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Case 1 A 40 yr old Canadian who is employed as a swimming pool instructor sees his physician because of a non healing ulcer on his left arm. He is afebrile & gives no history of night sweats, weight loss or other constitutional symptoms. Biopsy of the lesion grows granulomatous inflammation & rare acid fast organisms. A tuberculin test is negative. CASE 2: A 5 year old afebrile child develops unilateral, non tender anterior cervical nodes that have been enlarging over the past few weeks. A lymphnode biopsy reveals microabscesses with neutrophils. Culture results are pending. A mantoux test exhibits only 7 mm induration. Patient does not attend day care and there is no recent travel history. The patient has 2 pets, a gold fish & a turtle. Non Tuberculous Mycobacteria (NTM) Dr. Kavitha Santhosh, MD. Non tuberculous mycobacteria (Atypical mycobacteria) (Opportunistic mycobacteria) (Environmental mycobacteria) (MOTT) ( Mycobacteria Other Than TB) Mycobacterial spp other than organisms of M.tuberculosis complex & leprae Non Tuberculous Mycobacteria (NTM) Widely distributed in environment Symptomatic infections are often associated with defects in host defences Acid fast bacilli Runyon’s classification of Atypical Mycobacteria Classified into 4 gps based upon rate of growth & pigment prodn Photochromogens: pigment prodn only when exposed to light Scotochromogens: pigment prodn in the dark Non chromogens: no pigment Rapidly growing mycobacteria: 7 days Now: DNA probes for identification of common spp Runyon’s classification of Atypical Mycobacteria Pigment Gp Growth Light Dark Typical spp rate Slow Slow Slow + + _ _ + _ M.kansasi M.Marinum (Photo) I II III M.scrofulaceum (Scoto) Myc avium intracellulare complex (Non) M.Fortuitum- chelonei complex (Rapid) IV Rapid _ _ Epidemiology of atypical mycobacteria Waxy, hydrophobic, triple layered cell wall: unusually resistant to physical condition utilize wide variety of carbon & nitrogen sources : survive in nutrient poor environment So widely distributed in environment Water Soil Biofilms Numerous animal spp etc WORLDWIDE EPIDEMIOLOGY OF NTM Rate of infection /100,00 population Region Indolent Infection (“colonization”) North America 4 Advanced Infection (“disease”) 1-2 Europe Asia Africa 7 12 ? 1 3 ? Australia 5 1-2 Pathogenesis :Source of infection Pathogenesis of NTM infections Mode of entry: Cutaneous Respiratory Gastrointestinal Parenteral (rare) Organisms are ingested by host macrophages Intracellular survival, replication Symptomatic infection In immunocompetant host : granuloma formation Ultimate control of infection by intracellular killing of mycobacteria Requires Efficient CD4+T cell function Elaboration of IF-gamma & IL-12 HIV infections Inherited def in the prodn or response to IF-Ŷ Disseminated NTM infections Clinical Syndromes Cutaneous Diseases: M. abscessus, fortuitum, chelonae, marinum, ulcerans xenopi, malmonese Pulmonary Disease: MAC, kansasii, abscessus, Disseminated Disease : MAC, kansasii etc Other diseases at numerous anatomical locations Infections caused by NTM Group I : Photochromogens 1. M. kansasi Pulmonary disease Disseminated disease Pulmonary M. kansasi disease Clinically resembles TB N. America, Europe, S. Africa Predisposing factors COPD, Ca lung, silicosis, prior TB, poverty Source : Natural water sources Diagnosis Multiple sputum sample for AFB & culture In HIV + individual: Single positive sputum sample : significant Treatment Rifampin, isoniazid, Ethambutol for 18 months Disseminated M. kansasi disease Advanced AIDS (CD4+T cell count< 100/µl) Pts with leukemia, lymphoma or solid organ transplantations C/F : fever, weakness, weight loss, cough Diagnosis Isolation of Organism from a normally sterile parenchymal site or from blood Treatment Same as for pulmonary ds Pt receiving HAART : Rifabutin or clarithromycin 2. Mycobacterium marinum Swimming pool granuloma (fish tank granuloma) Abrasions incurred at swimming pools & aquariums Granulomatous