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My research

Introduction

This project focuses on the zoonotic visceral leishmaniasis (ZVL). Induced by protozoan flagellates parasites (L. infantum), this disease is transmitted from animal to vector to human, especially in tropical and subtropical areas, as well as in the Mediterranean basin, where the infection is endemic (Alvar, J. et al., 2012).

Animal reservoir hosts, along with sand flies, maintain the cycle in L. infantum-endemic regions where dogs are the only proven reservoir (Courtenay et al., 2014; Quinnell et al., 2009). As the infection is life threatening in absence of treatment, and in order to reduce mortality and case-fatality rates, endemic countries such as Brazil set up specific measures including early diagnosis and treatment of human cases, vector control with insecticides, reservoir (mainly dogs) control, and health education (Ministerio da Saude, Brazil, 2006).

To combat canine transmission, dogs are serologically screened for anti-Leishmania antibodies and positives subsequent culled. However, there is no scientific evidence indicating that dog culling reduces the incidence of the disease in humans (Costa et al., 2008). Consequently the mass slaughter policy is questioned on theoretical, scientific and ethical grounds. The current serological diagnostic tests have shown a too low performance to be used for large-scale epidemiological studies and control programmes. Current diagnostic tests focus on detecting infection, which means the presence of Leishmania antibodies in the blood. However, this can represent previous exposure to Leishmania, current infection, or/and current or latent infectious. Antibody titers do not decay rapidly following interruption of exposure or cure. Furthermore, not all dogs are equally infectious: most dogs never become infectious to sandflies vectors (Courtenay et al., 2002; Courtenay et al., 2014). In one longitudinal study specifically addressing this issue, only 43% of infected dogs become infectious, and a much smaller proportion of dogs (17%) were highly infectious. Those highly infectious dogs were responsible for more than 80% of all transmission to sand flies; these are labeled as “super-spreaders” (Stein, 2011). The further effect of killing seropositive dogs is that it increases the rate of dog population turnover because owners tend to replace removed dogs with newly susceptible puppies (Nunes et al., 2008), a proportion of these can become infectious.

The proportion of infectious dogs have a strong impact on the success of control strategies (Costa et al., 2013). According to Quinnell and Courtenay (2009), the efficacy of the dog culling strategy would be increased if only those dogs that were infectious could be identified in the

This PhD project aims to develop a serological assay on a rapid test platform with improved specificity with respect to infectiousness. A range of Leishmania antigens and combination antigen candidates will be tested including provided by IDRI (Infectious Diseases Research Institute).

Specific Objectives

This PhD project aims to test novel antigens or/and antigen combinations towards developing a more specifics tests to identify “super-spreaders” in the mixed canid population. In conjunction with mathematical modelling, the performance of these tests under varying epidemiological scenarios to reduce transmission will be explored for potential field efficacy.

(1) to prototype diagnostic assay development and evaluate novel antigens and antigen combinations to improve the specificity of a potential “roll-out” serological test to target super-spreaders.

(2) to adapt the antigen test to a rapid diagnostic test platform in collaboration with IDRI (Infectious Disease Research Institute) and InBios International, in Seattle, USA.

(3) to use these results in quantitative models to identify optimal testing regimes to impact on transmission to reduce infection. The novel data will be used to help parameterise future mathematical models:
(3.1) to predict the potential efficacy of new antigen RDT to reduce transmission;
(3.2) to plug some of the identified data gaps of current transmission and control models.