Chest X-Ray (CXR) remains a useful adjuvant test in smear-negative pulmonary TB to guide further patient management in high TB/HIV prevalence settings. Given the recent widespread roll-out of Xpert MTB/RIF in most low-income countries, we evaluated the role of CXR in the diagnosis of smear-negative TB among HIV-positive presumptive TB patients in the Xpert MTB/RIF era. Overall, we found poor performance of CXR interpretation in the diagnosis of culture- positive smear-negative TB among HIV-positive participants. We found that, although CXR increased sensitivity of Xpert MTB/RIF assay, this was at the expense of specificity. Given its high negative predictive value, a normal CXR could reliably exclude TB in HIV-positives with negative sputum smear, however, the applicability of CXR in settings with Xpert MTB/Rif is limited by the challenges of CXR application faced in most RLS. Our study further found that combining CXR with Xpert MTB/RIF reduced the specificity of Xpert MTB/RIF in the diagnosis of smear-negative TB. This implies that use of CXR as an adjuvant to Xpert MTB/RIF results into inaccurate diagnosis of TB among HIV co-infected presumptive TB patients with negative smear.
Our findings corroborate with earlier reports from high prevalence TB/HIV settings in SSA which also found poor performance, particularly low specificity, of CXR interpretation in the diagnosis of culture-confirmed TB among smear-negative HIV co-infected individuals (24, 26, 28–30).
Poor performance of CXR in TB diagnosis in HIV co-infected individuals is often attributed to the non-specific CXR patterns and difficulty in interpretation (23, 25). Results of a chest radiograph often depend on the severity and presentation of TB, which all depend on the stage of the HIV disease, with advanced HIV disease more likely to present with non-specific patterns compared to early-stage HIV disease. Moreover, CXR findings can be normal in up to 25–50% of patients with culture-confirmed TB (23, 25, 26). Our study population comprised HIV co-infected individuals, majority of whom had advanced HIV disease (median CD4 count 112 cells/mm3) and this could potentially explain the non-specific patterns inaccurately interpreted as TB, and thus the low specificity seen in our study.
CXR interpretation in HIV co-infection is further complicated by the presence of other HIV-related pulmonary diseases that could radiologically mimic TB; commonly, bacterial pneumonia (23, 24). Several studies from SSA (24, 26, 29) have reported presence of other HIV-related pulmonary conditions that radiologically mimic TB that have led to misinterpretation of chest radiographs as TB. This too could explain the poor CXR performance in this study that was performed among entirely HIV-positive individuals. However, our study did not evaluate other possible non-TB pulmonary conditions that could explain the inaccurate CXR interpretation.
Poor performance of CXR interpretation in this study could also be explained by poor quality of CXR films, which in turn is dependent on the skill of the technician, and the quality of the CXR equipment used. Studies have shown accuracy of CXR interpretation is dependent on the quality of the CXR film (23, 29). In most peripheral health centres in RLS where CXR services are available, the quality of the radiographs produced from the poor quality CXR equipment is often not good enough to improve interpretation (23). To improve accuracy of CXR interpretation in our study, CXR interpretation was performed by expert radiologists.
Our study further found that CXR interpretation did not complement Xpert MTB/RIF diagnostic performance in smear-negative TB diagnosis in this low-income country with high TB/HIV prevalence. Instead, we noted decreased accuracy with loss in specificity of Xpert MTB/RIF test when additively used with CXR interpretation i.e. Xpert MTB/RIF specificity dropped from 95.8% when used as stand-alone test to 51.6% when additively used with CXR interpretation. A similar trend was seen when results were stratified by setting (outpatients versus inpatients). Our findings are similar to an earlier report, which also found a reduction in specificity of Xpert MTB/RIF when additively used with CXR interpretation (30). The reduction in specificity is attributable to the non-specific nature of CXR patterns in HIV disease, which results into inaccurate interpretation (23, 26). These findings imply that use of CXR interpretation as an additive test to Xpert MTB/RIF test in centers where Xpert MTB/RIF is available as a TB diagnostic increases the likelihood of inaccurate diagnosis of TB, which consequently puts more financial strain to TB programs in RLS and leads to misuse of already scarce resources. However, based on our recent findings from the same patient population, CXR could complement urine TB Lipoarabinomannan (LAM) if Xpert MTB/RIF is not available (31). The previous findings showed that an algorithm in which CXR is performed following urine TB LAM test significantly improves diagnosis of TB among smear-negative HIV-positive patients with a high negative predictive value, especially when CD4 counts are < 100cells/mm3 (31). This was not the case when CXR was combined with Xpert MTB/RIF test in the diagnosis of TB in smear-negative HIV-positive patients.
Of note, our study found lower lung field infiltrates (41%) and pleural disease among the most frequent abnormalities reported by the expert radiologist. This is similar to earlier findings from other studies on CXR features among HIV co-infected individuals (23–26, 29). These atypical CXR features are not surprising in our study, which included entirely HIV co-infected patients, many of whom had immunologically advanced HIV disease. Advanced HIV disease could also explain the miliary TB disease CXR pattern seen in a few of our study patients. Cavities were rare among our study participants as is expected in HIV-positive patients with advanced disease (23, 25).
This study had strengths. First, our study included both sputum and blood MTB culture as the standard of reference, which improved the strength of our reference standard for TB diagnosis. Inadequacy of gold standard is often a limitation in TB diagnostics evaluations. Second, in order to improve CXR interpretation, we used two expert radiologists to interpret the chest radiographs, and in case of variability, a third radiologist was used as a tiebreaker. Third, our study population and setting well represent a real-world situation that is likely to be found in high prevalence HIV/TB settings in low-income countries. We studied a population of HIV-infected individuals with an increased risk of morbidity and mortality from TB that is targeted in the End TB strategy. Lastly, we used a relatively simple CXR evaluation form in the interpretation of the CXR, which is a more practical approach since hospitals in RLS often lack personnel that can interpret CXR with expertise and are often understaffed. By using a simple and easy-to-use CXR interpretation form, we assigned the accuracy of the CXR in this study more agreeable with resource-constrained settings.