Performance of the 2007 WHO Algorithm to Diagnose Smear-Negative Pulmonary Tuberculosis in a HIV Prevalent Setting

Abstract

BackgroundThe 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya.MethodsPTB smear-negative adult suspects were included in a prospective diagnostic study (2009–2011). In addition, program data (2008–2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard.Results380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09–0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment.ConclusionThe clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary.

Empiric TB Treatment of Severely Ill Patients With HIV and Presumed Pulmonary TB Improves Survival

“…Several published studies 16,17 evaluated the accuracy of the 2007 guidelines at detecting AFB smear-negative TB without evaluating the effect of guideline-adherent care on mortality. Our study evaluated the use of chest radiography but not the other diagnostic algorithms in the 2007 WHO guidelines (e.g.…”

“…18 Our evaluation of empiric treatment based on suggestive chest radiography was underpowered, but this failure to find benefit is consistent with previous studies showing that chest radiography does not increase the likelihood of a TB diagnosis in AFB smear-negative, HIV-seropositive patients, especially those with advanced immunosuppression. 5,15,16 Even if proven beneficial, routinely obtaining a chest radiograph might contribute diagnostic and treatment delay in low-income settings, where most HIV-infected, presumed TB patients present to private providers and peripheral government clinics where chest radiography services and interpretation are not readily accessible. 19 …”

Intra-gastric string test: an effective tool for diagnosing tuberculosis in adults unable to produce sputum

“…The decision to treat patients unable to expectorate is thus often based on less rigorous evidence, such as clinical examination and/or chest radiograph (CXR). [1][2][3][4][5] This is particularly common among human immunodeficiency virus (HIV) infected patients and children. Bronchoalveolar lavage, although considered the gold standard for patients unable to expectorate, is used only infrequently in low-resource countries due to its complexity, cost and safety risk.…”

Is introducing rapid culture into the diagnostic algorithm of smear-negative tuberculosis cost-effective?

“…In the Homa Bay District Hospital, 68% of suspected TB cases are among HIV-infected people. 7 Smear microscopy has low sensitivity (~50%) compared to the Mycobacterium tuberculosis culture reference standard. 8 This sensitivity is even lower in HIV-infected patients.…”

“…20 In this setting, median time to positivity is 15 days (interquartile range [IQR] 11-21) for TLA and 23 days (IQR 18-32) for LJ. 7 This study assesses whether introduction of the rapid non-commercial TLA and LJ culture methods is costeffective for initiating treatment in true smearnegative pulmonary TB patients.…”