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3.0 Laboratory diagnosis

BHIVA treatment guidelines for TB/HIV infection

The quality of any investigation is related to the quality of the specimen and the request.  There must therefore be close liaison with the mycobacterial laboratory. 

3.1 Microscopic smears

Microscopic smears remain an essential part of TB diagnosis.  Results should be available within 1 working day.

3.2 Cultures

These are central to the confirmation and identification of the mycobacterium and for drug susceptibility testing.  More rapid results are obtained from liquid media, which usually grows M.tuberculosis in 7 to 28 days. 

Identification of mycobacterium based on morphology, growth and biochemical characteristics are performed at mycobacterium reference centres.  Rapid gene probes can be used but this should be fully discussed with the laboratory. These are less sensitive than culture and are used mainly on respiratory specimens.  These are often requested when it is important to differentiate the diagnosis of MTB from other Mycobacteria for which treatment may be different and there are no infection control concerns.  However, it should be noted that all specimens even those that are negative on PCR still require culture and that a negative PCR does not exclude TB and a positive PCR does not indicate the drug susceptibility profile. In many cases the treatment conundrum is whether the patient has Mycobacterium avium or Mycobacterium tuberculosis and often the physician will wait for the routine identification before altering the standard 4-drug regimen.  Some physicians prefer to replace rifabutin for rifampicin in this situation.  When opportunist mycobacteria are identified then the regimen can be modified appropriately. 

3.3 Drug susceptibility tests

These are usually available within 10-21 days of the laboratory receipt of the isolates and are performed by standard assays.  Molecular detection of rifampicin resistance (and pyrazinamide) is available although it is not 100 percent sensitive. These molecular tests are useful when drug resistance is suspected, as about 95% of patients who are rifampicin resistant will also be isoniazid resistant.

Patients with gene probe positive rifampicin resistance should be treated as MDR-TB, until the full resistance profile from cultures are available.

3.4 Rapid detection of active and latent tuberculosis infection in HIV positive individuals

The lack of sensitivity of the tuberculin test and the poor specificity because of antigenic cross-reactivity with BCG vaccination means that an accurate test for active or latent TB in HIV individuals is needed.

Tests using either whole blood or blood mononuclear cells have been developed which measure interferon gamma production from TB-specific T cells responding to M. tuberculosis antigens ESAT-6 or CFP-10.12  

Using an enzyme linked immunospot [ELISPOT] assay, a study from Zambia and the UK diagnosed active TB in 90 percent of 39 individuals tested.  Unfortunately, although this technology was better at picking up latent TB than PPD testing in HIV positive persons it was still not as sensitive when compared to HIV negative patients Larger studies are needed and correlations of Elispot responses with patient’s CD4 counts need to be made.  The reproducibility of the test also needs to be evaluated in HIV positive patients and long term outcomes measured.