs in the United States and from diseased fish in the Red and Mediterranean Seas. All of these mycobacteria contain versions of the M. ulcerans pMUM plasmid, produce mycolactones, and show a high degree of genetic relatedness to both M. ulcerans and Mycobacterium marinum. Here, we show by multiple genetic methods, including multilocus sequence analysis and DNA-DNA hybridization, that all MPM have evolved from a common M. marinum progenitor to form a genetically cohesive group among a more diverse assemblage of M. marinum strains. Like M. ulcerans, the fish and frog MPM show multiple copies of the insertion sequence IS2404. Comparisons of pMUM and chromosomal gene sequences demonstrate that plasmid acquisition and the subsequent ability to produce mycolactone were probably the key drivers of speciation. Ongoing evolution among MPM has since produced at least two genetically distinct ecotypes that can be broadly divided into those typically causing disease in ectotherms (but also having a high zoonotic potential) and those causing disease in endotherms, such as humans. PMID:17172337

Family relationship, water contact and occurrence of Buruli ulcer in Benin.

PubMed

Sopoh, Ghislain Emmanuel; Barogui, Yves Thierry; Johnson, Roch Christian; Dossou, Ange Dodji; Makoutodé, Michel; Anagonou, Sévérin Y; Kestens, Luc; Portaels, Françoise

2010-07-13

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). Case control study. Department of Atlantique, Benin. BU-confirmed cases that were diagnosed and followed up at the BU detection and treatment center (CDTUB) of Allada (Department of the Atlantique, Benin) during the period from January 1st, 2006, to June 30th, 2008, with three matched controls (persons who had no signs or symptoms of active or inactive BU) for age, gender and village of residence per case. Contact with natural water sources, BU history in the family and the practice of consanguineous marriages. A total of 416 participants were included in this study, including 104 cases and 312 controls. BU history in the family (p<0.001), adjusted by daily contact with a natural water source (p = 0.007), was significantly associated with higher odds of having BU (OR; 95% CI = 5.5; 3.0-10.0). The practice of consanguineous marriage was not associated with the occurrence of BU (p = 0.40). Mendelian disorders could explain this finding, which may influence individual susceptibility by impairing immunity. This study suggests that a combination of genetic factors and behavioral risk factors may increase the susceptibility for developing BU.

Multiple Introductions and Recent Spread of the Emerging Human Pathogen Mycobacterium ulcerans across Africa.

PubMed

Vandelannoote, Koen; Meehan, Conor J; Eddyani, Miriam; Affolabi, Dissou; Phanzu, Delphin Mavinga; Eyangoh, Sara; Jordaens, Kurt; Portaels, Françoise; Mangas, Kirstie; Seemann, Torsten; Marsollier, Laurent; Marion, Estelle; Chauty, Annick; Landier, Jordi; Fontanet, Arnaud; Leirs, Herwig; Stinear, Timothy P; de Jong, Bouke C

2017-03-01

Buruli ulcer (BU) is an insidious neglected tropical disease. Cases are reported around the world but the rural regions of West and Central Africa are most affected. How BU is transmitted and spreads has remained a mystery, even though the causative agent, Mycobacterium ulcerans, has been known for more than 70 years. Here, using the tools of population genomics, we reconstruct the evolutionary history of M. ulcerans by comparing 165 isolates spanning 48 years and representing 11 endemic countries across Africa. The genetic diversity of African M. ulcerans was found to be restricted due to the bacterium's slow substitution rate coupled with its relatively recent origin. We identified two specific M. ulcerans lineages within the African continent, and inferred that M. ulcerans lineage Mu_A1 existed in Africa for several hundreds of years, unlike lineage Mu_A2, which was introduced much more recently, approximately during the 19th century. Additionally, we observed that specific M. ulcerans epidemic Mu_A1 clones were introduced during the same time period in the three hydrological basins that were well covered in our panel. The estimated time span of the introduction events coincides with the Neo-imperialism period, during which time the European colonial powers divided the African continent among themselves. Using this temporal association, and in the absence of a known BU reservoir or-vector on the continent, we postulate that the so-called "Scramble for Africa" played a significant role in the spread of the disease across the continent. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas

PubMed Central

Ortiz, R Hurtado; Leon, D Aguilar; Estevez, H Orozco; Martin, A; Herrera, J Luna; Romo, L Flores; Portaels, F; Pando, R Hernandez

2009-01-01

Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppresive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-β. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain. PMID:19604267

Seasonal Pattern of Mycobacterium ulcerans, the Causative Agent of Buruli Ulcer, in the Environment in Ghana.

PubMed

Aboagye, Samuel Yaw; Ampah, Kobina Assan; Ross, Amanda; Asare, Prince; Otchere, Isaac Darko; Fyfe, Janet; Yeboah-Manu, Dorothy

2017-08-01

This study aimed to contribute to the understanding of Mycobacterium ulcerans (MU) ecology by analysing both clinical and environmental samples collected from ten communities along two major river basins (Offin and Densu) associated with Buruli ulcer (BU) at different seasons. We collected clinical samples from presumptive BU cases and environmental samples from ten communities. Following DNA extraction, clinical samples were confirmed by IS2404 PCR and environmental samples were confirmed by targeting MU-specific genes, IS2404, IS2606 and the ketoreductase (KR) using real-time PCR. Environmental samples were first analysed for IS2404; after which, IS2404-positive samples were multiplexed for the IS2606 and KR gene. Our findings indicate an overall decline in BU incidence along both river basins, although incidence at Densu outweighs that of Offin. Overall, 1600 environmental samples were screened along Densu (434, 27 %) and Offin (1166, 73 %) and MU was detected in 139 (9 %) of the combined samples. The positivity of MU along the Densu River basin was 89/434 (20.5 %), whilst that of the Offin River basin was 50/1166 (4.3 %). The DNA was detected mainly in snails (5/6, 83 %), moss (8/40, 20 %), soil (55/586, 9 %) and vegetation (55/675, 8 %). The proportion of MU positive samples recorded was higher during the months with higher rainfall levels (126/1175, 11 %) than during the dry season months (13/425, 3 %). This study indicates for the first time that there is a seasonal pattern in the presence of MU in the environment, which may be related to recent rainfall or water in the soil.

Buruli ulcer disease prevalence in Benin, West Africa: associations with land use/cover and the identification of disease clusters

PubMed Central

Wagner, Tyler; Benbow, M Eric; Brenden, Travis O; Qi, Jiaguo; Johnson, R Christian

2008-01-01

Background Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example, urbanization

Buruli ulcer disease prevalence in Benin, West Africa: Associations with land use/cover and the identification of disease clusters

USGS Publications Warehouse

Wagner, T.; Benbow, M.E.; Brenden, T.O.; Qi, J.; Johnson, R.C.

2008-01-01

Background: Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results: Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion: Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example

Global and local environmental changes as drivers of Buruli ulcer emergence.

PubMed

Combe, Marine; Velvin, Camilla Jensen; Morris, Aaron; Garchitorena, Andres; Carolan, Kevin; Sanhueza, Daniel; Roche, Benjamin; Couppié, Pierre; Guégan, Jean-François; Gozlan, Rodolphe Elie

2017-04-26

Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.

The puzzle of Buruli ulcer transmission, ethno-ecological history and the end of "love" in the Akonolinga district, Cameroon.

PubMed

Giles-Vernick, Tamara; Owona-Ntsama, Joseph; Landier, Jordi; Eyangoh, Sara

2015-03-01

The "One World One Health Initiative" has attended little to the priorities, concepts and practices of resource-poor communities confronting disease and the implications of these concerns for its biomedical, ecological and institutional approach to disease surveillance and control. Using the example of Buruli ulcer (BU) and its bacterial etiology, Mycobacterium ulcerans, in south-central Cameroon, we build on debates about the contributions of "local knowledge" and "alternative models" to biomedical knowledge of disease transmission. BU's mode of transmission remains poorly understood. Our approach employs ethno-ecological histories - local understandings of the putative emergence and expansion of a locally important, neglected disease. We develop these histories from 52 individual and small group interviews, group discussions, and participant-observation of daily and seasonal activities, conducted in 2013-2013. These histories offer important clues about past environmental and social change that should guide further ecological, epidemiological research. They highlight a key historical moment (the late 1980s and 1990s); specific ecological transformations; new cultivation practices in unexploited zones that potentially increased exposure to M. ulcerans; and ecological degradation that may have lowered nutritional standards and heightened susceptibility to BU. They also recast transmission, broadening insight into BU and its local analog, atom, by emphasizing the role of social change and economic crisis in its emergence and expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Update on Medicinal Plants with Potency on Mycobacterium ulcerans

PubMed Central

Tsouh Fokou, Patrick Valere; Nyarko, Alexander Kwadwo; Appiah-Opong, Regina; Tchokouaha Yamthe, Lauve Rachel; Ofosuhene, Mark; Boyom, Fabrice Fekam

2015-01-01

Mycobacterium ulcerans disease has been a serious threat for people living in rural remote areas. Due to poverty or availability of traditional medicine these populations rely on herbal remedies. Currently, data on the anti-Mycobacterium ulcerans activity of plants, so far considered community-based knowledge, have been scientifically confirmed, concomitantly with some medicinal plants used to treat infectious diseases in general. Products derived from plants usually responsible for the biological properties may potentially control Mycobacterium ulcerans disease; numerous studies have aimed to describe the chemical composition of these plant antimicrobials. Thus, the present work provides the first compilation of medicinal plants that demonstrated inhibitory potential on Mycobacterium ulcerans. This work shows that the natural products represent potential alternatives to standard therapies for use as curative medicine for Mycobacterium ulcerans disease. PMID:26779539

Exploring the Buruli Ulcer Incidence across a socio-ecological landscape in Ghana

NASA Astrophysics Data System (ADS)

Naithani, K. J.; Konzelman, C.; Tschakert, P.; Smithwick, E. A. H.

2016-12-01

The Buruli Ulcer (BU) disease is one of the most prevalent, but poorly understood mycobacterial infections in the world. Fundamental ecological aspects of the disease causing bacteria (Mycobacterium ulcerans) are not understood completely, but its emergence is attributed to unidentified thresholds in human and natural systems. We explored the network of these interactions across socio-ecological landscapes of Ghana to understand the movement of bacteria and the emergence of BU in response to climate, disturbance, social and economic factors. We chose five communities, three endemic and two control, and explored the correlations of disease incidence with climate, landscape disturbance, water quality and social factors using path analysis. Our results show that water quality is strongly linked to disease emergence with high alkalinity, PO43-, NH4+, F, Mn, S, Cd, Fe, Pb, and Se were associated with higher disease incidents and high Cu concentration was associated with low or healthy communities. Contrary to previous studies, arsenic concentration in water was not linked to higher disease incidence. Water quality was linked to climate, type of mining, and agricultural practices. Higher annual precipitation and lower air temperature were found linked to higher disease incidence across communities. Our exploratory work provides insight into how human land use, social practices, demographics, and climatic factors influence the BU disease spread.

Associations of aquatic invertebrates and water quality in the ecology of an emerging tropical disease

NASA Astrophysics Data System (ADS)

Benbow, M.; Merritt, R. W.; Kimbirauskas, R.; Kolar, R.

2005-05-01

Mycobacterium ulcerans Infection is commonly called Buruli ulcer, a rapidly emerging skin disease that is often disfiguring and causes severe and lasting morbidity in developing nations of the tropics and sub-tropics. Outbreaks of BU are nearly always associated with slow-flowing aquatic habitats affected by human-mediated landscape changes, and biting aquatic insects are thought to play a role in transmission. As a part of a World Health Organization initiative, we are determining landscape factors that determine water quality conditions conducive for enhanced M. ulcerans growth and abundance in the aquatic environment. In June 2004 we collected water quality and invertebrate data from 12 water bodies near Accra, Ghana, Africa. Preliminary analyses found predator-dominated communities (from 47% - 64%) with Hemiptera (e.g., Belostomatidae and Naucoridae) most often collected. Using exploratory canonical correspondence analysis, sites separated out by functional feeding groups and water quality variables. Higher water hardness and total suspended solids was most associated with scrapers (i.e., snails) and shrimp, respectively. PCR evidence suggests that M. ulcerans is found among snails, fish and invertebrates. Future studies are proposed that take a multi-scale, multidisciplinary approach for identifying disturbance metrics that can be used to predict human Buruli ulcer incidence near monitored water bodies.

Genetic diversity of Staphylococcus aureus in Buruli ulcer.

PubMed

Amissah, Nana Ama; Glasner, Corinna; Ablordey, Anthony; Tetteh, Caitlin S; Kotey, Nana Konama; Prah, Isaac; van der Werf, Tjip S; Rossen, John W; van Dijl, Jan Maarten; Stienstra, Ymkje

2015-02-01

Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene.

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

PubMed

Maman, Issaka; Tchacondo, Tchadjobo; Kere, Abiba Banla; Piten, Ebekalisai; Beissner, Marcus; Kobara, Yiragnima; Kossi, Komlan; Badziklou, Kossi; Wiedemann, Franz Xaver; Amekuse, Komi; Bretzel, Gisela; Karou, Damintoti Simplice

2018-01-19

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. 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. 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. 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.

Contribution of the community health volunteers in the control of Buruli ulcer in Bénin.

PubMed

Barogui, Yves Thierry; Sopoh, Ghislain Emmanuel; Johnson, Roch Christian; de Zeeuw, Janine; Dossou, Ange Dodji; Houezo, Jean Gabin; Chauty, Annick; Aguiar, Julia; Agossadou, Didier; Edorh, Patrick A; Asiedu, Kingsley; van der Werf, Tjip S; Stienstra, Ymkje

2014-10-01

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.

Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease.

PubMed

Van Leuvenhaege, Chloé; Vandelannoote, Koen; Affolabi, Dissou; Portaels, Françoise; Sopoh, Ghislain; de Jong, Bouke C; Eddyani, Miriam; Meehan, Conor J

2017-01-01

Buruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting. Using 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies. Our study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.

[Corynebacterium ulcerans pulmonary infection].

PubMed

Thouvenin, Maxime; Beilouny, Bassam; Badell, Edgar; Guiso, Nicole

2016-01-01

Corynebacterium ulcerans is a bacterium able to infect humans by inducing a disease close to diphtheria. We describe the case of a 83-year-old patient hospitalized as a matter of urgency in intensive care for which C. ulcerans was isolated in pure culture in its bronchial samples. Even if the isolate was not secreting toxin in vitro, it possesses the tox gene which motivated the use of specific antitoxin serum. After two months of intensive care the patient went out of the service. It is about a remarkable case of clinicobiologic collaboration.

Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

PubMed

Hart, Bryan E; Lee, Sunhee

2016-12-01

Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

Aquatic macroinvertebrate assemblages of Ghana, West Africa: understanding the ecology of a neglected tropical disease.

PubMed

Eric Benbow, M; Kimbirauskas, Ryan; McIntosh, Mollie D; Williamson, Heather; Quaye, Charles; Boakye, Daniel; Small, Pamela L C; Merritt, Richard W

2014-06-01

Buruli ulcer (BU) is an emerging, but neglected tropical disease, where there has been a reported association with disturbed aquatic habitats and proposed aquatic macroinvertebrate vectors such as biting Hemiptera. An initial step in understanding the potential role of macroinvertebrates in the ecology of BU is to better understand the entire community, not just one or two taxa, in relation to the pathogen, Mycobacterium ulcerans, at a large spatial scale. For the first time at a country-wide scale this research documents that M. ulcerans was frequently detected from environmental samples taken from BU endemic regions, but was not present in 30 waterbodies of a non-endemic region. There were significant differences in macroinvertebrate community structure and identified potential indicator taxa in relation to pathogen presence. These results suggest that specific macroinvertebrate taxa or functional metrics may potentially be used as aquatic biological indicators of M. ulcerans. Developing ecological indicators of this pathogen is a first step for understanding the disease ecology of BU and should assist future studies of transmission.

Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen.

PubMed

Gama, José B; Ohlmeier, Steffen; Martins, Teresa G; Fraga, Alexandra G; Sampaio-Marques, Belém; Carvalho, Maria A; Proença, Fernanda; Silva, Manuel T; Pedrosa, Jorge; Ludovico, Paula

2014-08-01

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1) and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1). In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.

Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer.

PubMed

Amissah, Nana Ama; Chlebowicz, Monika A; Ablordey, Anthony; Sabat, Artur J; Tetteh, Caitlin S; Prah, Isaac; van der Werf, Tjip S; Friedrich, Alex W; van Dijl, Jan Maarten; Rossen, John W; Stienstra, Ymkje

2015-01-01

Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere(+) software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. SeqSphere(+) analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus.

Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients.

PubMed

O'Brien, Daniel P; Friedman, Deborah; Hughes, Andrew; Walton, Aaron; Athan, Eugene

2017-09-01

Antibiotics are the recommended first-line treatment for Mycobacterium ulcerans disease. Antibiotic toxicity is common in Australian patients, yet antibiotic complication rates and their risk factors have not been determined. To determine the incidence rate and risk factors for antibiotic toxicity in Australian patients treated for M. ulcerans disease. An analysis of severe antibiotic complications was performed using data from a prospective cohort of M. ulcerans cases managed at Barwon Health from 1 January 1998 to 30 June 2016. A severe antibiotic complication was defined as an antibiotic adverse event that required its cessation. Antibiotic complication rates and their associations were assessed using a Poisson regression model. A total of 337 patients was included; 184 (54.6%) males and median age 57 years (interquartile range (IQR) 36-73 years). Median antibiotic treatment duration was 56 days (IQR 49-76 days). Seventy-five (22.2%) patients experienced severe antibiotic complications after a median 28 days (IQR 17-45 days) at a rate of 141.53 per 100 person-years (95% confidence interval (CI) 112.86-177.47). Eleven (14.7%) patients required hospitalisation. Compared with rifampicin/clarithromycin combinations, severe complication rates were not increased for rifampicin/ciprofloxacin (rate ratio (RR) 1.49, 95% CI 0.89-2.50, P = 0.13) or rifampicin/moxifloxacin (RR 2.54, 95% CI 0.76-8.50, P = 0.13) combinations, but were significantly increased for 'other' combinations (RR 2.53, 95% CI 1.13-5.68, P = 0.03). In a multivariable analysis, severe complication rates were significantly increased with reduced estimated glomerular filtration rates (EGFR) (adjusted rate ratio (aRR) 2.65, 95% CI 1.24-5.65 for EGFR 60-89 mL/min and aRR 1.31, 95% CI 0.49-3.53 for EGFR 0-59 mL/min compared with EGFR ≥90 mL/min, P < 0.01) and female gender (aRR 2.15, 95% CI 1.38-3.30, P < 0.01). Severe antibiotic complications during M. ulcerans treatment are high with

Environmental Distribution and Seasonal Prevalence of Mycobacterium ulcerans in Southern Louisiana

PubMed Central

Hennigan, Caroline E.; Myers, Leann

2013-01-01

Mycobacterium ulcerans is an emerging environmental pathogen that causes debilitating, ulcerative disease in humans and other vertebrates. The majority of human cases occur in tropical and temperate regions of Africa and Australia, and outbreaks of piscine mycobacteriosis caused by M. ulcerans have been reported in disparate geographic locations spanning the globe. While exposure to a natural body of water is the most common risk factor for human infection, the environmental distribution of M. ulcerans in aquatic habitats has not been extensively studied. Although no human cases have been reported in the United States, a strain of M. ulcerans has been identified as the cause of a piscine mycobacteriosis in Striped bass (Morone saxatilis) within the Chesapeake Bay. Infected fish exhibit bright red ventral and lateral dermal lesions. We observed a possible outbreak causing similar lesions on red drum (Sciaenops ocellatus) in wetlands of southern Louisiana and detected M. ulcerans-specific genetic markers in lesion samples from these fish. Based on these findings, we studied the geographic and seasonal prevalence of these markers across southern Louisiana. M. ulcerans was detected in each of the nine areas sampled across the state. M. ulcerans prevalence was significantly lower in the fall samples, and the low prevalence coincided with decreased nutrient levels and an increase in water temperature. To our knowledge, this is the first study of M. ulcerans biomarkers in the southern United States. PMID:23396345

Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer

PubMed Central

Amissah, Nana Ama; Chlebowicz, Monika A.; Ablordey, Anthony; Sabat, Artur J.; Tetteh, Caitlin S.; Prah, Isaac; van der Werf, Tjip S.; Friedrich, Alex W.; van Dijl, Jan Maarten

2015-01-01

Background Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. Methodology This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere+ software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. Principal Findings SeqSphere+ analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus. PMID:26360794

A Community Based Study on the Mode of Transmission, Prevention and Treatment of Buruli Ulcers in Southwest Cameroon: Knowledge, Attitude and Practices.

PubMed

Akoachere, Jane-Francis K T; Nsai, Frankline S; Ndip, Roland N

2016-01-01

Buruli ulcer (BU) is a neglected tropical disease affecting the skin, tissues and in some cases the bones, caused by the environmental pathogen Mycobacterium ulcerans (M. ulcerans). Its mode of transmission is still elusive. Delayed treatment may cause irreversible disabilities with consequent social and economic impacts on the victim. Socio-cultural beliefs, practices and attitudes in endemic communities have been shown to influence timely treatment causing disease management, prevention and control a great challenge. An assessment of these factors in endemic localities is important in designing successful intervention strategies. Considering this, we assessed the knowledge, attitude and practices regarding BU in three endemic localities in the South West region, Cameroon to highlight existing misconceptions that need to be addressed to enhance prompt treatment and facilitate effective prevention and control. A cross-sectional study was executed in three BU endemic health districts. Using qualitative and quantitative approaches we surveyed 320 randomly selected household heads, interviewed BU patients and conducted three focus group discussions (FGDs) to obtain information on awareness, beliefs, treatment, and attitudes towards victims. The influence of socio-demographic factors on these variables was investigated. Respondents (84.4%) had a good knowledge of BU though only 65% considered it a health problem while 49.4% believed it is contagious. Socio-demographic factors significantly (P<0.05) influenced awareness of BU, knowledge and practice on treatment and attitudes towards victims. Although the majority of respondents stated the hospital as the place for appropriate treatment, FGDs and some BU victims preferred witchdoctors/herbalists and prayers, and considered the hospital as the last option. We documented beliefs about the disease which could delay treatment. Though we are reporting a high level of knowledge of BU, there exist fallacies about BU and

[Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports].

PubMed

Jenssen, Christian; Schwede, Ilona; Neumann, Volker; Pietsch, Cristine; Handrick, Werner

2017-10-01

History and clinical findings  We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis  A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases. Treatment and course  In all three patients, successful handling of the skin and soft tissue infections was possible by combining local treatment with antibiotics. Diphtheria antitoxin was not administered in any case. Conclusion  Based on a review of the recent literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of skin and soft tissue infections due to Corynebacterium ulcerans are discussed. Corynebacterium ulcerans should be considered as a potential cause of severe skin and soft tissue infections. Occupational or domestic animal contacts should be evaluated. © Georg Thieme Verlag KG Stuttgart · New York.

Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients.

PubMed

Amissah, Nana Ama; Chlebowicz, Monika A; Ablordey, Anthony; Tetteh, Caitlin S; Prah, Isaac; van der Werf, Tjip S; Friedrich, Alex W; van Dijl, Jan Maarten; Stienstra, Ymkje; Rossen, John W

2017-06-01

Buruli ulcer (BU) is a necrotizing infection of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU wounds may also be colonized with other microorganisms including Staphylococcus aureus. This study aimed to characterize the virulence factors of S. aureus isolated from BU patients. Previously sequenced genomes of 21 S. aureus isolates from BU patients were screened for the presence of virulence genes. The results show that all S. aureus isolates harbored on their core genomes genes for known virulence factors like α-hemolysin, and the α- and β-phenol soluble modulins. Besides the core genome virulence genes, mobile genetic elements (MGEs), i.e. prophages, genomic islands, pathogenicity islands and a Staphylococcal cassette chromosome (SCC) were found to carry different combinations of virulence factors, among them genes that are known to encode factors that promote immune evasion, superantigens and Panton-Valentine Leucocidin. The present observations imply that the S. aureus isolates from BU patients harbor a diverse repertoire of virulence genes that may enhance bacterial survival and persistence in the wound environment and potentially contribute to delayed wound healing. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa.

PubMed

O'Brien, Daniel P; Comte, Eric; Serafini, Micaela; Ehounou, Geneviève; Antierens, Annick; Vuagnat, Hubert; Christinet, Vanessa; Hamani, Mitima D; du Cros, Philipp

2014-05-01

Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Community Based Study on the Mode of Transmission, Prevention and Treatment of Buruli Ulcers in Southwest Cameroon: Knowledge, Attitude and Practices

PubMed Central

Akoachere, Jane-Francis K. T.; Nsai, Frankline S.; Ndip, Roland N.

2016-01-01

Background Buruli ulcer (BU) is a neglected tropical disease affecting the skin, tissues and in some cases the bones, caused by the environmental pathogen Mycobacterium ulcerans (M. ulcerans). Its mode of transmission is still elusive. Delayed treatment may cause irreversible disabilities with consequent social and economic impacts on the victim. Socio-cultural beliefs, practices and attitudes in endemic communities have been shown to influence timely treatment causing disease management, prevention and control a great challenge. An assessment of these factors in endemic localities is important in designing successful intervention strategies. Considering this, we assessed the knowledge, attitude and practices regarding BU in three endemic localities in the South West region, Cameroon to highlight existing misconceptions that need to be addressed to enhance prompt treatment and facilitate effective prevention and control. Methods and Findings A cross-sectional study was executed in three BU endemic health districts. Using qualitative and quantitative approaches we surveyed 320 randomly selected household heads, interviewed BU patients and conducted three focus group discussions (FGDs) to obtain information on awareness, beliefs, treatment, and attitudes towards victims. The influence of socio-demographic factors on these variables was investigated. Results Respondents (84.4%) had a good knowledge of BU though only 65% considered it a health problem while 49.4% believed it is contagious. Socio-demographic factors significantly (P<0.05) influenced awareness of BU, knowledge and practice on treatment and attitudes towards victims. Although the majority of respondents stated the hospital as the place for appropriate treatment, FGDs and some BU victims preferred witchdoctors/herbalists and prayers, and considered the hospital as the last option. We documented beliefs about the disease which could delay treatment. Conclusion Though we are reporting a high level of

The contribution of community health workers to the control of Buruli ulcer in the Ngoantet area, Cameroon.

PubMed

Vouking, Marius Zambou; Takougang, Innocent; Mbam, Léonard Mbam; Mbuagbaw, Lawrence; Tadenfok, Carine Nouboudem; Tamo, Claire Violette

2013-01-01

Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. It is the third most common mycobacterial infection after tuberculosis and leprosy. Community Health Workers (CHWs) hold the potential to support patients and their families at the community level. We conducted a cross-sectional descriptive study to assess the participation of CHWs in the early diagnosis and treatment of BU in Ngoantet, Cameroon. The CHWs performance was measured using: the number of cases referred to the Ngoantet Health Centre, the percentage of accomplished referrals, the percentage of cases referred by CHWs confirmed by the staff of Ngoantet Health Centre. Data was analyzed using Epi-info version 3.4.1. and Microsoft Office Excel 2003. The study focused on 51 CHWs in the Ngoantet health area. The referral rate was 95.0%. Most of the suspicious cases (91.5%) referred were confirmed by health workers. Most CHWs (78.4%) declared that they had identified at least one presumptive case of BU infection. We conclude that the CHWs can play a key role in scaling up BU control activities using a referral system. This study confirms the role of home visits and inspections in the early detection and treatment of BU.

Diagnosis delay and duration of hospitalisation of patients with Buruli ulcer in Nigeria.

PubMed

Meka, Anthony O; Chukwu, Joseph N; Nwafor, Charles C; Oshi, Daniel C; Madichie, Nelson O; Ekeke, Ngozi; Anyim, Moses C; Alphonsus, Chukwuka; Mbah, Obinna; Uzoukwa, Glory C; Njoku, Martin; Ntana, Kentigern; Ukwaja, Kingsley N

2016-09-01

Delayed diagnosis of Buruli ulcer can worsen clinical presentation of the disease, prolong duration of management, and impose avoidable additional costs on patients and health providers. We investigated the profile, delays in diagnosis, duration of hospitalisation, and associated factors among patients with Buruli ulcer in Nigeria. This was a prospective cohort study of patients with Buruli ulcer who were identified from a community-based survey. Data on the patients' clinical profile, delays in diagnosis and duration of hospitalisation were prospectively collected. Of 145 patients notified, 125 (86.2%) were confirmed by one or more laboratory tests (81.4% by PCR). The median age of the patients was 20 years, 88 (60.7%) were >15years old and 85 (58.6%) were females. In addition, 137 (94.5%) were new cases, 119 (82.1%) presented with ulcers and 110 (75.9%) had lower limb lesions. The mean time delay to diagnosis was 50.6 (±101.9) weeks. The mean duration of hospitalisation was 108 (±60) days. Determinants of time delay to diagnosis were higher disease category (p=0.001) and laboratory confirmation of disease (p=0.02). Determinants of longer hospitalisation were; multiple lesions (p=0.035), and having functional limitation at diagnosis and undertaking surgery (p=0.003). Patients with Buruli ulcer have very long time delays to diagnosis and long hospitalisation during treatment. This calls for early case-finding and improved access to Buruli ulcer services in Nigeria. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ulcerative cutaneous mycobacteriosis due to Mycobacterium ulcerans: report of two Mexican cases.

PubMed

Coloma, Josefa Novales-Santa; Navarrete-Franco, Gisela; Iribe, Pedro; López-Cepeda, Larissa Dorina

2005-03-01

We report two patients from Central Mexico, with ulcerated cutaneous lesions containing acid-fast bacilli (AFB) and ultimately diagnosed as Mycobacterium ulcerans disease. The first patient had a long history (11 years) of disease involving multiple lesions of both upper and lower extremities. Histopathological changes included necrosis of the subcutaneous tissue with large numbers of extracellular AFB. Cultures at 32 degrees C were "positive for mycobacteria," but were not further identified. The polymerase chain reaction for M. ulcerans performed on skin bopsies was positive. The lesions improved after treatment with rifampin and isoniazid (INH) for one month, followed by ethambutol and streptomycin. The second case followed trauma to the right hand, which spread over 2 years to the right upper extremity, the back, and both legs, with a loss of digits and metacarpal bones of the right hand. The histopathological findings were similar to the first case, including presence of AFB. PCR for M. ulcerans on extracts of skin biopsies was positive. Rifampin, INH, pyrazinamide, and levofloxacin resulted in marked improvement of the ulcer; ethambutol and streptomycin were later used, also. We report these cases because they are rare (approximately 6 previous cases were reported from Mexico), and both are unusually disseminated. They are significant in alerting the medical community to M. ulcerans infection, which is still active in Mexico, and the treatment used has not been reported previously.

