Tuberculosis and tuberculin quality: Best intentions, misleading results

OBJECTIVE: To compare the performance of three purified protein derivative (PPD) formulations: Tubersol (Connaught); RT23, Statens Serum Institut (SSI ); and R123, Mexico, tested in Mexican populations at low and high risk for tuberculosis (M). DESIGN: A double-blinded clinical trial. SETTING: A university hospital in Mexico City. PARTICIPANTS: The low-risk population was first or second-year medical stud ents with no patient contact; the high-risk population was healthcare worke rs at a university hospital. METHODS: Each of the study subjects received the three different PPD, prepa rations. Risk factors for TB, including age, gender, occupation, bacille Ca lmette-Guerin (BCG) status, and TB exposure, were recorded. A 0.1-mL aliquo t of each preparation was injected in the left and right forearms of volunt eers using the Mantoux technique. Blind readings were done 48 to 72 hours l ater. Sensitivity and specificity were calculated at 10 mm of induration us ing Tubersol as the reference standard. The SSI tested the potency of the d ifferent PPD, preparations in previously sensitized guinea pigs. RESULTS: The low-risk population had a prevalence of positive PPD of 26%. I n the low-risk population, RT23 prepared in Mexico, compared to the 5 TU of Tubersol, had a sensitivity of 51%, a specificity of 100%, a positive pred ictive value of 100% and a negative predictive value of 86%. The RT23 prepa red at the SSI had a sensitivity of 69%, a specificity of 99%, a positive p redictive value of 95%, and a negative predictive value of 90%. In the high -risk population, the prevalence of positive PPD was 57%. The RT23 prepared in Mexico had a sensitivity of 33%, a specificity of 100%, and a positive predictive value of 53%; the RT23 prepared at the SSI had a sensitivity of 91%, a specificity of 98%, a positive predictive value of 98%, and a negati ve predictive value of 89%. RT23 used in Mexico had a potency of only 23% o f that of the control. There was no statistical association among those wit h a positive PPD, irrespective of previous BCG vaccination (relative risk, 0.97; 95% confidence interval, 0.76-1.3; P=.78). CONCLUSIONS: Healthcare workers had twice the prevalence of positive PPD co mpared to medical students. RT23 prepared in Mexico had a low sensitivity i n both populations compared to 5 TU of Tubersol and RT23 prepared at the SS I. Previous BCG vaccination did not correlate with a positive PPD. Low pote ncy of the RT23 preparation in Mexico was confirmed in guinea pigs. Best in tentions in a TB program are not enough if they are not followed by high-qu ality control (Infect Control Hosp Epidemiol 2001;22:481-484).