Higher-than-expected prevalence of non-tuberculous mycobacteria in HIV setting in Botswana: Implications for diagnostic algorithms using Xpert MTB/RIF assay

<div><p>Background</p><p>Non-tuberculous mycobacteria (NTM) can cause pulmonary infection and disease especially among people living with HIV (PLHIV). PLHIV with NTM disease may clinically present with one of the four symptoms consistent with tuberculosis (TB). We describe the prevalence of NTM and <i>Mycobacterium tuberculosis complex</i> (MTBC) isolated among PLHIV who presented for HIV care and treatment.</p><p>Methods</p><p>All PLHIV patients presenting for HIV care and treatment services at 22 clinical sites in Botswana were offered screening for TB and were recruited. Patients who had ≥1 TB symptom were asked to submit sputa for Xpert MTB/RIF and culture. Culture growth was identified as NTM and MTBC using the SD-Bioline TB Ag MPT64 Kit and Ziehl Neelsen microscopy. NTM and MTBC isolates underwent species identification by the Hain GenoType CM and AS line probe assays.</p><p>Results</p><p>Among 16, 259 PLHIV enrolled 3068 screened positive for at least one TB symptom. Of these, 1940 submitted ≥1 sputum specimen, 427 (22%) patients had ≥1 positive-culture result identified phenotypically for mycobacterial growth. Of these 247 and 180 patients were identified as having isolates were NTM and MTBC, respectively. Of the 247 patients identified with isolates containing NTM; 19 were later excluded as not having NTM based on additional genotypic testing. Among the remaining 408 patients 228 (56%, 95% confidence interval, 46–66%) with NTM. <i>M</i>. <i>intracellulare</i> was the most common isolated (47.8%). Other NTMs commonly associated with pulmonary disease included <i>M</i>. <i>malmoense</i> (3.9%), <i>M</i>. <i>avium</i> (2.2%), <i>M</i>. <i>abscessus</i> (0.9%) and <i>M</i>. <i>kansasii</i> (0.4%). After excluding NTM isolates that were non-speciated and <i>M</i>. <i>gordonae</i> 154 (67.5%) of the NTM isolates were potential pathogens.</p><p>Conclusions</p><p>In the setting of HIV care and treatment, over-half (56%) of a positive sputum culture among PLHIV with TB symptoms was NTM. Though we were not able to distinguish in our study NTM disease and colonization, the study suggests culture and species identification for PLHIV presenting with TB symptoms remains important to facilitate NTM diagnosis and hasten time to appropriate treatment.</p></div

Additional file 2: of Implementation of a pragmatic, stepped-wedge cluster randomized trial to evaluate impact of Botswana’s Xpert MTB/RIF diagnostic algorithm on TB diagnostic sensitivity and early antiretroviral therapy mortality

CONSORT 2010 checklist of information to include when reporting a cluster randomised trial–XPRES Trial Checklist. (PDF 392 kb

NTM isolated among PLHIV presenting with TB symptoms in Botswana and corresponding Xpert MTB/RIF result.

<p>NTM isolated among PLHIV presenting with TB symptoms in Botswana and corresponding Xpert MTB/RIF result.</p

Characteristics of patients with positive-culture for NTM and MTBC in a multilevel logistic regression model.

<p>Characteristics of patients with positive-culture for NTM and MTBC in a multilevel logistic regression model.</p

“Patients with at least one sputum culture results by mycobacterium species August 2012 –November 2014” Notes: * Of the total 16, 259, the 6041 were enrolled prospectively and the 10, 218 retrospectively; ** only 10, 213 were screened for TB symptoms due to amendment on main study (XPRES) data collection procedure; *** of the 3068 screened positive for TB symptom, 2296 were among prospective and 772 from retrospective cohort.

<p>“Patients with at least one sputum culture results by mycobacterium species August 2012 –November 2014” Notes: * Of the total 16, 259, the 6041 were enrolled prospectively and the 10, 218 retrospectively; ** only 10, 213 were screened for TB symptoms due to amendment on main study (XPRES) data collection procedure; *** of the 3068 screened positive for TB symptom, 2296 were among prospective and 772 from retrospective cohort.</p

Type of unsuccessful tests by Xpert testing sites.

<p>Type of unsuccessful tests by Xpert testing sites.</p

Error, invalid, and no result rates by quarter following initial implementation October 2012 to November 2014.

<p>Error rates showed increasing trend over 8 quarters, <i>p = 0</i>.<i>008</i>. Invalid rates showed decreasing trend over 8 quarters, <i>p<0</i>.<i>001</i>. No result showed increasing trend over 8 quarters, <i>p = 0</i>.<i>099</i>. Note for Fig 2. By the time of analysis all 13 sites have experienced at least four quarters. Q5 –eleven sites (ATH, WC, BOB, BK8, DRM, EXT, GAN, KAD, LMH, NRH and SDA). Q6 –ten sites (ATH, AWC, BOB, BK8, DRM, GAN, KAD, LMH, NRH and SDA). Q7. Five sites (ATH, AWC, BK8, KAD and LMH). Q8 –two sites (ATH and KAD).</p