(Running title: Induction of changes in human behaviour by Toxoplasma)
J. FLEGR1, Š. ZITKOVÁ1, P. KODYM2 and D. FRYNTA3
1 Department of Parasitology, Charles University, Vinièná 7, Prague 128 44, Czech Republic
2 National Diagnostic Laboratory for Toxoplasmosis, National Institute of Public Health, Prague 110 00, Czech Republic
3 Department of Zoology, Charles University, Vinièná 7, Prague 128 44, Czech Republic
Address: Jaroslav Flegr, Dep. Parasitol., Fac.Science, Charles Univ., Vinièná 7, Prague 128 44, Czech Republic, tel. 00422-24915522, fax 00422-299713, E-mail FLEGR@CSEARN.BITNET
Toxoplasma gondii, the coccidian parasite, is known to induce changes in the behaviour of its intermediate hosts. The high prevalence of this parasite in the human population (20-80%) offers the opportunity of studying the influence of the parasite on human behaviour by screening of a normal population.
Two hundred and twenty-four men and one hundred and seventy women were tested for toxoplasmosis and their personality profiles were measured by Cattell's questionnaire. Highly significant differences between Toxoplasma infected and uninfected subjects were observed (p < 0.01). For men the factors G (low superego strength, p<0.02), and possibly L (protension), O (guilt proneness), and A (sizothymia) prevailed in infected subjects. For women the prevailing factors were A (afectothymia, p<0.01), and possibly L (alaxia) and N (shrewdness). To reveal whether toxoplasmosis induces personality factor-shifts or whether certain combinations of personality factors influence the probability of acquiring Toxoplasma infection, we examined the personality profiles of 164 male patients diagnosed with acute toxoplasmosis during the past 13 years. The existence of a positive correlation between the duration of latent toxoplasmosis and the intensity of superego strength decrease (p<0.02) suggested that the decrease of superego strength (the willingness to accept group moral standards) was induced by T. gondii infection.
Key words: Toxoplasma, behaviour, manipulation hypothesis, personality, Cattell's questionnaire.
The ability of parasites to manipulate host behaviour has been observed in many animal models (Barnard & Behnke, 1990). Parasites with complicated life cycles often induce changes in the behaviour of their intermediate hosts that increase the susceptibility of a parasitised animal to predation. Among parasitic protozoa from the Sarcocystidae Poche, 1913, the phenomenon has been observed in Sarcocystis-Microtus (Hoogenboom & Dijkstra, 1987), Sarcocystis-Dicrostonyx , (Quinn, Brooks & Cawthorn,1987), Toxoplasma-Rattus (Webster, 1994; Webster et al. 1994), Toxoplasma-Mus (Arnott et al. 1990; Hay, Aitken & Amott, 1985; Hay et al. 1983; Hutchison et al. 1980ab) systems. The last parasite, Toxoplasma gondii, is an intestinal coccidian of felids with an unusually wide range of intermediate hosts, including humans. After an acute phase of infection (promoted by tachyzoites), pseudocysts are formed mainly in the neural and muscular tissues of infected hosts. The parasites (bradyzoites) cause little or no harm to immunocompetent individuals while inside the cysts and probably persist as viable parasites for the life-span of the host (Remington & Krahenbuhl, 1982). Transmission of Toxoplasma gondii from the intermediate to the definitive host is by carnivorism. Since sexual reproduction of T. gondii can be accomplished only in cats, strong selection pressure on Toxoplasma exists to evolve a mechanism of manipulating intermediate host-behavior.
The high incidence of latent toxoplasmosis in different countries (about 22% of pregnant women in London, 32% in New York City, and 84% in Paris (Desmonts & Couvreul, 1974)) offers the opportunity to study the possible influence of latent toxoplasmosis on human behaviour.
This study is concerned with the effect of latent Toxoplasma gondii infection on human behaviour and involves the comparison of three hundred and ninety-four (394) personality profiles of health subjects. The causality of the observed association of personality factor-shift and latent toxoplasmosis is studied by searching for a positive correlation between the extent of the shift and the duration of latent toxoplasmosis on another experimental set of one hundred and sixty-four (164) men diagnosed with acute toxoplasmosis during the past thirteen years.
2. MATERIALS AND METHODS
Data were collected over a period of 26 months in1992-1994. The first experimental set (Biologists) was composed of 224 men and 170 women, mostly zoology departments staff and biology students. The second set (Patients) contained 190 men diagnosed with acute toxoplasmosis during the past thirteen years in various Prague hospitals. All subjects gave their informed consent before they were accepted for the study.
(b) Personality tests
Cattell's sixteen factor questionnaire (form A) (Cattell, 1970) was used for the characterization of personalities. This questionnaire is widely used for personality studies in many countries, including the Czech Republic. It covers sixteen personality factors (Tab. 1). The main advantage of this traditional test is that it contains only one hundred and eighty-seven (187) questions. Therefore, it can
|reserved, detached, critical||warmhearted, outgoing, easygoing|
|LOW INTELLIGENCE||B||HIGH INTELLIGENCE|
|EGO WEAKNESS||C||HIGH EGO STRENGTH|
|SUBMISSIVENESS||E||DOMINANCE OR ASCENDANCE|
|sober, taciturn, serious||enthusiastic, heedless, hapy- go -lucky|
|LOW SUPEREGO STRENGTH||G*||SUPEREGO STRENGTH or CHARACTER|
|disregards rules, expedient||conscientious, persistent, moralistic, staid|
|trusting, accepting conditions, tolerant||suspecting, jealous, dogmatic|
|forthright, unpretentious||astute, worldly, polished|
|UNTROUBLED ADEQUACY||O||GUILT PRONENESS|
|CONSERVATISM OF TEMPERAMENT||Q1||RADICALISM|
|sociably group dependent, "joiner"||self-sufficient, resourceful, prefers own decisions|
|LOW SELF-SENTIMENT INTEGRATION||Q3*||HIGH STRENGTH OF SELF SENTIMENT|
|uncontrolled, lax, follows own urges||controlled, exacting will power, socially precise|
|LOW ERGIC TENSION||Q4||HIGH ERGIC TENSION|
List of sixteen personality factors monitored by Cattell's questionnaire. The names and characteristics in the left column are for persons with low values of the factor, those in the right column for persons with high values of the factor. Asterisks designate the factors responsible for differences between the sets of Toxoplasma-infected and Toxoplasma-free subjects (MANCOVA results). The labels and designate the trait which was positively influenced by T. gondii in the men's and women's subset, respectively (discriminant analysis).
be completed by most subjects within one hour. In the first experimental set all subjects (except twenty-two parasitologists) completed their questionnaires before the results of the toxoplasmosis test were known. In the second set the subjects obtained the questionnaire by mail. In the enclosed letter they were informed about the general aim of the research (a study of the influence of toxoplasmosis on human personality) and were asked to participate in the project. No differences between the sets of responders (190) and nonresponders (360) were observed in age, length of infection, occupation or any other characteristic compared.
(c) Immunological tests for toxoplasmosis
For the purposes of this study latent toxoplasmosis if defined by the presence of anti-Toxoplasma immunity in human subjects without any clinical symptoms of acute disease. The existence of specific immunity was assessed by an intradermal delayed hypersensitivity test (IDHT) (Feldman, 1954). The test was performed using Toxoplasmin (SEVAC, USOL Prague) as the antigen and shame injection of pure solute as negative control. Positive reactions were of the delayed tuberculin type and were measured 48 hours after antigen administration. The large-scale use of the skin test in population surveys has shown excellent correlation between the results of this test and the presence or absence of humoral antibodies (Remington & Krahenbuhl, 1982). The ability to elicit delayed hypersensitivity to Toxoplasma antigens in man may require a period of months or even years after initial infection to develop and usually lasts for the rest of the host's life, so it is the best method for the diagnosis of latent infection (Remington & Krahenbuhl, 1982).
The serological data and the addresses of patients with acute toxoplasmosis were obtained from the database of patients at the National Diagnostic Laboratory for Toxoplasmosis, National Institute of Public Health, Prague, Czech republic. Acute toxoplasmosis was diagnosed on the basis of clinical symptoms and results of different serological tests, including indirect fluorescent antibody test, IFAT, (Goldman, 1957), complement fixation test, CFT, (Warren & Sabin, 1942), and IgG and IgM ELISA (Pokorný et al. 1989, 1990).
