04. Tuberculosis

OTHER NAMES
TB; tuberculosis - pulmonary
DEFINITION
Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. Tuberculosis most commonly attacks the lungs (as pulmonary TB) but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, bones, joints and even the skin. Other mycobacteria such as Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti can also cause tuberculosis, but these species do not usually PATHOPHYSIOLOGY

About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease. However, if untreated, the death rate for these active TB cases is more than 50%.

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus. Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. Further spread is through the bloodstream to the more distant tissues and organs where secondary TB lesions can develop in lung apices, peripheral lymph nodes, kidneys, brain, and bone. All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroidinfect healthy adults

PREVENTION
Routine skin testing for tuberculosis is done during routine well-baby exams. Infants are normally screened at 1 year and children at 5 years. Individuals exposed to tuberculosis should be skin tested immediately and the skin test repeated in 3 to 6 months if the initial skin test is negative.
Detection of early cases and prompt treatment are paramount in controlling the spread of tuberculosis.
A BCG vaccination for tuberculin-negative people who have been exposed to TB is given in some situations, but its effectiveness is under dispute. BCG is routinely used in some countries in Europe but is not routinely used in the United States. People who have had BCG should not be skin tested for tuberculosis.
SYMPTOMS
- initially not apparent, or limited to minor cough and mild fever
- fatigue
- weight loss
- coughing up blood

slight fever and night sweats
Additional symptoms that may be associated with this disease:
- wheezing
- rales
- sweating. excessive
- joint pain
- hearing loss
- diarrhea
- chest pain
- breathing difficulty
- positive Babinski’s reflex
- clubbing of the fingers or toes
SIGNS AND TESTS
Examination of the lungs by stethoscope (auscultation) reveals crackles.
Tests often include:
- chest X-ray
- sputum cultures
- tuberculin skin test
- bronchoscopy
- open lung biopsy
Treatment Options      

Treatment Strategy

    In the case of hemoptysis, the patient must be treated emergently to prevent   asphyxiation. Chest x-ray, sputum, and culture tests are administered when diagnosis is   suspected. Patients are often treated presumptively until results of lab tests return.   Multidrug, not single-drug, antituberculous agents are prescribed. The 1998 consensus   statement of the Public Health Tuberculosis Guidelines Panel found that rates of   treatment completion are most likely to exceed 90% with directly observed therapy (DOT).   The more action that is taken to administer medications, the higher the completion rates.   Directly observed therapy should be employed whenever possible.         

Drug Therapies

    The patient is tested for drug resistance to determine the most effective combination of   medications. Multidrug regimens taken regularly and for a sufficient period of time are   required to effectively eradicate M. tuberculosis. Drug therapy regimens last 6 to 9   months for most patients, 9 to 12 months for HIV-infected patients, and a minimum of 12   months with extrapulmonary tuberculosis. For patients with HIV, preventive therapy   reduces incidence of active tuberculosis and decreases mortality rates for those with   positive skin tests. Drug regimens are divided into an initial bactericidal phase followed by   a sterilization phase.   Standard antibiotics for tuberculosis include:    _... Isoniazid-adults 5 mg/kg/day, children 10 to 20 mg/kg/day, 300 mg maximum for   both; side effects: hepatitis (risk increased with alcohol consumption), peripheral   neuropathy, rash, fever; additional drug interactions and toxicity for patients with   HIV     _... Rifampin-adults 10 mg/kg/day, maximum 600 mg/day, children 10 to 20   mg/kg/day; side effects: gastrointestinal upset, hepatitis, orange discoloration of   body fluids (and contact lenses); additional drug interactions and toxicity for   patients with HIV     _... Pyrazinamide-15 to 30 mg/kg/day, 2 g maximum; side effects: hepatitis,   hyperuricemia possibly with polyarthralgias (both reduced by concurrent rifampin   administration)     _... Ethambutol-least potent against M. tuberculosis; 15 to 25 mg/kg/day for 2   months, then reduce to 15 mg/kg/day; side effects: retrobulbar optic neuritis and   color perception problems, avoid with children     _... Streptomycin-used least often because of toxicity; intramuscular or intravenous   administration of 10 to 15 mg/kg/day, maximum 1 g/day, up to 5 times per week   for adults, 20 to 40 mg/kg/day with 1 g/day maximum for children; side effects:   ototoxicity (both hearing loss and vestibular dysfunction), nephrotoxicity,   teratogenic     _... Pyridoxine (vitamin B6) added to regimen particularly in populations at risk for   vitamin deficiency (e.g., malnourished, alcoholics, elderly, pregnant and nursing   mothers) or at risk for neuropathy (diabetics, HIV, chronic renal failure)   Experimental drugs:    _... Rifapentine-longer acting, allowing dosing twice a week     _... Fluoroquinolones (e.g., ciprofloxacin)-antibacterial; concentrations higher in   respiratory secretions than in serum; well tolerated, but insufficient data to use as   standard treatment; less effective with HIV     _... Rifabutin-as effective as rifampin with concurrent HIV, but reduces time to   sputum conversion; 150 mg/day associated with fewest adverse effects; possible   role with multidrug resistance         