Multilocus Variable-Number Tandem Repeat Typing of Mycobacterium ulcerans

PubMed Central

Ablordey, Anthony; Swings, Jean; Hubans, Christine; Chemlal, Karim; Locht, Camille; Portaels, Françoise; Supply, Philip

2005-01-01

The apparent genetic homogeneity of Mycobacterium ulcerans contributes to the poorly understood epidemiology of M. ulcerans infection. Here, we report the identification of variable number tandem repeat (VNTR) sequences as novel polymorphic elements in the genome of this species. A total of 19 potential VNTR loci identified in the closely related M. marinum genome sequence were screened in a collection of 23 M. ulcerans isolates, one Mycobacterium species referred to here as an intermediate species, and five M. marinum strains. Nine of the 19 loci were polymorphic in the three species (including the intermediate species) and revealed eight M. ulcerans and five M. marinum genotypes. The results from the VNTR analysis corroborated the genetic relationships of M. ulcerans isolates from various geographical origins, as defined by independent molecular markers. Although these results further highlight the extremely high clonal homogeneity within certain geographic regions, we report for the first time the discrimination of the two South American strains from Surinam and French Guyana. These findings support the potential of a VNTR-based genotyping method for strain discrimination within M. ulcerans and M. marinum. PMID:15814964

Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

PubMed Central

Bratschi, Martin W.; Bolz, Miriam; Minyem, Jacques C.; Grize, Leticia; Wantong, Fidèle G.; Kerber, Sarah; Njih Tabah, Earnest; Ruf, Marie-Thérèse; Mou, Ferdinand; Noumen, Djeunga; Um Boock, Alphonse; Pluschke, Gerd

2013-01-01

Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake. PMID:23785529

[Emerging infectious diseases: complex, unpredictable processes].

PubMed

Guégan, Jean-François

2016-01-01

In the light of a double approach, at first empirical, later theoretical and comparative, illustrated by the example of the Buruli ulcer and its mycobacterial agent Mycobacterium ulcerans on which I focused my research activity these last ten years by studying determinants and factors of emerging infectious or parasitic diseases, the complexity of events explaining emerging diseases will be presented. The cascade of events occurring at various levels of spatiotemporal scales and organization of life, which lead to the numerous observed emergences, nowadays requires better taking into account the interactions between host(s), pathogen(s) and the environment by including the behavior of both individuals and the population. In numerous research studies on emerging infectious diseases, microbial hazard is described rather than infectious disease risk, the latter resulting from the confrontation between an association of threatening phenomena, or hazards, and a susceptible population. Beyond, the theme of emerging infectious diseases and its links with global environmental and societal changes leads to reconsider some well-established knowledge in infectiology and parasitology. © Société de Biologie, 2017.

Burden and Historical Trend of Buruli Ulcer Prevalence in Selected Communities along the Offin River of Ghana.

PubMed

Ampah, Kobina Assan; Asare, Prince; Binnah, Daniel De-Graft; Maccaulley, Samuel; Opare, William; Röltgen, Katharina; Pluschke, Gerd; Yeboah-Manu, Dorothy

2016-04-01

Buruli ulcer (BU) is a neglected tropical skin disease caused by Mycobacterium ulcerans with more than two thirds of the global cases reported in West Africa. A nationwide active BU case search conducted in 1999 identified two health districts along the Offin River as two of the three most endemic districts in Ghana. Based on recent anecdotal accounts that transmission is unstable along the Offin River, we conducted from March to June 2013 an exhaustive household survey and active case search in 13 selected communities within a five-kilometer radius along the Offin River. The overall prevalence of BU was 2.3% among the surveyed population of 20,390 inhabitants and 477 of the total 480 cases detected (99.4%) were historical (healed) cases. By estimating the year of occurrence for each case per community and taking into account available passive surveillance records of health facilities and the District Health Directorate, we observed a general trend of continuous emergence of cases in communities located midstream the Offin River whereas downstream communities showed more sporadic patterns. We monitored the incidence of cases after the survey and recorded a cumulative incidence rate of 0.04% for the 13 communities over a 17-month active surveillance period from August 2013 to December 2014. Our data reveal an overall decline in BU incidence along the Offin River similar to the general decline in BU incidence in recent years reported by the World Health Organization for West Africa.

Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, Cesar A.; Unkefer, Clifford J.; Swanson, Basil I.

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Association with lipid carriers would have substantial implications for the toxin’s distribution within a host organism, delivery to cellular targets, diagnostic susceptibility, and mechanisms of pathogenicity. Yet the toxin’smore » interactions with, and distribution in, lipids are unknown. Herein we have used coarse-grained molecular dynamics simulations, guided by all-atom simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties. The computed water-octanol partition coefficient indicates that mycolactone prefers to be in an organic phase rather than in an aqueous environment. Our results show that in a solvated membrane environment the exotoxin mainly localizes in the water-membrane interface, with a preference for the glycerol moiety of lipids, consistent with the reported studies that found it in lipid extracts of the cell. The calculated association constant to the model membrane is similar to the reported association constant for Wiskott-Aldrich syndrome protein. Mycolactone is shown to modify the physical properties of membranes, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and

Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans

DOE PAGES

Lopez, Cesar A.; Unkefer, Clifford J.; Swanson, Basil I.; ...

2018-02-05

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Association with lipid carriers would have substantial implications for the toxin’s distribution within a host organism, delivery to cellular targets, diagnostic susceptibility, and mechanisms of pathogenicity. Yet the toxin’smore » interactions with, and distribution in, lipids are unknown. Herein we have used coarse-grained molecular dynamics simulations, guided by all-atom simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties. The computed water-octanol partition coefficient indicates that mycolactone prefers to be in an organic phase rather than in an aqueous environment. Our results show that in a solvated membrane environment the exotoxin mainly localizes in the water-membrane interface, with a preference for the glycerol moiety of lipids, consistent with the reported studies that found it in lipid extracts of the cell. The calculated association constant to the model membrane is similar to the reported association constant for Wiskott-Aldrich syndrome protein. Mycolactone is shown to modify the physical properties of membranes, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and

A Simple PCR Method for Rapid Genotype Analysis of Mycobacterium ulcerans

PubMed Central

Stinear, Timothy; Davies, John K.; Jenkin, Grant A.; Portaels, Françoise; Ross, Bruce C.; OppEdIsano, Frances; Purcell, Maria; Hayman, John A.; Johnson, Paul D. R.

2000-01-01

Two high-copy-number insertion sequences, IS2404 and IS2606, were recently identified in Mycobacterium ulcerans and were shown by Southern hybridization to possess restriction fragment length polymorphism between strains from different geographic origins. We have designed a simple genotyping method that captures these differences by PCR amplification of the region between adjacent copies of IS2404 and IS2606. We have called this system 2426 PCR. The method is rapid, reproducible, sensitive, and specific for M. ulcerans, and it has confirmed previous studies suggesting a clonal population structure of M. ulcerans within a geographic region. M. ulcerans isolates from Australia, Papua New Guinea, Malaysia, Surinam, Mexico, Japan, China, and several countries in Africa were easily differentiated based on an array of 4 to 14 PCR products ranging in size from 200 to 900 bp. Numerical analysis of the banding patterns suggested a close evolutionary link between M. ulcerans isolates from Africa and southeast Asia. The application of 2426 PCR to total DNA, extracted directly from M. ulcerans-infected tissue specimens without culture, demonstrated the sensitivity and specificity of this method and confirmed for the first time that both animal and human isolates from areas of endemicity in southeast Australia have the same genotype. PMID:10747130

Comparison of Two Assays for Molecular Determination of Rifampin Resistance in Clinical Samples from Patients with Buruli Ulcer Disease

PubMed Central

Phillips, Richard Odame; Badziklou, Kossi; Piten, Ebekalisai; Maman, Issaka; Sarfo, Fred Stephen; Huber, Kristina Lydia; Rhomberg, Agata; Symank, Dominik; Wagner, Magdalena; Wiedemann, Franz; Nitschke, Jörg; Banla Kere, Abiba; Herbinger, Karl-Heinz; Adjei, Ohene; Löscher, Thomas; Bretzel, Gisela

2014-01-01

This study evaluates a novel assay for detecting rifampin resistance in clinical Mycobacterium ulcerans isolates. Although highly susceptible for PCR inhibitors in 50% of the samples tested, the assay was 100% M. ulcerans specific and yielded >98% analyzable sequences with a lower limit of detection of 100 to 200 copies of the target sequence. PMID:24478404

Landscape Fragmentation as a Risk Factor for Buruli Ulcer Disease in Ghana

PubMed Central

Wu, Jianyong; Smithwick, Erica A. H.

2016-01-01

Land cover and its change have been linked to Buruli ulcer (BU), a rapidly emerging tropical disease. However, it is unknown whether landscape structure affects the disease prevalence. To examine the association between landscape pattern and BU presence, we obtained land cover information for 20 villages in southwestern Ghana from high resolution satellite images, and analyzed the landscape pattern surrounding each village. Eight landscape metrics indicated that landscape patterns between BU case and reference villages were different (P < 0.05) at the broad spatial extent examined (4 km). The logistic regression models showed that landscape fragmentation and diversity indices were positively associated with BU presence in a village. Specifically, for each increase in patch density and edge density by 100 units, the likelihood of BU presence in a village increased 2.51 (95% confidence interval [CI] = 1.36–4.61) and 4.18 (95% CI = 1.63–10.76) times, respectively. The results suggest that increased landscape fragmentation may pose a risk to the emergence of BU. PMID:27185767

Ethnopharmacological reports on anti-Buruli ulcer medicinal plants in three West African countries.

PubMed

Tsouh Fokou, Patrick Valere; Nyarko, Alexander Kwadwo; Appiah-Opong, Regina; Tchokouaha Yamthe, Lauve Rachel; Addo, Phyllis; Asante, Isaac K; Boyom, Fabrice Fekam

2015-08-22

Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014. The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the

Implementation of a decentralized community-based treatment program to improve the management of Buruli ulcer in the Ouinhi district of Benin, West Africa.

PubMed

Amoussouhoui, Arnaud Setondji; Sopoh, Ghislain Emmanuel; Wadagni, Anita Carolle; Johnson, Roch Christian; Aoulou, Paulin; Agbo, Inès Elvire; Houezo, Jean-Gabin; Boyer, Micah; Nichter, Mark

2018-03-01

Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin's most endemic districts previously served by centralized hospital-based care. We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control.

New Foci of Buruli Ulcer, Angola and Democratic Republic of Congo

PubMed Central

Kibadi, Kapay; Panda, Mbutu; Tamfum, Jean-Jacques Muyembe; Fraga, Alexandra G.; Filho, Adhemar Longatto; Anyo, Gladys; Pedrosa, Jorge; Nakazawa, Yoshinori; Suykerbuyk, Patrick; Meyers, Wayne M.

2008-01-01

We report 3 patients with laboratory-confirmed Buruli ulcer in Kafufu/Luremo, Angola, and Kasongo-Lunda, Democratic Republic of Congo. These villages are near the Kwango/Cuango River, which flows through both countries. Further investigation of artisanal alluvial mining as a risk factor for Buruli ulcer is recommended. PMID:18976574

Buruli Ulcer (Mycobacterium ulcerans Infection)

MedlinePlus

... Pacific WHO in countries » Overview Statistics Cooperation strategies Democratic Republic of the Congo » Emergencies Focus on » Bangladesh Rohingya Democratic Republic of the Congo Iraq Nigeria Somalia South ...

Notes from the field: respiratory diphtheria-like illness caused by toxigenic Corynebacterium ulcerans --- Idaho, 2010.

PubMed

2011-01-28

On September 12, 2010, the Idaho Department of Health and Welfare was notified of a case of respiratory diphtheria-like illness in an Idaho man aged 80 years whose pharyngeal specimens yielded Corynebacterium ulcerans. Although C. ulcerans is zoonotic, the patient reported no animal contact or consumption of an unpasteurized dairy product. His vaccination history was unknown. Respiratory diphtheria-like illness from C. ulcerans is uncommon but has been reported in industrialized countries where respiratory diphtheria is rare. The last case of diphtheria-like illness caused by C. ulcerans in the United States was reported in 2005.

Persisting Social Participation Restrictions among Former Buruli Ulcer Patients in Ghana and Benin

PubMed Central

de Zeeuw, Janine; Omansen, Till F.; Douwstra, Marlies; Barogui, Yves T.; Agossadou, Chantal; Sopoh, Ghislain E.; Phillips, Richard O.; Johnson, Christian; Abass, K. Mohammed; Saunderson, Paul; Dijkstra, Pieter U.; van der Werf, Tjip S.; Stientstra, Ymkje

2014-01-01

Background Buruli ulcer may induce severe disabilities impacting on a person's well-being and quality of life. Information about long-term disabilities and participation restrictions is scanty. The objective of this study was to gain insight into participation restrictions among former Buruli ulcer patients in Ghana and Benin. Methods In this cross-sectional study, former Buruli ulcer patients were interviewed using the Participation Scale, the Buruli Ulcer Functional Limitation Score to measure functional limitations, and the Explanatory Model Interview Catalogue to measure perceived stigma. Healthy community controls were also interviewed using the Participation Scale. Trained native interviewers conducted the interviews. Former Buruli ulcer patients were eligible for inclusion if they had been treated between 2005 and 2011, had ended treatment at least 3 months before the interview, and were at least 15 years of age. Results In total, 143 former Buruli ulcer patients and 106 community controls from Ghana and Benin were included in the study. Participation restrictions were experienced by 67 former patients (median score, 30, IQR; 23;43) while 76 participated in social life without problems (median score 5, IQR; 2;9). Most restrictions encountered related to employment. Linear regression showed being female, perceived stigma, functional limitations, and larger lesions (category II) as predictors of more participation restrictions. Conclusion Persisting participation restrictions were experienced by former BU patients in Ghana and Benin. Most important predictors of participation restrictions were being female, perceived stigma, functional limitations and larger lesions. PMID:25392915

Toxigenic Corynebacterium ulcerans in a fatal human case and her feline contacts, France, March 2014.

PubMed

Vandentorren, S; Guiso, N; Badell, E; Boisrenoult, P; Micaelo, M; Troché, G; Lecouls, P; Moquet, M J; Patey, O; Belchior, E

2014-09-25

In March 2014, a person in their eighties who was diagnosed with extensive cellulitis due to toxigenic Corynebacterium ulcerans died from multiple organ failure. Environmental investigation also isolated C. ulcerans in biological samples from two stray cats in contact with the case. This finding provides further evidence that pets can carry toxigenic C. ulcerans and may be a source of the infection in humans.

Toxigenic Corynebacterium ulcerans isolated from a free-roaming red fox (Vulpes vulpes).

PubMed

Sting, Reinhard; Ketterer-Pintur, Sandra; Contzen, Matthias; Mauder, Norman; Süss-Dombrowski, Christine

2015-01-01

Corynebacterium (C.) ulcerans could be isolated from the spleen of a red fox (Vulpes vulpes) that had been found dead in the state of Baden-Württemberg, Germany. Pathohistological examination suggested that the fox had died of distemper, as was confirmed by PCR. The isolate was identified biochemically, by MALDI-TOF MS, FT-IR and by partial 16S rRNA, rpoB and tox gene sequencing. Using the Elek test the C. ulcerans isolate demonstrated diphtheria toxin production. FT-IR and sequencing data obtained from the C. ulcerans isolate from the red fox showed higher similarity to isolates from humans than to those from wild game.

Fighting mycobacterial infections by antibiotics, phytochemicals and vaccines.

PubMed

Bamberger, Denise; Jantzer, Nora; Leidner, Katharina; Arend, Joachim; Efferth, Thomas

2011-07-01

Buruli ulcer is a neglected disease caused by Mycobacterium ulcerans and represents the world's third most common mycobacterial infection. It produces the polyketide toxins, mycolactones A, B, C and D, which induce apoptosis and necrosis. Clinical symptoms are subcutaneous nodules, papules, plaques and ulcerating oedemae, which can enlarge and destroy nerves and blood vessels and even invade bones by lymphatic or haematogenous spread (osteomyelitis). Patients usually do not suffer from pain or systematic inflammation. Surgery is the treatment of choice, although recurrence is common and wide surgical excisions including healthy tissues result in significant morbidity. Antibiotic therapy with rifamycins, aminoglycosides, macrolides and quinolones also improves cure rates. Still less exploited treatment options are phytochemicals from medicinal plants used in affected countries. Vaccination against Buruli ulcer is still in its infancy. Copyright © 2010. Published by Elsevier SAS.

Implementation of a decentralized community-based treatment program to improve the management of Buruli ulcer in the Ouinhi district of Benin, West Africa

PubMed Central

Amoussouhoui, Arnaud Setondji; Wadagni, Anita Carolle; Johnson, Roch Christian; Aoulou, Paulin; Agbo, Inès Elvire; Houezo, Jean-Gabin; Boyer, Micah; Nichter, Mark

2018-01-01

Background Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control. PMID:29529087

Identification of Ser/Thr kinase and Forkhead Associated Domains in Mycobacterium ulcerans: Characterization of Novel Association between Protein Kinase Q and MupFHA

PubMed Central

Singhal, Anshika; Joshi, Jayadev; Virmani, Richa; Gupta, Meetu; Verma, Nupur; Maji, Abhijit; Misra, Richa; Baronian, Grégory; Pandey, Amit K.; Molle, Virginie; Singh, Yogendra

2014-01-01

Background Mycobacterium ulcerans, the causative agent of Buruli ulcer in humans, is unique among the members of Mycobacterium genus due to the presence of the virulence determinant megaplasmid pMUM001. This plasmid encodes multiple virulence-associated genes, including mup011, which is an uncharacterized Ser/Thr protein kinase (STPK) PknQ. Methodology/Principal Findings In this study, we have characterized PknQ and explored its interaction with MupFHA (Mup018c), a FHA domain containing protein also encoded by pMUM001. MupFHA was found to interact with PknQ and suppress its autophosphorylation. Subsequent protein-protein docking and molecular dynamic simulation analyses showed that this interaction involves the FHA domain of MupFHA and PknQ activation loop residues Ser170 and Thr174. FHA domains are known to recognize phosphothreonine residues, and therefore, MupFHA may be acting as one of the few unusual FHA-domain having overlapping specificity. Additionally, we elucidated the PknQ-dependent regulation of MupDivIVA (Mup012c), which is a DivIVA domain containing protein encoded by pMUM001. MupDivIVA interacts with MupFHA and this interaction may also involve phospho-threonine/serine residues of MupDivIVA. Conclusions/Significance Together, these results describe novel signaling mechanisms in M. ulcerans and show a three-way regulation of PknQ, MupFHA, and MupDivIVA. FHA domains have been considered to be only pThr specific and our results indicate a novel mechanism of pSer as well as pThr interaction exhibited by MupFHA. These results signify the need of further re-evaluating the FHA domain –pThr/pSer interaction model. MupFHA may serve as the ideal candidate for structural studies on this unique class of modular enzymes. PMID:25412098

Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer.

PubMed

Katsukawa, Chihiro; Komiya, Takako; Umeda, Kaoru; Goto, Minami; Yanai, Tokuma; Takahashi, Motohide; Yamamoto, Akihiko; Iwaki, Masaaki

2016-03-01

Toxigenic Corynebacterium ulcerans is a zoonotic pathogen that produces diphtheria toxin and causes a diphtheria-like illness in humans. The organism is known to infect and circulate among dogs, which can then transmit it to humans. Furthermore, previous studies have found that C. ulcerans is carried by wild animals, including game animals. In the present study, we tested hunting and companion dogs for the presence of toxigenic C. ulcerans and succeeded in isolating the bacterium from a hunting dog. Moreover, several hunting dogs had serum diphtheria antitoxin titers that were higher than the titers required for protection in humans, suggesting a history of exposure to toxigenic Corynebacterium strains. Notably, ribotyping, pulsed-field gel electrophoresis and tox gene sequencing demonstrated that the isolate from the hunting dog clustered with previously characterized C. ulcerans strains isolated from wild animals, as opposed to groups of isolates from humans and companion dogs. Interestingly, the wild animal cluster also contains an isolate from an outdoor breeding dog, which could have formed a bridge between isolates from wild animals and those from companion dogs. The results presented herein provide insight into the mechanism by which the zoonotic pathogen C. ulcerans circulates among wild animals, hunting and companion dogs, and humans. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

PubMed

Anand, U; Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

2016-01-01

Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Mycolactone induces toxic effects in DRG

Buruli ulcer in Nigeria: results of a pilot case study in three rural districts.

PubMed

Ukwaja, Kingsley N; Meka, Anthony O; Chukwuka, Alphonsus; Asiedu, Kingsley B; Huber, Kristina L; Eddyani, Miriam; Chukwu, Joseph N; Anyim, Moses C; Nwafor, Charles C; Oshi, Daniel C; Madichie, Nelson O; Ekeke, Ngozi; Njoku, Martin; Ntana, Kentigern

2016-04-22

Buruli ulcer (BU), also known as Mycobacterium ulcerans disease, is the third most common mycobacterial disease worldwide. Although BU disease has been diagnosed among Nigerians in neighbouring West African countries, data on the burden of the disease in Nigeria itself are scanty. This study aimed to assess the magnitude and epidemiology of BU in the South South region of Nigeria. We conducted a cross-sectional survey in the Ogoja territory (comprising 31 communities). We undertook sensitisation programmes centred on BU in 10 of the communities. Participants were asked to identify community members with long-standing ulcers, who were then invited for evaluation. We also contacted traditional healers to refer their clients who had non-healing ulcers. All suspected cases had a full clinical evaluation and laboratory testing. Confirmed cases were given treatment in a referral hospital in the territory. We diagnosed 41 clinical BU cases; 36 (87.8 %) of which were confirmed by quantitative polymerase chain reaction (qPCR). These 36 PCR-confirmed cases were diagnosed in a total population of 192,169 inhabitants. Therefore, the estimated crude prevalence of BU was 18.7 per 100,000 population, varying from 6.0 to 41.4 per 100,000 in the districts surveyed. The majority (66.7 %) of the cases were females. About 92 % of the BU lesions were located on the patients' extremities. No differences were observed between the sexes in terms of the location of the lesions. The age of the patients ranged from four to 60 years, with a median age of 17 years. All 35 (100 %) patients who consented to treatment completed chemotherapy as prescribed. Of the treated cases, 29 (82.9 %) needed and received surgery. All cases healed, but 29 (82.9 %) had some limitations in movement. Healing with limitations in movement occurred in 18/19 (94.7 %) and 8/10 (80.0 %) of patients with lesions >15 cm (Category III) and 6-15 cm in diameter (Category II), respectively. The median duration of treatment

Mycobacterium ulcerans Ecological Dynamics and Its Association with Freshwater Ecosystems and Aquatic Communities: Results from a 12-Month Environmental Survey in Cameroon

PubMed Central

Garchitorena, Andrés; Roche, Benjamin; Kamgang, Roger; Ossomba, Joachim; Babonneau, Jérémie; Landier, Jordi; Fontanet, Arnaud; Flahault, Antoine

2014-01-01

Background Mycobacterium ulcerans (MU) is the agent responsible for Buruli Ulcer (BU), an emerging skin disease with dramatic socioeconomic and health outcomes, especially in rural settings. BU emergence and distribution is linked to aquatic ecosystems in tropical and subtropical countries, especially to swampy and flooded areas. Aquatic animal organisms are likely to play a role either as host reservoirs or vectors of the bacilli. However, information on MU ecological dynamics, both in space and time, is dramatically lacking. As a result, the ecology of the disease agent, and consequently its mode of transmission, remains largely unknown, which jeopardizes public health attempts for its control. The objective of this study was to gain insight on MU environmental distribution and colonization of aquatic organisms through time. Methodology/Principal Findings Longitudinal sampling of 32 communities of aquatic macro-invertebrates and vertebrates was conducted from different environments in two BU endemic regions in Cameroon during 12 months. As a result, 238,496 individuals were classified and MU presence was assessed by qPCR in 3,084 sample-pools containing these aquatic organisms. Our study showed a broad distribution of MU in all ecosystems and taxonomic groups, with important regional differences in its occurrence. Colonization dynamics fluctuated along the year, with the highest peaks in August and October. The large variations observed in the colonization dynamics of different taxonomic groups and aquatic ecosystems suggest that the trends shown here are the result of complex ecological processes that need further investigation. Conclusion/Perspectives This is the largest field study on MU ecology to date, providing the first detailed description of its spatio-temporal dynamics in different aquatic ecosystems within BU endemic regions. We argue that coupling this data with fine-scale epidemiological data through statistical and mathematical models will provide a

Experimental demonstration of the possible role of Acanthamoeba polyphaga in the infection and disease progression in Buruli Ulcer (BU) using ICR mice

PubMed Central

Azumah, Bright K.; Addo, Phyllis G.; Dodoo, Alfred; Awandare, Gordon; Mosi, Lydia; Boakye, Daniel A.

2017-01-01

The transmission of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), remains puzzling although a number of hypothesis including through bites of infected aquatic insects have been proposed. We report the results of experiments using ICR mice that give credence to our hypothesis that Acanthamoeba species may play a role in BU transmission. We cocultured MU N2 and MU 1615 which expresses red fluorescent protein (RFP) and Acanthamoeba polyphaga (AP), and confirmed infected AP by Ziehl-Neelsen (ZN) staining. We tested for viability of MU inside AP and observed strong RFP signals inside both trophozoites and cysts after 3 and 42 days of coculturing respectively. ICR mice were topically treated, either on shaved intact or shaved pinpricked rumps, with one of the following; MU N2 only (2.25 x 106 colony forming units [CFU] / ml), MU N2:AP coculture (2.96 x 104 CFU: 1.6 x 106 cells/ml), AP only (1.6 x 106 cells/ml), PYG medium and sterile distilled water. Both MU N2 only and MU N2:AP elicited reddening on day (D) 31; edema on D 45 and D 44 respectively, and ulcers on D 49 at pinpricked sites only. To ascertain infectivity and pathogenicity of MU N2 only and MU N2:AP, and compare their virulence, the standard mouse footpad inoculation method was used. MU N2:AP elicited reddening in footpads by D 3 compared to D 14 with MU N2 only of the same dose of MU N2 (2.96 x 104 CFU). ZN-stained MU were observed in both thin sectioned and homogenized lesions, and aspirates from infected sites. Viable MU N2 were recovered from cultures of the homogenates and aspirates. This study demonstrates in ICR mice MU transmission via passive infection, and shows that punctures in the skin are prerequisite for infection, and that coculturing of MU with AP enhances pathogenesis. PMID:28329001

Draft Genome Sequence of Corynebacterium ulcerans FRC58, Isolated from the Bronchitic Aspiration of a Patient in France

PubMed Central

Silva, Andréia do Socorro de Sousa; Baraúna, Rafael Azevedo; de Sá, Pablo Caracciolo Gomes; das Graças, Diego Assis; Carneiro, Adriana Ribeiro; Thouvenin, Maxime; Azevedo, Vasco; Badell, Edgar; Guiso, Nicole; da Silva, Artur Luiz da Costa

2014-01-01

Corynebacterium ulcerans is a bacterial species with high importance because it causes infections in animals and, rarely, in humans. Its virulence mechanisms remain unclear. The current study describes the draft genome of C. ulcerans FRC58, which was isolated from the bronchitic aspiration of a patient in France. PMID:24407640

Functional Diversity as a New Framework for Understanding the Ecology of an Emerging Generalist Pathogen.

PubMed

Morris, Aaron; Guégan, Jean-François; Benbow, M Eric; Williamson, Heather; Small, Pamela L C; Quaye, Charles; Boakye, Daniel; Merritt, Richard W; Gozlan, Rodolphe E

2016-09-01

Emerging infectious disease outbreaks are increasingly suspected to be a consequence of human pressures exerted on natural ecosystems. Previously, host taxonomic communities have been used as indicators of infectious disease emergence, and the loss of their diversity has been implicated as a driver of increased presence. The mechanistic details in how such pathogen-host systems function, however, may not always be explained by taxonomic variation or loss. Here we used machine learning and methods based on Gower's dissimilarity to quantify metrics of invertebrate functional diversity, in addition to functional groups and their taxonomic diversity at sites endemic and non-endemic for the model generalist pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer. Changes in these metrics allowed the rapid categorisation of the ecological niche of the mycobacterium's hosts and the ability to relate specific host traits to its presence in aquatic ecosystems. We found that taxonomic diversity of hosts and overall functional diversity loss and evenness had no bearing on the mycobacterium's presence, or whether the site was in an endemic area. These findings, however, provide strong evidence that generalist environmentally persistent bacteria such as M. ulcerans can be associated with specific functional traits rather than taxonomic groups of organisms, increasing our understanding of emerging disease ecology and origin.

Risk factors for buruli ulcer in Ghana-a case control study in the Suhum-Kraboa-Coaltar and Akuapem South Districts of the eastern region.

PubMed

Kenu, Ernest; Nyarko, Kofi Mensah; Seefeld, Linda; Ganu, Vincent; Käser, Michael; Lartey, Margaret; Calys-Tagoe, Benedict Nii Laryea; Koram, Kwodwo; Adanu, Richard; Razum, Oliver; Afari, Edwin; Binka, Fred N

2014-01-01

Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/-5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR=3.9, 95% CI=1.9-8.2), insect bites in water/mud (OR=5.7, 95% CI=2.5-13.1), use of adhesive when injured (OR=2.7, 95% CI=1.1-6.8), and washing in the Densu river (OR=2.3, 95% CI=1.1-4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR=0.21, 95% CI=0.008-0.57) and wearing long sleeves for farming (OR=0.29, 95% CI=0.14-0.62) showed protection against BU. This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors.

