Table 2. Optimal cut-off points for the study population stratified by age and BCG status.

Optimal cut points were computed for the prevalence identified in the study population. OCP = Optimal Cut-off Point, CP = Cut-off Point, PPV = Positive Predictive Values, NPV = Negative Predictive Values. The range of cut-off points on either side of the OCP which only increased the error rate by a maximum of 2% was also identified for each group. In our study population, TST performance was most accurate in unvaccinated children aged 2-16 in whom approximately 9 out of every 10 diagnoses will be correct. Performance is slightly lower in BCG naïve children aged <2 years, where 7 out of 8 diagnoses will be correct. In vaccinated children aged 2-16, TST was erroneous once in every 5 diagnoses for those with 1 BCG scar, and once in every 3 diagnoses for those with more than 1 BCG scar.

				Minimise total error rate							Minimise disutility score with cost FN twice cost of FP
Age	BCG scars	Sample size	Prevalence* (%)	OCP	CP with error rates within 2% of OCP	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Error rate of CP (%)	OCP	CP with scores within 2% of OCP	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Error rate of CP (%)
<2	0	33	33	13	(10–15)	69	97	91	86†	13	10	(7-13)	72	95	87	87	13
<2	1	97	22	16	(14–17)	62	98	91	90†	10	16	(13-16)	62	98	73	91	10
2-16	0	176	56	2	(2–15)	91	88	90	89	10	2	(2-10)	91	88	90	89	10
2-16	1	555	42	15	(11–18)	73	86	79	81	20	10	(2-15)	84	74	70	86	22
2-16	>1	118	42	20	(18–21)	61	82	72	74	27	16	(11-19)	78	63	61	80	31

^*The results are based on the observed prevalence of infection in the 5 population subgroups. Optimal cut-off points were also computed for three arbitrary prevalences of infection; 5%, 20% and 40%. At 40% infection prevalence the optimal cut-off points were lower than at lower levels of prevalence. In children aged <2 years, optimal cut-off points appeared relatively unaffected by infection prevalence: a cut-off point of ≥15mm was robust except in unvaccinated children where disease prevalence was 40%, when a lower cut-off point of ≥10mm had the lowest error rate (16%). Cut-off point selection in children aged >2 years was more directly affected by prevalence. For unvaccinated children, cut-off points of ≥20, ≥15 and ≥10mm fell within a 2% margin of error of the optimal computed cut-off points at prevalences of 5%, 20% and 40%, respectively. Cut-off points for children with one scar were around 5mm higher, and for those with 2 or more scars around 10mm higher than in unvaccinated children (data not shown). Despite the use of optimal cut-off points tailored to different levels of infection prevalence, the overall error rate of TST relative to ELISpot increased with increasing prevalence of infection in the target population (data not shown).

^†Despite the lower sensitivity of TST in children aged under 2 years, the NPV in this age group is similar to that observed in older children because the prevalence of infection in children under 2 years is half that in the older children.