Case 8: Tuberculosis

One of the patients in your long-term care facility has a positive smear for Acid Fast Bacilli from a sputum sample. This gentleman resides in a four-bed ward and has been actively coughing blood-tinged sputum for the last two weeks following what appeared to be a flu-like illness. He is of Chinese descent and his family states that he has never been known to be exposed to tuberculosis. A rapid diagnostic test is done which confirms that the organism is indeed M.tuberculosisimageimage

Case Eight Questions:

1. How is the diagnosis of active tuberculosis made? Compare and contrast traditional culture methods versus newer rapid tests.

Diagnosis of active TB may be made with the use of “acid-fast bacilli on smear microscopy and/or culture of Mycobacterium tuberculosis, or…amplification and detection of M. tuberculosis complex (MTBC) nucleic acids using nucleic acid amplification tests (NAATs).” (Public Health Agency of Canada, PHAC, 2013).

Traditionally a chest X-ray was used in a TB diagnosis however an X-ray alone cannot provide conclusive diagnosis. Currently, a microbiologic testing is needed for conclusive diagnosis (PHAC, 2013).

In addition to NAAT, microscopic smear, and M. tuberculosis bacterial culture (in liquid and solid media), sputum samples should be collected. Minimum 3 samples collected a minimum 1 hour apart are needed (PHAC, 2013). If TB is suspected, three fluorescent smears should be tested. In new TB patients (with positive smear test) should have at least one respiratory specimen tested with a public health agency validated or approved NAAT (PHAC, 2013).

Traditional culture vs newer rapid testing:

Chest X-ray – has a sensitivity of only 70% – 80% for the diagnosis of active TB based on abnormal presentations and only 10% of HIV infected patients will score positive TB chest X-rays (PHAC, 2013).

Acid fast bacilli on smear microscopy – The most widely used rapid test.

The benefits of smear microscopy:

  • inexpensive
  • identifies the most infectious TB patients

The draw backs of smear microscopy:

• Sensitivity is modest and variable (20%-80%) depending upon the type of specimen, patient population, stain used and the experience of the microscopist. Thus, multiple sputum smears are recommended to increase the overall sensitivity and yield. Sensitivity is higher for respiratory than for nonrespiratory specimens, particularly body fluids.

• In low TB incidence settings, smear microscopy has lower specificity – a positive smear could be due to nontuberculous mycobacteria (NTM).

• Smear microscopy has lower sensitivity in childhood TB and extrapulmonary disease, especially in HIV-infected people.

• Smear microscopy cannot be used to determine drug resistance.” (PHAC, 2013)

Media Culture of M. Tuberculosis – “Mycobacterial culture, using both solid and liquid media, is considered the gold standard for diagnosis, and the use of broth-based culture methods for DST is the standard of practice in North America” (PHAC, 2013).

The benefits of culture:

  • identification
  • DST
  • further use of culture isolates for molecular epidemiology using DNA fingerprinting.
  • Culture can be performed on all specimen types.

The draw backs of culture:

  • results typically take 2-8 weeks, depending on the culture method used and the number of MTBC bacteria in the inoculum.

Nucleaic acid amplification test (NAAT)

The benefits of NAAT:

  • enables multi-drug resistant TB strain detection (unlike the other testing methods).
  • specificity of the commercial NAAT is very high in all specimens (90%-100%)
  • sensitivity of commercial NAATs to detect TB is high (>95%) in sputum smear-positive samples (PHAC, 2013)

The drawbacks of NAAT:

  • costly
  • inaccessible to the poorer regions and remote areas in the world
  • sensitivity is lower (50%-70%) when smear-negative/culture-positive specimens are tested.
  • sensitivity is also lower in extrapulmonary specimens.
  • a negative NAAT result should not be used to rule out TB, especially in paucibacillary forms of TB (i.e. smear-negative and extrapulmonary TB).
  • requires sophisticated laboratory infrastructure and highly skilled technicians
  • The risk of contaminating the test site with amplified DNA requires stringent quality control procedures and a specific infrastructure to limit contamination (PHAC, 2013)

2. What should be done for the patient and his roommates? Assuming he attended activities/procedures outside his room during his stay – would you follow the other patients?

This patient should be placed in a single room and placed on airborne infection isolation in a negative pressure room (Lautenbach, p. 335). If that is not possible place each patient on airborne and contact precautions seeing as the patient has been coughing  for 2 weeks in this shared space in close to his other roomates/patients. It is important to note that “If appropirate facilites for isolation of potentially infectious patients are not available on-site, an agreement should be in place to faciliate prompt transfer of such patients to alternate facilites” (Lautenbach, p354)

Yes I would follow and closely monitor all patients, visitors and staff who were in this patient’s proximity, tracing back contacts over the 2 weeks he was coughing. All contacts who were potentially exposed should undergo comprehensive tuberculin skin testing (Lautenbach, p. 335)

Lautenbach, p. 354, states that long term care facilities need to monitor for:

  • skin test conversions among residents and staff
  • identify and promptly evaulate patients with pulmonary symotoms or radiologic findings consistent with tuberculosis
  • immediately isolate patients with potential of proven pulminary tuberculosis
  • trace exposed patients and staff
  • initate prophylactic isoniazid therphy

3. What advice will you give to the staff in terms of their follow-up and protection? What are the Canadian recommendations regarding initial and routine screening of hospital staff for tuberculosis?

