Tuberculosis Transmission from Patients with Smear‐Negative Pulmonary Tuberculosis in Sub‐Saharan Africa

To the Editor—We read with interest the report by Tostmann et al. [1] of a national study of tuberculosis (TB) transmission in The Netherlands from 1996 through 2004. The relative TB transmission rate among patients with smear-negative, culture-positive pulmonary disease, compared with patients with smear-positive disease, was found to be 0.24. Overall, 13% of TB transmission events were attributable to source patients with sputum smear-negative, culture-positive disease. These important findings are in close agreement with similar studies from San Francisco, California, and Vancouver, British Columbia [2, 3], collectively showing that in high-income countries, 10%–20% of TB transmission at the population level is attributable to source cases with smear-negative pulmonary TB. Tostmann et al. [1] speculated on the relevance of their data for countries in which HIV infection is endemic and rates of smear-negative TB disease are high. In sub-Saharan Africa, HIV infection has had a devastating impact on TB control [4, 5]. In a study of a community in a township in Cape Town, South Africa, for example, the antenatal HIV seroprevalence rate is ∼30%, and the annual TB notification rate has increased to >1500 cases per 100,000 population [5]—almost 200-fold higher than TB rates in The Netherlands [4]. This has been associated with a major and disproportionate increase in the rate of smear-negative disease among HIV-infected individuals [5]. Moreover, the prevalence of undiagnosed TB (a key determinant of transmission) among HIV-infected patients in this community is very high, and disease duration before diagnosis is prolonged [6]. In view of these observations, transmission attributable to smear-negative pulmonary TB cases at the community level may be important. Antiretroviral treatment services continue to expand in sub-Saharan Africa [7]. The high burden of TB in these clinical settings presents a great challenge with regard to morbidity, mortality, and risk of TB transmission [8, 9]. Nosocomial outbreaks of both drug-susceptible and drug-resistant TB virus constitute a major threat [10]. In a recent study in an antiretroviral treatment service in Gugulethu Township, Cape Town, we did routine microbiological screening for TB in all newly referred antiretroviral treatment–naive patients who had not already received a diagnosis of TB. Using automated MGIT 960 liquid culture (Becton Dickinson) of sputum, we found that >25% of patients had culture-confirmed pulmonary TB [11]. In this highly immunocompromised patient group, however, >80% of this disease was sputum smear-negative despite use of fluorescence microscopy; culture-based diagnosis took >3 weeks, on average. Recurrent attendance of patients at these overcrowded facilities over a period of several weeks while their TB remains undiagnosed represents an unacceptable hazard. These data have important implications for screening for TB among patients entering HIV care and treatment services in Africa. Rapid and appropriate diagnostic tests that are able to detect smear-negative pulmonary TB are urgently needed to reduce risk of transmission in these clinical environments. In summary, we suspect that TB transmission associated with smear-negative culture-positive TB in communities in Africa with high HIV prevalence may be important, especially in the context of antiretroviral treatment services, where this is the preponderant form of TB. Financial support.S.D.L. is funded by the Wellcome Trust, London, United Kingdom. R.W. is funded in part by the National Institutes of Health (RO1 A1058736-01A1) and Comprehensive International Program of Research on AIDS (1U19AI53217-01). Potential conflicts of interest.All authors: no conflicts.

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