Household cost of out-patient treatment of Buruli ulcer in Ghana: a case study of Obom in Ga South Municipality

PubMed Central

2013-01-01

Background The economic burden of diseases has become increasingly relevant to policy makers as healthcare expenditure keep rising in the face of limited and competing resources. Buruli ulcer (BU), a neglected but treatable tropical disease caused by Mycobacterium ulcerans, the only known environmental mycobacterium is capable of causing long term disability when left untreated. However, most BU studies have tended to focused on its bacteriology, epidemiology, entomology and other social determinants to the neglect of its economic evaluation. This paper reports estimated the household economic costs of BU and describe the intangible cost suffered by BU patients in an endemic area. Methods Retrospective one year cost data was used. A total of 63 confirmed BU cases were randomly sampled for the study. Economic cost and cost burden of BU were estimated. Sensitivity analysis was conducted to test the robustness of the cost estimates. Intangible cost measured stigmatization, pain, functional limitation and social isolation of children. Results The annual total household economic cost was US$35,915.98, of which about 65% was cost incurred by children with a mean cost of US$521.04. The mean annual household cost was US$570.09. The direct cost was 96% of the total cost. Non-medical cost accounts for about 97% of the direct cost with a mean cost of US$529.27. The mean medical cost was US$18.94. The main cost drivers of the household costs were transportation (78%) and food (12%). Caregivers and adult patients lost a total of 535 productive days seeking care, which gives an indirect cost valued at US$1,378.67 with a mean of US$21.88. A total of 365 school days (about 1 year) were lost by 19 BU patients (mean, 19.2 days). Functional loss and pain were low, and stigma rated moderate. Most children suffering from BU (84%) were socially isolated. Conclusion Household cost burden of out-patient BU ulcer treatment was high. Household cost of BU is therefore essential in the

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa

PubMed Central

Garchitorena, Andrés; Ngonghala, Calistus N.; Guegan, Jean-Francois; Texier, Gaëtan; Bellanger, Martine; Bonds, Matthew; Roche, Benjamin

2015-01-01

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions. PMID:26538592

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa.

PubMed

Garchitorena, Andrés; Ngonghala, Calistus N; Guegan, Jean-Francois; Texier, Gaëtan; Bellanger, Martine; Bonds, Matthew; Roche, Benjamin

2015-11-07

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions. © 2015 The Author(s).

Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time-Delay to Diagnosis on Clinical Forms and Severe Phenotypes.

PubMed

Capela, Carlos; Sopoh, Ghislain E; Houezo, Jean G; Fiodessihoué, René; Dossou, Ange D; Costa, Patrício; Fraga, Alexandra G; Menino, João F; Silva-Gomes, Rita; Ouendo, Edgard M; Rodrigues, Fernando; Pedrosa, Jorge

2015-01-01

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal

Rapid Detection and Molecular Differentiation of Toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans Strains by LightCycler PCR ▿

PubMed Central

Sing, Andreas; Berger, Anja; Schneider-Brachert, Wulf; Holzmann, Thomas; Reischl, Udo

2011-01-01

The systemic symptoms of diphtheria are caused by the tox-encoded diphtheria toxin (DT) which is produced by toxigenic Corynebacterium spp. Besides the classical agent C. diphtheriae, the zoonotic pathogen C. ulcerans has increasingly been reported as an emerging pathogen for diphtheria. The reliable detection of toxigenic Corynebacterium spp. is of substantial importance for both diphtheria surveillance in the public health sector and the clinical workup of a patient with diphtherialike symptoms. Since the respective tox genes of C. diphtheriae and C. ulcerans differ from each other in both DNA and amino acid sequence, both tox genes should be covered by novel real-time PCR methods. We describe the development and validation of a LightCycler PCR assay which reliably recognizes tox genes from both C. diphtheriae and C. ulcerans and differentiates the respective target genes by fluorescence resonance energy transfer (FRET) hybridization probe melting curve analysis. PMID:21593261

Screening of antifungal azole drugs and agrochemicals with an adapted alamarBlue-based assay demonstrates antibacterial activity of croconazole against Mycobacterium ulcerans.

PubMed

Scherr, Nicole; Röltgen, Katharina; Witschel, Matthias; Pluschke, Gerd

2012-12-01

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans.

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

PubMed Central

Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl–Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

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

Implementation of a national reference laboratory for Buruli ulcer disease in Togo.

PubMed

Beissner, Marcus; Huber, Kristina Lydia; Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl-Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

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. 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. 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%. High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78

Screening of Antifungal Azole Drugs and Agrochemicals with an Adapted alamarBlue-Based Assay Demonstrates Antibacterial Activity of Croconazole against Mycobacterium ulcerans

PubMed Central

Röltgen, Katharina; Witschel, Matthias; Pluschke, Gerd

2012-01-01

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans. PMID:23006761

Risk Factors for Buruli Ulcer in Ghana—A Case Control Study in the Suhum-Kraboa-Coaltar and Akuapem South Districts of the Eastern Region

PubMed Central

Kenu, Ernest; Nyarko, Kofi Mensah; Seefeld, Linda; Ganu, Vincent; Käser, Michael; Lartey, Margaret; Calys-Tagoe, Benedict Nii Laryea; Koram, Kwodwo; Adanu, Richard; Razum, Oliver; Afari, Edwin; Binka, Fred N.

2014-01-01

Background Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. Methods We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/−5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. Results A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR = 3.9, 95% CI = 1.9–8.2), insect bites in water/mud (OR = 5.7, 95% CI = 2.5–13.1), use of adhesive when injured (OR = 2.7, 95% CI = 1.1–6.8), and washing in the Densu river (OR = 2.3, 95% CI = 1.1–4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR = 0.21, 95% CI = 0.008–0.57) and wearing long sleeves for farming (OR = 0.29, 95% CI = 0.14–0.62) showed protection against BU. Conclusion This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors. PMID:25411974

Chemical and mineralogical characteristics of French green clays used for healing

USGS Publications Warehouse

Williams, Lynda B.; Haydel, Shelley E.; Giese, Rossman F.; Eberl, Dennis D.

2008-01-01

The worldwide emergence of infectious diseases, together with the increasing incidence of antibiotic-resistant bacteria, elevate the need to properly detect, prevent, and effectively treat these infections. The overuse and misuse of common antibiotics in recent decades stimulates the need to identify new inhibitory agents. Therefore, natural products like clays, that display antibacterial properties, are of particular interest.The absorptive properties of clay minerals are well documented for healing skin and gastrointestinal ailments. However, the antibacterial properties of clays have received less scientific attention. French green clays have recently been shown to heal Buruli ulcer, a necrotic or ‘flesh-eating’ infection caused by Mycobacterium ulcerans. Assessing the antibacterial properties of these clays could provide an inexpensive treatment for Buruli ulcer and other skin infections.Antimicrobial testing of the two clays on a broad-spectrum of bacterial pathogens showed that one clay promotes bacterial growth (possibly provoking a response from the natural immune system), while another kills bacteria or significantly inhibits bacterial growth. This paper compares the mineralogy and chemical composition of the two French green clays used in the treatment of Buruli ulcer.Mineralogically, the two clays are dominated by 1Md illite and Fe-smectite. Comparing the chemistry of the clay minerals and exchangeable ions, we conclude that the chemistry of the clay, and the surface properties that affect pH and oxidation state, control the chemistry of the water used to moisten the clay poultices and contribute the critical antibacterial agent(s) that ultimately debilitate the bacteria.

Situated knowledge of pathogenic landscapes in Ghana: Understanding the emergence of Buruli ulcer through qualitative analysis.

PubMed

Tschakert, Petra; Ricciardi, Vincent; Smithwick, Erica; Machado, Mario; Ferring, David; Hausermann, Heidi; Bug, Leah

2016-02-01

Successfully addressing neglected tropical diseases requires nuanced understandings of pathogenic landscapes that incorporate situated, contexualized community knowledge. In the case of Buruli ulcer (BU), the role of social science is vital to investigate complex human-environment interactions and navigate different ways of knowing. We analyze a set of qualitative data from our interdisciplinary project on BU in Ghana, drawing from participatory mapping, focus group discussions, semi-structured interviews, and open-ended survey questions to explore how people in endemic and non-endemic areas see themselves embedded in changing environmental and social landscapes. We pay particular attention to landscape disturbance through logging and small-scale alluvial gold mining. The results from our participatory research underscore the holistic nature of BU emergence in landscapes, encapsulated in partial and incomplete local descriptions, the relevance of collective learning to distill complexity, and the potential of rich qualitative data to inform quantitative landscape-disease models. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed Central

Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beissner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw; Frimpong, Michael; Kabiru, Abass Mohammed; Piten, Ebekalisai; Maman, Issaka; Bidjada, Bawimodom; Koba, Adjaho; Awoussi, Koffi Somenou; Kobara, Basile; Nitschke, Jörg; Wiedemann, Franz Xaver; Kere, Abiba Banla; Adjei, Ohene; Löscher, Thomas; Fleischer, Bernhard; Bretzel, Gisela; Herbinger, Karl-Heinz

2015-01-01

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-Guérin (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. PMID:25569674

Health Facility Cost of Buruli Ulcer Wound Treatment in Ghana: A Case Study.

PubMed

Asare, Kofi Hene; Aikins, Moses

2014-09-01

To estimate the wound treatment cost borne by the Buruli Ulcer Treatment Centre of the Amasaman Government Hospital, Ghana. Three different types of data collection approaches were used, namely, 1) observation checklist, 2) in-depth interviews, and 3) expenditure data review. Wound dressing processes were observed. Retrospective health facility cost data of Buruli ulcer (BU) wound treatment for the year 2011 were used. Cost data gathered covered medical and nonmedical items. Cost analyses were carried out to determine the health facility's financial and economic costs. The total annual financial cost was US $121,189.16, of which 99% was recurrent cost. This constitutes about 13% of the expenditure by the Amasaman Government Hospital for the year 2011. The total annual economic cost was US $143,609.22, of which 93% was recurrent cost. The main cost driver for both financial and economic costs was personnel. The annual BU wound treatment costs per capita were US $1615.86 for financial cost and US $1914.79 for economic cost, respectively. The study did not cover household patient costs. The cost of BU wound treatment takes a considerable amount of the hospital's expenditure. This shows the importance of health facility cost as one of the decision-making tools for both resource allocation and mobilization. Hospital management must therefore constantly examine its staffing norms and the associated cost to improve the hospital's resource allocation. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Assessment of water, sanitation, and hygiene practices and associated factors in a Buruli ulcer endemic district in Benin (West Africa).

PubMed

Johnson, Roch Christian; Boni, Gratien; Barogui, Yves; Sopoh, Ghislain Emmanuel; Houndonougbo, Macaire; Anagonou, Esai; Agossadou, Didier; Diez, Gabriel; Boko, Michel

2015-08-19

Control of neglected tropical diseases (NTDs) requires multiple strategic approaches including water, sanitation and hygiene services (WASH). Buruli ulcer (BU), one of the 17 NTDs, remains a public health issue in Benin particularly in the district of Lalo. The availability of water as well as good hygiene are important for the management of Buruli ulcer particularly in the area of wound care one of the main component of the treatment of BU lesions. Given the growing importance of WASH in controlling NTDs and in order to assess the baseline for future cross-cutting interventions, we report here on the first study evaluating the level of WASH and associated factors in Lalo, one of the most BU-endemic districts in Benin. A cross-sectional study was carried to assess WASH practices and associated factors in the district of Lalo. Data were collected from 600 heads of household using structured pretested questionnaire and observations triangulated with qualitative information obtained from in-depth interviews of patients, care-givers and community members. Univariate and multivariate analysis were carried to determine the relationships between the potential associated factors and the sanitation as well as hygiene status. BU is an important conditions in the district of Lalo with 917 new cases detected from 2006 to 2012. More than 49 % of the household surveyed used unimproved water sources for their daily needs. Only 8.7 % of the investigated household had improved sanitation facilities at home and 9.7 % had improved hygiene behavior. The type of housing as an indicator of the socioeconomic status, the permanent availability of soap and improved hygiene practices were identified as the main factors positively associated with improved sanitation status. In the district of Lalo in Benin, one of the most endemic for BU, the WASH indicators are very low. This study provides baseline informations for future cross-cutting interventions in this district.

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

PubMed

Bartralot, R; García-Patos, V; Sitjas, D; Rodríguez-Cano, L; Mollet, J; Martín-Casabona, N; Coll, P; Castells, A; Pujol, R M

2005-04-01

Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.

Combining PCR with Microscopy to Reduce Costs of Laboratory Diagnosis of Buruli Ulcer

PubMed Central

Yeboah-Manu, Dorothy; Asante-Poku, Adwoa; Asan-Ampah, Kobina; Ampadu, Emelia Danso Edwin; Pluschke, Gerd

2011-01-01

The introduction of antibiotic therapy as first-line treatment of Buruli ulcer underlines the importance of laboratory confirmation of clinical diagnosis. Because smear microscopy has very limited sensitivity, the technically demanding and more expensive IS2404 diagnostic polymerase chain reaction (PCR) has become the main method for confirmation. By optimization of the release of mycobacteria from swab specimen and concentration of bacterial suspensions before smearing, we were able to improve the detection rate of acid-fast bacilli by microscopy after Ziehl–Neelsen staining. Compared with IS2404 PCR, which is the gold standard diagnostic method, the sensitivity and specificity of microscopy with 100 concentrated specimens were 58.4% and 95.7%, respectively. We subsequently evaluated a stepwise laboratory confirmation algorithm with detection of AFB as first-line method and IS2404 PCR performed only with those samples that were negative in microscopic analysis. This stepwise approach reduced unit cost by more than 50% to $5.41, and the total costs were reduced from $917 to $433. PMID:22049046

Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors

PubMed Central

Garchitorena, Andrés; Guégan, Jean-François; Léger, Lucas; Eyangoh, Sara; Marsollier, Laurent; Roche, Benjamin

2015-01-01

Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors. DOI: http://dx.doi.org/10.7554/eLife.07616.001 PMID:26216042

Vectorborne diseases in West Africa: geographic distribution and geospatial characteristics.

PubMed

Ratmanov, Pavel; Mediannikov, Oleg; Raoult, Didier

2013-05-01

This paper provides an overview of the methods in which geographic information systems (GIS) and remote sensing (RS) technology have been used to visualise and analyse data related to vectorborne diseases (VBD) in West Africa and to discuss the potential for these approaches to be routinely included in future studies of VBDs. GIS/RS studies of diseases that are associated with a specific geographic landscape were reviewed, including malaria, human African trypanosomiasis, leishmaniasis, lymphatic filariasis, Loa loa filariasis, onchocerciasis, Rift Valley fever, dengue, yellow fever, borreliosis, rickettsioses, Buruli ulcer and Q fever. RS data and powerful spatial modelling methods improve our understanding of how environmental factors affect the vectors and transmission of VBDs. There is great potential for the use of GIS/RS technologies in the surveillance, prevention and control of vectorborne and other infectious diseases in West Africa.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

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

PubMed

Ackumey, Mercy M; Gyapong, Margaret; Pappoe, Matilda; Kwakye-Maclean, Cynthia; Weiss, Mitchell G

2012-05-11

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. 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. 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 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 healing is perceived to make ideas of witchcraft as a PC more

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

PubMed Central

2012-01-01

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 healing is perceived

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons

PubMed Central

Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

2016-01-01

Background Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Results Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Conclusion Mycolactone

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

PubMed Central

Beissner, Marcus; Phillips, Richard Odame; Battke, Florian; Bauer, Malkin; Badziklou, Kossi; Sarfo, Fred Stephen; Maman, Issaka; Rhomberg, Agata; Piten, Ebekalisai; Frimpong, Michael; Huber, Kristina Lydia; Symank, Dominik; Jansson, Moritz; Wiedemann, Franz Xaver; Banla Kere, Abiba; Herbinger, Karl-Heinz; Löscher, Thomas; Bretzel, Gisela

2015-01-01

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

The potent effect of mycolactone on lipid membranes

PubMed Central

Maniti, Ofelia; Marion, Estelle; Marsollier, Laurent; Dufourc, Erick J.; Canaan, Stéphane

2018-01-01

Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated. We investigated the capacity of mycolactone to interact with membranes, to evaluate its effects on membrane lipid organization following its diffusion across the cell membrane. We used Langmuir monolayers as a cell membrane model. Experiments were carried out with a lipid composition chosen to be as similar as possible to that of the plasma membrane. Mycolactone, which has surfactant properties, with an apparent saturation concentration of 1 μM, interacted with the membrane at very low concentrations (60 nM). The interaction of mycolactone with the membrane was mediated by the presence of cholesterol and, like detergents, mycolactone reshaped the membrane. In its monomeric form, this toxin modifies lipid segregation in the monolayer, strongly affecting the formation of ordered microdomains. These findings suggest that mycolactone disturbs lipid organization in the biological membranes it crosses, with potential effects on cell functions and signaling pathways. Microdomain remodeling may therefore underlie molecular events, accounting for the ability of mycolactone to attack multiple targets and providing new insight into a single unifying mechanism underlying the pleiotropic effects of this molecule. This membrane remodeling may act in synergy with the other known effects of mycolactone on its intracellular targets, potentiating these effects. PMID:29320578

Molecular Species Delimitation and Morphology of Aquatic and Sub-Aquatic Bugs (Heteroptera) in Cameroon

PubMed Central

Le Gall, Philippe; Chen, Ping-Ping; Nieser, Nico; Guilbert, Eric; Njiokou, Flobert; Marsollier, Laurent; Guégan, Jean-François; Pluot-Sigwalt, Dominique; Eyangoh, Sara; Harry, Myriam

2016-01-01

Aquatic and semi-aquatic bugs (Heteroptera) represent a remarkable diversity and a resurging interest has been given to documenting at the species level these insects inhabiting Cameroon in Central Africa due to their potential implication in the transmission of the bacterium Mycobacterium ulcerans, the causal agent of Buruli ulcer, an emerging human disease. A survey was carried out over two years in Cameroon. Morphological analyses were done in two steps. A first step consisted in separating the specimens based on broadly shared characters into morphotypes. The specimens were then separated into two independent batches containing each the same representation of each morphotype. One batch (309 specimens) was used by taxonomy experts on aquatic bugs for species level identification and/or to reconcile nymph with their corresponding adult species. The second batch (188 specimens) was used to define species based on the COI DNA sequences (standard sequence used for “DNA barcoding”) and using the Automatic Barcode Gap Discovery (ABGD) method. The first morphological analysis step separated the specimens into 63 different morphotypes (49 adults and 14 nymphs), which were then found to belong to 54 morphological species in the infra-orders Gerromorpha and Nepomorpha based on the species-level morphological identification, and 41–45 putative molecular species according to the gap value retained in the ABGD. Integrating morphology and “DNA barcoding” reconciled all the specimens into 62 aquatic bug species in Cameroon. Generally, we obtained a good congruence between species a priori identified based on morphology from adult morphotypes and molecular putative species. Moreover, molecular identification has allowed the association of 86% of nymphs with adults. This work illustrates the importance of integrative taxonomy. PMID:27149077

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

PubMed

Conti, Francesca; Lugo-Reyes, Saul Oswaldo; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Güzide; Borges de Oliveira, Edgar; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G; Emiroglu, Melike; Öz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Pérez, Nestor; Regairaz, Lorena; Guidos Morales, Héctor Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Ortega, Maria Claudia; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret Bano; Vogt, Guillaume; Blanche, Stéphane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J; Kütükçüler, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, Jacinta

2016-07-01

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Our objective was to assess the effect of mycobacterial disease in patients with CGD. We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases.

PubMed

Garchitorena, A; Sokolow, S H; Roche, B; Ngonghala, C N; Jocque, M; Lund, A; Barry, M; Mordecai, E A; Daily, G C; Jones, J H; Andrews, J R; Bendavid, E; Luby, S P; LaBeaud, A D; Seetah, K; Guégan, J F; Bonds, M H; De Leo, G A

2017-06-05

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases

PubMed Central

Sokolow, S. H.; Ngonghala, C. N.; Jocque, M.; Lund, A.; Barry, M.; Mordecai, E. A.; Daily, G. C.; Andrews, J. R.; Bendavid, E.; Luby, S. P.; LaBeaud, A. D.; Seetah, K.; Guégan, J. F.; De Leo, G. A.

2017-01-01

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438917

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone

PubMed Central

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-01-01

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822

Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

PubMed

Sommerfeld, J; Oduola, A M J

2007-01-01

The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.

A unique Mycobacterium species isolated from an epizootic of striped bass (Morone saxatilis).

PubMed Central

Rhodes, M. W.; Kator, H.; Kotob, S.; van Berkum, P.; Kaattari, I.; Vogelbein, W.; Floyd, M. M.; Butler, W. R.; Quinn, F. D.; Ottinger, C.; Shotts, E.

2001-01-01

We isolated a Mycobacterium sp. resembling Mycobacterium marinum and M. ulcerans from diseased striped bass (Morone saxatilis) during an epizootic of mycobacteriosis in the Chesapeake Bay. This isolate may represent an undescribed Mycobacterium species, based on phenotypic characteristics and comparative 16S rRNA gene sequence. PMID:11747708

Dermatologic Infectious Diseases in International Travelers.

PubMed

Wilson, Mary E.; Chen, Lin H.

2004-02-01

Skin lesions provide an important clue to the diagnoses of many infections in returned travelers. New information related to epidemiology, recognition, diagnosis, or management is described for the systemic infections--dengue fever, several of the rickettsial infections, African trypanosomiasis, and coccidioidomycosis. Many pathogens cause focal skin findings. Recent findings are presented for cutaneous leishmaniasis, Buruli ulcer, gnatho-stomiasis, cutaneous larva migrans, myiasis, tungiasis, and scabies. This paper describes the most common skin problems in returning travelers and outlines the types of infections that cause skin lesions, as defined by morphologic characteristics.

Diphtheria in the Postepidemic Period, Europe, 2000–2009

PubMed Central

White, Joanne M.; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S.; Neal, Shona; Efstratiou, Androulla

2012-01-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections. PMID:22304732

Social stigma towards neglected tropical diseases: a systematic review.

PubMed

Hofstraat, Karlijn; van Brakel, Wim H

2016-03-01

People affected by neglected tropical diseases (NTDs) are frequently the target of social stigmatization. To date not much attention has been given to stigma in relation to NTDs. The objective of this review is to identify the extent of social stigma and the similarities and differences in the causes, manifestations, impact of stigma and interventions used between the NTDs. A systematic review was conducted in Pubmed, ScienceDirect, PsycINFO and Web of Knowledge. The search encompassed 17 NTDs, including podoconiosis, but not leprosy as this NTD has recently been reviewed. However, leprosy was included in the discussion. The 52 selected articles provided evidence on stigma related to lymphatic filariasis (LF), podoconiosis, Buruli ulcer, onchocerciasis, schistosomiasis, leishmaniasis, Chagas disease, trachoma, soil-transmitted helminthiasis (STH) and human African trypanosomiasis. The similarities predominated in stigma related to the various NTDs; only minimal differences in stigma reasons and measures were found. These similarities suggest that joint approaches to reduce stigmatization may be feasible. Lessons from leprosy and other stigmatized health conditions can be used to plan such joint approaches. Further research will be necessary to study the efficacy of joint interventions and to investigate stigma related to NTDs for which no evidence is available yet. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identification of nonlipophilic corynebacteria isolated from dairy cows with mastitis.

PubMed

Hommez, J; Devriese, L A; Vaneechoutte, M; Riegel, P; Butaye, P; Haesebrouck, F

1999-04-01

Nonlipophilic corynebacteria associated with clinical and subclinical mastitis in dairy cows were found to belong to four species: Corynebacterium amycolatum, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, and Corynebacterium minutissimum. These species may easily be confused. However, clear-cut differences between C. ulcerans and C. pseudotuberculosis were found in their acid production from maltotriose and ethylene glycol, susceptibility to vibriostatic agent O129, and alkaline phosphatase. Absence of growth at 20 degrees C and lack of alpha-glucosidase and 4MU-alpha-D-glycoside hydrolysis activity differentiated C. amycolatum from C. pseudotuberculosis and C. ulcerans. The mastitis C. pseudotuberculosis strains differed from the biovar equi and ovis reference strains and from caprine field strains in their colony morphologies and in their reduced inhibitory activity on staphylococcal beta-hemolysin. C. amycolatum was the most frequently isolated nonlipophilic corynebacterium.

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis.

PubMed

Tomczyk, Sara; Deribe, Kebede; Brooker, Simon J; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

2014-01-01

The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0

Evaluation of the medicinal use of clay minerals as antibacterial agents

PubMed Central

Williams, Lynda B.; Haydel, Shelley E.

2010-01-01

Natural clays have been used to heal skin infections since the earliest recorded history. Recently our attention was drawn to a clinical use of French green clay (rich in Fe-smectite) for healing Buruli ulcer, a necrotizing fasciitis (‘flesh-eating’ infection) caused by Mycobacterium ulcerans. These clays and others like them are interesting as they may reveal an antibacterial mechanism that could provide an inexpensive treatment for this and other skin infections, especially in global areas with limited hospitals and medical resources. Microbiological testing of two French green clays, and other clays used traditionally for healing, identified three samples that were effective at killing a broad-spectrum of human pathogens. A clear distinction must be made between ‘healing clays’ and those we have identified as antibacterial clays. The highly adsorptive properties of many clays may contribute to healing a variety of ailments, although they are not antibacterial. The antibacterial process displayed by the three identified clays is unknown. Therefore, we have investigated the mineralogical and chemical compositions of the antibacterial clays for comparison with non-antibacterial clays in an attempt to elucidate differences that may lead to identification of the antibacterial mechanism(s). The two French green clays used to treat Buruli ulcer, while similar in mineralogy, crystal size, and major element chemistry, have opposite effects on the bacterial populations tested. One clay deposit promoted bacterial growth whereas another killed the bacteria. The reasons for the difference in antibacterial properties thus far show that the bactericidal mechanism is not physical (e.g., an attraction between clay and bacteria), but by a chemical transfer or reaction. The chemical variables are still under investigation. Cation exchange experiments showed that the antibacterial component of the clay can be removed, implicating exchangeable cations in the antibacterial

Evaluation of the medicinal use of clay minerals as antibacterial agents.

PubMed

Williams, Lynda B; Haydel, Shelley E

2010-07-01

Natural clays have been used to heal skin infections since the earliest recorded history. Recently our attention was drawn to a clinical use of French green clay (rich in Fe-smectite) for healing Buruli ulcer, a necrotizing fasciitis ('flesh-eating' infection) caused by Mycobacterium ulcerans. These clays and others like them are interesting as they may reveal an antibacterial mechanism that could provide an inexpensive treatment for this and other skin infections, especially in global areas with limited hospitals and medical resources.Microbiological testing of two French green clays, and other clays used traditionally for healing, identified three samples that were effective at killing a broad-spectrum of human pathogens. A clear distinction must be made between 'healing clays' and those we have identified as antibacterial clays. The highly adsorptive properties of many clays may contribute to healing a variety of ailments, although they are not antibacterial. The antibacterial process displayed by the three identified clays is unknown. Therefore, we have investigated the mineralogical and chemical compositions of the antibacterial clays for comparison with non-antibacterial clays in an attempt to elucidate differences that may lead to identification of the antibacterial mechanism(s).The two French green clays used to treat Buruli ulcer, while similar in mineralogy, crystal size, and major element chemistry, have opposite effects on the bacterial populations tested. One clay deposit promoted bacterial growth whereas another killed the bacteria. The reasons for the difference in antibacterial properties thus far show that the bactericidal mechanism is not physical (e.g., an attraction between clay and bacteria), but by a chemical transfer or reaction. The chemical variables are still under investigation.Cation exchange experiments showed that the antibacterial component of the clay can be removed, implicating exchangeable cations in the antibacterial process

Identification of Nonlipophilic Corynebacteria Isolated from Dairy Cows with Mastitis

PubMed Central

Hommez, Jozef; Devriese, Luc A.; Vaneechoutte, Mario; Riegel, Philippe; Butaye, Patrick; Haesebrouck, Freddy

1999-01-01

Nonlipophilic corynebacteria associated with clinical and subclinical mastitis in dairy cows were found to belong to four species: Corynebacterium amycolatum, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, and Corynebacterium minutissimum. These species may easily be confused. However, clear-cut differences between C. ulcerans and C. pseudotuberculosis were found in their acid production from maltotriose and ethylene glycol, susceptibility to vibriostatic agent O129, and alkaline phosphatase. Absence of growth at 20°C and lack of α-glucosidase and 4MU-α-d-glycoside hydrolysis activity differentiated C. amycolatum from C. pseudotuberculosis and C. ulcerans. The mastitis C. pseudotuberculosis strains differed from the biovar equi and ovis reference strains and from caprine field strains in their colony morphologies and in their reduced inhibitory activity on staphylococcal β-hemolysin. C. amycolatum was the most frequently isolated nonlipophilic corynebacterium. PMID:10074508

Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

PubMed

Yotsu, Rie Roselyne; Kouadio, Kouamé; Vagamon, Bamba; N'guessan, Konan; Akpa, Amari Jules; Yao, Aubin; Aké, Julien; Abbet Abbet, Rigobert; Tchamba Agbor Agbor, Barbine; Bedimo, Roger; Ishii, Norihisa; Fuller, L Claire; Hay, Roderick; Mitjà, Oriol; Drechsler, Henning; Asiedu, Kingsley

2018-05-01

Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process. We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary. Of a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3-26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance. We carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d'Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned

Steps Toward Creating A Therapeutic Community for Inpatients Suffering from Chronic Ulcers: Lessons from Allada Buruli Ulcer Treatment Hospital in Benin

PubMed Central

Amoussouhoui, Arnaud Setondji; Johnson, Roch Christian; Sopoh, Ghislain Emmanuel; Agbo, Ines Elvire; Aoulou, Paulin; Houezo, Jean-Gabin; Tingbe-Azalou, Albert; Boyer, Micah; Nichter, Mark

2016-01-01

Background Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their

Association between Footwear Use and Neglected Tropical Diseases: A Systematic Review and Meta-Analysis

PubMed Central

Brooker, Simon J.; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

2014-01-01

Background The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. Methodology We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Principal Findings Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR = 0.15; 95% CI: 0.08–0.29), CLM (OR = 0.24; 95% CI: 0.06–0.96), tungiasis (OR = 0

Rapid microbiochemical identification of Corynebacterium diphtheriae and other medically important corynebacteria.

