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J Pediatr Infect Dis 2017; 12(04): 202-208
DOI: 10.1055/s-0037-1603942
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Fetomaternal and Pediatric Toxoplasmosis

Helieh S. Oz
1   Department of Physiology and Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky, United States
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Publication History

12 January 2017

12 April 2017

Publication Date:
19 June 2017 (online)

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Abstract

Toxoplasmosis is one of the most important causes of foodborne illnesses and inflammatory complications, as well as congenital disorders. Promiscuous Toxoplasma is transmitted by contaminated food and animal produce, water, vegetations, fruits, and sexually through semen. Toxoplasma infects nucleated cells with a unique tropism for muscles and central nervous system and a mind bugging malicious effect. Pregnant women with acute or reactivated toxoplasmosis can transmit Toxoplasma via transplacental transmission to the fetus. The severity of congenital toxoplasmosis depends on the gestation period, as infection in early pregnancy causes more severe consequences. Congenital toxoplasmosis complications include miscarriage, encephalitis, neurological retardation, mental illnesses, auditory, and visual inflammatory disorders, cardiovascular abnormalities, and pains. Current therapies are inefficient for congenital and chronic toxoplasmosis or have severe side effects with life-threatening complications. There is an urgent need for effective and safe therapeutic modalities to treat complications of toxoplasmosis and effective vaccines to eliminate the infectious agent. This investigation will discuss the pathogenesis of fetomaternal, congenital, and pediatric toxoplasmosis, the currently available therapies in practice, and explore those therapeutic modalities in experimental stages for promising future trials.

Keywords

toxoplasma - fetomaternal - congenital - pediatric toxoplasmosis - mind alteration - sexual transmission
 

