TAILIEUCHUNG - Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Before the advent of chemotherapy, tuberculosis was one of the major causes of death in both Western [1] and also several non- Western countries [2]. While effective chemotherapy for tuberculosis has been available since the 1950s (isoniazid (INH) was introduced in 1952, the less effective para-aminosalicylic acid (PAS) and streptomycin slightly earlier [3]) the prognosis of untreated tuberculosis is still of great importance, as many patients will not receive appropriate treatment because their condition was never properly diagnosed as tuberculosis. For example, both the Cambodian [4] and Vietnamese [5] prevalence survey show that only about 20% of tuberculosis-patients identified in these surveys were on treatment at the time of the survey | OPEN 3 ACCESS Freely available online PLosone Natural History of Tuberculosis Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients A Systematic Review Edine W. Tiemersma1 2 Marieke J. van der Werf1 2 Martien W. Borgdorff3 Brian G. Williams4 Nico J. D. Nagelkerke5 1 KNCV Tuberculosis Foundation The Hague The Netherlands 2Center for Infection and Immunity Amsterdam CINIMA Academic Medical Center University of Amsterdam Amsterdam The Netherlands 3 Cluster Infectious Disease Control Municipal Health Service GGD Amsterdam Amsterdam The Netherlands 4 South African Centre for Epidemiological Modelling and Analysis Stellenbosch South Africa 5 Department of Community Medicine Faculty of Medicine and Health Sciences UAE University Al Ain United Arab Emirates Abstract Background The prognosis specifically the case fatality and duration of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. MethodologyandPrincipalFindings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53 and 86 with a weighted mean of 70 . Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20 . The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year but their case fatality estimates of 70 for

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