PubMed Central

Thompson, J S; Gates-Davis, D R; Yong, D C

1983-01-01

A rapid biochemical method based on the fermentation of carbohydrates, the hydrolysis of urea, and the reduction of nitrate was used to identify Corynebacterium diphtheriae, C. ulcerans, C. pseudodiphtheriticum, C. haemolyticum, C. pseudotuberculosis, C. pyogenes, C. ovis, the Centers for Disease Control JK group, and Rhodococcus (Corynebacterium) equi. With this procedure identification was confirmed for 133 stock cultures and clinical isolates of corynebacteria. Most were identified within 1 h and all were identified within 4 h after inoculation into the test substrates. PMID:6355166

Prevention and control of neglected tropical diseases: overview of randomized trials, systematic reviews and meta-analyses

PubMed Central

Kappagoda, Shanthi

2014-01-01

Abstract Objective To analyse evidence from randomized controlled trials (RCTs) on the prevention and control of neglected tropical diseases (NTDs) and to identify areas where evidence is lacking. Methods The Cochrane Central Register of Controlled Trials and PubMed were searched for RCTs and the Cochrane Database of Systematic Reviews and PubMed were searched for meta-analyses and systematic reviews, both from inception to 31 December 2012. Findings Overall, 258 RCTs were found on American trypanosomiasis, Buruli ulcer, dengue, geohelminth infection, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis or trachoma. No RCTs were found on cysticercosis, dracunculiasis, echinococcosis, foodborne trematodes, or human African trypanosomiasis. The most studied diseases were geohelminth infection (51 RCTs) and leishmaniasis (46 RCTs). Vaccines, chemoprophylaxis and interventions targeting insect vectors were evaluated in 113, 99 and 39 RCTs, respectively. Few addressed how best to deliver preventive chemotherapy, such as the choice of dosing interval (10) or target population (4), the population coverage needed to reduce transmission (2) or the method of drug distribution (1). Thirty-one publications containing 32 systematic reviews (16 with and 16 without meta-analyses) were found on American trypanosomiasis, dengue, geohelminths, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis or trachoma. Together, they included only 79 of the 258 published RCTs (30.6%). Of 36 interventions assessed, 8 were judged effective in more than one review. Conclusion Few RCTs on the prevention or control of the principal NTDs were found. Trials on how best to deliver preventive chemotherapy were particularly rare. PMID:24839325

40 CFR 725.421 - Introduced genetic material.

Code of Federal Regulations, 2010 CFR

2010-07-01

... elongation factor 2, leading to inhibition of protein synthesis in target respiratory, heart, kidney, and... protein synthesis inhibitor. Sequence Source Toxin Name Corynebacterium diphtheriae & C. ulcerans...

Patent landscape of neglected tropical diseases: an analysis of worldwide patent families.

PubMed

Akinsolu, Folahanmi Tomiwa; de Paiva, Vitor Nobre; Souza, Samuel Santos; Varga, Orsolya

2017-11-14

"Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees. Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of

Broad-spectrum in vitro antibacterial activities of clay minerals against antibiotic-susceptible and antibiotic-resistant bacterial pathogens

PubMed Central

HAYDEL, SHELLEY E.; REMENIH, CHRISTINE M.; WILLIAMS, LYNDA B.

2008-01-01

SYNOPSIS Objectives The capacity to properly address the worldwide incidence of infectious diseases lies in the ability to detect, prevent, and effectively treat these infections. Therefore, identifying and analyzing inhibitory agents are worthwhile endeavors in an era when few new classes of effective antimicrobials have been developed. The use of geological nanomaterials to heal skin infections has been evident since the earliest recorded history, and specific clay minerals may prove valuable in the treatment of bacterial diseases, including infections for which there are no effective antibiotics, such as Buruli ulcer and multi-drug resistant infections. Methods We have subjected two iron-rich clay minerals, which have previously been used to treat Buruli ulcer patients, to broth culture testing of antibiotic-susceptible and -resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents. Results One specific mineral, CsAg02, demonstrated bactericidal activity against pathogenic Escherichia coli, extended-spectrum β-lactamase (ESBL) E. coli, S. enterica serovar Typhimurium, Pseudomonas aeruginosa, and Mycobacterium marinum and a combined bacteriostatic/bactericidal effect against Staphylococcus aureus, penicillin-resistant S. aureus (PRSA), methicillin-resistant S. aureus (MRSA), and Mycobacterium smegmatis, while another mineral with similar structure and bulk crystal chemistry, CsAr02, had no effect on or enhanced bacterial growth. The <0.2 μm fraction of CsAg02 and CsAg02 heated to 200°C or 550°C retained bactericidal activity, while cation-exchanged CsAg02 and CsAg02 heated to 900°C no longer killed E. coli. Conclusions Our results indicate that specific mineral products have intrinsic, heat-stable antibacterial properties, which could provide an inexpensive treatment against numerous human bacterial infections. PMID:18070832

[Nursing perspective on the care of people with leprosy in Ivory Coast].

PubMed

Lecocq, Dan

Lucien Gbadié is a nurse at the Raoul-Follereau Institute in Adzopé, Ivory Coast. In this article, he describes how people with leprosy or Buruli ulcer are treated and supported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

PubMed Central

Both, Leonard; Collins, Sarah; de Zoysa, Aruni; White, Joanne; Mandal, Sema

2014-01-01

Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required. PMID:25502525

A modified Elek test for detection of toxigenic corynebacteria in the diagnostic laboratory.

PubMed

Engler, K H; Glushkevich, T; Mazurova, I K; George, R C; Efstratiou, A

1997-02-01

The detection of toxigenicity among Corynebacterium diphtheriae and Corynebacterium ulcerans strains is the most important test for the microbiological diagnosis of diphtheria. Difficulties with current methods, in particular the Elek test, are well documented. We therefore describe a modified Elek test which provides an accurate result after only 16 h of incubation, in contrast to 48 h for the conventional test.

Caenorhabditis elegans star formation and negative chemotaxis induced by infection with corynebacteria.

PubMed

Antunes, Camila Azevedo; Clark, Laura; Wanuske, Marie-Therès; Hacker, Elena; Ott, Lisa; Simpson-Louredo, Liliane; de Luna, Maria das Gracas; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Hodgkin, Jonathan; Burkovski, Andreas

2016-01-01

Caenorhabditis elegans is one of the major model systems in biology based on advantageous properties such as short life span, transparency, genetic tractability and ease of culture using an Escherichia coli diet. In its natural habitat, compost and rotting plant material, this nematode lives on bacteria. However, C. elegans is a predator of bacteria, but can also be infected by nematopathogenic coryneform bacteria such Microbacterium and Leucobacter species, which display intriguing and diverse modes of pathogenicity. Depending on the nematode pathogen, aggregates of worms, termed worm-stars, can be formed, or severe rectal swelling, so-called Dar formation, can be induced. Using the human and animal pathogens Corynebacterium diphtheriae and Corynebacterium ulcerans as well as the non-pathogenic species Corynebacterium glutamicum, we show that these coryneform bacteria can also induce star formation slowly in worms, as well as a severe tail-swelling phenotype. While C. glutamicum had a significant, but minor influence on survival of C. elegans, nematodes were killed after infection with C. diphtheriae and C. ulcerans. The two pathogenic species were avoided by the nematodes and induced aversive learning in C. elegans.

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections.

PubMed

Sina, Haziz; Ahoyo, Théodora A; Moussaoui, Wardi; Keller, Daniel; Bankolé, Honoré S; Barogui, Yves; Stienstra, Ymkje; Kotchoni, Simeon O; Prévost, Gilles; Baba-Moussa, Lamine

2013-08-08

Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin.

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

PubMed Central

2013-01-01

Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

Mycobacterium shottsii sp. nov., a slowly growing species isolated from Chesapeake Bay striped bass (Morone saxatilis)

USGS Publications Warehouse

Rhodes, M.W.; Kator, H.; Kotob, S.; van Berkum, P.; Kaattari, I.; Vogelbein, W.; Quinn, F.; Floyd, M.M.; Butler, W.R.; Ottinger, C.A.

2003-01-01

Slowly growing, non-pigmented mycobacteria were isolated from striped bass (Morone saxatilis) during an epizootic of mycobacteriosis in the Chesapeake Bay. Growth characteristics, acid-fastness and results of 16S rRNA gene sequencing were consistent with those of the genus Mycobacterium. A unique profile of biochemical reactions was observed among the 21 isolates. A single cluster of eight peaks identified by analysis of mycolic acids (HPLC) resembled those of reference patterns but differed in peak elution times from profiles of reference species of the Mycobacterium tuberculosis complex. One isolate (M175T) was placed within the slowly growing mycobacteria by analysis of aligned 16S rRNA gene sequences and was proximate in phylogeny to Mycobacterium ulcerans and Mycobacterium marinum. However, distinct nucleotide differences were detected in the 16S rRNA gene sequence among M175T, M. ulcerans and M. marinum (99.2% similarity). Isolate M175T could be differentiated from other slowly growing, non-pigmented mycobacteria by its inability to grow at 37??C, production of niacin and urease, absence of nitrate reductase and resistance to isoniazid (1 ??g ml-1), thiacetazone and thiophene-2-carboxylic hydrazide. Based upon these genetic and phenotypic differences, isolate M175T (= ATCC 700981T = NCTC 13215T) is proposed as the type strain of a novel species, Mycobacterium shottsii sp. nov.

Polymerase chain reaction for screening clinical isolates of corynebacteria for the production of diphtheria toxin.

PubMed

Pallen, M J; Hay, A J; Puckey, L H; Efstratiou, A

1994-04-01

To assess the performance of the polymerase chain reaction (PCR) when used to screen rapidly large numbers of corynebacteria for toxin production; and to determine the incidence of false positive PCR results with non-toxigenic Corynebacterium diphtheriae isolates. Eighty seven recent British isolates of corynebacteria were assayed by PCR. All isolates were assayed from both blood and tellurite agar within a five day period. Thirty three non-toxigenic isolates of C diphtheriae from six countries were also tested by PCR and by the Elek immunodiffusion assay. There was complete concordance between the results of PCR and traditional methods on the recent British isolates, with one exception: an Elek positive "C ulcerans" isolate, which was PCR positive from tellurite but not from blood agar. One of the thirty three (3%) non-toxigenic isolates of C diphtheriae was PCR positive. These results suggest that PCR compares favourably with traditional methods for the detection of toxigenic corynebacteria and that it represents a powerful new tool in the diagnosis of an old disease.

Polymerase chain reaction for screening clinical isolates of corynebacteria for the production of diphtheria toxin.

PubMed Central

Pallen, M J; Hay, A J; Puckey, L H; Efstratiou, A

1994-01-01

AIMS--To assess the performance of the polymerase chain reaction (PCR) when used to screen rapidly large numbers of corynebacteria for toxin production; and to determine the incidence of false positive PCR results with non-toxigenic Corynebacterium diphtheriae isolates. METHODS--Eighty seven recent British isolates of corynebacteria were assayed by PCR. All isolates were assayed from both blood and tellurite agar within a five day period. Thirty three non-toxigenic isolates of C diphtheriae from six countries were also tested by PCR and by the Elek immunodiffusion assay. RESULTS--There was complete concordance between the results of PCR and traditional methods on the recent British isolates, with one exception: an Elek positive "C ulcerans" isolate, which was PCR positive from tellurite but not from blood agar. One of the thirty three (3%) non-toxigenic isolates of C diphtheriae was PCR positive. CONCLUSIONS--These results suggest that PCR compares favourably with traditional methods for the detection of toxigenic corynebacteria and that it represents a powerful new tool in the diagnosis of an old disease. Images PMID:8027375

Development, validation and implementation of a quadruplex real-time PCR assay for identification of potentially toxigenic corynebacteria.

PubMed

De Zoysa, Aruni; Efstratiou, Androulla; Mann, Ginder; Harrison, Timothy G; Fry, Norman K

2016-12-01

Toxigenic corynebacteria are uncommon in the UK; however, laboratory confirmation by the national reference laboratory can inform public health action according to national guidelines. Standard phenotypic tests for identification and toxin expression of isolates can take from ≥24 to ≥48 h from receipt. To decrease the time to result, a real-time PCR (qPCR) assay was developed for confirmation of both identification of Corynebacterium diphtheriae and Corynebacterium ulcerans/Corynebacterium pseudotuberculosis and detection of the diphtheria toxin gene. Target genes were the RNA polymerase β-subunit-encoding gene (rpoB) and A-subunit of the diphtheria toxin gene (tox). Green fluorescent protein DNA (gfp) was used as an internal process control. qPCR results were obtained within 3 to 4 h after receipt of isolate. The assay was validated according to published guidelines and demonstrated high diagnostic sensitivity (100 %), high specificity (98-100 %) and positive and negative predictive values of 91 to 100 % and 100 %, respectively, compared to both block-based PCR and the Elek test, together with a greatly reduced time from isolate receipt to reporting. Limitations of the qPCR assay were the inability to distinguish between C. ulcerans and C. pseudotuberculosis and that the presence of the toxin gene as demonstrated by qPCR may not always predict toxin expression. Thus, confirmation of expression of diphtheria toxin is always sought using the phenotypic Elek test. The new qPCR assay was formally introduced as the front-line test for putative toxigenic corynebacteria to inform public health action in England and Wales on 1 April 2014.

Corynebacterium species nasopharyngeal carriage in asymptomatic individuals aged ≥ 65 years in Germany.

PubMed

Teutsch, Barbara; Berger, Anja; Marosevic, Durdica; Schönberger, Katharina; Lâm, Thiên-Trí; Hubert, Kerstin; Beer, Steffi; Wienert, Peter; Ackermann, Nikolaus; Claus, Heike; Drayß, Maria; Thiel, Kathrin; van der Linden, Mark; Vogel, Ulrich; Sing, Andreas

2017-10-01

The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium (C.) species (C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly.

Synthesis and biological activity of alkynoic acids derivatives against mycobacteria

PubMed Central

Vilchèze, Catherine; Leung, Lawrence W.; Bittman, Robert; Jacobs, William R.

2015-01-01

2-alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2- alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development. PMID:26256431

A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis

PubMed Central

Khajehnoori, Masoomeh; O'Brien, Tim

2016-01-01

Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence. This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

PubMed

Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

2016-01-11

Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

Definitive or conservative surgery for perforated gastric ulcer?--An unresolved problem.

PubMed

Sarath Chandra, Sistla; Kumar, S Siva

2009-04-01

Gastric ulcer perforation has not been the focus of many studies. In addition there is a need to analyze the results of gastric perforation separately and not along with duodenal perforations, to identify the factors influencing the outcome and to develop strategies for its management. Retrospective analysis of 54 patients presenting with gastric perforation. Mean age of the patients was 44.5 years with male preponderance. Morbidity following Closure of the perforation, acid reduction surgery and resection was not significantly different. Overall mortality was 16.6% with highest mortality 24.1% following simple closure. Mortality following simple closure and definitive surgery was not significantly different. Univariate analysis revealed preoperative shock, associated medical illness and surgical delay to be significant factors for mortality whereas on multivariate analysis, preoperative shock was the only independent predictor of mortality. Mortality increased with increasing Boey score but the association between the type of surgery and probability of survival was not statistically significant. Boey risk score is useful in predicting the outcome of surgical treatment for gastric perforation. Definitive surgery is not associated with greater morbidity or mortality compared to simple closure.

Disease networks. Uncovering disease-disease relationships through the incomplete interactome.

PubMed

Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan Dina; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

2015-02-20

According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes. Copyright © 2015, American Association for the Advancement of Science.

Some Important Diseases of Tree Fruits - Diseases of Vegetable Crops - Diseases of Grapes - Diseases of Tree Nuts.

ERIC Educational Resources Information Center

Petersen, Donald H.; And Others

This agriculture extension service publication from Pennsylvania State University consists of four sections on plant disease recognition and control. The titles of these four sections are: (1) Some Important Diseases of Tree Fruits; (2) Diseases of Vegetable Crops; (3) Diseases of Crops; and (4) Diseases of Tree Nuts. The first section discusses…

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids.

PubMed

Schick, Judith; Etschel, Philipp; Bailo, Rebeca; Ott, Lisa; Bhatt, Apoorva; Lepenies, Bernd; Kirschning, Carsten; Burkovski, Andreas; Lang, Roland

2017-07-01

Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic Corynebacterium strains directly bound to recombinant Mincle in vitro Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcRγ) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular C. diphtheriae strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors. Copyright © 2017 American Society for Microbiology.

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids

PubMed Central

Schick, Judith; Etschel, Philipp; Bailo, Rebeca; Ott, Lisa; Bhatt, Apoorva; Lepenies, Bernd; Kirschning, Carsten

2017-01-01

ABSTRACT Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic Corynebacterium strains directly bound to recombinant Mincle in vitro. Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcRγ) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular C. diphtheriae strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors. PMID:28483856

Preliminary investigation into the prevalence of mucormycosis in the platypus (Ornithorhynchus anatinus) in three catchments in north-west Tasmania.

PubMed

Macgregor, J W; Holyoake, C S; Munks, S A; Robertson, I D; Warren, K S

2010-05-01

To investigate the distribution and prevalence of mucormycosis in platypus (Ornithorhynchus anatinus) from the Inglis, Emu and Black-Detention catchment areas in north-west Tasmania. A field study was performed and resulted in the examination of 44 wild platypuses; in addition, one dead platypus and two live platypuses were examined after they were independently submitted to a local veterinary clinic. No cases of mucormycosis were conclusively diagnosed. One platypus with signs consistent with those previously described in cases of mucormycosis was captured in the Emu River catchment. However, laboratory tests did not provide a definitive diagnosis for the lesion. Two platypuses from the Inglis catchment area had signs very similar to those previously described in cases of mucormycosis, but laboratory tests found Corynebacterium ulcerans to be the likely cause of the cutaneous ulcers on one of these platypuses and an unidentified fungal agent to be the cause of a cutaneous nodule in the other. These findings do not prove that mucormycosis is absent from the populations studied. However, they may indicate that the prevalence of disease is low. The possibility that Mucor amphibiorum is present in a subclinical form in platypuses, or infecting another reservoir, is not excluded. The findings also suggest that caution should be exercised when diagnosing mucormycosis based on clinical findings alone and raise the possibility that some cases may have been incorrectly diagnosed.

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia

PubMed Central

Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

2016-01-01

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1–14.8), with the highest incidence in age groups 5–19 and 40–49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. PMID:27934582

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia.

PubMed

Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

2016-12-01

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. This article is copyright of The Authors, 2016.

Contribution to the taxonomy of haemolytic corynebacteria.

PubMed

Julák, J; Mára, M; Patocka, F; Potuzníková, B; Zadrazil, S

1978-01-01

In an attempt to assess the taxonomic relationships among human (Corynebacterium haemolyticum), animal (Corynebacterium pyogenes bovis) haemolytic corynebacteria, typical corynebacteria (Corynebacterium diphteriae mitis, C. ovis, C. ulcerans) and group A and G streptococci, a number of biochemical parameters were established: the DNA content of G + C, the presence of the cytochrome system, composition of fatty acids in free lipids and production of carboxylic acids as end products of fermentation. It was found that according to the above criteria, streptococci differed significantly from the corynebacteria studied. In addition, it was possible to differentiate a subgroup of typically aerobic haemolytic corynebacteria (different from both human and animal corynebacteria), possessing a complete cytochrome system, producing propionic acid and having a different composition of fatty acids.

Contribution to the taxonomy of haemolytic corynebacteria.

PubMed

Julák, J; Mára, M; Patočka, F; Potužníková, B; Zadražil, S

1978-05-01

In an attempt to assess the taxonomic relationships among human (Corynebacterium haemolyticum), animal (Corynebacterium pyogenes bovis) haemolytio corynebacteria, typical corynebacteria (Corynebacterium diphteriae mitis, C. ovis, C. ulcerans) and group A and G streptococci, a number of biochemical parameters were established: the DNA content of G + C, the presence of the cytochrome system, composition of fatty acids in free lipids and production of carboxylic acids as end products of fermentation. It was found that according to the above criteria, streptococci differed significantly from the corynebacteria studied. In addition, it was possible to differentiate a subgroup of typically aerobic haemolytic corynebacteria (different from both human and animal corynebacteria), possessing a complete cytochrome system, producing propionic acid and having a different composition of fatty acids.

Renal disease in patients with celiac disease.

PubMed

Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

2018-04-01

Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.

Inflammatory bowel disease and airway diseases.

PubMed

Vutcovici, Maria; Brassard, Paul; Bitton, Alain

2016-09-14

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

[Periodontal disease in pediatric rheumatic diseases].

PubMed

Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A

2014-01-01

Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Coronary Artery Disease - Coronary Heart Disease

MedlinePlus

... disease even for nonsmokers. Learn about smoking and cardiovascular disease High blood cholesterol As blood cholesterol rises, so ... Overweight and obese adults with risk factors for cardiovascular disease such as high blood pressure, high cholesterol, or ...

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

Large-Scale Discovery of Disease-Disease and Disease-Gene Associations

PubMed Central

Gligorijevic, Djordje; Stojanovic, Jelena; Djuric, Nemanja; Radosavljevic, Vladan; Grbovic, Mihajlo; Kulathinal, Rob J.; Obradovic, Zoran

2016-01-01

Data-driven phenotype analyses on Electronic Health Record (EHR) data have recently drawn benefits across many areas of clinical practice, uncovering new links in the medical sciences that can potentially affect the well-being of millions of patients. In this paper, EHR data is used to discover novel relationships between diseases by studying their comorbidities (co-occurrences in patients). A novel embedding model is designed to extract knowledge from disease comorbidities by learning from a large-scale EHR database comprising more than 35 million inpatient cases spanning nearly a decade, revealing significant improvements on disease phenotyping over current computational approaches. In addition, the use of the proposed methodology is extended to discover novel disease-gene associations by including valuable domain knowledge from genome-wide association studies. To evaluate our approach, its effectiveness is compared against a held-out set where, again, it revealed very compelling results. For selected diseases, we further identify candidate gene lists for which disease-gene associations were not studied previously. Thus, our approach provides biomedical researchers with new tools to filter genes of interest, thus, reducing costly lab studies. PMID:27578529

Cardiovascular disease biomarkers across autoimmune diseases.

PubMed

Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

2015-11-01

Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Prion Diseases as Transmissible Zoonotic Diseases

PubMed Central

Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

2013-01-01

Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt–Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea. PMID:24159531

Link Between Celiac Disease and Inflammatory Bowel Disease.

PubMed

Shah, Ayesha; Walker, Marjorie; Burger, Daniel; Martin, Neal; von Wulffen, Moritz; Koloski, Natasha; Jones, Mike; Talley, Nicholas J; Holtmann, Gerald J

2018-05-14

The aim of this analysis was to assess in patients with inflammatory bowel disease (IBD) the risk of celiac disease and in celiac disease patients the risk of IBD. Previous studies report a possible association between IBD and celiac disease; however, this link is controversial. Using the search terms "inflammatory bowel disease" and "celiac disease," we identified initially 1525 publications. In total 27 studies met inclusion criteria. Proportions and 95% confidence intervals (CIs) for the prevalence of IBD in celiac disease and vice versa were compared with published prevalence rates for the respective geographic regions. We included 41,482 adult IBD patients (20,357 with Crohn's disease; 19,791 with ulcerative colitis; and 459 patients with celiac disease). Overall, in IBD patients the prevalence of celiac disease was 1110/100,000 (95% CI, 1010-1210/100,000) as compared with a prevalence of 620/100,000 (95% CI, 610-630/100,000) in the respective populations (odds ratio, 2.23; 95% CI, 1.99-2.50). In contrast, in patients with celiac disease, 2130/100,000 had IBD (95% CI, 1590-2670/100,000) as compared with 260/100,000 (95% CI, 250/100,000-270/100,000) in the respective populations (odds ratio, 11.10; 95% CI, 8.55-14.40). This effect was not different for ulcerative colitis and Crohn's disease. Although there was no evidence for publication bias for celiac disease in IBD, the funnel plot suggested that the association between IBD in celiac disease might be influenced by publication bias. The data are consistent with the notion that celiac disease is a risk factor for IBD and to lesser degree patients with IBD have an increased risk of celiac disease.

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

PubMed

Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

2011-01-01

Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

Future targeted disease modifying drugs for Alzheimer's disease.

PubMed

Dash, Sandip K

2011-01-01

Alzheimer's disease is the most common form of dementia. Alzheimer's disease will be responsible for an enormous burden on the individual and the society, as with the aging of the population, the incidence and the prevalence will grow. Presently, the drugs used in Alzheimer's disease are only effective symptomatically and improve functioning. They do not halt the progression of the disease. With the recent advances in our understanding of the pathogenesis of this disease, there have been tremendous advances in the clinical trials of compounds that can modify the disease process. Numerous therapeutic interventions and neuroprotective approaches are also in trial phase. It seems that in near future some of these compounds may be found effective and safe for use in this disease there by reducing the incidence of this disease in years to come, thereby lessen the burden due to it. In this article various compounds that can modify the course of the disease are discussed. Some recent patents and inventions for the treatment of Alzheimer's disease have also been discussed.

The Relationship Between Fatty Liver Disease and Periodontal Disease

DTIC Science & Technology

2017-03-22

Periodontitis is a highly prevalent and destructive chronic disease. Numerous studies support an association between periodontal disease and other...systemic diseases (diabetes, cardiovascular disease, chronic kidney disease, adverse pregnancy outcome, etc.). Non-alcoholic fatty liver disease is a... chronic inflammatory disease that is characterized by accumulation of triglycerides and fat in the liver which may lead to fibrosis and even cirrhosis

Heart Disease

MedlinePlus

... receive Heart Disease and Stroke email updates Submit Heart disease Heart disease is the number one killer of ... about heart disease on other websites View more Heart disease resources Related information Heart-healthy eating Diabetes Stress ...

A pathway-based view of human diseases and disease relationships.

PubMed

Li, Yong; Agarwal, Pankaj

2009-01-01

It is increasingly evident that human diseases are not isolated from each other. Understanding how different diseases are related to each other based on the underlying biology could provide new insights into disease etiology, classification, and shared biological mechanisms. We have taken a computational approach to studying disease relationships through 1) systematic identification of disease associated genes by literature mining, 2) associating diseases to biological pathways where disease genes are enriched, and 3) linking diseases together based on shared pathways. We identified 4,195 candidate disease associated genes for 1028 diseases. On average, about 50% of disease associated genes of a disease are statistically mapped to pathways. We generated a disease network which consists of 591 diseases and 6,931 disease relationships. We examined properties of this network and provided examples of novel disease relationships which cannot be readily captured through simple literature search or gene overlap analysis. Our results could potentially provide insights into the design of novel, pathway-guided therapeutic interventions for diseases.

Parkinson's Disease

MedlinePlus

... Staying Safe Videos for Educators Search English Español Parkinson's Disease KidsHealth / For Kids / Parkinson's Disease What's in this ... symptoms of something called Parkinson's disease. What Is Parkinson's Disease? Parkinson's disease is a disorder of the central ...

[Medical therapy of inflammatory bowel diseases: Crohn's disease].

PubMed

Lakatos, László; Lakatos, Péter László

2007-06-17

The therapy of inflammatory bowel diseases is based on 5-aminosalicylates (5-ASAs) that are the forefront of treatment of mild-to-moderate active disease and maintenance; steroids are used for the treatment of moderate-to-severe active disease; immunosuppressives and sometimes antibiotics in moderate-to-severe disease; maintenance and for the treatment of selected complications. The last few years have witnessed a significant change in the treatment of Crohn's disease. Based on evidence from new clinical studies and recent meta-analyses, the role of and indications for conventional therapy have been reassessed. The 5-ASAs are nowadays less frequently used in both active disease and maintenance therapy. Instead, budesonide has been introduced in the treatment of mild-to-moderate ileal disease. Besides the modest use of 5-ASAs, steroids are prescribed for active colonic disease. Immunosuppressives, especially azathioprine, are more commonly used in moderate-to-severe disease as well as in maintenance. The preferred maintenance regimen following medically- and surgically-induced remission, in addition to relationship between medical and surgical therapies, has also changed. The recent introduction of new "biological" therapy represents a major, promising change in the therapy of resistant and penetrating disease.

Gaucher Disease

MedlinePlus

... of the disease, but the procedure carries a high risk and is rarely performed in individuals with Gaucher disease. People with Gaucher disease type 1 are at increased risk for Parkinson's disease and Lewy Body Dementia. Gaucher disease type 2 is usually fatal ...

NIH disease funding levels and burden of disease.

PubMed

Gillum, Leslie A; Gouveia, Christopher; Dorsey, E Ray; Pletcher, Mark; Mathers, Colin D; McCulloch, Charles E; Johnston, S Claiborne

2011-02-24

An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.

SpliceDisease database: linking RNA splicing and disease.

PubMed

Wang, Juan; Zhang, Jie; Li, Kaibo; Zhao, Wei; Cui, Qinghua

2012-01-01

RNA splicing is an important aspect of gene regulation in many organisms. Splicing of RNA is regulated by complicated mechanisms involving numerous RNA-binding proteins and the intricate network of interactions among them. Mutations in cis-acting splicing elements or its regulatory proteins have been shown to be involved in human diseases. Defects in pre-mRNA splicing process have emerged as a common disease-causing mechanism. Therefore, a database integrating RNA splicing and disease associations would be helpful for understanding not only the RNA splicing but also its contribution to disease. In SpliceDisease database, we manually curated 2337 splicing mutation disease entries involving 303 genes and 370 diseases, which have been supported experimentally in 898 publications. The SpliceDisease database provides information including the change of the nucleotide in the sequence, the location of the mutation on the gene, the reference Pubmed ID and detailed description for the relationship among gene mutations, splicing defects and diseases. We standardized the names of the diseases and genes and provided links for these genes to NCBI and UCSC genome browser for further annotation and genomic sequences. For the location of the mutation, we give direct links of the entry to the respective position/region in the genome browser. The users can freely browse, search and download the data in SpliceDisease at http://cmbi.bjmu.edu.cn/sdisease.

Disease staging as a measure of disease severity.

PubMed

Kohyama, Jun; Fujitani, Shigeki; Umesato, Yoshimasa; Kataoka, Hitomi

2015-06-24

Disease staging, first developed in 1970, has been used to assess the levels of biological severity, defined as the risk of organ failure or death, of specific medical diseases. Because few studies to date have evaluated disease staging in Japan, a small pilot study was designed to determine whether disease staging is available and useful in actual medical practice in Japan. The relationships between disease staging and length of stay, medical costs and age were retrospectively evaluated in patients admitted to Japan Association for Development of Community Medicine - Tokyo Bay Urayasu Ichikawa Medical Center for appendicitis, type 2 diabetes mellitus, and cerebrovascular diseases from April 2012 to March 2013. Patients were easily staged based on information at the time of hospital discharge. Disease stages were found to be affected significantly by length of hospital stay and medical costs. Age also affected disease stages in patients with appendicitis. These findings indicate that disease staging was available in Japan and was affected by hospital resources, including length of hospital stay and medical costs.

