Detection and Quantification of Mycobacterium tuberculosis in the Sputum of Culture-Negative HIV-infected Pulmonary Tuberculosis Suspects: A Proof-of-Concept Study.
PLoS One
; 11(7): e0158371, 2016.
Article
em En
| MEDLINE
| ID: mdl-27391604
ABSTRACT
RATIONALE Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease. METHODS:
We evaluated the Totally Optimized PCR (TOP) TB assay, a new molecular test that we hypothesize is more sensitive than culture. After pre-clinical studies, we estimated TOP's per-patient sensitivity and specificity in a convenience sample of 261 HIV-infected pulmonary TB suspects enrolled into a TB diagnostic study in Mbarara, Uganda against MGIT culture, Xpert MTB/RIF and a composite reference standard. We validated results with a confirmatory PCR used for sequencing M. tuberculosis. MEASUREMENTS ANDRESULTS:
Using culture as reference, TOP had 100% sensitivity but 35% specificity. Against a composite reference standard, the sensitivity of culture (27%) and Xpert MTB/RIF (27%) was lower than TOP (99%), with similar specificity (100%, 98% and 87%, respectively). In unadjusted analyses, culture-negative/TOP-positive patients were more likely to be older (P<0·001), female (P<0·001), have salivary sputum (P = 0·05), sputum smear-negative (P<0.001) and less advanced disease on chest radiograph (P = 0.05). M. tuberculosis genotypes identified in sputum by DNA sequencing exhibit differential growth in culture.CONCLUSIONS:
These findings suggest that the TOP TB assay is accurately detecting M. tuberculosis DNA in the sputum of culture-negative tuberculosis suspects. Our results require prospective validation with clinical outcomes. If the operating characteristics of the TOP assay are confirmed in future studies, it will be justified as a "TB rule out" test.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Escarro
/
Tuberculose Pulmonar
/
Infecções por HIV
/
Reação em Cadeia da Polimerase
/
Sequenciamento de Nucleotídeos em Larga Escala
/
Mycobacterium tuberculosis
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Africa
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos