ABSTRACT
Introducción: la micobacteria no terberculosa (NTM) forma un grupo heterogéneo de microorganismos que pueden causar infección en humanos. Las micobacterias no pigmentadas de rápido crecimiento (MNPCR) son de interés clínico debido al creciente número de pacientes infectados por ellos y a la dificultad del tratamiento. Dentro de este grupo, Mycobacterium fortuitum, Mycobacterium abscessus y Mycobacterium chelonae son reconocidos como patógenos potenciales; estas especies se han aislado de infecciones pulmonares y extrapulmonares. Objetivo: el objetivo de este trabajo es encontrar la frecuencia de aislamiento de especies micobacterianas de rápido crecimiento, específicamente el complejo Mycobacterium fortuitum, de muestras clínicas utilizando la técnica molecular de diagnóstico GenoType Mycobacterium CM. Material y Método: se analizaron 249 aislados de micobacterias no tuberculosas obtenidas de muestras pulmonares y extrapulmonares de pacientes sintomáticos en el período enero 2018-diciembre de 2022. La técnica molecular GenoType Mycobacterium CM se utilizó para identificar la especie. Resultados: Se obtuvieron 77 (3,9%) aislados de especies no pigmentadas de rápido crecimiento, estas se identificaron en orden decreciente: Mycobacterium fortuitum 65 (84,41%), Mycobacterium abcessus 9 (11,68%) y Mycobacterium chelonae 3 (4%). Conclusiones: los resultados reafirman que el complejo Mycobacterium fortuitum es responsable de la mayoría de las infecciones causadas por la micobacteria en rápido crecimiento en humanos. La técnica diagnóstica GenoType Mycobacterium CM es una herramienta útil para la rápida identificación de micobacterias; proporciona resultados precisos en menos tiempo, acortando significativamente el tiempo diagnóstico, permite la aplicación temprana de tratamiento específico, evitando así la propagación de la infección.
Introduction: non-tuberculous mycobacteria (NTM) form a heterogeneous group of mi-croorganisms that can cause infection in humans. Fast-growing non-pigmented my-cobacteria (MNPCR) are of clinical interest due to the increasing number of patients infected by them and the difficulty of treatment. Within this group, Mycobacterium fortuitum, Mycobacterium abscessus and Mycobacterium chelonae are recognized as potential pathogens; these species have been isolated from both pulmonary and ex-trapulmonary infections. Objective: the objective of this work is to find the frequency of isolation of fast-growing non-pigmented mycobacterial species, specifically the Myco-bacterium fortuitum complex, from clinical samples using the GenoType® Mycobacteri-um CM diagnostic molecular technique. Material and Method: 249 isolates of non-tu-berculous mycobacteria obtained from pulmonary and extrapulmonary samples from symptomatic patients in the period January 2018-December 2022 were analyzed. The G e n oTy p e® Mycobacterium CM molecular technique was used to identify the species. Results: 77 (30.9%) isolates of fast-growing non-pigmented species were obtained, these were identified in decreasing order: Mycobacterium fortuitum 65 (84.41%), Myco-bacterium abcessus 9 (11.68%) and Mycobacterium chelonae 3 (4%). Conclusions: the results reaffirm that the Mycobacterium fortuitum complex is responsible for most in-fections caused by fast-growing mycobacteria in humans. The GenoType® Mycobacte-riumCM diagnostic technique is a useful tool for the rapid identification of mycobacte-ria; it provides accurate results in less time, significantly shortening the diagnostic time, it allows the early application of specific treatment, thus avoiding the spread of infec-tion.