  • References

  • 1 Hoffmann S, Batz MB, Morris Jr JG. Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. J Food Prot 2012; 75 (07) 1292-1302
    CrossrefPubMedGoogle Scholar
  • 2 Oz HS. Maternal and congenital toxoplasmosis, currently available and novel therapies in horizon. Front Microbiol 2014; 5: 385 . doi: 10.3389/fmicb.2014.00385
    PubMedGoogle Scholar
  • 3 Dubey JP, Jones JL. Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol 2008; 38 (11) 1257-1278
    CrossrefPubMedGoogle Scholar
  • 4 Elsheikha HM, Büsselberg D, Zhu XQ. The known and missing links between Toxoplasma gondii and schizophrenia. Metab Brain Dis 2016; 31 (04) 749-759
    CrossrefPubMedGoogle Scholar
  • 5 Bierly AL, Shufesky WJ, Sukhumavasi W, Morelli AE, Denkers EY. Dendritic cells expressing plasmacytoid marker PDCA-1 are Trojan horses during Toxoplasma gondii infection. J Immunol 2008; 181 (12) 8485-8491
    CrossrefPubMedGoogle Scholar
  • 6 Scallan E, Griffin PM, Angulo FJ, Tauxe RV, Hoekstra RM. Foodborne illness acquired in the United States--unspecified agents. Emerg Infect Dis 2011; 17 (01) 16-22
    CrossrefPubMedGoogle Scholar
  • 7 Hotez PJ. Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2008; 2 (06) e256
    CrossrefPubMedGoogle Scholar
  • 8 Wolf A, Cowen D, Paige B. Human toxoplasmosis: occurrence in infants as an encephalomyelitis verification by transmission to animals. Science 1939; 89 (2306): 226-227
    CrossrefPubMedGoogle Scholar
  • 9 Jones JL, Lopez A, Wilson M, Schulkin J, Gibbs R. Congenital toxoplasmosis: a review. Obstet Gynecol Surv 2001; 56 (05) 296-305
    CrossrefPubMedGoogle Scholar
  • 10 Dehkordi FS, Borujeni MR, Rahimi E, Abdizadeh R. Detection of Toxoplasma gondii in raw caprine, ovine, buffalo, bovine, and camel milk using cell cultivation, cat bioassay, capture ELISA, and PCR methods in Iran. Foodborne Pathog Dis 2013; 10 (02) 120-125
    CrossrefPubMedGoogle Scholar
  • 11 Sharif M, Sarvi Sh, Shokri A. , et al. Toxoplasma gondii infection among sheep and goats in Iran: a systematic review and meta-analysis. Parasitol Res 2015; 114 (01) 1-16
    PubMedGoogle Scholar
  • 12 Oz HS. Fetal and maternal toxoplasmosis. In: Lee CM. , ed. Recent Advances in Toxoplasmosis Research. Lexington, KY: Nova Science Publications; 2014: 1-34
    Google Scholar
  • 13 Muzzio DO, Soldati R, Rolle L, Zygmunt M, Zenclussen AC, Jensen F. B-1a B cells regulate T cell differentiation associated with pregnancy disturbances. Front Immunol 2014; 5: 6 . doi: 10.3389/fimmu.2014.00006
    PubMedGoogle Scholar
  • 14 Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med 2001; 345 (19) 1400-1408
    CrossrefPubMedGoogle Scholar
  • 15 Dubey JP, Lago EG, Gennari SM, Su C, Jones JL. Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. Parasitology 2012; 139 (11) 1375-1424
    CrossrefPubMedGoogle Scholar
  • 16 Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R. Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling. Lancet 1999; 353 (9167): 1829-1833
    CrossrefPubMedGoogle Scholar
  • 17 Remington JS, McLeod R, Wilson CB, Desmonts G. Toxoplasmosis. In: Remington JS, Klein JO, Wilson CB, Nizet V, Maldonado YA. , eds. Infectious Diseases of the Fetus and Newborn Infant. 7th Edition. Philadelphia, PA: Elsevier Saunders; 2011: 915-1041
    Google Scholar
  • 18 Gilbert R, Gras L. ; European Multicentre Study on Congenital Toxoplasmosis. Effect of timing and type of treatment on the risk of mother to child transmission of Toxoplasma gondii. BJOG 2003; 110 (02) 112-120
    CrossrefPubMedGoogle Scholar
  • 19 Gras L, Wallon M, Pollak A. , et al; European Multicenter Study on Congenital Toxoplasmosis. Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres. Acta Paediatr 2005; 94 (12) 1721-1731
    CrossrefPubMedGoogle Scholar
