the world health organization ( who ) , in 2012 , indicated there were an estimated 8.6 million new cases of active tb and 1.3 million tb deaths .
the world health organization reported saudi arabia as having a moderate tb incidence rate , with 15 for every 100,000 .
tb remains an important public health problem in saudi arabia , affecting all age groups and regions , and is associated with higher mortalities among saudis . since pulmonary tb
this has become even more important with the development of drug - resistant tb , making effective treatment even more difficult .
tuberculosis was accepted as a diagnosis if the sputum culture was positive for mycobacterium tuberculosis ( mtb ) .
the interferon alpha release assay ( qft - g ) is a new diagnostic test for latent tuberculosis infection ( ltbi ) .
qft - g is similar to the tuberculin skin test ( tst ) , but can not differentiate between ltbi and active tb .
however , despite the limitation of qft - g in the diagnosis of active disease , it has been recommended by some investigators and it has been used in the diagnosis of active tuberculosis in the private sector .
, using qft - g , was performed for the diagnosis of active tuberculosis in 13 studies , and there were 13 studies on cases with known active tuberculosis .
the overall sensitivity of qft - g in the diagnosis of active tuberculosis was 6983% .
another meta - analysis by dai y et al . revealed the overall sensitivity and specificity of qft - g in the diagnosis of active tuberculosis to be 85 and 84% .
few other studies recommended the use of qft - g for ruling out active tuberculosis , especially in high - income countries where the prevalence of tuberculosis was low .
legesse m et al . documented in their study that the sensitivity and specificity of qft - g , using the manufacturer 's cut - off value , was very low in the diagnosis of active tuberculosis in tuberculosis - endemic regions . the qft - g - tb gold kit ( cellestis limited , melbourne , australia )
was approved in 2009 for use in king abdulaziz medical city - riyadh ( kamc - r ) for the diagnosis of latent tb .
local saudi guidelines on the management of latent tuberculosis did not recommend using qft - g for the diagnosis of active tuberculosis .
the clinical use of qft - g has expanded dramatically in the diagnosis of tuberculosis disease .
this expanded use was not based on local studies , which confirmed or refuted such practice in saudi arabia .
it was clear that the use of qft - g in the diagnosis of active tuberculosis should be based on the local prevalence of the disease , local data , and many other logistic and resource considerations .
the aim of this study was to assess the sensitivity and specificity of the qft - g test in the diagnosis of tuberculosis in patients admitted with pneumonia , when it was ordered to rule out tuberculosis .
a retrospective study was conducted at kamc - r saudi arabia from january 2009 to december 2013 .
the study included all patients admitted with a diagnosis of pneumonia , and qft - g was ordered to rule out active tuberculosis . all cases with pneumonia or a final diagnosis of tuberculosis , but with no qft - g results available ,
only patients aged 18 years or older with available qft - g tests were included in the analysis .
the qft - g results were divided into three categories : positive , indeterminate , and negative .
the procedures for the qft - g test in our hospitals have been explained in detail in our previous published study .
the following data were extracted from the hospital records - demographic and clinical characteristics and qft - g results .
descriptive statistics such as means and standard deviation , mean  sd , were used to describe the age of the patients .
frequencies and percentages n(% ) were used to describe the gender and the qft - g test results .
the diagnostic performance of the qft - g test was assessed using sensitivity , specificity , and positive / negative predictive values .
we used independent sample t - tests to compare the patients ages across the tuberculosis and pneumonia cases .
the chi - square tests were used to assess the associations between the demographic characteristics and groups ( tuberculosis and pneumonia cases ) .
the percentage of positive qft - g results in each disease group and gender group was assessed by the chi - square tests .
we examined whether the age was significantly different between the positive and negative qft - g results of the two groups .
statistical analyses were performed using sas 9.2 ( sas institute , cary , nc , usa ) .
over the study period , 6907 patients were admitted with diagnoses of pneumonia , and 639 ( 9% ) of them were diagnosed with tuberculosis .
the results of qft - g test were available in 368 patients : 142 ( 38.6% ) patients with active tb and 226 ( 61.4% ) patients with pneumonia .