Subject(s)
Humans , Nontuberculous Mycobacteria/isolation & purification , Mycobacterium Infections, Nontuberculous/diagnosis , Therapeutics , Molecular Diagnostic Techniques/methodsABSTRACT
Objective To analyze the distribution characteristics and drug resistance of nontuberculous mycobacteria(NTM),and to provide guidance for the selection of targeted agents in clinical treatment. Methods The clinical data of inpatients in our hospital from April 2019 to February 2021 were collected,the culture and strain identification of non tuberculosis mycobacteria were carried out,the drug sensitivity test of anti tuberculosis drugs was carried out,and the drug resistance of non tuberculosis mycobacteria to first-line anti tuberculosis drugs was analyzed. Results A total of 1 326 strains of mycobacterium were isolated,including 1 154(87.03%)strains of mycobacterium tuberculosis and 172(12.97%)strains of non-mycobacterium tuberculosis.Nine species of nontuberculous mycobacteria were detected,including slow-growing mycobacteria such as Mycobacterium kansasii and Mycobacterium avium-intracellulare complex,belonging to Groups I-III,and fast-growing mycobacteria such as Mycobacterium chelonae and Mycobacterium smegmatis,belonging to Group IV. Among them , Mycobacterium avium-intracellulare complex and Mycobacterium chelonae were dominant,accounting for 26.16%and 36.63%,respectively.Drug susceptibility tests showed that the resistance rate of Mycobacterium avium-intracellulare complex to streptomycin was 100.00%,the drug resistance rate of Mycobacterium chelonae to isoniazid,rifampicin and streptomycin was 100.00%,and the drug resistance rate of Mycobacterium smegmatis and Mycobacterium abscessus to most antibacterial drugs was 100.00%.The resistance rate of major NTM bacteria to clarithromycin was relatively low.There was no statistically significant difference in the susceptibility rates of slow and fast-growing mycobacteria to isoniazid and clarithromycin(P>0.05) ; The susceptibility rates of slow-growing mycobacteria to amikacin,clarithromycin and rifambutin were 62.86%,92.86%and 72.86%,all above 50.00%.The susceptibility rate of the fast-growing mycobacteria to clarithromycin was also more than 50.00%,being 87.25%.The susceptibility rate of slow-growing mycobacteria to other antibiotics was higher than that of fast-growing mycobacteria(P<0.05).The drug resistance of Mycobacterium tuberculosis to first-line anti tuberculosis drugs was significantly lower than that of non Mycobacterium tuberculosis(P<0.05). Conclusion Non-tuberculous mycobacteria have high drug resistance,especially fast-growing mycobacteria,so drug susceptibility tests are of great value in clinical treatment.
ABSTRACT
Objective: To explore CT characteristics of mycobacterium intracellulare pulmonary diseases compared with mycobacterium kansasii, mycobacterium abscess/chelonei pulmonary diseases. Methods: CT images of 35 patients with mycobacterium intracellulare pulmonary diseases, 18 with mycobacterium kansasii pulmonary disease and 22 with mycobacterium abscess/chelonei pulmonary disease confirmed by clinical data and laboratory tests were retrospectively analyzed, and imaging findings were evaluated and compared. Results: Mycobacterium intracellulare pulmonary disease involved both lungs (33/35, 94.29%), multiple lobes (18/35, 51.43%) or all lobes (16/35, 45.71%). CT characteristics included cord shadow (34/35, 97.14%), air space consolidation (33/35, 94.29%), centrilobular nodules or tree in bud (32/35, 91.43%), thickened pleura (32/35, 91.43%), ground glass opacity (31/35, 88.57%), traction bronchiectasis (30/35, 85.71%), non-traction bronchiectasis (25/35, 71.43%), nodes (24/35, 68.57%), calcification (24/35, 68.57%) and cavity (23/35, 65.71%). Ground glass opacity was more frequently observed in mycobacterium intracellulare than mycobacterium kansasii (P=0.001) and mycobacterium abscess/chelonei pulmonary disease (P<0.001). Walls of the cavity were thicker in mycobacterium intracellulare than mycobacterium kansasii (P=0.019) and mycobacterium abscess/chelonei pulmonary disease (P=0.024). Calcifications were more frequently observed in mycobacterium intracellulare than in mycobacterium kansasii (P=0.014) and mycobacterium abscess/chelonei pulmonary disease (P=0.007). Conclusion: Compared with mycobacterium kansasii and abscess/chelonei pulmonary disease, CT findings of mycobacterium intracellulare have certain characteristics, which may be helpful to differential diagnosis.