  • 20 McLeod R, Boyer K, Karrison T. , et al; Toxoplasmosis Study Group. Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis 2006; 42 (10) 1383-1394
    CrossrefPubMedGoogle Scholar
  • 21 Boyer K, Hill D, Mui E. , et al; Toxoplasmosis Study Group. Unrecognized ingestion of Toxoplasma gondii oocysts leads to congenital toxoplasmosis and causes epidemics in North America. Clin Infect Dis 2011; 53 (11) 1081-1089
    CrossrefPubMedGoogle Scholar
  • 22 Mead PS, Slutsker L, Dietz V. , et al. Food-related illness and death in the United States. Emerg Infect Dis 1999; 5 (05) 607-625
    CrossrefPubMedGoogle Scholar
  • 23 Carral L, Kaufer F, Olejnik P, Freuler C, Durlach R. Prevention of congenital toxoplasmosis in a Buenos Aires hospital [in Spanish]. Medicina (B Aires) 2013; 73 (03) 238-242
    PubMedGoogle Scholar
  • 24 Buxton D, Thomson K, Maley S, Wright S, Bos HJ. Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant. Vet Rec 1991; 129 (05) 89-93
    CrossrefPubMedGoogle Scholar
  • 25 Oz HS, Tobin T. Atovaquone ameliorate gastrointestinal toxoplasmosis complications in a pregnancy model. Med Sci Monit 2012; 18 (09) BR337-BR345
    PubMedGoogle Scholar
  • 26 House PK, Vyas A, Sapolsky R. Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats. PLoS One 2011; 6 (08) e23277 . doi: 10.1371/journal.pone.0023277
    CrossrefPubMedGoogle Scholar
  • 27 Knight K. How pernicious parasites turn victims into zombies. J Exp Biol 2013; 216 (Pt 1): i-iv
    PubMedGoogle Scholar
  • 28 Wanderley FS, Porto WJ, Câmara DR. , et al. Experimental vaginal infection of goats with semen contaminated with the “CPG” strain of Toxoplasma gondii. J Parasitol 2013; 99 (04) 610-613
    CrossrefPubMedGoogle Scholar
  • 29 Arantes TP, Lopes WD, Ferreira RM. , et al. Toxoplasma gondii: Evidence for the transmission by semen in dogs. Exp Parasitol 2009; 123 (02) 190-194
    CrossrefPubMedGoogle Scholar
  • 30 Lopes WD, Rodriguez JD, Souza FA. , et al. Sexual transmission of Toxoplasma gondii in sheep. Vet Parasitol 2013; 195 (1-2): 47-56
    CrossrefPubMedGoogle Scholar
  • 31 Brown AS, Schaefer CA, Quesenberry Jr CP, Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry 2005; 162 (04) 767-773
    CrossrefPubMedGoogle Scholar
  • 32 Bachmann S, Schröder J, Bottmer C, Torrey EF, Yolken RH. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii. Psychopathology 2005; 38 (02) 87-90
    CrossrefPubMedGoogle Scholar
  • 33 Wang HL, Wang GH, Li QY, Shu C, Jiang MS, Guo Y. Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia. Acta Psychiatr Scand 2006; 114 (01) 40-48
    CrossrefPubMedGoogle Scholar
  • 34 Flegr J. Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. J Exp Biol 2013; 216 (Pt 1): 127-133
    CrossrefPubMedGoogle Scholar
  • 35 Fekadu A, Shibre T, Cleare AJ. Toxoplasmosis as a cause for behaviour disorders--overview of evidence and mechanisms. Folia Parasitol (Praha) 2010; 57 (02) 105-113
    CrossrefPubMedGoogle Scholar
  • 36 Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull 2007; 33 (03) 729-736
    CrossrefPubMedGoogle Scholar
  • 37 Pedersen MG, Mortensen PB, Norgaard-Pedersen B, Postolache TT. Toxoplasma gondii infection and self-directed violence in mothers. Arch Gen Psychiatry 2012; 69 (11) 1123-1130
    PubMedGoogle Scholar
  • 38 Zhang Y, Träskman-Bendz L, Janelidze S. , et al. Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry 2012; 73 (08) 1069-1076
    CrossrefPubMedGoogle Scholar
  • 39 Kaňková S, Sulc J, Křivohlavá R, Kuběna A, Flegr J. Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life. Early Hum Dev 2012; 88 (11) 879-884
    CrossrefPubMedGoogle Scholar
  • 40 Gale SD, Berrett AN, Brown B, Erickson LD, Hedges DW. No association between current depression and latent toxoplasmosis in adults. Folia Parasitol (Praha) 2016; 63: 32
    PubMedGoogle Scholar
  • 41 Shapira Y, Agmon-Levin N, Selmi C. , et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun 2012; 39 (1-2): 112-116
