Congenital Toxoplasmosis

Congenital Toxoplasmosis SUSAN E. RITTER, CNM, MSN, MPH, A N D STEN H. VERMUND, MD, MSc, DPH Infection with Toxoplasma gondii, which occurs in both men and women, is usually subclinical and benign. Infection during pregnancy, however, may be a serious and even life-threatening event for the fetus. Antenatal education should focus on avoidance of contact with the sources of infection: the domestic cat and raw or rare meats. A review of toxoplasmosis is presented, and means for its primary prevention through antenatal education are outlined.

At least 3000 congenitally infected infants are born in the United States each year to mothers who contract toxoplasmosis while pregnant.' The organism was first noted in 1908 in mononuclear cells of the North African rodent gondi,* and was named Toxoplasma gondii from the Greek "toxon," which means arc. In 1923, the first case of congenital toxoplasma was reported by an ophthalmologist who found parasitic cysts in the retina of an 11-month-old child with congenital hydrocephalus and m i c r ~ p h t h a l m o sAn.~ tenatal transmission to the fetus was documented in the late 1 9 3 0 By ~ ~1948, Sabin and Feldman had originated a serologic dye test that made possible the epidemiologic and clinical study of i n f e ~ t i o n .Re~ cently, T. gondii was defined as a coccidian protozoal parasite whose host is the cat.6

BIOLOGY

T. gondii has been found in the tissue of most vertebrate species, but its full development can only occur in the small intestines of domesticated cats and probably in wild felines as well. The organism exists in three morphologic forms: the tachyzoite (or trophozoite), the bradyzoite o r tissue cyst, and the oocyst. As in malaria, sexual and asexual reproductive cycles exist (Figure l).' The tachyzoite is seen in the acute stage of infection when it invades every type of mammalian cell but has a predilection for the brain Accepted: April 1984.

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and the skeletal and heart muscles.8 This asexual form of the organism is used in serologic tests. The second asexual form, the bradyzoite, forms within the host cell and is transmitted to man and other animals by ingestion of undercooked meat containing bradyzoites. Because these viable parasites can live a s long a s the animal host, demonstration of cysts in histologic sections does not necessarily mean that the infection was acquired recently. The third form, the oocyst, reflects the sexual stage in the organism's definitive host, the cat. Upon maturation, the oocysts a re excreted in the cat feces but d o not become infective unti'l they have undergone an internal development (sporulation) for about two to three days; the sporulated oocysts remain infective for one to three weeks. Inadvertent ingestion of oocysts by man or cat will cause infection. Oocysts are easily dispersed by wind, water, o r fomites and may also be transportable by cockroaches, flies, and similar paratenic hosts, although this has not been p r ~ v e nOocysts .~ a r e usually shed by young cats (between six and 12 months of age) when the passive immunity transferred by their mothers is lost and the hunting of rodent hosts whose raw meat may contain bradyzoites has begun."

OCCURRENCE A N D TRANSMISSION Congenital toxoplasmosis in man may occur when the mother acquires a primary infection during pregnancy. The risk to the fetus appears to be related to

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Figure 1. Life cycle of Toxoplasrna gondii. Reprinted from Katz M, Despommiers DD, Gwadz R. Parasitic diseases. New York: Springer-Verlag, 1982:145 with permission of the authors and the publisher.’

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the time of maternal infection.* Maternal infection ir, the first trimester infrequently results in transmission of the organism to the fetus, but if such transmission does occur, severe disease will often result. When acquired late in pregnancy, the protozoan is more readily transmitted to the fetus, but the infection is less virulent.l 1 Congenital toxoplasmosis does not, in theory, recur in consecutive pregnancies, although its rare occurrence has been reported in women with Chronic infection may predisa chronic pose to spontaneous abortion, but this remains spec~ lati ve . An ’ ~ unlikely route of infection is by blood transfusion. Infection through ingestion of breastmilk or unpasteurized milk has not been demonstrated.*.l5 Toxoplasmosis can be particularly dangerous in the immunologically compromised host. If chronic infection is present, recrudescent toxoplasmosis may occur whenever the patient’s immune defenses ar e impaired. Six of 1000 pregnant women in the United States will acquire primary infection during pregnancy, and about 45% of these women will give birth to a congenitally infected infanL8
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Table 1. Prevalence of Toxoplasma Antibodies* in Children and Adultst Per Cent Positive Origin of Sera

6 mo-I 0 yr

30-40 yr

Austria El Salvador Navajo Indians (Ariz:ona) New Orleans, LA Pittsburgh, PA Finland Portland, OR England (Wales) St. Louis, MO Paris Tahiti Trinidad Southern California

7 40 0

62 93 5 42 45 35 26 25 33 87 77 45 27

21 8 7 7

8 6 33 45 29 10

Dye test titer more than 1:I6.

t Reprinted with permission from Remington JS, Desmonts G. Toxoplasmosis. In: Remington JS, Klein J, ed. Infectious disease of the fetus and newborn infant. 2nd ed. Philadelphia: WB Saunders. 1983.

