Mycobacteria... Physiology and Structure Weakly gram-positive, strongly acid-fast, aerobic rods Lipid-rich cell wall, making the organism resistant to disinfectants, detergents, common antibacterial antibiotics, and traditional stains Grow slowly The mycobacteria grow more slowly than other pathogenic bacteria, and their diseases are chronic, slowly progressive illnesses. Staining Undetectable by routine histologic techniques or Gram stain The waxy lipids of the cell wall make the mycobacteria acid fast Acid-fast : carbolfuchsin (Ziehl-Neelsen acid-fast technique)

The organisms produce no known toxins. They damage human tissues by inducing inflammatory and immune responses. Most mycobacterial pathogens replicate within cells of the monocyte/macrophage lineage and elicit granulomatous inflammation. The outcome of mycobacterial infection is largely determined by the host's capacity to contain the organism through delayed-type hypersensitivity mechanisms and cell- mediated immune responses.

Mycobacteria... Auromine_Rhodamine Culture ZN

Mycobacterial Pathogens Mycobacterium tuberculosis -Mycobacterium hominis -Mycobacterium bovis Mycobacterium leprae Atypical mycobacteria (almost 30 species)

OTHER MYCOBACTERIAL INFECTIONS Atypical Mycobacterial Infections M. avium complex (MAC)  M. avium + M. intracellulare They are related to M.tuberculosis but differ significantly in their distribution and pathogenicity Atypical mycobacteria are widespread in everywhere (soil, water, plants, animal excreta). Human infections are derived directly from the environment, no person-to-person transmission.

These bacilli are predominantly opportunistic. The lungs are the most common site –with occasional cases involving lymph nodes, bones and joints, the skin, and wounds Disseminated disease due to MAC is common in advanced AIDS and occurs occasionally in other immunosuppressed states, including organ transplantation and hairy cell leukemia. –For example, in AIDS patients from developed countries, the role of M. Tuberculosis is often taken by M. Avium-intracellulare, causing rapidly progressing systemic infection.

Mycobacterium Avium-intracellulare

Microscopy of the Atypical Mycobacterial Infection

There is a hereditary problem in which patients are extremely susceptible to atypical mycobacteria. The problem seems to be inability to make  -TNF appropriately (  -TNF is a monokine). Table: Atypical mycobacterial infections BacillusDiseaseRemarks M.kansasii M.avium-intracellulare Vicious lung infections Common form. In chronic lung patients M.scrofulaceum M.avium-intracellulare Cervical adenitisIn children M. ulcerans M. marinum Ulcerative skin lesions The latter grows in home fish- tanks. M. fortuitum M. chelonei Injection abscesses Occur sporadically M.avium-intracellulareWidespread RES involvement In severly immunosupressed patients (AIDS, lymphoma)

Leprosy Leprosy (Hansen’s disease) is a slowly progressive mycobacterial infection affecting mostly the skin and peripheral nerves. There are almost 12 million active leprosy patients, most living in poor tropical countries (large number of infections remain subclinical or undetected). Mycobacterium leprae is an acid-fast (by Fite-Faraco’s stain) intracellular organism that grows only within host cells.The lepra bacillus has never been cultured succesfully. Only humans and nine-banded armadillo are naturally susceptible. The lepromin skin test (a bacterial extract; analogous to the tuberculin) is positive at 24 hours (Fernandez reaction) and once again at 3-4 weeks (Mitsuda reaction).

Mycobacterium leprae has a unique tropism for peripheral nerves, skin, and mucous membranes.

Approximately 775,000 new cases of Leprosy were detected during 2001

The Clinical Course of Leprosy The clinical course of leprosy may be considered as depent on a continuing host-bacillus relation in which the response of the host is largely predetermined by his innate capacity to lyse the invading agents. The bacillus itself is of low pathogenicity and possesses only slight invasive powers. Indeterminate leprosy (Idt): The lesions in Idt are single or multiple macules, and occur characteristically trunk and upper aspects of limbs. It may become evident as localized skin areas of slight, transient changes in pigmentation, tactile sensitivity, and sweating. Tuberculoid leprosy (TT): The TT lesions are single or multipl, macular, and show variable loss of pigmentation, sweating and tactile sensitivity. Borderline leprosy (BB): The BB lesions are polymorphic, reddish papules, nodules or macules with a shiny surface. There is little or no sensory loss. Lepromatous leprosy (LL): The lesions in LL are generally are numerous pale nodules. The thickened skin becomes shiny and corrugated, the facies leonine. Aggregations of granulomas appear on the ears, face,and on the trunk and limbs.

Spectrum of Leprosy TuberculoidBorderlineLepromatous Epitheloid cells ++-- Macrophages (lepra cells) --/+++ Langhans’ giant cells ++-- Lymphocytes +++- Bacilli --+ Lepromin, Fernandez Lepromin, Mitsuda +++--

Clinical Findings in Leprosy Macula: a discolored spot on the skin that is not elevated above the surface. Papule: a small circumscribed, superficial, solid elevation of the skin. Nodule: a small node which is solid and can be detected by touch.

Complications Peripheral nerve involvement (common in ulnar and facial nerves) Plantar ulcers Lagophthalmos (may lead to corneal trauma, scarring, and blindness) Nasal cartilage perforation and tooth loss (maxillary incisors) Impotence Renal complications (amyloidosis and immune complex GN)

Treated and Non-treated patients of Leprosy