We have shown that 12% of ambulatory HIV-infected patients in Tanzania undergoing comprehensive screening are treated for presumptive and previously undiagnosed active TB. Our results suggest that the optimal diagnosis of TB in this setting requires assessment of both symptomatic and asymptomatic HIV-positive patients using chest x-ray and sputum culture, an observation that differs from consensus international recommendations and has obvious implications for the resources needed to conduct effective and optimal treatment of persons with HIV infection. Confirmation of this preliminary finding will be available when our expert panel completes classification of TB endpoints among the eligible subjects in the trial, including independent review of chest x-rays and response to treatment.
An abnormal chest x-ray in the absence of symptoms was the most common basis for the suspicion of TB. This finding differs from an initial report from Botswana in which an abnormal chest x-ray was very rare among HIV- infected subjects with no symptoms of TB  and a study in South Africa where symptom-based screening was effective . However, our results and those of other recent surveys [13, 14] including a more recent report from Botswana  suggest that the chest x-ray is important in screening and that the standard recommendation to screen for TB based on symptoms alone may be unreliable and insensitive in sub-Saharan Africa . Based on our data, if AFB smear had only been performed on patients with symptoms, 55 patients would have had an AFB smear and only 8 of these (6% of all treated cases) would have been positive and been treated.
Prevalence rates for TB depend on the patient population, screening methods and TB case definitions employed. The 12% point prevalence of TB treatment in our study compares to rates of 3–12% in other studies among HIV- infected persons living in TB endemic countries [12, 13, 17–22]. A recent study from South Africa using chest x-ray, sputum culture and a clinical definition category for TB found that 11% of subjects in an ART program had previously undiagnosed TB at baseline and that rates of incident TB in those on ART for 3 years continued to be 5–10 fold higher than those for HIV-uninfected persons living in the same region .
Microbiologic studies confirmed the diagnosis of TB in 31% of those with suspect disease. Our relatively low rate of positive sputum cultures for TB might have been influenced by overly vigorous decontamination of sputum specimens as suggested by our low sputum culture contamination rate of 1%. However, by routinely performing sputum microbiology in this population, including in those without symptoms, we were able to identify a unique group of subjects with "subclinical TB", i.e., active, culture-positive disease without symptoms (including study definition symptoms as well as absence of additional symptoms such as weight loss or fever <2 weeks) or x-ray findings. A previous report from our study focused on 10 such patients whom we encountered among the initial 500 subjects screened; that report also presented detailed data to eliminate the possibility of false positive cultures and follow-up data to indicate that the early treatment was associated with a more favorable prognosis than typically seen with HIV-associated tuberculosis . The 13 patients in the present series comprise 9% of all patients treated for TB. Rates of subclinical TB might be found to be even higher if more sensitive liquid based media had been used for sputum culture . Investigators in Uganda, India, New York and London have also described HIV-infected subjects with subclinical forms of TB [7, 24–26]; in some of these studies "subclinical" includes any active disease without symptoms, regardless of chest x-ray findings.
Sputum culture not only makes an important contribution to the diagnosis of both clinical and subclinical TB in patients with HIV [20, 25]. It will also be an increasingly important TB diagnostic tool for another reason: the detection and spread of XDR TB in sub-Sarharan Africa . As we showed previously in Kenya  and others have confirmed , blood culture for M. tuberculosis may make an additional contribution in hospitalized patients with advanced and symptomatic HIV infection but did not contribute to detection of TB in ambulatory subjects with earlier stage HIV infection.
Our overall study is focused on ambulatory HIV-infected persons with CD4 = 200 residing in an area with endemic tuberculosis. We believe our subjects are generally representative of such patients, although there are potential sources of bias. Conceivably, persons with subtle or unreported symptoms of TB might have been preferentially drawn to a TB vaccine trial. Conversely, because all subjects had received BCG at birth, this could have reduced the rate of active TB. In general populations, BCG immunization does not typically affect adult TB rates  and among HIV-infected persons limited retrospective data is conflicting [30, 31].
Our goal in this report was to describe the frequency and characteristics of subjects who were judged by TB clinicians to require treatment for presumptive TB at the time of screening. Our evaluations were conducted by trained, experienced local physicians, supported by expert radiologic interpretation, albeit by a single radiologist aware of the suspicion of TB. In a study from the United States expert radiologists agreed on chest x-ray suspicion of tuberculosis in 139 subjects (HIV status not stated) approximately 70% of the time, and this suspicion appeared to accurately identify smear negative tuberculosis in 48% of cases . We cannot confirm that all patients treated for TB without microbiologic confirmation had active disease because they were ineligible for our vaccine study and did not have follow-up to assess response to therapy. Current microbiologic methods often fail to confirm disease in subjects who have classic TB symptoms with x-ray changes and subsequent radiologic and clinical response to therapy for TB. In other published series of HIV-associated TB 19–66% of subjects have met a "clinical" definition of TB with negative microbiology [21, 33, 34].