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Toxoplasmosis during pregnancy
Ariel Many, MD, Gideon Koren, MD, FRCPC
One of my female patients was tested for Toxoplasma and found positive for immunoglobulin G (IgG). She is planning to get pregnant soon. What are the risks for her and her baby?
Up to 25% of Canadians are IgG-positive for Toxoplasma due to past exposure. Immunoglobulin M (IgM) titres indicate current infection. Toxoplasma gondii is an obligate intracellular protozoan that has several forms during its life cycle: oocyte, tachyzoite, and cyst.
L'une de mes patientes a subi un test de dépistage du Toxoplasma et ses résultats se sont révélés positifs quant à la présence d'immunoglobuline G (IgG). Elle prévoit une grossesse sous peu. Quels sont les risques pour la mère et l'enfant?
Quelque 25% des Canadiens ont des résultats positifs quant à la présence d'IgG pour le Toxoplasma en raison d'une exposition antérieure. Les titres d'immunoglobuline M (IgM) indiquent une infection présente actuellement. Les Toxoplasma gondii sont des protozoaires intracellulaires obligatoires qui prennent diverses formes durant leur cycle de vie: oocyte, tachyzoïte et kyste.
Members of the cat family are definitely hosts of Toxoplasma. The parasite replicates in the cat's intestine. Millions of oocytes are shed in a cat's feces during its first infection. The oocytes become infectious when they are ingested by mammals and develop into tachyzoites. This form of the parasite is disseminated in blood and infects all tissues, mainly the central nervous system, eyes, muscles, and placenta. Some infected mammals have clinical manifestations. The cysts can remain in infected mammals for life in the skeletal muscles and brain. Development of the tachyzoite form can cause reactivation of disease in immunocompromised people infected with the cysts.
Humans can be infected through undercooked or raw meat (lamb, pork) infected with cysts or through food or water contaminated with oocytes excreted by cats (eg, unwashed vegetables). Transmission of Toxoplasma has also been reported through contaminated drinking water.1 The infection usually has no symptoms or very mild symptoms (fever, malaise, lymphadenopathy, hepatosplenomegaly); in immunocompromised patients, the infection can be very serious.
The incidence of positive serology for Toxoplasma varies in various regions and cultures. In North America, about 23% of the adult population is estimated to be seropositive.2 According to a recent Motherisk report, incidence in Canada could be somewhat lower.3
Women who contract Toxoplasma infections before pregnancy usually do not transmit it to their fetuses. If a mother becomes infected during pregnancy, the pathogen can be transmitted to her fetus across the placenta. Incidence of congenital Toxoplasma is about 1/10 000 live births in the New England region4 (but it is not mandatory to report it), but other reports suggest it could be up to 1/1000. This ratio would translate into 40 to 400 cases annually in Canada and would pose a major public health problem.
Effects on a fetus
Clinical manifestations of toxoplasmosis in fetuses and neonates vary. The typical triad of hydrocephalus, chorioretinitis, and intracranial calcifications does not always occur. Hepatosplenomegaly, thrombocytopenia, microcephaly, convulsions, fever, and small-for-gestational-age newborns all suggest Toxoplasma. Nevertheless, most neonates are asymptomatic at birth on routine pediatric examination. Deafness, mental retardation, and learning difficulties are often detected only later in life.
Risk of congenital toxoplasmosis is somewhat lower if infection occurs during the first trimester (10% to 25%) than if it occurs during the third trimester (60% to 90%). But the severity of congenital infection is substantially higher if infection occurs during the first trimester.5 These risks should be communicated clearly to women and their families.
Efforts to control Toxoplasma infection during pregnancy are often successful and greatly reduce the incidence of congenital toxoplasmosis.6 Health care providers should make preconception and prenatal education about toxoplasmosis a standard of care for pregnant women. Some preventive measures are listed in Table 1.7
Some countries in Europe where the incidence of Toxoplasma is high (France, Belgium) have screening programs for Toxoplasma for all pregnant women. If results of the screen are negative, serologic testing is done every month or trimester thereafter. In most countries where incidence is low, no screening is recommended. For example, the Royal College of Obstetricians and Gynaecologists in the United Kingdom and the American College of Obstetricians and Gynecologists8 do not recommend universal screening.