ulcerative lesion Natural habitat : fresh & salt waters Diagnosis Mycobacterial culture of biopsied lesion Demonstration of granuloma or AFB in biopsy sample Treatment Clarithromycin + Ethambutol Fish tank granuloma by M.marinum Group II : Scotochromogens M. scrofulaceum Causes scrofula (granulomatous cervical adenitis) Organism enters thro’ oropharynx infects draining lymphnode Habitat : Environmental water sources Treatment: Surgical excision of affected lymphnode Scrofula King Charles II of England’s healing touch for “King’s evil” : Scrofula Group III : Non chromogens 1. Mycobacterium avium-intracellulare complex (MAI, MAC) Composed of 2 species : M. avium & M. intracellulare Most common bacterial cause of disease in AIDS patients Widespread in the environment (water, soil) Southeastern US It causes Pulmonary disease Disseminated disease Pulmonary MAC disease More common than Myc.TB in USA 2 patterns Primary : healthy non smokers (Lady Windermere syndrome) Secondary : Pts with preexisting pulmonary disease Clinical features Chronic cough, dyspnea, fatigue Diagnosis CT scan : charecteristic cylindrical bronchiectasis with nodule formation Chest X ray, Sputum for AFB, culture Treatment Daily ethambutol & rifabutin plus a macrolide for 1218months Chest X ray: Cavitary lung lesion caused by MAC Disseminated MAC disease Occurs principally among pts with advanced HIV living in developed countries & not receiving antiretroviral therapy. CD4+ T cell count < 100/µl HAART eliminates the risk when CD4+ T cell count > 100/µl for 3 months Clinical features Fever, weakness, weight loss Wasting syndrome in pts who are not receiving HAART Immune reconstitution syndrome in pts with subclinical infection who are receiving HAART Treatment Clarithromycin + Ethambutol with or without rifabutin along with HAART for HIV At least 12 mths till CD4+T> 100/µl for >6 mths Chemoprophylaxis: For prevention of disseminated M.avium infection in AIDS When CD4+T < 50/µl or a HIV pt has had a AIDS defining opportunistic inf Weekly azithromycin till CD4+T> 100/µl for >6 mths 2. M. ulcerans Causes Buruli ulcer (cutaneous infections) Endemic area: Africa, S.America, Malaysia, Indonesia, Papua New Guinea, Australia Bare arms of children living near river, lakes or swamps Transmission : minor trauma/ bite of aquatic insect Closely related to M.marinum Initial lesion : painless nodule deep ulcer Sloughing of skin & subcutaneous tissues Extensive necrosis Buruli Ulcer Tissue destruction due to mycolactone (toxin) Diagnosis Biopsy of lesion : AFB Treatment Surgical treatment Skin grafting Antibiotics: not beneficial Immunization with BCG reduces the risk by 50% Group IV (rapidly growing mycobacteria) 1. M. fortuitum-chelonei complex Two spp: M.fortuitum & M. chelonei Saprophyes: soil, water & nosocomial sources Infections in 2 populations Immunocompromised pts Disseminated cutaneous disease Pts with prosthetic hip joint & indwelling catheter Localized cutaneous infections in surgical/traumatic wounds 2. M. abscessus: Pulmonary infections In patients with underlying lung disease such as cystic fibrosis Rapidly growing NTM: common lab contaminant False alarms in the form of pseudoepidemics reported Treatment Amikacin + Doxycycline Case 1 A 40 yr old Canadian who is employed as a swimming pool instructor sees his physician because of a non healing ulcer on his left arm. He is afebrile & gives no history of night sweats, weight loss or other constitutional symptoms. Biopsy of the lesion grows granulomatous inflammation & rare acid fast organisms. A tuberculin test is negative. CASE 2: A 5 year old afebrile child develops unilateral, non tender anterior cervical nodes that have been enlarging over the past few weeks. A lymphnode biopsy reveals microabscesses with neutrophils. Culture results are pending. A mantoux test exhibits only 7 mm induration. Patient does not attend day care and there is no recent travel history. The patient has 2 pets, a gold fish & a turtle.
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