MYCOBACTERIA

SLOW-GROWING NONTUBERCULOUS MYCOBACTERIA

Photochromogens Scotochromogens Nonphotochromogens

SPECIMEN PROCESSING

Processing to recover AFB from clinical specimen involve several complex steps with one of each carried out with precision Specimens from sterile sites can be inoculated directly into the media because sometimes these specimens have small volume or concentrated to reduce volume Other specimens required decontamination and concentration Specimens submitted to the lab will undergo the three steps before inoculations

Runyon's system devised when

1959

slow growth results in the formation of visible colonies in ___ to ___ days at optimum temperature.

2 to 60 days

A single cell's generation time (the time required for a cell to divide into two independent cells) may range from approximately ___ hours to ___ hours for ______ ____ .

20 hours to 36 hours for Mycobacterium ulcerans

Small percentage of patients, organs besides the lungs can become involved after infection with M. tuberculosis complex organism. These organs includes:

Genital Urinary Tract GUT, cervical lymph nodes, CNS: meningitis, bone and joints: arthritis and osteomyelitis, peritoneum and pericardium

Transparent colonies mean:

more virulent = more drug resistant are more commonly isolated in the blood of patients with AIDS appear more virulent in macrophage and animal models

Disadvantage of PPD test

not 100% sensitive or specific, and a positive reaction to the skin test does not necessarily signify the presence of disease

Groups 1 to 4 are based on the

phenotypic characteristics of the various species, most notably the growth rate and colonial pigmentation

he most common infection associated with RGM is

post- traumatic wound infection

Some of these NTM are considered _____ _____ for humans, whereas others are rarely associated with disease.

potentially pathogenic

Mycobacteria Grow more ____ than most other human pathogenic bacteria because of their ________

slowly; hydrophobic cell surface.

TB mimics other dse like

- pneumonia, neoplasm or fungal infections

Most important mode of transmission for M leprae

the inhalation of M. leprae discharged in the nasal secretions of an infected individual.

is mycobacteria easy or hard to stain

- Because of its structure, it is hard to stain with gram staining; cannot be readily stained - Resist decolorization with acidified alcohol (3% hydrochloric acid) after prolonged application of the basic fuchsin dye or w/ heating of this dye after application

MYOBACTERIUM TUBERCULOSIS

- Common agent of tuberculosis in most developing countries - Estimated 1.7 billion people or 1/3 of the world's population are infected w M. tb

Signs and Symptoms of Tuberculosis:

- Common presenting symptoms include low-grade fever, night sweats, fatigue, anorexia (loss of appetite), and weight loss. - A patient who presents with pulmonary tuberculosis usually has a productive cough, along with low-grade fever, chills, myalgias (aches), and sweating however these SS are similar w influenza, acute bronchitis, and pneumonia

cell wall of mycobacteria contains

- N-glycolylmuramic acid instead of N-acetylmuramic acid It has a very high lipid content -> which creates a hydrophobic permeability barrier

morphology of mycobacteria

- Some species may display a branching morphology - Have an unusual cell wall structure - Generally considered Gram Positive

Clinical manifestation in patients affected with M. tuberculosis complex may range from asymptomatic to acutely symptomatic

- Symptomatic patients may have systemic symptoms, either pulmonary symptoms, signs and symptoms related to other organ involvement such as the kidney or a combination of these features - Cases of pulmonary disease caused by M. tuberculosis complex are clinically, radiologically or pathologically indistinguishable - Pulmonary or primary tuberculosis typically are considered as a disease of the respiratory tract

Possible Outcomes of M TB:

- Tissue Necrosis - Caseous Necrosis Meningeal or Miliary (disseminated) tuberculosis - patients with depressed or ineffective cellular immunity

