Abstract
BackgroundSputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting.MethodsBetween January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment.ResultsOf 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28–39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065).ConclusionsMycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm3), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting.
Highlights
Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in human immunodeficiency virus (HIV)-infected symptomatic patients and increases the likelihood that mycobacterial infections disseminated TB will be missed; delays in diagnosis can be fatal
Study participants’ characteristics Of the 501 TB suspects who provided blood for TB blood culture testing, 394 were sputum smear-negative and eligible for the analysis (Figure 1); 63.7% were female with a median age (IQR) and CD4 cell count (IQR) of 32 (28–39) years and 106 (24–308) cells/mm3, respectively (Table 1)
Similar to prior reports from sub-Saharan Africa (SSA) [12,18,19,20,28], we found a high prevalence of mycobacteremia among TB/HIV co-infected patients whose TB was not diagnosed by routine smear microscopy
Summary
Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. Sputum smear-negative pulmonary TB [7,8] is associated with delayed diagnosis and treatment with subsequently high mortality [9,10,11] especially in TB-HIV co-infected patients. Given the duration required for MTB growth in blood culture, clinical predictors of MTB bacteremia and rapid diagnostic tests may improve early diagnosis of mycobacteremia in settings with increased HIV /TB co infection. Mortality in HIV- infected, smear-negative TB patients could be reduced through early identification and treatment of patients who have MTB bacteremia
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