[Nomadic plastic surgery: 1 NGO, 10 years, 30 missions].

PubMed

Knipper, P; Antoine, P; Carré, C; Baudet, J

2015-06-01

This publication presents the results of 10 years of nomadic plastic surgery missions by a small French non-governmental organization: Interplast-France/surgery without borders (www.Interplast-France.net). This NGO is specialized in reconstructive surgery in challenging conditions and works in developing countries. We present a view of 10 years of missions carried out between 2003 and 2013. This experience covers a uniform period both by the objectives proposed and the regularity of missions observed. This work shows the way surgical missions take place and the methodology used. We carried out 30 missions. We made more than 4000 consultations and we operated 1500 patients. Interventions are divided into one quarter cleft, one quarter tumors, one quarter burn injuries and one quarter of various diseases such as noma and Buruli ulcer. We show some adaptations such as autonomy during missions, the adjustment guidance in relation to this new environment and the integration of local traditions in our therapeutic action. We offer practical notions on the surgical procedures and some reflections on the societal level. This work aims primarily to pay tribute to all the invisible actors in this long chain of humanity, and thanks to the simple intervention of men, a patient can have the same medical treatment whether he is in an industrial country or in some isolated place on this earth. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Women's Heart Disease: Heart Disease Risk Factors

MedlinePlus

... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

Mining disease state converters for medical intervention of diseases.

PubMed

Dong, Guozhu; Duan, Lei; Tang, Changjie

2010-02-01

In applications such as gene therapy and drug design, a key goal is to convert the disease state of diseased objects from an undesirable state into a desirable one. Such conversions may be achieved by changing the values of some attributes of the objects. For example, in gene therapy one may convert cancerous cells to normal ones by changing some genes' expression level from low to high or from high to low. In this paper, we define the disease state conversion problem as the discovery of disease state converters; a disease state converter is a small set of attribute value changes that may change an object's disease state from undesirable into desirable. We consider two variants of this problem: personalized disease state converter mining mines disease state converters for a given individual patient with a given disease, and universal disease state converter mining mines disease state converters for all samples with a given disease. We propose a DSCMiner algorithm to discover small and highly effective disease state converters. Since real-life medical experiments on living diseased instances are expensive and time consuming, we use classifiers trained from the datasets of given diseases to evaluate the quality of discovered converter sets. The effectiveness of a disease state converter is measured by the percentage of objects that are successfully converted from undesirable state into desirable state as deemed by state-of-the-art classifiers. We use experiments to evaluate the effectiveness of our algorithm and to show its effectiveness. We also discuss possible research directions for extensions and improvements. We note that the disease state conversion problem also has applications in customer retention, criminal rehabilitation, and company turn-around, where the goal is to convert class membership of objects whose class is an undesirable class.

MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases

PubMed Central

2011-01-01

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress. PMID:22194706

Periodontal disease.

PubMed

Niemiec, Brook A

2008-05-01

Periodontal disease is the most commonly diagnosed problem in small animal veterinary medicine. In the vast majority of cases, however, there are little to no outward clinical signs of the disease process, and, therefore, therapy often comes very late in the disease course. Consequently, periodontal disease is also the most undertreated animal health problem. In addition, unchecked periodontal disease has numerous dire consequences both locally and systemically. These consequences are detailed in the article and should be utilized to educate clients and encourage compliance of therapeutic recommendations. The local consequences include oronasal fistulas, class II perio-endo lesions, pathologic fractures, ocular problems, osteomyelitis, and an increased incidence of oral cancer. Systemic diseases linked to periodontal disease include: renal, hepatic, pulmonary, and cardiac diseases; osteoporosis, adverse pregnancy effects, and diabetes mellitus. Before the discussion of consequences, this article covers the pathogenesis of periodontal disease, followed by clinical features and diagnostic tests.

Cardiovascular Disease Risk in Children With Kidney Disease.

PubMed

Sethna, Christine B; Merchant, Kumail; Reyes, Abigail

2018-05-01

Cardiovascular disease is a major cause of death in individuals diagnosed with kidney disease during childhood. Children with kidney disease often incur a significant cardiovascular burden that leads to increased risk for cardiovascular disease. Evidence has shown that children with kidney disease, including chronic kidney disease, dialysis, kidney transplantation, and nephrotic syndrome, develop abnormalities in cardiovascular markers such as hypertension, dyslipidemia, left ventricular hypertrophy, left ventricular dysfunction, atherosclerosis, and aortic stiffness. Early identification of modifiable risk factors and treatment may lead to a decrease of long-term cardiovascular morbidity and mortality, but evidence in this population is lacking. Copyright © 2018 Elsevier Inc. All rights reserved.

Nonalcoholic fatty liver disease - A multisystem disease?

PubMed Central

Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease.

PubMed

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-07-28

To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 +/- 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 +/- 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

Chronic Inflammatory Disease, Lifestyle and Risk of Disease

ClinicalTrials.gov

2018-04-06

Autoimmune Diseases; Inflammatory Bowel Diseases; Crohn Disease (CD); Ulcerative Colitis (UC); Arthritis, Rheumatoid (RA); Spondylarthropathies; Arthritis, Psoriatic (PsA); Psoriasis (PsO); Multiple Sclerosis (MS)

The Disease Portals, disease-gene annotation and the RGD disease ontology at the Rat Genome Database.

PubMed

Hayman, G Thomas; Laulederkind, Stanley J F; Smith, Jennifer R; Wang, Shur-Jen; Petri, Victoria; Nigam, Rajni; Tutaj, Marek; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary

2016-01-01

The Rat Genome Database (RGD;http://rgd.mcw.edu/) provides critical datasets and software tools to a diverse community of rat and non-rat researchers worldwide. To meet the needs of the many users whose research is disease oriented, RGD has created a series of Disease Portals and has prioritized its curation efforts on the datasets important to understanding the mechanisms of various diseases. Gene-disease relationships for three species, rat, human and mouse, are annotated to capture biomarkers, genetic associations, molecular mechanisms and therapeutic targets. To generate gene-disease annotations more effectively and in greater detail, RGD initially adopted the MEDIC disease vocabulary from the Comparative Toxicogenomics Database and adapted it for use by expanding this framework with the addition of over 1000 terms to create the RGD Disease Ontology (RDO). The RDO provides the foundation for, at present, 10 comprehensive disease area-related dataset and analysis platforms at RGD, the Disease Portals. Two major disease areas are the focus of data acquisition and curation efforts each year, leading to the release of the related Disease Portals. Collaborative efforts to realize a more robust disease ontology are underway. Database URL:http://rgd.mcw.edu. © The Author(s) 2016. Published by Oxford University Press.

Celiac disease and new diseases related to gluten

PubMed

Jiménez Ortega, Ana Isabel; Martínez García, Rosa María; Quiles Blanco, María José; Majid Abu Naji, Jamil Abdel; González Iglesias, María José

2016-07-12

Celiac disease is the most common chronic intestinal disease. Nowadays it´s known that this is a multisistemic pathology of immune mechanism, triggered by gluten, which occurs in genetically susceptible individuals. It affects approximately 1% of the world population, which is a very high prevalence, affects all age groups and has symptoms both digestive and extra-digestive. Since it is a disease that requires maintaining a gluten-free diet and medical monitoring for life, it is important to know it and establish its diagnosis properly. Along with celiac disease a number of new diseases related to gluten are diagnosed increasingly, including the non celiac gluten sensitivity or wheat allergy. The suffering of celiac disease, or other related diseases, by conditioning diet changes of the affected individual, it may be associated with nutritional imbalances that need to monitor and try to solve. Therefore patients with this problem need special nutritional advice.

Heart Disease

MedlinePlus

... vary by type of heart disease. Causes of cardiovascular disease While cardiovascular disease can refer to different heart or blood vessel ... Atherosclerosis is also the most common cause of cardiovascular disease. It can be caused by correctable problems, such ...

Dermatological diseases in patients with chronic kidney disease.

PubMed

Gagnon1, Amy L; Desai, Tejas

2013-04-01

There are a variety of dermatological diseases that are more commonly seen in patients with chronic kidney disease (CKD) and renal transplants than the general population. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Some cutaneous diseases are clearly unique to this population. Of them, Lindsay's Nails, xerosis cutis, dryness of the skin, nephrogenic systemic fibrosis and acquired perforating dermatosis have been described in chronic kidney disease patients. The most common malignancy found in all transplant recipients is non-melanoma skin cancer. It is important for patients and physicians to recognize the manifestations of skin disease in patients suffering from chronic kidney disease to mitigate the morbidity associated with these conditions.

Fabry Disease

MedlinePlus

... Page You are here Home » Disorders » All Disorders Fabry Disease Information Page Fabry Disease Information Page What research is being done? The ... treat and prevent lipid storage diseases such as Fabry disease. Researchers hope to identify biomarkers--signs that may ...

Heart Diseases

MedlinePlus

... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

PubMed

Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

2016-01-01

Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population.

A conceptual disease model for adult Pompe disease.

PubMed

Kanters, Tim A; Redekop, W Ken; Rutten-Van Mölken, Maureen P M H; Kruijshaar, Michelle E; Güngör, Deniz; van der Ploeg, Ans T; Hakkaart, Leona

2015-09-15

Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions. We conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making.

Dermatological diseases in patients with chronic kidney disease

PubMed Central

Gagnon1, Amy L.; Desai, Tejas

2013-01-01

Context: There are a variety of dermatological diseases that are more commonly seen in patients with chronic kidney disease (CKD) and renal transplants than the general population. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Results: Some cutaneous diseases are clearly unique to this population. Of them, Lindsay’s Nails, xerosis cutis, dryness of the skin, nephrogenic systemic fibrosis and acquired perforating dermatosis have been described in chronic kidney disease patients. The most common malignancy found in all transplant recipients is non-melanoma skin cancer. Conclusions: It is important for patients and physicians to recognize the manifestations of skin disease in patients suffering from chronic kidney disease to mitigate the morbidity associated with these conditions. PMID:24475435

Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

PubMed

Arora, Umang; Kedia, Saurabh; Garg, Prerna; Bopanna, Sawan; Jain, Saransh; Yadav, Dawesh P; Goyal, Sandeep; Gupta, Vipin; Sahni, Peush; Pal, Sujoy; Dash, Nihar Ranjan; Madhusudhan, Kumble Seetharama; Sharma, Raju; Makharia, Govind; Ahuja, Vineet

2018-06-01

The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

Comparison of phenotypic and genotypic methods for detection of diphtheria toxin among isolates of pathogenic corynebacteria.

PubMed

Efstratiou, A; Engler, K H; Dawes, C S; Sesardic, D

1998-11-01

We have compared molecular, immunochemical, and cytotoxic assays for the detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans originally isolated in five different countries. The suitabilities and accuracies of these assays for the laboratory diagnosis of diphtheria were compared and evaluated against the "gold standard" in vivo methods. The in vivo and Vero cell cytotoxicity assays were accurate in their abilities to detect diphtheria toxin but were time-consuming; however, the cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence test. There was complete concordance between all the phenotypic methods. Genotypic tests based upon PCR were rapid; however, PCR must be used with caution because some isolates of C. diphtheriae possessed toxin genes but failed to express a biologically active toxin. Therefore, phenotypic confirmation of toxigenicity for the microbiological diagnosis of diphtheria is recommended.

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease

PubMed Central

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-01-01

AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn’s disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients. PMID:19630105

[Coexistence of coeliac disease and inflammatory bowel disease in children].

PubMed

Krawiec, Paulina; Pawłowska-Kamieniak, Agnieszka; Pac-Kożuchowska, Elżbieta; Mroczkowska-Juchkiewcz, Agnieszka; Kominek, Katarzyna

2016-01-01

Coeliac disease and inflammatory bowel disease are chronic inflammatory conditions of gastrointestinal tract with complex aetiology with genetic, environmental and immunological factors contributing to its pathogenesis. It was noted that immune-mediated disorders often coexist. There is well-known association between coeliac disease and type 1 diabetes and ulcerative colitis and primary sclerosing cholangitis. However, growing body of literature suggests the association between coeliac disease and inflammatory bowel disease, particularly ulcerative colitis. This is an extremely rare problem in paediatric gastroenterology. To date there have been reported several cases of children with coexisting coeliac disease and inflammatory bowel disease. Herewith we present review of current literature on coexistence of coeliac disease and inflammatory bowel disease in children. © 2016 MEDPRESS.

[Valvular heart disease associated with coronary artery disease].

PubMed

Yildirir, Aylin

2009-07-01

Nowadays, age-related degenerative etiologies have largely replaced the rheumatic ones and as a natural result of this etiologic change, coronary artery disease has become associated with valvular heart disease to a greater extent. Degenerative aortic valve disease has an important pathophysiological similarity to atherosclerosis and is the leader in this association. There is a general consensus that severely stenotic aortic valve should be replaced during bypass surgery for severe coronary artery disease. For moderate degree aortic stenosis, aortic valve replacement is usually performed during coronary bypass surgery. Ischemic mitral regurgitation has recently received great attention from both diagnostic and therapeutic points of view. Ischemic mitral regurgitation significantly alters the prognosis of the patient with coronary artery disease. Severe ischemic mitral regurgitation should be corrected during coronary bypass surgery and mitral valve repair should be preferred to valve replacement. For moderate degree ischemic mitral regurgitation, many authors prefer valve surgery with coronary bypass surgery. In this review, the main characteristics of patients with coronary artery disease accompanying valvular heart disease and the therapeutic options based on individual valve pathology are discussed.

Disease phobia and disease conviction are separate dimensions underlying hypochondriasis.

PubMed

Fergus, Thomas A; Valentiner, David P

2010-12-01

The current study uses data from a large nonclinical college student sample (N = 503) to examine a structural model of hypochondriasis (HC). This model predicts the distinctiveness of two dimensions (disease phobia and disease conviction) purported to underlie the disorder, and that these two dimensions are differentially related to variables important to health anxiety and somatoform disorders, respectively. Results were generally consistent with the hypothesized model. Specifically, (a) body perception variables (somatosensory amplification and anxiety sensitivity - physical) emerged as significant predictors of disease phobia, but not disease conviction; (b) emotion dysregulation variables (cognitive avoidance and cognitive reappraisal) emerged as significant predictors of disease conviction, but not disease phobia; and (c) both disease phobia and disease conviction independently predicted medical utilization. Further, collapsing disease phobia and disease conviction onto a single latent factor provided an inadequate fit to the data. Conceptual and therapeutic implications of these results are discussed. 2010 Elsevier Ltd. All rights reserved.

Lyme Disease

PubMed Central

Murray, Thomas S.; Shapiro, Eugene D.

2013-01-01

Synopsis Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicrobials for from 2-4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with non-specific symptoms such as fatigue or arthralgia without signs of infection. PMID:20513553

Mondor's disease of penis: a forgotten disease.

PubMed

Kumar, B; Narang, T; Radotra, B D; Gupta, S

2005-12-01

Mondor's disease of penis is an uncommon genital condition involving the penile sulcus in a circumferential manner. Although this disorder is almost always self limited, it is associated with considerable psychological stress and sexual disharmony. All patients attending the sexually transmitted disease clinic during 1991-2003 were examined for evidence of Mondor's disease of penis. Detailed history and clinical findings were recorded in a specially designed proforma. Histopathological examination and staining with CD31 and CD34 monoclonal antibodies was also done in 11 patients. 18 out of 1296 patients attending the sexually transmitted diseases (STD) clinic during the study period were found to have penile Mondor's disease, giving an incidence of 1.39%. 17 patients had history of one or more episodes of STDs. Histopathological specimens showed prominent vessels with plump endothelial cells and thickened blood vessel walls. The occasional vessel showed complete occlusion of its lumen. In our study we did not find any evidence of lymphatic involvement. Non-lymphatic vessels, mainly veins, were predominantly involved. In our opinion Mondor's phlebitis of penis or Mondor's disease of penis are better terms to describe the condition rather than non-venereal sclerosing lymphangitis.

Meningococcal Disease

MedlinePlus

... and Control of Meningococcal Disease Resources Beyond the Science: Putting a Face on Meningococcal Disease National Meningitis Association Facts about Meningococcal Disease for Adults adultvaccination.org Meningococcal ...

Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

PubMed

Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

2011-01-01

The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

The "fourth disease" of childhood: reevaluation of a nonexistent disease.

PubMed

Morens, D M; Katz, A R

1991-09-15

Observed and described between 1884 and 1900, "fourth disease" (Dukes disease) followed measles, scarlet fever, and rubella as the fourth clinically characterized childhood exanthem. Like rubella ("third disease") and erythema infectiosum ("fifth disease"), accepted by the medical community at about the same time, the existence of fourth disease was initially controversial. Over the following decades descriptions of hundreds of cases, outbreaks, and laboratory studies were published in the indexed medical literature. Unlike rubella and fifth disease, however, fourth disease was not subsequently proven to exist by either epidemiologic criteria or isolation of an etiologic agent. By the 1930s, it was infrequently recognized and by the 1960s had been dropped from textbooks. In this study, the authors use epidemiologic methods to reevaluate published data on English schoolchildren from 1892 to 1900 upon which the original fourth disease claim of Dukes was based. The authors conclude that fourth disease never existed. Reinterpretation of the original data suggests that cases can be completely explained as misdiagnosed rubella and scarlet fever. Misidentification of fourth disease is attributed to failures in the critical abilities of the medical and scientific communities at the time. The implications of erroneously identifying a nonexistent disease suggest that modern scientific approaches to disease identification are sound.

Periodontal Disease and Systemic Diseases: An Update for the Clinician.

PubMed

John, Vanchit; Alqallaf, Hawra; De Bedout, Tatiana

2016-01-01

A link between periodontal disease and various systemic diseases has been investigated for several years. Interest in unearthing such a link has grown as the health care profession is looking for a better understanding of disease processes and their relationships to periodontal and other oral diseases. The article aims to provide recent information on the relationship between periodontal disease and systemic diseases such as; cardiovascular, respiratory, endocrine, musculoskeletal, and reproductive system related abnormalities.

Addison's disease.

PubMed

Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar

2012-10-01

Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered.

Addison's disease

PubMed Central

Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar

2012-01-01

Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered. PMID:23633816

Lysosomal storage diseases

PubMed Central

Ferreira, Carlos R.; Gahl, William A.

2016-01-01

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458

[Inpatients days in patients with respiratory diseases and periodontal disease].

PubMed

Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; González-Cruz, Herminia; Casa-Medina, Guillermo; García-Sancho, Cecilia

2017-01-01

Periodontal disease is a chronic inflammatory gingival process that has been associated with the severity of respiratory diseases. In Mexico a prevalence of 78% was found in population with social security and > 60 years old. The aim of this study is to establish the association between periodontal disease and respiratory diseases according to the inpatient days. A cross-sectional study was conducted from January to December 2011. We included hospitalized patients, ≥ 18 years of age, without sedation or intubated. A dentist classified patients into two groups according to the severity of the periodontal disease: mild-to-moderate and severe. We estimated medians of inpatient days by disease and severity. Negative binomial models were adjusted to estimate incidence rate ratios and predicted inpatient days. 3,059 patients were enrolled. The median of observed and predicted inpatient days was higher in the group of severe periodontal disease (p < 0.05). Patients with chronic obstructive pulmonary disease, tuberculosis, and influenza had the highest incidence rates ratios of periodontal disease (p < 0.05). The severity of periodontal disease is positively -associated with inpatient days of patients with respiratory diseases.

Parkinson's Disease

MedlinePlus

... Education Visitor Information RePORT NIH Fact Sheets Home > Parkinson’s Disease Small Text Medium Text Large Text Parkinson’s Disease Parkinson’s disease (PD) is a neurodegenerative disorder, that ...

Prevalence of coeliac disease in Italian patients affected by Addison's disease.

PubMed

Biagi, Federico; Campanella, Jonia; Soriani, Alessandra; Vailati, Alberto; Corazza, Gino R

2006-03-01

It is well known that coeliac disease is associated with autoimmune endocrine diseases, such as autoimmune thyroid disease and insulin-dependent diabetes mellitus. Recently, coeliac disease has been shown in approximately 10% of patients with autoimmune Addison's disease. Addison's disease is the most common cause of primary adrenocortical insufficiency and it shares several clinical features with coeliac disease. Although hyperpigmentation and hypotension are the most specific signs, gastrointestinal symptoms are common and can be the first complaints of the patients. The aim of our study was to investigate the prevalence of coeliac disease in Italian patients with Addison's disease. Seventeen consecutive patients affected by Addison's disease (14 F, mean age 53.9 years, range 26-79 years) were enrolled in the study. Eleven of them were affected by Addison's disease associated with autoimmune thyroid disease and/or insulin-dependent diabetes mellitus; the other 6 patients were suffering from isolated Addison's disease. Diagnosis had been performed at the age of 40.5 years (range 23-55). Steroid treatment had already been started in 16 of the patients. Endomysial antibodies were tested in all of them and a duodenal biopsy was taken in those found to be positive for antiendomysial antibody (EMA). One out of 17 patients was found to be EMA positive. Duodenal biopsy confirmed the diagnosis of coeliac disease by showing subtotal villous atrophy. Although we studied only a small sample, our preliminary results confirmed that Addison's disease is associated with coeliac disease, being present in 5.9% of patients with Addison's disease. Since the symptoms can be similar and treatment of Addison's disease can mask coeliac disease, this association should always be actively investigated.

Inflammatory Bowel Disease and the Risk of Autoimmune Diseases.

PubMed

Wilson, J Claire; Furlano, Raoul I; Jick, Susan S; Meier, Christoph R

2016-02-01

An increased risk of autoimmune disease has been reported in patients with inflammatory bowel disease [IBD]. Using data from the Clinical Practice Research Datalink [CPRD], this study set out to further examine this relationship. Patients with a first-time IBD diagnosis were randomly matched to an equal-sized IBD-free comparison group. Incidence rates for new-onset autoimmune diseases were estimated. A nested case-control analysis comprising IBD patients was conducted, using conditional logistic regression to assess whether IBD severity, duration, or treatment influences the risk of developing autoimmune diseases. During follow-up, 1069 IBD and 585 IBD-free patients developed an incident autoimmune disease. An increased incidence of autoimmune disease was observed in IBD patients (incidence rate [IR] 9.65, 95% confidence interval [CI] 9.09-10.24) compared with the non-IBD comparison group [IR 5.22, 95% CI 4.82-5.66]. In IBD patients, increased disease severity was associated with an increased risk of autoimmune disease development (odds ratio [OR] 1.62, 95% CI 1.28-2.05). Current antibiotic use was also associated with an increased risk [adjusted OR 1.72, 95% CI 1.07-2.78]. A reduced risk of incident autoimmune diseases was observed for current long-term users of aminosalicylates [adjusted OR 0.72, 95% CI 0.57-0.91]. Individuals with IBD had an increased risk of developing an autoimmune disease. Increased disease severity and current antibiotic use were associated with an increased relative risk of developing additional autoimmune diseases in IBD patients. Long-term current aminosalicylate use was associated with a reduced risk. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Self-perception of disease in patients with chronic diseases].

PubMed

Adrián-Arrieta, L; Casas-Fernández de Tejerina, J M

2017-11-18

The aim of this study is to assess the self-perception of disease by patients with chronic diseases and determine factors related to their perception of disease. Cross-sectional descriptive study performed between September 2014 and April 2015 in nine (6 urban and 3 rural) Health Centres of Navarra, Spain. The participants were recruited by convenience sampling of 196 patients aged over 65 years with at least one chronic disease. The outcome variable was: Perception of disease evaluated through The Brief Illness Perception Questionnaire (9 items. Assessment of the cognitive and emotional representation of the disease. A higher total score indicates a greater threat of disease to the patient). Explanatory variables: Evaluation of the care received through the Patient Assessment of Chronic Illness Care, Katz index, Gijon's socio-family evaluation scale and quality of life using the EQ5D questionnaire. Other variables studied were: gender, age, education, Charlson index, and number of chronic diseases. The association between the total The Brief Illness Perception Questionnaire value and the rest of the variables was calculated. The self-perception of disease is more negative for a larger number of diseases (rho: 0.242; p=.001), greater patient dependence (rho: -0.193; P=.007), and a poorer self-perceived quality of life (EQ VAS rho: -0.484; P<.001. EQ5D5L Index value rho: -0.507; P<.001). The perception that chronic patients have about their disease worsens as their diseases and their dependence increase, and also worsens their quality of life. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

PubMed

Campbell, Desmond D; Li, Yiming; Sham, Pak C

2018-03-01

Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported methodology based on a liability-threshold model. Multifactorial disease models incorporating all the following features in combination are handled: quantitative risk factors (including polygenic scores), categorical risk factors (including major genetic risk loci), stratified age of onset curves, and the partition of the population variance in disease liability into genetic, shared, and unique environment effects. It allows the application of such models to disease pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree members, (ii) n year risk for unaffected pedigree members, and (iii) the disease pedigree's joint liability distribution. Risk prediction for each pedigree member is based on using the constructed disease model to appropriately weigh evidence on disease risk available from personal attributes and family history. Evidence is used to construct the disease pedigree's joint liability distribution. From this, lifetime and n year risk can be predicted. Example disease models and pedigrees are provided at the website and are used in accompanying tutorials to illustrate the features available. The website is built on an R package which provides the functionality for pedigree validation, disease model construction, and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current. © 2017 WILEY PERIODICALS, INC.

Repeat expansion disease: Progress and puzzles in disease pathogenesis

PubMed Central

La Spada, Albert R.; Taylor, J. Paul

2015-01-01

Repeat expansion mutations cause at least 22 inherited neurological diseases. The complexity of repeat disease genetics and pathobiology has revealed unexpected shared themes and mechanistic pathways among the diseases, for example, RNA toxicity. Also, investigation of the polyglutamine diseases has identified post-translational modification as a key step in the pathogenic cascade, and has shown that the autophagy pathway plays an important role in the degradation of misfolded proteins – two themes likely to be relevant to the entire neurodegeneration field. Insights from repeat disease research are catalyzing new lines of study that should not only elucidate molecular mechanisms of disease, but also highlight opportunities for therapeutic intervention for these currently untreatable disorders. PMID:20177426

Screen-detected gallstone disease and autoimmune diseases - A cohort study.

PubMed

Shabanzadeh, Daniel Mønsted; Linneberg, Allan; Skaaby, Tea; Sørensen, Lars Tue; Jørgensen, Torben

2018-06-01

Gallstone disease is highly prevalent and is associated with systemic inflammation. To determine whether screen-detected gallstones or cholecystectomy are associated with the occurrence of autoimmune and autoinflammatory diseases and the most common subgroups thereof. A cohort study of three randomly selected general population samples from Copenhagen was performed. Participants (n = 5928) were examined in the period 1982-1992, underwent abdominal ultrasound examination to detect gallstone disease, and followed through national registers until December 2014 (median 24.7 years) for occurrence of immunological diseases. Multivariable Cox regression analyses were performed. Gallstone disease was identified in 10% (591/5928) of participants, of whom 6.8% had gallstones and 3.2% had cholecystectomy at baseline. Gallstone disease was associated with incidence of autoimmune diseases (12.9% versus 7.92%; hazard ratio 1.46; 95% confidence interval [CI], [1.11;1.91]), diabetes mellitus type 1 (5.95% versus 3.67%; 1.53; [1.02;2.30]), and autoimmune thyroid disease (3.70% versus 1.59%; 2.06; [1.26;3.38]). Rheumatoid arthritis, autoinflammatory diseases, or any subgroups thereof were not associated. In a large general population sample, screen-detected gallstone disease was associated with the development of autoimmune diseases during long-term follow-up. Future research efforts are needed to further explore common disease mechanisms. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Discovering disease-disease associations by fusing systems-level molecular data

PubMed Central

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-01-01

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion. PMID:24232732

Discovering disease-disease associations by fusing systems-level molecular data.

PubMed

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-11-15

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion.

[Imported diseases, the epidemiological challenge of communicable diseases (author's transl)].

PubMed

Gsell, O

1978-06-01

Imported infectious diseases being seen more often in consequence of intensive human contacts with developing countries through labourers and tourists, but also in consequence of immigration and of import of exotic diseases and of food, favoured by the quick air traffic, can be divided into 5 groups: 1. Imported diseases from the tropics (exotic diseases) 2. Imported agents from the tropics with human infection in the native country 3. Re-importation of diseases which were eliminated in the homelands 4. Diseases which are as well imported as also native 5. Single disease importations from neighboured countries. The imported infections are discussed systematically, caused by viruses, rickettsias, bacteries, protozoes, fungi, and followed by references to statistics, laboratory infection reports, questions of insurance. Imported diseases of the future are especially mentioned. Knowledge of the tropical infections as a main danger for our "civilized" world should be part of the medical training, since imported infectious diseases cause an epidemiologic challenge in the modern picture of communicable infections.

Mondor's disease of penis: a forgotten disease

PubMed Central

Kumar, B; Narang, T; Radotra, B; Gupta, S

2005-01-01

Background: Mondor's disease of penis is an uncommon genital condition involving the penile sulcus in a circumferential manner. Although this disorder is almost always self limited, it is associated with considerable psychological stress and sexual disharmony. Methods: All patients attending the sexually transmitted disease clinic during 1991–2003 were examined for evidence of Mondor's disease of penis. Detailed history and clinical findings were recorded in a specially designed proforma. Histopathological examination and staining with CD31 and CD34 monoclonal antibodies was also done in 11 patients. Results: 18 out of 1296 patients attending the sexually transmitted diseases (STD) clinic during the study period were found to have penile Mondor's disease, giving an incidence of 1.39%. 17 patients had history of one or more episodes of STDs. Histopathological specimens showed prominent vessels with plump endothelial cells and thickened blood vessel walls. The occasional vessel showed complete occlusion of its lumen. Conclusions: In our study we did not find any evidence of lymphatic involvement. Non-lymphatic vessels, mainly veins, were predominantly involved. In our opinion Mondor's phlebitis of penis or Mondor's disease of penis are better terms to describe the condition rather than non-venereal sclerosing lymphangitis. PMID:16326851

Lewy Body Disease: Clinical and Pathological "Overlap Syndrome" Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease).

PubMed

Foguem, Clovis; Manckoundia, Patrick

2018-04-08

Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics. This manuscript discusses current understanding of overlapping symptoms and the particular features of LBD, PD, and AD. It also describes features that could facilitate the diagnosis of each of these diseases. We concluded that the concept of neurodegenerative "overlap" syndrome, which includes the accepted diagnosis of LBD, may be taken in account and should contribute to clarifying LBD and definitions of close differential diagnoses. This should allow clinicians to suspect LBD at an earlier stage and provide better patient care.

