title: The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.
abstract: BACKGROUND
  In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy.
  
  
  OBJECTIVE
  The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes.
  
  
  METHODS
  A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm.
  
  
  RESULTS
  Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms.
  
  
  CONCLUSIONS
  The results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.
authors.affiliation: Northern State Medical University, Arkhangelsk, Russian Federation.
authors.forename: Platon
authors.initials: P
authors.lastname: Eliseev
authors.affiliation: Northern Arctic Federal University, Arkhangelsk, Russian Federation.
authors.forename: Grigory
authors.initials: G
authors.lastname: Balantcev
authors.affiliation: Arkhangelsk Clinical Antituberculosis Dispensary, Arkhangelsk, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Nikishova
authors.affiliation: Arkhangelsk Clinical Antituberculosis Dispensary, Arkhangelsk, Russian Federation.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Gaida
authors.affiliation: Northern Arctic Federal University, Arkhangelsk, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Bogdanova
authors.affiliation: The International Union Against Tuberculosis and Lung Disease, Paris, France.
authors.forename: Donald
authors.initials: D
authors.lastname: Enarson
authors.affiliation: The International Union Against Tuberculosis and Lung Disease, Paris, France.
authors.forename: Tara
authors.initials: T
authors.lastname: Ornstein
authors.affiliation: The International Union Against Tuberculosis and Lung Disease, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Detjen
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Russell
authors.initials: R
authors.lastname: Dacombe
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Gospodarevskaya
authors.affiliation: MRC Clinical Trials Unit at UCL, London, United Kingdom.
authors.forename: Patrick P J
authors.initials: PP
authors.lastname: Phillips
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mann
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Stephen Bertel
authors.initials: SB
authors.lastname: Squire
authors.affiliation: Northern State Medical University, Arkhangelsk, Russian Federation.
authors.forename: Andrei
authors.initials: A
authors.lastname: Mariandyshev
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012426:Russia / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*