1.8.1 Study setting
As described above, an epidemic of human echinococcosis appears to be developing in Kyrgyzstan, due to factors associated with independence from the Soviet Union over 20 years ago (Torgerson et al., 2003a), with indications that Kyrgyzstan may be a substantial focus of E. multilocularis transmission in particular (Usubalieva et al., 2013; Giraudoux et al., 2013b; Torgerson et al., 2015). Despite this, relatively little work has
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been conducted in Kyrgyzstan, especially in the southern districts of Osh province, which appear to have a high prevalence of human alveolar echinococcosis (Professor Bakhadyr Bebezov, Kyrgyz-Russian Slavic University, personal communication). Following on from pilot studies in the area, a decision was made to conduct a multidisciplinary study of echinococcosis in the area: focussing on canine infection, human infection and rodent infection/distribution. Along with the original two villages of Sary-Mogol and Taldu-Suu, two additional villages were visited: Kashka’Suu (Кашка’Суу) and Kara-Kabak (Кара-Кабак); both of which are located to the west of Sary-Mogol and Taldu-Suu, in the adjacent district of Chon-Alay. Although these villages are further from Osh (around 220km), they are considerably closer to their raion capital, Daroot-Korgon (around 40km away).
In May and October 2012, dogs in these four villages were registered and faecal samples collected. Dogs in Sary-Mogol and Taldu-Suu were given praziquantel, and those in the other two did were not given praziquantel. Coincidentally, a World Bank– funded canine praziquantel dosing campaign (World Bank, 2010) was commenced in the area in late 2012, and offered an opportunity to investigate the epidemiology of Echinococcus spp in this area. Praziquantel dosing continued in all four villages under this campaign, which continued for the remainder of the study (until September 2014). Faecal samples were collected from dogs in all four villages twice annually over this time.
1.8.2 Study aims
The central aims of the current study are to investigate the epidemiology of Echinococcus spp infection amongst dogs in rural communities in the Alay valley, evaluate an ongoing praziquantel-based control scheme, and identify possible methods of improving surveillance and control in remote areas such as those in the Alay valley. This latter focus is the major thesis aim, since whilst surveillance is well accepted to be a central component of any control scheme, little work to date has investigated how to achieve this in the remote, rural communities most impacted by echinococcosis, and where obtaining high quality data will be challenging.
58 1.8.3 Chapter description
Chapter 2 describes the collection, testing, and initial interpretation of faecal samples
over the 28 months of the study. All samples underwent coproantigen ELISA testing (Deplazes et al., 1992; Allan et al., 1992), which gives an optical density (OD) value for each sample. Evaluation and identification of methods of interpretation of this output was the main focus of chapters 3 and 4. A selection of samples also underwent coproPCR testing, using three primers: two of which have been previously described (Boufana et al., 2013), and one of which was developed as part of the current work (van Kesteren, 2015). A method of combining PCR results with coproELISA results was investigated in chapter 5, and both PCR and ELISA data were interpreted independently in chapter 6.
Chapter 3 describes an evaluation of different strategies for determination of a cut-off
value for coproELISA OD data. This was evaluated using faecal samples collected from dogs of known Echinococcus status (as identified by necropsy) in Xinjiang province (van Kesteren et al., 2015). Different approaches were then applied to a number of samples of unknown status in order to evaluate the effects of differences in cut-off on the estimated coproprevalence and the adjusted true prevalence of infection.
Chapter 4 develops a novel strategy for interpretation of coproantigen ELISA data
which does not depend upon dichotomisation, using a Bayesian mixture model. This approach uses a panel of concurrently tested samples of suspected negative status to estimate the probability of any individual sample being a true ‘positive’ sample, and also gives an estimate of the true prevalence of infection amongst the samples tested. This output is then combined with the output of a Bayesian logistic regression in order to allocate a score relating to the expected log worm burden to each sample. This approach therefore can allow extra information to be obtained from the coproantigen test.
Chapter 5 describes a method of combining the results of ELISA and PCR testing
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analysis was conducted on the individual dog data collected prior to the start of the control scheme in order to broadly identify dog types, and associations between these and the results of diagnostic testing were identified. It is hoped that strategies such as this will help to better characterise communities and improve ongoing surveillance and control.
Chapter 6 describes a logistic regression analysis of trends in coproantigen and
coproPCR prevalence over time, during the control scheme. As individual dog identity was not known for individual samples, data were aggregated by household, which may offer a useful strategy for evaluation of control schemes in areas with multi-dog households where it is not possible to sample individual dogs directly.
Chapter 7 details a framework for a novel mathematical model of Echinococcus
transmission in areas coendemic for both E. granulosus (sensu lato) and E. multilocularis, incorporating seasonal effects and prepatent periods prior to fertility in the intermediate and definitive host. Whilst most of the chapter discusses the model framework and parameterisation, simulation outputs for trends over time in the presence and absence of dog dosing strategies are shown and described.
Chapter 8 gives an overview of the thesis, drawing general conclusions from the
previous chapters and details possible strategies for ongoing surveillance and control in Kyrgyzstan. Areas worthy of further work and investigation are also described.
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