table 1 demonstrates the patients demographic and clinical characteristics in relation to the disease status .
out of 368 patients , 188 ( 51.1% ) were female and 180 ( 48.9% ) were male .
most of the 368 patients were saudis : 363 ( 98.6% ) . in both groups ( tuberculosis and pneumonia ) , the results of the qft - g tests were observed to be negative in 183 cases ( 49.7% ) , positive in 143 cases ( 38.9% ) , and indeterminate in 42 cases ( 11.4% ) . when the 368 patients were classified by the disease status , the qft - g test appeared to have a higher positivity rate among the tuberculosis cases ( 68.3% ) than the pneumonia cases ( 20.4% ) , p - value = 0.001 .
the result of the qft - g test was observed to be negative in 33 cases ( 23.2% ) and indeterminate in 12 cases ( 8.5% ) in the tuberculosis group , whereas , the qft - g test was observed to be negative in 150 cases ( 66.4% ) and indeterminate in 30 cases ( 13.3% ) in the pneumonia group [ table 1 and figure 1 ] .
the patients ages were significantly higher among the pneumonia group ( 64.4  17.4 , range 19107 years ) than the tuberculosis group ( 54.9  19.4 , range 1892 ) , p - value = 0.001 .
there were no differences between males and females across the two groups ( p - value = 0.755 ) .
demographic characteristics and quantiferon results in relation to disease status ( n = 368 ) diagnostic accuracy of the quantiferon test among cases with pneumonia or tuberculosis table 2 shows the patients demographic and disease status in relation to qft - g results , excluding 42 patients with indeterminate results . the 42 patients who had indeterminate results were excluded because no follow - up qft - g test was performed on these patients .
the mean age for the negative qft - g ( n = 183 ) results was shown to be 62.50  18.0 years , which was significantly higher than that for the positive qft - g ( n = 143 ) results ( 57.7  19.7 years ) , p - value = 0.021 .
there was no significant difference between the positive qft - g results comparing males ( 42.9% ) and females ( 44.7% ) , p - value = 0.749 .
the positive results of qft - g were higher in patients with tuberculosis disease than in patients with pneumonia disease ( 74.6 vs. 23.5% , p - value = 0.001 ) .
table 3 shows the sensitivity , specificity , and positive / negative predictive values of the qft - g test .
the sensitivity of the qft - g test was 74.6% [ 95% ci : 66.09 to 81.65% ] , while its specificity was 76.53% [ 95% ci : 69.85 to 82.15% ] .
the positive predictive value of the qft - g test was 67.83% [ 95% ci : 59.43% , 75.25% ] and the negative predictive value was 81.97% [ 95% ci : 75.46% , 87.10% ] . among 130 tuberculosis cases , the false negative rate was 25.4% ( 33/130 tuberculosis cases ) . among 196 pneumonia cases , the false positive of the qft - g test was 23.5% ( 46/196 pneumonia cases ) .
furthermore , figure 2 shows how well the qft - g test separates the two groups , tuberculosis and pneumonia , with an area under the curve of 75.60% [ 95% ci : 70.1081.10% ] .
demographic characteristics in relation to quantiferon results , excluding 42 patients with indeterminate results ( n = 326 ) diagnostic accuracy of the qft - g test , excluding 42 indeterminate results ( n = 326 ) receiver operating characteristic ( roc ) curve of qft - g test
early diagnosis of active tuberculosis is essential to ensure early treatment and prevention of infection .
sputum culture with microbiological confirmation remains the gold standard for the clinical diagnosis of active tb , but requires a long follow - up .
qft - g held a promise to provide a rapid and reliable test to diagnose active tb . in this study ,
the sensitivity of qft - g for the diagnosis of tuberculosis was 74.6% and specificity was 76.53% .
however , several studies subsequently showed only a modest sensitivity of the qft - g test to detect tb , although it performed better than tuberculin skin test ( tst ) .
lai cc et al . reported 66% sensitivity and specificity ( 76% ) , which was comparable to our findings . in their meta - analysis of 26,680 participants , rangaka et al . concluded that qft - g did not have high accuracy for the prediction of active tuberculosis , although the use of qft - g in high - risk populations might reduce the number of people considered for preventive treatment .
