Infectious Diseases - TB

7/23/2019 Infectious Diseases - TB

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Kingdom:Bacteria

Phylum:Actinobacteria

Order:Actinomycetales

Suborder:Corynebacterineae

Family:Mycobacteriaceae

Genus:Mycobacterium

Species:M. tuberculosis

Binominal name: Mycobacterium tuberculosis


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Incidence of active TB per 100000 person-years in Victorian

immigrants from high-low risk regions of origin, by time since arrival.

McBryde and Denholm; Risk of active tuberculosis in immigrants: effects of age, region of origin and time since arrival in a low -exposure setting Med J Aust 2012; 197 (8): 458-461.


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A 24 year old lady from Indonesia and mother of five

children presents with a two week history of cough and

weight loss

A 21 year old overseas student from Indiapresents with

malaise, mild shortness of breath and low grade fevers


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Chest. 2012;142(3):761-773. doi:10.1378/chest.12-0142


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1) Primary TB2) Re-activation TB3) ..4) .5) ..6)


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Many studies show significantnumbers of asymptomaticsubjects

- Fever

- Pleuritic chest pain

- Retrosternal pain

- Inter-scapular pain

POULSEN A. Some clinical features of tuberculosis. Acta Tuberc Scand 1957; 33:37.
http://www.uptodate.com/contents/clinical-manifestations-and-evaluation-of-pulmonary-tuberculosis/abstract/3http://www.uptodate.com/contents/clinical-manifestations-and-evaluation-of-pulmonary-tuberculosis/abstract/3


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Constitutional signsfever, night sweats, weight loss, anorexia

chronic +/- productive +/- haemoptysis +/- purulence

MacGregor RR. A year's experience with tuberculosis in a private urban teaching hospital in thepostsanatorium era. Am J Med 1975; 58:221.
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Caseating granulomas AFB Ziehl Neelsen

.


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AFB stain depends onconcentration -

sensitivity of 45% to80%

Routine cultures -

solid media - mediantime to positivity is 3to 4 weeks

MacGregor RR. A year's experience with tuberculosis in a private urban teaching hospital in thepostsanatorium era. Am J Med 1975; 58:221.
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QUESTION 1


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Asymptomatic

2 Tests

Mantoux Tuberculin Skin Test (TST)

Interferon-Release Assays (IGRAs). .

Jensen PA, Lambert LA, Iademarco MF, et al. Guidelines for preventing the transmission of Mycobacterium

tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005; 54:1.
http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16http://www.uptodate.com/contents/diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-hiv-negative-adults/abstract/16


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Injection of purified protein derivative and measurement ofinduration (NOT erythema) 48 to 72 hours later

FURTHER studies of geographic variation in naturally acquired tuberculin sensitivity. Bull World Health

Organ 1955; 12:63.
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QUESTION 2

A 23-year-old man undergoes preliminary evaluation. He has just been admitted to adetoxification center because of injection drug use.

On physical examination, temperature is 36.8 C (98.2 F), blood pressure is 125/75 mmHg, pulse rate is 90/min, and respiration rate is 18/min. Findings of physical examinationdemonstrate evidence of injection drug use on the bilateral upper extremities but areotherwise normal.

Tuberculin skin testing induces 6 mm of induration. The patient has not had previous

tuberculin skin tests. Results of a serologic test for HIV infection are negative

What is the most appropriate next step?

A) Chest radiograph

B) IsoniazidC) Isoniazid, rifampin, pyrazinamide, and ethambutol

D) No additional therapy or evaluation


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Interpretation of Tuberculin Skin Test Results

5 mm Induration

HIV-positive persons

Recent contacts of persons with active TB

Persons with fibrotic changes on chest radiograph consistent with old TB

Patients with organ transplants and other immunosuppressive conditions

10 mm Induration

Recent (


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QUESTION 3

A 63-year-old man undergoes annual screening for tuberculosis. The patient is a physician,and this screening is required for maintaining his hospital appointment. His medical historyis significant for bladder cancer diagnosed 1 year ago that was treated with bacillusCalmette-Gurin. There is no current evidence of active bladder cancer on follow-upcystoscopy, and he has no respiratory or systemic symptoms.

On physical examination, vital signs are normal. The remaining physical examinationfindings, including cardiopulmonary examination, are normal

Which investigation is most appropriate?

A) Chest radiographB) Interferon-release assay

C) Tuberculin skin test

D) Two-step tuberculin skin testing


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As sensitive, more specific than TST

Two available: the QuantiFERON-TB Gold In-Tube (QFT-GIT)assay and the T-SPOT.TB assay.

Preferred in context of BCG vaccine/therapy or the

unreliable patient

Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010.MMWR Recomm Rep 2010; 59:1.
http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection/abstract/5


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QUESTION 4

A patient is referred in for health screening by the Department of Healthafter they travelled from Africa to Australia two weeks ago. The personsitting next to them was diagnosed with multi-drug resistant TB followingtheir arrival in Australia. Your patient is otherwise healthy and recent HIVtesting and tuberculin skin tests were negative

Which of the following management options would be the mostappropriate?

a) CXR in 6 weeks

b) Immediate CXR

c) Tuberculin test or interferon gamma release assay in 6 weeks

d) Prophylactic chemotherapy for MDR-TB

e) Isoniazid prophylaxis


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Active and Latent TB


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QUESTION 5

A 24 year old lady from Indonesia and mother of five childrenpresents with a two week history of cough and weight loss. Shealso complains of night sweats and a low grade fever. Hersputum is positive for acid fast bacilli. What is the most

appropriate initial treatment whilst awaiting for culture?

a) Isoniazid and Rifampicin

b) Isoniazid, Rifampicin and Ethambutol

c) Isoniazid, Rifampicin, Pyrazinamide and Ethambutold) Ceftriaxone and Azithromycin

e) Trimethoprim-sulfamethoxazole


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Treatment phase: RIPE

2-months: Rifampicin, Isoniazid, Pyrazinamide and Ethambutol

Continuation phase:RI

4-months: Isoniazid and Rifampicin

Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment oftuberculosis. Am J Respir Crit Care Med 2003; 167:603.
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QUESTION 6

A 30-year-old man is admitted to the hospital with a 1-month history of fever,night sweats, cough, weight loss, and chest pain. The patient is homeless. Adiagnosis of pericardial tamponade is established.

Pericardiocentesis is performed, following which there is no recurrence of asignificant pericardial effusion. Microbiologic examination of pericardial fluid

identifies Mycobacterium tuberculosis.

In addition to four-drug antituberculous therapy, which of the following is themost appropriate next treatment?

A)Indomethacin and colchicineB) Pericardial window

C) Prednisone

D) Surgical pericardiectomy


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RIPE and RI for extra-pulmonary

Exception: TB Meningitis/Pericarditis:

ADJUNCTIVE STEROIDS

longer duration of therapy (9-12mo)



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Isoniazid, 9 month course.

Alternatives:1) 4 months: Rifampicin

2) 3 months: once-weekly Rifapentine/ Isoniazid combination



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QUESTION 7


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QUESTION 8

A 25-year-old woman undergoes evaluation. Treatment for active pulmonary tuberculosis was initiated6 weeks ago. The mycobacteria were susceptible to all first-line antituberculous agents, and a 2-monthcourse of isoniazid, rifampin, ethambutol, and pyrazinamide was prescribed as initial therapy. However,the patient was lost to follow-up for 3 weeks, during which time she discontinued all medications.

On physical examination, temperature is 37.7 C (99.9 F), blood pressure is 110/70 mm Hg, pulserate is 90/min, and respiration rate is 18/min. The remainder of her physical examination is normal.

What is the best course of action?

A) Continue the same treatment to complete the planned total number of doses, provided all dosesare completed within 3 months

B) Repeat sputum smear for acid-fast bacilli; if results are negative, treatment can be consideredcomplete

C) Restart different treatment with at least two new drugs to which the mycobacteria wereoriginally susceptible

D) Restart the same treatment from the beginning


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Interruption > 2 weeks during the initial 2-month phase oftherapy requires restarting the same regimen from the

beginning.

Interruption < 2 weeks, initial regimen should be continueduntil the planned total number of doses is taken, provided thatall doses are taken within 3 months.


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TB and HIV

Worldwide, TB is one of the leading causes of death amongpeople living with HIV.

TB disease is an AIDS-defining condition in HIV infection.

HIV infection is the strongest known risk factor for

progression of latent TB

Jones BE, Young SM, Antoniskis D, et al. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiencyvirus infection. Am Rev Respir Dis 1993; 148:1292.
http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4


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Presentation more likely extra-pulmonary + associated withatypical chest radiographic findings.


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QUESTION 9

A 33-year-old man is evaluated after learning that a person living in his home was recentlyfound to have active tuberculosis. The patient has no acute symptoms. He was recentlydiagnosed with HIV infection, and his CD4 cell count is 250/L. He has no history ofincarceration, homelessness, or travel to areas with an increased prevalence of tuberculosis. Hetakes no medications but had been planning to begin antiretroviral therapy at his next officevisit.

On physical examination, vital signs are normal. The remainder of the examination, includingcardiopulmonary findings, is normal.A tuberculin skin test induces 0 mm of induration. A chest radiograph is normal.

What is the most appropriate action?

A) Begin Isoniazid and PyridoxineB) Begin Isoniazid, Rifampicin, Pyrazinamide Pyridoxine,

and EthambutolC) Begin Rifampicin and PyrazinamideD) No additional therapy or evaluation is required.


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Dose adjustments for antiretroviral therapy and Rifamycinagents

patients with HIV infection and recent TB exposure shouldreceive treatment for latent tuberculosis infection after active

disease has been excluded.

Jones BE, Young SM, Antoniskis D, et al. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis1993; 148:1292.
http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4http://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-tuberculosis-in-hiv-infected-patients/abstract/4


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World Health Organization. Global tuberculosis control: WHO report 2011. Geneva: World HealthOrganization; 2011.


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QUESTION 10

Multidrug resistant tuberculosis (MDR-TB) is characterised byresistance to Isoniazid and which other agent?

a) Ethambutol

b) Azithromycin

c) Rifampicin

d) Gentamicine) Doxycycline


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MDR - Resistant to at least Isoniazid and RifampicinXDRMDR resistant to Fluoroquinolones and at least one of the following

2ndline drugs: Kanamycin, Capreomycin, and Amikacin, Streoptomycin


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CDC. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992; 41 (No. RR-

11): 5971.


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QUESTION 11

Which of the following resistance patterns is the most resistantto TB?

a) Streptomycin and Isoniazid

b) Streptomycin and Amikacin

c) Rifampicin and Isoniazid

d) Rifampicin and Ethambutol


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World Health Organization. Global tuberculosis control: WHO report 2011. Geneva: World Health

Organization; 2011.


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GeneXpert


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Automated test for (MTB)DNA and resistance to Rifampicinby nucleic acid amplification technique (NAAT)

Results within 2 hours.

Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med

2010; 363:1005.
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Positive predictive value NAA testing: > 95% in context of

AFB-positive smears

Positive predictive value NAA testing: 50-80% in context of

AFB-negative, culture positive smears

Positive predictive value < 50% in setting of low clinicalsuspicion.

Accuracy for identification of Rifampicin resistance: 98 %.

Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin

resistance. N Engl J Med 2010; 363:1005.
http://www.uptodate.com/contents/diagnosis-treatment-and-prevention-of-drug-resistant-tuberculosis/abstract/12http://www.uptodate.com/contents/diagnosis-treatment-and-prevention-of-drug-resistant-tuberculosis/abstract/12http://www.uptodate.com/contents/diagnosis-treatment-and-prevention-of-drug-resistant-tuberculosis/abstract/12http://www.uptodate.com/contents/diagnosis-treatment-and-prevention-of-drug-resistant-tuberculosis/abstract/12


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ABS (Australian Bureau of Statistics) 2007, 2006 Census of Population and Housing, ABS, Canberra.

American Thoracic Society and CDC. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000; 161 (4):13761395

Australian Bureau of Statistics. 3412.0 - Migration, Australia, 2009-10: Australian Bureau of Statistics,; 2011.

Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society ofAmerica: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167:603.

Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010; 363:1005.

CDC. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992; 41 (No. RR-11): 5971

Chest. 2012;142(3):761-773. doi:10.1378/chest.12-0142

FURTHER studies of geographic variation in naturally acquired tuberculin sensitivity. Bull World Health Organ 1955; 12:63.

Jensen PA, Lambert LA, Iademarco MF, et al. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005.MMWR Recomm Rep 2005; 54:1.

Jones BE, Young SM, Antoniskis D, et al. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virusinfection. Am Rev Respir Dis 1993; 148:1292.

Lumb R, Bastian I , Carter R, Jelfs P, Keehner T, Sievers A. Tuberculosis In Australia: Bacteriologically confirmed Cases And Drug Resistance, 2010. CommDis Intell 2013;37(1):E40-46.

Kim JH, Langston AA, Gallis HA. Miliary tuberculosis: epidemiology, clinical manifestations, diagnosis, and outcome. Rev Infect Dis 1990; 12:583.

MacGregor RR. A year's experience with tuberculosis in a private urban teaching hospital in the postsanatorium era. Am J Med 1975; 58:221.

Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection -United States, 2010. MMWR Recomm Rep 2010; 59:1.

McBryde and Denholm; Risk of active tuberculosis in immigrants: effects of age, region of origin and t ime since arrival in a low-exposure settingMed J Aust2012; 197 (8): 458-461.

Parmar MS. Lower lung field tuberculosis. Am Rev Respir Dis 1967; 96:310.

POULSEN A. Some clinical features of tuberculosis. Acta Tuberc Scand 1957; 33:37.

Shim YS. Endobronchial tuberculosis. Respirology 1996; 1:95.

Small P and Fujiwara P, Management of Tuberculosis in the United StatesNEngl J Med 2001; 345:189-200

Verhagen LM, van den Hof S, van Deutekom H, Hermans PW, Kremer K, Borgdorff MW, et al. Mycobacterial factors relevant for transmission oftuberculosis. J Infect Dis. May 2011;203(9):1249-55.

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