An assessment of nucleic acid amplification testing for active mycobacterial infection

Clinical pathway

The clinical management algorithms for patients with the signs and symptoms of active TB are shown in Figure and Figure . The pathways underwent public consultation and incorporated both expert opinion and guidance from the Centers for Disease Control⁹. There is a view by experts that the major factor in the current clinical management of a patient with the signs and symptoms of active TB is the patient’s pre-test probability of having TB.

Figure presents current and proposed clinical management algorithms for patients with the clinical signs and symptoms of active TB and for whom AFB microscopy can be done; that is, the patient can provide a sample for testing. This includes samples such as sputum, bronchoalveolar lavage, bronchial aspirates, gastric aspirates and stool for the diagnosis of pulmonary TB; and samples such as cerebrospinal fluid (CSF), urine, lymph node fine-needle aspirates (FNAs) or any other body fluid or tissue sample for the diagnosis of extrapulmonary TB. Currently, clinicians rely on the results of AFB microscopy, as well as whether the patient has a high or low pre-test probability that they will have active TB, as the basis to initiate or defer antibiotic treatment. NAAT is suggested as an adjunctive test that would be performed concurrently with AFB microscopy and culture.

Figure presents current and proposed clinical management algorithms for patients who present with the clinical signs and symptoms of active TB and from whom it is not possible to obtain a specimen suitable for AFB microscopy. The only patients that could be identified to fit this profile were those for whom it was not possible to obtain a sample for any purpose. Due to the lack of a sample, the effectiveness of NAAT is not assessible in these patients. Thus, this algorithm could not be addressed in the assessment and will not be discussed further.

Figure presents current and proposed clinical management algorithms for patients who are suspected of having an NTM infection. It should be noted that the NTM population eligible for NAAT has been expanded from the population specified in the protocol, in order to include patients presenting with specimens other than tissue biopsies, such as sputum specimens to be tested for MAC disease or blood samples for disseminated NTM. It should also be noted that histology is not able to differentiate between MTB and NTM infections and it is assumed that culture will also be performed. The expanded population base was necessary due to the insufficient evidence-base for NTM infections as a whole. The proposed use of NAAT will substitute for current testing.

Figure Current clinical management of TB and proposed use of NAAT for active TB where AFB is obtained

AFB = acid-fast bacilli; DST = drug susceptibility testing; MTB = Mycobacterium tuberculosis; NAAT = nucleic acid amplification testing; TB = tuberculosis

Figure Current clinical management and proposed algorithm with use of NAAT for active TB where AFB microscopy is not able to be obtained

AFB = acid-fast bacilli; DST = drug susceptibility testing; MTB = Mycobacterium tuberculosis; NAAT = nucleic acid amplification testing; TB = tuberculosis

Figure Current clinical management algorithm and proposed algorithm with use of NAAT for patients who are suspected of having an NTM infection

AFB = acid-fast bacilli; DST = drug susceptibility testing; MTB = Mycobacterium tuberculosis; NAAT = nucleic acid amplification testing