equally , the qft - g has suboptimal accuracy for confirming or ruling active tuberculosis disease . in a meta - analysis comparing commercial interferon - gamma release assays for detecting active tb
, the authors found that commercial qft - gs were superior to tsts for detecting confirmed active tb disease , especially when performed in developed countries . the overall pooled sensitivity and specificity of quantiferon tb gold was 6985% and 5184% , which was similar to our study .
a study from china reported a higher overall sensitivity of 81.4% and up to 86.6% in smear - positive cases , while having a specificity of 97% , which was comparable to our findings .
another study from indonesia revealed the sensitivity of qft - g to be 88.7% in active tb cases , which was higher than our study .
our study had three advantages : first it was from an intermediate tb - prevalent region and included large numbers of culture - positive , confirmed , tb cases , therefore , it was probably a better representation of the region , with an intermediate prevalence of tb compared to other studies .
pre - test probability is a very important factor for a better interpretation of a positive qft - g test in cases of active tb suspicion .
interferon- release assays can be used more reliably in excluding tb , particularly extrapulmonary , in patients originating from areas of low tuberculosis incidence .
other factors influencing discordant results of the qft - g test in patients with active tb include older age , lower lymphocyte count , total protein and albumin levels , and high crp levels . in both groups ,
the elderly patients were more likely to have negative results of qft - g ( 62.50  18.0 years ) than positive results of qft - g ( 57.7  19.7 years ) .
nevertheless , no gender differences between pneumonia and tuberculosis groups were found in our study .
there was some evidence that the qft - g response could be diminished in cases with advanced tb .
the advantage of our study was having a large number of patients with a confirmed culture positive tuberculosis the major limitations included the fact that it was a retrospective study with known limitations .
we did not include tst as an additional test to the qft - g and we did not include pre - test probability of active tuberculosis when ordering the qft - g test .
the indeterminate results of the qft - g tests were not common in tuberculosis ( 8.5% ) compared to pneumonia ( 13.2% ) , which was similar to other studies .
it is imperative to indicate that there are two commercial qft - g tests ( tb gold and tb spot ) .
they differ in their positive and negative predictive values , and the concordance of the two tests is modest in both immunocompetent and immunocompromised patients , for both latent and active tb . although our findings that quantiferon tb gold can be used as an adjunct tool in the diagnosis of active tb , it certainly can not be used solely and indiscriminately , separate from other clinical epidemiological and radiological factors , and the pre - test probability remains very important for the interpretation of these tests .
 background : the utility of quantiferon - tb gold in - tube ( qft - g ) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis - prevalent ( tb ) countries . 
 aim : the aim of this study is to assess the performance of the qft - g test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country.setting and design : a retrospective study at the king abdulaziz medical city - riyadh ( kamc - r)materials and methods : we retrospectively reviewed all the patients with a diagnosis of pneumonia , including tuberculosis , admitted to kamc - r between 1 january 2009 and 31 december 2013 . 
 we included only patients with an available result of the qft - g test . 
 a total of 142 tuberculosis cases and 226 pneumonia cases were studied , to assess the utility of the qft - g test in diagnosing tuberculosis cases.results:among the tuberculosis ( n = 142 ) cases , the qft - g tested positive in 68.3% , negative in 23.2% , and indeterminate in 12 cases ( 8.5% ) . 
 of the 226 pneumonia cases , the qft - g tested positive in only 20.4% , while a majority of 66.4% tested negative , with 30 cases ( 13.3% ) being indeterminate . 
 when we excluded 42 patients with indeterminate results , the qft - g test achieved a sensitivity of 74.6% [ 95% ci : 66.09 to 81.65% ] and specificity of 76.53 % [ 95% ci : 69.85 to 82.15% ] in the diagnosis of tuberculosis cases.conclusions:this study concludes that the qft - g test is a useful tool for detecting tuberculosis disease when used as an adjunct tool for the diagnosis of active tb cases . 
 it certainly can not be used solely and indiscriminately , separate from other clinical and radiological information , in the diagnosis of active tuberculosis cases . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION