Tuberculosis

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Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Laboratory 8 Radiology 9 Management 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

More Specific Terms

• extensively drug-resistant tuberculosis (XDR-TB)
• HIV1/tuberculosis coinfection
• scrofula
• silicotuberculosis
• tuberculous meningitis

Etiology

• inhalation of aerosilized droplets containing MTB
• direct inoculation of abraded skin
• risk factors for primary progression or reactivation of quiescent disease

• malnutrition
• immunosupression
• stress
• cigarette smoking may be risk factor [17]

Epidemiology

• lifetime risk of a person infected with tuberculosis for developing active disease is 5-10%
• coinfection of HIV & tuberculosis

• when coinfected with MTB & HIV, risk of active TB is increased to 8-40%/year
• average CD4 count of AIDS patients developing tuberculosis is 150-200/ mm3
• >= 8% of patients with MTB are coinfected with HIV [19]

• outbreaks of multi-drug resistant tuberculosis have occurred in urban populations at risk for TB & HIV
• 5.1 cases/100,000 people in 2003 [9]
• 60% of new TB cases in foreign born individuals [9]; 30% of these cases diagnosed within 2 years of entry into the US
• prevalence of tuberculosis is 10 times higher in foreign- born US residents than US-born residents [4]

Pathology

• pulmonary disease (most frequent clinical presentation)
• lymphatic/ reticuloendothelial disease
• genitourinary disease
• osteomyelitis (lower spine 'Pott's disease')
• meningitis, peritonitis, pericarditis, adrenalitis
• miliary TB
• Mycobacterial isocitrate lyase protects MTB against interferon-mediated macrophage elimination

• a human-like protein kinase G renders mycobacteria resistant to bactericidal activity of macrophages, probably by inhibiting fusion of phagosomes with lysosomes [10]

• iron-binding acute phase protein detected with variable frequency in serum of patients with tuberculosis (non-specific)

Genetics

• genetic variations in vitamin D3 receptor may determine Mycobacterium tuberculosis susceptibility
• genetic variations in SLC11A1 determine Mycobacterium tuberculosis susceptibility

Clinical-manifestations

• fatigue
• anorexia
• weight loss
• fever with night sweats
• productive cough over weeks or months
• hemoptysis
• chest pain
• dyspnea with extensive disease or pleural effusion
• if CNS involvement, basilar meningitis & cranial nerve palsy
• may be asymptomatic, especially

• initial phase
• HIV patients [4]

Laboratory

• sputum: acid fast smears provide presumptive ID, but Nocardia & other Mycobacterium spp also appear acid fast on smear
• sputum culture
• blood culture: positive in 26-42% of AIDS patients
• PCR/ southern blot ( serum, CSF)
• QuantiFERON-TB test ( latent tuberculosis)
• HIV testing, CD4 count if positive; with CNS involvement, CD4 count generally > 300/ uL [4]

Radiology

• chest X-ray

• upper lobe cavitary lesions with reactivation of latent TB
• infiltrates, pleural effusion
• hilar lymphadenopathy
• interstitial disease, bilateral infiltrates & pleural effusions may be seen in patients with severe immunosuppression
• HIV infection strongest predictor of non upper- lobe lesion [12]

Management

• pulmonary TB:

• INH 300 mg PO QD + (50 mg pyridoxine PO QD)
• rifampin 600 mg PO QD
• pyrazinamide 1.5-2.0 g PO QD
• ethambutol 15 mg/kg PO QD or streptomycin 15 mg/kg IM QD
• if isolate is found to be susceptible to INH & rifampin, ethambutol or streptomycin may be dropped & 3 drugs: INH, rifampin, & pyrazinamide continued for 8 weeks followed by 16 weeks of INH & rifampin.
• respiratory isolation

• all hospitalized patients with pulmonary TB in a negative pressure room
• remove from respiratory isolation when patient is on adequate anti- tuberculous drug therapy and

• has had a significant clinical response, or
• has had 3 consecutive negative sputum smears

• hospitalization for respiratory isolation is not required

• extrapulmonary TB:

• treat same as pulmonary TB for 6-9 months

• INH-resistant TB:
• rifampin 600 mg PO QD
• pyrazinamide 1.5-2.0 g PO QD
• ethambutol 15 mg/kg PO QD or
• streptomycin 15 mg/kg IM QD
• duration of therapy 6 months
• multidrug resistant TB:

• empiric therapy should consist of 5- 6 drugs

• isoniazid ( INH), rifampin, pyrazinamide, ethambutol, streptomycin, fluoroquinolone

• treatment should consist of at least 3 drugs to which the organism is sensitive
• consider surgery for which the bulk of the disease is resectable
• continue treatment for at least 18-24 months or for 12 months after culture negative
• associated with increased mortality [4]

• patients who must be treated parenterally

• INH 300 mg IV QD + (50 mg pyridoxine PO QD)
• rifampin 600 mg IV QD
• amikacin 500 mg IV every 12 hours

• other 1st line agents

• rifapentine
• rifabutin

• other 2nd line agents

• cycloserine
• ethionamide
• kanamycin plus amikacin
• fluoroquinolones

• ciprofloxacin, oflaxacin, levofloxacin, moxifloxacin, gatifloxacin

• para-aminosalicylate

• new drug(s) on the horizon

• R207910, a diarylquinolone [11]

• 10-fold more effective than INH or rifampin

• monitoring therapy:

• pulmonary TB:

• weekly sputum smears & cultures for the 1st 6 weeks of therapy
• smears & cultures obtained thereafter until cultures are negative
• continued positive smears or cultures after 3 months suggest drug-resistance or non-compliance with medications

• baseline laboratory values:

• serum alanine aminotransferase ( serum ALT)
• serum aspartate aminotransferase ( serum AST)
• serum bilirubin
• complete blood count ( CBC)
• serum creatinine

• liver function should be monitored often, perhaps as often as every 2 weeks [8]
• patients taking EMB should be tested for visual acuity & red-green color perception.

• treatment does not affect HIV antiretroviral therapy [15]
• never add a single drug to a failing regimen [4]
• screening for tuberuculosis

• PPD vs chest X-ray
• immigrants from Asia, Africa, Latin America, Eastern Europe, Russia
• health care workers who care for high-risk patients
• medically underserved, low-income populations
• injection drug use
• incarceration [4]

• chemoprophylaxis: (see chemoprophylaxis for tuberculosis)
• The Health Dept. should be notified in all cases of TB.
• N95 respirator is used by medical personel in contact with tuberculosis patients [13]

More General Terms

• mycobacterial infection
• lung disease
• granulomatous disease

Additional Terms

• chemoprophylaxis for tuberculosis Mycobacterium tuberculosis (MTB)
• PCR/southern blot for Mycobacterium tuberculosis
• purified protein derivative (PPD, Tubersol)
• QuantiFERON-TB test
• tuberculin-skin testing (TST)

Internet Database

OMIM: 607948

References

1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995
2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 183-86
3. American Thoracic Society: Am J Crit Care Med 149:1359-1374 1994
4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, American College of Physicians, Philadelphia 1998, 2006, 2009
5. Prescriber's Letter 7(7):40 2000
6. Journal Watch 20(19):153, 2000
7. Davies P. Tuberculosis in the elderly. Epidemiology and optimal management. Drugs Aging, 8:436, 1996 PMID: [1]
8. Journal Watch 21(19):155, 2001 Centers for Disease Control and Prevention (CDC). Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations
   - United States, 2001. MMWR Morb Mort Wkly Rep 50:733, 2001 PMID: [2]
9. Journal Watch 24(8):64, 2004 Centers for Disease Control and Prevention (CDC). Trends in Tuberculosis - United States 1998-2003, MMWR Morb Mort Wkly Rep 52:209, 2004 <PubMed> PMID: [3] <Internet> [4]
10. Journal Watch 24(13):107, 2004 Walburger A, Koul A, Ferrari G, Nguyen L, Prescianotto-Baschong C, Huygen K, Klebl B, Thompson C, Bacher G, Pieters J. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science. 2004 Jun 18;304(5678):1800-4. Epub 2004 May 20. PMID: [5]
11. Journal Watch 25(4):31-32, 2005 Andries K, Verhasselt P, Guillemont J, Gohlmann HW, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005 Jan 14;307(5707):223-7. Epub 2004 Dec 09. PMID: [6]
12. Journal Watch 25(15):121, 2005 Geng E, Kreiswirth B, Burzynski J, Schluger NW. Clinical and radiographic correlates of primary and reactivation tuberculosis: a molecular epidemiology study. JAMA. 2005 Jun 8;293(22):2740-5. PMID: [7]
13. Veterans Administration, Mather CA
14. Controlling Tuberculosis in the United States Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America MMWR: Recommendations and Reports November 4, 2005 / 54(RR12);1-81 [8]
    - Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005 Dec 30;54(17):1-141. PMID: [9]
15. Breen RAM et al, Virological response to highly active antiretroviral therapy is unaffected by tuberculosis therapy. J Infect Dis 2006; 193:1437 PMID: [10]
16. Liu Y et al Overseas screening for tuberculosis in U.S.-bound immigrants and refugees. N Engl J Med 2009 Jun 4; 360:2406. PMID: [11]
17. Shang S et al. Cigarette smoke increases susceptibility to tuberculosis - Evidence from in vivo and in vitro models. J Infect Dis 2011 May 1; 203:1240 PMID: [12]
18. Tuberculosis: NIH Institute and Center Resources [13]
    - Recommendations and Reports Prevention and Control of Tuberculosis in Correctional and Detention Facilities: Recommendations from CDC MMWR July 7, 2006 July 7, 2006 / 55(RR09);1-44 Corresponding NGC guideline withdrawn Dec 2011 [14]
19. Centers for Disease Control and Prevention Trends in Tuberculosis — United States, 2011 MMWR March 23, 2012 / 61(11);181-185 [15]
20. Centers for Disease Control and Prevention TB Guidelines [16]
21. National Guideline Clearinghouse
    - Managing drug interactions in the treatment of HIV-related tuberculosis. ngc-guideline: [17]
    - Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. ngc-guideline: [18]
    - Guidelines for preventing the transmission of Mycobacterium tuberculosisin health-care settings, 2005. Centers for Disease Control and Prevention ngc-guideline: [19]
    - Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. National Collaborating Centre for Chronic Conditions ngc-guideline: [20]
    - Case-finding strategies. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [21]
    - Category IV recording and reporting system. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [22]
    - DR-TB and HIV infection. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [23]
    - Drug resistance and infection control. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [24]
    - Initial evaluation, monitoring of treatment and management of adverse effects. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [25]
    - Laboratory aspects. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [26]
    - Management of contacts of MDR-TB patients. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [27]
    - Management of patients after MDR-TB treatment failure. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [28]
    - Management of second-line antituberculosis drugs. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [29]
    - Managing DR-TB through patient-centred care. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [30]
    - Mono-resistant and poly-resistant strains. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [31]
    - Treatment delivery and community-based DR-TB support. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [32]
    - Treatment of DR-TB in special conditions and situations. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [33]
    - Treatment strategies for MDR-TB and XDR-TB. In: Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization ngc-guideline: [34]
    - Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource- constrained settings. World Health Organization ngc-guideline: [35]
    - Guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update. World Health Organization ngc-guideline: [36]

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