Surgical Procedures

      _... Bone and joint: curettage and bone grafting of extra-articular lesions; joint or bone   resection; excision of soft tissue abscess; amputation         

Complementary and Alternative Therapies

    The control of tuberculosis worldwide depends on the effectiveness of vaccination   programs and antibiotic therapy. Recent studies have determined that dietary deficiencies   of proteins, zinc, and vitamins A, C, and D are linked to multiple abnormalities in immune   function; these abnormalities may result in a poor immunologic response to tuberculosis   and to the BCG vaccine, especially among the elderly, children, alcoholics, the homeless,   and HIV-infected individuals.  Although the antimicrobial properties of plant species are not comparable to the potency   of antimicrobial agents produced by microorganisms, researchers continue to conduct in   vitro studies in an effort to uncover effective plant compounds that will inhibit M.   tuberculosis. A definitive review of this research was compiled by Newton and her   colleagues (2000).         

Nutrition

    Most data concerning nutrients and tuberculosis are derived from animal studies and in   vitro experiments using cultured macrophages infected with M. tuberculosis. Extrapolating   relevant data for human subjects must therefore be done cautiously.   Protein Deficiency  Protein deficiency in guinea pigs resulted in (McMurray et al. 1990):     _... Loss of protection from BCG vaccine     _... Reduction in E rosette-forming T cells     _... Loss of PPD-lymphocyte responses     _... Altered production of interleukin-2 (IL-2)   A reversal of all immune dysfunction occurred after good nutrition was reestablished.  Vitamins B12  The high incidence of tuberculosis among a vegetarian population was attributed to   defective macrophage killing of M. tuberculosis secondary to vitamin B12   (cyanocobalamin) deficiency. Levels of methylmalonic acid (MMA) tend to accumulate in   cases of B12 deficiency and MMA can be used by mycobacteria for constructing their cell   walls. The authors hypothesized, therefore, that chronic vitamin B12 deficiency may   predispose individuals to infection by mycobacteria (Chanarin and Stephenson 1998).  Vitamin D Deficiency   Vitamin D deficiency results in (McMurray et al. 1990):     _... Reduced tuberculin skin reactions     _... Impaired PPD-induced lymphocyte proliferation     _... Inability to control M. tuberculosis infection    Results of a hospital-based, case-controlled study in Asia suggest that persons with   tuberculosis who are vitamin D (25-hydroxycholecalciferol) deficient are more susceptible   to tuberculosis. Undetectable levels of vitamin D were associated with the highest risk   (Wilkinson 2000). In a previous study, an active metabolite of vitamin D (1,25-  dihydroxyvitamin D3) was reported to help mononuclear phagocytes restrict the   intracellular growth of M. tuberculosis in vitro; the combination of 1,25-dihydroxyvitamin   D3 with gamma interferon appears to potentiate this growth inhibition further. These   findings may help explain case reports of the value of vitamin D as adjunctive treatment   for tuberculosis (Rook et al. 1986).  Zinc Deficiency  The results of studies concerning the role of zinc supplementation on immune cell   function are somewhat controversial. Zinc deficiency is thought to result in (McMurray et   al. 1990):     _... Impaired thymic function     _... Loss of T-cell mediated responses     _... Subsequent increased susceptibility to infection   Respiratory infection with virulent M. tuberculosis in zinc-deficient guinea pigs led to:     _... Tuberculin anergy      _... Decreased numbers of circulating E rosette-forming T cells     _... Decreased response of peritoneal exudate cells to PPD in vitro    In addition, recent human studies demonstrated that immune system function in patients   with acute respiratory disease (e.g., tuberculosis, bacterial pneumonia) is dependent on   zinc levels. Zinc has been shown to regulate the production of interleukin-1 alpha by   alveolar macrophages in patients with tuberculosis and bacterial pneumonia. Zinc in   concert with interleukin-1 (IL-1) is thought to stimulate other mediators that help regulate   the host immune system, such as IL-2, IL-6, and IL-8 (Abul et al. 1995). However, the   dose and stage of infection during which zinc is administered may be critical for   determining whether immunologic responses to antigen are evoked or inhibited (Abul et   al. 1995).   Essential Fatty Acids: Omega-3  Animal studies suggest that tuberculosis is more severe in guinea pigs fed omega-3   polyunsaturated fatty acids (e.g., eicosapentaenoic acid, docosahexaenoic acid) than in   guinea pigs fed saturated fatty acids or omega-6 fatty acids (Paul et al. 1997). Omega-3   fatty acids impair the intracellular killing of mycobacteria in general, and this may account   for the reduced resistance to M. tuberculosis (Rastogi and David 1988).  Vitamin A  A double-blind clinical trial sought to determine the effect of vitamin A repletion therapy in   a pediatric population with pulmonary tuberculosis and vitamin A deficiency (<20 mcg/dL).   The researchers found that while vitamin A therapy had no effect on the outcome of the   tuberculosis, after 6 weeks the respiratory status of the placebo group had improved in   significantly more children than in the treatment group, leading to the conclusion that   there may be adverse effects to vitamin A therapy.

Other Considerations

      Prevention

      _... BCG vaccine from M. bovis-efficacy 0% to 80%; used at birth in high risk   countries     _... Isoniazid-used alone for preventive therapy (300 mg/day for 6 months for adults   or 10 to 15 mg/kg/day for 9 months for children; 12 months with HIV, may extend   survival time with HIV; supervised prophylactic dose is 900 mg two times per   week)     _... Rapid diagnosis and appropriate treatment     _... Patient and health care worker education     _... Surgical masks limit patients' transmission of M. tuberculosis; dust-mite   respirators must be used by medical staff for high-risk procedures.     _... Ultraviolet radiation tends to destroy M. tuberculosis.     _... All patients with tuberculosis should be tested for HIV infection.         

Complications/Sequelae

      _... Drug-resistant tuberculosis-defined as resistance to two or more antituberculous   agents; occurs from inadequate treatment that may be due to irregular drug   availability, inappropriate regimens, or poor compliance; also results from   transmission of drug-resistant M. tuberculosis; potentially lethal; isolate patient;   96% cure rates with prompt recognition     _... Extrapulmonary disease-increased at faster rate than pulmonary tuberculosis   since 1984; frequently associated with HIV     _... Tuberculosis meningitis in children-basilar meningitis, infarction, vasculitis;   affects 1% to 2% of untreated cases     _... Pneumothorax     _... Massive hemoptysis-possibly caused by aspergilloma     _... Lymph nodes that rupture into the pericardium

EXPECTATIONS (PROGNOSIS)
Symptoms may improve in 2 to 3 weeks, with improvement seen in the chest X-ray lagging behind clinical improvement.
COMPLICATIONS
All medications used to treat TB have some toxicity. Rifampin and isoniazid may both cause a noninfectious hepatitis.
Rifampin may also cause an orange or brown coloration of tears and urine.
Other complications include drug resistance to particular TB strains and a relapse of the disease in some patients.

Courtesy:

Compiled and Shared By: Habib Anwar 

habib.anwar@hotmail.com