title: Rapid antigen detection tests for malaria diagnosis in severely ill Papua New Guinean children: a comparative study using Bayesian latent class models.
abstract: BACKGROUND
  Although rapid diagnostic tests (RDTs) have practical advantages over light microscopy (LM) and good sensitivity in severe falciparum malaria in Africa, their utility where severe non-falciparum malaria occurs is unknown. LM, RDTs and polymerase chain reaction (PCR)-based methods have limitations, and thus conventional comparative malaria diagnostic studies employ imperfect gold standards. We assessed whether, using Bayesian latent class models (LCMs) which do not require a reference method, RDTs could safely direct initial anti-infective therapy in severe ill children from an area of hyperendemic transmission of both Plasmodium falciparum and P. vivax.
  
  
  RESULTS
  We studied 797 Papua New Guinean children hospitalized with well-characterized severe illness for whom LM, RDT and nested PCR (nPCR) results were available. For any severe malaria, the estimated prevalence was 47.5% with RDTs exhibiting similar sensitivity and negative predictive value (NPV) to nPCR (≥96.0%). LM was the least sensitive test (87.4%) and had the lowest NPV (89.7%), but had the highest specificity (99.1%) and positive predictive value (98.9%). For severe falciparum malaria (prevalence 42.9%), the findings were similar. For non-falciparum severe malaria (prevalence 6.9%), no test had the WHO-recommended sensitivity and specificity of >95% and >90%, respectively. RDTs were the least sensitive (69.6%) and had the lowest NPV (96.7%).
  
  
  CONCLUSIONS
  RDTs appear a valuable point-of-care test that is at least equivalent to LM in diagnosing severe falciparum malaria in this epidemiologic situation. None of the tests had the required sensitivity/specificity for severe non-falciparum malaria but the number of false-negative RDTs in this group was small.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors.forename: Laurens
authors.initials: L
authors.lastname: Manning
authors.forename: Moses
authors.initials: M
authors.lastname: Laman
authors.forename: Anna
authors.initials: A
authors.lastname: Rosanas-Urgell
authors.forename: Berwin
authors.initials: B
authors.lastname: Turlach
authors.forename: Susan
authors.initials: S
authors.lastname: Aipit
authors.forename: Cathy
authors.initials: C
authors.lastname: Bona
authors.forename: Jonathan
authors.initials: J
authors.lastname: Warrell
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology; D001499:Bayes Theorem; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D007223:Infant; D008288:Malaria / Q000175:diagnosis*; D008297:Male; D008390:Markov Chains; D009010:Monte Carlo Method; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D000953:Antigens, Protozoan