The raw data (age- nonstandardized) from the questionnaire were used in statistical analysis to prevent information loss during the transformation of twenty seven-point raw scales into ten-point age-standardized scales and to avoid an application of general population-based correction factors on the "nonstandard" subpopulation of biologists. The effect of age was controlled either by using residuals of regression between age and the raw personality factors, or by using multidimensional statistical methods with the age of a person as a covariate
The Statistica® program was used for all statistical testing: A multivariate analysis of covariance MANCOVA was used to study the effects of toxoplasmosis, gender and toxoplasmosis-gender interactions on personality factors. Discriminant analysis was used for personality factor-based diagnosis of toxoplasmosis and for stepwise covariance analysis of personality factors. A multiple linear regression was used to estimate the correlation between the length of latent toxoplasmosis and the extent of personality factor-shift.
(a) Difference between Toxoplasma infected and Toxoplasma free subjects
Personality profiles of 224 men and 170 women, mostly university professors and students, were estimated by Cattell's personality questionnaire. After collecting the personality factors data, the subjects were tested for cellular immunity against Toxoplasma gondii by IDHT. Sixty-three (63) men (27.1%) and forty (40) women (23.5%) tested positive. The personality profiles (sixteen personality factors) of Toxoplasma-infected and Toxoplasma-free persons (Table 1) were compared with the MANCOVA test using gender and the result of IDTH as independent variables and the age as a covariate. The effect of the toxoplasmosis-gender interaction was highly significant (Rao´s R (16, 374) = 2.05, p = 0.0097). Of the 16 personality factors estimated by Cattell´s questionnaire the five factors that apparently caused the difference (these with the highest specific effects), A (p=0.0008), G (p=0.003), L (p=0.005), N (p=0.024), and Q3 (p=0.021) are indicated and described in Table 1. Because an opposite trend in the toxoplasmosis-associated shift of these factors was observed in men and women, we decided to analyse these two subsets separately. The results of MANCOVA analysis for both sexes are given in Table 2.
The results of MANCOVA analysis. The left two columns show the specific effects of particular personality factors, namely the statistical significance of the difference between Toxoplasma-infected and Toxoplasma-free subjects (gender and results of IDHT as independent variables). The middle two and right two columns show the significance for men and women, respectively.
To reveal which personality factors differ because of their correlation with toxoplasmosis and which ones because of their correlation with other (toxoplasmosis correlated) personality factors we employed a discriminant analysis. This statistical method was primarily designed for classification of objects into previously defined groups. It can also be used for estimating correlation effects between factors by an approach based on analysis of covariance (Bouska et al. 1990). We classified either men or women into Toxoplasma-infected and Toxoplasma-free groups by their personality profiles. In the men's subset the factors L, G, F, and Q2 entered classification function. In the group of eighteen (18) men classified by their personality profiles the frequency of IDTH positive persons was 72.2% (a priori frequency for our sample was 27.1%). In the women's subset the factors A, L, and Q2 entered classification function and among nineteen (19) women classified as Toxoplasma_infected the frequency of IDTH positive persons was 63.2% (a priori frequency was 23.5%).
The personality profile-based "diagnosis" of toxoplasmosis performed ineffectively within the negative subset. Among two hundred and six (206) men and one hundred and fifty one (151) women classified as Toxoplasma-free the frequency of correct diagnosis was only 75.7% (a priori frequency 72.9%) and 81.5% (a priori frequency 76.5%), respectively. This may suggest that while the development of anti-toxoplasma immunity takes a short time, the transformation of human personality (and the manifestation of the changes) could be a prolonged process.
(b) Correlation between the extent of personality shifts and the duration of toxoplasmosis
The possible existence of time-lag between the infection and the personality changes offers the possibility of deciding the causation of the phenomenon, namely to test if toxoplasmosis induces the personality factor-shift or if the combination of personality factors influences the probability of being infected by Toxoplasma gondii. To answer this question we distributed the Cattell's questionnaire to five hundred and fifty (550) men in which the acute toxoplasmosis was diagnosed during the past 13 years. We received data for one hundred and ninety (190) patients for whom the duration of latent toxoplasmosis was known. Fifteen (15) men infected within the past six months and eleven (11) men diagnosed for toxoplasmosis before the age of six were excluded from the analysis (see the discussion). The influence of the duration of toxoplasmosis on the age-nonstandardized personality factors was estimated with regression analysis
Correlations between personality factors and the duration of chronic toxoplasmosis. The raw personality data were used as dependent variables and the age of the subjects as a covariate.