Spectrum of Disease: Tuberculosis

- Upon respiratory infection with M. tuberculosis complex organism, the cellular immune system T cells and macrophages migrate to the lungs and the organisms are phagocytized by the macrophages - However, these organisms are capable of intracellular multiplication in the macrophages - Often, the host is unable to eliminate the microorganism and the result is the systemic hypersensitivity to mycobacterium antigens - Granulomas or a hard tubercle forms in the lung from the lymphocytes, macrophages, and cellular pathology including giant cell formation or the cellular fusion display multiple nuclei

BCG what for

- Used to immunize susceptible individuals against tuberculosis - Bc of mycobacteria, are the classic examples of intracellular pathogens and the body's response to BCG hinges on cell-mediated immunoreactivity - Immunized individuals are expected to react more aggressively against all antigens that elicit cell-mediated immunity - In rare cases, an unfortunate individual's immune system is so compromised that it cannot handle the BCG and so systemic BCG infection may develop

Mycobacterium bovis may penetrate the

- gastrointestinal mucosa or invade the lymphatic tissue of the oropharynx - Done after ingestion of Milk from Infected cow

If the mycobacterium antigen concentration is high, the hypersensitivity reaction may result in

- tissue necrosis caused by enzymes released by the macrophages - In this case, no granuloma will form and the solid or semisolid caseous material is left at the primary lesion site; caseous = consistency is like cheese - In some patients affected w primary active TB, the disease may spread through the lymphatic system or hematogenously leading to meningeal or miliary (disseminated TB) This often occurs in px with depressed or ineffective cellular immunity

Disease of MTB occurs

- years after the initial infection when the person's immune system breaks down for some reason aside from the presence of tubercle bacilli in the lung - Small percentage of infected hosts, the disease becomes systemic which affects a variety of organs

SPECIMEN COLLECTION AND TRANSPORT MTB:

AFB can infect almost any tissue or organ in the body Successful isolation of AFB depends on the quality of the specimen obtained, the use of appropriate processing, and culture techniques In suspected mycobacterial disease, as in all other infectious diseases, the diagnostic procedure begins at the patient's bedside Collection of proper clinical specimen requires careful attention to detail by all HC professionals Most specimens are respiratory samples, such as sputum, tracheal or bronchial aspirates, and specimens obtained by bronchial alveolar lavage. Other samples may include urine, gastric aspirates, tissue biopsy specimen, CSF, and pleural and pericardial fluid Blood or fecal specimen may be collected in immunocompromised patients Specimens should be collected in sterile, leak- proof, disposable, and appropriately labeled containers without fixatives and placed in bags to contain leakage. Fixative: formalin or any other substance If transport and processing will be delayed longer than 1 hour, All specimens except blood should be refrigerated at 4° C until processed.

Specimen Collection: Fecal Specimens

Acid Fast Staining or culture of stool or both from patients with HIV or AIDs have been used to identify patients who could be at risk for getting disseminated MAC disease Use is controversial but if screening stains are (+) then disseminated MAC disease follows Feces should be submitted in a clean, dry, wax-free container without preservative or diluent. Contamination with urine should be strictly avoided.

important characteristic that distinguishes mycobacteria from other genera

Acid Fastness

gen char of mycobacteria

Aerobic (although some may grow in reduced oxygen concentrations) Non-spore forming (except for M. marinum) Nonmotile Very thin, slightly curved or straight rods (0.2 to 0.6 × 1 to 10 μm).

Special Considerations in Specimen Collection:

Aerosol-induced sputum should be treated as sputum even if induced Gastric lavages should be processed within 4 hours of collection or neutralized with 10% sodium carbonate and refrigerated until processed as for sputum. Ex: if we collect at midnight then there is delay of specimen then we must neutralize and refrigerate Urine specimens should be divided into a maximum of four 50-mL centrifuge tubes and centrifuged at 3600× g for 30 minutes. The supernatant should be decanted, leaving approximately 2 mL of sediment in each tube. Fecal specimens, approximately 0.2 g of stool (a portion about the size of a pea) is emulsified in 11 mL of sterile, filtered, distilled water. Swabs and wound aspirates should be transferred to a sterile, 50-mL conical centrifuge tube containing a liquid medium (Middlebrook 7H9, Dubos Tween albumin broth) at a ratio of 1 part specimen to 5 to 10 parts liquid medium The specimen is vortexed vigorously and allowed to stand for 20 minutes. The swab is removed, and the resulting suspension is processed as for sputum. Large pieces of tissue should be finely minced with a sterile scalpel and scissors. This material is homogenized in a sterile tissue grinder with a small amount of sterile saline (0.85%) or sterile 0.2% bovine albumin; the suspension then is processed as for sputum. If the tissue is collected aseptically, it may be processed without being treated with NALC-NaOH.