ABSTRACT
Resumen Se comunican dos casos clínicos poco frecuentes de micobacteriosis cutáneas; uno adquirido en la comunidad y uno en medio hospitalario, ambos pacientes del género masculino, con dermatosis crónicas constituidas por úlceras, fístulas y placas de aspecto papilomatoso. El diagnóstico fue tardío y la evolución no fue satisfactoria, a pesar de prescribir tratamiento adecuado contra Mycobacterium chelonae. El propósito de este artículo es mostrar la manifestación clínica de las lesiones para sospecha diagnóstica temprana y oportuna de las diferentes disciplinas médicas que participan en la atención de los pacientes con estas infecciones.
Abstract This paper reports the two rare clinical cases of cutaneous mycobacterial infections. One of them acquired the infection within the community while the other was a nosocomial case, both cases were male with chronic ulcers, fistulae and papilloma-like lesions. In both cases diagnosis was late and evolution, despite correct Mycobacterium chelonae treatment, was unsatisfactory. The purpose of this paper is to show the clinical presentation and accurate suspicion of infection of the different medical areas involved in its management.
ABSTRACT
Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacterium. The skin and soft tissue infections due to this organism are steadily on the rise and need to be delineated specifically as most of these are not responsive to routine antituberculosis treatment. Here, we report 3 different presentations caused by Mycobacterium chelonae in traumatic and surgical wounds. Mycobacterium chelonae can complicate surgical or traumatic wounds.This infection may also present as injection site abscesses. Diabetics on insulin injections are especially at risk. A high index of suspicion is necessary in long standing culture negative lesions for clinching the diagnosis. PCR can be helpful in confirming the diagnosis.
ABSTRACT
No abstract available.
Subject(s)
Acupuncture , Mycobacterium chelonae , Mycobacterium , Nontuberculous MycobacteriaABSTRACT
Around 50 mycobacteria species cause human disease. Immunosuppressive states predispose to non-tuberculous mycobaterium infection, such as Mycobacterium chelonae: AFB, non-tuberculous, fast growth of low virulence and uncommon as a human pathogen. It may compromise the skin and soft tissues, lungs, lymph nodes and there is also a disseminated presentation. The diagnosis involves AFB identification and culture on Agar and Lowenstein-Jensen medium base. A 41-year-old female with MCTD (LES predominance) is reported, presenting painless nodules in the right forearm. She denied local trauma. Immunosuppressed with prednisone and cyclophosphamide for 24 months. Lesion biopsy has demonstrated positive bacilloscopy (Ziehl-Neelsen stain) and M.chelonae in culture (Lowenstein-Jensen medium base), therefore clarithromycin treatment has been started (best therapy choice in the literature).
Subject(s)
Adult , Female , Humans , Mixed Connective Tissue Disease/drug therapy , Mycobacterium Infections, Nontuberculous/immunology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium chelonae/isolation & purification , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Immunocompetence/immunology , Immunosuppressive Agents/adverse effects , Mixed Connective Tissue Disease/complications , Mycobacterium Infections, Nontuberculous/drug therapyABSTRACT
We aim to communicate the experience gathered during the management of infections by atypical mycobacteria in immunocompetent patients in a general practice. Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections were identified: 2 with cutaneous involvement and 3 with lung infection. None of them had evidence of immunosuppression. A patient with elbow bursitis by M. chelonae presented with a high mononuclear count in fluid analysis with mycobacterial growth at the fifth day of culture. He evolved satisfactorily with clarithromycin. A case with M. fortuitum skin infection had a delayed initial diagnosis with progression to local draining lymph nodes; the culture when requested was positive after 13 days of incubation. Patients with pulmonary infection presented with prolonged cough and sputum and had in common to be postmenopausal women displaying small nodules and bronchiectases at lung images, a classical pattern. Time elapsed between respiratory sampling and a definitive inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non-immunosuppresed patients can generate diagnostic and therapeutic challenges. Delay in identification contributes to this problem.