using the age of a person as a covariate. The results are summarised in Table 3. From 16 factors studied, only G (superego strength) systematically changed (decreased) during the 13 years following Toxoplasma gondii infection (R* = 0.02, t(162)=2.14, p=0.017, one-tailed t test) (see Fig. 1). It was the same factor that was significantly lower (F(1, 221)=5.92, p=0.016) in Toxoplasma infected men in our first experimental set (Biologists). A statistically insignificant tendency also existed (R*=0.016, t(162)=-1.88, p=0.062, a two-tailed t test) for the decrease of B (intelligence). This decrease became significant (p=0.014) when the data of eleven (11) persons diagnosed with toxoplasmosis before the age of six (possibly congenital toxoplasmosis) were also included into analysis.
Correlation between the length of infection and superego strength.The abscissa shows the residuals of regression between age and the raw personality factor G, the ordinate shows the time (in months) from the first positive test for acute toxoplasmosis.
Our results demonstrated the existence of a correlation between anti-toxoplasma immunity (monitored by IDTH) and certain personality factors in men and women. The existence of a correlation between the extent of personality factor shift and the duration of toxoplasmosis suggests that toxoplasmosis induces a shift in human personality, rather than the personality factor shift influences the probability of being infected with Toxoplasma gondii.
Positive reaction in IDHT indicates the existence of cellular immunity. Cellular immunity against T. gondii may require months to develop. It lasts many years, possibly for the rest of the host's life. These two facts make IDHT superior in comparison with any serological test for diagnosis of latent infection (Remington & Krahenbuhl, 1982). It is not known, however, if cellular immunity necessarily indicates latent toxoplasmosis, e.g. the presence of live parasites in cysts in nervous and muscular tissues of the immune subject. Experience with AIDS patients suggests that the frequency of latent toxoplasmosis in human population may be identical with the frequency of Toxoplasma-immune subjects (Roberts, Murrell & Marks, 1994). Also our results on correlation of the shift of factor G (decrease of the superego strength) with the duration of toxoplasmosis indicate that the parasites in the cysts may be alive and biologically active for many years after infection. However, it must still be clarified whether the process of the personality factor-shift is directed by the encysted Toxoplasma bradyzoites, or whether it is only triggered by the acute stage of the infection.
The results from the MANCOVA suggest that personality factors G, L, and possibly O, A, and Q3 might be shifted in Toxoplasma-infected men, and factors A, L, and possibly N and Q3 in Toxoplasma infected women. On the other hand, in the discriminant analysis (and so in Logistic regression, results not shown) another group of factors (L, G, F, Q2 for men and A, L, Q2 for women) proved to be most useful for the identification of Toxoplasma-infected subjects. This discrepancy can be explained by differences in the mathematical background of these two methods. Discriminant analysis includes a stepwise covariance analysis. In every step, F-to-enter values are affected by the variables already present in the classification function. When a strong correlation exists between two variables (e.g. factor G and Q3) only the one with a higher F value might enter the classification function. On the other hand, when low or no correlation exists among variables, all might enter the function despite their relatively low F values in the step zero of discriminant analysis (or in MANCOVA).
In the men's subset the factors G (low superego strength), L (protension), F (desurgency), and Q2 (group dependency) are positively influenced by toxoplasmosis (as indicated by discriminant analysis). In the women's subset the factors A (afectothymia), L (alaxia) and Q2 (self sufficiency) are more pronounced in the Toxoplasma-infected subjects. The nature of involved factors (see Table 1) as well as the fact, that the same factors are often shifted in the opposite direction in the men and women subsets, make the biological or psychological interpretation of the toxoplasmosis-induced changes of the personality profiles very difficult. It has been demonstrated that T. gondii-infected animals (rodents) are less anxious (Hutchison et al. 1980a), less neophobic (Webster et al. 1994), more active (Hutchison, 1980a; Webster et al.1994) and aggressive (Arnott et al. 1990) than the controls. It can be speculated whether the low superego strength, i.e. tendencies to disregard the societal rules, may be determined or influenced by lack of fear of punishment and/or by an aggression in men and by another factor in the women. Analogically A (afectothymia), i.e. warmheartedness, outgoingness, easygoingness may be controlled or influenced by lack of fear in the women, and by other factor(s) in men, depending on the difference between men's and women's social roles. The existence of gender-specific differences in the composition of certain personality factors is suggested by the difference in the structures of covariance matrices of Cattell's personality factors for men and women (results not shown).
