Research Article: Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

Date Published: January 27, 2009

Publisher: Public Library of Science

Author(s): Bruno Levecke, Nathalie De Wilde, Els Vandenhoute, Jozef Vercruysse, Juerg Utzinger

Abstract: BackgroundSoil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug efficacy estimates are scarce.Methodology/Principal FindingsIn the present study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0% [95% confidence interval (CI): 82.4–83.6%]) and the ether-based concentration technique (76.6% [95% CI: 75.8–77.3%]). McMaster was the least sensitive (61.7% [95% CI: 60.7–62.6%]) and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85–0.93; p<0.0001). However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus), followed by the ether-based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample). Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators.Conclusions/SignificanceThe results of this study demonstrated that McMaster is a promising technique when making use of FEC to monitor drug efficacy in Trichuris.

Partial Text: Worldwide, infections with soil-transmitted heminths (STHs) such as Trichuris trichiura, Ascaris lumbricoides and hookworms (Ancylostoma duodenale and Necator americanus) are of major importance for public health, particularly in tropical and subtropical countries where climate factors combined with poor environmental, domestic and personal hygiene ease transmission [1],[2]. Current efforts to control STH infections involve periodic mass drug treatment of people, particularly of school-aged children, in all endemic areas [3]. Since these large-scale interventions are likely to intensify as more attention is addressed to the importance of these neglected diseases [4], monitoring drug efficacy will become indispensable in order to detect the emergence of resistance [5],[6] and/or identify confounding factors affecting the drug efficacy [7]. Thus far, the efficacy of anthelmintics has mostly been monitored qualitatively based on the cure rate. However, the fecal egg count reduction test (FECRT) is presently under examination for monitoring the drug efficacy quantitatively [8], implying the need for a sensitive detection technique which will allow the accurate estimation of the infection intensity based on fecal egg counts (FEC). Various techniques have been used for the detection of STH eggs, yet studies comparing detection techniques based on FEC are scarce. Moreover, little attention has been addressed to their feasibility for mass diagnosis under field conditions (poorly equipped laboratories and short of professionally trained personnel) and their ability to estimate the efficacy of administered drugs, in particular in different settings of pre-drug administration infection intensities.

In the present study, four techniques were compared for the qualitative and quantitative detection of Trichuris in stools of nonhuman primates, as well as their feasibility for mass diagnosis under field conditions. In addition, their ability to give accurate estimates of the ‘true’ drug efficacy was studied based on a statistical simulation. Overall, the observed prevalence of Trichuris in these animals was 47% (95% CI: 37–57%) and remained unchanged when the test results of the 4 techniques were combined. Although the test properties might be overestimated due to the absence of a diagnostic ‘gold’ standard, it is clear that FLOTAC is the most sensitive technique, followed by the Parasep SF and the ether-based concentration technique. McMaster is the least sensitive, because it often fails to detect low FECs due to its relative high detection limit (50 EPG). Multiple comparisons of the 4 techniques revealed a linear correlation in FEC. Nevertheless, both the Parasep SF and ether techniques are likely to be less appropriate for an accurate estimation of FEC, since the McMaster and the FLOTAC detected significantly more eggs.



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