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. 2017 Dec 8;11(12):e0006102.
doi: 10.1371/journal.pntd.0006102. eCollection 2017 Dec.

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

Michelle N Clements  1 , Christl A Donnelly  2 , Alan Fenwick  1 , Narcis B Kabatereine  3 , Sarah C L Knowles  1   4 , Aboulaye Meité  5 , Eliézer K N'Goran  6 , Yolisa Nalule  1 , Sarah Nogaro  1 , Anna E Phillips  1 , Edridah Muheki Tukahebwa  7 , Fiona M Fleming  1
Affiliations

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

Michelle N Clements et al. PLoS Negl Trop Dis. .

Abstract

Background: The 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 findings: We 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.

Conclusions: Incorporation 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Bar chart showing the proportion of children tested in each country with specified test results.
For example, ‘pos/pos’ denotes the proportion of children in each country testing positive for both tests, and ‘pos/tr’ denotes the proportion of children in each country testing positive by Kato-Katz and trace by CCA. Note that the bar showing the proportion of children negative on both tests (75% in Côte d’Ivoire and 76% in Uganda) has been removed from the graph to enable easier comparison of non-negative results.
Fig 2
Fig 2. Plots showing the posterior distributions of sensitivity (left) and specificity (right) of each test in Côte d’Ivoire (blue) and Uganda (green) estimated from a Bayesian Latent Class Analysis.
Note that the x-axis for the specificity has been truncated to begin at 80% to enable easier comparison between tests.
Fig 3
Fig 3. Estimated infection prevalence and tests prevalence from each test in Côte d’Ivoire and Uganda obtained from LCA.
See this image and copyright information in PMC

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