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

PubMed

Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

2018-02-05

Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

Crohn's Disease

MedlinePlus

Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...

Huntington's Disease

MedlinePlus

Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste away. ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of getting ...

Parkinson's Disease

MedlinePlus

... common diseases to help prevent disease and improve human health. Explore Research Funding Opportunities Grants Grants Explore Grants ... health sciences to understand human disease and improve human health. Use the search box to see research highlights ...

Universal etiology, multifactorial diseases and the constitutive model of disease classification.

PubMed

Fuller, Jonathan

2018-02-01

Infectious diseases are often said to have a universal etiology, while chronic and noncommunicable diseases are said to be multifactorial in their etiology. It has been argued that the universal etiology of an infectious disease results from its classification using a monocausal disease model. In this article, I will reconstruct the monocausal model and argue that modern 'multifactorial diseases' are not monocausal by definition. 'Multifactorial diseases' are instead defined according to a constitutive disease model. On closer analysis, infectious diseases are also defined using the constitutive model rather than the monocausal model. As a result, our classification models alone cannot explain why infectious diseases have a universal etiology while chronic and noncommunicable diseases lack one. The explanation is instead provided by the Nineteenth Century germ theorists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recognizing global burden of cardiovascular disease and related chronic diseases.

PubMed

Kelly, Bridget B; Narula, Jagat; Fuster, Valentín

2012-01-01

Cardiovascular disease is the leading cause of death worldwide, affecting not only high-income but also low- and middle-income countries. Nearly 80 percent of all estimated cardiovascular disease-related deaths worldwide now occur in low- and middle-income countries, where nearly 30 percent of all deaths are attributable to cardiovascular disease. The health burden of cardiovascular disease and other chronic diseases is also accompanied by a significant deleterious economic impact at the level of both national economies and households. The global trends in the health and economic burden of cardiovascular disease provide a compelling argument in support of prioritizing urgent yet carefully planned efforts to prevent and control cardiovascular disease worldwide-and especially in low- and middle-income countries. After decades of escalating efforts to draw attention to the high burden of cardiovascular disease and other chronic diseases, this critically important issue is now emerging as a more central part of the global health and development agenda. The breadth of behavioral, biological, social, environmental, and systems-level factors that contribute to cardiovascular disease necessitates multisectoral approaches across the lifecourse that promote healthful lifestyles, reduce risk, and reduce cardiovascular-disease morbidity and mortality through the delivery of quality health care services. Given that the complex interactions among the determinants of cardiovascular disease vary in different contexts, real progress in control efforts will come through approaches that are driven by a country's disease burden and risk profile, capacities, resources, and priorities-approaches that are led by a country's key decision-makers and stakeholders, including governments, civil society, the private sector, and communities. Many countries are already establishing efforts to address chronic diseases. In addition to these locally driven efforts, success will require active

Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

MedlinePlus

... Adult Diseases Resources Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English (US) Español (Spanish) ... important step in staying healthy. If you have cardiovascular disease, talk with your doctor about getting your vaccinations ...

Prostate Diseases

MedlinePlus

... Home › Aging & Health A to Z › Prostate Diseases Font size A A A Print Share Glossary Basic ... body. Approximately 3 million American men have some type of prostate disease. The most common prostate diseases ...

Hodgkin Disease

MedlinePlus

... blood tests, and a biopsy. Treatment depends on how far the disease has spread. It often includes radiation therapy or chemotherapy. The earlier the disease is diagnosed, the more effective the treatment. In most cases, Hodgkin disease can ...

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

PubMed Central

Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

2018-01-01

BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection. PMID:29412344

Kyasanur Forest Disease (KFD): Rare Disease of Zoonotic Origin.

PubMed

Muraleedharan, M

2016-09-01

Kyasanur forest disease (KFD) is a rare tick borne zoonotic disease that causes acute febrile hemorrhagic illness in humans and monkeys especially in southern part of India. The disease is caused by highly pathogenic KFD virus (KFDV) which belongs to member of the genus Flavivirus and family Flaviviridae. The disease is transmitted to monkeys and humans by infective tick Haemaphysalisspinigera. Seasonal outbreaks are expected to occur during the months of January to June. The aim of this paper is to briefly summarize the epidemiology, mode of transmission of KFD virus, clinical findings, diagnosis, treatment, control and prevention of the disease..

Retinal Diseases

MedlinePlus

... You are here Home Listen Retinal Diseases Macular Degeneration Age-related macular degeneration (AMD) is a retinal degenerative disease that causes ... is the most common form of inherited juvenile macular degeneration. The progressive vision loss associated with Stargardt disease ...

Unfoldomics of human diseases: linking protein intrinsic disorder with diseases

PubMed Central

Uversky, Vladimir N; Oldfield, Christopher J; Midic, Uros; Xie, Hongbo; Xue, Bin; Vucetic, Slobodan; Iakoucheva, Lilia M; Obradovic, Zoran; Dunker, A Keith

2009-01-01

Background Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack stable tertiary and/or secondary structure yet fulfills key biological functions. The recent recognition of IDPs and IDRs is leading to an entire field aimed at their systematic structural characterization and at determination of their mechanisms of action. Bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. These activities complement the functions of structured proteins. IDPs and IDRs were shown to participate in both one-to-many and many-to-one signaling. Alternative splicing and posttranslational modifications are frequently used to tune the IDP functionality. Several individual IDPs were shown to be associated with human diseases, such as cancer, cardiovascular disease, amyloidoses, diabetes, neurodegenerative diseases, and others. This raises questions regarding the involvement of IDPs and IDRs in various diseases. Results IDPs and IDRs were shown to be highly abundant in proteins associated with various human maladies. As the number of IDPs related to various diseases was found to be very large, the concepts of the disease-related unfoldome and unfoldomics were introduced. Novel bioinformatics tools were proposed to populate and characterize the disease-associated unfoldome. Structural characterization of the members of the disease-related unfoldome requires specialized experimental approaches. IDPs possess a number of unique structural and functional features that determine their broad involvement into the pathogenesis of various diseases. Conclusion Proteins associated with various human diseases are enriched in intrinsic disorder. These disease-associated IDPs and IDRs are real, abundant, diversified, vital, and dynamic. These proteins and regions comprise the disease-related unfoldome, which covers a significant part

The lysosomal storage disease continuum with ageing-related neurodegenerative disease.

PubMed

Lloyd-Evans, Emyr; Haslett, Luke J

2016-12-01

Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing. The lysosome should no longer be considered as just the stomach of the cell or as a suicide bag, it has an emerging role in cellular signalling, nutrient sensing and recycling. The lysosome is of fundamental importance in the pathophysiology of diseases of ageing and by comparing against the LSDs we not only identify common pathways but also therapeutic targets so that ultimately more effective treatments can be developed for all neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

Coronary Artery Disease | Coronary Artery Disease | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Coronary Artery Disease Coronary Artery Disease Past Issues / Fall 2010 Table of Contents David ... up inside your arteries. One atherosclerosis-related disease, coronary artery disease (CAD) is the most common heart disease and ...

Lyme disease

MedlinePlus

... Borrelia burgdorferi Tick, deer engorged on the skin Lyme disease - Borrelia burgdorferi organism Tick, deer - adult female Lyme disease ... Accessed January 11, 2018. Steere AC. Lyme disease (Lyme borreliosis) due to Borrelia burgdorferi . In: Bennett JE, Dolin R, Blaser MJ, ...

Disease control operations

USGS Publications Warehouse

Friend, Milton; Franson, J. Christian

1987-01-01

Individual disease outbreaks have killed many thousands of animals on numerous occasions. Tens of thousands of migratory birds have died in single die-offs with as many as 1,000 birds succumbing in 1 day. In mammals, individual disease outbreaks have killed hundreds to thousands of animals with, for example, hemorrhagic disease in white-tailed deer, distemper in raccoon, Errington's disease in muskrat, and sylvatic plague in wild rodents. The ability to successfully combat such explosive situations is highly dependent n the readiness of field personnel to deal with them. Because many disease agents can spread though wildlife populations very fast, advance preparation is essential in preventing infected animals from spreading disease to additional species and locations. Carefully though-out disease contingency plans should be developed as practical working documents for field personnel and updated as necessary. Such well-designed plans can prove invaluable in minimizing wildlife losses and costs associated with disease control activities. Although requirements for disease control operations vary and must be tailored to each situation, all disease contingency planning involved general concepts and basic biological information. This chapter, intended as a practical guide, identifies the major activities and needs of disease control operations, and relates them to disease contingency planning.

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

PubMed Central

Aguisanda, Francis; Thorne, Natasha; Zheng, Wei

2017-01-01

Wolman disease (WD) and cholesteryl ester storage disease (CESD) are lysosomal storage diseases (LSDs) caused by a deficiency in lysosomal acid lipase (LAL) due to mutations in the LIPA gene. This enzyme is critical to the proper degradation of cholesterol in the lysosome. LAL function is completely lost in WD while some residual activity remains in CESD. Both are rare diseases with an incidence rate of less than 1/100,000 births for WD and approximate 2.5/100,000 births for CESD. Clinical manifestation of WD includes hepatosplenomegaly, calcified adrenal glands, severe malabsorption and a failure to thrive. As in CESD, histological analysis of WD tissues reveals the accumulation of triglycerides (TGs) and esterified cholesterol (EC) in cellular lysosomes. However, the clinical presentation of CESD is less severe and more variable than WD. This review is to provide an overview of the disease pathophysiology and the current state of therapeutic development for both of WD and CESD. The review will also discuss the application of patient derived iPSCs for further drug discovery. PMID:28401034

Prevalence of periodontal disease, its association with systemic diseases and prevention

PubMed Central

Nazir, Muhammad Ashraf

2017-01-01

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care. PMID:28539867

Prevalence of periodontal disease, its association with systemic diseases and prevention.

PubMed

Nazir, Muhammad Ashraf

2017-01-01

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.

Best practice assessment of disease modelling for infectious disease outbreaks.

PubMed

Dembek, Z F; Chekol, T; Wu, A

2018-05-08

During emerging disease outbreaks, public health, emergency management officials and decision-makers increasingly rely on epidemiological models to forecast outbreak progression and determine the best response to health crisis needs. Outbreak response strategies derived from such modelling may include pharmaceutical distribution, immunisation campaigns, social distancing, prophylactic pharmaceuticals, medical care, bed surge, security and other requirements. Infectious disease modelling estimates are unavoidably subject to multiple interpretations, and full understanding of a model's limitations may be lost when provided from the disease modeller to public health practitioner to government policymaker. We review epidemiological models created for diseases which are of greatest concern for public health protection. Such diseases, whether transmitted from person-to-person (Ebola, influenza, smallpox), via direct exposure (anthrax), or food and waterborne exposure (cholera, typhoid) may cause severe illness and death in a large population. We examine disease-specific models to determine best practices characterising infectious disease outbreaks and facilitating emergency response and implementation of public health policy and disease control measures.

Coronary heart disease

MedlinePlus

Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...

Miscellaneous fungal diseases

USGS Publications Warehouse

Friend, M.

1999-01-01

As for other types of disease, fungal infections probably are more common causes of disease in wild birds than is currently recognized. Also, the similarity in gross lesions produced by some fungi mask the detection of less common fungi as disease agents. Numerous types of disease-causing fungi in addition to Aspergillus fumigatus and Candida albicans have been isolated from birds; most isolations have been from poultry and wild birds being maintained in captivity. Enhanced disease surveillance that is often associated with privately owned birds and greater opportunity to detect disease in confined birds are reasons for these findings rather than any known differences in the occurrence of fungal diseases in free-ranging and captive birds. Many of the reported infections appear to have been opportunistic invasions by the fungi involved. The important points are that many fungi are capable of causing disease in birds but their collective impacts do not rival A. fumigatus as a single cause of disease in wild birds. Nevertheless, it is important to be aware of the diversity of pathogenic or disease causing fungi.

Meniere's Disease.

ERIC Educational Resources Information Center

Schessel, David A.

1997-01-01

Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

PubMed

van Lier, Alies; McDonald, Scott A; Bouwknegt, Martijn; Kretzschmar, Mirjam E; Havelaar, Arie H; Mangen, Marie-Josée J; Wallinga, Jacco; de Melker, Hester E

2016-01-01

Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961) and influenza (8670 DALYs/year; 95% UI: 8468-8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011

PubMed Central

Bouwknegt, Martijn; Kretzschmar, Mirjam E.; Mangen, Marie-Josée J.; Wallinga, Jacco; de Melker, Hester E.

2016-01-01

Background Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. Methods and Findings The average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five

Newcastle disease

USGS Publications Warehouse

Docherty, D.E.; Friend, M.

1999-01-01

Newcastle Disease (ND) in domestic poultry is a focus for concern throughout much of the world’s agricultural community because of severe economic losses that have occurred from illness, death, and reduced egg production following infection with pathogenic or disease causing strains. Prior to 1990, this disease had rarely been reported as a cause of mortality in the free-living native birds of the United States or Canada. Repeated large-scale losses of double-crested cormorants from ND in both countries has resulted in a need for enhanced awareness of ND as a disease of wild birds and, therefore, its inclusion within this Manual. Background information about ND in poultry is needed to provide a perspective for understanding the complexity of the disease agent, Newcastle disease virus (NDV). Some general information about ND in other avian species is also provided, but the primary focus for this chapter is the effect of NDV on double-crested cormorants.

[Emerging noninfectious diseases].

PubMed

Consiglio, Ezequiel

2008-11-01

In recent years, emerging diseases were defined as being infectious, acquiring high incidence, often suddenly, or being a threat or an unexpected phenomenon. This study discusses the hallmarks of emerging diseases, describing the existence of noninfectious emerging diseases, and elaborating on the advantages of defining noninfectious diseases as emerging ones. From the discussion of various mental health disorders, nutritional deficiencies, external injuries and violence outcomes, work injuries and occupational health, and diseases due to environmental factors, the conclusion is drawn that a wide variety of noninfectious diseases can be defined as emergent. Noninfectious emerging diseases need to be identified in order to improve their control and management. A new definition of "emergent disease" is proposed, one that emphasizes the pathways of emergence and conceptual traits, rather than descriptive features.

DiseaseConnect: a comprehensive web server for mechanism-based disease–disease connections

PubMed Central

Liu, Chun-Chi; Tseng, Yu-Ting; Li, Wenyuan; Wu, Chia-Yu; Mayzus, Ilya; Rzhetsky, Andrey; Sun, Fengzhu; Waterman, Michael; Chen, Jeremy J. W.; Chaudhary, Preet M.; Loscalzo, Joseph; Crandall, Edward; Zhou, Xianghong Jasmine

2014-01-01

The DiseaseConnect (http://disease-connect.org) is a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. The traditional disease classification system groups diseases with similar clinical symptoms and phenotypic traits. Thus, diseases with entirely different pathologies could be grouped together, leading to a similar treatment design. Such problems could be avoided if diseases were classified based on their molecular mechanisms. Connecting diseases with similar pathological mechanisms could inspire novel strategies on the effective repositioning of existing drugs and therapies. Although there have been several studies attempting to generate disease connectivity networks, they have not yet utilized the enormous and rapidly growing public repositories of disease-related omics data and literature, two primary resources capable of providing insights into disease connections at an unprecedented level of detail. Our DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease–disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug–disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments. PMID:24895436

Rheumatic heart disease: infectious disease origin, chronic care approach.

PubMed

Katzenellenbogen, Judith M; Ralph, Anna P; Wyber, Rosemary; Carapetis, Jonathan R

2017-11-29

Rheumatic heart disease (RHD) is a chronic cardiac condition with an infectious aetiology, causing high disease burden in low-income settings. Affected individuals are young and associated morbidity is high. However, RHD is relatively neglected due to the populations involved and its lower incidence relative to other heart diseases. In this narrative review, we describe how RHD care can be informed by and integrated with models of care developed for priority non-communicable diseases (coronary heart disease), and high-burden communicable diseases (tuberculosis). Examining the four-level prevention model (primordial through tertiary prevention) suggests primordial and primary prevention of RHD can leverage off existing tuberculosis control efforts, given shared risk factors. Successes in coronary heart disease control provide inspiration for similarly bold initiatives for RHD. Further, we illustrate how the Chronic Care Model (CCM), developed for use in non-communicable diseases, offers a relevant framework to approach RHD care. Systems strengthening through greater integration of services can improve RHD programs. Strengthening of systems through integration/linkages with other well-performing and resourced services in conjunction with policies to adopt the CCM framework for the secondary and tertiary prevention of RHD in settings with limited resources, has the potential to significantly reduce the burden of RHD globally. More research is required to provide evidence-based recommendations for policy and service design.

Mad Cow Disease

MedlinePlus

... Safe Videos for Educators Search English Español Mad Cow Disease KidsHealth / For Teens / Mad Cow Disease What's ... are people to get it? What Is Mad Cow Disease? Mad cow disease is an incurable, fatal ...

Lyme Disease.

ERIC Educational Resources Information Center

Taylor, George C.

1991-01-01

This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…

Serum Immune Responses Predict Rapid Disease Progression among Children with Crohn’s Disease: Immune Responses Predict Disease Progression

PubMed Central

Dubinsky, Marla C.; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J.; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A.; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M.; Elson, Charles O.; Targan, Stephan R.; Taylor, Kent D.; Rotter, Jerome I.; Yang, Huiying

2007-01-01

BACKGROUND AND AIM Crohn’s disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. METHODS Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. RESULTS Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5–80.4); p = 0.03). Pediatric CD patients positive for ≥1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). CONCLUSIONS The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients. PMID:16454844

Interstitial Lung Diseases

MedlinePlus

Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

Identifying Future Disease Hot Spots: Infectious Disease Vulnerability Index.

PubMed

Moore, Melinda; Gelfeld, Bill; Okunogbe, Adeyemi; Paul, Christopher

2017-06-01

Recent high-profile outbreaks, such as Ebola and Zika, have illustrated the transnational nature of infectious diseases. Countries that are most vulnerable to such outbreaks might be higher priorities for technical support. RAND created the Infectious Disease Vulnerability Index to help U.S. government and international agencies identify these countries and thereby inform programming to preemptively help mitigate the spread and effects of potential transnational outbreaks. The authors employed a rigorous methodology to identify the countries most vulnerable to disease outbreaks. They conducted a comprehensive review of relevant literature to identify factors influencing infectious disease vulnerability. Using widely available data, the authors created an index for identifying potentially vulnerable countries and then ranked countries by overall vulnerability score. Policymakers should focus on the 25 most-vulnerable countries with an eye toward a potential "disease belt" in the Sahel region of Africa. The infectious disease vulnerability scores for several countries were better than what would have been predicted on the basis of economic status alone. This suggests that low-income countries can overcome economic challenges and become more resilient to public health challenges, such as infectious disease outbreaks.

Disease risk curves.

PubMed

Hughes, G; Burnett, F J; Havis, N D

2013-11-01

Disease risk curves are simple graphical relationships between the probability of need for treatment and evidence related to risk factors. In the context of the present article, our focus is on factors related to the occurrence of disease in crops. Risk is the probability of adverse consequences; specifically in the present context it denotes the chance that disease will reach a threshold level at which crop protection measures can be justified. This article describes disease risk curves that arise when risk is modeled as a function of more than one risk factor, and when risk is modeled as a function of a single factor (specifically the level of disease at an early disease assessment). In both cases, disease risk curves serve as calibration curves that allow the accumulated evidence related to risk to be expressed on a probability scale. When risk is modeled as a function of the level of disease at an early disease assessment, the resulting disease risk curve provides a crop loss assessment model in which the downside is denominated in terms of risk rather than in terms of yield loss.

Celiac Disease: Diagnosis.

PubMed

Byrne, Greg; Feighery, Conleth F

2015-01-01

Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.

Wireless Monitoring for Patients with Cardiovascular Diseases and Parkinson's Disease.

PubMed

Kefaliakos, Antonios; Pliakos, Ioannis; Charalampidou, Martha; Diomidous, Marianna

2016-01-01

The use of applications for mobile devices and wireless sensors is common for the sector of telemedicine. Recently various studies and systems were developed in order to help patients suffering from severe diseases such as cardiovascular diseases and Parkinson's disease. They present a challenge for the sector because such systems demand the flow of accurate data in real time and the use of specialized sensors. In this review will be presented some very interesting applications developed for patients with cardiovascular diseases and Parkinson's disease.

[Finnish disease heritage].

PubMed

Kestilä, Marjo; Ikonen, Elina; Lehesjoki, Anna-Elina

2010-01-01

The Finnish disease heritage refers to rare hereditary diseases that occur in the Finnish population in a relatively larger proportion than in other populations. The genes underlying all of the 36 diseases of the disease heritage have been identified. Together with her group and collaborators, Leena Palotie identified 15 of these, and this review includes the description of some of these achievements. As a result of the so-called founder effect, one predominant mutation underlying these diseases occurs in our population, facilitating the diagnostics of these diseases in our country.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

PubMed

Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

2017-11-01

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

Genotator: a disease-agnostic tool for genetic annotation of disease.

PubMed

Wall, Dennis P; Pivovarov, Rimma; Tong, Mark; Jung, Jae-Yoon; Fusaro, Vincent A; DeLuca, Todd F; Tonellato, Peter J

2010-10-29

Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked data that remains current with the pace of research in the disease

Randomized controlled trials for Alzheimer disease and Parkinson disease.

PubMed

Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

2016-06-01

The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients.

Disease management improves end-stage renal disease outcomes.

PubMed

Sands, Jeffrey J

2006-01-01

Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence-based guidelines, and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. As we more fully measure clinical outcomes and total healthcare costs, including payments from all insurance and government entities, pharmacy costs and out of pocket expenditures, the full implications of disease management can be better defined. The results of this analysis will have a profound influence on United States healthcare policy. At present current data suggest that the promise of disease management, improved care at reduced cost, can and is being realized in end-stage renal disease. Copyright 2006 S. Karger AG, Basel.

Chronic obstructive pulmonary disease and chronic heart failure: two muscle diseases?

PubMed

Troosters, Thierry; Gosselink, Rik; Decramer, Marc

2004-01-01

Chronic obstructive pulmonary disease and congestive heart failure are two increasingly prevalent chronic diseases. Although care for these patients often is provided by different clinical teams, both disease conditions have much in common. In recent decades, more knowledge about the systemic impact of both diseases has become available, highlighting remarkable similarities in terms of prognostic factors and disease management. Rehabilitation programs deal with the systemic consequences of both diseases. Although clinical research also is conducted by various researchers investigating chronic obstructive pulmonary disease and chronic heart failure, it is worthwhile to compare the progress in relation to these two diseases over recent decades. Such comparison, the purpose of the current review, may help clinicians and scientists to learn about progress made in different, yet related, fields. The current review focuses on the similarities observed in the clinical impact of muscle weakness, the mechanisms of muscle dysfunction, the strategies to improve muscle function, and the effects of exercise training on chronic obstructive pulmonary disease and chronic heart failure.

Two adolescent patients with coexistent Graves' disease and Moyamoya disease in Korea.

PubMed

Cheon, Chong Kun; Kim, Su Yung; Yoo, Jae-Ho

2014-06-01

Moyamoya disease is a cerebrovascular condition that results in the narrowing of the vessels of the circle of Willis and collateral vessel formation at the base of the brain. Although relationships between Graves' disease and cerebrovascular accidents in Moyamoya disease are obscure, the coexistence of the two diseases is noteworthy. Moyamoya disease has been rarely reported in adolescent patients with thyrotoxicosis. Recently, we encountered two adolescent Korean patients with Moyamoya disease associated with Graves' disease who presented with episodic right-sided hemiparesis and syncope. These two girls who had Graves' disease had no history of other diseases or head trauma. A thyroid function test revealed a euthyroid state and a high thyroid-stimulating hormone (TSH) receptor antibody titer at that time. The patients were diagnosed with Moyamoya disease based on brain magnetic resonance angiography and cerebral four-vessel angiography. The patients underwent cranial revascularization by encephalo-duroarterio-synangiosis as soon as a diagnosis was made, which resulted in successful symptom resolution. They fared well and had no additional neurological symptoms as of their last follow-up visits. Here, we report these two cases of confirmed Moyamoya disease complicated by Graves' disease with a review of the literature, and discuss the possible association between the two diseases. To our knowledge, this is the first report in South Korea on Moyamoya disease associated with Graves' disease in adolescents with a euthyroid.

Comparison of Phenotypic and Genotypic Methods for Detection of Diphtheria Toxin among Isolates of Pathogenic Corynebacteria

PubMed Central

Efstratiou, Androulla; Engler, Kathryn H.; Dawes, Charlotte S.; Sesardic, Dorothea

1998-01-01

We have compared molecular, immunochemical, and cytotoxic assays for the detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans originally isolated in five different countries. The suitabilities and accuracies of these assays for the laboratory diagnosis of diphtheria were compared and evaluated against the “gold standard” in vivo methods. The in vivo and Vero cell cytotoxicity assays were accurate in their abilities to detect diphtheria toxin but were time-consuming; however, the cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence test. There was complete concordance between all the phenotypic methods. Genotypic tests based upon PCR were rapid; however, PCR must be used with caution because some isolates of C. diphtheriae possessed toxin genes but failed to express a biologically active toxin. Therefore, phenotypic confirmation of toxigenicity for the microbiological diagnosis of diphtheria is recommended. PMID:9774560

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

PubMed

Haywood, Matthew James; Vijendren, Ananth; Acharya, Vikas; Mulla, Rohinton; Panesar, Miss Jaan

2017-03-06

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans , with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery. 2017 BMJ Publishing Group Ltd.

Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se.

PubMed

Ball, Elizabeth; Newburger, Amy; Ackerman, A Bernard

2003-08-01

Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.

Disease control operations

USGS Publications Warehouse

Friend, M.; Franson, J.C.

1999-01-01

Individual disease outbreaks have killed many thousands of animals on numerous occasions. Tens of thousands of migratory birds have died in single die-offs with as many as 1,000 birds succumbing in 1 day. The ability to successfully combat such explosive situations is highly dependent on the readiness of field personnel to deal with them. Because many disease agents can spread through wildlife populations very quickly, advance preparation is essential for preventing infected animals from spreading disease to additional species and locations. Carefully thought-out disease contingency plans should be developed as practical working documents for field personnel and updated as necessary. Well-designed plans can prove invaluable in minimizing wildlife losses and the costs associated with disease control activities.Although requirements for disease control operations vary and must be tailored to each situation, all disease contingency planning involves general concepts and basic biological information. This chapter, which is intended to be a practical guide, identifies the major activities and needs of disease control operations, and relates them to disease contingency planning.

Periodontal disease and anemias associated with Crohn's disease. A case report.

PubMed

Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L

2012-03-01

Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.

Is the disease course predictable in inflammatory bowel diseases?

PubMed Central

Lakatos, Peter Laszlo; Kiss, Lajos S

2010-01-01

During the course of the disease, most patients with Crohn’s disease (CD) may eventually develop a stricturing or a perforating complication, and a significant number of patients with both CD and ulcerative colitis will undergo surgery. In recent years, research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients, identify individual patient profiles, including clinical, laboratory and molecular markers, which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up. This review summarizes the available evidence on clinical, endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases. PMID:20518079

Identifying patterns of immune-related disease: use in disease prevention and management.

PubMed

Dietert, Rodney R; Zelikoff, Judith T

2010-05-01

Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches. Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors. Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric

Infectious diseases and global warming: Tracking disease incidence rates globally

DOE Office of Scientific and Technical Information (OSTI.GOV)

Low, N.C.

1995-09-01

Given the increasing importance of impact of global warming on public health, there is no global database system to monitor infectious disease and disease in general, and to which global data of climate change and environmental factors, such as temperature, greenhouse gases, and human activities, e.g., coastal development, deforestation, can be calibrated, investigated and correlated. The author proposes the diseases incidence rates be adopted as the basic global measure of morbidity of infectious diseases. The importance of a correctly chosen measure of morbidity of disease is presented. The importance of choosing disease incidence rates as the measure of morbidity andmore » the mathematical foundation of which are discussed. The author further proposes the establishment of a global database system to track the incidence rates of infectious diseases. Only such a global system can be used to calibrate and correlate other globally tracked climatic, greenhouse gases and environmental data. The infrastructure and data sources for building such a global database is discussed.« less

Chronic granulomatous disease mimicking early-onset Crohn's disease with cutaneous manifestations.

PubMed

Barbato, Maria; Ragusa, Giovanni; Civitelli, Fortunata; Marcheggiano, Adriana; Di Nardo, Giovanni; Iacobini, Metello; Melengu, Taulant; Cucchiara, Salvatore; Duse, Marzia

2014-06-20

Chronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered. We report the case of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed. This case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

[Celiac disease - disease of children and adults: symptoms, disease complications, risk groups and comorbidities].

PubMed

Majsiak, Emilia; Cichoż-Lach, Halina; Gubska, Olena; Cukrowska, Bożena

2018-01-23

About 1% of human population suffers from celiac disease (CD) and it is one of the most commonly diagnosed autoimmune disorders. Until recently it was believed that CD affects mainly children, but as the newest studies show, up to 60% recently diagnosed patients are adults, often over the age of 60. CD's medical signs are nonspecific. Atypical course of the disease with extraintestinal symptoms is being increasingly observed. The disease may also be asymptomatic over many years. The studies show that the average diagnosis of CD takes more than 10 years since the first symptoms appear. Nonspecific medical signs cause undiagnosed patients suffering from CD to visit gastroenterologists, endocrinologists, allergists, gynaecologists and other medical specialists. However, most frequently general practitioners have the first encounter with patients suffering from CD, therefore they are able to recognize symptoms of the disease at the earliest and refer the patient to a gastroenterologist. Early diagnosis and beginning of the treatment reduce complications of untreated CD. The aim of this paper is to show general practitioners symptoms, disease complications, risk groups and comorbidities of CD.

Phenotype and Clinical Course of Inflammatory Bowel Disease with Co-Existent Celiac Disease.

