Module Two: Diseases Of Poverty

     

Mycobacterial Diseases: Tuberculosis

Miliary TB

Background

Tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis. The organism is transmitted by inhaling airborne M. tuberculosis bacilli from a person with active TB. Bacilli multiply in alveoli and are carried by blood and lymphatic vessels to distant sites. Those at higher risk for TB infection include persons who are less than 4 years old, urban, homeless, migrant workers, institutionalized, health care workers, immunocompromised (resulting from HIV, steroid therapy, malnutrition, or measles), and suffering from chronic diseases. Outcome of infection is determined by the efficacy of the host's immune response. The immune system usually is able to limit bacterial replication. Latent TB infection is asymptomatic, noninfectious, and usually only detected by positive skin test. Active TB occurs in 10% of infected people who do not receive preventive therapy. Immunosupression and age increase the risk of developing active TB.

Symptoms and Signs

• Cough, hemoptysis
  
  
• Fever, malaise, weight loss
  
  
• Adenopathy, hepatosplenomegaly
  
  
• Symptoms related to specifically infected organ systems
  
  
• Pulmonary TB is the most common form of disease due to M. tuberculosis. Extrapulmonary TB occurs in less than 20% of cases and can occur in any organ or tissue of the body.
  
  
• M. bovis is a pathogen of cattle, and is transmitted to humans through ingestion of unpasteurized milk. M. bovis typically causes cervical lymphadenitis or gastrointestinal TB.

• Differential diagnosis includes other pneumonias, lymphomas, and pulmonary fungal infections.
  
  
• Nonspecific laboratory findings include anemia, monocytosis, thrombocytosis, sterile pyuria, and hypergammaglobulinemia.
  
  
• Use of steroids, malnutrition, viral infections, HIV, or overwhelming TB infection may cause a false-negative skin test.
  
  
• Bacille Calmette-Guérin (BCG) vaccination may cause a false-positive skin test.
  
  
• Chest X-ray (CXR) may demonstrate infiltrate, cavitary lesions, hilar adenopathy, or a miliary pattern. Findings are most common in the apical posterior portion of the lung. Compression of bronchi from enlarged nodes can cause segmental or lobar collapse.
  
  
• Persons with TB should be also tested for HIV.
  
  
• If extrapulmonary TB is suspected, other diagnostic tests may be indicated.
  
  
• Intermediate strength purified protein derivative (PPD) should be read at 2 to 3 days.
  
  
• PPD is positive if > 5 mm of induration for patients with: (1) close contacts who have TB, (2) CXR findings of TB, (3) immunosuppression, or (4) chronic diseases (such as diabetes mellitus, severe renal insufficiency, malnutrition, leukemia, or lymphoma).
  
  
• PPD is positive if induration > 10 mm and age < 4 years or in the presence of other risk factors.
  
  
• PPD is positive if induration > 15 mm, age > 4 years, and no other risk factors are present.
  
  
• For suspected pulmonary TB, obtain at least three morning sputum samples for acid-fast bacillus (AFB) stain and culture. Gastric aspirate or bronchoalveolar lavage may also be tested if needed.
  
  
• AFB stain can give a presumptive diagnosis.
  
  
• TB should never be ruled out on the basis of a negative AFB stain alone.
  
  
• Culture confirms the diagnosis, but may not often be available.

• Persons already infected with TB are at increased risk of disease progression following HIV infection. HIV infection should also be considered in new TB patients.
  
  
• Appearance of extrapulmonary TB is more common in HIV-infected patients.
  
  
• HIV-infected patients who have TB commonly present with fever of unknown origin, night sweats, weight loss, and pulmonary symptoms. Fever is most commonly due to opportunistic infections and/or neoplasms.

• Extrapulmonary TB most commonly involves the cervical nodes (scrofula). Node enlargement is slow and painless. Over time, the nodes become fixed together without local signs of inflammation.
  
  
• Caseous nodes may rupture through the skin, forming a draining sinus tract.
  
  
• Constitutional symptoms are frequently absent.

• Renal TB is relatively common because of the kidneys' high blood flow and oxygen tension. Symptoms of renal TB include dysuria, urinary frequency, hematuria, and renal colic. Acid-fast smears of urine have poor sensitivity, though sterile pyuria is regularly present.
  