    CrossrefPubMedGoogle Scholar
  • 42 Oz HS. Toxoplasmosis, Pancreatitis, Obesity and Drug Discovery. Pancreat Disord Ther 2014; 4 (02) 1-3 . doi: http://dx.doi.org/10.4172/2165-7092.1000138. Accessed June 8, 2017
    PubMedGoogle Scholar
  • 43 Oz HS, Chen T, de Villiers WJ. Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models. Front Immunol 2013; 4 (132) 132 . doi: 10.3389/fimmu.2013.00132
    PubMedGoogle Scholar
  • 44 Oz HS, Chen T, Ebersole JL. A model for chronic mucosal inflammation in IBD and periodontitis. Dig Dis Sci 2010; 55 (08) 2194-2202
    CrossrefPubMedGoogle Scholar
  • 45 Brandtzaeg P. Inflammatory bowel disease: clinics and pathology. Do inflammatory bowel disease and periodontal disease have similar immunopathogeneses?. Acta Odontol Scand 2001; 59 (04) 235-243
    CrossrefPubMedGoogle Scholar
  • 46 Epple HJ. Therapy- and non-therapy-dependent infectious complications in inflammatory bowel disease. Dig Dis 2009; 27 (04) 555-559
    CrossrefPubMedGoogle Scholar
  • 47 Oz HS. Toxoplasmosis complications and novel therapeutic synergism combination of diclazuril plus atovaquone. Front Microbiol 2014; 5: 484
    PubMedGoogle Scholar
  • 48 Oz HS, Tobin T. Diclazuril protects against maternal gastrointestinal syndrome and congenital toxoplasmosis. Int J Clin Med 2014; 5 (03) 93-101
    CrossrefPubMedGoogle Scholar
  • 49 Erridge C, Duncan SH, Bereswill S, Heimesaat MM. The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5. PLoS One 2010; 5 (02) e9125 . doi: 10.1371/journal.pone.0009125
    CrossrefPubMedGoogle Scholar
  • 50 Lidar M, Langevitz P, Barzilai O. , et al. Infectious serologies and autoantibodies in inflammatory bowel disease: insinuations at a true pathogenic role. Ann N Y Acad Sci 2009; 1173: 640-648
    CrossrefPubMedGoogle Scholar
  • 51 Portugal LR, Fernandes LR, Alvarez-Leite JI. Host cholesterol and inflammation as common key regulators of toxoplasmosis and artherosclerosis development. Expert Rev Anti Infect Ther 2009; 7 (07) 807-819
    CrossrefPubMedGoogle Scholar
  • 52 Lige B, Sampels V, Coppens I. Characterization of a second sterol-esterifying enzyme in Toxoplasma highlights the importance of cholesterol storage pathways for the parasite. Mol Microbiol 2013; 87 (05) 951-967
    CrossrefPubMedGoogle Scholar
  • 53 Carter CJ. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders. J Pathog 2013; 2013: 1-29 http://dx.doi.org/10.1155/2013/965046
    PubMedGoogle Scholar
  • 54 Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis 1996; 23 (02) 277-282
    CrossrefPubMedGoogle Scholar
  • 55 Petersen E, Schmidt DR. Sulfadiazine and pyrimethamine in the postnatal treatment of congenital toxoplasmosis: what are the options?. Expert Rev Anti Infect Ther 2003; 1 (01) 175-182
    CrossrefPubMedGoogle Scholar
  • 56 Armstrong L, Isaacs D, Evans N. Severe neonatal toxoplasmosis after third trimester maternal infection. Pediatr Infect Dis J 2004; 23 (10) 968-969
    CrossrefPubMedGoogle Scholar
  • 57 Teixeira LE, Kanunfre KA, Shimokawa PT. , et al. The performance of four molecular methods for the laboratory diagnosis of congenital toxoplasmosis in amniotic fluid samples. Rev Soc Bras Med Trop 2013; 46 (05) 584-588
    CrossrefPubMedGoogle Scholar
  • 58 Dando C, Gabriel KE, Remington JS, Parmley SF. Simple and efficient method for measuring anti-toxoplasma immunoglobulin antibodies in human sera using complement-mediated lysis of transgenic tachyzoites expressing beta-galactosidase. J Clin Microbiol 2001; 39 (06) 2122-2125
    CrossrefPubMedGoogle Scholar
  • 59 Mizejewski GJ. Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Exp Biol Med (Maywood) 2007; 232 (08) 993-1004
    CrossrefPubMedGoogle Scholar
  • 60 Kaur M, Verma IC. Serum alpha feto-protein screening in high risk pregnancies. Indian J Pediatr 1995; 62 (01) 101-107
