title: Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease.
abstract: BACKGROUND
  The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available.
  
  
  OBJECTIVE
  To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas.
  
  
  METHODS
  We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits.
  
  
  METHODS
  This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis.
  
  
  METHODS
  Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards.
  
  
  RESULTS
  Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and rKE16 ICT) recruiting 4271 participants (2605 with VL) were included. We carried out a meta-analysis for the rK39 ICT (including 18 studies; 3622 participants) and the latex agglutination test (six studies; 1374 participants). The results showed considerable heterogeneity. For the rK39 ICT, the overall sensitivity was 91.9% (95% confidence interval (95% CI) 84.8 to 96.5) and the specificity 92.4% (95% CI 85.6 to 96.8). The sensitivity was lower in East Africa (85.3%; 95% CI 74.5 to 93.2) than in the Indian subcontinent (97.0%; 95% CI 90.0 to 99.5). For the latex agglutination test, overall sensitivity was 63.6% (95% CI 40.9 to 85.6) and specificity 92.9% (95% CI 76.7 to 99.2).
  
  
  CONCLUSIONS
  The rK39 ICT shows high sensitivity and specificity for the diagnosis of visceral leishmaniasis in patients with febrile splenomegaly and no previous history of the disease, but the sensitivity is notably lower in east Africa than in the Indian subcontinent. Other rapid tests lack accuracy, validation, or both.
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.forename: Kristien
authors.initials: K
authors.lastname: Verdonck
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.forename: Temmy
authors.initials: T
authors.lastname: Sunyoto
authors.forename: Johan
authors.initials: J
authors.lastname: van Griensven
authors.forename: Francois
authors.initials: F
authors.lastname: Chappuis
authors.forename: Suman
authors.initials: S
authors.lastname: Rijal
mesh_terms: D000351:Africa, Eastern; D000372:Agglutination Tests / Q000379:methods*; D000953:Antigens, Protozoan / Q000032:analysis*; D058345:Asymptomatic Infections; D015415:Biomarkers / Q000032:analysis; D002846:Chromatography, Affinity / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007194:India; D007841:Latex Fixation Tests / Q000379:methods; D007898:Leishmaniasis, Visceral / Q000175:diagnosis*; D009390:Nepal; D015800:Protozoan Proteins / Q000032:analysis*; D012680:Sensitivity and Specificity
chemical_list: D000953:Antigens, Protozoan; D015415:Biomarkers; D015800:Protozoan Proteins; C079253:K39 antigen, Leishmania