El objetivo de este trabajo es reportar la experiencia acumulada sobre infecciones por micobacterias atípicas en pacientes sin inmunosupresión. Entre el año 2008 y 2013 se observaron cinco pacientes con infección por micobacterias atípicas: dos con infección cutánea y tres con infección pulmonar. Ninguno de estos pacientes tenía evidencias de inmunosupresión. Un paciente con bursitis de codo por M. chelonae tuvo un estudio citoquímico con aumento de celularidad de predominio mononuclear y desarrollo de bacterias al quinto día; respondió favorablemente a claritromicina. Un caso con infección cutánea por M. fortuitum evolucionó en forma prolongada con supuración ganglionar antes del diagnóstico y el cultivo solicitado a los 13 días fue positivo. Los tres pacientes con aislados pulmonares presentaron tos y expectoración y tenían en común ser mujeres en edad post-menopáusica y presentar pequeños infiltrados nodulares asociados a bronquiectasias en el estudio de imágenes pulmonares, un patrón descrito en la literatura científica. En estos tres casos, la latencia entre la toma de muestra y el informe definitivo tuvo un rango de 40 a 89 días. El aislamiento de micobacterias atípicas en muestras de expectoración en pacientes sin inmunosupresión se da en un contexto típico pero plantea dificultades diagnósticas y terapéuticas. El lento crecimiento de estos microorganismos en el laboratorio contribuye a este problema.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Mycobacterium Infections, Nontuberculous/diagnosis , Nontuberculous Mycobacteria/isolation & purification , Bronchiectasis/diagnosis , Delayed Diagnosis , Lymphatic Diseases/pathology , Multiple Pulmonary Nodules/diagnosis , Mycobacterium Infections, Nontuberculous/microbiologyABSTRACT
Mycobacterium chelonae is a rapidly growing mycobacterium that is found all over the environment, including sewage and tap water. They are important species associated with chronic non-healing wounds. We report a case in a 41 year old female patient who underwent multiple surgeries for an ovarian cyst, tuboovarian abscesses with peritonitis and a repair of an abdominal incisional hernia.
ABSTRACT
Non-tubecrulosis mycobacterium infections were increasingly reported either pulmonary or extrapulmonary in the past decades. In Taiwan, we noticed several reports about the soft tissue infections caused by rapid growing mycobacterium such as Mycobacterium abscessus, Mycobacterium chelonae, on newspaper, magazines, or the multimedia. Most of them occurred after a plastic surgery, and medical or non-medical procedures. Here, we reported two cases of these infections following medical procedures. We also discussed common features and the clinical course of the disease, the characteristics of the infected site, and the treatment strategy. The literatures were also reviewed, and the necessity of the treatment guidelines was discussed.
Subject(s)
Multimedia , Mycobacterium chelonae , Mycobacterium Infections , Mycobacterium , Periodical , Periodicals as Topic , Soft Tissue Infections , Surgery, Plastic , TaiwanABSTRACT
No abstract available.
Subject(s)
Humans , Immunosuppression Therapy , Mycobacterium chelonaeABSTRACT
<p><b>OBJECTIVE</b>To identify the novel species 'Mycobacterium fukienense' sp. nov of Mycobacterium chelonae/abscessus complex from tuberculosis patients in Fujian Province, China.</p><p><b>METHODS</b>Five of 27 clinical Mycobacterium isolates (Cls) were previously identified as M. chelonae/abscessus complex by sequencing the hsp65, rpoB, 16S-23S rRNA internal transcribed spacer region (its), recA and sodA house-keeping genes commonly used to describe the molecular characteristics of Mycobacterium. Clinical Mycobacterium isolates were classified according to the gene sequence using a clustering analysis program. Sequence similarity within clusters and diversity between clusters were analyzed.</p><p><b>RESULTS</b>The 5 isolates were identified with distinct sequences exhibiting 99.8% homology in the hsp65 gene. However, a complete lack of homology was observed among the sequences of the rpoB, 16S-23S rRNA internal transcribed spacer region (its), sodA, and recA genes as compared with the M. abscessus. Furthermore, no match for rpoB, sodA, and recA genes was identified among the published sequences.</p><p><b>CONCLUSION</b>The novel species, Mycobacterium fukienense, is identified from tuberculosis patients in Fujian Province, China, which does not belong to any existing subspecies of M. chelonea/abscessus complex.</p>
Subject(s)
Humans , Bacterial Proteins , Genetics , Base Sequence , China , Epidemiology , Cluster Analysis , DNA, Bacterial , Genetics , Molecular Sequence Data , Mycobacterium , Classification , Genetics , Mycobacterium Infections, Nontuberculous , Epidemiology , Microbiology , Mycobacterium chelonae , Classification , Genetics , Phylogeny , Sequence Alignment , Tuberculosis , Epidemiology , MicrobiologyABSTRACT
Mycobacterium chelonae lung disease is very rare. We report a case of lung disease caused by M. chelonae in a previously healthy woman. A 69-year-old woman was referred to our hospital because of hemoptysis. A computed tomography (CT) scan of the chest revealed bronchiolitis associated with bronchiectasis in the lingular division of the left upper lobe. Nontuberculous mycobacteria were isolated three times from sputum specimens. All isolates were identified as M. chelonae by various molecular methods that characterized rpoB and hsp65 gene sequences. Although some new lesions including bronchiolitis in the superior segment of the left lower lobe developed on the chest CT scan 35 months after diagnosis, she has been followed up without antibiotic therapy because of her mild symptoms. To the best of our knowledge, this is the first case of M. chelonae lung disease in Korea in which the etiologic organisms were confirmed using molecular techniques.
