Three sputum specimens preferably early morning are indicated to maximise yield. In children, gastric aspiration is a useful surrogate.
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Nebulised hypertonic saline may induce sputum production and rarely bronchoscopy is used. Collection should occur away from other people, and into a jar with a threaded lid.
Sputum should be delivered promptly to the laboratory but can be stored in the refrigerator for 1—2 days. Acid-fast microscopy is rapid within 24 hours, less than an hour if urgent and inexpensive. Approximately bacilli per mL of sputum are required for a positive smear.
The Ziehl-Neelsen stain is standard, and utilises the particular staining properties of the waxy coats of the mycobacterial cell walls. Culture or molecular assays are then required to confirm if acid-fast bacilli are MTB complex. Culture is the most sensitive test. Automatic liquid cultures are preferred as they are more rapid and sensitive than solid culture mediums and can also test drug susceptibility.
The cultured isolate should be tested against first line treatment agents isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin. Resistant strains are then tested against second line drugs. Multidrug resistant cases MDR are defined by resistance to both isoniazid and rifampicin.
Rifampicin resistant strains are usually also isoniazid resistant.
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These tests become positive 4—6 weeks after infection. Preventive chemotherapy is typically with isoniazid alone 9 months on average rather than requiring combination therapy. The risk of progression to disease is greatest within the first 2—3 years, and especially within 1 year. The TST — or Mantoux test — assesses inflammation in the dermis following intradermal injection of tuberculin protein.
The test needs to be read 48—72 hours after administration. The diameter of induration gives a semiquantitative assessment of the likelihood of LTBI. General practitioners should liaise with their local laboratories about the availability of testing in their area. Interferon gamma release assays utilise the ability of human lymphocytes to survive for a short period in a test tube. If primed by previous TB infection, lymphocytes will produce detectable amounts of gamma interferon. Interferon gamma release assays are unaffected by previous BCG vaccination.
The venous sample does not require special timing or preparation by the patient.
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A Medicare rebate is available only if the patient is immunosuppressed. This may be due to either current infection or a remote past infection. Interferon gamma release assays do not diagnose active TB — microbiological tests are needed. Despite numerous trials and subsequent meta-analyses, how best to incorporate IGRAs into diagnostic algorithms remains somewhat controversial. Interferon gamma release assays are easier to interpret in patients vaccinated with BCG and should perform better in immunosuppressed patients, but there is no evidence of this. No detectable immune response anergy can cause a false negative TST test.
Table 3 compares important features of the two main types of tests for detecting LTBI. Any positive result needs to be discussed with a clinician experienced in TB management before commencing treatment. Extrapulmonary TB is diagnosed by sending a sample in normal saline for microscopy and culture. Histopathology may identify typical changes necrotising granulomas, caseation and acid-fast bacilli.
General practitioners are advised to liaise with their laboratory about the best sample handling if they have a suspected case. Serological tests for TB are commonly performed in some overseas countries, but these are insensitive and nonspecific and not recommended in Australia. Liver enzymes should be monitored as several treatment drugs may cause a chemical hepatitis.
Hepatitis B and C appear to increase the risk of hepatotoxicity, hence check serology before treatment. Vitamin D deficiency may increase the risk of TB progression, although the value of assay and replacement is unclear. The contribution of Dr Andrew Burke in reviewing the manuscript is gratefully appreciated.
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References | Tuberculosis in the Workplace | The National Academies Press
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