It must be also stressed that the character of toxoplasmosis induced changes in the behaviour of humans and rodents may be dramatically different even if they are induced by the same mechanism. In the rodent system the ability to decrease neophobia and anxiety and to increase the activity of its intermediate host is highly adaptive for Toxoplasma. Such manipulation can positively influence the probability of transmission of T.gondii into the definitive host (felid) by carnivorism. In modern man such parasite activity is non-productive so the parasite is expected to be better adapted for manipulation of rodent behaviour. The changes in human behaviour (monitored by the changes in the personality profiles in our study) probably only indirectly reflect some activity of T. gondii, possibly the synthesis or induction of synthesis of dopamine (Stibbs, 1985) or of other biologically active substances (Silverman & Varela, 1958) in the host brain tissue.
In our previous study (Flegr & Hrdy, 1994) we found effects of latent toxoplasmosis on the personality profile of men (not women). This is also the reason why we chose male toxoplasmosis patients for our study of correlation of the extent of personality factor-shift with the duration of T. gondii infection. The present reanalysis of the old and new data showed that after the application of finer method of the elimination of the effect of age, the results of statistical tests were different then originally reported. The difference between Toxoplasma infected and Toxoplasma free women became significant and the significance of the shift of factor G increased and of the factor L decreased for men. Our original inability to recognize the increase of the factor A in women was caused partly by lower n (143) and partly by the information loss caused by use of age-standardised personality factors, instead of the age-nonstandardized data with age as a covariate. The main reason why the former approach should be avoided is that in the general population for which the age correcting-factors are tabulated and published the frequency of Toxoplasma-infected subjects and especially the kinetics of an age-dependent increase of this frequency (Robertson, 1966) can be different from that of an experimental set.
The data from fifteen patients infected within the past six months were excluded from our correlation analysis. Acute toxoplasmosis often shows a symptomatic period with fever, general malaise, headache, dizziness, sore throat, coughing. Accompanying psychopathological features are very common and frequently include depression, apathy and anxiety, often anxiety spells, and paraesthesia (Ladee, Scholten & Posthumus Meyes, 1966 ). Many of these neurological and psychopathological symptoms may be toxoplasmosis-nonspecific. In our study a dramatic shift in personality profiles was detected in a group of fifteen patients recently infected by T. gondii as well as in a group of forty-three patients with toxoplasmosis-like symptoms but with negative results in toxoplasmosis immunological tests (complement fixing reaction, ELISA IgM, ELISA IgA, indirect fluorescent antibody test) (data not shown). Similar effects of acute toxoplasmosis have already been reported by others (Höschl & Balon, 1980).
The data from eleven men diagnosed with toxoplasmosis before age six and therefore suspected of having a congenital form of toxoplasmosis were also excluded from the analysis. The neurological manifestation of congenital toxoplasmosis due to meningoencephalitis is relatively frequent, and the sequelae includes psychomotor and mental retardation (Koppe & Rothova, 1989). We suppose that the observed correlation between the decrease of factor B (intelligence) and the length of latent toxoplasmosis might be caused by the presence of unrecognised cases of congenital toxoplasmosis in our acquired toxoplasmosis-experimental set (mainly within the long-duration toxoplasmosis subset).
