MYCOBACTERIA 2/2 M. leprae & Atypical Professor Sudheer Kher

KEYWORDS Atypical Runyon groups Antibiotic resistance Acid Fast Ziehl-Neelsen Stain 5% H2SO4 Mycolic acids M. leprae Non cultivable Armadillo, Mouse footpad Lepromin test Ridely Jopling classification Tuberculoid / Lepromatous Lab diagnosis –Skin clippings Atypical Runyon groups Antibiotic resistance Opportunistic infection Skin pathogens M.marinum & M. ulcerans Buruli ulcer

Mycobacteria Mycobacterium leprae

Hansen's disease, leprosy Chronic granulomatous communicable disease occurring in tropical and subtropical regions; characterized by inflamed nodules beneath the skin and wasting of body parts; caused by the Mycobacterium leprae. Chronic disease, disfigurement, common in third world, millions of cases Infects the skin –neural involvement, low temperature

Ridley Jopling Classification of Leprosy Basis - Immunological RR-Reversal reaction; ENL-Erythema nodosum leprosum; PB-Paucibacillary, MB-Multibacillary

Ulcers, resorption of bone worsened from careless use of hands (nerve damage)

Leprosy tuberculoid few organisms active cell-mediated immunity lepromatous many organisms immunosuppression

Production of M. leprae antigens and pathogenesis studies in vitro uncultivable in vivo growth low temperature armadillo mouse footpad

Leprosy lepromin skin testing acid-fast stains skin biopsies clinical picture

Tuberculoid Leprosy

Lepromatous leprosy

Skin biopsy shows intradermal formation of epithelioid granulomas without caseous necrosis (HE). The papillary dermis is involved. Acid-fast staining is negative. Diagnostic hints include clinical information of numbness and histologic identification of nerve involvement by the granulomatous lesion.

Lepromatous leprosy (35 y-o) Male           Biopsy from erythematous and scaling nodules on the extremities. The bacilli forming "globi" are stained with PAS method.

Lepromin test A test utilizing an intradermal injection of a lepromin, such as the Dharmendra antigen or Mitsuda antigen, to classify the stage of leprosy based on the lepromin reaction, such as the Fernandez reaction or Mitsuda reaction. It differentiates tuberculoid leprosy, in which there is a positive delayed reaction at the injection site, from lepromatous leprosy, in which there is no reaction (i.e., a negative test result) despite the active malignant Mycobacterium leprae infection; the test is not diagnostic, since normal uninfected persons may react.

Erythema Nodosum Leprosum (ENL) An inflammatory complication of leprosy that results in painful skin lesions on the arms and legs and face Cause – Type III hypersensitivity Immune complex Vasculitis.

Lab Diagnosis Leprosy Easy in Lepromatous, difficult in Tuberculoid. Demonstration of AFB Nasal mucosa Skin Lesion Ear lobule Skin clippings from 5-6 areas Buttocks Forehead Chin Cheek Ear

Mycobacteria Atypical Mycobacteria

Mycobacteria other than human or bovine tubercle Synonyms – Atypical Anonymous Unclassified Non tuberculous mycobacteria Paratubercle Tuberculoid MOTT Mycobacteria Other Than Tubercle

Runyon Classification (1959) Basis – Pigment production & Rate of growth Group I – Photochromogens Form pigment after exposure to light Example – M. kansasii Habitat – Water & animals Causes Pulmonary, skin, systemic, LN infections. Group II – Scotochromogens Pigment produced in dark Example – M. scrofulaceum Habitat – Water, soil, fomites Causes cervical lymphadenitis in children Group III- Nonphotochromogens No pigment production Examples – M. intracellulare, M. avium & M. xenopi Habitat – Soil, Seawater, animals Causes Pulmonary, gastrointestinal, renal, systemic, LN infections Pulmonary, epididymis Group IV –Rapid growers Colonies appear within seven days Example –M. fortuitum, Habitat- Water, soil & animals Causes Pulmonary, gastrointestinal, renal, systemic, LN infections

Atypical mycobacteria infect immunocompromised host not transmitted man -man healthy people

