Abstract
BackgroundCases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges.Methods and FindingsBetween February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3). HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals.ConclusionWe found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay.
Highlights
Southern Africa has experienced steeply rising TB incidence rates driven by the HIV epidemic, and carries over threequarters of the global burden of HIV-positive TB cases [1,2]
The mounting evidence of low sensitivity of smear microscopy [6] and the high mortality, loss to follow-up and rate at which clinical deterioration occurs during diagnostic work up of HIV-positive smear negative TB suspects [7,8] prompted a recent change in international management guidelines
Baseline characteristics and follow-up Between February 21, 2006 and June 6 2007, 5731 adults participated in the cluster-randomised parent study, and had two negative sputum smears
Summary
Southern Africa has experienced steeply rising TB incidence rates driven by the HIV epidemic, and carries over threequarters of the global burden of HIV-positive TB cases [1,2]. The mounting evidence of low sensitivity of smear microscopy [6] and the high mortality, loss to follow-up and rate at which clinical deterioration occurs during diagnostic work up of HIV-positive smear negative TB suspects [7,8] prompted a recent change in international management guidelines. In 2007, new guidelines [9] for use in settings with generalised HIV epidemics promoted diagnostic HIV testing of TB suspects, earlier use of radiography, increased access to sputum culture, a lower threshold for starting TB treatment in HIV-infected patients, and greater recognition of the symptoms of extra-pulmonary and disseminated TB (such as rapid weight loss and night sweats) in addition to chronic cough. Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges
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