Tuberculosis Disease

DESCRIPTION

A common disease transmitted by inhaling airborne bacilli from a person with active tuberculosis (TB). The bacilli multiply in the alveolus and are carried by macrophages, lymphatics and blood to distant sites (eg. lung pleura, brain, kidney and bone). Tissue hypersensitivity usually halts infection within 10 weeks.

Infected persons: are asymptomatic, are not infectious, and usually have a positive tuberculin skin test
- TB: active disease - occurs in 10% of infected individuals without preventive therapy. Chance of disease increases with immunosuppression and is highest for all individuals within 2 years after infection - 85% of cases are pulmonary which is infectious.
Primary TB: disease resulting from the initial pulmonary infection which the immune system is unable to control
Recrudescent TB: active disease occurring after a period of latent asymptomatic infection
Miliary TB: disseminated disease
System(s) affected: Pulmonary, Hemic/Lymphatic/Immunologic, Renal/Urologic, Gastrointestinal, Nervous, Endocrine/Metabolic, Musculoskeletal
Genetics: N/A
Incidence/Prevalence in USA:
- Decreasing overall incidence of TB: 6.8/100,000, but greater among high risk
- 15 million have latent infection
Predominant age:
- Primary infection - any age, especially pediatric
- Recrudescent disease - adults and elderly
Predominant sex: Male > Female

SIGNS AND SYMPTOMS

Cough
Hemoptysis
Fever and night sweats
Weight loss
Malaise
Adenopathy
Pleuritic chest pain
Hepatosplenomegaly
Renal, bone or CNS disease are late findings

CAUSES

Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium africanum

RISK FACTORS

For infection: Urban, homeless, minority, migrant workers; institutional (e.g., prison, nursing home); close contact with infected individual; foreign born (Asia, Africa, Latin America); healthcare workers
For disease: HIV; recent infection; IV drug abuse; lymphoma; diabetes mellitus; chronic renal failure; malnutrition; steroids, immunosuppressive drugs; silicosis

LABORATORY

Tine test: not recommended for screening
PPD [5 units (0.1 cc) intermediate strength, 0.1 cc volar forearm; measure induration at 72 hrs]
- > 5 mm - positive if HIV infection (or suspected), immunosuppressed, exposed household contact, clinical evidence of active or old disease on chest x-ray
- > 10 mm - positive if other risk factor or < 4 years old
- > 15 mm - positive if older than 4 years and no risk factors
- Two step testing if: no recent PPD, age > 55 years, nursing home, prison or healthcare worker
Nonspecific laboratory includes anemia, monocytosis, thrombocytosis, hypergammaglobulinemia, SIADH and sterile pyuria

Drugs that may alter lab results:

BCG: false-positive skin test but unreliable
Steroids: false-negative skin test

Disorders that may alter lab results: Recent viral infections, new (<10 weeks) infection, severe malnutrition, HIV, anergy, age < 6 months. Overwhelming TB: false-negative skin test

PATHOLOGICAL FINDINGS

Granulomas with foci of caseating necrosis surrounded by epithelioid histiocytes and giant cells, in turn surrounded by lymphocytes
AFB stains positive

SPECIAL TESTS

Persons with TB should be tested for HIV
If extrapulmonary suspected, urine, CSF, bone marrow and liver biopsy for culture
Direct nucleic acid amplification approved if AFB stain positive and < 7 days of antiTB treatment, provides rapid accurate detection, but expensive

IMAGING

CXR with primary disease: may show infiltrate with or without effusion, atelectasis, or adenopathy
With recrudescent TB: cavitary lesions and upper lobe disease with hilar adenopathy common. Diffuse miliary pattern possible with appearance of "millet seeds"
HIV: atypical findings with primary infection - right upper lobe atelectasis
CXR useful to rule out TB in asymptomatic infected persons
CT chest - good sensitivity

DIAGNOSTIC PROCEDURES

AFB stain can give a presumptive diagnosis
Culture confirms diagnosis; 4-6 weeks on solid media or 2 weeks on BATEK broth system
For suspected pulmonary TB, obtain at least 3 morning sputum samples for AFB stain and culture - use aerosol induction, gastric aspirate (children) or bronchoalveolar lavage if needed
Other specimens: bone marrow, urine, tissue, CSF, peritoneal/pleural fluids
Culture and sensitivity guide treatment