  
• Male genital TB usually presents as epididymitis or prostatitis, and infertility is common.
  
  
• Female genital TB most commonly presents as infertility, amenorrhea, and pelvic pain due to inflammation of the fallopian tubes.

• The spine, hip, and knee are most commonly affected sites by skeletal TB.
  
  
• Spinal TB usually involves the lower thoracic spine and leads to pain and an unwillingness to bend over. As the disease progresses, vertebral bodies may collapse and neurological compromise may occur.

• TB of the gastrointestinal (GI) tract most commonly infects the terminal ileum, and typically presents with abdominal pain, mass effect, and bowel obstruction.
  
  
• Rectal TB should be considered in the differential diagnosis of patients who have an anal fistula.

• Peritoneal TB commonly causes ascites and constitutional symptoms that, in high-risk locations, must be distinguished from other etiologies, including schistosomiasis, hepatocarcinoma, and alcoholism.
  
  
• TB infects the peritoneum via hematogenous dissemination, rupture of caseous mesenteric nodes, or spillage of genitourinary TB through the fallopian tubes.
  
  
• Some peritoneal TB patients have minimal ascites and instead have findings of tender abdominal masses-the classic "doughy" abdomen.

• Low-grade fever, malaise, headache, irritability, and neck stiffness of insidious onset should prompt consideration of TB meningitis. As the disease advances, cranial nerve palsies and hemiplegia may occur.
  
  
• Brain tuberculomas present with clinical findings of space-occupying lesions, including focal neurological signs or signs of increasing intracranial pressure. Nausea, vomiting, and decreased consciousness may herald hydrocephalus.
  
  
• Cerebrospinal fluid (CSF) analysis classically shows elevated white blood cell (WBC) count with a high lymphocyte component, high protein, and low glucose.AFB is uncommonly identified.
  
  
• Without treatment, meningeal and brain TB is rapidly fatal.

• Fever, chest pain, and a pericardial friction rub are common findings.
  
  
• TB bacilli infect the pericardium via hematogenous spread or via direct extension from lungs or lymph nodes.
  
  
• Pericardial TB causes some patients to develop large pericardial effusions with risk of pericardial tamponade, while other patients develop a thickened pericardium with risk of constrictive pericarditis.

• For active disease, treatment in the initial 2-month phase usually includes isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Two drugs, usually INH and RIF, are used in the continuation phase from 4 to 7 months. Consider pyridoxine (PDX) supplement.
  
  
• Multiple other TB medications, such as EMB and streptomycin, may be considered and included in TB therapy protocols.
  
  
• Treatment should be extended to 12 months in miliary disease, bone and joint TB, and TB meningitis.
  
  
• Children should be treated in essentially the same way as adults, using appropriately adjusted doses.
  
  
• HIV patients respond to standard regimens. Follow the patient closely for evidence of relapse. Lifelong suppression with INH may be indicated in patients who are severely immunocompromised.
  
  
• Many countries have national guidelines for the management of TB. These regimens should be followed in routine cases.
  
  
• Treatment adherence plans using directly observed treatment short course (DOTS) by a responsible person have the highest completion rates.
  
  
• For patients who are PPD converters or who have inactive pulmonary TB on CXR, prescribe INH for 9 months.
  
  
• Monitor liver enzymes periodically for adverse effects of TB medications.

• Resistance should be suspected if: (1) sputum remains smear positive after 3 months of treatment; (2) history of previous TB therapy exists; or (3) the source of the patient's infection is suspected to be drug-resistant TB.
  
  
• When drug resistance is suspected: (1) add at least two new drugs; (2) perform susceptibility testing; (3) fully supervise therapy: and (4) plan a long course of therapy, at least 12 months after sputum has converted to AFB-negative.

• Maintain adequate nutrition.
  
  
• Avoid crowded living conditions.
  
  
• Consider BCG vaccination. (BCG vaccination offers limited protection against TB and causes a false-positive PPD that limits the diagnostic usefulness of this test.)
  
  
• Identify and treat contagious persons.
  
  
• Provide respiratory isolation for infectious pulmonary TB until there is a clinical response and three AFB smears are negative.

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