Preventing Congenital Toxoplasmosis

The material in this report was prepared for publication by:

National Center for Infectious Diseases 
James M. Hughes, M.D.
Director

Division of Parasitic Diseases 
Daniel G. Colley, Ph.D.
Director

Preventing Congenital Toxoplasmosis

Adriana Lopez, M.H.S.
Vance J. Dietz, M.D.
Marianna Wilson, M.S.
Thomas R. Navin, M.D.
Jeffrey L. Jones, M.D., M.P.H.
Division of Parasitic Diseases
National Center for Infectious Diseases

Abstract

Scope of the Problem: Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (e.g., mental retardation, blindness, and epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each year in the United States. Of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be caused by eating contaminated meat, making toxoplasmosis the third leading cause of foodborne deaths in this country.

Etiologic Factors: Toxoplasma can be transmitted to humans by three principal routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of oocysts, an environmentally resistant form of the organism that cats pass in their feces, with exposure of humans occurring through exposure to cat litter or soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly infected pregnant woman passing the infection to her unborn fetus.

Recommendations for Prevention: Toxoplasma infection can be prevented in large part by a) cooking meat to a safe temperature (i.e., one sufficient to kill Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before eating; c) cleaning cooking surfaces and utensils after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly; and e) not feeding raw or undercooked meat to cats and keeping cats inside to prevent acquisition of Toxoplasma by eating infected prey.

Research Agenda: Priorities for research were discussed at a national workshop sponsored by CDC in September 1998 and include a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic tests to determine when a person becomes infected with Toxoplasma, and c) determining the applicability of national screening programs.

Conclusion: Many cases of congenital toxoplasmosis can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and prevent severe illness in newborn infants.

INTRODUCTION

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. In the United States, an estimated 23% of adolescents and adults have laboratory evidence of infection with T. gondii (1; CDC, unpublished data, 1994). Although these infections are usually either asymptomatic or associated with self-limited symptoms (e.g., fever, malaise, and lymphadenopathy), infection in immunosuppressed persons (e.g., persons with acquired immunodeficiency syndrome [AIDS]) can be severe. In addition, infections in pregnant women can cause serious health problems in the fetus if the parasites are transmitted (i.e., congenital toxoplasmosis) and cause severe sequelae in the infant (e.g., mental retardation, blindness, and epilepsy). Although congenital toxoplasmosis is not a nationally reportable disease and no national data are available regarding its occurrence, extrapolation from regional studies indicates that an estimated 400-4,000 cases occur in the United States each year. In addition, of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be foodborne, making toxoplasmosis the third leading cause of foodborne deaths in this country (2).

In 1997, the U.S. Department of Health and Human Services, the U.S. Department of Agriculture (USDA), and the U.S. Environmental Protection Agency (EPA) collaborated to develop the National Food Safety Initiative (3). The project aims to reduce the incidence of foodborne illness by enhancing surveillance, improving risk assessment, developing new research methods, and furthering food-safety education. Because congenital toxoplasmosis poses a substantial public health problem, CDC has developed prevention recommendations to reduce the risk for congenital infections.

In September 1998, CDC convened the National Workshop on Toxoplasmosis: Preventing Congenital Toxoplasmosis (NWTPCT) in Atlanta, Georgia, to discuss research priorities for preventing the disease. Approximately 30 international and national experts in toxoplasmosis participated, representing universities, practitioner associations, research institutions, health-care centers, and other federal agencies. Specific objectives of NWTPCT included defining approaches for reducing the prevalence of congenital toxoplasmosis, determining the data needed to evaluate and implement these strategies, and identifying critical research and prevention efforts for the future. This report summarizes the recommendations from this workshop and the activities that have been undertaken by CDC in response to these recommendations.*

SCOPE OF THE PROBLEM

Burden of Toxoplasmosis in the United States

Toxoplasmosis is not a nationally reportable disease in the United States, and no reliable data are available at the national level about the number of cases diagnosed each year. The most reliable information about the burden of toxoplasmosis in the general population is derived from serosurveys, which determine the percentage of persons with elevated levels of Toxoplasma-specific IgG antibodies.