ditis, o r pneumonitis may rarely ensue. Retinochoroiditis, which occurs with some frequency after congenital infection, seems to have occurred in only a few cases following acquired i n f e ~ t i o n . ’ ~ Serologic tests for specific T. gondii antibodies have been the preferred means of diagnosis. The test results should be interpreted according to what is known about the time of appearance and duration of these antibodies (Figure 2).*O Because serologic tests a re not standardized, it is important to know the techniques employed by th e reference laboratory used. If primary infection is suspected, the patient’s serum should be tested by indirect immunofluorescence antibody (IFA) for immunoglobulin M (IgM), ideally within the first few weeks of exposure. Assay by immunoglobulin C (1gG)-IFA or by the Sabin-Feldman

SFDT or IgG-IFA

CF

0

I

2

3

4

5

6

7

8

9

10 II 12” 18”30”>48

Month after onset of clinical illness

Figure 2. Mean titers of Sabin-Feldman dye test (SFDT) or IgGimmunofluorescent antibody test (IgG-IFA). Complement Fixation (CF), and IgM-immunofluorescent antibody test (IgM-IFA) at various times after onset of illness due to Toxoplasma gondiiin 27 patients. Adapted from Reference 20.

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dye test (SFDT) is recommended if exposure occurred several months before the serum is obtained. The Sabin-Feldman dye test requires use of live parasites and is, therefore, less practical than the indirect immunofluorescence antibody. The diagnosis of congenital toxoplasmosis can be made by identification of immunoglobulin M antibodies in the cord or neonatal serum (IgM-IFA) or by isolation of T.gondii organisms from the placenta or cord blood. (Histologic examination and isolation procedures are difficult to perform and take a longer time for confirmation than serology.) An infant whose immunoglobulin G (IgG) titers are high at birth (demonstrated by Sabin-Feldman dye test or IgG-IFA) may have maternal immunoglobulin G that has crossed the placenta; in the absence of a suggestive IgM-IFA result, congenital infection is not documented unless the immunoglobulin G titers rise or persist at high levels for several months. Complement fixation (CF) is often useful (Figure 2). Indirect hemagglutination (IHA) is less sensitive than the indirect immunofluorescence antibody and the complement fixation. The enzyme-linked immunosorbent assay (ELISA) may be more commonly used in the future because of ease of technical execution and improved sensitivity.” Between one and 41% of the domestic cat population sheds oocysts, depending upon where the cats live and feed.” About 40 to 60% of the cat population in the United States has latent or asymptomatic toxoplasmosis and, thus, it does not seem cost beneficial for pet cats to be routinely tested serologically. In any case, such tests are poor markers of cat infectivity because infectious oocysts can be discharged before the cat develops antibodiesz3

TREATMENT No treatment is usually necessary for chronic asymptomatic toxoplasmosis. If infection is acquired during pregnancy, therapeutic abortion should be considered only when the likelihood of infection is very high.” Drug therapy in the mother with pyrimethamine plus a sulfonamide (trisulfapyrimidine or sulfadiazine) has been beneficial against the proliferative form of Toxoplusmu but is potentially teratogenic and, therefore, not recommended. Spiramycin has been used in pregnancy in various countries” but is not approved in the United States. Postnatal treatment of the infant has been efficacious in some ins t a n c e ~Given . ~ ~ the uncertain safety and efficacy of intrapartum therapy and the unavailability of a vaccine, serologic screening of pregnant women is considered by some experts to be cost effective.16 438

Primary prevention remains the strategy of choice in control of congenital toxoplasmosis, and antenatal education has succeeded in reducing rates of seroconversion in pregnan~y.’~ Avoidance of infection is particularly important for seronegative pregnant Women and immunocompromised individuals. Based on the life cycle of T. gondii (Figure l), a number of preventive measures can be recommended antenatally. The pregnant woman should avoid ingestion of tissue cysts by thorough cooking of meat to at least 150°F or by equivalent meat processing.z6Hands need to be well washed after handling raw meat, and contact with eyes and mucous membranes should be avoided during food preparation. Mutton, pork, and probably undercooked beef are often impli~ated.’~ Seronegative women of childbearing age should be cautioned when traveling in areas of high prevalence to avoid local foods like “steak tartare” and sausages that may contain contaminated meats. Cats should be kept from hunting and fed dry, canned, or cooked meats only to eliminate the shedding of oocysts in cat feces. Pregnant women should avoid caring for cats and should delegate cleaning of litterpans to someone else. Cat feces should be disposed of daily (before oocysts sporulate) by incineration or flushing down a toilet. Although generally resistant to antiseptics, oocysts can be killed by cleaning the litterpan with boiling water for five minutes or disinfecting it with five percent ammonium hydroxide for 10 minutes. Women who work in gardens or with soil should wear gloves and should wash their hands thoroughly before eating or touching the face. Outdoor sandboxes should be covered when they are not in use. Potential paratenic hosts such as flies and cockroaches should be controlled. Drinking water obtained from streams, ponds, or lakes that may be frequented by cats should be boiled.

