Rapid antigen detection tests for malaria diagnosis in severely ill Papua New Guinean children: a comparative study using Bayesian latent class models

PLoS One. 2012;7(11):e48701. doi: 10.1371/journal.pone.0048701. Epub 2012 Nov 5.

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.

Methods and findings: 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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / immunology
  • Bayes Theorem
  • Child, Preschool
  • Female
  • Humans
  • Immunologic Tests*
  • Infant
  • Malaria / diagnosis*
  • Male
  • Markov Chains
  • Monte Carlo Method
  • Papua New Guinea
  • Plasmodium falciparum / immunology*
  • Plasmodium vivax / immunology*
  • Sensitivity and Specificity

Substances

  • Antigens, Protozoan

Grant support

This study was funded by a National Health and Medical Research Council (NHMRC) of Australia grant (#513782). The authors also acknowledge infrastructure support from the MalariaGen Genomic Epidemiology Network. ML was supported by a Fogarty Foundation scholarship, LM by a Basser scholarship from the Royal Australasian College of Physicians and an NHMRC scholarship, and TMED by an NHMRC Practitioner Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.