Subject(s)
Female , Humans , Bronchiectasis , Bronchiolitis , Hemoptysis , Korea , Lung , Lung Diseases , Mycobacterium , Mycobacterium chelonae , Nontuberculous Mycobacteria , Sputum , ThoraxABSTRACT
The Mycobacterium chelonae/abscessus (M.chelonae/abscessus) complex belongs to the rapidly growing genus Mycobacterium (RGM).It is one of the most important pathogenic members of Mycobacterium leading to nosocomial infections and outbreaks.It includes members of M.chelonae,M.immnunogenum,M.abscessus,M.massiliense,and M.bolletii.In order to investigate the epidemiological characteristics of the M.chelonae/abscessus complex in China and to conduct the molecular methods for species identification of M.chelonae/abscessus,we collected clinical M.chelonae/abscessus complex strains identified by phenotypic tests.Members were verified by sequencing of 16S rRNA,Species and subspecies were identified by hsp65 and rpoB PCR RFLP methods.In total,27 clinical specimens were identified as Mycobacterium chelonae/abscessus complex by phenotypic tests.16s rRNA gene sequence analysis of all 27 clinical samples shared over 99.7％ similarity with M.chelonae and M.abscessus.Species identification with hsp65 PCR-RFLP and rpoB PCR-RFLP revealed that 18 specimens were M.abscessus and 4 were M.absecces.The remaining 5 samples displayed a pattern that failed to match any previously reported pattern.Thus,this might represent a novel species that is part of the Mycobacterium chelonae/abscessus complex.We identified that a majority of the chronic lung infection in China is caused by the M.chelonae/abscessus complex.Specifically,the M.abscessus species might be the most infectious,while other species in the complex can still cause infection.Interestingly,there may be a novel or previously unidentified species that is a part of the complex.Finally,we show that species identification can be carried out more accurately by combined use of hsp65 and rpoB PCR-RFLP.
ABSTRACT
The pathogenic potential of the rapidly growing mycobacteria (RGM) has started being recognized. This is due to more sensitive and specific techniques in the laboratory. The RGM are generally defined as nontuberculous species of mycobacteria that show visible growth on agar media within 7 days. RGM are widely distributed in nature and have been isolated from natural water, tap water, and soil. Several biochemical tests, high performance liquid chromatography, and molecular techniques have been developed for rapid identification of these species. The American Thoracic Society and the Infectious Disease Society of America recommend that RGM should be identified to the species level using a recognized acceptable methodology such as polymerase chain reaction restriction enzyme analysis or biochemical testing and routine susceptibility testing of RGM should include amikacin, imipenem, doxycycline, the fluorinated quinolones, a sulphonamide or trimethoprim-sulphamethoxazole, cefoxitin, clarithromycin, linezolid, and tobramycin. The diseases caused by these organisms have varied manifestations. They have been responsible for a number of healthcare-associated outbreaks and pseudo-outbreaks. For recognition of outbreaks, it is important to be familiar with the causative organisms like RGM which are most frequently involved in healthcare-associated outbreaks and pseudo outbreaks. It is essential to intervene as soon as possible to interrupt this transmission. Large gaps still exist in our knowledge of RGM. Unquestionably more studies are required. Through this review, we wish to emphasize that reporting of RGM from clinical settings along with their sensitivity patterns is an absolute need of the hour.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteriological Techniques/methods , Cross Infection/diagnosis , Cross Infection/microbiology , Humans , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/isolation & purificationABSTRACT
Mycobacterium chelonae is a rapidly growing atypical mycobacterium found in soil and water. In a healthy person, it causes cutaneous infection after an invasive procedure or surgery. Herein, we present a case of a 52-year-old man with multiple erythematous plaques and nodules on the back and left arm, and these occurred at the site of bee sting therapy by a herbal medical doctor. The histologic findings showed a granulomatous infiltration composed of numerous neutrophils, lymphocytes, eosinophils, histiocytes and multinucleated giant cells. Acid fast bacilli were detected by Ziehl-Neelsen stain and Mycobacterium chelonae infection was confirmed by an INNO-LiPA mycobacteria kit. The patient was treated with 1 g of clarithromycin and 200 mg of doxycycline for 6 months and his condition improved considerably.
