Article

Evaluation of the Xpert MTB/RIF Assay for the Diagnosis of Pulmonary Tuberculosis in a High HIV Prevalence Setting

Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 04/2011; 184(1):132-40. DOI: 10.1164/rccm.201101-0056OC
Source: PubMed

ABSTRACT Xpert MTB/RIF is a novel automated molecular diagnostic recently endorsed by the World Health Organization. However, performance-related data from high HIV prevalence settings are limited.
The impact of sample-related factors on performance and the significance of Xpert MTB/RIF-positive culture-negative discordance remain unclear.
Xpert MTB/RIF was evaluated using single archived spot-sputum samples from 496 South African patients with suspected TB. Mycobacterium tuberculosis culture positivity and phenotypic resistance to rifampicin served as reference standards.
Overall, Xpert MTB/RIF detected 95% (95% confidence interval [CI], 88-98%; 89 of 94) of smear-positive culture-positive cases and the specificity was 94% (91-96%; 320 of 339). The sensitivity in smear-negative cases was 55% (35-73%; 12 of 22) when the analysis was restricted to 1 ml of unprocessed sputum and culture time-to-positivity of less than or equal to 28 days. Compared with smear microscopy (n=94), Xpert MTB/RIF detected an additional 17 cases (n=111) representing an 18% (11-27%; 111 vs. 94) relative increase in the rapid TB case detection rate. Moreover, compared with smear microscopy, the inclusion of Xpert MTB/RIF-positive culture-negative TB cases (ruled-in by an alternative diagnostic method) resulted in the detection of a further 16 cases (n=127), thus significantly increasing the rapid TB case detection rate to 35% (95% CI, 26-45%; 94 to 111 vs. 94 to 127; P<0.01), the overall specificity to 99.1% (97-100%; 320 of 323; P<0.001), and sensitivity in smear-negative TB to 60% (P=0.12). Performance strongly correlated with smear status and culture time-to-positivity. In patients infected with HIV compared with patients uninfected with HIV Xpert MTB/RIF showed a trend to reduced sensitivity (P=0.09) and significantly reduced negative predictive value (P=0.01). The negative predictive value for rifampicin resistance was 99.4%.
XpertMTB/RIF outperformed smear microscopy, established a diagnosis in a significant proportion of patients with smear-negative TB, detected many highly likely TB cases missed by culture, and accurately ruled out rifampicin-resistant TB. Sample-specific factors had limited impact on performance. Performance in patients infected with HIV, especially those with advanced immunosuppression, warrants further study.

Full-text

Available from: Hridesh Mishra, May 30, 2015
5 Followers
 · 
187 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is a paucity of clinical and histopathological data about HIV-associated lymphocytic interstitial pneumonitis (LIP) in adults from HIV endemic settings. The role of Ebstein-Barr virus (EBV) in the pathogenesis remains unclear. We reviewed the clinical, radiographic and histopathological features of suspected adult LIP cases at the Groote Schuur Hospital, Cape Town South Africa, over a 6 year period. Archived tissue sections were stained for CD3, CD4, CD8, CD20 and LMP-1 antigen (an EBV marker). 42 cases of suspected LIP(100% HIV-infected) were identified. 75% of patients were empirically treated for TB prior to being referred to the chest service for further investigation. Tissue samples were obtained using trans-bronchial biopsy. 13/42 were classified as definite LIP (lymphocytic infiltrate with no alternative diagnosis), 19/42 probable LIP (lymphocytic infiltrate but evidence of anthracosis or fibrosis) and 10 as non-LIP (alternative histological diagnosis). Those with definite LIP were predominantly young females (85%) with a median CD4 count of 194 (IQR 119-359). Clinical or radiological features had poor predictive value for LIP. Histologically, the lymphocytic infiltrate comprised mainly B cells and CD8 T cells. The frequency of positive EBV LMP-1 antigen staining was similar in definite and non- LIP patients [(2/13 (15%) vs. 3/10 (30%); p = 0.52]. In a HIV endemic setting adult HIV-associated LIP occurs predominantly in young women. The diagnosis can often be made on transbronchial biopsy and is characterized by a predominant CD8 T cell infiltrate. No association with EBV antigen was found.
    BMC Pulmonary Medicine 04/2015; 15(1):38. DOI:10.1186/s12890-015-0030-2 · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.
    PLoS ONE 02/2015; 10(2):e0116721. DOI:10.1371/journal.pone.0116721 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Translating the potential of Xpert(®) MTB/RIF into more effective tuberculosis (TB) care and control in low-income settings is challenged by operational issues. We report the experience in introducing this technology in Burkina Faso through a centralised approach. Xpert was successfully integrated into the diagnostic algorithm of multidrug-resistant TB cases. However, barriers to Xpert use for the diagnosis of TB in vulnerable populations, such as persons living with human immunodeficiency virus infection and children, were observed, mainly due to lack of coordination between services. Lessons learnt can be exploited to optimise the roll-out of this technology at country level.
    The International Journal of Tuberculosis and Lung Disease 03/2015; 19(3):285-287. DOI:10.5588/ijtld.14.0629 · 2.76 Impact Factor