PubMed

Tse, Chung Sang; Deepak, Parakkal; De La Fuente, Jaime; Bledsoe, Adam C; Larson, Joseph J; Murray, Joseph A; Papadakis, Konstantinos A

2018-05-07

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, and celiac disease are among the most common immune-mediated gastrointestinal diseases. We aim to elucidate the clinical course and outcomes of patients with concomitant inflammatory bowel disease and celiac disease, a unique population that remains scarcely studied to date. A retrospective matched case-control study of adults with coexistent inflammatory bowel disease and celiac disease was performed at a tertiary referral institution in North America. Logistic regression and Kaplan-Meier curves compared disease characteristics and clinical outcomes of the two groups. A total of 342 inflammatory bowel disease patients were included in this study, of which 114 had coexistent celiac disease and 228 did not. Patients with coexistent inflammatory bowel disease and celiac disease had higher rates of primary sclerosing cholangitis (19.3% vs 5.7%; odds ratio, 4.4; 95% confidence interval, 2.1-9.4; p<0.001), extensive ulcerative colitis (78.1% vs 59.0%; odds ratio, 2.8; 95% confidence interval 1.5-5.5, p=0.002), and family history of celiac disease (10.5% vs 3.5%; odds ratio 3.2; 95% confidence interval 1.3-8.2; p=0.01), compared to patients without concomitant celiac disease. Patients with inflammatory bowel disease with concomitant celiac disease have unique phenotypic features compared to non-celiac inflammatory bowel disease, with higher risks for colitis-related hospitalizations, extensive colitis, and primary sclerosing cholangitis. Increased recognition of coexistent IBD and celiac disease can prompt clinicians to investigate for concomitant disease sooner, particularly in patients with seemingly refractory disease.

Mast cells in airway diseases and interstitial lung disease.

PubMed

Cruse, Glenn; Bradding, Peter

2016-05-05

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. Published by Elsevier B.V.

Salivary gland disease.

PubMed

Thomas, Bethan L; Brown, Jackie E; McGurk, Mark

2010-01-01

Salivary gland disease covers a wide range of pathological entities, including salivary gland-specific disease, as well as manifestations of systemic diseases. This chapter discusses the recent advances in managing obstructive salivary gland disease, the move from gland excision to gland preservation, the dilemmas in diagnosing and managing tumours of the salivary glands, and the international data collection to understand the aetiology and progression of Sjögren's disease. Copyright 2010 S. Karger AG, Basel.

Carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Hobday, Timothy J; Abel, Martin D; Pellikka, Patricia A

2007-01-01

Carcinoid heart disease is a rare form of valvular heart disease. The management of these patients is complex, as the systemic malignant disease and the cardiac involvement have to be considered at the same time. Progress in the treatment of patients with carcinoid disease has resulted in improved symptom control and survival. Development and progression of carcinoid heart disease are associated with increased morbidity and mortality. In patients with severe cardiac involvement and well-controlled systemic disease, cardiac surgery has been recognized as the only effective treatment option. Valve replacement surgery may not only be beneficial in terms of symptom relief, but may also contribute to the improved survival observed over the past 2 decades in patients with carcinoid heart disease. Early diagnosis and early surgical treatment in appropriately selected patients may provide the best results. In this article, we review the current literature regarding the biology, diagnosis, treatment, and prognosis of carcinoid heart disease.

Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases.

PubMed

Witoelar, Aree; Jansen, Iris E; Wang, Yunpeng; Desikan, Rahul S; Gibbs, J Raphael; Blauwendraat, Cornelis; Thompson, Wesley K; Hernandez, Dena G; Djurovic, Srdjan; Schork, Andrew J; Bettella, Francesco; Ellinghaus, David; Franke, Andre; Lie, Benedicte A; McEvoy, Linda K; Karlsen, Tom H; Lesage, Suzanne; Morris, Huw R; Brice, Alexis; Wood, Nicholas W; Heutink, Peter; Hardy, John; Singleton, Andrew B; Dale, Anders M; Gasser, Thomas; Andreassen, Ole A; Sharma, Manu

2017-07-01

Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. The study findings provide novel mechanistic

Diseases

Treesearch

Thomas E. Hinds

1985-01-01

Although many diseases attack aspen, relatively few kill or seriously injure living trees. The common leaf diseases, in general, are widely distributed throughout the range of aspen, whereas there are subtle differences in distribution between the important decay fungi, and apparently entirely different areas of distribution of major cankercausing organisms. However,...

Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

PubMed Central

Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

2014-01-01

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review

PubMed Central

Abiramasundari, Rajagopal Selladurai; Essa, Musthafa Mohamed; Akbar, Mohammed D.

2016-01-01

Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases. PMID:28116038

Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

ERIC Educational Resources Information Center

Klein, Susan D.; Simmons, Roberta G.

As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

Transgenic mouse models of Parkinson's disease and Huntington's disease.

PubMed

Skaper, Stephen D; Giusti, Pietro

2010-08-01

Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Another neurodegenerative disorder, Huntington's disease (HD), is characterized by striking movement abnormalities and the loss of medium-sized spiny neurons in the striatum. Current medications only provide symptomatic relief and fail to halt the death of neurons in these disorders. A major hurdle in the development of neuroprotective therapies is due to limited understanding of disease processes leading to the death of neurons. The etiology of dopaminergic neuronal demise in PD is elusive, but a combination of genetic and environmental factors seems to play a critical role. The majority of PD cases are sporadic; however, the discovery of genes linked to rare familial forms of disease and studies from experimental animal models has provided crucial insights into molecular mechanisms of disease pathogenesis. HD, on the other hand, is one of the few neurodegenerative diseases with a known genetic cause, namely an expanded CAG repeat mutation, extending a polyglutamine tract in the huntingtin protein. One of the most important advances in HD research has been the generation of various mouse models that enable the exploration of early pathological, molecular, and cellular abnormalities produced by the mutation. In addition, these models for both HD and PD have made possible the testing of different pharmacological approaches to delay the onset or slow the progression of disease. This article will provide an overview of the genetics underlying PD and HD, the animal models developed, and their potential utility to the study of disease pathophysiology.

[Cardiovascular disease and systemic inflammatory diseases].

PubMed

Cuende, José I; Pérez de Diego, Ignacio J; Godoy, Diego

2016-01-01

More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Legionnaires' disease.

PubMed

Cunha, Burke A; Burillo, Almudena; Bouza, Emilio

2016-01-23

Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disease mongering.

PubMed

Shankar, P R; Subish, P

2007-04-01

Convincing healthy people that they are sick and require medicines can enormously expand the market. Disease mongering can turn ordinary ailments like baldness into medical problems, consider risk factors such as hypertension and osteoporosis as diseases and frame prevalence estimates to increase potential markets. In Asia, conditions like erectile dysfunction, male pattern baldness, attention deficit hyperactivity disorder and irritable bowel syndrome, and the drugs to treat them, are widely promoted. Fairness creams and traditional medicines are also widely used. The cost of disease mongering to the individual and the community is expected to be high. Some authors have argued that medicalisation of illnesses may not be a problem and the real problem may be the lack of medicines. Doctors will play a key role in combating disease mongering. Disentanglement from the pharmaceutical industry and development of a capacity for critical analysis are required. Educating patients and empowering them to make decisions are important. Several initiatives have been undertaken to combat disease mongering. Initiatives at the level of the patient and the physician are especially important. Studies on the extent and knowledge of disease mongering among doctors and medical students, and their economic and social consequences are urgently required.

Involvement of Gaucher Disease Mutations in Parkinson Disease.

PubMed

Vilageliu, Lluisa; Grinberg, Daniel

2017-01-01

Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison's etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Degenerative Nerve Diseases

MedlinePlus

... may include toxins, chemicals, and viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ataxia Huntington's disease ...

A Disease or Not a Disease? Aging As a Pathology.

PubMed

Gladyshev, Timothy V; Gladyshev, Vadim N

2016-12-01

The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

PubMed Central

Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A.; Sanz, Ferran; Furlong, Laura I.

2011-01-01

Background Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. Principal Findings We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. Conclusions For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

PubMed

Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

2011-01-01

Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The

DOSim: an R package for similarity between diseases based on Disease Ontology.

PubMed

Li, Jiang; Gong, Binsheng; Chen, Xi; Liu, Tao; Wu, Chao; Zhang, Fan; Li, Chunquan; Li, Xiang; Rao, Shaoqi; Li, Xia

2011-06-29

The construction of the Disease Ontology (DO) has helped promote the investigation of diseases and disease risk factors. DO enables researchers to analyse disease similarity by adopting semantic similarity measures, and has expanded our understanding of the relationships between different diseases and to classify them. Simultaneously, similarities between genes can also be analysed by their associations with similar diseases. As a result, disease heterogeneity is better understood and insights into the molecular pathogenesis of similar diseases have been gained. However, bioinformatics tools that provide easy and straight forward ways to use DO to study disease and gene similarity simultaneously are required. We have developed an R-based software package (DOSim) to compute the similarity between diseases and to measure the similarity between human genes in terms of diseases. DOSim incorporates a DO-based enrichment analysis function that can be used to explore the disease feature of an independent gene set. A multilayered enrichment analysis (GO and KEGG annotation) annotation function that helps users explore the biological meaning implied in a newly detected gene module is also part of the DOSim package. We used the disease similarity application to demonstrate the relationship between 128 different DO cancer terms. The hierarchical clustering of these 128 different cancers showed modular characteristics. In another case study, we used the gene similarity application on 361 obesity-related genes. The results revealed the complex pathogenesis of obesity. In addition, the gene module detection and gene module multilayered annotation functions in DOSim when applied on these 361 obesity-related genes helped extend our understanding of the complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity-related diseases. DOSim can be used to detect disease-driven gene modules, and to annotate the modules for functions and pathways. The DOSim package

The integrated disease network.

PubMed

Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša

2014-11-01

The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.

Parkinson disease.

PubMed

Poewe, Werner; Seppi, Klaus; Tanner, Caroline M; Halliday, Glenda M; Brundin, Patrik; Volkmann, Jens; Schrag, Anette-Eleonore; Lang, Anthony E

2017-03-23

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

Gaucher disease

MedlinePlus

Glucocerebrosidase deficiency; Glucosylceramidase deficiency; Lysosomal storage disease - Gaucher ... 2016:chap 86. Krasnewich DM, Sidransky E. Lysosomal storage diseases. In: Goldman L, Schafer AI, eds. Goldman- ...

Induced Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Neurodegenerative Diseases.

PubMed

Cao, Lei; Tan, Lan; Jiang, Teng; Zhu, Xi-Chen; Yu, Jin-Tai

2015-08-01

Although most neurodegenerative diseases have been closely related to aberrant accumulation of aggregation-prone proteins in neurons, understanding their pathogenesis remains incomplete, and there is no treatment to delay the onset or slow the progression of many neurodegenerative diseases. The availability of induced pluripotent stem cells (iPSCs) in recapitulating the phenotypes of several late-onset neurodegenerative diseases marks the new era in in vitro modeling. The iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in these diseases and provides a novel human stem cell platform for screening new candidate therapeutics. Modeling human diseases using iPSCs has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. In this review, we introduce iPSC-based disease modeling in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In addition, we discuss the implementation of iPSCs in drug discovery associated with some new techniques.

Rheumatic diseases and sexuality: Disease impact and self-management strategies.

PubMed

Helland, Ylva; Kjeken, Ingvild; Steen, Eldri; Kvien, Tore K; Hauge, Mona-Iren; Dagfinrud, Hanne

2011-05-01

To explore how intimate relationships and sexuality are influenced by rheumatic diseases and to describe self-management strategies used to manage disease consequences. To ensure that data were grounded in patients' language and experiences, individual and focus group interviews were conducted. Purposeful sampling was used to ensure variation in age, sex, disease duration, diagnosis, and marital status among the informants. Participants were men and women ages 18 years or older, were diagnosed with inflammatory rheumatic disease by a rheumatologist, and had a disease duration of ≥2 years. The mean age of the 23 participants was 44 years, the mean disease duration was 13.6 years, and the mean ± SD modified Health Assessment Questionnaire score was 1.58 ± 0.46. Four key themes summarized the main issues described by the informants: between disease and normality, relational aspects, disease-related sexual challenges, and self-management strategies. The results reveal that the disease constituted a disruption in life, requiring a new orientation of sexual identity and relationship. Participants' experiences of sexuality went beyond specific sexual activity, including aspects such as body image and relational issues, illustrating a multidimensional perception of sexuality. A large inter- and intrapersonal variety of impact and a wide range of management strategies were reported. This study shows that sexuality is a vital area of life for people living with arthritis. It is a source of physical pleasure and intimacy with their partner, but may cause anxiety and distress when affected by rheumatic disease. However, various self-management strategies are applied to enhance intimate relationships and sexual activity. Knowledge and openness concerning sexual issues need to be emphasized as part of the competence of health professionals and researchers. Copyright © 2011 by the American College of Rheumatology.

Intersection of Cardiovascular Disease and Kidney Disease: Atrial Fibrillation

PubMed Central

Bansal, Nisha; Hsu, Chi-yuan; Go, Alan S.

2014-01-01

Purpose of review Atrial fibrillation (AF) is the most common sustained arrhythmia in the patients with kidney disease. The purpose of this review is to describe the burden of AF in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), postulate possible mechanisms to explain this burden of disease, understand the clinical consequences of AF and review the treatment options for AF specific to patients with kidney disease. Recent findings Recent literature has revealed that the clinical multi-organ impact of AF in patients with CKD and ESRD is substantial. Although novel oral anticoagulants to treat AF and prevent associated complications have been tested in large trials in the general population, there is a paucity of data on the efficacy and safety of these agents in patients with advanced CKD and ESRD. Summary AF is a significant comorbidity in patients with CKD and ESRD with important prognostic implications. More research is needed to understand the mechanisms that contribute to the disproportionate burden of this arrhythmia in patients with kidney disease and treatment options specific to this population of high-risk patients. PMID:24709949

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer’s disease

PubMed Central

Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian

2017-01-01

Abstract Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer’s disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer’s disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer’s disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks—the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer’s disease patients with and without cerebrovascular disease. Alzheimer’s disease patients without cerebrovascular disease, but not Alzheimer’s disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer’s disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer’s disease patients with and without cerebrovascular disease. Across Alzheimer’s disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer’s disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer’s disease patients with cerebrovascular disease showed increased executive control network structural

Kidney disease - resources

MedlinePlus

Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Institute of Diabetes and Digestive and Kidney Disease -- www.niddk.nih.gov/health-information/kidney- ...

Heart disease - resources

MedlinePlus

Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association -- www.heart.org Centers for Disease Control and Prevention -- www.cdc.gov/heartdisease

Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

PubMed

Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

2009-09-01

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

Bladder Diseases

MedlinePlus

... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

[Treatment of Crohn's disease].

PubMed

Vavricka, St R; Rogler, G

2009-01-21

The therapy of Crohn's disease depends on its disease activity. For those different disease activities (such as flare, chronic active disease, remission) varying treatment concepts are followed. This overview presents important concepts in the treatment of Crohn's disease.

Celiac disease - resources

MedlinePlus

... Association -- www.csaceliacs.org Gluten Intolerance Group -- www.gluten.org National Institute of Diabetes and Digestive and Kidney Disease -- www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease Beyond Celiac -- www. ...

[Infectious diseases research].

PubMed

Carratalà, Jordi; Alcamí, José; Cordero, Elisa; Miró, José M; Ramos, José Manuel

2008-12-01

There has been a significant increase in research activity into infectious diseases in Spain in the last few years. The Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) currently has ten study groups, with the cooperation of infectious diseases specialists and microbiologists from different centres, with significant research activity. The program of Redes Temáticas de Investigación Cooperativa en Salud (Special Topics Cooperative Health Research Networks) is an appropriate framework for the strategic coordination of research groups from the Spanish autonomous communities. The Spanish Network for Research in Infectious Diseases (REIPI) and the Network for Research in AIDS (RIS) integrate investigators in Infectious Diseases from multiple groups, which continuously perform important research projects. Research using different experimental models in infectious diseases, in numerous institutions, is an important activity in our country. The analysis of the recent scientific production in Infectious Diseases shows that Spain has a good position in the context of the European Union. The research activity in Infectious Diseases carried out in our country is a great opportunity for the training of specialists in this area of knowledge.

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

PubMed

Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

2015-06-01

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The elusive baseline of marine disease: Are diseases in ocean ecosystems increasing?

USGS Publications Warehouse

Ward, Jessica R.; Lafferty, Kevin D.

2004-01-01

Disease outbreaks alter the structure and function of marine ecosystems, directly affecting vertebrates (mammals, turtles, fish), invertebrates (corals, crustaceans, echinoderms), and plants (seagrasses). Previous studies suggest a recent increase in marine disease. However, lack of baseline data in most communities prevents a direct test of this hypothesis. We developed a proxy to evaluate a prediction of the increasing disease hypothesis: the proportion of scientific publications reporting disease increased in recent decades. This represents, to our knowledge, the first quantitative use of normalized trends in the literature to investigate an ecological hypothesis. We searched a literature database for reports of parasites and disease (hereafter “disease”) in nine marine taxonomic groups from 1970 to 2001. Reports, normalized for research effort, increased in turtles, corals, mammals, urchins, and molluscs. No significant trends were detected for seagrasses, decapods, or sharks/rays (though disease occurred in these groups). Counter to the prediction, disease reports decreased in fishes. Formulating effective resource management policy requires understanding the basis and timing of marine disease events. Why disease outbreaks increased in some groups but not in others should be a priority for future investigation. The increase in several groups lends urgency to understanding disease dynamics, particularly since few viable options currently exist to mitigate disease in the oceans.

miRNAs as Circulating Biomarkers for Alzheimer's Disease and Parkinson's Disease.

PubMed

Mushtaq, Gohar; Greig, Nigel H; Anwar, Firoz; Zamzami, Mazin A; Choudhry, Hani; Shaik, Munvar M; Tamargo, Ian A; Kamal, Mohammad A

2016-01-01

Detection of biomarkers for neurodegenerative disorders (NDDs) within brain tissues of Alzheimer's disease (AD) and Parkinson's disease (PD) patients has always been hampered by our inability to access and biopsy tissue of key brain regions implicated in disease occurrence and progression. Currently, diagnosis of NDDs is principally based on clinical observations of symptoms that present at later stages of disease progression, followed by neuroimaging and, possibly, CSF evaluation. One way to potentially detect and diagnose NDDs at a far earlier stage is to screen for abnormal levels of specific disease markers within the peripheral circulation of patients with NDDs. Increasing evidence suggests that there is dysregulation of microRNAs (miRNAs) in NDDs. Peripheral blood mononuclear cells, as well as biofluids, such as plasma, serum, urine and cerebrospinal fluid, contain miRNAs that can be identified and quantified. Circulating miRNAs within blood and other biofluids may thus be characterized and used as non-invasive, diagnostic biomarkers that facilitate the early detection of disease and potentially the continual monitoring of disease progression for NDDs such as AD and PD. Plainly, such a screen is only possible with a clear understanding of which miRNAs change with disease, and when these changes occur during the progression of AD and PD. Such information is becoming increasingly available and, in the near future, may not only support disease diagnosis, but provide the opportunity to evaluate therapeutic interventions earlier in the disease process.

AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.

PubMed

Hamrahian, Amir H; Yuen, Kevin C J; Hoffman, Andrew R

2014-07-01

To review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice. PubMed searches were performed to identify all of the available published data on medical management of Cushing disease. Medical therapy is usually not the first-line treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase. Medical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies.

Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

PubMed

Crowder, L A; Yedlin, V A; Weinstein, E R; Kortte, K B; Aucott, J N

2014-09-01

A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

[Genetic basis for skeletal disease. Dental management of patients with bone diseases].

PubMed

Shintani, Seikou; Ooshima, Takashi

2010-08-01

Malformation of teeth can be found in patients with bone diseases, which was induced when the disease occurred during the tooth formation. The tooth malformation shows typical manifestations of the disease, which may demonstrate the occurrence of the bone disease. In this article, dental management of the patients with bone diseases such as X-linked hypophosphatemic rickets, osteogenesis imperfecta, and hypophosphatasia was presented.

Management of upper extremity dysfunction in people with Parkinson disease and Huntington disease: facilitating outcomes across the disease lifespan.

PubMed

Quinn, Lori; Busse, Monica; Dal Bello-Haas, Vanina

2013-01-01

Parkinson Disease (PD) and Huntington Disease (HD) are degenerative neurological diseases, which can result in impairments and activity limitations affecting the upper extremities from early in the disease process. The progressive nature of these diseases poses unique challenges for therapists aiming to effectively maximize physical functioning and minimize participation restrictions in these patient groups. Research is underway in both diseases to develop effective disease-modifying agents and pharmacological interventions, as well as mobility-focused rehabilitation protocols. Rehabilitation, and in particular task-specific interventions, has the potential to influence the upper extremity functional abilities of patients with these degenerative conditions. However to date, investigations of interventions specifically addressing upper extremity function have been limited in both PD, and in particular HD. In this paper, we provide an update of the known pathological features of PD and HD as they relate to upper extremity function. We further review the available literature on the use of outcome measures, and the clinical management of upper extremity function in both conditions. Due to the currently limited evidence base in both diseases, we recommend utilization of a clinical management framework specific for degenerative conditions that can serve as a guideline for disease management. Copyright © 2013. Published by Elsevier Inc.

Infectious disease

NASA Technical Reports Server (NTRS)

Pierson, Duane L.

1990-01-01

This is a collection of viewgraphs on the Johnson Space Center's work on infectious disease. It addresses their major concern over outbreaks of infectious disease that could jeopardize the health, safety and/or performance of crew members engaged in long duration space missions. The Antarctic environment is seen as an analogous location on Earth and a good place to carry out such infectious disease studies and methods for proposed studies as suggested.

Krabbe Disease (GLD)

MedlinePlus

... del paciente Transplant process Diseases treated by transplant Acute myeloid leukemia Adrenoleukodystrophy (ALD) Chronic Lymphocytic Leukemia (CLL) ... SCID) Sickle cell disease (SCD) Wiskott-Aldrich syndrome Acute lymphoblastic leukemia (ALL) Other diseases Treatment decisions Learn ...

Fatty Liver Disease

MedlinePlus

... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

Chronic Diseases Overview

MedlinePlus

... cases of blindness among adults. 6 Health Risk Behaviors that Cause Chronic Diseases Health risk behaviors are ... The Cost of Chronic Diseases and Health Risk Behaviors In the United States, chronic diseases and conditions ...

Management of neurodegenerative disorders: Parkinson's disease and Alzheimer's disease.

PubMed

Pal, P K; Netravathi, M

2005-03-01

Neurodegenerative disorders result from premature progressive degeneration of specific neurons, and manifest as diseases or syndromes with varied combinations of cognitive, motor, sensory and autonomic dysfunctions. The management involves pharmacotherapy as well as non-pharmacological measures and also to lessen the burden of the care-givers. The medications available for medical treatment are: Levodopa, dopamine agonists, amantadine, anticholinergics, enzyme inhibitors, etc. Advanced Parkinson's disease is concerned with management of motor complications and non-motor complications. Recently surgical treatment is a great option for managing motor complication. Orthostatic hypotension, gait distiurbances, emotional and psychiatric problems, sleep disturbances can be managed and had been discussed in brief. Currently there is no medication available for the cure of Alzheimer's disease. The specific medications claimed to improve patient's well being and cognition include cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonist, anti-oxidants, and anti-amyloid therapy. While medical and surgical treatments for Parkinson's disease have revolutionised the management, still drug therapy for Alzheimer's disease is dismal.

Spreading disease: a controversy concerning the metaphysics of disease.

PubMed

D'Amico, R

1998-01-01

This article concerns the metaphysics of disease. Is disease a fixed feature of the world or a social value or preference? I argue that disease is not a value-laden concept and thus debates concerning it differ fundamentally from debates concerning health, harm, or suffering where evaluative judgements are central. I show how the so-called social constructionist view of disease has been motivated both by ethical concerns with medical practices and general theoretical doubts about scientific naturalism. If I can show that ethical concerns about medical treatment can be answered without adopting social constructionism, that leaves only the broader theoretical question of naturalism. I cannot completely answer those theoretical doubts, but I show that the theoretical motivation is less convincing when it is separated from the moral challenge often accompanying it. I conclude that a convincing defense of the non-naturalistic conception of disease is rarely attempted and proves more difficult and counter-intuitive than its proponents assume.

Cancer risk associated with chronic diseases and disease markers: prospective cohort study

PubMed Central

Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng

2018-01-01

Abstract Objectives To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Design Prospective cohort study. Setting Standard medical screening program in Taiwan. Participants 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Main outcome measures Cancer incidence and cancer mortality. Results A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among

Von Hippel-Lindau Disease

MedlinePlus

What is Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a rare disease that causes tumors and cysts to grow in your body. They ... can become cancerous. What causes Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a ...

Kidney Disease Basics

MedlinePlus

... My Kidneys Fail? Clinical Trials What Is Chronic Kidney Disease? Chronic kidney disease (CKD) means your kidneys ... work, be active, and enjoy life. Will my kidneys get better? Kidney disease is often “progressive”, which ...

Lyme Disease Transmission

MedlinePlus

... cases of Lyme disease have been linked to blood transfusion, scientists have found that the Lyme disease bacteria ... through the use of tick control products for animals. You will not get Lyme disease from eating ...

Biomarker for Glycogen Storage Diseases

ClinicalTrials.gov

2017-07-03

Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII

Infectious Diseases

MedlinePlus

... may carry the bacterium that causes Lyme disease. Food contamination Another way disease-causing germs can infect you is through contaminated food and water. This mechanism of transmission allows germs ...

Understanding cardiovascular disease

MedlinePlus

... page: //medlineplus.gov/ency/patientinstructions/000759.htm Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...

Pediatric Celiac Disease

MedlinePlus

... Free Recipe Article What is Celiac Disease Video Support Organizations National Foundation for Celiac Awareness (NFCA) Celiac Central Canadian Celiac Association Celiac Disease Foundation Celiac Sprue ... Educational support for the NASPGHAN Foundation's Celiac Disease Education Campaign ...

Lyme disease (image)

MedlinePlus

Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...

Behcet's disease.

PubMed

Suzuki Kurokawa, M; Suzuki, N

2004-09-01

Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody

Gaucher disease: the role of the specialist on metabolic bone diseases.

PubMed

Masi, Laura; Brandi, Maria Luisa

2015-01-01

According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

Gaucher disease: the role of the specialist on metabolic bone diseases

PubMed Central

Masi, Laura; Brandi, Maria Luisa

2015-01-01

Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

Digestive diseases

MedlinePlus

... this page: //medlineplus.gov/ency/article/007447.htm Digestive diseases To use the sharing features on this page, please enable JavaScript. Digestive diseases are disorders of the digestive tract, which ...

Tick-borne disease.

PubMed

Bratton, Robert L; Corey, Ralph

2005-06-15

Tick-borne diseases in the United States include Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, tularemia, babesiosis, Colorado tick fever, and relapsing fever. It is important for family physicians to consider these illnesses when patients present with influenza-like symptoms. A petechial rash initially affecting the palms and soles of the feet is associated with Rocky Mountain spotted fever, whereas erythema migrans (annular macule with central clearing) is associated with Lyme disease. Various other rashes or skin lesions accompanied by fever and influenza-like illness also may signal the presence of a tick-borne disease. Early, accurate diagnosis allows treatment that may help prevent significant morbidity and possible mortality. Because 24 to 48 hours of attachment to the host are required for infection to occur, early removal can help prevent disease. Treatment with doxycycline or tetracycline is indicated for Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, and relapsing fever. In patients with clinical findings suggestive of tick-borne disease, treatment should not be delayed for laboratory confirmation. If no symptoms follow exposure to tick bites, empiric treatment is not indicated. The same tick may harbor different infectious pathogens and transmit several with one bite. Advising patients about prevention of tick bites, especially in the summer months, may help prevent exposure to dangerous vector-borne diseases.

Parkinson disease

MedlinePlus

... this page: //medlineplus.gov/ency/article/000755.htm Parkinson disease To use the sharing features on this page, please enable JavaScript. Parkinson disease results from certain brain cells dying. These cells ...

Poverty-related diseases (PRDs): unravelling complexities in disease responses in Cameroon.

PubMed

Makoge, Valerie; Maat, Harro; Vaandrager, Lenneke; Koelen, Maria

2017-01-01

In Cameroon, poverty-related diseases (PRDs) are a major public health concern. Research and policies addressing PRDs are based on a particular understanding of the interaction between poverty and disease, usually an association between poverty indicators and health indicators for a specific country or region. Such indicators are useful but fail to explain the nature of the linkages between poverty and disease or poverty and health. This paper presents results of a study among university students, unravelling how they perceive diseases, the linkages with poverty, their responses to diseases and the motivations behind reported responses. Based on the health belief model, this cross-sectional study was carried out among 272 students at the universities of Buea and Yaoundé in Cameroon. Data were collected using questionnaires containing items matching the research objectives. The questionnaires were self-completed. Malaria was considered as the most common disease perceived and also a major PRD. Contrary to official rankings of HIV/AIDS and TB, cholera and diarrhoea were considered as other major PRDs. Also, typhoid fever was perceived to be more common and a PRD than HIV/AIDS and TB combined. The most prominently attributed cause for disease was (lack of) hygiene. In response, students deployed formal and/or informal healthcare strategies, depending on factors like available money, perceived severity of the disease and disease type. Discrepancies were observed in respondents' response to diseases generally and to malaria in particular. Even though, overall, respondents pre-dominantly reported a formal healthcare response toward diseases in general, for malaria, informal responses dominated. There was an overall strong awareness and (pro)activity among students for dealing with diseases. Although the high use of informal facilities and medication for malaria may well be a reason why eradication is problematic, this seems to be a deliberate strategy linked to an

Inflammatory Bowel Disease.

PubMed

2016-01-01

Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed.

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Using internet search queries for infectious disease surveillance: screening diseases for suitability.

PubMed

Milinovich, Gabriel J; Avril, Simon M R; Clements, Archie C A; Brownstein, John S; Tong, Shilu; Hu, Wenbiao

2014-12-31

Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009-13 using Spearman's rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases.

Addison's disease secondary to connective tissue diseases: a report of six cases.

PubMed

Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

2009-04-01

Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Cancer risk associated with chronic diseases and disease markers: prospective cohort study.

PubMed

Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng; Wu, Xifeng

2018-01-31

To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Prospective cohort study. Standard medical screening program in Taiwan. 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Cancer incidence and cancer mortality. A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk

Lyme disease antibody

MedlinePlus

... Lyme disease organism, Borrelia burgdorferi Deer ticks Ticks Lyme disease - Borrelia burgdorferi organism Tick imbedded in the skin Antibodies ... Saunders; 2013:745-747. Steere AC. Lyme disease (Lyme borreliosis) due to Borrelia burgdorferi . In: Bennett JE, Dolin R, Blaser MJ, ...

