Assessment by Meta-Analysis of PCR for Diagnosis of Smear-Negative Pulmonary Tuberculosis

Abstract

We conducted a meta-analysis to assess the performance of PCR for the diagnosis of smear-negative pulmonary tuberculosis (SPT) and to identify factors that account for differences in the diagnostic accuracy of different studies. Studies published before February 2002 were included if sensitivity and specificity of PCR in smear-negative respiratory or gastric-aspirate specimens could be calculated. Analysis was conducted by using summary receiver operating characteristics models. Sensitivity and specificity ranged from 9 to 100% and from 25 to 100%, respectively. Fewer than 40% of the 50 studies reported results by number of patients, reported clinical characteristics of patients, or used as a reference standard combined culture and clinical criteria. Studies that included bronchial specimens showed higher accuracy than studies that evaluated only sputum specimens or included gastric aspirates. Studies that did not report that tests were applied blindly showed higher accuracy than those reporting blind testing. Increased sensitivity due to the use of DNA purification methods was associated with decreased specificity. Studies published after 1995, using Amplicor or dUTP-UNG, were associated with an increase in specificity at the expense of lower sensitivity. We concluded that PCR is not consistently accurate enough to be routinely recommended for the diagnosis of SPT. However, PCR of bronchial specimens could be useful in highly suspicious SPT cases. Studies not reporting blind testing are likely to overestimate accuracy of PCR. Future evaluation of PCR accuracy should be conducted by patient and type of respiratory specimen, blindly, by using a reference standard that combines culture and clinical criteria and addresses the issue of how patient characteristics affect PCR accuracy.Tuberculosis remains an important public health problem worldwide, accounting for ca. 8.0 million new cases per year (25). Smear-negative cases pose an important public health hazard and burden, accounting for as much as 17% of Mycobacterium tuberculosis transmission (11). Some patients convert to smear positivity, leading to a more severe morbidity (20). Approximately 20 to 50% of patients with pulmonary tuberculosis are smear negative, and 10% of these patients are culture negative (6,25).PCR reduces the time required for the identification of the Mycobacterium and may enhance the detection of smear-negative pulmonary tuberculosis (SPT) cases. However, qualitative reviews (4,23,27,30,64) and interlaboratory studies (46, 47) have pointed out the low sensitivity of PCR for the diagnosis of SPT and the significant variability in sensitivity and specificity in different studies. Proposed explanations for these findings have included differences in decontamination procedures (47), cross contamination (46), inhibition (27), sampling error (27), quality of the reference standard (27), and mixture of respiratory and other specimens (30).Although numerous studies have contributed to our understanding of PCR performance for the diagnosis of pulm...

Tuberculosis diagnostics trials: do they lack methodological rigor?

“…A total of ten eligible studies (in English) were identified [12][13][14][15][16][17][18][19][20][21]. To this list, we added two meta-analyses published as abstracts [22,23].…”

Búsqueda Activa de Individuos con Tuberculosis Pulmonar y Extrapulmonar en Calarcá-Quindío, Colombia-2005

“…No obstante, dado que aproximadamente entre el 20 y el 50 % de los pacientes con tuberculosis pulmonar son negativos a la baciloscopia y el 10 % de estos son negativos también al cultivo (20) se observa la necesidad de incorporar métodos diagnósticos más sensibles y de caracterización molecular de los aislados (21,22), lo cual permitiría la realización de un diagnostico rápido, una intervención oportuna y precisa. Así mismo, el empleo de estos métodos moleculares permite generar información epidemiológica de gran aplicación al momento de diseñar nuevas estrategias locales y regionales mejorando la efectividad de los programas de control.…”

Tuberculose pleural

“…No entanto, uma recente meta-análise demonstrou que a dosagem de ADA seria mais efetiva em termos de custo do que a dosagem de interferon-γ para o diagnóstico de TB. (23) Por esses motivos, não recomendamos o uso rotineiro do interferon-γ na prá-tica clínica atual.…”

“…(23) Um estudo avaliando o rendimento da reação em cadeia da polimerase no líquido pleural de 111 pacientes (57 com TB pleural) mostrou sensibilidade de 17% e especificidade 98%. (24) Além disso, as técnicas de amplificação de seqüên-cias de ácidos nucléicos ainda não foram validadas para uso em amostras não respiratórias como o líquido pleural.…”