Since the 1960s, rates of infection with Toxoplasma in the United States appear to be declining. In the 1960s, a study of U.S. military recruits indicated that the overall seroprevalence of Toxoplasma was 14% (5). In 1989, a second study of military recruits indicated a seroprevalence of 9.6% (6). Similar downward trends have been observed in France and Sweden (7,8).

The most reliable estimate of Toxoplasma seroprevalence in the United States is derived from the third National Health and Nutrition Examination Survey (NHANES III) (1), which was conducted during 1988-1994. The survey design was a cluster sample of U.S. residents. Serum samples from 17,658 persons were tested at CDC for Toxoplasma-specific IgG antibodies; 23% were positive. Of 5,988 women of childbearing age (i.e., age 12-49 years), 14% were seropositive (CDC, unpublished data, 1994). No recent U.S. studies of a large population of pregnant women have been conducted to determine the incidence of new infections during pregnancy.

Although serosurveys of the general population help define temporal trends in Toxoplasma seropositivity rates and can be used to estimate the number of women of childbearing age who are at risk for acquiring Toxoplasma infections and potentially transmitting it to their fetuses, serosurveys are less helpful in estimating the number of cases of congenital toxoplasmosis. Three prospective studies provide useful information regarding the number of congenital toxoplasmosis cases in the United States.

Two prospective studies in the 1970s both reported rates of congenital toxoplasmosis of approximately 10 per 10,000 live births. In one study in the early 1970s, 7,500 consecutive live births at a hospital in Birmingham, Alabama, were screened for Toxoplasma infection; of these, 10 (13 per 10,000 live births) were seropositive (9). In a study of acute Toxoplasma infection in 4,048 pregnant women in New York during 1967-1969, six (0.2%) women seroconverted during their pregnancies, and 17 others (0.4%) had at least an eightfold rise in antibody titers during pregnancy (10). Of the 23 infants born to these 23 women, three had congenital toxoplasmosis, representing an infection rate of 7 per 10,000 live births in the study population.

More recent data regarding the rate of congenital toxoplasmosis are available from the New England Regional Newborn Screening Program (11). All infants born in the catchment area of this program are tested for evidence of congenital toxoplasmosis; infected infants undergo clinical evaluation and treatment for 1 year. During 1986-1992, of 635,000 infants who underwent serologic testing, 52 were infected, representing an infection rate of approximately 1 per 10,000 live births. Only two (4%) of these infants were recognized to have congenital toxoplasmosis before the screening results were known; however, follow-up examinations of 19 (40%) of the 48 infants evaluated revealed signs of disease (e.g., abnormal cerebrospinal fluid examinations, hydrocephalus, and retinal lesions).

Whether the rates of congenital infection in these three studies are representative of the entire U.S. population is unknown. However, if these rates (i.e., 1 per 10,000 and 10 per 10,000 ) were extrapolated to the approximately 4 million live births in the United States each year, an estimated 400-4,000 infants would be born each year with congenital toxoplasmosis.

Limited data are available to assist in estimating the portion of the disease burden of toxoplasmosis attributable to meat consumption. A recent study compared results from a cross-sectional seroprevalence study of Seventh Day Adventists, a religious group that follows a diet containing no meat, with serologic results from a control group of volunteers who were not Seventh Day Adventists (12). Results from this study documented a significantly lower rate of Toxoplasma infection in Seventh Day Adventists than the control group (24% versus 50%, respectively; p < 0.01). Thus, approximately one half of Toxoplasma exposure might be caused by eating contaminated meat. Furthermore, a statistically significant decrease in risk for infection was observed among nonmeat eaters even after the data were adjusted for age and sex (odds ratio = 0.2; 95% confidence interval = 0.1-0.5). Because this study was originally designed to evaluate the possible association between eating shellfish and Vibrio and Norwalk virus infections, important questions regarding toxoplasmosis (i.e., amount of meat consumed, contact with or ownership of cats, or history of outdoor activity) were not asked in the interview.

A report conducted by USDA's Economic Research Service concluded that one half of the toxoplasmosis cases in the United States are caused by eating contaminated meat. The estimated economic burden of these infections is $7.7 billion each year, primarily from congenital toxoplasmosis (13).

