Progression of subclinical culture-positive tuberculosis to symptomatic disease in HIV-infected individuals

The prevalence of culture-positive tuberculosis (TB) detectable among patients screened prior to starting antiretroviral therapy (ART) in the southern African region is so high (17–25%) that routine microbiological screening of such patients has been advocated [1–3]. When such a strategy is adopted and HIV-infected patients are systematically screened regardless of clinical symptoms, a proportion of individuals who are asymptomatic nevertheless produce sputum samples from which Mycobacterium tuberculosis can be cultured [4]. In such patients, the clinician may have difficulty deciding whether this represents laboratory contamination or disease. Alternatively, it has also been questioned whether this phenomenon could represent transient excretion of M. tuberculosis rather than actual disease as has been well documented in children following recent primary infection [5]. Data on the clinical outcome of such patients are lacking. Data from studies performed in Cape Town, South Africa, using laboratory facilities with rigorous quality assurance procedures, now shed more light on this phenomenon. In our current study cohort evaluating TB, diagnostic strategies among patients during pre-ART screening in a high TB burden township (a proportion of this cohort has been reported previously [3]), 89 patients (median CD4 count, 131 cells/μl) tested sputum culture-positive. Of these, 16 (18%) patients were asymptomatic at screening. Prolonged time to culture-positivity and delays inherent in the process of recalling patients with positive results for treatment provided the opportunity to prospectively evaluate the clinical status of patients up to the time of starting TB treatment. During follow-up, 10 of these patients developed symptoms by the time TB treatment was started and two others developed symptoms within the first month of ART with a clinical presentation consistent with ‘unmasking’ TB [6]. Thus, overall, 12 (75%) initially asymptomatic patients progressed to develop TB symptoms between 5 days and 2 months of follow-up. The other four patients remained asymptomatic up to the time of starting TB treatment after a mean of 11 weeks follow-up despite two of them having clearly abnormal chest radiographs. All four received TB treatment and three received ART. It is not known whether these patients would have later developed symptomatic disease in the absence of TB treatment. Data from another study recently reported by Oni et al.[7] in Cape Town are consistent with these observations. They reported a high frequency of sputum cultures testing positive for M. tuberculosis among asymptomatic ART-naive HIV-infected individuals with a higher median CD4 cell count of 249 cells/μl. During follow-up of the 16 patients who were retained in care, nine (56%) developed symptoms between 3 days and 2 months later. Collectively, data from these two studies strongly support the concept that, across a range of CD4 cell counts, asymptomatic HIV-infected individuals producing sputum samples that are culture-positive for M. tuberculosis have subclinical disease that soon progresses to symptomatic disease in a majority of cases. Acknowledgements SDL is funded by the Wellcome Trust, London, UK and RW is funded in part by the National Institutes of Health (NIH) through grants RO1 A1058736–01A1, 5UO1A1069519–02 and USAID grant 3UO1A1069924-O2S. Conflicts of interests There are no conflicts of interest.