Congenital toxoplasmosis: Clinical features and diagnosis
- Nicholas G Guerina, MD, PhD
Nicholas G Guerina, MD, PhD
- Adjunct Assistant Clinical Professor
- Tufts University School of Medicine
- Jennifer Lee, MD, MS
Jennifer Lee, MD, MS
- Instructor in Pediatrics
- Harvard Medical School
- Ruth Lynfield, MD
Ruth Lynfield, MD
- Adjunct Professor of Medicine
- University of Minnesota
- Section Editors
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
- Leonard E Weisman, MD
Leonard E Weisman, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
Toxoplasma gondii is a ubiquitous protozoan parasite that infects animals and humans. Toxoplasma infection typically is asymptomatic in immunocompetent hosts. However, serious disease can occur, most frequently in the setting of immunosuppression or congenital infection. The fetus, newborn, and young infant with congenital Toxoplasma infection are at risk of infection-associated complications, particularly retinal disease that can occur into adulthood.
The clinical features and diagnosis of congenital toxoplasmosis in infants and children will be reviewed here. The treatment, outcome, and prevention of congenital toxoplasmosis and acquired toxoplasmosis in pregnancy, immunocompetent hosts, and HIV-infected patients are discussed separately. (See "Congenital toxoplasmosis: Treatment, outcome, and prevention" and "Toxoplasmosis and pregnancy" and "Toxoplasmosis in immunocompetent hosts" and "Toxoplasmosis in HIV-infected patients".)
Congenital toxoplasmosis is caused by T. gondii, an intracellular protozoan parasite. Toxoplasma has a unique biphasic life cycle that consists of a sexual cycle that occurs exclusively in felines and an asexual cycle that can occur in other animals and humans (figure 1). Cats acquire the infection by ingesting oocysts in soil or tissue cysts from small prey. Replication occurs in the intestine of the cat, and oocysts are formed, excreted, and become infectious after 24 hours. During the primary infection, the cat can shed millions of oocysts daily for up to three weeks. Humans who come in contact with cat feces containing Toxoplasma oocysts may inadvertently ingest contaminated material, and the asexual phase of Toxoplasma replication begins. Oocysts rupture to release sporozoites that divide and become tachyzoites, which are characteristic of the acute stage of infection. Tachyzoites spread throughout the body via the bloodstream and lymphatics. With an adequate immune response, the tachyzoites are sequestered in tissue cysts and form bradyzoites. Bradyzoites are indicative of the chronic stage of infection and can persist for the life of the individual.
Congenital toxoplasmosis occurs throughout the world. The prevalence varies geographically according to the risk of primary Toxoplasma infection in women of child-bearing age [1-3]. (See "Toxoplasmosis and pregnancy", section on 'Incidence'.)
The highest rates of infection with T. gondii have been reported in Europe, Central America, Brazil, and Central Africa . The environment plays a key role in perpetuating the life cycle of T. gondii, and warm, humid climates are ideal. In parts of Central America, seropositivity starts around one year of age, when children begin playing in contaminated soil, and it reaches 50 to 75 percent by adolescence. In other areas, transmission occurs primarily through the ingestion of undercooked meat. In these areas, depending on eating customs, seropositivity may begin in adolescence (or sooner) and can continue throughout adulthood. In many parts of the world, the pattern is mixed. (See "Toxoplasmosis in immunocompetent hosts", section on 'Prevalence of infection'.)
- Berger F, Goulet V, Le Strat Y, Desenclos JC. Toxoplasmosis among pregnant women in France: risk factors and change of prevalence between 1995 and 2003. Rev Epidemiol Sante Publique 2009; 57:241.
- Remington JS, McLeod R, Wilson CB, Desmonts G. Toxoplasmosis. In: Infectious Diseases of the Fetus and Newborn Infant, 7th ed, Remington, JS, Klein, JO, Wilson, CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.918.
- McAuley JB, Boyer KM, Remington JS, McLeod RL. Toxoplasmosis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.2987.
- Guerina NG, Hsu HW, Meissner HC, et al. Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. The New England Regional Toxoplasma Working Group. N Engl J Med 1994; 330:1858.
- Varella IS, Canti IC, Santos BR, et al. Prevalence of acute toxoplasmosis infection among 41,112 pregnant women and the mother-to-child transmission rate in a public hospital in South Brazil. Mem Inst Oswaldo Cruz 2009; 104:383.
- Prusa AR, Kasper DC, Pollak A, et al. The Austrian Toxoplasmosis Register, 1992-2008. Clin Infect Dis 2015; 60:e4.
- Dubey JP, Jones JL. Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol 2008; 38:1257.
- American Academy of Pediatrics. Toxoplasma gondii infections (Toxoplasmosis). In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.787.
- Montoya JG, Remington JS. Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 2008; 47:554.
- SYROCOT (Systematic Review on Congenital Toxoplasmosis) study group, Thiébaut R, Leproust S, et al. Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data. Lancet 2007; 369:115.
- Lynfield R, Ogunmodede F, Guerina NG. Toxoplasmosis. In: Oski's Pediatrics Principles and Practice, 4th ed, McMillan JA, Feigin RD, DeAngelis CD, Jones MD (Eds), Lippincott Williams & Wilkins, Philadelphia 2006. p.1351.
- Jamieson SE, de Roubaix LA, Cortina-Borja M, et al. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis. PLoS One 2008; 3:e2285.
- Gilbert RE, Freeman K, Lago EG, et al. Ocular sequelae of congenital toxoplasmosis in Brazil compared with Europe. PLoS Negl Trop Dis 2008; 2:e277.
- Tamma P. Toxoplasmosis. Pediatr Rev 2007; 28:470.
- Desmonts G, Couvreur J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med 1974; 290:1110.
- Lebech M, Andersen O, Christensen NC, et al. Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group . Lancet 1999; 353:1834.
- Couvreur J, Desmonts G, Tournier G, Szusterkac M. [A homogeneous series of 210 cases of congenital toxoplasmosis in 0 to 11-month-old infants detected prospectively]. Ann Pediatr (Paris) 1984; 31:815.
- Alford CA Jr, Stagno S, Reynolds DW. Congenital toxoplasmosis: clinical, laboratory, and therapeutic considerations, with special reference to subclinical disease. Bull N Y Acad Med 1974; 50:160.
- McAuley J, Boyer KM, Patel D, et al. Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chicago Collaborative Treatment Trial. Clin Infect Dis 1994; 18:38.
- McLeod R, Boyer K, Karrison T, et al. Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis 2006; 42:1383.
- Eichenwald HF. A study of congenital toxoplasmosis with particular emphasis on clinical manifestations, sequelae and therapy. In: Human Toxoplasmosis, Siim JC (Ed), Munksgaard, Copenhagen 1959.
- Wilson CB, Remington JS, Stagno S, Reynolds DW. Development of adverse sequelae in children born with subclinical congenital Toxoplasma infection. Pediatrics 1980; 66:767.
- Sever JL, Ellenberg JH, Ley AC, et al. Toxoplasmosis: maternal and pediatric findings in 23,000 pregnancies. Pediatrics 1988; 82:181.
- Koppe JG, Loewer-Sieger DH, de Roever-Bonnet H. Results of 20-year follow-up of congenital toxoplasmosis. Lancet 1986; 1:254.
- Phan L, Kasza K, Jalbrzikowski J, et al. Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life. Am J Ophthalmol 2008; 146:375.
- Phan L, Kasza K, Jalbrzikowski J, et al. Longitudinal study of new eye lesions in treated congenital toxoplasmosis. Ophthalmology 2008; 115:553.
- Mets MB, Holfels E, Boyer KM, et al. Eye manifestations of congenital toxoplasmosis. Am J Ophthalmol 1996; 122:309.
- Mets MB, Holfels E, Boyer KM, et al. Eye manifestations of congenital toxoplasmosis. Am J Ophthalmol 1997; 123:1.