The influence of severe forms of acute toxoplasmosis on human personality has been reported by many clinicians (Burkinshaw, Kirman & Sorsby, 1953; Minto & Roberts, 1959; Ladee et al. 1966; Freytag & Haas, 1979). In literature, attention is frequently focused on psychoses with schizophrenic features that accompany latent toxoplasmosis or toxoplasmosis acquired in childhood or early adult life (for review see Ladee et al. 1966). Numerous studies have also shown an excess of Toxoplasma-infected subjects among patients in mental hospitals, (Robertson, 1966; Thalhammer, 1962; Garcia, 1979; Garrido et al. 1978). Typically, however, the effects of acquired toxoplasmosis on immunocompetent subjects are mild; only a negligible fraction of infected subjects ever learn that they are parasitized. Latent toxoplasmosis acquired in adult life is usually considered asymptomatic (Remington, 1974). In this respect the existence of easily detected differences between Toxoplasma-infected and Toxoplasma-free biologists was unexpected. One can only speculate, whether these activities of the parasite are connected with an attempt (in modern humans a nonproductive one) of the parasite to manipulate the host behaviour, or are only byproducts of a nonspecific decline in the quality of host life. Infected subjects might theoretically suffer more frequent or more severe diseases because of an interference by the parasite with their immune system (Krahenbuhl & Remington, 1982; Remington & Krahenbuhl, 1982). Such effects of toxoplasmosis, however, have never been reported.
This research was supported by the Czech Biological Foundation and grant GUK95. We thank A. Exnerova for her help with psychological questionnaires and K. Zvara for help with the statistical analysis. We also thank our colleagues who participated in the experiments.
ARNOTT, M. A., CASSELLA, J. P., AITKEN, P. P. & HAY, J. (1990). Social interactions of mice with congenital Toxoplasma infection. Annals of Tropical Medicine and Parasitology 84, 149-56.
BARNARD, C.J. & BEHNKE, J.M. (eds.) (1990). Parasitism and Host Behaviour. New York, Philadelphia, London: Taylor and Francis.
BOUŠKA, V., DELANO, J. W., MASLOWSKÁ, H. & ŘANDA, Z. (1990). Discriminant analysis of the moldavite data set. Acta Universitatis Carolinae-Geologica 3, 243-58.
BURKINSHAW, J., KIRMAN, B. H. & SORSBY, A. (1953). Toxoplasmosis in relation to mental deficiency. British Medical Journal 702, 1-6.
CATTELL, R.B. (1970). Handbook for the sixteen personality factors questionnaire (16PF). Champaign: Institute for Personality and Ability Testing.
DESMONTS, G. & COUVREUR, J. (1974). Congenital toxoplasmosis. A prospective study of 378 pregnancies. New England Journal of Medicine 290, 1110-16.
FELDMAN, H. A. (1954). Laboratory methods in current use for the study of toxoplasmosis. Advances in Ophthalmology Vol. III, (ed. E. B. Streiff), Lausanne Bibliotheca Ophthalmologica Fascicles 39, 1-11.
FLEGR, J. & HRDY, I. (1994). Influence of chronic toxoplasmosis on some human personality factors. Folia Parasitologica 41, 122-26.
FREYTAG, H. W. & HAAS, H. (1979). Zur Psychopathologie der erworbener Toxoplasmose. Nervenarzt 50, 128-31.
GARCIA, G. D. (1979). Toxoplasmosis y enfermedades mentales. (Toxoplasmosis and mental diseases) Revista Cubana de medicica tropicales 31, 127-31.
GARRIDO, J.A., BOVEDA, M. I. C. & DEBECERRA, J. O. (1978). Estudio de la toxoplasmosis en un medio hospitalario psiquiatrico. Consecuencias clinicas y epidemiologicas (Studies on toxoplasmosis in the mental hospitals. Clinical and epidemiological aspects.) Diagnostico biologico XXVII, 267-88.
GOLDMAN, M. (1957). Staining Toxoplasma gondii with fluorescein-labelled antibody. I. The reaction in smears of peritoneal exudate. Journal of Experimental Medicine 105, 549-56.
HAY, J., HUTCHISON, W. M., AITKEN, P. P. & GRAHAM, D. I. (1983). The effect of congenital and adult-acquired Toxoplasma infections on activity and responsiveness to novel stimulation in mice. Annals of Tropical Medicine and Parasitology 77, 483-95.
HAY, J., AITKEN, P. P. & AMOTT, M. A. (1985). The influence of congenital toxoplasma infection on spontaneous running activity of mice. Zeitschrift für Parasitenkunde 71, 459-62.
HOOGENBOOM, I. & DIJKSTRA, C. (1987). Sarcocystis cernae: a parasite increasing the risk of predation of its intermediate host, Microtus arvalis. Oecologia 74, 86-92.
HÖSCHL, C. & BALON, R. (1980). Výsledky psychiatrického vyšetřování nemocných toxoplasmózou. (Results of psychiatric investigation of patients with toxoplasmosis). Časopis Lékaru českych 119, 366-68.
