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M
embers of the cat family are defi nitely hosts of Toxoplasma. Th e 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 mam- mals 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. Th e 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 immunocompro- mised 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 Th e infection usu- ally has no symptoms or very mild symptoms (fever, malaise, lymphadenopathy, hepatosplenomegaly);
in immunocompromised patients, the infection can be very serious.
Th e incidence of positive serology for Toxoplasma varies in various regions and cultures. In North America, about 23% of the adult population is esti- mated 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
Toxoplasmosis during pregnancy
Ariel Many, MD Gideon Koren, MD, FRCPC
ABSTRACT
QUESTION 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?
ANSWER 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.
RÉSUMÉ
QUESTION 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?
RÉPONSE 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.
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translate into 40 to 400 cases annually in Canada and would pose a major public health problem.
Eff ects on a fetus
Clinical manifestations of toxoplasmosis in fetuses and neonates vary. Th e typical triad of hydrocepha- lus, chorioretinitis, and intracranial calcifi cations does not always occur. Hepatosplenomegaly, throm- bocytopenia, microcephaly, convulsions, fever, and small-for-gestational-age newborns all sug- gest Toxoplasma. Nevertheless, most neonates are asymptomatic at birth on routine pediatric exami- nation. Deafness, mental retardation, and learning diffi culties are often detected only later in life.
Risk of congenital toxoplasmosis is somewhat lower if infection occurs during the fi rst trimester (10% to 25%) than if it occurs during the third tri- mester (60% to 90%). But the severity of congenital infection is substantially higher if infection occurs during the fi rst trimester.5 Th ese risks should be communicated clearly to women and their families.
Prevention
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 pre- natal education about toxoplasmosis a standard of care for pregnant women. Some preventive mea- sures are listed in Table 1.7
Screening
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 coun- tries where incidence is low, no screening is recom- mended. 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
Diagnosis of toxoplasmosis is usually based on clin- ical 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 suffi ciently specifi c 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 con- firmatory assay should be performed at a refer- ence laboratory. Another test that can aid in dating infection is IgG avidity. If the avidity is high, infec- tion occurred 3 to 5 months before testing.
Testing for in utero infection
Th e most common way to test for in utero infec- tion is a polymerase chain reaction test of amni- otic fl uid 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 pos- itive, sonographic follow up is indicated. Signs such as calcifi cations, microcephaly, hydrocepha- lus, and severe in utero growth restriction strongly suggest in utero infection in the presence of docu- mented maternal infection.8
Table 1. Recommendations for preventing Toxoplasma infection during pregnancy Wash vegetables and fruit thoroughly
Wash your hands and utensils after touching unwashed vegetables or uncooked meat
Avoid direct contact with soil and sand
Avoid changing cat litter. If you have to, use gloves and wash your hands Eat only well cooked meat. Pork, lamb, beef, veal, and poultry should be cooked until the meat reaches 80oC in the centre
Adapted from Lopez et al.7
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Treatment
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 gastrointesti- nal 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 preg- nancy, but several reports have mentioned use of this agent among pregnant women.11
There are few data and no randomized clini- cal trials on the eff ectiveness of treatment in the presence of seroconversion during pregnancy. A European multicentre study suggested that treat- ment during pregnancy decreases the severity of congenital Toxoplasma in newborns but does not aff ect transmission rates.11,12
References
1. Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB, et al. Outbreak of toxo- plasmosis associated with municipal drinking water. Th e BC Toxoplasma Investigation Team. Lancet 1997;350:173-7.
2. 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.
3. 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.
4. Guerina NG, Hsu HW, Meissner HC, Maguire JH, Lynfi eld R, Stechenberg B, et al.
Neonatal serologic screening and early treatment for congenital Toxoplasma gon- dii infection. Th e New England Regional Toxoplasma Working Group. N Engl J Med 1994;330(26):1858-63.
5. Dunn D, Wallon M, Peyron F, Peterson E, Peckham C, Gilbert R. Mother-to-child transmis- sion of toxoplasmosis: risk estimates for clinical counseling. Lancet 1999;353:1829-33.
6. 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.
7. Lopez A, Dietz VJ, Wilson M, Navin TR, Jones JL. Preventing congenital toxoplasmosis.
MMWR Recomm Rep 2000;49(RR-2):59-68.
8. American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infec- tions. ACOG Pract Bull 2000, no. 20 (replaces educational bulletin number 177, February 1993). Int J Gynaecol Obstet 2002;76(1):95-107.
9. Wilson M, Remington JS, Clavet C, Varney G, Press C, Ware D. Evaluation of six commer- cial kits for detection of human immunoglobulin M antibodies to Toxoplasma gondii. Th e FDA Toxoplasmosis Ad Hoc Working Group. J Clin Microbiol 1997;35:3112-5.
10. Hohlfeld P, Daff os F, Costa JM, Th ulliez P, Forestier F, Vidaud M. Prenatal diagnosis of con- genital toxoplasmosis with PCR test on amniotic fl uid. N Engl J Med 1994;331:695-9.
11. 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 trans- mission and children’s sequelae at age 1 year. Am J Obstet Gynecol 1999;180:410-5.
12. Gilbert R, Gras I; European Multicentre Study on Congenital Toxoplasmosis. Eff ect of tim- ing 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.
Do you have questions about the safety of drugs, chemi- cals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at (416) 813-7562; they will be addressed in future Motherisk Updates.
Published Motherisk Updates are available on the College of Family Physicians of Canada website (www.cfpc.ca) and also on the Motherisk website (www.motherisk.org).
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