APPROPRIATE HEALTH CARE

Prophylaxis for positive PPD at any age if: HIV, close contact, recent converter (< 2 years), IV drug use, abnormal CXR, high risk medical condition or if age < 35 in other high risk group. Use INH (or rifampin if resistant) in usual daily dose for minimum 6 months. Consider twice a week DOT if adherence not assured.
For inactive pulmonary TB on chest x-ray, use INH for 12 months
For active disease, use minimum of 3 drugs for 2 months, then 2 drugs to complete 6 months - start with 4 drugs if resistance possible. Several regimen options available using DOT.
If HIV infected:
- Active TB, treat at least 6 months after culture negative
- Prophylaxis, use isoniazid (INH) daily for 9 months or INH twice a week with DOT or rifampin (RIF) + pyrazinamide (PZA) daily for two months (if patient taking antiretroviral drugs, substitute rifapentine [RFP] for RIF)

GENERAL MEASURES

Careful reevaluation required. Only change to twice weekly dosing if using DOT.

SURGICAL MEASURES

For extra pulmonary complications (spinal cord compression, constrictive pericarditis)

ACTIVITY

As tolerated - respiratory isolation for infectious pulmonary TB
Children without cough and negative sputum smears: no isolation required after treatment started

DIET

Regular. Consider pyridoxine (10-50 mg/day) supplement.

PATIENT EDUCATION

Teach pathogenesis, emphasize importance of drug therapy, warn of effects and/or interactions, and find contacts
Inform local health department

PREVENTION/AVOIDANCE

PPD screening
Identify and treat contagious persons. Notify public health department and hospital infection control if admitted
Inpatient - use personal sealed respirators, negative pressure ventilation, ultraviolet
Ambulatory patients use mask and tissues
Not infectious if: favorable clinical response after 2-3 weeks of therapy and 3 AFB smears are negative

POSSIBLE COMPLICATIONS

Cavitary lesions can be secondarily infected
Spread to susceptible persons of all ages
Drug resistance - suspect if immigrant, drug resistant source or noncompliant

EXPECTED COURSE AND PROGNOSIS

Generally few complications and full resolution if drugs taken for full course as prescribed

ASSOCIATED CONDITIONS

HIV infection (see special protocols)

AGE-RELATED FACTORS

Pediatric:

Caution with ethambutol
Children on medication may attend school
Disseminated TB more common in infants; prompt treatment with 4 drugs if TB suspected
Congenital infection may occur with miliary TB of maternal bacillemia, endometritis or amniotic aspiration. If suspected, get PPD, CXR, LP, culture placenta and infant, then start treatment promptly
Protocol for newborn with mother/household member with infection or disease
- Member with positive PPD, but no disease: no special evaluation or treatment. Skin test all household members; prophylaxis if infected.
- Member has abnormal CXR: separate infant until infectious status known; if not contagious, monitor infant PPD
- Member with disease and possibly contagious: evaluate infant for congenital TB and test for HIV; separate newborn until member is noninfectious
- If congenital TB suspected, treat as above
- If no congenital disease, INH for 3-4 months, then repeat PPD: if positive, reassess for infant disease. If negative, finish 6 months INH. If repeat PPD negative and source not infectious, stop INH and monitor infant.
Consider BCG

Geriatric:

Symptoms may be more subtle and may be attributed to associated conditions or to aging
Should have a PPD prior to entering a chronic-care facility using two step protocols
Side effects of INH more pronounced

Others: N/A

PREGNANCY

Treat pregnant woman with INH, rifampin (and ethambutol, if resistance suspected); add pyridoxine
Avoid streptomycin and pyrazinamide
Prophylaxis - postpone INH until postpartum unless recent contact
Breast feeding okay while taking TB drugs

OTHER NOTES

BCG vaccine, live attenuated Mycobacterium bovis
- 50% efficacy for pediatric pulmonary TB
- In USA, consider BCG for children with negative PPD and HIV tests with unavoidable high risk and for health care workers at high risk for drug resistant infection
- Abscess, ulceration and regional lymphadenitis occur in 1-2%, osteitis and fatal infection can occur in immunosuppressed
- Used more commonly in developing countries to prevent complications of TB

ABBREVIATIONS

PPD = purified protein derivative
BCG = Bacillus Calmette-Guérin
DOT = directly observed treatment

Clinical Investigations

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