Evidence on the presence of latent bacilli
| Clinical |
| Late reactivation after a large period of chemotherapy 2 |
| Chemoprophylaxis trials: the longer the period, the lower the chance of reactivation 3, 4 |
| Natural history: formation and healing of primary complex in basal zones of the lung. Development of post-primary TB a long time after the haematogenous dissemination to the apex 5–10 |
| Experiments in vitro |
| Higher bactericidal capacity of rifampicin in “intermittent” incubation 11 |
| Bacillary survival in sealed cultures at 37°C after 12 yrs 12 |
| Adaptation of bacilli to a low oxygen pressure 13–15 |
| Higher resistance to stressful conditions in bacilli from stationary-phase cultures 16 |
| Transcription of genes (e.g. SigF) related to the sporulation cascade in other bacteria, under stressful conditions 17–19 |
| Dormant “noncultureable” bacilli can be “resuscitated” with phospholipids and a specific factor (Rpf) synthesised by growing bacilli 20–24 |
| Experiments in animal models |
| The Cornell model in mice 25 |
| Bacilli from chronical lesions are better adapted to stressful conditions than the acute ones 26 |
| Specific M. tuberculosis gene knock-out strains have revealed the indispensable role of some genes expressed in stressful conditions for persistence in a chronic infection 27–29 |
TB: tuberculosis; Rpf: resuscitation promoting factor; M. tuberculosis: Mycobacterium tuberculosis