Atypical mycobacterial diseases tuberculosis-like leprosy-like

M. avium is much less virulent than M. tuberculosis Mycobacteria and AIDS M. avium is much less virulent than M. tuberculosis does not infect healthy people infects AIDS patients M. avium infects when CD4 (helper T cell) count greatly decreased M. tuberculosis infection infects healthy people earlier stage of disease more systemic

Other atypicals pigmented or not pigmentation in the light in the dark growth fast slow

Mycolic acids mycobacteria longest chain length strongly acid fast nocardia intermediate chain length weakly acid fast corynebacteria shortest chain length not acid fast

Most found in US – Rare in Africa. Annual frequency in AIDS – 10-20%. Mycobacterium avium complex (MAC) Most common bacterial opportunistic infection (OI) in adults infected with HIV in the developed world. Most found in US – Rare in Africa. Annual frequency in AIDS – 10-20%. Occurs late in HIV infection. Mean CD4+ Count ~ 10-30/μL. (TB occurs early.) Inhaled or ingested from environment. Spreads via lymphatics then hematogenously. Taken up in reticuloendothelial organs.

Mycobacterium avium complex (MAC) Symptoms in the AIDS Patient: Disseminated Gastrointestinal Fever Chronic Diarrhea & Night Sweats Abdominal Pain Weight Loss Malabsorption Malaise Cholestatic Jaundice Anemia Elevated LFTs (Alkaline Phosphatase)

MAC in the Non-HIV/AIDS Patient: More common as a cause of pulmonary disease in persons born in United States than TB. 2) Increasing in incidence over the last 20-30 years. 3) Progressive pulmonary disease on x-ray and clinically. 4) Sputum culture positive. 5) Dissemination rare to non-existent.

Diagnosis of MAC in AIDS Biopsy of the involved reticuloendothelial organs with acid fast stain and/or culture. Blood culture. (85% of patients with disseminated MAC are mycobacteremic.) EID CDC

← MAC infection of lymph node. Acid-fast bacilli within plump histiocytes. CDC/Dr. Edwin P. Ewing, Jr. Colon Biopsy Mycobacterium avium – Acid Fast Stain → © Dr. Peter Anderson, University of Alabama at Birmingham, Dept of Path.

Mycobacteria SKIN PATHOGENS

NAME OF DISEASE: Buruli ulcers, Mycoburuli ulcers ETIOLOGICAL AGENT: Mycobacterium ulcerans. It grows only at temperatures below 37° C, is non-chromogenic and niacin-negative and extracellular   OVERVIEW: An ulcer of the skin and underlying tissue is the sole symptom due to the unique temperature requirements of the organism. The disease is most common along the Nile River but is also found in Southeast Asia, Australia and Mexico. PATHOGENESIS: The organism can apparently penetrate the unbroken skin where it produces an ulcer. Despite extensive necrosis, lesions are painless, symptoms of systemic disease are absent and there is little histological evidence of an initial acute inflammatory response. Focal necrosis extends through the dermis and adipose tissue and into muscle. The cause of this necrosis is mycolactone.

Mycobacterium marinum Swimming pool granuloma: Localized nodular skin inflammation (small reddish raised areas of skin) caused by a bacterium called Mycobacterium marinum Atypical Mycobacterium found in salt and fresh water. M marinum is the most common atypical Mycobacterium to cause infection in humans. Infection occurs following primary inoculation of a skin abrasion or puncture and manifests as a localized granuloma Contact with an aquarium, salt water, or marine animals such as fish or turtles. Exposure to M marinum via swimming pools is rare these days because most pools are chlorinated. Cultures at 25-32°C may grow acid-fast bacilli in 7-21 days. The organisms are photochromogens

KEYWORDS Atypical Runyon groups Antibiotic resistance Acid Fast Ziehl-Neelsen Stain 5% H2SO4 Mycolic acids M. leprae Non cultivable Armadillo, Mouse footpad Lepromin test Ridely Jopling classification Tuberculoid / Lepromatous Lab diagnosis –Skin clippings Atypical Runyon groups Antibiotic resistance Opportunistic infection Skin pathogens M.marinum & M. ulcerans Buruli ulcer