Tuberculosis

Tuberculosis

THE ORGANISMS

• Mycobacterium tuberculosis (M. tuberculosis) is a bacterium carried in airborne droplet nuclei.

EPIDEMIOLOGY

• Ninety five percent of tuberculosis (TB) cases occur in developing countries where co-infection with human immunodeficiency virus (HIV) is also common.
• Between 19 and 43 % of the world’s population is infected with M.tuberculosis. In the United States, although the rate of TB infection has declined, 15 million people are infected with M. tuberculosis (2).
• TB kills more people than any other infectious disease, including malaria and acquired immune deficiency syndrome (AIDS). Each year, more than 3 million people die and 8 million people develop disease (1).
• High-risk groups are considered people living in urban areas, institutions (prisons, nursing homes), homeless, minorities, immigrants, drug users, people with immunosuppression or HIV, healthcare workers and others in close contact with infected individuals.
• 8 to 10% of those infected with HIV develop TB.
• Incidence in USA: Overall 7.4/100,0000. In high-risk groups: 32-100/100,000.

DIAGNOSIS

Clinical

• Systemic symptoms of tuberculosis include anorexia, weight loss, weakness, night sweats, fatigability, malaise and fever.
• Pulmonary TB presents with cough progressing from non- productive to productive and rarely, hemoptysis and dyspnea.
• The majority of pulmonary TB infections in those with normal immune function are clinically and radiographically undetectable. A positive TB skin test is often the only indication of infection.
• These latent infections, without active disease, are not infectious and the organism cannot be transmitted.
• 10% of individuals with latent infection, if untreated, will develop active TB (2).
  

Laboratory

• The gold standard for identifying M. tuberculosis infection without disease is the skin test with tuberculin purified protein derivative (PPD).
• A 5-unit dose of PPD is 0.1 ml (1 mg) and should be applied intradermally.
• Result interpretation at 48 to 72 hours by measuring the size of induration (2)
• 5 mm - positive (in persons with HIV infection, immunosuppression, in close contact with infectious case or with radiological findings consistent with TB).
• 10 mm - positive (in persons with risk factors: foreign born, IV drug use, low income, long term care facilities residents, medical conditions with risk of infection and age less than 4 years.
• 15 mm - positive (in older than 4 years of age and no risk factors)(3)
• Identification of organisms is critical in the diagnosis of tuberculosis.
•  Clinical specimens for detection of organisms may include sputum, bronchial washings, urine, blood, cerebrospinal fluid, tissue and other body fluids (2).
• Acid-fast bacilli (AFB) in stained smears is evidence of Mycobacteria presence; easy and fast; is quantitative and can estimate degree of infectiousness: negative in up to 20% which does not rule out disease (2).
• Culture: 4-6 weeks on solid media or 2 weeks on Bactec broth system.
  At least 3 morning sputum samples (or other body fluid) are needed for AFB stain and culture (2).
• Presumptive diagnosis is made through identification of AFB in smears and the diagnosis is confirmed when possible through isolation of the organism on culture (4).
• Polymerase chain reaction (PCR) is a rapid technique which allows for direct identification of M. tuberculosis in clinical specimens.
• Drug susceptibility tests of the infecting organism should be performed in order to determine resistance and the most effective treatment (2).

• History of positive PPD or vaccination with BCG warrants a chest x-ray.
• Chest radiography should be performed in all patients with clinical signs and symptoms of pulmonary tuberculosis.
• Findings vary depending on extent and progression of disease and co-morbidities (i.e. HIV infection).
• MRI and CT may help to further define lesions found on chest x-ray (3).

TREATMENT(4)

• Therapy should always include multiple agents. It is best managed by and expert who works with the public health department. Directly Observed Therapy (DOT) is the most effective way to assure compliance.
• Isoniazid (INH) should be included in all treatment regimens except in cases of significant resistance to the drug.
• Rifampin (RMP) is the second major line of therapy.
• Isoniazid and Rifampin are bactericidal to both rapidly and slow growing TB organisms.
• Both pyrazinamide (PZA) and ethambutol are essential components of four-drug regimen therapy (Isoniazid, Rifampin, PZA, and Ethambutol) for resistant cases.
• Nine months of treatment with INH and RMP is effective for most cases of drug sensitive tuberculosis.
• Available second-line agents are more toxic and/or less efficacious (5).

FOLLOW-UP

• DOT (directly observed therapy): twice-weekly therapy (standard)
• Sputum for AFB: monthly
• CXR: at 3 months and at completion of therapy
• Not infectious if…clinical response after 2-3 weeks therapy and 3 negative AFB smears.

GOALS OF PREVENTION AND CONTROL

1. Decrease the risk of transmission through early identification and treatment of patients who have active infectious TB.
2. Identification of cases with latent infection and use preventive therapy with isoniazid to avoid progression to active disease (6).

PREVENTION
In the health care setting

• TB prevention and control plans must be established in all health care settings and regularly evaluated for effectiveness
• TB screening programs (PPDs) for all health care workers
• Health care worker training and education
• Use of preventive therapy (Isoniazid) to treat latent infection
• Report suspected tuberculosis cases to the local health department
• Reduce transmission through:
• Identifying patients at risk and isolating them immediately
• prompt and specific drug therapy
• hospitalizing patients with severe illness or social situation preventing adequate treatment at home
• placing patients with pulmonary tuberculosis in a private room with negative-pressure ventilation
• teaching patients to cover both mouth and nose when sneezing and coughing
• uninfected persons (i.e. HCW) should wear personal respiratory protective devices
• handwashing and cleaning practices must be strictly maintained
  
• Use airborne isolation: until 2 (-) AFB smears from expectorated sputum. See policy for further instructions for discontinuing isolation.
• Minimal air quality standard is 6-air exchanges/ hour (In 1 hour all droplet nuclei are removed from the air).

 In the community

• Identify and treat infectious cases to decrease transmission.
• Reduce or eliminate conditions increasing the spread of infection (i.e. over crowding).
• Educate the public regarding transmission, control methods and the importance of early diagnosis and treatment.
• Adherence to prescribed therapy for tuberculosis should be emphasized and enforced (i.e. DOT) (4).
• Quarantine is NOT necessary in most cases.
• TB testing (PPD) of all close contacts. Chest x-rays should be performed on all with positive screening tests.
• 3 months preventive treatment is recommended for close contacts who are skin test negative. Skin test should be repeated after 3 months to determine the need for further therapy (4).

VACCINATION

• Bacillus of Calmette and Guerin (BCG) vaccine.
• Prevents progression to clinical disease not an infection.
• Not routinely used in the US or other industrialized nations due to the relatively low risk of infection in these areas.
• 60-80% effective in reducing the incidence of TB in children.
• May be useful in areas with high prevalence of TB infection.
• Administer only if tuberculin-negative.
• May be indicated for tuberculin-negative close contacts of a TB infected person who is untreated or ineffectively treated for pulmonary tuberculosis or who is infected with a drug resistant strain (4,5,6).

References

1. WHO. 1996. Groups at Risk: WHO Report on the Tuberculosis Epidemic.
   
2. Diagnostic standards and classification of tuberculosis in adults and children. MMWR, April 2000. Am. J. Respir. Crit. Care Med.2000; Vol 161, 1376-1395.
   
3. Dooley, S.W., Jarvis, W.R., & Snider, D.E. (). Mycobacterium tuberculosis. In: Hospital Epidemiology and Infection Control In Special Circumstances.
   
4. Benenson, A.S. (Ed.) (1995). Control of Communicable Diseases Manual. (16th ed.). American Public Health Association: Washington, DC.
   
5. Mandell, G.L., Bennett, J.E., & Dolin, R. (2000). Principles and Practice of Infectious Diseases. (5th ed.). Churchill Livingstone: Philadelphia, PA.
   
6. CDC. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. MMWR April 1996, 45, RR-4; 1-18.