Although this was developed for a resource-poor setting it is comprehensive and is a useful checklist.

There are three components to this case definition:

(A) Antecedent requirements 

Both of the two following requirements must be met

  • Diagnosis of tuberculosis: the tuberculosis diagnosis was made before starting antiretroviral therapy and this should fulfil WHO criteria for diagnosis of smear-positive pulmonary tuberculosis, smear-negative pulmonary tuberculosis or extrapulmonary tuberculosis.
  • Initial response to tuberculosis treatment: the patient’s condition should have stabilized or improved on appropriate tuberculosis treatment before antiretroviral therapy initiation – e.g. cessation of night sweats, fevers, cough and weight loss. (Note: this does not apply to patients starting antiretroviral therapy within 2 weeks of starting tuberculosis treatment as insufficient time may have elapsed for a clinical response to be reported.)

(B) Clinical criteria

The onset of tuberculosis-associated IRIS manifestations should be within 3 months of antiretroviral therapy initiation, reinitiation, or regimen change because of treatment failure.

Of the following, at least one major criterion or two minor clinical criteria are required:

Major criteria

  • New or enlarging lymph nodes, cold abscesses, or other focal tissue involvement – e.g. tuberculous arthritis.
  • New or worsening radiological features of tuberculosis [found by chest radiography, abdominal ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI)].
  • New or worsening CNS tuberculosis (meningitis or focal neurological deficit – e.g. caused by tuberculoma).
  • New or worsening serositis (pleural effusion, ascites, or pericardial effusion).

Minor criteria

  • New or worsening constitutional symptoms such as fever, night sweats or weight loss.
  • New or worsening respiratory symptoms such as cough, dyspnoea or stridor.
  • New or worsening abdominal pain accompanied by peritonitis, hepatomegaly, splenomegaly or abdominal adenopathy.

(C) Alternative explanations for clinical deterioration must be excluded if possible

  • Failure of tuberculosis treatment because of tuberculosis drug resistance
  • Poor adherence to tuberculosis treatment.
  • Another opportunistic infection or neoplasm (it is particularly important to exclude an alternative diagnosis in patients with smear-negative pulmonary tuberculosis and extrapulmonary tuberculosis where the initial tuberculosis diagnosis has not been microbiologically confirmed).