Table 1.
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome – knowledge summary
| Knowledge summary | Key references | |
| Incidence | Adults overall: 18% (95% CI 16–21%), with a range of 4–54%; higher rates in patients with lower CD4 counts (up to 57% in patients with CD4 count <200 cells/μl). | Reviewed in [2] Recent cohort described in [3▪] |
| South African children: 6.7% reported in a recent prospective study | [4] | |
| Risk factors | Low CD4 count at ART initiation; High HIV viral load at ART initiation | Reviewed in [2] |
| Shorter time between TB treatment initiation and ART initiation | Meta-analyses reported in [5,6] | |
| Disseminated TB/high mycobacterial load. | [3▪,7▪] | |
| Clinical presentation | Systemic, pulmonary and lymph node presentations most common | Reviewed in [2] |
| In a recent study, median days to symptom onset reported as 6 (range 1–23) | [3▪] | |
| Mortality | All-cause mortality rate of 7% (95% CI 4–11%) and IRIS-attributable deaths of 2% (95% CI 1–3%) | Reviewed in [2] |
| Higher mortality in CNS TB-IRIS | Reviewed in [8] | |
| Pathogenesis | Innate immune cell activation, including neutrophils, monocytes and NK cells; Antigen-specific upregulation of cytotoxic mediators Inflammasome activation; Hypercytokinaemia (including IL-1β, IL-6 and TNF-α) and MMP upregulation/secretion | Reviewed in [9]; see also, [3▪,7▪,10▪] |
| Treatment | Prednisone (1.5 mg/kg for 2 weeks followed by 0.75 mg/kg for 2 weeks) for treatment of paradoxical TB-IRIS reduced length of hospital admission and number of therapeutic procedures required, and improved symptoms in paradoxical TB-IRIS | Randomized-controlled trial reported in [11] |
| Consensus is not to stop ART, but to investigate fully for alternative causes, and provide symptomatic treatment | Reviewed in [9] | |
| Prevention | Prednisone (40 mg daily for 2 weeks, followed by 20 mg daily for 2 weeks) from ART initiation reduces the risk of future paradoxical TB-IRIS by 30% | [12▪▪] |
| Do not delay ART initiation beyond 2 weeks after TB treatment initiation in patients with CD4 count <50 cells/mm3, unless CNS TB diagnosed (then delay 4–8 weeks). Early ART improves survival in patients with CD4 < 50 cells/mm3 even though it increases TB-IRIS risk > two-fold | Meta-analyses reported in [5,6] |