Do Xpert MTB/RIF Cycle Threshold Values Provide Information about Patient Delays for Tuberculosis Diagnosis?
BACKGROUND
Early diagnosis and initiation to appropriate treatment is vital for tuberculosis (TB) control. The XpertMTB/RIF (Xpert) assay offers rapid TB diagnosis and quantitative estimation of bacterial burden through Cycle threshold (Ct) values. We assessed whether the Xpert Ct value is associated with delayed TB diagnosis as a potential monitoring tool for TB control programme performance.


METHODS
This analysis was nested in a prospective study under the routine TB surveillance procedures of the National TB Control Program in Manhiça district, Maputo province, Mozambique. Presumptive TB patients were tested using smear microscopy and Xpert. We explored the association between Xpert Ct values and self-reported delay of Xpert-positive TB patients as recorded at the time of diagnosis enrolment. Patients with >60 days of TB symptoms were considered to have long delays.


RESULTS
Of 1,483 presumptive TB cases, 580 were diagnosed as TB of whom 505 (87.0%) were due to pulmonary TB and 302 (94.1%) were Xpert positive. Ct values (range, 9.7-46.4) showed a multimodal distribution. The median (IQR) delay was 30 (30-45) days. Ct values showed no correlation with delay (R2 = 0.001, p = 0.621), nor any association with long delays: adjusted odds ratios (AOR) (95% confidence interval [CI]) comparing to >28 cycles 0.99 (0.50-1.96; p = 0.987) for 23-28 cycles, 0.93 (0.50-1.74; p = 0.828) for 16-22 cycles; and 1.05 (0.47-2.36; p = 0.897) for <16 cycles. Being HIV-negative (AOR [95% CI]), 2.05 (1.19-3.51, p = 0.009) and rural residence 1.74 (1.08-2.81, p = 0.023), were independent predictors of long delays.


CONCLUSIONS
Xpert Ct values were not associated with patient delay for TB diagnosis and cannot be used as an indicator of TB control program performance.
Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Department of Medical Microbiology, College of Health Sciences Makerere University, Kampala, Uganda.
Willy
W
Ssengooba
Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
Durval
D
Respeito
Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
Edson
E
Mambuque
ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
Silvia
S
Blanco
Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
Helder
H
Bulo
Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério da Saúde, Maputo, Mozambique.
Inacio
I
Mandomando
Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
Bouke C
BC
de Jong
Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|KNCV Tuberculosis Foundation, The Hague, the Netherlands.
Frank G
FG
Cobelens
Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
Alberto L
AL
García-Basteiro
D000328:Adult; D057210:Delayed Diagnosis; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011933:Reagent Kits, Diagnostic; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000175:diagnosis*
D011933:Reagent Kits, Diagnostic; D012293:Rifampin