TUBERCULOSIS Tuberculosis TB is an infectious disease caused

TUBERCULOSIS

Tuberculosis (TB) is an infectious disease caused by inhalation of aerosolized Mycobacterium tuberculosis (MTB) bacteria, a small, stricktly aerobic, nonmotile bacillus, which is covered with a mycolic acid layer. The TB infection sequence goes: primary infection —> latent infection —> reactivation.

Primary tuberculosis occurs when aerosolized, contaminated droplets are inhaled and droplet nuclei reach the alveoli, where bacteria multiply locally for a while and then spread to areas of the body with high oxygen tension (bone, brain, kidneys, apices o f lungs). Cell-mediated immunity kicks in to arrest dissemination and growth of organisms during this initial stage. Latent: In the exposed patient with a functional immune system, the organisms are held at bay by the formation of granulomas (and the patient does not develop primary infection). In the lung, the granulomas sometimes calcify and can be observed as Ghon complexes. *Ghon complex: Ghon foci + lymphadenopathy. *Rhanke Complex: Calcified, healed, and fibrotic Ghon Complex.

Reactivation: With aging and development of comorbidities, the cellmediated immune system sometimes loses its ability to keep the organisms in check, and the patient develops “reactivation TB. ” Reactivation disease occurs at the sites of initial dissemination (lung apices, brain, kidney, bones). The risk o f reaction is highest after exposure (5% within the first 2 years and another 5% thereafter; HIV/AIDS patients are an exception and have 40% risk of reactivation within months). Common presenting signs of reactivation tuberculosis include: fever, weakness, night sweats, and weight loss. Pulmonary disease is indicated by cough, pleuritic chest pain, and hemoptysis.

Miliary tuberculosis is the term given to uncontrolled hematogenous spread of M tuberculosis. The clinical picture is variable—from overwhelming disease with multisystem organ failure (in primary infection) to chronic wasting (in reactivation infection). The classic chest x-ray is a faint and diffuse reticulonodular infiltrate. (fine 1– 2 mm lesions (‘millet seed’) distributed throughout the lung fields)

Clinical features: extrapulmonary disease Extrapulmonary TB accounts for 20% of cases in those who are HIV-negative but is more common in HIV-positive patients

Lymphadenitis: Lymph nodes are the most common extrapulmonary site of disease, Cervical and mediastinal glands are affected most frequently, followed by axillary and inguinal. The nodes are usually painless and initially mobile but become matted together with time. When caseation and liquefaction occur, the swelling becomes fluctuant and may discharge through the skin with the formation of a ‘collar-stud’ abscess and sinus formation. During or after treatment, paradoxical enlargement, development of new nodes and suppuration may all occur but without evidence of continued infection

Gastrointestinal tuberculosis: Ileocaecal disease accounts for approximately half of abdominal TB cases. Fever, night sweats, anorexia and weight loss are usually prominent and a right iliac fossa mass may be palpable. Ultrasound or CT may reveal thickened bowel wall, abdominal lymphadenopathy. Diagnosis rests on obtaining histology by either colonoscopy or mini-laparotomy. Tuberculous peritonitis is characterized by abdominal distension, pain and constitutional symptoms. white ‘tubercles’ over the peritoneal and omental surfaces

Pericardial disease Disease occurs in two forms: pericardial effusion and constrictive pericarditis. Pulsus paradoxus, a raised JVP, hepatomegaly, prominent ascites and peripheral oedema are common to both types. Pericardial effusion is associated with increased pericardial dullness and a globular enlarged heart on chest X-ray, and pericardial calcification occurs in around 25% of cases. Constriction is associated with an early third heart sound and, occasionally, atrial fibrillation. Diagnosis is based on the clinical, radiological and echocardiographic findings. The addition of glucocorticoids to antituberculosis treatment has been shown to help both forms of pericardial disease.

Central nervous system disease: Meningeal disease represents the most important form of central nervous system TB. Unrecognised and untreated, it is rapidly fatal. Even when appropriate treatment is prescribed, mortality rates of 30% have been reported. Headache, vomiting, seizures, delirium Lymphocytic meningitis Hydrocephalus, Space-occupying lesion(tuberculoma).

