Mathematical modelling of Echinococcus multilocularis abundance in foxes in Zurich, Switzerland

Background In Europe, the red fox (Vulpes vulpes) is the main definitive host of Echinococcus multilocularis, the aetiological agent of a severe disease in humans called alveolar echinococcosis. The distribution of this zoonotic parasite among the fox population is remarkably aggregated with few heavily infected animals harbouring much of the parasite burdens and being responsible for most of the environmental parasitic egg contamination. Important research questions explored were: (i) spatial differences in parasite infection pressure related to the level of urbanization; (ii) temporal differences in parasite infection pressure in relation to time of the year; (iii) is herd immunity or an age-dependent infection pressure responsible for the observed parasite abundance; (iv) assuming E. multilocularis infection is a clumped process, how many parasites results from a regular infection insult. Methods By developing and comparing different transmission models we characterised the spatio-temporal variation of the infection pressure, in terms of numbers of parasites that foxes acquired after exposure per unit time, in foxes in Zurich (Switzerland). These included the variations in infection pressure with age of fox and season and the possible regulating effect of herd immunity on parasite abundance. Results The model fitting best to the observed data supported the existence of spatial and seasonal differences in infection pressure and the absence of parasite-induced host immunity. The periodic infection pressure had different amplitudes across urbanization zones with higher peaks during autumn and winter. In addition, the model indicated the existence of variations in infection pressure among age groups in foxes from the periurban zone. Conclusions These heterogeneities in infection exposure have strong implications for the implementation of targeted control interventions to lower the intensity of environmental contamination with parasite eggs and, ultimately, the infection risk to humans

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Latent class models for Echinococcus multilocularis diagnosis in foxes in Switzerland in the absence of a gold standard

Background: In Europe the principal definitive host for Echinococcus multilocularis, causing alveolar echinococcosis in humans, is the red fox (Vulpes vulpes). Obtaining reliable estimates of the prevalence of E. multilocularis andrelevant risk factors for infection in foxes can be difficult if diagnostic tests with unknown test accuracies are used. Latent-class analysis can be used to obtain estimates of diagnostic test sensitivities and specificities in the absence of a perfect gold standard. Samples from 300 foxes in Switzerland were assessed by four different diagnostic tests including necropsy followed by sedimentation and counting technique (SCT), an egg-PCR, a monoclonal and a polyclonal copro-antigen ELISA. Information on sex, age and presence of other cestode species was assessed as potential covariates in the Bayesian latent class models. Different Bayesian latent-class models were run, considering dichotomized test results and, additionally, continuous readings resulting in empirical ROC curves. Results: The model without covariates estimated a true parasite prevalence of 59.5% (95% CI: 43.1–66.4%). SCT, assuming a specificity of 100%, performed best among the four tests with a sensitivity of 88.5% (95% CI: 82.7–93.4%). The egg-PCR showed a specificity of 93.4% (95% CI: 87.3–99.1%), although its sensitivity of 54.8% was found moderately low (95% CI: 48.5–61.0%). Relatively higher sensitivity (63.2%, 95% CI: 55.3–70.8%) and specificity (70.0%, 95% CI: 60.1–79.4%) were estimated for the monoclonal ELISA compared to the polyclonal ELISA with a sensitivity and specificity of 56.0% (95% CI: 48.0–63.9%) and 65.9% (95% CI: 55.8–75.6%), respectively. In the Bayesian models, adult foxes were found to be less likely infected than juveniles. Foxes with a concomitant cestode infection had double the odds of an E. multilocularis infection. ROC curves following a Bayesian approach enabled the empirical determination of the best cut-off point. While varying the cut-offs of both ELISAs, sensitivity and specificity of the egg-PCR and SCT remained constant in the Bayesian latent class models. Conclusions: Adoption of a Bayesian latent class approach helps to overcome the absence of a perfectly accurate diagnostic test and gives a more reliable indication of the test performance and the impact of covariates on the prevalence adjusted for diagnostic uncertainty

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Dynamics of the force of infection: insights from echinococcus multilocularis infection in foxes

Characterizing the force of infection (FOI) is an essential part of planning cost effective control strategies for zoonotic diseases. Echinococcus multilocularis is the causative agent of alveolar echinococcosis in humans, a serious disease with a high fatality rate and an increasing global spread. Red foxes are high prevalence hosts of E. multilocularis. Through a mathematical modelling approach, using field data collected from in and around the city of Zurich, Switzerland, we find compelling evidence that the FOI is periodic with highly variable amplitude, and, while this amplitude is similar across habitat types, the mean FOI differs markedly between urban and periurban habitats suggesting a considerable risk differential. The FOI, during an annual cycle, ranges from (0.1,0.8) insults (95% CI) in urban habitat in the summer to (9.4, 9.7) (95% CI) in periurban (rural) habitat in winter. Such large temporal and spatial variations in FOI suggest that control strategies are optimal when tailored to local FOI dynamics

Additional file 8: Figure S1. of Latent class models for Echinococcus multilocularis diagnosis in foxes in Switzerland in the absence of a gold standard

Polyclonal ELISA ROC curves produced using the classical and the Bayesian approach (4 tests). (TIFF 501 kb

Additional file 2: Text S2. of Mathematical modelling of Echinococcus multilocularis abundance in foxes in Zurich, Switzerland

R code. (DOC 44 kb

Additional file 1: Data S1. of Mathematical modelling of Echinococcus multilocularis abundance in foxes in Zurich, Switzerland

File containing original data. (XLSX 20 kb