Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.Author summary: Soil-transmitted helminths are categorised as a neglected tropical disease and comprise four dominant species (two hookworms, Trichuris trichuria & Ascaris lumbricoides) that affect the poorest people in the world. The World Health Organisation (WHO) has made great strides in reducing the morbidity induced by STH infections in pre-school aged and school-aged children through mass drug administration. Many countries are now considering moving from morbidity reduction in school-aged children to community-wide treatment with the aim of transmission elimination. These helminths reproduce sexually within a human host and therefore both male and female worms must be present to produce fertilized eggs. The density of female and male worms below which mating success is too low to sustain parasite populations is defined as the ‘breakpoint’ in transmission. Both the prevalence and intensity of infection are very low as this breakpoint is approached when worm numbers are highly aggregated in their distribution within the human host population. Consequently, it becomes increasingly challenging to identify infected individuals using standard microscopic diagnostic tools (such as Kato-Katz). New and more sensitive molecular diagnostics tools, such as qPCR, are a necessity in settings where communities are moving towards the interruption of transmission. This paper demonstrates that the threshold to declare interruption of transmission is 50% lower when microscopic techniques are applied compared with molecular techniques.