Bone and joint disease: The spine is the most common site for bony TB (Pott’s disease), which usually presents with chronic back pain and typically involves the lower thoracic and lumbar spine, causing angulation of the vertebrae with subsequent kyphosis. Paravertebral and psoas abscess. CT or MRI is valuable in gauging the extent of disease, the amount of cord compression, and the site for needle biopsy or open exploration. TB can affect any joint but most frequently involves the hip or knee. Presentation is usually insidious, with pain and swelling. Radiological changes are often non-specific but, as disease progresses, reduction in joint space and erosions appear.

Diagnosis: The CDC-recommended approach to diagnose active pulmonary TB includes: -TB skin test or interferon gamma release assay (IGRA). -Chest x-ray. -Acid-fast smears and cultures of the sputum. -At least 1 nucleic acid amplification test (NAAT; PCR).

Screening for Latent TB Infection: Who gets screened? High-risk groups including: -HIV or high-risk for HIV -Close contacts of those with reactivation tuberculosis -IV drug abusers -Low-income, medically underserved populations -Homeless -Migrant workers -Residents of long-term care facilities (nursing homes and jails)

PPD: The standard Mantoux test is an intradermal injection of 0. 1 m. L (5 tuberculin units) of purified protein derivative (PPD) tuberculin in the forearm. The injection site is evaluated 48 -72 hours after the injection. The reading is based on the diameter of the indurated/swollen area—not the erythematous area.

All of the following are considered significant (i. e. , should be treated) skin tests: > 15 mm is significant for the low-risk group. This includes most people in the community

> 10 mm is significant for those in the intermediate-risk group: -Homeless persons -Recent immigrants (within 5 years) from high-prevalence countries. -Injection drug users who are HIV-negative. -Prisoners -Health care workers! -Nursing home patients and staff. -Patients with diabetes, silicosis, malignancy, and malnutrition.

> 5 mm is significant for those in the high-risk group: -HIV or major cell-mediated dysfunction -Fibrotic changes on chest x-ray consistent with prior TB -Close contact with a documented case -Patients with organ transplants and other immunosuppressed patients (receiving the equivalent of > 15 mg/d of prednisone for 1 month or more, or receiving TNF-inhibitor or chemotherapy)

Treatment for LTBI Treatment with INH for 9 months is recommended for everyone except those with known exposure to INH resistant organisms or history of INH intolerance —these patients should get rifampin for 4 months instead. Do not use pyrazinamide (PZA) in pregnancy because it causes birth defects.

Treatment of Active TB: The 4 -drug regimen: -Isoniazid (INH) -Rifampin (RIF) -Pyrazinamide (PZA) -Either ethambutol (oral; preferred) or streptomycin (injection)

all patients with active tuberculosis are initially to be treated for 2 months with 4 -drug therapy. Give the first 3 drugs for the full 2 months, while the 4 th drug may be dropped if the susceptibility testing shows sensitivity to the first 3 drugs. After the first 2 months, give INH + RIF for an additional 4 months— i. e. , 6 months total. When can 3 drugs be used? Only if there is a slight chance of drug-resistant infection. All the following criteria must be met: -New TB patient and < 4% primary resistance to INH in the community. -No known exposure to a patient with a drug-resistant infection. -Is not from a high-prevalence country.

Additional notes : -Give vitamin B 6 (pyridoxine) with INH-containing regimens to prevent peripheral neuropathy and mild central nervous system effects. -If the patient cannot take PZA, give INH and RIF for a total of 9 months. -If the TB is resistant to INH only, stop INH and give the other 3 drugs for 6 months (total) or RIF and ethambutol for 12 months.

-INH, RIF, and PZA are all hepatotoxic. -Ethambutol is not hepatotoxic, but it can cause a decrease in visual acuity. Often, decreased color perception is the 1 st sign of this deterioration. -Patients treated with rifampicin should be advised that their urine, tears and other secretions will develop a bright, orange/ red coloration, and women taking the oral contraceptive pill must be warned that its efficacy will be reduced and alternative contraception may be necessary

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