Diagnosis of toxoplasmosis is usually based on clinical symptoms and serologic tests. During acute infection, IgM and IgG are detected in serum within 1 to 2 weeks. In pregnant women, dating the likely start of infection is critical. If only IgG is detected and no IgM is detected, infection likely took place 6 to 12 months before. If IgM and IgG are detected, then a more thorough workup should be performed to try to determine the time of infection.
Testing for IgM for Toxoplasma can have false-positive results because some commercial kits are not sufficiently specific and because IgM antibodies can be detected more than a year after an acute infection. For these reasons, the United States Food and Drug Administration has issued guidelines for Toxoplasma antibody testing.9 When serum tests positive for IgM, an additional confirmatory assay should be performed at a reference laboratory. Another test that can aid in dating infection is IgG avidity. If the avidity is high, infection occurred 3 to 5 months before testing.
Testing for in utero infection
The most common way to test for in utero infection is a polymerase chain reaction test of amniotic fluid for Toxoplasma.10 Fetal blood sampling (cordocentesis) is not usually done because the fetal risk is higher than with amniocentesis, and cordocentesis is less sensitive. If results are positive, sonographic follow up is indicated. Signs such as calcifications, microcephaly, hydrocephalus, and severe in utero growth restriction strongly suggest in utero infection in the presence of documented maternal infection.8
Spiramycin, a macrolide antibiotic, is one of the drugs of choice for toxoplasmosis. It is approved for use during pregnancy in Europe, but in the United States it can be purchased only from the manufacturer. The adverse effects of spiramycin are usually mild and mainly produce gastrointestinal symptoms. Sulfonamides may also be used, but they have been associated with neonatal jaundice. Pyrimethamine is an antagonist of folic acid and is generally not recommended for use during pregnancy, but several reports have mentioned use of this agent among pregnant women.11
There are few data and no randomized clinical trials on the effectiveness of treatment in the presence of seroconversion during pregnancy. A European multicentre study suggested that treatment during pregnancy decreases the severity of congenital Toxoplasma in newborns but does not affect transmission rates.11,12
- Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB, et al. Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team. Lancet 1997;350:173-7.
- Jones JL, Kruszon-Moran D, Wilson M, McQuillan G, Navin T, McAuley JB. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am J Epidemiol 2001;154:357-65.
- Shuhaiber S, Koren G, Boskovic R, Einarson TR, Soldin OP, Einarson A. Seroprevalence of Toxoplasma gondii infection among veterinarian staff in Ontario, Canada: implications for teratogenic risk. BMC Infect Dis 2003;3:8.
- Guerina NG, Hsu HW, Meissner HC, Maguire JH, Lynfield R, Stechenberg B, 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(26):1858-63.
- Dunn D, Wallon M, Peyron F, Peterson E, Peckham C, Gilbert R. Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counseling. Lancet 1999;353:1829-33.
- Foulon W, Naessens A, Lauwers S, De Meuter F, Amy JJ. Impact of primary prevention on the incidence of toxoplasmosis during pregnancy. Obstet Gynecol 1988;72(3 Pt 1):363-6.
- Lopez A, Dietz VJ, Wilson M, Navin TR, Jones JL. Preventing congenital toxoplasmosis. MMWR Recomm Rep 2000;49(RR-2):59-68.
- American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infections. ACOG Pract Bull 2000, no. 20 (replaces educational bulletin number 177, February 1993). Int J Gynaecol Obstet 2002;76(1):95-107.
- Wilson M, Remington JS, Clavet C, Varney G, Press C, Ware D. Evaluation of six commercial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii. The FDA Toxoplasmosis Ad Hoc Working Group. J Clin Microbiol 1997;35:3112-5.
- Hohlfeld P, Daffos F, Costa JM, Thulliez P, Forestier F, Vidaud M. Prenatal diagnosis of congenital toxoplasmosis with PCR test on amniotic fluid. N Engl J Med 1994;331:695-9.
- Foulon W, Villena I, Stray-Pedersen B, Decoster A, Lappalainen M, Pinon JM, et al. Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children’s sequelae at age 1 year. Am J Obstet Gynecol 1999;180:410-5.
- Gilbert R, Gras I; 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;110:112-20.
Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Many is a member and Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation and, in part, by a grant from the Canadian Institutes of Health Research. He holds the Ivey Chair in Molecular Toxicology at the University of Western Ontario in London.Published Motherisk Updates are available on the College of Family Physicians of Canada website (http://www.cfpc.ca).