Hirschsprung disease.

PubMed

Haricharan, Ramanath N; Georgeson, Keith E

2008-11-01

Hirschsprung disease is a relatively common condition managed by pediatric surgeons. Significant advances have been made in understanding its etiologies in the last decade, especially with the explosion of molecular genetic techniques and early diagnosis. The surgical management has progressed from a two- or three-stage procedure to a primary operation. More recently, definitive surgery for Hirschsprung disease through minimally invasive techniques has gained popularity. In neonates, the advancement of treatment strategies for Hirschsprung disease continues with reduced patient morbidity and improved outcomes.

DISEASES: text mining and data integration of disease-gene associations.

PubMed

Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi; Binder, Janos X; Jensen, Lars Juhl

2015-03-01

Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The DISEASES resource is accessible through a web interface at http://diseases.jensenlab.org/, where the text-mining software and all associations are also freely available for download. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Celiac Disease

MedlinePlus

... immune disease in which people can't eat gluten because it will damage their small intestine. If you have celiac disease and eat foods with gluten, your immune system responds by damaging the small ...

Alexander Disease

MedlinePlus

... there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. Alexander disease is a ... there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. Alexander disease is a ...

Kidney Diseases

MedlinePlus

... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

Eye Diseases

MedlinePlus

... the back of the eye Macular degeneration - a disease that destroys sharp, central vision Diabetic eye problems ... defense is to have regular checkups, because eye diseases do not always have symptoms. Early detection and ...

Addison Disease

MedlinePlus

... blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...

Endocrine Diseases

MedlinePlus

... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

Mitochondrial Diseases

MedlinePlus

... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...

Liver Diseases

MedlinePlus

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

Autoimmune Diseases

MedlinePlus

... Disease Symptoms Alopecia areata (Al-uh-PEE-shuh AR-ee-AYT-uh) The immune system attacks hair ... spine is involved. Rheumatoid arthritis (ROO-muh-toid ar-THREYE-tuhss) A disease in which the immune ...

Canavan Disease

MedlinePlus

... Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians. Canavan disease can be ... Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians. Canavan disease can be ...

Thyroid Disease

MedlinePlus

... the disease and what symptoms you have. For example, if you get symptoms of hyperthyroidism in the ... the disease and what symptoms you have. For example, if you get symptoms of hyperthyroidism in the ...

Fifth Disease

MedlinePlus

... past. The others included measles, rubella (German measles), chicken pox, scarlet fever, and roseola. Fifth disease is ... The first signs of fifth disease are mild flu- or cold-like symptoms, including: low-grade fever ...

[Chronic non-communicable diseases in Brazil: priorities for disease management and research].

PubMed

Duncan, Bruce Bartholow; Chor, Dóra; Aquino, Estela M L; Bensenor, Isabela M; Mill, José Geraldo; Schmidt, Maria Inês; Lotufo, Paulo Andrade; Vigo, Alvaro; Barreto, Sandhi Maria

2012-12-01

Chronic Non-Communicable Diseases are the main source of disease burden in Brazil. In 2011, the Brazilian Ministry of Health launched the Strategic Plan of Action for Management of Chronic Non-Communicable Diseases focusing on population-based interventions to manage cardiovascular diseases, diabetes, cancer, and chronic respiratory diseases mainly through fighting tobacco use, unhealthy diets, physical inactivity and the harmful use of alcohol. Although a significant number of scientific studies on chronic diseases and their risk factors have been undertaken in Brazil, few are of cohort design. In this context, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105 Brazilian public servants reflects the reality of high prevalences of diabetes, hypertension and the main chronic diseases risk factors. The diversity of information that the Study will produce can provide important input to better understand the causes of chronic diseases and to support public policies for fighting them.

Crohn disease

PubMed Central

Stappenbeck, Thaddeus S.; Rioux, John D.; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J.

2011-01-01

Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.1 Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk. PMID:20729636

Kawasaki Disease

PubMed Central

2006-01-01

Kawasaki disease is an acute febrile, systemic vasculitic syndrome of an unknown etiology that primarily occurs in children younger than five years of age. The principal presentations of Kawasaki disease include fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develops in 15% to 25% of untreated children with the disease, which may later lead to myocardial infarction, sudden death, or ischemic heart disease. Treatment with intravenous gamma globulin (IVIG) is effective, but the mode of action is still unclear. The development of a diagnostic test, a more specific therapy, and ultimately the prevention of this potentially fatal illness in children are all dependent upon the continued advances in determining the etiopathogenesis of this fascinating disorder. PMID:17191303

Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

Infectious Disease Specialist: What Is an Infectious Disease Specialist?

MedlinePlus

... More: Facts about ID Infectious Diseases Society of America 1300 Wilson Boulevard Suite 300 Arlington, VA 22209 | ... Us © Copyright IDSA 2018 Infectious Diseases Society of America Full Site Mobile Site

Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases.

PubMed

Torres, Joana; Caprioli, Flavio; Katsanos, Konstantinos H; Lobatón, Triana; Micic, Dejan; Zerôncio, Marco; Van Assche, Gert; Lee, James C; Lindsay, James O; Rubin, David T; Panaccione, Remo; Colombel, Jean-Frédéric

2016-12-01

Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course. As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient. © European Crohn’s and Colitis Organisation 2016.

Kawasaki disease

MedlinePlus

... signs of heart disease, adding steroids or tumor necrosis factor (TNF) inhibitors such as infliximab (Remicade) or ... Possible Complications Kawasaki disease can cause inflammation of blood vessels in the arteries, especially the coronary arteries. This ...

Lung Diseases

MedlinePlus

... 000 times. People with lung disease have difficulty breathing. Millions of people in the U.S. have lung ... pneumonia and tuberculosis, lung cancer, and many other breathing problems. Some lung diseases can lead to respiratory ...

Alzheimer disease

MedlinePlus

... likely need to plan for their loved one's future care. The final phase of the disease may ... disease and other dementias. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

Why infectious diseases.

PubMed

Bartlett, John G

2014-09-15

Infectious diseases is a broad discipline that is almost unique in contemporary medicine with its ability to cure and prevent disease, to identify specific disease causes (microbes), and to deal with diverse, sometimes massive outbreaks. The value of the infectious disease practitioner is now magnified by the crisis of antibiotic resistance, the expanding consequences of international travel, the introduction of completely new pathogen diagnostics, and healthcare reform with emphasis on infection prevention and cost in dollars and lives. Infectious disease careers have great personal rewards to the practitioner based on these observations. It is unfortunate that we have been so effective in our work, but relatively ineffective in convincing the healthcare system of this value. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Celiac disease and other autoimmune diseases in patients with collagenous colitis.

PubMed

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

PubMed

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p<0.01) and among patients with severe motor dysfunction (90% vs. 35%; p<0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

About Chronic Kidney Disease

MedlinePlus

... Donate A to Z Health Guide About Chronic Kidney Disease Tweet Share Print Email Chronic kidney disease ( ... about Glomerular Filtration Rate (GFR) What is chronic kidney disease (CKD)? Chronic kidney disease includes conditions that ...

Heart disease - risk factors

MedlinePlus

Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

Hashimoto's Disease

MedlinePlus

... disease often leads to reduced thyroid function, or hypothyroidism. Hypothyroidism is a disorder that occurs when the thyroid ... Hashimoto’s disease is the most common cause of hypothyroidism in the United States. 1 Read more in ...

Legionnaires' Disease

MedlinePlus

Legionnaires' disease is a type of pneumonia caused by bacteria. You usually get it by breathing in mist from ... spread from person to person. Symptoms of Legionnaires' disease include high fever, chills, a cough, and sometimes ...

Raynaud's Disease

MedlinePlus

Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...

Wilson Disease

MedlinePlus

Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...

Parkinson's Disease

MedlinePlus

Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

Chagas Disease

MedlinePlus

Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

Liver disease

MedlinePlus

... Coccidioidomycosis Delta agent (hepatitis D) Drug-induced cholestasis Fatty liver disease Hemochromatosis Hepatitis A Hepatitis B Hepatitis C ... abscess Reye syndrome Sclerosing cholangitis Wilson disease Images Fatty liver, CT scan Liver with disproportional fattening, CT scan ...

Whipple's Disease

MedlinePlus

... function in one or more connecting or supporting structures of the body. celiac disease —a digestive disease that damages the small intestine and interferes with the absorption of nutrients from food. People who have celiac ...

Epigenetics of kidney disease.

PubMed

Wanner, Nicola; Bechtel-Walz, Wibke

2017-07-01

DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

Vogt-Koyanagi-Harada disease.

PubMed

Burkholder, Bryn M

2015-11-01

The purpose of this article is to review the current literature on Vogt-Koyanagi-Harada (VKH) disease, including current treatment options and new research directions. Recent publications on VKH disease show an increased focus on the immunogenetics and immune pathways associated with the development of VKH disease. There have also been advances in imaging modalities and techniques that may help to better elucidate the disease process in eyes with VKH disease. VKH disease is an autoimmune, multisystem inflammatory disorder, the cause of which is still incompletely understood. Continued research may elucidate the causes and triggers of immune dysregulation in this disease, and in doing so, identify novel therapeutic targets.

Serum prolactin in coeliac disease: a marker for disease activity

PubMed Central

Reifen, R.; Buskila, D.; Maislos, M.; Press, J.; Lerner, A.

1997-01-01

Accepted 21 April 1997
 Prolactin, a polypeptide hormone of anterior pituitary origin, has pronounced physiological effects on growth, reproduction, and osmoregulation. Increasing evidence indicates that prolactin also has an immunomodulatory influence on the immune system. The status of prolactin in patients with coeliac disease was investigated by obtaining serum samples from 48 patients with active and non-active coeliac disease. These were compared with samples from 20 children with familial Mediterranean fever and 65 normal controls. Serum prolactin in patients with active coeliac disease was significantly higher than in the other groups studied and reference values. Serum prolactin correlated well with the degree of mucosal atrophy and with the serum concentration of antiendomysial antibodies. Prolactin may play a part in immune modulation in the intestinal damage of coeliac disease and serve as a potential marker for disease activity.

 PMID:9301358

Disease management.

PubMed Central

Hunter, D. J.; Fairfield, G.

1997-01-01

The disease management approach to patient care seeks to coordinate resources across the healthcare delivery system. The growing interest in evidence based medicine and outcomes, and a commitment to integrated care across the primary, secondary, and community care sectors, all contribute to making disease management an attractive idea. A combination of patient education, provider use of practice guidelines, appropriate consultation, and supplies of drugs and ancillary services all come together in the disease management process. But its effectiveness is largely untested, so evaluation is essential. PMID:9233330

Immunoglobulin G4-related disease: a rare disease with an unusual presentation.

PubMed

Khan, Muhammad Waqas; Hadley, Terrance; Kesler, Melissa; Gul, Zartash

2016-07-01

IgG4-RD can also present in the skeletal muscle, mimicking several other diseases. It is unusual for this relatively new classification of diseases to present in the muscles and can be mistakenly diagnosed as other autoimmune diseases rendering a delay in the appropriate management and progression of the disease.

Celiac Disease Changes Everything

MedlinePlus

... but a true gift. Read More "Celiac Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis and Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten- ...

What Is Celiac Disease?

MedlinePlus

... and saliva are destroyed Read More "Celiac Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis and Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten- ...

A disease state fingerprint for evaluation of Alzheimer's disease.

PubMed

Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho; Simonsen, Anja; van Gils, Mark; Waldemar, Gunhild; Soininen, Hilkka; Lötjönen, Jyrki

2011-01-01

Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization system is proposed for supporting clinical diagnosis of AD. The proposed system computes an evidence-based estimate of a patient's AD state by comparing his or her heterogeneous neuropsychological, clinical, and biomarker data to previously diagnosed cases. The AD state in this context denotes a patient's degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease progression from elderly healthy controls to AD and its ability to predict conversion from mild cognitive impairment (MCI) to AD were assessed. It was found that the DSI provides well-behaving AD state estimates, corresponding well with the actual diagnoses. For predicting conversion from MCI to AD, the DSI attains performance similar to state-of-the-art reference classifiers. The results suggest that the DSF establishes an effective decision support and data visualization framework for improving AD diagnostics, allowing clinicians to rapidly analyze large quantities of diverse patient data.

Kidney Disease

MedlinePlus

... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...

Fifth Disease

MedlinePlus

Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...

Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

NASA Astrophysics Data System (ADS)

Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

2012-10-01

The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

PubMed

Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

2012-01-01

The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Christopher P.; Ferré-D'Amaré, Adrian R.

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. In this paper, we report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg 2+ ion. We show that themore » affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. Finally, the ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.« less

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains

DOE PAGES

Jones, Christopher P.; Ferré-D'Amaré, Adrian R.

2015-08-17

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. In this paper, we report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg 2+ ion. We show that themore » affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. Finally, the ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.« less

Heart disease and women

MedlinePlus

... NOT consider heart disease a woman's disease. Yet cardiovascular disease is the leading killer of women over age ... gov/pubmed/25070666 . Gulati M, Bairey Merz CN. Cardiovascular disease in women. In: Mann DL, Zipes DP, Libby ...

Heart Disease and Stroke

MedlinePlus

... receive Heart Disease and Stroke email updates Submit Heart Disease and Stroke Heart disease and stroke are important ... Stroke Stroke symptoms Stroke risk factors View more Heart Disease and Stroke resources Related information Heart-healthy eating ...

Undifferentiated Connective Tissue Disease

MedlinePlus

... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

Association of maternal chronic disease with risk of congenital heart disease in offspring

PubMed Central

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-01-01

Background: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. Methods: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan’s National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. Results: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66–3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60–3.12), hypertension (adjusted OR 1.87, 95% CI 1.69–2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45–3.80), anemia (adjusted OR 1.31, 95% CI 1.25–1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19–1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08–1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11–1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. Interpretation: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. PMID:27729382

Association of maternal chronic disease with risk of congenital heart disease in offspring.

PubMed

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-12-06

Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan's National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66-3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60-3.12), hypertension (adjusted OR 1.87, 95% CI 1.69-2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45-3.80), anemia (adjusted OR 1.31, 95% CI 1.25-1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19-1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08-1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11-1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. © 2016 Canadian Medical Association or its licensors.

Sexual transmission of Lyme disease: challenging the tickborne disease paradigm.

PubMed

Stricker, Raphael B; Middelveen, Marianne J

2015-01-01

Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. In this article, we explore the clinical, epidemiological and experimental evidence for sexual transmission of Lyme disease in animal models and humans. Although the likelihood of sexual transmission of the Lyme spirochete remains speculative, the possibility of Lyme disease transmission via intimate human contact merits further study.

Kawasaki Disease

MedlinePlus

... descent. The disease is more likely to affect boys than girls. Most cases occur in children younger than 5 ... descent. The disease is more likely to affect boys than girls. Most cases occur in children younger than 5 ...

Viral Disease Networks?

NASA Astrophysics Data System (ADS)

Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

2010-03-01

Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

National disease management plans for key chronic non-communicable diseases in Singapore.

PubMed

Tan, C C

2002-07-01

In Singapore, chronic, non-communicable diseases, namely coronary heart disease, stroke and cancer, account for more than 60% of all deaths and a high burden of disability and healthcare expenditure. The burden of these diseases is likely to rise with our rapidly ageing population and changing lifestyles, and will present profound challenges to our healthcare delivery and financing systems over the next 20 to 30 years. The containment and optimal management of these conditions require a strong emphasis on patient education and the development of integrated models of healthcare delivery in place of the present uncoordinated, compartmentalised way of delivering healthcare. To meet these challenges, the Ministry of Health's major thrusts are disease control measures which focus mainly on primary prevention; and disease management, which coordinates the national effort to reduce the incidence of these key diseases and their predisposing factors and to ameliorate their long-term impact by optimising control to reduce mortality, morbidity and complications, and improving functional status through rehabilitation. The key initiatives include restructuring of the public sector healthcare institutions into two clusters, each comprising a network of primary health care polyclinics, regional hospitals and tertiary institutions. The functional integration of these healthcare elements within each cluster under a common senior administrative and professional management, and the development of common clinical IT systems will greatly facilitate the implementation of disease management programmes. Secondly, the Ministry is establishing National Disease Registries in coronary heart disease, cancer, stroke, myopia and kidney failure, which will be valuable sources of clinical and outcomes data. Thirdly, in partnership with expert groups, national committees and professional agencies, the Ministry will produce clinical practice guidelines which will assist doctors and healthcare

[Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases].

PubMed

Frikha, F; Marzouk, S; Frigui, M; Jallouli, M; Kechaou, M; Kaddour, N; Boudawara, T; Jlidi, R; Bahloul, Z

2008-02-01

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.

Fifth disease

MedlinePlus

Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and mouth ...

Pilonidal Disease

MedlinePlus

... ensuring high-quality patient care by advancing the science, prevention and management of disorders and diseases of the colon, rectum and anus. These brochures are inclusive but not prescriptive. Their purpose is to provide information on diseases and processes, ...

[Atherosclerosis in inflammatory diseases].

PubMed

Páramo, José A; Rodríguez, José A; Orbe, Josune

2007-05-19

The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.

Acquired Cystic Kidney Disease

MedlinePlus

... care provider about when to begin screening. Eating, Diet, and Nutrition No specific diet will prevent or delay acquired ... Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

The impact of perianal disease in young patients with inflammatory bowel disease.

PubMed

Zwintscher, Nathan P; Shah, Puja M; Argawal, Amit; Chesley, Patrick M; Johnson, Eric K; Newton, Christopher R; Maykel, Justin A; Steele, Scott R

2015-09-01

Perianal disease is a potentially significant source of morbidity for patients with inflammatory bowel disease (IBD). We sought to identify the impact of perianal disease on IBD outcomes in children, adolescents, and young adults. We studied 12,465 inpatient admissions for patients ≤20 years old with IBD in 2009 using the Kids' Inpatient Database (KID). Patients were stratified by their principal diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). Perianal disease (perianal abscess, anal fissure, or anal fistula), complex fistulas (rectourethral, rectovaginal, or enterovesical), and growth failure were defined by ICD-9 codes. Logistic regression was performed adjusting for CD or UC, gender, age, need for surgical intervention, fistulas, or growth failure. Of the 511 (4.1%) patients with perianal disease, 480 had CD (94%, p < 0.001). Girls were less likely to suffer perianal disease (OR = 0.63, CI 0.52-0.76, p < 0.001). Those with perianal disease were more likely to suffer complex fistulas (OR = 3.5, CI 1.98-6.20, p < 0.001) but less likely to suffer enteroenteral fistulas (OR = 0.30, CI 0.15-0.63, p = 0.001) than those without perianal disease. Perianal disease did not increase the incidence of growth failure (p = 0.997) but doubled the likelihood of an operation of any type during admission (p < 0.001). Additionally, patients with perianal disease spent on average 1.29 more days in the hospital (7.45 vs. 6.16 days, p < 0.001) and accrued $5838 extra in hospital charges (p = 0.005). Perianal disease in younger patients is associated with a longer length of stay, higher hospital charges, and increased rates of both perineal and abdominal operative procedures. These data support the notion that, similar to adults, the presence of perianal disease in pediatric Crohn's patients is associated with a more severe course.

E-Learning for Rare Diseases: An Example Using Fabry Disease.

PubMed

Cimmaruta, Chiara; Liguori, Ludovica; Monticelli, Maria; Andreotti, Giuseppina; Citro, Valentina

2017-09-24

Rare diseases represent a challenge for physicians because patients are rarely seen, and they can manifest with symptoms similar to those of common diseases. In this work, genetic confirmation of diagnosis is derived from DNA sequencing. We present a tutorial for the molecular analysis of a rare disease using Fabry disease as an example. An exonic sequence derived from a hypothetical male patient was matched against human reference data using a genome browser. The missense mutation was identified by running BlastX, and information on the affected protein was retrieved from the database UniProt. The pathogenic nature of the mutation was assessed with PolyPhen-2. Disease-specific databases were used to assess whether the missense mutation led to a severe phenotype, and whether pharmacological therapy was an option. An inexpensive bioinformatics approach is presented to get the reader acquainted with the diagnosis of Fabry disease. The reader is introduced to the field of pharmacological chaperones, a therapeutic approach that can be applied only to certain Fabry genotypes. The principle underlying the analysis of exome sequencing can be explained in simple terms using web applications and databases which facilitate diagnosis and therapeutic choices.

Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

PubMed

Wolters, Frank L; Joling, Catelijne; Russel, Maurice G; Sijbrandij, Jildou; De Bruin, Marion; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Bodini, Paolo; Ryan, Barbara; O'Morain, Colm; Mouzas, Ioannis A; Tsianos, Epameinondas; Vermeire, Severine; Monteiro, Estela; Limonard, Charles; Vatn, Morten; Fornaciari, Giovanni; Rodriguez, Dolores; Groot, Wim; Moum, Bjørn; Stockbrügger, Reinhold W

2007-03-01

Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

HIV and Cardiovascular Disease

MedlinePlus

... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

Newcastle disease in poultry (Avian pneumoencephalitis, Exotic or velogenic Newcastle disease)

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND) is an infection of domestic poultry and other bird species with virulent Newcastle disease virus (vNDV). It is a worldwide problem that presents primarily as an acute respiratory disease, but depression, nervous manifestations, or diarrhea may be the predominant clinical form...

Emerging zoonotic viral diseases.

PubMed

Wang, L-F; Crameri, G

2014-08-01

Zoonotic diseases are infectious diseases that are naturally transmitted from vertebrate animals to humans and vice versa. They are caused by all types of pathogenic agents, including bacteria, parasites, fungi, viruses and prions. Although they have been recognised for many centuries, their impact on public health has increased in the last few decades due to a combination of the success in reducing the spread of human infectious diseases through vaccination and effective therapies and the emergence of novel zoonotic diseases. It is being increasingly recognised that a One Health approach at the human-animal-ecosystem interface is needed for effective investigation, prevention and control of any emerging zoonotic disease. Here, the authors will review the drivers for emergence, highlight some of the high-impact emerging zoonotic diseases of the last two decades and provide examples of novel One Health approaches for disease investigation, prevention and control. Although this review focuses on emerging zoonotic viral diseases, the authors consider that the discussions presented in this paper will be equally applicable to emerging zoonotic diseases of other pathogen types.

Miscellaneous bacterial diseases

USGS Publications Warehouse

Friend, M.

1999-01-01

Disease in free-ranging birds is caused by many other pathogenic bacteria in addition to those illustrated within this section. These other diseases are currently considered less important because of their infrequent occurrence, the small numbers of birds generally lost annually, or because they primarily result from infection by opportunistic pathogens and they require concurrent disease processes for them to become apparent. The following brief highlights about the more important of these diseases are included to acquaint readers with their existence and provide some basic information about their ecology.

The link between chronic kidney disease and cardiovascular disease.

PubMed

Said, Sarmad; Hernandez, German T

2014-07-01

It is well known that patients with chronic kidney disease (CKD) have a strong risk of cardiovascular disease (CVD). However, the excess risk of cardiovascular disease in patients with CKD is only partially explained by the presence of traditional risk factors, such as hypertension and diabetes mellitus. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Chronic kidney disease even in its early stages can cause hypertension and potentiate the risk for cardiovascular disease. However, the practice of intensive blood pressure lowering was criticized in recent systematic reviews. Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mmHg as recommended in the guidelines improves clinical outcomes more than a target of less than 140/90 mmHg in adults with CKD. The association between CKD and CVD has been extensively documented in the literature. Both CKD and CVD share common traditional risk factors, such as smoking, obesity, hypertension, diabetes mellitus, and dyslipidemia. However, cardiovascular disease remains often underdiagnosed und undertreated in patients with CKD. It is imperative that as clinicians, we recognize that patients with CKD are a group at high risk for developing CVD and cardiovascular events. Additional studies devoted to further understand the risk factors for CVD in patients with CKD are necessary to develop and institute preventative and treatment strategies to reduce the high morbidity and mortality in patients with CKD.

Menopause and Rheumatic Disease.

PubMed

Talsania, Mitali; Scofield, Robert Hal

2017-05-01

Menopause occurs naturally in women at about 50 years of age. There is a wealth of data concerning the relationship of menopause to systemic lupus erythematosus, rheumatoid arthritis, and osteoarthritis; there are limited data concerning other rheumatic diseases. Age at menopause may affect the risk and course of rheumatic diseases. Osteoporosis, an integral part of inflammatory rheumatic diseases, is made worse by menopause. Hormone replacement therapy has been studied; its effects vary depending on the disease and even different manifestations within the same disease. Cyclophosphamide can induce early menopause, but there is underlying decreased ovarian reserve in rheumatic diseases. Published by Elsevier Inc.

Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

PubMed

Kozaki, Kouji; Yamagata, Yuki; Mizoguchi, Riichiro; Imai, Takeshi; Ohe, Kazuhiko

2017-06-19

Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems. We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases. We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images. Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information

Inflammatory Mechanisms Linking Periodontal Diseases to Cardiovascular Diseases

PubMed Central

Schenkein, Harvey A.; Loos, Bruno G.

2015-01-01

Aims In this paper, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases (CVD) are reviewed. Materials and Methods and Results This paper is a literature review. Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory responses in atheromatous lesions due to periodontal infections. These include increased systemic levels of inflammatory mediators stimulated by bacteria and their products at sites distant from the oral cavity, elevated thrombotic and hemostatic markers that promote a prothrombotic state and inflammation, cross-reactive systemic antibodies that promote inflammation and interact with the atheroma, promotion of dyslipidemia with consequent increases in proinflammatory lipid classes and subclasses, and common genetic susceptibility factors present in both disease leading to increased inflammatory responses. Conclusions Such mechanisms may be thought to act in concert to increase systemic inflammation in periodontal disease and to promote or exacerbate atherogenesis. However, proof that the increase in systemic inflammation attributable to periodontitis impacts inflammatory responses during atheroma development, thrombotic events, or myocardial infarction or stroke is lacking. PMID:23627334

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre.

PubMed

Kocsis, Dorottya; Tóth, Zsuzsanna; Csontos, Ágnes A; Miheller, Pál; Pák, Péter; Herszényi, László; Tóth, Miklós; Tulassay, Zsolt; Juhász, Márk

2015-10-19

Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population.

[The disease burden of cardiovascular and circulatory diseases in China, 1990 and 2010].

PubMed

Liu, Jiangmei; Liu, Yunning; Wang, Lijun; Yin, Peng; Liu, Shiwei; You, Jinling; Zeng, Xinying; Zhou, Maigeng

2015-04-01

To analyze the death status of disease burden of cardiovascular and circulatory diseases in 1990 and 2010 in China, and to provide the basic information for cardiovascular and circulatory disease prevention and control. Using the results of the Global Burden of Diseases Study 2010 (GBD 2010) to describe the cardiovascular and circulatory diseases deaths status and disease burden in China. The measurement index included the mortality, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). At the same time, we used the population from 2010 national census as standard population to calculate the age-standardized mortality rate and DALY rate, YLL rate and YLD rates which will describe the mortality status and disease burden of total and different types of cardiovascular disease. We also calculated the change in 1990 and 2010 for all indexes, to describe the change of the burden of disease in the 20 years. In 2010, the total deaths of cardiovascular and circulatory diseases reached 3.136 2 million, the mortality rate reached 233.70 per 100 000 people and the age-standardized mortality rate was 256.90 per 100 000 people. The total DALYs, YLLs, and YLDs of cardiovascular and circulatory diseases reached 58.2055, 54.0488, and 4.1568 million person-years, respectively, and the age-standardized DALY rate, YLL rate and YLD rate were 4 639.04, 4 313.13, 325.91 per 100 000. In 1990, the deaths only 2.1675 million and the DALYs, YLLs and YLDs were 45.2679, 42.2922, and 2.9757 million person-years. The age-standardized mortality rate was 300.30 per 100 000 people. And the age-standardized DALY rate, YLL rate and YLD rate were 5 872.58, 5 523.42 and 349.16 per 100 000. Compared with the result in 1990, the total deaths, DALYs, YLLs, and YLDs were increased 44.72%, 28.58%, 27.80%, and 39.68%, respectively, while the age-standardized mortality rate, age-standardized DALY rate, age-standardized YLL rate, and

Dupuytren disease: an evolving understanding of an age-old disease.

PubMed

Black, Eric M; Blazar, Philip E

2011-12-01

Dupuytren disease, a clinical entity originally described more than 400 years ago, is a progressive disease of genetic origin. Excessive myofibroblast proliferation and altered collagen matrix composition lead to thickened and contracted palmar fascia; the resultant digital flexion contractures may severely limit function. The pathophysiology is multifactorial and remains a topic of research and debate. Genetic predisposition, trauma, inflammatory response, ischemia, and environment, as well as variable expression of proteins and growth factors within the local tissue, all play a role in the disease process. Common treatments of severe disease include open fasciectomy or fasciotomy. These procedures may be complicated by the complex anatomic relationships between cords (pathologic contracted fascia) and adjacent neurovascular structures. Recent advances in the management of Dupuytren disease involve less invasive treatments, such as percutaneous needle fasciotomy and injectable collagenase Clostridium histolyticum. Postoperative management focuses on minimizing the cellular response of cord disruption and maximizing range of motion through static or dynamic extension splinting.

Pharmacological treatments and infectious diseases in pediatric inflammatory bowel disease.

PubMed

Dipasquale, Valeria; Romano, Claudio

2018-03-01

The incidence of pediatric inflammatory bowel disease (IBD) is rising, as is the employment of immunosuppressive and biological drugs. Most patients with IBD receive immunosuppressive therapies during the course of the disease. These molecules are a double-edged sword; while they can help control disease activity, they also increase the risk of infections. Therefore, it is important that pediatricians involved in primary care, pediatric gastroenterologists, and infectious disease physicians have a thorough knowledge of the infections that can affect patients with IBD. Areas covered: A broad review of the major infectious diseases that have been reported in children and adolescents with IBD was performed, and information regarding surveillance, diagnosis and management were updated. The possible correlations with IBD pharmacological tools are discussed. Expert commentary: Opportunistic infections are possible in pediatric IBD, and immunosuppressive and immunomodulator therapy seems to play a causative role. Heightened awareness and vigilant surveillance leading to prompt diagnosis and treatment are important for optimal management.

Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease.

PubMed

Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen; Nordestgaard, Børge G; Hallas, Jesper; Lange, Peter

2015-01-01

We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P < 0.001), and more of them had a history of respiratory infections (6.8 vs 1.4%, P < 0.001) than individuals with COPD but without gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3-5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6-2.7, P = 0.63). Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly. © 2014 Asian Pacific Society of Respirology.