SummaryWe examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term ʻT. gondii-rat manipulation-schizophrenia modelʼ and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.

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Toxoplasma gondii is an indirectly transmitted protozoan parasite, of which members of the cat family (Felidae) are the only definitive hosts and small mammals such as rats serve as intermediate hosts. The innate aversion of rodents to cat odor provides an obstacle for the parasite against successful predation by the feline definitive host. Previous research has demonstrated that T. gondii appears to alter a rat's perception of the risk of being preyed upon by cats. Although uninfected rats display normal aversion to cat odor, infected rats show no avoidance and in some cases even show attraction to cat odor, which we originally termed the "Fatal Feline Attraction." In this study, we tested for the first time whether the "Fatal Feline Attraction" of T. gondii-infected rats differed according to the type of feline odor used, specifically whether it came from domestic cats (Felis silvestris catus) or wild cats-cheetahs (Acinonyx jubatus) or pumas (Felis concolor). In two-choice odor trials, where wild and domestic cat odors were competed against one another, consistent with previous findings we demonstrated that infected rats spent more time in feline odor zones compared with uninfected rats. However, we further demonstrated that all cat odors are not equal: infected rats had a stronger preference for wild cat odor over that of domestic cats, an effect that did not differ significantly according to the type of wild cat odor used (cheetah or puma). We discuss these results in terms of the potential mechanism of action and their implications for the current and evolutionary role of wild, in addition to domestic, cats in transmission of T. gondii.

intervention impact (relative reduction in MSM HIV prevalence after 10 years: A: 18.2% (95% CI 11.0 to 29.2%), B: 18.1% (10.6 to 29.7%)). Conclusions The choice of method used to balance insertive and receptive contacts in an HIV transmission model affected the estimates for the amount of like-with-like mixing within different MSM groups, but the estimated impact of an intervention was robust to the method used. Background Cross-sectional surveys of female sex workers (FSW) in multiple districts in Southern India show a strong ecological association between HIV and HSV-2 prevalence. Modelling was used to determine if this association is primarily due to shared behavioural risk factors (such as partner change rate) or if biological interactions between the two viruses also play a major role. Methods Linear regression was used to find significant predictors of FSW HIV prevalence in 17 districts in Southern India (using data from Avahan, the India AIDS Initiative). Explanatory variables investigated included prevalence of different STIs in FSW and clients, mean duration of being an FSW or client, and mean reported number of clients per FSW or FSW visited per client. A deterministic HIV/HSV-2 transmission model without behavioural heterogeneity or transmission co-factors was parameterised using district-specific FSW and client behavioural data and fitted to HIV and HSV-2 prevalence data for each district by varying the per partnership HIV and HSV-2 transmission probabilities. The model was firstly fit to all districts simultaneously assuming a constant HIV and HSV-2 transmission probability to see whether district-level variations in behaviour were sufficient to explain the trends seen, and then fit separately for each district to test for trends in the estimated transmission parameters in different settings. Results FSW HSV-2, syphilis, gonorrhoea and chlamydia prevalence, client HIV prevalence and mean number of clients per FSW per week P1-

Latent infection with the common intracellular protozoan parasite Toxoplasma gondii has been shown to result in altered behaviour of its host. This behaviour manipulation has been proposed to increase predation of the intermediate host (e.g. rodents and birds) enhancing parasite transmission. Other psychologicalsequalae have also been associated with latent toxoplasmosis including human affective disorders, as human are accidental hosts for Toxoplasma. During cyst stages of the life cycle found in the brain and other tissues, there is a complex interaction between the parasite and the host. Our research is concerned with the possibility that the parasite-induced behavioural changes are mediated by neurotransmitters. Potential factors in neurotransmitter levels include the location of the cyst, the host immune response, and direct parasite products. The cyst is found in many brain regions but elevated numbers have been reported in the hippocampus, amygdala, and nucleus accumbens. The host response involves interferon gamma suppressing growth through tryptophan degradation that could decrease serotonin levels. The parasite could directly manipulate the host brain through altering dopamine levels. We have found a change in dopamine associated with infection. Indeed, the parasite itself encodes the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase. Dopamine's role is also supported by finding haloperidol, a dopamine antagonist, blocks manipulation of rodents by Toxoplasma. Our current investigations of alterations in neurotransmitter levels during chronic infection and association with brain cysts will be presented. Our data presents an interesting interplay with the ‘dopamine hypothesis’ that has postulated a link between elevated dopamine and schizophrenia.

IntroductionRecognition of the role of infectious agents in a range of both acute and chronic diseases is increasing. One key example is the potential epidemiological and neuropathological association between some cases of schizophrenia with the protozoan Toxoplasma gondii. T. gondii establishes persistent infection within the CNS and can alter host behaviour. Altered dopamine levels have been reported for both T. gondii infection and schizophrenia. Several medications used to treat schizophrenia demonstrate anti-T. gondii properties, and haloperidol, a dopamine antagonist, can prevent the development of T. gondii-altered behaviour in rodents. Furthermore, T. gondii may actually be a source of dopamine, as it encodes a copy of the mammalian enzyme tyrosine hydroxylase, which represents the rate-limiting step in dopamine synthesis.AimsUsing the epidemiologically and clinically applicable rat-T. gondii model, and incorporating a battery of classical and novel non-invasive behavioural and physiological assays, we aim to further elucidate the impact of T. gondii on behaviour and the mechanisms involved.ResultsT. gondii increases the rats’ propensity for predation risk through enhanced activity, visibility and manipulation of their perception of predation risk, turning innate aversion into a ‘suicidal’ feline attraction. There is little indication that T. gondii alters the rats generalized anxiety, nor potential to enhanced predation by non-definitive mammalian host species. Preliminary associative analyses into the relationship between individual behavioural alterations and neurotransmitter and brain cysts localisation profiles will be presented.ConclusionsOur results provide further evidence for a role of T. gondii in the aetiology of some cases of schizophrenia.

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