Interpreting ambiguous 'trace' results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard.

Sarah C L Knowles,Fiona M Fleming,Aboulaye Meité,Edridah Muheki Tukahebwa,Narcis B Kabatereine,Christl A Donnelly,Sarah Nogaro,Eliézer K N'Goran,Michelle N Clements,Yolisa Nalule,Alan Fenwick,Anna E Phillips

doi:10.1371/journal.pntd.0006102

Abstract

BackgroundThe development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results.Methodology/Principle findingsWe show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population.Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries.ConclusionsIncorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence.

Highlights

It is estimated that 237 million individuals require treatment for schistosomiasis [1]
Our results showed that cathodic antigen (CCA) with trace as positive most accurately estimated infection prevalence
Despite a growing body of studies looking at distribution (e.g. [2,3,4]), we do not have a true representation of the number of people infected with S. mansoni as there is no definitive ‘gold standard’ field diagnostic test

Summary

Introduction

It is estimated that 237 million individuals require treatment for schistosomiasis [1]. Accurate prevalence estimates of those infected are important, as even low infection intensities have associated morbidity [5]. Frequency of treatment and who receives the drugs are dependent on the prevalence of schistosomiasis in the local area [6], as determined by the parasitological diagnostic test Kato-Katz, where eggs are detected in faecal samples examined microscopically [7, 8]. Kato-Katz has low sensitivity in those with low infection intensities and in areas of low prevalence, as egg output varies both within and between days [9] and infection can be missed [10]. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results

Objectives

Results

Conclusion