Since tuberculosis was declared a global emergency in 1993 by the World Health Organization (WHO), new cases of tuberculosis and deaths from the disease have dropped dramatically in several countries with a high burden of the disease. (1) All six WHO regions are on track to meet the Millennium Development Goal target of reducing tuberculosis incidence and deaths from tuberculosis by half between 1990 and 2015 (1,2) and, with the sole exception of the African Region, all are on track to halve tuberculosis mortality rates) Nevertheless, the situation remains precarious. (3) Twenty-two predominantly low- and middle-income countries were estimated to account for 82% of the 5.7 million tuberculosis cases notified in 20101 and high rates of death from tuberculosis among people living with human immunodeficiency virus (HIV) infection prevail in much of sub-Saharan Africa. (4,5)
Rapid case identification of individuals with sputum smear-positive tuberculosis and rapid initiation of anti-tuberculosis chemotherapy are key to controlling tuberculosis (6) and are promoted as part of the DOTS strategy model of passive case-finding that has been adopted by most national tuberculosis programmes (NTPs). (7) From the patient's perspective, the tuberculosis diagnostic and care pathway (Fig. 1) begins with a recognition of symptoms that prompt care seeking. Individuals may drop out of care during the diagnostic process ("loss to follow-up during diagnostic period"), before initiating treatment ("pre-treatment loss to follow-up", formerly known as "initial default") or after treatment has begun. Patients diagnosed with smear-positive tuberculosis who do not initiate treatment represent an important failing in the provision of care. (8,9) High rates of mortality are reported in this group. (10) Moreover, bringing these patients into care could reduce tuberculosis transmission to others. (11) Patients with a diagnosis of tuberculosis who are lost to follow-up before they receive treatment are not included in routine reporting by NTPs. Thus, programme effectiveness may be overestimated. (8)
Efforts to improve tuberculosis case detection rates have centred on ensuring rapid treatment for all individuals diagnosed with smear-positive tuberculosis. (12,13) With this goal in mind, WHO has recently changed its policy, which now calls for two sputum specimens instead of three and same-day collection. (13,14) However, assessing the impact of these changes on linkage to treatment has been hampered by a lack of understanding of the extent of pre-treatment loss to follow-up (8) and of the patient, provider and health system factors that contribute to it. (15)
Although nearly 50 years have passed since high rates of pre-treatment loss to follow-up were first identified as a potential major contributor to the failure of tuberculosis control programmes, researchers and policy-makers have paid little attention to the fate of patients who do not access treatment after receiving a diagnosis of tub erculosis. (16,17,18) Indeed, the "Piot model" used to describe loss to care at different stages for any disease was first developed for tuberculosis. (18)
This study had two main objectives: (i) to systematically quantify pre-treatment loss to follow-up in low- and lower-middle income countries and in countries with a high burden of tuberculosis; and (ii) to describe the reasons for drop-out and the outcomes seen in individuals with a tuberculosis diagnosis who do not initiate treatment. A secondary objective was to assess the quality of the studies reporting on pre-treatment loss to follow-up.
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We followed PRISMA reporting guidelines for systematic reviews. (19) To define the points at which tuberculosis patients drop out of care, we developed the tuberculosis diagnostic and care pathway described in Fig. 1 using terms recommended recently that replace previously used terms such as "initial default". …