title: Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?
abstract: BACKGROUND
  Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss.
  
  
  METHODS
  A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB.
  
  
  RESULTS
  Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9).
  
  
  CONCLUSIONS
  Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority.
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru. martin.lauraj@gmail.com.|Section of Infectious Diseases & Immunity & Wellcome Trust Imperial College Centre for Clinical Tropical Medicine, Imperial College London, London, UK. martin.lauraj@gmail.com.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Martin
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.
authors.forename: Martha H
authors.initials: MH
authors.lastname: Roper
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.|Section of Infectious Diseases & Immunity & Wellcome Trust Imperial College Centre for Clinical Tropical Medicine, Imperial College London, London, UK.|LSHTM TB Centre and Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Louis
authors.initials: L
authors.lastname: Grandjean
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.|Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.
authors.forename: Luz
authors.initials: L
authors.lastname: Caviedes
authors.affiliation: Section of Infectious Diseases & Immunity & Wellcome Trust Imperial College Centre for Clinical Tropical Medicine, Imperial College London, London, UK.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras, Lima, Peru.|LSHTM TB Centre and Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.|Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000328:Adult; D003955:Diagnostic Tests, Routine / Q000706:statistics & numerical data; D005260:Female; D015276:Health Care Rationing / Q000592:standards; D006295:Health Resources; D006297:Health Services Accessibility / Q000592:standards; D054624:Health Status Disparities; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000592:standards*; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000453:epidemiology*
keywords: Drug Susceptibility Testing; Microscopic-observation drug-susceptibility assay; Multidrug-resistant tuberculosis; Tuberculosis