Joanne P. Webster

Biological and biomedical implications of the co-evolution of pathogens and their hosts

Co-evolution between host and pathogen is, in principle, a powerful determinant of the biology and genetics of infection and disease. Yet co-evolution has proven difficult to demonstrate rigorously in practice, and co-evolutionary thinking is only just beginning to inform medical or veterinary research in any meaningful way, even though it can have a major influence on how genetic variation in biomedically important traits is interpreted. Improving our understanding of the biomedical significance of co-evolution will require changing the way in which we look for it, complementing the phenomenological approach traditionally favored by evolutionary biologists with the exploitation of the extensive data becoming available on the molecular biology and molecular genetics of host–pathogen interactions.

Fatal attraction in rats infected with Toxoplasma gondii

We tested the hypothesis that the parasite Toxoplasma gondii manipulates the behaviour of its intermediate rat host in order to increase its chance of being predated by cats, its feline definitive host, thereby ensuring the completion of its life cycle. Here we report that, although rats have evolved anti–predator avoidance of areas with signs of cat presence, T. gondiis manipulation appears to alter the rats perception of cat predation risk, in some cases turning their innate aversion into an imprudent attraction. The selectivity of such behavioural changes suggests that this ubiquitous parasite subtly alters the brain of its intermediate host to enhance predation rate whilst leaving other behavioural categories and general health intact. This is in contrast to the gross impediments frequently characteristic of many other host–parasite systems. We discuss our results in terms of their potential implications both for the epidemiology of toxoplasmosis and the neurological basis of anxiety and cognitive processes in humans and other mammals.

The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism

The highly prevalent parasite Toxoplasma gondii manipulates its hosts behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasites life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.

Schistosomiasis: challenges for control, treatment and drug resistance.

Purpose of review Schistosomiasis is a parasitic disease that has recently attracted increased focus and funding for control. Despite shifts in global health policy towards the implementation of mass chemotherapeutic control programmes at the national scale in sub-Saharan Africa, however, many challenges still exist. Recent findings Publications reviewed for this article cover: the development of treatment strategies; the planning, implementation and impact of control programmes; the re-evaluation of the burden of schistosomiasis; improved tools for control; new drugs; the safety of treatment during pregnancy; and the development of resistance against praziquantel. Summary The morbidity due to schistosomiasis has been shown to be greater than was previously thought. The reduction in morbidity of schistosomiasis by control programmes has been demonstrated, while new tools include a validated dose pole for delivering the correct treatment, geographical information systems mapping for determining high-risk areas, and Lot Quality Assurance Sampling for determining treatment strategies at the local level. Sustainability and future funding are issues to be addressed. Despite some positive results, myrrh is apparently ineffective against schistosomiasis, but fortunately no resistance to praziquantel has developed. We predict the impact of schistosomiasis control will be a healthier generation of children within 5 years.

Bayesian spatial analysis and disease mapping: tools to enhance planning and implementation of a schistosomiasis control programme in Tanzania

Objective  To predict the spatial distributions of Schistosoma haematobium and S. mansoni infections to assist planning the implementation of mass distribution of praziquantel as part of an on‐going national control programme in Tanzania.

Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour

With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan Toxoplasma gondii. Reasons for this include T. gondiis ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated in vitro to possess anti-parasitic, and in particular anti-T. gondii, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their in vivo inhibition of T. gondii replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-T. gondii model system, and following a previously described and neurologically characterized ‘feline attraction’ protocol that haloperidol (an anti-psychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of T. gondii-associated behavioural and cognitive alterations as the standard anti-T. gondii chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while T. gondii appears to alter the rats’ perception of predation risk turning their innate aversion into a ‘suicidal’ feline attraction, anti-psychotic drugs prove as efficient as anti-T. gondii drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.

Rats, cats, people and parasites: the impact of latent toxoplasmosis on behaviour

The manipulation hypothesis states a parasite may alter host behaviour for its own benefit, often by enhancing its transmission rate through the food chain. This paper reviews studies on the potential impact of one parasite, Toxoplasma gondii, on host behaviour, both on rodents, where altered responses may be proposed to benefit the parasite, and humans, where altered responses may arise as a side-effect of infection with no current adaptive significance.

Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren

OBJECTIVE We aimed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003. METHODS We conducted longitudinal surveys on infection status, haemoglobin concentration and clinical morbidity in 1871 randomly selected schoolchildren from 37 schools in eight districts across Uganda at three time points - before chemotherapy and after one year and two years of annual mass chemotherapy. FINDINGS Mass treatment with praziquantel and albendazole led to a significant decrease in the intensity of Schistosoma mansoni - 70% (95% confidence interval (CI): 66-73%) after one year and 82% (95% CI: 80-85%) after two years of treatment. Intensity of hookworm infection also decreased (75% and 93%; unadjusted). There was a significant increase in haemoglobin concentration after one (0.135 g/dL (95% CI: 0.126-0.144)) and two years (0.303 g/dL (95% CI: 0.293-0.312)) of treatment, and a significant decrease in signs of early clinical morbidity. The impact of intervention on S. mansoni prevalence and intensity was similar to that predicted by mathematical models of the impact of chemotherapy on human schistosomiasis. Improvements in haemoglobin concentration were greatest among children who were anaemic or harbouring heavy S. mansoni infection at baseline. CONCLUSION Anthelmintic treatment delivered as part of a national helminth control programme can decrease infection and morbidity among schoolchildren and improve haemoglobin concentration.

Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus.

The effect of Toxoplasma gondii on neophobic behaviour (the avoidance of novel stimuli) was assessed in four groups of wild rats with naturally occurring Toxoplasma infection. Two groups were placed in individual cages and tested in a series of experiments which examined the effect of Toxoplasma on the rats reaction to 3 food-related novel stimuli (odour, food-container, food). A trappability study was performed on the other two groups to test whether Toxoplasma had an effect on probability of capture. The results show that low neophobia was significantly associated with positive Toxoplasma titres in 3 out of 4 groups. We suggest that differences between infected and uninfected wild rats arise from pathological changes caused by Toxoplasma cysts in the brains of infected rats. Such behavioural changes may be selectively advantageous for the parasite as they may render Toxoplasma-infected rats more susceptible to predation by domestic cats (the definitive host of Toxoplasma) and, as a side-effect, more susceptible to trapping and poisoning during post control programmes.

Parasites of wild brown rats ( Rattus norvegicus ) on UK farms

Wild brown rats (Rattus norvegicus) from 11 rural UK farmsteads were found to carry 13 zoonotic and 10 non-zoonotic parasitic species, many of which (e.g. Cryptosporidium, Pasteurella, Listeria, Yersinia, Coxiella and Hantavirus) have rarely or never been previously investigated for wild rats. The study suggests that wild brown rats, serving as vectors of disease, represent a serious risk to the health of humans and domestic animals in the UK.