Comparison of GeneXpert cycle threshold values with smear microscopy and culture as a measure of mycobacterial burden in five regional referral hospitals of Uganda- A cross-sectional study

Abstract

Background Determining mycobacterial burden is important in assessing severity of disease, evaluating infectiousness and predicting patient treatment outcomes. Mycobacterial burden assessed by smear microscopy grade and time to culture positivity is clearly interpretable by most physicians. GeneXpert (Xpert) has been recommended by WHO as a first line tuberculosis (TB) diagnostic test as an alternative to smear microscopy. Xpert gives cycle threshold (Ct) values as a potential measure for mycobacterial burden. For physicians to clearly interpret Ct values as measures of mycobacterial burden, this study compared the Xpert quantification capabilities with those of smear microscopy and culture. The study also determined a linear relationship between Xpert Ct values and MGIT culture time to positivity (MGIT-TTP) and associated factors. A cut off Ct value which best predicts smear positivity was also determined using the Receiver Operator Curve analysis method. Results Excluding missing results and rifampicin resistant TB cases, a moderately strong correlation of 0.55 between Xpert Ct value and smear grade was obtained. A weak correlation of 0.37 was obtained between Xpert Ct values and MGIT time to positivity while that between Xpert Ct values and LJ culture was 0.34. The Xpert Ct values were found to increase by 2.57 for every unit increase in days to positive and HIV status was significantly associated with this relationship. A cut off Ct value of 23.62 was found to best predict smear positivity regardless of HIV status. Conclusion Our study findings show that GeneXpert Ct values are comparable to smear microscopy as a measure of M . tuberculosis burden and can be used to replace smear microscopy. However, given the low correlation between Xpert Ct value and culture positivity, Xpert Ct values cannot replace culture as a measure of M . tuberculosis burden among TB patients.

The Xpert® MTB/RIF diagnostic test for pulmonary and extrapulmonary tuberculosis in immunocompetent and immunocompromised patients: Benefits and experiences over 2 years in different clinical contexts

“…The Xpert test was positive in all patients with positive smears, indicating that results of both methods correlate well. Similar results were previously reported [ 15 , 41 ], wherein comparison of the GeneXpert cycle threshold with the smear results showed that most of the "low" and "very low" Ct values in the molecular test were negative in the smear, thus proving its value in the early identification of bacilli before the culture result [ 28 ]. When compared with CRS-positive results, both AFB and culture had a similar sensitivity of 20% and 25% respectively.…”

Epidemiological profile of multidrug-resistant and extensively drug-resistant Mycobacterium Tubrculosis among Congolese patients 

“…This could be explained by the fact that tuberculosis is the most common opportunistic disease in HIVinfected patients. This nding has also been made by several authors (Harries et al, 2019;Najjingo et al, 2019;Phyo et al, 2019).…”

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“…The Xpert test was positive in all patients with positive smears, indicating that results of both methods correlate well. Similar results were previously reported [15,41], wherein comparison of the GeneXpert cycle threshold with the smear results showed that most of the "low" and "very low" Ct values in the molecular test were negative in the smear, thus proving its value in the early identification of bacilli before the culture result [28]. When compared with CRS-positive results, both AFB and culture had a similar sensitivity of 20% and 25% respectively.…”