Follow-up and protection:

  • Staff should use N95 respirators when caring for the infected patient in his negative pressure room (Lautenbach, p335)
  • UV germicial irradiation of all potentially exposed contact surfaces should be undertaken to prevent infection spread via those surfaces (Lautenbach, p. 335)
  • Potentially exposed patients and staff should be tested for TB based on risk assessment and CDC guidelines (Lautenbach, p. 322).
  • Staff with underlying immunocompromising conditions should be discouraged from caring for the patient with TB.
  • Seeing as this patient’s family state he has not been known to be exposed to tuberculosis, nosocomial or cummunity acquired infection should be suspected and with that suspcision an immediate investigation should be undertaken and active, corrective steps should be implemented (Lautenbach, p. 325)
  • Consulation with public health official and experts in healthcare epidemiology and infection control should occur
  • based on the risk assessment, appropriate administrative, environmental and respiratory protection policies to prevent occupational exposure to and nosocomial transmission from the infectious or potentially infectious individual should put be in place (Lautenbach, p. 335).

Initial and routine screening:

“Prior to admission and employment all residents and employees of these facilities are to be assessed for their risk of tuberculosis.” (PICNET, p9).

  • Patients under 60 years – tuberculin skin test. Chest x-ray for those with a positive tuberculin reaction. (PICNET, p9)
  • Patients 60 years and over – chest x-ray only. Where there is difficulty obtaining a chest x-ray prior to or at the time of admission a normal chest x-ray completed within one year preceding admission for asymptomatic residents is acceptable (PICNET, p9).

For staff “The occupational medicine, hospital epidemiology and institutional biosafety programs should work together to establish effective ongoing tuberculosis prevention and management program” (Lautenbach, p. 320).

  • new employees should receive intradermal Mantoux skin testing unless they have the employee has prior documentation of active TB, previous positive skin test, and/or completion of therapy for infection (Lautenback, p. 320).
  • The whole blood interferon-y release assay could also be used, however discordant results have been reported between this and the skin test. (Lautenbach, p320)

4. What should be done for the patient and his roommates? Assuming he attended activities during the day, should you follow the rest of the patients on the ward?

note question 2 is very similiar therefore see it for answer.

5.Do you think this represents primary or reactivation tuberculosis? Justify your answer and explain what primary and reactivation tuberculosis means.

Considering that the family states this patient has not been knowingly exposed to TB we might consider sources for his infection. That said this patient is elderly, in long term care and would have few avenues of contracting a novel TB infection, with a weakened immune system dormant TB may reactive.

“All residents entering long term care facilities should have a baseline diagnosis test for LTBI performed… unless they are documented to have had a positive result previously” (Lautenbach, p. 338). We can hope we would have a TB test indicating the patient’s status upon admission.

If this patient’s infection represents a primary infection then potential sources he was exposed to need to be investiaged, such as staff, family members, visitors and patients.

Given age and accompanying immunocompromising factors along with the rigorous testing of all newly admitted patients and newly employed staff it is most probably that this patient has reactivation TB. However without knowing this patient’s TB immunity status prior to admission it is also possible the patient could have acquaried a primary infection from travelling family members or staff newly infected, other patients with re-activation (who also have been assumed to simply have a flu-like illness thus far). The results of the outbreak investigation and testing of patients and staff in the facility along with the patient’s TB test admission results would be needed to answer this question for certain.

From U.S. CDC Guidelines for the investigation of contacts of persons with infectious Tuberculosis the following data needs collecting in order to proceed with an thorough answer to this question:

“Multiple factors are relevant to a contact investigation, including the following: • history of previous exposure to TB,

• history of previous TB disease and treatment,

• anatomical sites of TB disease,

• symptoms of the illness,

• date of onset,

• chest radiograph results,

• other results of diagnostic imaging studies,

• diagnostic specimens that were sent for histologic or bac- teriologic analysis (with dates, specimen tracking num- bers, and destinations),

• current bacteriologic results,

• anti-TBchemotherapyregimen(withdates,medications, dosages, and treatment plan),

• results from HIV testing,

• the patient’s concurrent medical conditions (e.g., renal failure implies that a renal dialysis center might be part of the patient’s recent experience),

• other diagnoses (e.g., substance abuse, mental illness, or dementia) that impinge directly on the interview, and

• identifying demographic information (e.g., residence, employment, first language, given name and street names, aliases, date of birth, telephone numbers, other electronic links, and next-of-kin or emergency connections).” (MMWR, 2005)

Primary tuberculosis: the “first infection by Mycobacterium tuberculosis, typically seen in children but also occurs in adults, characterized in the lungs by the formation of a primary complex consisting of small peripheral pulmonary focus with spread to hilar or paratracheal lymph nodes; may proceed to cavitate or heal with scarring or may progress.” (Farlex, 2012).

Reactivation tuberculosis: is “a form of secondary tuberculosis that recurs as a result of the activation of a dormant endogenous infection. Causes of the reactivation may include loss of immunity, hormonal changes, or poor nutrition.” (Mosby’s, 2009).

6. What infection control measures would you have implemented if this had been non-tuberculous Mycobacterium?

Non-tuberculin mycobacterium are opportunistic organisms affecting immunocompromized and immunocompetent patients with a broad spectrum of virulence (Ryu, Koh and Daley, 2016). The most common Mycobacterial species causing infection are  Mycobacterium avium complex (MAC), M. abscessus complex (MABC) and M. kansasii (Ryu, Koh and Daley, 2016).

Due to variable virulence, airborne, droplet (airborne covers this) and contact precautions should be implemented until lab results return identifying strain. From there a treatment plan can be drawn up according to the specific strain. Note that though mode of infection is difficult to identify, infiection via  ingestion, inhalation or implantation (Johnson and Odell, 2014). Sources of infection such as probable inhalation of aerosoled droplets small enough to enter lung alveoli are the source of pulmonary NTM. Non-tubuculosis Mycobacterium exist in water and soil proving the patient’s general environment could also be a source of infection(Johnson and Odell, 2014).

However, identification of Mycobacterium organisms in pulminary specimen culture does not always indicate active infection (Johnson and Odell, 2014). That said it is difficult to treat and recurrences of infection due to the original organism is common (Johnson and Odell, 2014) and long courses of antibiotic treatment are necessary.

Mycobacterium are aerobic, non-motile bacterial that have lipid rich, hydrophobic cell walls much thicker than other bacterial strains (Johnson and Odell, 2014). The thick cell walls pose infection control obstacles as it enables the bacterium resistance to disinfectants, antibiotics and heavy metals (Johnson and Odell, 2014). Non-tubuculosis mycobacterium (NTM)  are associated with biofilms which promote it’s antibiotic and disintectant resistant properties. NTM are hydrophobic and readily aeorsolize from water, they are also quite resitant to high temperatures and low pH posing further sterilization and infection control challenges (Johnson and Odell, 2014).

Water systems such as those in general hospital, hemodialysis and dental centers have high rates of Mycobacterium colonization (Johnson and Odell, 2014) so methods of sterilizing water should be assessed by infection control if the facility’s water supply proves contaminated.
7. What is MDR? XDR? What are the treatment and Infection Control implications?

MDR stands for Multi-drug resistant.

XDR is extensively drug-resistant TB. “XDR TB is a rare type of multidrug-resistant tuberculosis (MDR TB) that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). MDR TB is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs.” (CDC, 2013).

Treatment and Infection Control implications:

  • XDR TB is resistant to the most treatment options
  • the limited, remaining treatment options are less effective (30-50%), have more side effects, and are more expensive.
  • HIV infected patients or those with other immunocompromizing conditions are at far greater risk of contracting TB and XDR TB
  • Co-infected TB and HIV patients have a far higher mortality rates than others once TB is contracted. (CDC, 2013)

XDR TB is on the rise globally and is more common in patients who:

  • Have HIV
  • Do not take their TB medicine regularly
  • Do not take all of their TB medicines as prescribed by their doctor
  • Develop  re-activation TB
  • Reside in or have immigrated from areas of the world where drug-resistant TB is common
  • Have spent time with someone known to have drug-resistant TB disease (CDC, 2013)

References:

1. Lautenbach, E., Woeltje, K., and Malani, P. 2010. Practical HealthcareEpidemiology, 3rd ed.

2. Johnson, M. M., & Odell, J. A. (2014). Nontuberculous mycobacterial pulmonary infections. Journal of Thoracic Disease, 6(3), 210–220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949190/

3. Public Health Agency of Canada. (2013). Canadian Tuberculosis Standards. 7th ed. Accessed April 16 from http://www.respiratoryguidelines.ca/tb-standards-2013

4. Ryu, Y. J., Koh, W.-J., & Daley, C. L. (2016). Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians’ Perspectives. Tuberculosis and Respiratory Diseases, 79(2), 74–84. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823187/

5. PICNET. (2011).  Residential Care Infection Prevention and Control Manual. Accessed April 17, 2017 from https://www.picnet.ca/wp-content/uploads/PICNet_Residential_Care_Manual_2011.pdf

6. Elsevier. (2009). Mosby’s Medical Dictionary, 9th edition.

7. Farlex. (2012). Farlex Partner Medical Dictionary.

8. Department of health and human services centers for disease control and prevention. (2005). Guidelines for the investigation of contacts of persons with infectious Tuberculosis. Accessed April 18, 2017 from https://www.cdc.gov/mmwr/pdf/rr/rr5415.pdf

9. CDC. (2013). Extensively Drug-Resistant Tuberculosis (XDR TB). Accessed April 18, 2017 from https://www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm

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