Acid Fast Stain: Cold Kinyoun Method

Aka: Cold Stain procedure The method is similar to Ziehl-Neelsen staining, but no heat is used. If present, typical acid-fast bacilli appear as purple to red, slightly curved, short or long rods (2 to 8 μm); they also may appear beaded or banded (M. kansasii). For some nontuberculous species, such as M. avium complex, they appear pleomorphic, usually coccoid.

ACID FAST STAIN: Ziehl-Neelsen Method (1st step)

Aka: hot stain procedure Cell walls of mycobacterium contain long chain multiply crosslinked acids called mycolic acids Mycolic acids uses complex basic dyes contributing to characteristic of acid-fastness that distinguishes mycobacterium from other Classic carbolfuchsin stain (Ziehl-Neelsen) requires heating of the slide for better penetration of the stain into the mycobacterial cell wall. Mycobacterium spp. appear red or have a red-blue, beaded appearance, whereas nonmycobacteria appear blue.

Pathogenesis of M leprae

Although the host immune response plays a key role in control of infection, the immune response is also responsible for the damage to the skin and nerves Leprosy is both a bacterial and an immunologic disease After acquisition of M. leprae, the infections passes through many stages characterized by their histopathologic and clinical features

Specimen Collection: Wounds, Skin Lesions, and Aspirates

An aspirate is the best type of specimen for culturing of a skin lesion or wound. Skin should be cleansed with alcohol before aspiration of the material into the syringe If the volume is insufficient for aspiration, pus and exudates may be obtained on a swab and then placed in a transport medium, such as Amie's or Stuart's medium (dry swabs are unacceptable). A negative culture of a specimen obtained on a swab is not considered reliable and should be noted in the culture report

Specimen processing steps

Decontamination NaOH method Zephiran-trisodium phosphate method N-acetyl-L-cysteine (NALC)- 2% NaOH method Concentration concentrated by centrifugation at greater than or equal to 3000× g / 3000 RPGs per minute Oxalic acid is very useful for treating specimens known to harbor gram-negative rods, particularly Pseudomonas and Proteus spp Oxalic acid, NaOH, and mild hydrogen chloride (HCl) may reduce the recovery of M. ulcerans. (take note because if we are after these M. ulcerans, then we should limit the use of oxalic acid, NaOH and HCl) NaOH = reduces contamination but also reduces recovery of other Mycobacterium spp.

QuantiFERON-TB Gold

Due to the issues of the Tuberculin test a new test developed by the FDA has become available Enzyme-linked immunosorbent assay (ELISA) The assay measures a component of the cell-mediated immune response to M. tuberculosis to diagnose latent tuberculosis infection and current tuberculosis It is based on the quantification of interferon- gamma released from sensitized lymphocytes in heparinized whole blood that has been incubated overnight with a mixture of synthetic peptides simulating two proteins in M. tuberculosis. The test assesses responses to multiple antigens can be performed in a single patient visit Less subject to reader bias and error An important feature is that the results of the assay are unaffected by previous BCG vaccine

Runyon's system categorizes them into 4 groups

First categorizes the slow-growing NTM (Runyon groups I to III) and then the rapid-growers (Runyon group IV).

Specimen Collection: Tissue and Body Fluid Specimens

For TB meningitis (very uncommon), occurs in both immunocompetent and immunosuppressed px Sufficient quantity of specimen is crucial for isolation of AFB from CSF Very few organisms are present in the CSF making detection very difficult At least 10 mL of CSF is recommended for recovery of mycobacteria. All other body fluids: pleural, peritoneal, and pericardial fluids, should be collected in a sterile container or syringe with a Luer-tip cap (10 to 15 mL minimum). Tissues may immersed in saline or wrapped in gauze and swabs are discourage because the recovery of organism is decreased

Specimens Not Requiring Decontamination:

If such a specimen appears contaminated because of color, cloudiness, or foul odor, Gram staining is performed to detect bacteria other than acid-fast bacilli. CSF should be handled aseptically and centrifuged for 30 minutes at 3600× g to concentrate the bacteria. If insufficient quantity of spinal fluid is received, the specimen should be used directly for smear and culture. Pleural fluid should be collected in sterile anticoagulant (1 mg/mL ethylenediaminetetraacetic acid [EDTA] or 0.1 mg/mL heparin). Joint fluid and other sterile exudates can be handled aseptically and inoculated directly to media. Bone marrow aspirates Either inoculated directly to media or, if clotted, treated with sputolysin or glass beads and distilled water before concentration.

Specimen Collection: Blood

Immunocompromised patients, particularly those infected with HIV can have disseminated mycobacterial infection Most of these infections are caused by MAC Blood culture positive for MAC is always associated with clinical evidence of disease Recovery of mycobacterium is involved in either a broth or the isolator lysis centrifugation system Blood for culture of mycobacteria should be collected as for routine blood cultures Blood collected in regular phlebotomy procedures in anticoagulants such as sodium polyanethol sulfonate (SPS), heparin, and citrate may be used to inoculate cultures for the recovery of Mycobacterium species. Conventional blood culture collection systems are unacceptable for the isolation of Mycobacterium spp.

Specimen Collection: Urine Specimens

Incidence of urogenital infection shows little evidence of decreasing About 2-3% of px with pulmonary tuberculosis show urinary tract involvement but 30-40% of patient with genitourinary disease have tuberculosis at some other site The clinical manifestations of urinary tuberculosis, which are variable, include frequency of urination (most common), dysuria, hematuria, and flank pain. Definitive diagnosis requires recovery of acid-fast bacilli from the urine. Early morning voided urine specimens (40 mL minimum) in sterile containers should be submitted daily for at least 3 days. Collection of specimen is the same as MSCC The 24-hour urine specimen is undesirable due to excessive dilution, higher contamination, and difficulty in concentrating Catheterization should be used only if a midstream voided specimen cannot be collected.

Pathogenesis of MTB

Inhalation of a single viable organism has been shown to lead to infection, although close contact is usually necessary. - Immunocompromised state - 15-20% people develop the disease

Inadequate Specimens and Rejection Criteria

Insufficient volume contamination with saliva dried swabs (discouraged so this is why it should be placed immediately in transport media) pooled sputum or pooled urine container has been compromised broken or leaking length of time from collection to processing is too long

MYCOBACTERIUM AVIUM COMPLEX (MAC)

Largely because of the increasing populations of immunosuppressed patients, the incidence of infection caused by MAC, as well as these organisms, clinical significance has changed significantly since they were first recognized as human pathogens in the 1950s

One other NTM:

M. leprae Cannot be cultivated in an artificial media Also reviewed

Mycobacterium tuberculosis complex specie

M. tuberculosis M. bovis M. bovis BCG M. africanum M. caprae M. microti M. canettii M. pinnipedii

Lepromatous leprosy: Disseminated Form

Patients are anergic (decreased immunity or lack of immunity to antigen) to M. leprae because of a defect in their cell-mediated immunity. Bc organism's growth is unimpeded, individuals develop extensive skin lesions containing numerous acid-fast bacilli Organism can spill over into the blood and still disseminate

Laboratory specimen recommendations for MTB

M. tuberculosis has a very low infective dose for humans (i.e., an infection rate of approximately 50% with exposure to fewer than 10 acid-fast bacilli). All tuberculin-negative personnel should have a skin test at least annually. The CDC recommends Biosafety Level 2 practices, containment equipment, and facilities for preparing acid-fast smears and culture for nonaerosolizing manipulations. Biologic safety cabinet (BSC) class II safety precautions are required for propagation and manipulation of M. TB with Biosafety Level 3 practices. BSC Level 3 practices are recommended for opening centrifuge vials, adding reagents to biochemical testing medias, and sonication.

MYCOBACTERIUM AVIUM COMPLEX (MAC) General characteristics

MAC is an important pathogen in both immunocompromised and immunocompetent populations. Noteworthy for potentially pathogenic role in pulmonary infections in patients with AIDS and also in patients who are not infected with HIV. Ubiquitous (present everywhere)in the environment and have been isolated from natural water, soil, dairy products, pigs, chickens, cats, and dogs. Natural waters serve as the major reservoir for most human infections. Infections caused by MAC are acquired by inhalation or ingestion Pathogenesis is not clearly understood and are commonly associated with respiratory disease clinically similar to TB in adults, lymph adenitis in children, the disseminated infections in patients with HIV They can persist well over a year in tap water, and MAC tolerates temperature extremes. M. avium can infect and replicate in protozoa. Amoeba grown M. avium is more invasive towards human epithelium and macrophage cells MAC cultures can have an opaque, a translucent, or a transparent colony morphology

NONCULTIVATABLE NONTUBERCULOUS MYCOBACTERIA

MYCOBACTERIUM LEPRAE Close relative of M. tuberculosis

DETECTION METHODS

Microscopy is considered as the reasonable, sensitive, and rapid procedure for the presumptive identification of mycobacterium spp. as clinical specimen ACID FAST STAIN: Ziehl-Neelsen Method (1st step) Acid Fast Stain: Cold Kinyoun Method

RAPIDLY GROWING NONTUBERCULOUS MYCOBACTERIA (RGM)

Mycobacteria that produce colonies on solid media in 7 days or earlier constitute the second major group of NTM. The large group of organisms that constitute the RGM is divided into six major groups of potentially pathogenic species, based on pigmentation and molecular studies Most rapid-growers can grow on routine bacteriologic media and on media specific for cultivation of mycobacteria. On Gram staining, these organisms appear as weakly gram-positive rods resembling diphtheroids. Rapid growing mycobacteria containing potentially pathogenic could cause disease in either healthy or immunocompromised patients Like many other NTM, these organisms are ubiquitous in environment and are present worldwide ubiquitous in the environment found in soil, marshes, rivers, and municipal water supplies (tap water) and in marine and terrestrial life forms. Infections caused by rapidly growing mycobacteria can be part of the community from environmental sources They also can be nosocomial infections, resulting from medical interventions (including bone marrow transplantation), wound infections, and catheter sepsis. These organisms may be commensals on the skin. They gain entry into the host by inoculation into the skin and subcutaneous tissues as a result of trauma, injections, or surgery, or through animal contact. The RGM also can cause disseminated cutaneous infections.

NONTUBERCULOUS MYCOBACTERIA gen char

NTM are present everywhere in the environment and sometimes colonize the skin and respiratory and GI tracts of healthy individuals. Little is known about how it is acquired

NONTUBERCULOUS MYCOBACTERIA

NTM include all mycobacteria species not belonging to the M. tuberculosis complex Currently, around 130 species have been recognized

Tuberculin Test or Purified Protein Derivative (PPD) test

One way to diagnose tuberculosis Basis of Test: individual develops a delayed hypersensitivity cell-mediated immunity to certain antigenic components of the organism To determine whether or not someone has been infected, a culture extract of MTB is inject intracutaneously After 48-72 hours, an infected individual will show a delayed hypersensitivity reaction to the PPD: characterized by erythema or redness and most importantly, induration or firmness as a result of the influx of immune cells Diameter of induration is measured and interpreted as to whether or not there is infection Interpretative criteria differ with populations

Two primary phases:

Silent Phase: leprosy bacilli multiply in the skin and in macrophages Intermediate phase: bacilli multiply in peripheral nerves and begin to cause sensory impairment More severe stages may follow

Photochromogens

Slow-growing NTM that produce colonies that require light to form pigments. Of the five, M. kansasii is the one that causes chronic pulmonary disease and extrapulmonary diseases ALL ARE POTENTIALLY PATHOGENIC

Scotochromogens

Slow-growing NTM that produce pigmented colonies whether grown in the dark or the light. Epidemiology of the potentially pathogenic scotochromogens have not been definitely described In contrast to potentially pathogenic non-photochromogen, these agents are rarely recovered within the lab NON PATHOGENIC: GORDONAE, COOKIE, HIBERNIAE

Non-Photochromogen

Slow-growing NTM that produce unpigmented colonies whether grown in the dark or the light. The nonphotochromogens belonging to Mycobacterium avium complex are frequently isolated in the clinical laboratory and are able to cause infection in the human host. Among this group, M. teri complex and M. gastri are considered non-pathogenic for humans. The others are considered potentially pathogenic and are frequently recovered in the lab

Specimen Collection: Pulmonary Specimen

Specimens could be: spontaneously produced or induced sputum, gastric lavage, transtracheal aspiration, bronchoscopy, and laryngeal swabbing. Spontaneously produced sputum is the specimen of choice. Aerosolized induced sputum, bronchoscopic aspiration are gastric lavage samples Saliva and nasal secretions should not be collected, nor should the patient use oral antiseptics during the collection period. Sputum specimens must be free of food particles, residues, and other extraneous matter. Aerosol-induced or aerosol-saline induction procedures can be best done on ambulatory patients who can follow instructions Aerosol-induced sputum specimens have been collected from children as young as 5 years of age; however, it should be performed in an enclosed area with appropriate air flow. Operator should wear particular respirators and take appropriate safety measures to avoid exposure To raise sputum, patients are instructed to take a deep breath, hold it momentarily and cough deeply and vigorously Patients should also be instructed to cover their mouths carefully while coughing and to discard tissues in the appropriate receptacle While doing this, patient is told that the procedure is done to induce coughing, to raise sputum that the patient cannot raise spontaneously, and to warn the patient that the salt solution is irritating Patient is instructed to inhale slowly and deeply through the mouth and to cough deeply and vigorously into the collection tube The procedure is discontinued if the patient fails to raise sputum after 10 minutes or feels any discomfort. Ten mL of sputum should be collected; if the patient continues to raise sputum, a second specimen should be collected and submitted. Specimens should be delivered promptly to the laboratory and refrigerated if processing is delayed. Sputum collection guidelines recommend collection of an early morning specimen for 3 consecutive days. In many cases, the third collection demonstrates minimal recovery of organism and this collection may not be recommended in some labs. Pooled specimens are unacceptable because of an increased risk of contamination

Laboratory diagnosis of M. tuberculosis infection

Specimens received by the HC worker or anyone else must be handled in a safe manner because Mycobacterium ranks high in hospital acquired infections so there must be proper PPE to reduce the risk

MYCOBACTERIA generalities

TB is an airborne disease About 1 million Filipinos have active TB 3rd highest prevalence rate in the world Highly curable but still the #1 killer among all infectious diseases Everyday more than 70 people lose their lives to TB in PH Many more patients develop drug resistance to tuberculosis which are more expensive and difficult to treat

M. leprae: Two Major Forms of Disease

Tuberculoid leprosy: Localized form Lepromatous leprosy: Disseminated Form

Epidemiology of M leprae

Understanding both its epidemiology and pathology is hampered by the inability to grow the organism in culture In tropical countries where disease is most prevalent, it may be acquired from infected humans; however, infectivity is very low Prolonged close contact of the host's immunologic status plays a role in infectivity

