Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer
| العنوان: | Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer |
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| المؤلفون: | Richard Phillips, Eveline van der Veer, Tjip S. van der Werf, Yves Thierry Barogui, Cleo van Diemen, Sandor-Adrian Klis, Ymkje Stienstra, Roch Christian Johnson |
| المساهمون: | Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Microbes in Health and Disease (MHD) |
| المصدر: | PLoS Neglected Tropical Diseases, 10(4):e0004594. PUBLIC LIBRARY SCIENCE PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004594 (2016) PLoS Neglected Tropical Diseases |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Buruli ulcer, Male, Bacterial Diseases, Organic chemistry, Pathology and Laboratory Medicine, Gastroenterology, DISEASE, 0302 clinical medicine, Anti-Infective Agents, Antibiotics, MYCOLACTONE, INFECTION, Medicine and Health Sciences, ANTIMICROBIAL TREATMENT, 030212 general & internal medicine, Treatment Failure, Vitamin D, Buruli Ulcer, Cation Transport Proteins, Immune Response, Randomized Controlled Trials as Topic, biology, Antimicrobials, lcsh:Public aspects of medicine, Drugs, Vitamins, 3. Good health, Physical sciences, Actinobacteria, Chemistry, Infectious Diseases, Mycobacterium ulcerans, Streptomycin, MYCOBACTERIUM-ULCERANS, ANTIBIOTIC-TREATMENT, Female, medicine.symptom, Research Article, Neglected Tropical Diseases, VITAMIN-D DEFICIENCY, medicine.medical_specialty, Tuberculosis, lcsh:Arctic medicine. Tropical medicine, Genotype, lcsh:RC955-962, 030231 tropical medicine, Immunology, Radioimmunoassay, Genetic Predisposition, TUBERCULOSIS, Polymorphism, Single Nucleotide, Microbiology, vitamin D deficiency, Lesion, 03 medical and health sciences, Chemical compounds, Signs and Symptoms, Diagnostic Medicine, Internal medicine, Microbial Control, Organic compounds, medicine, Genetic predisposition, Vitamin D and neurology, Genetics, MANAGEMENT, Humans, Genetic Predisposition to Disease, CLINICAL-EFFICACY, Pharmacology, Bacteria, business.industry, Public Health, Environmental and Occupational Health, Organisms, Paradoxical reaction, Biology and Life Sciences, lcsh:RA1-1270, biology.organism_classification, medicine.disease, Tropical Diseases, Mycobacterium Ulcerans, Genetics of Disease, Lesions, business |
| الوصف: | Introduction Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU. Methods The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable. Results Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ2), larger lesions (p = .021 by Χ2) and genetic factors. The polymorphisms 3’UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms. Conclusions Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene. Author Summary Buruli ulcer is an infectious disease of skin, subcutaneous fat and sometimes bone, mainly affecting children in West Africa. It is considered as one of the Neglected Tropical Diseases but the disease occurs also in moderate climates like South East Australia and Japan where it may also affect adults. Once a patient has started antibiotic treatment, lesions may increase in size even if the antimicrobial treatment is effective; this is highly confusing for doctors and patients as they may think that treatment actually fails. The cause of Buruli ulcer is Mycobacterium ulcerans, related to other mycobacteria that cause disease in man, like leprosy and tuberculosis. Using data from two different studies in West Africa, we show that these paradoxical reactions are associated with trunk localization and that they occur more often in larger lesions. The chance to develop these reactions appeared partly inherited: carrying the homozygous ins/ins genotype of 3’UTR TGTG 285 polymorphism in the SLC11A1 gene increased the risk of paradoxical reactions. Vitamin D is important for the immune defense against infections by mycobacteria. Vitamin D blood concentrations were not associated with paradoxical reactions; patients generally did well, and we did not need corticosteroid immune suppression to overcome these reactions. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1935-2735 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d338c26b1e71ffeb825837ff59576d5Test https://hdl.handle.net/11370/50d879bd-5e48-4362-a9a3-b7a535d99e96Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4d338c26b1e71ffeb825837ff59576d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 |
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