Subject(s)
Humans , Middle Aged , Arm , Bees , Bites and Stings , Clarithromycin , Doxycycline , Eosinophils , Giant Cells , Histiocytes , Lymphocytes , Mycobacterium chelonae , Neutrophils , Nontuberculous Mycobacteria , SoilABSTRACT
Although injectable soft-tissue augmentation materials are extremely well-tolerated, undesirable effects sometimes occur. Whereas minor adverse events such as erythema, edema or bruising are generally reversible, the formation of foreign body granuloma, atypical mycobacterial infections or tissue necrosis may cause serious irreversible damages and disfigurement. We present here the case of a 50-year-old woman with an indurated painful nodule and patch on the right cheek, and this occurred after an unlicensed nonspecialist injected filler of unknown ingredients. The histopathologic findings showed granulomatous inflammation composed of lymphocytes, histiocytes and multinucleated giant cells with a Swiss cheese appearance. Although any acid-fast bacilli were not observed on Ziehl-Neelsen staining, the mycobacterial culture demonstrated an ivory-colored wet colony that was identified as M. chelonae by polymerase chain reaction-restriction fragment length polymorphism. The patient was treated with 1 g of clarithromycin for seven weeks, and the lesion improved considerably.
Subject(s)
Female , Humans , Middle Aged , Cheek , Cheese , Clarithromycin , Edema , Erythema , Foreign Bodies , Giant Cells , Granuloma, Foreign-Body , Histiocytes , Inflammation , Lymphocytes , Mycobacterium , Mycobacterium chelonae , NecrosisABSTRACT
Mycobacterium chelonae is a rapidly-growing, atypical mycobacterium that can cause both systemic and cutaneous infections as a human pathogen. This saprophyte is ubiquitous in the environment and has been found in water, soil, and dust particles. Clustered outbreaks usually occur after inoculation with contaminated fluids or injectable medications. We report a case of M. chelonae infection in a 53-year-old female, who presented with multiple, tender, firm, erythematous nodules and plaques on the face which occurred 2 months after a filler injection. Culture demonstrated coagulase negative staphylococcus and atypical mycobacterium, which was identified as M. chelonae by polymerase chain reaction.
Subject(s)
Female , Humans , Middle Aged , Coagulase , Disease Outbreaks , Dust , Mycobacterium chelonae , Nontuberculous Mycobacteria , Polymerase Chain Reaction , Soil , StaphylococcusABSTRACT
A previously healthy, 54-year-old woman presented with Mycobacterium chelonae soft tissue infection and osteomyelitis of her left lower leg. The infection had started from soft tissue emerging at the medial aspect of the distal femur and had spread through the bone because of delayed diagnosis. The largely indolent, 8-month course to diagnosis was attributable to unremarkable clinical manifestations combined with a low index of suspicion such as immunocompetent patient and/or inadequate finding of acid-fast bacilli in a lesion smear, characteristic histopathological features, and culture techniques. Soft tissue infection and osteomyelitis were successfully treated without surgical intervention and with a 6-month course of chemotherapy.