Xpert MTB/RIF as a measure of sputum bacillary burden

Variation by HIV status and immunosuppression

Colleen Hanrahan, Grant Theron, Jean Bassett, Keertan Dheda, Lesley Scott, Wendy Stevens, Ian Sanne, Annelies Van Rie

Research output: Contribution to journalArticle

Abstract

Rationale: Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited. Objectives: Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity. Methods: Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity. Measurements and Main Results: Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P <0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P <0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity. Conclusions: We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.

Original languageEnglish (US)
Pages (from-to)1426-1434
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume189
Issue number11
DOIs
StatePublished - Jun 1 2014
Externally publishedYes

Fingerprint

Sputum
Immunosuppression
HIV
CD4 Lymphocyte Count
Microscopy
South Africa
Pulmonary Tuberculosis
HIV Infections

Keywords

  • Diagnostics
  • South Africa
  • Tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Xpert MTB/RIF as a measure of sputum bacillary burden : Variation by HIV status and immunosuppression. / Hanrahan, Colleen; Theron, Grant; Bassett, Jean; Dheda, Keertan; Scott, Lesley; Stevens, Wendy; Sanne, Ian; Van Rie, Annelies.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 189, No. 11, 01.06.2014, p. 1426-1434.

Research output: Contribution to journalArticle

Hanrahan, Colleen ; Theron, Grant ; Bassett, Jean ; Dheda, Keertan ; Scott, Lesley ; Stevens, Wendy ; Sanne, Ian ; Van Rie, Annelies. / Xpert MTB/RIF as a measure of sputum bacillary burden : Variation by HIV status and immunosuppression. In: American Journal of Respiratory and Critical Care Medicine. 2014 ; Vol. 189, No. 11. pp. 1426-1434.
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abstract = "Rationale: Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited. Objectives: Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity. Methods: Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity. Measurements and Main Results: Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P <0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P <0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity. Conclusions: We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.",
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