Saturday, December 03, 2005
Mycobacteria
General Concepts
Mycobacterium tuberculosis Complex:
Mycobacterium tuberculosis, M bovis
Clinical Manifestations
Tuberculosis primarily affects the lower respiratory system and is characterized by a chronic productive cough, low-grade fever, night sweats, and weight loss.
Structure
Mycobacteria are slender, curved rods that are acid fast and resistant to acids, alkalis, and dehydration. The cell wall contains complex waxes and glycolipids. Multiplication on enriched media is very slow, with doubling times of 18 to 24 hours; clinical isolates may require 4 to 6 weeks to grow.
Classification and Antigenic Types
On the basis of growth rate, catalase and niacin production, and pigmentation in light or dark, mycobacteria are classified into members of the Mycobacterium tuberculosis complex (M tuberculosis, M bovis, M africanum, M microtii) and nontuberculous species. Gene probe technology now facilitates this distinction.
Pathogenesis
Tuberculous mycobacteria enter the alveoli by airborne transmission. They resist destruction by alveolar macrophages and multiply, forming the primary lesion or tubercle; they then spread to regional lymph nodes, enter the circulation, and reseed the lungs. Tissue destruction results from cell-mediated hypersensitivity.
Host Defenses
Susceptibility is influenced by genetic and ethnic factors. Acquired resistance is mediated by T lymphocytes, which lyse infected macrophages directly or activate them via soluble mediators (e.g., gamma interferon) to destroy intracellular bacilli; antibodies play no protective role.
Epidemiology
M tuberculosis is contagious, but only 5-10 percent of infected normal individuals develop active disease. Tuberculosis is most common among the elderly, poor, malnourished, or immunocompromised, especially persons infected with human immunodeficiency virus (HIV). Persistent infection may reactivate after decades owing to deterioration of immune status; exogenous reinfection also occurs.
Diagnosis
Recent infection with M tuberculosis results in conversion to a positive Mantoux skin test with purified protein derivative (PPD). A diagnosis of active disease is based on clinical manifestations, an abnormal chest radiograph, acid-fast bacilli in sputum or bronchoscopic specimens and recovery of the organism. Assays based upon amplification of mycobacterial genes in clinical specimens are currently being tested.
Treatment and Control
Therapy consists of a 6 to 9 month course of isoniazid, rifampin, pyrazinamide and ethambutol. Additional drugs may be used if drug resistance is suspected (e.g., infection in Southeast Asian immigrants or in areas where outbreaks of drug-resistant tuberculosis have been documented). If the patient is HIV-positive, treatment for longer periods (9-12 months) is recommended. PPD conversion without other signs or symptoms may warrant prophylactic isoniazid therapy for 6 months. M bovis BCG vaccine is used in more than 120 countries, but its efficacy is controversial. Although BCG has not been used routinely in the U.S., the current epidemic has prompted a reevaluation of its use, especially in high-risk populations.
Nontuberculous Mycobacteria
Clinical Manifestations
Patients exhibit lower respiratory disease similar to tuberculosis (M kansasii, M avium-intracellulare), cervical lymphadenitis (M scrofulaceum), skin and soft tissue infections (M ulcerans, M marinum), or disseminated disease in persons infected with HIV.
Structure
Nontuberculous mycobacteria resemble other mycobacteria. Multiplication is similar to that of other mycobacteria, except for rapidly growing strains (e.g. M. fortuitum).
Classification and Antigenic Types
Nontuberculous mycobacteria are classified by pigmentation in the light or dark and by growth rate. Several species contain many serotypes, based upon lipooligosaccharides or peptidoglycolipids.
Pathogenesis
Pathogenesis is similar to that of other mycobacteria. There may be granuloma formation and delayed hypersensitivity.
Host Defenses
Host defenses are similar to those of other mycobacteria. Cell-mediated resistance is important.
Epidemiology
The infection is not transmissible between humans, but is acquired from natural sources (e.g., soil and water). Nontuberculous mycobacteria are important opportunistic pathogens in immunocompromised patients (e.g., patients infected with HIV).
Diagnosis
Diagnosis requires culture and identification.
Treatment
Many of these mycobacteria are resistant to the usual antituberculosis drugs. Therefore, different drugs are often necessary. Surgical resection is sometimes required. No vaccine is available.
Mycobacterium leprae
Clinical Manifestations
Leprosy is an infection of the skin, peripheral nerves, and mucous membranes, leading to lesions, hypopigmentation, and loss of sensation (anesthesia), particularly in the cooler areas of the body.
Structure
Mycobacterium leprae is similar to other mycobacteria; the cell wall contains unique phenolic glycolipids. It cannot be cultivated in vitro: it multiplies very slowly in vivo (12-day doubling time).
Classification and Antigenic Types
All isolates of M leprae, both human and sylvatic, appear to be the same by DNA homology.
Pathogenesis
The spectrum of leprosy (Hansen's disease) ranges from lepromatous (disseminated, multibacillary, with loss of specific cell-mediated immunity) to tuberculoid (localized, paucibacillary, with strong cell-mediated immunity).
Host Defenses
Host defenses are similar to those against other mycobacteria.
Epidemiology
Transmission requires prolonged contact and occurs directly through intact skin, mucous membranes, or penetrating wounds. Armadillos in Louisiana and Texas are naturally infected.
Diagnosis
Diagnosis is based on acid-fast stain and cytologic examination of affected skin and response to the lepromin skin test;
M leprae cannot be cultured.
Treatment
Treatment (including prophylaxis in close contacts) with multi-drug therapy or MDT (dapsone, rifampin, and clofazimine) is performed on an outpatient basis for 3 to 5 years; vaccination with M bovis BCG has been effective in some endemic areas.
Nocardia
Clinical Manifestations
The most common manifestation of nocardial infection is pneumonia: fever, weight loss, cough, pleuritic chest pain, and dyspnea. In about 20 percent of patients there are granulomatous skin lesions and/or central nervous system abnormalities.
Structure
The bacteria are Gram-positive, partially acid-fast rods, which grow slowly in branching chains resembling fungal hyphae.
Classification and Antigenic Types
Three species cause nearly all human infections: N asteroides, N brasiliensis, and N caviae. These are distinguished by proteolytic and fermentation patterns in culture.
Pathogenesis
Infection is by inhalation of airborne bacilli from an environmental source (soil or organic material); the disease is not contagious. Skin lesions caused by N brasiliensis often result from direct inoculation. Nocardia subverts antimicrobial mechanisms of phagocytes, causing abscess or rarely granuloma formation with hematogenous or lymphatic dissemination to the skin or central nervous system. Mortality is up to 45 percent even with therapy.
Host Defenses
The natural resistance to infection is high in normal individuals, and the disease is usually associated with cellular immune dysfunction, immunoglobulin deficiencies, or leukocyte defects. Acquired resistance is complex and involves activated macrophages, cytotoxic T cells, and neutrophil inhibition.
Epidemiology
Nocardiosis is rare in normal persons. It usually occurs in recipients of organ transplants; in patients with leukemia, lymphoma, humoral, or leukocyte defects; or after prolonged steroid therapy.
Diagnosis
Diagnosis is by Gram stain, modified acid-fast stain, and culturing of organisms from sputum, bronchoscopic specimens (washing, brushing), aspirates of abscesses, or by biopsy.
Treatment
Nocardiosis is treated by prolonged (up to 1 year) therapy with trimethoprim-sulfamethoxazole.
David N. McMurray
