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Impaired health status and increased incidence of diseases in Toxoplasma-seropositive subjects – an explorative cross-sectional study

Published online by Cambridge University Press:  10 October 2016

J. FLEGR  and
D. Q. ESCUDERO
J. FLEGR*
Affiliation:
Division of Biology, Faculty of Science, Charles University in Prague, Vinicna 7, 128 44, Prague, Czech Republic National Institute of Mental Health, Klecany, 250 67, Czech Republic
D. Q. ESCUDERO
Affiliation:
Division of Biology, Faculty of Science, Charles University in Prague, Vinicna 7, 128 44, Prague, Czech Republic
*
*Corresponding author. Division of Biology, Faculty of Science, Charles University in Prague, Vinicna 7, 128 44, Prague, Czech Republic. E-mail: flegr@cesnet.cz
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Summary

The global seroprevalence of latent toxoplasmosis is estimated to be higher than 30%. The presence of slowly dividing parasites in tissue cysts located mainly in immunoprivileged organs was long considered asymptomatic. Recently, many studies have shown that latent Toxoplasma infections could have serious impacts on human health. Here we ran a cross-sectional study in a population of 1486 volunteers. The results showed that 333 infected subjects scored worse than 1153 controls in 28 of 29 health-related variables. Similarly, they reported higher rates of 77 of a list of 134 disorders reported by at least 10 participants of the study. Toxoplasmosis was associated most strongly with musculoskeletal (τ = 0·107, P < 0·0005), followed by neurological (τ = 0·088, P < 0·0005), immune (τ = 0·085, p < 0·0005), metabolic (τ = 0·079, P < 0·0005), respiratory (τ = 0·068, P = 0·0001), allergic (τ = 0·053, P = 0·004), digestive system (τ = 0·052, P = 0·004) and mental health disorders (τ = 0·050, P = 0·008). Results of the present cohort study, along with the previous data from many case-control studies or ecological studies suggest that latent toxoplasmosis represents a large and so far underrated public health problem.

Keywords

Parasitepublic healthdisease burdenneglected diseaseneglected zoonosistoxoplasmosisToxoplasma gondii
Type
Research Article
Information
Parasitology , Volume 143 , Issue 14 , December 2016 , pp. 1974 - 1989
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Copyright
Copyright © Cambridge University Press 2016 

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References

REFERENCES

Addebbous, A., Adarmouch, L., Tali, A., Laboudi, M., Amine, M., Aajly, L., Rhajaoui, M., Chabaa, L. and Zougaghi, L. (2012). IgG anti-Toxoplasma antibodies among asymptomatic HIV-infected patients in Marrakesh-Morocco. Acta Tropica 123, 49–52.CrossRefGoogle ScholarPubMed
Akanmu, A. S., Osunkalu, V. O., Ofomah, J. N. and Olowoselu, F. O. (2010). Pattern of demographic risk factors in the seroprevalence of anti-Toxoplasma gondii antibodies in HIV infected patients at the Lagos University Teaching Hospital. Nigerian Quarterly Journal of Hospital Medicine 20, 1–4.CrossRefGoogle ScholarPubMed
Alvarado-Esquivel, C., Torres-Castorena, A., Liesenfeld, O., Estrada-Martinez, S. and Urbina-Alvarez, J. D. (2012). High seroprevalence of Toxoplasma gondii infection in a subset of Mexican patients with work accidents and low socioeconomic status. In Parasites & Vectors, Vol. 5. doi: 10.1186/1756-3305-5-13.Google Scholar
Benjamini, Y. and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B-Methodological 57, 289–300.Google Scholar
Berenreiterova, M., Flegr, J., Kubena, A. A. and Nemec, P. (2011). The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis. PLoS ONE 6, e28925.CrossRefGoogle ScholarPubMed
Bhadra, R., Cobb, D. A., Weiss, L. M. and Khan, I. A. (2013). Psychiatric disorders in Toxoplasma seropositive patients - CD8 connection. Schizophrenia Bulletin 39, 485–489.CrossRefGoogle ScholarPubMed
Blomstrom, A., Karlsson, H., Wicks, S., Yang, S., Yolken, R. H. and Dalman, C. (2012). Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring–a matched case-control study. Schizophrenia Research 140, 25–30.CrossRefGoogle ScholarPubMed
Coppens, I. (2006). Contribution of host lipids to Toxoplasma pathogenesis. Cell Microbiol 8, 1–9.Google Scholar
Flegr, J. (2010). Influence of latent toxoplasmosis on the phenotype of intermediate hosts. Folia Parasitologica 57, 81–87.CrossRefGoogle ScholarPubMed
Flegr, J. (2013 a). How and why Toxoplasma makes us crazy. Trends in Parasitology 29, 156–163.Google Scholar
Flegr, J. (2013 b). Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. Journal of Experimental Biology 216, 127–133.CrossRefGoogle ScholarPubMed
Flegr, J. (2016). Could contamination of data with misclassified individuals increase the probability of false positive results of statistical tests?. Figshare. https://dx.doi.org/10.6084/m9.figshare.3806553.v1.Google Scholar
Flegr, J. and Hodny, Z. (2016). Cat scratches, not bites, are associated with unipolar depression - cross-sectional study. Parasites & Vectors 9. doi: 10.1186/s13071-015-1290-7.CrossRefGoogle Scholar
Flegr, J. and Hrdý, I. (1994). Influence of chronic toxoplasmosis on some human personality factors. Folia Parasitologica 41, 122–126.Google Scholar
Flegr, J. and Stříž, I. (2011). Potential immunomodulatory effects of latent toxoplasmosis in humans. BMC Infectious Diseases 11, 274.Google Scholar
Flegr, J., Zitkova, S., Kodym, P. and Frynta, D. (1996). Induction of changes in human behaviour by the parasitic protozoan Toxoplasma gondii . Parasitology 113, 49–54.CrossRefGoogle ScholarPubMed
Flegr, J., Havlíček, J., Kodym, P., Malý, M. and Šmahel, Z. (2002). Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infectious Diseases 2, art-11.CrossRefGoogle ScholarPubMed
Flegr, J., Preiss, M., Klose, J., Havlíček, J., Vitáková, M. and Kodym, P. (2003). Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii. Dopamine, a missing link between schizophrenia and toxoplasmosis? Biological Psychology 63, 253–268.Google Scholar
Flegr, J., Lindová, J. and Kodym, P. (2008). Sex-dependent toxoplasmosis-associated differences in testosterone concentration in humans. Parasitology 135, 427–431.CrossRefGoogle ScholarPubMed
Flegr, J., Klose, J., Novotná, M., Berenreitterová, M. and Havlíček, J. (2009). Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infectious Diseases 9, art. 72.CrossRefGoogle ScholarPubMed
Flegr, J., Hampl, R., Černochová, D., Preiss, M., Bičíkova, M., Sieger, L., Příplatová, L., Kaňková, S. and Klose, J. (2012). The relation of cortisol and sex hormone levels to results of psychological, performance, IQ and memory tests in military men and women. Neuroendocrinology Letters 33, 224–235.Google ScholarPubMed
Flegr, J., Prandota, J., Sovickova, M. and Israili, Z. H. (2014). Toxoplasmosis - A global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS ONE 9. doi: 10.1371/journal.pone.0090203.Google Scholar
Fuks, J. M., Arrighi, R. B., Weidner, J. M., Kumar Mendu, S., Jin, Z., Wallin, R. P., Rethi, B., Birnir, B. and Barragan, A. (2012). GABAergic signaling is linked to a hypermigratory phenotype in dendritic cells infected by Toxoplasma gondii . PLoS Pathogens 8, e1003051.CrossRefGoogle ScholarPubMed
Gale, S. D., Brown, B. L., Berrett, A., Erickson, L. D. and Hedges, D. W. (2014). Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults. Folia Parasitologica 61, 285–292.CrossRefGoogle ScholarPubMed
Gaskell, E. A., Smith, J. E., Pinney, J. W., Westhead, D. R. and McConkey, G. A. (2009). A unique dual activity amino acid hydroxylase in Toxoplasma gondii . PLoS ONE 4, e4801.CrossRefGoogle ScholarPubMed
Guthrie, K. A. and Sheppard, L. (2001). Overcoming biases and misconceptions in ecological studies. Journal of the Royal Statistical Society: Series A (Statistics in Society) 164, 141–154.CrossRefGoogle Scholar
Havlíček, J., Gašová, Z., Smith, A. P., Zvára, K. and Flegr, J. (2001). Decrease of psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis. Parasitology 122, 515–520.CrossRefGoogle ScholarPubMed
Hsu, P. C., Groer, M. and Beckie, T. (2014). New findings: depression, suicide, and Toxoplasma gondii infection. Journal of the American Association of Nurse Practitioners 26, 629–637.CrossRefGoogle ScholarPubMed
Jones, J. L. and Holland, G. N. (2010). Annual burden of ocular toxoplasmosis in the US. American Journal of Tropical Medicine and Hygiene 82, 464–465.CrossRefGoogle ScholarPubMed
Kaňková, Š., Kodym, P. and Flegr, J. (2011). Direct evidence of Toxoplasma-induced changes in serum testosterone in mice. Experimental Parasitology 128, 181–183.Google Scholar
Kankova, S., Prochazkova, L., Flegr, J., Calda, P., Springer, D. and Potlukova, E. (2014). Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy. PLoS ONE 9. doi: 10.1371/journal.pone.0110878.Google Scholar
Kankova, S., Flegr, J. and Calda, P. (2015 a). The influence of latent toxoplasmosis on women's reproductive function: four cross-sectional studies. Folia Parasitologica 62, 041. doi: 10.14411/fp.2015.041.CrossRefGoogle ScholarPubMed
Kaňková, Š., Flegr, J. and Calda, P. (2015 b). An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant women with latent toxoplasmosis. Folia Parasitologica 62, 1–6.Google Scholar
Kapoor, S. (2012). The close relationship between toxoplasmosis and kidney function. Revista do Instituto de Medicina Tropical de Sao Paulo 54, 318–318.CrossRefGoogle ScholarPubMed
Koseoglu, E., Yazar, S. and Koc, I. (2009). Is Toxoplasma gondii a causal agent in migraine? American Journal of the Medical Sciences 338, 120–122.CrossRefGoogle ScholarPubMed
Lambert, H., Dellacasa-Lindberg, I. and Barragan, A. (2011). Migratory responses of leukocytes infected with Toxoplasma gondii . Microbes and Infection 13, 96–102.CrossRefGoogle ScholarPubMed
Lim, A., Kumar, V., Hari Dass, S. A. and Vyas, A. (2013). Toxoplasma gondii infection enhances testicular steroidogenesis in rats. Molecular Ecology 22, 102–110.CrossRefGoogle ScholarPubMed
Lindová, J., Novotná, M., Havlíček, J., Jozífková, E., Skallová, A., Kolbeková, P., Hodný, Z., Kodym, P. and Flegr, J. (2006). Gender differences in behavioural changes induced by latent toxoplasmosis. International Journal for Parasitology 36, 1485–1492.Google Scholar
Lindová, J., Kuběna, A. A., Šturcová, A., Křivohlavá, R., Novotná, M., Rubešová, A., Havlíček, J., Kodym, P. and Flegr, J. (2010). Pattern of money allocation in experimental games supports the stress hypothesis of gender differences in Toxoplasma gondii-induced behavioural changes. Folia Parasitologica 57, 136–142.Google Scholar
Ling, V. J., Lester, D., Mortensen, P. B. and Postolache, T. T. (2011). Toxoplasma gondii seropositivity and completed suicide in 20 European countries. Biological Psychiatry 69, 500.Google Scholar
Markovitz, A. A., Simanek, A. M., Yolken, R. H., Galea, S., Koenen, K. C., Chen, S. and Aiello, A. E. (2015). Toxoplasma gondii and anxiety disorders in a community-based sample. Brain, Behavior, and Immunity 43, 192–197.Google Scholar
Mead, P. S., Slutsker, L., Dietz, V., McCaig, L. F., Bresee, J. S., Shapiro, C., Griffin, P. M. and Tauxe, R. V. (1999). Food-related illness and death in the United States. Emerging Infectious Diseases 5, 607–625.Google Scholar
Montoya, J. G. and Liesenfeld, O. (2004). Toxoplasmosis. Lancet 363, 1965–1975.Google Scholar
Nagineni, C. N., Detrick, B. and Hooks, J. J. (2002). Transforming growth factor-beta expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis. Clinical and Experimental Immunology 128, 372–378.CrossRefGoogle ScholarPubMed
Nejad, M. R., Rostami, K., Cheraghipour, K., Mojarad, E. N., Volta, U., Al Dulaimi, D. and Zali, M. R. (2011). Celiac disease increases the risk of Toxoplasma gondii infection in a large cohort of pregnant women. American Journal of Gastroenterology 106, 548–549.CrossRefGoogle Scholar
Ngoungou, E. B., Bhalla, D., Nzoghe, A., Darde, M.-L. and Preux, P.-M. (2015). Toxoplasmosis and epilepsy - systematic review and meta analysis. PLoS Neglected Tropical Diseases 9. doi: 10.1371/journal.pntd.0003525.Google Scholar
Palmer, B. S. (2007). Meta-analysis of three case controlled studies and an ecological study into the link between cryptogenic epilepsy and chronic toxoplasmosis infection. Seizure 16, 657–663.Google Scholar
Pappas, G., Roussos, N. and Falagas, M. E. (2009). Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. International Journal for Parasitology 39, 1385–1394.Google Scholar
Paspalaki, P. K., Mihailidou, E. P., Bitsori, M., Tsagkaraki, D. and Mantzouranis, E. (2001). Polyomyositis and myocarditis associated with acquired toxoplasmosis in an immunocompetent girl. BMC Musculoskeletal Disorders 2, 8.CrossRefGoogle Scholar
Pearce, B. D., Kruszon-Moran, D. and Jones, J. L. (2012). The relationship between Toxoplasma gondii infection and mood disorders in the Third National Health and Nutrition Survey. Biological Psychiatry 72, 290–295.CrossRefGoogle ScholarPubMed
Pedersen, M. G., Mortensen, P. B., Norgaard-Pedersen, B. and Postolache, T. T. (2012). Toxoplasma gondii infection and self-directed violence in mothers. Archives of General Psychiatry 69, 1123–1130.Google Scholar
Porter, S. B. and Sande, M. A. (1992). Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. New England Journal of Medicine 327, 1643–1648.Google Scholar
Prandota, J. (2009). The importance of Toxoplasma gondii infection in diseases presenting with headaches. Headaches and aseptic meningitis may be manifestations of the Jarisch-Herxheimer reaction. International Journal of Neuroscience 119, 2144–2182.Google Scholar
Prandota, J. (2010). Neuropathological changes and clinical features of autism spectrum disorder participants are similar to that reported in congenital and chronic cerebral toxoplasmosis in humans and mice. Research in Autism Spectrum Disorders 4, 103–118.Google Scholar
Prandota, J. (2012). Gastrointestinal tract abnormalities in autism, inflammatory bowel disease and many other clinical entities may be due to T. gondii infection. Open Access Scientific Reports 1, 256.Google Scholar
Prandovszky, E., Gaskell, E., Martin, H., Dubey, J. P., Webster, J. P. and McConkey, G. A. (2011). The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS ONE 6, e23866.Google Scholar
Radford, A., Williams, S. N., Kane, B. and Groer, M. (2012). Relationships of Toxoplasma antibody titers and dysphoric moods in female veterans. Brain Behavior and Immunity 26, S23.Google Scholar
Sanchis-Belenguer, R., Cuadrado-Mendez, L. and Ortiz Munoz, A. B. (1984). [Possible interactions between Toxoplasma gondii infection and the presence of carcinomas of female genitalia and the breast]. Revista Espanola de Oncologia 31, 247–255.Google ScholarPubMed
Scallan, E., Hoekstra, R. M., Angulo, F. J., Tauxe, R. V., Widdowson, M. A., Roy, S. L., Jones, J. L. and Griffin, P. M. (2011). Foodborne illness acquired in the United States-major pathogens. Emerging Infectious Diseases 17, 7–15.CrossRefGoogle ScholarPubMed
Shapira, Y., Agmon-Levin, N., Selmi, C., Petrikova, J., Barzilai, O., Ram, M., Bizzaro, N., Valentini, G., Matucci-Cerinic, M., Anaya, J.-M., Katz, B.-S. P. and Shoenfeld, Y. (2012). Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. Journal of Autoimmunity 39, 112–116.Google Scholar
Siegel, S. and Castellan, N. J. (1988). Nonparametric Statistics for the Behavioral Sciences, 2nd Edn. McGraw-Hill, New York.Google Scholar
Singh, S., Singh, N., Pandav, R., Pandav, C. S. and Karmarkar, M. G. (1994). Toxoplasma gondii infection & its association with iodine deficiency in a residential school in a tribal area of Maharashtra. Indian Journal of Medical Research 99, 27–31.Google Scholar
Skallová, A., Novotná, M., Kolbeková, P., Gašová, Z., Veselý, V. and Flegr, J. (2005). Decreased level of novelty seeking in blood donors infected with Toxoplasma . Neuroendocrinology Letters 26, 480–486.Google Scholar
Stommel, E. W., Seguin, R., Thadani, V. M., Schwartzman, J. D., Gilbert, K., Ryan, K. A., Tosteson, T. D. and Kasper, L. H. (2001). Cryptogenic epilepsy: an infectious etiology? Epilepsia 42, 436–438.CrossRefGoogle ScholarPubMed
Tenter, A. M., Heckeroth, A. R. and Weiss, L. M. (2000). Toxoplasma gondii: from animals to humans. International Journal for Parasitology 30, 1217–1258.CrossRefGoogle ScholarPubMed
Tomairek, H. A., Saeid, M. S., Morsy, T. A. and Michael, S. A. (1982). Toxoplasma gondii as a cause of rheumatoid arthritis. Journal of the Egyptian Society of Parasitology 12, 17–23.Google ScholarPubMed
Toporovski, J., Romano, S., Hartmann, S., Benini, W. and Chieffi, P. P. (2012). Nephrotic syndrome associated with toxoplasmosis: Report of seven cases. Revista do Instituto de Medicina Tropical de Sao Paulo 54, 61–64.Google Scholar
Torrey, E. F. and Yolken, R. H. (2001). The schizophrenia-rheumatoid arthritis connection: infectious, immune, or both? Brain Behavior and Immunity 15, 401–410.Google Scholar
Torrey, E. F., Bartko, J. J., Lun, Z. R. and Yolken, R. H. (2007). Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophrenia Bulletin 33, 729–736.Google Scholar
Torrey, E. F., Bartko, J. J. and Yolken, R. H. (2012). Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophrenia Bulletin 38, 642–647.Google Scholar
Ustun, S., Aksoy, U., Dagci, H. and Ersoz, G. (2004). Incidence of toxoplasmosis in patients with cirrhosis. World Journal of Gastroenterology 10, 452–454.Google Scholar
Vaillant, V., de Valk, H., Baron, E., Ancelle, T., Colin, P., Delmas, M. C., Dufour, B., Pouillot, R., Le Strat, Y., Weinbreck, P., Jougla, E. and Desenclos, J. C. (2005). Foodborne infections in France. Foodborne Pathogens and Disease 2, 221–232.Google Scholar
van Velthuysen, M. L. and Florquin, S. (2000). Glomerulopathy associated with parasitic infections. Clinical Microbiology Reviews 13, 55–66.Google Scholar
Vethanyagam, A. and Bryceson, A. D. (1976). Acquired toxoplasmosis presenting as hepatitis. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 524–525.Google Scholar
Vos, G. H. (1987). Population studies showing cross-reactivity of Toxoplasma gondii antibodies with antibodies to malignant cervical tissue antigens. South African Medical Journal 71, 78–82.Google ScholarPubMed
Wakefield, J. and Salway, R. (2001). A statistical framework for ecological and aggregate studies. Journal of the Royal Statistical Society: Series A (Statistics in Society) 164, 119–137.Google Scholar
Webster, J. P. (1994). The effect of Toxoplasma gondii and other parasites on activity levels in wild and hybrid. Rattus norvegicus Parasitology 109, 583–589.Google Scholar
Yagmur, F., Yazar, S., Temel, H. O. and Cavusoglu, M. (2010). May Toxoplasma gondii increase suicide attempt - preliminary results in Turkish subjects? Forensic Science International 199, 15–17.Google Scholar
Yazar, S., Gur, M., Ozdogru, I., Yaman, O., Oguzhan, A. and Sahin, I. (2006). Anti-Toxoplasma gondii antibodies in patients with chronic heart failure. Journal of Medical Microbiology 55, 89–92.Google Scholar
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