SUMMARY At least 3000 congenitally infected infants are born in the United States each year to women who contract toxoplasmosis while pregnant. Because congenital toxoplasmosis can be prevented, antenatal counseling should always include practical suggestions for the prevention of toxoplasmosis.

REFERENCES 1. Krick J, Remington J. Toxoplasmosis in the adult-an overview. New Engl J Med 1978;298:550-3.

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2. Nicolle C, Manceaux I. Sur une infection h corps d e Leishman (ou organismes voisins) du gondi. Comptes Rendus d e Academic Des Sciences 1908;147:763-6. 3. Janku J. Die Pathogenese und pathologische Anatomie des gelben Fleckes im normal grossen sowie im mikrophtalmischen Auge mit Parasitenbefund in der Netzhaut. Ceskoslovenska Parasitologie 1959;6:9-57. 4. Wolf A, Cowem D, Paige B. Human toxoplasmosis: occurrence in infants as encephalomyelitis: verification by transmission to animals. Science 1939;89:226-7. 5 . Sabin A, Feldman H. Dyes as microchemical indicators of a new immunity phenomenon affecting a protozoon parasite (Toxoplasma). Science 1948;108:660-3. 6. Frenkel J , Dubey J, Miller N. Toxoplasmagondiiin cats: fecal stages identified a s coccidian oocysts. Science 1970;167:893-6. 7. Katz M , Despommiers D, Gwatz R. Parasitic diseases. New York: Springer-Verlag, 1982. 8. Rernington JS, Desmonts G. Toxoplasmosis. In: Remington JS, Klein J, ed. Infectious disease of the fetus and newborn infant. 2nd ed. Philadelphia: WB Saunders, 1983. 9. Ruiz A, Frankel J. Intermediate and transport hosts of Toxoplasma gondii in Costa Rica. Am J Trop Med Hyg 1980;29:1161-6. 10. Fayer R. Toxoplasmosis update and public health implications. Canadian Veterinary Journal 1981;22:344-52. 11. Desmonts G, Couvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. N Engl J Med 1974;290:1110-6. 12. Handrick W, Neumann G, Neugebauer A, et al. Uber einen Fall von konnataler Toxoplasmose nach einer drei Jahre zuruckliegenden Toxoplasmainfektion der Mutter. Kinderaerztl Prax 1973;41:263-7. 13. Stray-Pedersen B, Lorentzen-Styr A. Uterine toxoplasma infections and repeated abortions. Am J Obstet Gynecol 1977;128:716-21. 14. Kirnball A, Kean B, Kellner A. The risk of transmitting toxoplasmosis by blood transfusion. Transfusion 1965;5: 447-51. 15. Wilson B, Remington J. What can be done to prevent congenital toxoplasmosis? Amer J Obstet Gynecol 1980;13tk3S7-63. 16. Stray-Pedersen B. A prospective study of acquired toxoplasmosis among 8048 pregnant women in the Oslo area. Am J Obstet Gynecol 1980;136:399-406.

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17. Beach PG. Prevalence of antibodies to Toxoplasma gondii in pregnant women in Oregon. J Infect Dis 1979;140: 780-3. 18. Khodr G , Matossian R. Hydrops fetales and congenital toxoplasmosis: value of direct immunofluorescence test. Obstet Gynecol 1978;51:74-7. 19. Asbell PA, Vermund SH, Hofeldt AJ. Presumed toxoplasmic retinochoroiditis in four siblings. Am J Ophthalmol 1982;94:656-63. 20. Welch PC, Masur H, Jones TC, et al. Serologic diagnosis of acute lymphadenopathic toxoplasmosis. J Infect Dis 1980;142~256-64. 21. Naot Y, Desmonts G, Remington JS. IgM enzyme-linked immunosorbent assay test for the diagnosis of congenital toxoplasma infection. J Pediatr 1981;98:32-6. 22. Dubey JP. Toxoplasma hammondia, Besnoitia, Sarcocystis, and other tissue cyst-forming coccidia of man and animals. In: Kreier JP, ed. Parasitic protozoa; vol3. New York: Academic Press, 1977. 23. Frenkel J. Toxoplasmosis in cats and man. Feline Practice 1975;5:28-41. 24. Coradello H, Lubec G, Simbruner G. Angeborene Toxoplasmose bei 2 Neugeborenen. Wien Klin Wochenschr 1981;93:93-6. 25. Roux C, Desmonts G, Mulliez N, et al. Toxoplasmosis and pregnancy. J Gynecol Obstet Biol Reprod 1976;5: 249-64. 26. Work K. Resistance of Toxoplasma gondii encysted in pork. Acta Pathol Microbiol Scand 1968;73:85-92. 27. Kean B, Kimball A, Christenson W. An epidemic of acute toxoplasmosis. JAMA 1969;208:1002-4.

Address for correspondence: Susan Ritter, CNM, 126 Stoddard St., East Lansing, MI 48823.

Susan Ritter is a nurse-midwife with the Barny-Eaton District Health Department, Charlotte, Michigan. Sten Verrnund is assistant professor of Epidemiology, Social Medicine, and Pediatrics at Montefiore Hospital, Albert-Einstein Medical Center, Bronx, New York.

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