- Setian N, Andrade RS, Kuperman H, et al. Precocious puberty: an endocrine manifestation in congenital toxoplasmosis. J Pediatr Endocrinol Metab 2002; 15:1487.
- Meenken C, Assies J, van Nieuwenhuizen O, et al. Long term ocular and neurological involvement in severe congenital toxoplasmosis. Br J Ophthalmol 1995; 79:581.
- Massa G, Vanderschueren-Lodeweyckx M, Van Vliet G, et al. Hypothalamo-pituitary dysfunction in congenital toxoplasmosis. Eur J Pediatr 1989; 148:742.
- Wright R, Johnson D, Neumann M, et al. Congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or Cytomegalovirus infection. Pediatrics 1997; 100:E9.
- Hutson SL, Wheeler KM, McLone D, et al. Patterns of Hydrocephalus Caused by Congenital Toxoplasma gondii Infection Associate With Parasite Genetics. Clin Infect Dis 2015; 61:1831.
- McAuley JB. Toxoplasmosis in children. Pediatr Infect Dis J 2008; 27:161.
- Centers for Disease Control and Prevention. Laboratory identification of parasites of public health concern. Toxoplasmosis [Toxoplasma gondii]. http://www.dpd.cdc.gov/dpdx/HTML/Toxoplasmosis.htm (Accessed on December 13, 2010).
- Wong SY, Hajdu MP, Ramirez R, et al. Role of specific immunoglobulin E in diagnosis of acute toxoplasma infection and toxoplasmosis. J Clin Microbiol 1993; 31:2952.
- Naot Y, Desmonts G, Remington JS. IgM enzyme-linked immunosorbent assay test for the diagnosis of congenital Toxoplasma infection. J Pediatr 1981; 98:32.
- Decoster A, Darcy F, Caron A, Capron A. IgA antibodies against P30 as markers of congenital and acute toxoplasmosis. Lancet 1988; 2:1104.
- Stepick-Biek P, Thulliez P, Araujo FG, Remington JS. IgA antibodies for diagnosis of acute congenital and acquired toxoplasmosis. J Infect Dis 1990; 162:270.
- Contopoulos-Ioannidis D, Montoya JG. Toxoplasma gondii (toxoplasmosis). In: Principles and Practice of Pediatric Infectious Diseases, 4th, Long SS, Pickering LK, Prober CG. (Eds), Elsevier Saunders, Edinburgh 2012. p.1308.
- Boyer KM. Diagnostic testing for congenital toxoplasmosis. Pediatr Infect Dis J 2001; 20:59.
- Filisetti D, Cocquerelle V, Pfaff A, et al. Placental testing for Toxoplasma gondii is not useful to diagnose congenital toxoplasmosis. Pediatr Infect Dis J 2010; 29:665.
- Olariu TR, Remington JS, Montoya JG. Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatr Infect Dis J 2014; 33:566.
- Rabilloud M, Wallon M, Peyron F. In utero and at birth diagnosis of congenital toxoplasmosis: use of likelihood ratios for clinical management. Pediatr Infect Dis J 2010; 29:421.
- Wallon M, Dunn D, Slimani D, et al. Diagnosis of congenital toxoplasmosis at birth: what is the value of testing for IgM and IgA? Eur J Pediatr 1999; 158:645.
- Gilbert RE, Thalib L, Tan HK, et al. Screening for congenital toxoplasmosis: accuracy of immunoglobulin M and immunoglobulin A tests after birth. J Med Screen 2007; 14:8.
- CLINICAL FEATURES
- Subclinical infection
- Clinically apparent disease
- Late manifestations
- - Chorioretinitis
- - Other late manifestations
- DIFFERENTIAL DIAGNOSIS
- EVALUATION AND DIAGNOSIS
- Clinical suspicion
- Clinical evaluation
- Laboratory evaluation
- - Serology
- - Demonstration of T. gondii
- - Other laboratory tests
- SUMMARY AND RECOMMENDATIONS