    CrossrefPubMedGoogle Scholar
  • 61 Olariu TR, Remington JS, Montoya JG. Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatr Infect Dis J 2014; 33 (06) 566-570
    CrossrefPubMedGoogle Scholar
  • 62 di Carlo P, Romano A, Casuccio A. , et al. Investigation and management of Toxoplasma gondii infection in pregnancy and infancy: a prospective study. Acta Pharmacol Sin 2011; 32 (08) 1063-1070
    CrossrefPubMedGoogle Scholar
  • 63 Centers for Disease Control and Prevention. Parasites -toxoplasmosis (Toxoplasma infection). Available at: https://www.cdc.gov/parasites/toxoplasmosis/ . Accessed March 2017
    PubMedGoogle Scholar
  • 64 Avelino MM, Amaral WN, Rodrigues IM. , et al. Congenital toxoplasmosis and prenatal care state programs. BMC Infect Dis 2014; 14: 33
    CrossrefPubMedGoogle Scholar
  • 65 Habib FA. Post-treatment assessment of acute Toxoplasma infection during pregnancy. J Obstet Gynaecol 2008; 28 (06) 593-595
    CrossrefPubMedGoogle Scholar
  • 66 Bessières MH, Berrebi A, Cassaing S. , et al. Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosis. Mem Inst Oswaldo Cruz 2009; 104 (02) 389-392
    CrossrefPubMedGoogle Scholar
  • 67 Hudson AT, Dickins M, Ginger CD. , et al. 566C80: a potent broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. Drugs Exp Clin Res 1991; 17 (09) 427-435
    PubMedGoogle Scholar
  • 68 Dunay IR, Heimesaat MM, Bushrab FN. , et al. Atovaquone maintenance therapy prevents reactivation of toxoplasmic encephalitis in a murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother 2004; 48 (12) 4848-4854
    CrossrefPubMedGoogle Scholar
  • 69 Cortina-Borja M, Tan HK, Wallon M. , et al; European Multicentre Study on Congenital Toxoplasmosis (EMSCOT). Prenatal treatment for serious neurological sequelae of congenital toxoplasmosis: an observational prospective cohort study. PLoS Med 2010; 7 (10) e1000351 . doi: 10.1371/journal.pmed.1000351
    CrossrefPubMedGoogle Scholar
  • 70 Hughes WT, Oz HS. Successful prevention and treatment of babesiosis with atovaquone. J Infect Dis 1995; 172 (04) 1042-1046
    CrossrefPubMedGoogle Scholar
  • 71 Oz HS, Westlund KH. “Human babesiosis”: an emerging transfusion dilemma. Int J Hepatol 2012; 2012: 1-5 . doi: 10.1155/2012/431761
    PubMedGoogle Scholar
  • 72 Freyre A, Falcón J, Méndez J, González M. Toxoplasma gondii: an improved rat model of congenital infection. Exp Parasitol 2008; 120 (02) 142-146
    CrossrefPubMedGoogle Scholar
  • 73 Srivastava IK, Vaidya AB. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother 1999; 43 (06) 1334-1339
    CrossrefPubMedGoogle Scholar
  • 74 Rolan PE, Mercer AJ, Tate E, Benjamin I, Posner J. Disposition of atovaquone in humans. Antimicrob Agents Chemother 1997; 41 (06) 1319-1321
    CrossrefPubMedGoogle Scholar
  • 75 Köhler S, Delwiche CF, Denny PW. , et al. A plastid of probable green algal origin in Apicomplexan parasites. Science 1997; 275 (5305): 1485-1489
    CrossrefPubMedGoogle Scholar
  • 76 Hackstein JH, Mackenstedt U, Mehlhorn H, Meijerink JP, Schubert H, Leunissen JA. Parasitic apicomplexans harbor a chlorophyll a-D1 complex, the potential target for therapeutic triazines. Parasitol Res 1995; 81 (03) 207-216
    PubMedGoogle Scholar
  • 77 Zhou W, Quan JH, Lee YH, Shin DW, Cha GH. Toxoplasma gondii Proliferation Require Down-Regulation of Host Nox4 Expression via Activation of PI3 Kinase/Akt Signaling Pathway. PLoS One 2013; 8 (06) e66306
    CrossrefPubMedGoogle Scholar
  • 78 Oz HS. Novel synergistic protective efficacy of atovaquone and diclazuril on fetal-maternal toxoplasmosis. Int J Clin Med 2014; 5 (15) 921-932
    CrossrefPubMedGoogle Scholar
  • 79 Assis RC, Luns FD, Beletti ME. , et al. Histomorphometry and macroscopic intestinal lesions in broilers infected with Eimeria acervulina. Vet Parasitol 2010; 168 (3-4): 185-189
    CrossrefPubMedGoogle Scholar