title: The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis.
abstract: BACKGROUND
  WHO estimates that a third of the world's population has latent tuberculosis infection and that less than 5% of those infected are diagnosed and treated to prevent tuberculosis. We aimed to systematically review studies that report the steps from initial tuberculosis screening through to treatment for latent tuberculosis infection, which we call the latent tuberculosis cascade of care. We specifically aimed to assess the number of people lost at each stage of the cascade.
  
  
  METHODS
  We did a systematic review and meta-analysis of study-level observational data. We searched MEDLINE (via OVID), Embase, and Health Star for observational studies, published between 1946 and April 12, 2015, that reported primary data for diagnosis and treatment of latent tuberculosis infection. We did meta-analyses using random and fixed effects analyses to identify percentages of patients with latent tuberculosis infection completing each step in the cascade. We also estimated pooled proportions in subgroups stratified by different characteristics of interest to assess risk factors for losses.
  
  
  RESULTS
  We identified 58 studies, describing 70 distinct cohorts and 748 572 people. Steps in the cascade associated with greater losses included completion of testing (71·9% [95% CI 71·8-72·0] of people intended for screening), completion of medical evaluation (43·7% [42·5-44·9]), recommendation for treatment (35·0% [33·8-36·4]), and completion of treatment if started (18·8% [16·3-19·7]). Steps with fewer losses included receiving test results, referral for evaluation if test positive, and accepting to start therapy if recommended. Factors associated with fewer losses were immune-compromising medical indications, being part of contact investigations, and use of rifamycin-based regimens.
  
  
  CONCLUSIONS
  We identify major losses at several steps in the cascade of care for latent tuberculosis infection. Improvements in management of latent tuberculosis will need programmatic approaches to address the losses at each step in the cascade.
  Canadian Institutes of Health Research.
authors: Montreal Chest Institute, McGill University, Montreal, QC, Canada.
authors: Hannah
authors: H
authors: Alsdurf
authors: Centre for International Health, University of Otago, Dunedin, New Zealand.
authors: Philip C
authors: PC
authors: Hill
authors: Global TB Programme, WHO, Geneva, Switzerland; Clinic of Infectious and Tropical Diseases, WHO Collaborating Center for TB/HIV and TB Elimination, University of Brescia, Brescia, Italy.
authors: Alberto
authors: A
authors: Matteelli
authors: Global TB Programme, WHO, Geneva, Switzerland.
authors: Haileyesus
authors: H
authors: Getahun
authors: Montreal Chest Institute, McGill University, Montreal, QC, Canada; Global TB Programme, WHO, Geneva, Switzerland. Electronic address: dick.menzies@mcgill.ca.
authors: Dick
authors: D
authors: Menzies
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D003266:Continuity of Patient Care; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy*; D059012:Lost to Follow-Up; D012294:Rifamycins / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D000995:Antitubercular Agents; D012294:Rifamycins; C023808:rifamycin SV; D007538:Isoniazid