An assessment of nucleic acid amplification testing for active mycobacterial infection

Systematic review Included studies	Total participants (N)	Total cases (N)	Adjusted rate per 1,000
Adjusted mortality per 1,000
Forget and Menzies (2006) k=10	64,278	399	9.2	0.43

Forget and Menzies (2006) found that there was heterogeneity between these 10 studies, although they did not provide a statistical summary. In particular, the definition of a hepatic AE varied between studies; for example, the definition of ‘hepatitis’ ranged from asymptomatic elevation in liver enzymes to clinical hepatitis. Study populations varied in the proportion of female participants (45.6% to 100% in studies that reported this factor) and in age. A prospective study in children (mean age 11 years) reported a low case rate of 11.6 per 1,000 when compared with a retrospective cohort study in which participants had a mean age of 76 years and reported a case rate of 49.9 per 1,000; however, both articles reported a mortality rate of zero.

Nine of the 10 studies reported completion/compliance rates at 12 months following initiation of treatment. Rates ranged from 16%/46% (completion/compliance at 6 months) in a retrospective cohort of 3,681 female patients who began therapy during pregnancy, to 95% completion in the prospective study of 434 children previously mentioned. The cohort of pregnant females also reported the highest adjusted mortality rate¹³ (1.18 per 1,000). Four of the 10 studies reported adjusted mortality rates of 0 per 1,000.

Incidence of hepatic AEs (adjusted rate per 1,000)¹⁴ ranged from 1.5 in an Asian cohort of 11,141 patients who were monitored through monthly interviews following a standardised protocol (Nolan, Goldberg & Buskin 1999) to 79.6 in a US cohort of 1,000 for which cases were defined biochemically (Byrd et al. 1979). In a US Public Health Service surveillance study involving 13,838 participants a more moderate incidence of 13.6 per 1,000 was reported (Kopanoff, Snider & Caras 1978). This 1978 study reported that increasing age was a predominant factor for higher risk of developing isoniazid-related hepatitis.

Other anti-TB drugs and regimens

Forget and Menzies (2006) reported incidence data for overall rates of side effects for patients on various anti-TB medications (Table ). The authors report that populations, and in particular, definition of AEs showed heterogeneity between studies (no statistical measure given). Also reported was that older age was associated with the development of hepatitis, and skin rashes were more common in patients who were female, older, HIV infected or from Asia. Patients with chronic renal failure tend to have a higher incidence of adverse effects to an anti-TB regimen, in particular neuropsychiatric events.

Interestingly, more patients discontinued treatment on isoniazid mono-therapy (7%) when compared with rifampicin (2%), pyrazinamide (5%), ethambutol (0.2–0.3%) and streptomycin (3%). Patients on isoniazid also had more-elevated simple transaminases than those on the other drugs, but experienced hepatitis less often (0.4%) than rifampicin (1%) or pyrazinamide (1.5%). In children on TB mono-therapies, AEs occurred less often than in adults and tended to result in less morbidity; however, a large proportion of this data came from studies of prophylactic treatment.

Table Incidence of AEs for drugs and regimens for first-line and prophylactic TB treatment