Specimen Collection: Gastric Lavage Specimens

The procedure is limited to: senile, nonambulatory patients children younger than 3 years of age (specimen of choice for this age group) patients who fail to produce sputum by aerosol induction The most desirable gastric lavage is collected at the patient's bedside before the patient arises and before exertion empties the stomach These are the specimens of choice for detecting nontuberculous mycobacteria and other opportunistic pathogens in patients with immune dysfunction. Levine collection tube is inserted through the nostril and the px is instructed to swallow the tube When fully inserted, the syringe is attached to the end of the tube and filtered distilled water into the tube The syringe is then used to withdraw 5 to 10 mL of gastric secretions, which is expelled slowly down the sides of the 50-mL conical collecting tube. Samples should be adjusted to a neutral pH. The laboratory may choose to provide sterile receptacles containing 100 mg of sodium carbonate to reduce the acidity; this improves the recovery of organisms. Three specimens should be collected over a period of consecutive days. Specimens should be processed within 4 hours.

Therapy for MTB

Therapy directed against M. tuberculosis depends on the susceptibility of the isolate to various antimicrobial agents.

MYCOBACTERIUM LEPRAE General characteristics

This organism causes leprosy (also called Hansen's disease). Leprosy is a chronic disease of the skin, mucous membranes, and nerve tissue. Leprosy remains to be a worldwide public health concern as a result of the development of drug resistant isolated M. leprae has not yet been cultivated in vitro, although it can be cultivated in the armadillo and in the footpads of mice. Diagnosis of leprosy is based on distinct clinical manifestations, such as hypopigmented skin lesions and peripheral nerve involvement, in conjunction with a skin smear that tests positive for acid-fast bacilli.

Major Groups of Myobacteria is classified by

according to fundamental differences in epidemiology and association with the disease

An attenuated strain of M. bovis is

bacillus Calmette-Guérin (BCG), has been used extensively in many years around the world

Mycobacterium spp. synthesize

carotenoids (a group of yellow to red pigments) in varying amounts and thus can be categorized into three groups based on the production of these pigments

Tuberculoid leprosy: Localized form

do not have an immune defect, so the disease is localized to the skin and nerves; few organisms are observed in skin lesions. Most of the serious sequelae associated with leprosy are the result of the organism's tropism (growth or turning movement of biological organism)on the peripheral nerves

The primary reservoir for M. leprae is

infected humans. The disease is transmitted person to person through inhalation or contact with infected skin.

The most common two-drug regimen

isoniazid (INH, also known as isonicotinylhydrazine) and rifampin. INH + RIFAMPIN = The combination is administered for 9 months in cases of uncomplicated tuberculosis; if pyrazinamide is added to this regimen during the first 2 months, the total duration of therapy can be shortened to 6 months. - Ethambutol may also be added to the regimen. - INH prophylaxis is recommended for individuals with a recent skin test conversion who are disease free.

To prevent the selection of resistant mutants, treatment of tuberculosis requires four drugs :

isoniazid, rifampin, ethambutol, and pyrazinamide. Initial therapy includes all four drugs for 8 weeks.

M. avium subsp. paratuberculosis

known to cause an inflammatory bowel disease (known as Johne's disease) in cattle, sheep, and goats. It also has been isolated from the bowel mucosa of patients with Crohn's disease: chronic inflammatory bowel disease in humans The organism is extremely fastidious, seems to require a growth factor mycobactin, produced by other species of mycobacteria and may take as long as 6 to 18 months for primary isolation.

MOT of NTB

trauma, inhalation of infectious aerosols, and ingestion; a few diseases are nosocomial or are acquired as an iatrogenic infection In contrast to MTB complex, NTM are not usually transmitted from person to person; nor does isolation of organisms necessarily mean they are associated with disease process Interpretation of (+) culture of NTM is complicated due to the wide distribution of it in nature Pathogenic potential varies from one specie to another and so, humans can be colonized by mycobacteria without developing the disease or infection