HUTCHISON, W. M., AITKEN, P. P. & WELLS, B. (1980a). A chronic Toxoplasma infections and familiarity-novelty discrimination in the mouse. Annals of Tropical Medicine and Parasitology 74, 337-45.
HUTCHISON, W. M., BRADLEY, M., CHEYNE, W. M., WELLS, B. W. P. & HAY, J. (1980 b). Behavioural abnormalities in Toxoplasma-infected mice. Annals of Tropical Medicine and Parasitology 74, 337-45.
KOPPE, J. G. & ROTHOVA, A. (1989). Congenital toxoplasmosis. A long-term follow-up of 20 years. International Ophthalmology 13, 387-90.
KRAHENBUHL, J. L. & REMINGTON, J. S. (1982). The immunology of Toxoplasma and toxoplasmosis. In Immunology of Human Infections, Part II A.(eds. J. Mahmias. & J O'Reily ), New York: Plenum Publishing Corporation.
LADEE, G. A., SCHOLTEN, J. M. & POSTHUMUS MEYES, F. E. (1966). Diagnostic problems in psychiatry with regards to acquired toxoplasmosis. Psychiatria Neurologia, Neurochirurgia 69, 65-82.
MINTO, A. & ROBERTS, F.J. (1959). The psychiatric complications of toxoplasmosis. The Lancet 275, 1180-82.
POKORNÝ, J., FRUHBAUER, Z., POLEDÒÁKOVÁ, S., SÝKORA, J., ZÁSTÌRA, M. & FIALOVÁ, D. (1989). Stanoveni antitoxoplasmickych protilatek IgG metodou ELISA. (Assessment of antitoxoplasmatic IgG antibidies with the ELISA method.) Èskoslovenska Epidemiologie 38, 355-61.
POKORNÝ, J., FRUHBAUER, TOMÁŠKOVÁ, V., KRAJHANZLOVÁ, L., SÝKORA, J. & ZÁSTERA, M. (1990). Stanoveni antitoxoplasmickych protilatek IgM metodou ELISA. (Estimation of antitoxoplasmatic IgM antibidies with the ELISA method.) Èeskoslovenska Epidemiologie 39, 57-62.
QUINN, S. C., BROOKS, R. J. & CAWTHORN, R. J. (1987). Effects of protozoan parasite Sarcocystis rauchorum on open-field behaviour of its intermediate vertebrate host, Dicrostonyx richardsoni. Journal of Parasitology 1973, 265-71.
REMINGTON, J.S. (1974). Toxoplasmosis in the adult. Bulletin of the New York Academy of Medicine 50, 211-27.
REMINGTON, J.S. & KRAHENBUHL, J.L. (1982). Immunology of Toxoplasma gondii. In Immunology of Human Infection Part II (eds Nahmias, A. J. & O'Reilly, J.), pp. 327-371. New York: Plenum Publishing Corporation.
ROBERTS, T., MURRELL, K. D. & MARKS, S. (1994). Economic losses caused by foodborne parasitic diseases. Parasitology Today 10, 419-23.
ROBERTSON J. S. (1966). Toxoplasmin sensitivity: subnormality and environment. Journal of Hygiene 64, 405-10.
SILVERMAN & B. VARELA, G. (1958). Toxoplasmosis, mental disease and LSD-25. Revista del Instituto de salubridat y enfermedades tropicales 18, 191-94.
STIBBS, H. H. (1983). Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Annals of Tropical Medicine and Parasitology 79, 153-57.
THALHAMMER, O. (1962). Congenital toxoplasmosis. The Lancet I 278, 23-24.
WARREN, J. & SABIN, A.B. (1942). The complement fixation reaction in toxoplasmic infection. Proceedings of the Society for experimental Biology and Medicine 51, 11-16.
WEBSTER, J. P. (1994). The effect of Toxoplasma gondii and other parasites on activity levels in wild and hybrid Rattus norvegicus. Parasitology 109, 583-89.
WEBSTER, J. P., BRUNTON, C.F.A. & MACDONALD, D. W. (1994). Effect of Toxoplasma gondii on neophobic behaviour in wild brown rats, Rattus norvegicus. Parasitology 109, 37-43.