Pork has been implicated by some authorities as the meat most commonly associated with foodborne toxoplasmosis (14). In some areas, market pigs from small producers have had higher rates of Toxoplasma infections than pigs from larger producers (15); however, overall rates appear to be declining over time (16). In 1992, a large survey in Illinois documented that 3.1% of market pigs had serologic evidence of Toxoplasma infection (16). Toxoplasma infection has also been identified in other meats, but their contribution to the burden of disease is believed to be small (14).

Although Toxoplasma infections are associated either with eating contaminated meat or with ingesting oocysts passed in the feces of cats, no laboratory test exists that can determine the origin of a Toxoplasma infection in a specific person and whether it was associated with foodborne, catborne, or soilborne transmission. Epidemiologic studies of the transmission of toxoplasmosis have been hindered by an inability to determine the origin of isolated infections.

Diagnosis and Treatment

Acute toxoplasmosis is rarely diagnosed by detecting the parasite in body fluids, tissue, or secretions; the most common method of diagnosis is based on antibody detection. The presence of elevated levels of Toxoplasma-specific IgG antibodies indicates infection has occurred at some point but does not distinguish between an infection acquired recently and one acquired in the distant past. The presence of a high Toxoplasma-specific IgM antibody titer combined with a high IgG titer probably indicates an acute infection within the previous 3 months. A low-to-medium IgM titer and a high IgG titer might indicate an acute infection 3-6 months previously, but IgM antibodies have been detected as long as 18 months after initial infection (17). Determining when Toxoplasma infection occurred in a pregnant woman is particularly important because infection before conception poses no substantial risk for transmission of infection to the fetus; however, infection after conception does pose such risk.

In the United States, commercial test kits for Toxoplasma-specific IgG and IgM antibodies are readily available. Some commercial IgM tests have had problems with specificity, resulting in unacceptably high rates of false-positive test results. In 1996, FDA and CDC conducted extensive evaluations of the six most commonly used commercial IgM kits in the United States to determine the extent of the problem with the specificity of these kits. Sensitivity and specificity rates for these six kits ranged from 93.3% to 100.0% and from 77.5% to 99.1%, respectively (18).

As a result of these findings, in 1997 FDA distributed an advisory to physicians in the United States highlighting these test limitations. The agency provided a guide for interpreting test results and issued a recommendation to laboratory personnel and physicians advising them to be aware of the problems associated with the test kits before making decisions about the clinical management of their patients. In addition, IgM-positive results should be confirmed by a Toxoplasma reference laboratory (18).

Treatment of toxoplasmosis in immunocompetent persons other than pregnant women is generally not indicated unless symptoms are severe or persistent (19-21). In immunocompromised persons, treatment usually consists of pyrimethamine and sulfadiazine. Depending on gestational age and whether the fetus is known to be infected, pregnant women have been treated with the antibiotic spiramycin or with sulfadiazine alone or the combination of pyrimethamine and sulfadiazine. Treatment of acute infection during pregnancy has been associated with an approximately 50% reduction in fetal infection (22).

ETIOLOGIC FACTORS

T. gondii has a complex life cycle consisting of three stages: a) tachyzoite -- during the acute stage of infection, this form of the parasite invades and replicates within cells; b) bradyzoite -- during latent infections, this form of the parasite is present in tissue cysts; and c) sporozoite -- this form of the parasite is found in oocysts, which are environmentally resistant. Members of the family Felidae (including domestic and feral cats) are the definitive hosts of Toxoplasma. During acute infections, cats excrete unsporulated (i.e., uninfectious) oocysts in their feces; after several days to several weeks, depending on environmental conditions, the oocysts sporulate and become infectious. Under favorable conditions (i.e., in warm, moist soil), oocysts can remain infectious for approximately 1 year. They do not survive in arid, cool climates and can be destroyed by heating (17,19,20,23,24).

Toxoplasmosis can be transmitted to humans by three principal routes. First, humans can eat raw or inadequately cooked infected meat or eat uncooked foods that have come in contact with contaminated meat. Second, humans can inadvertently ingest oocysts that cats have passed in their feces, either in a cat litter box or outdoors in soil (e.g., soil from gardening or unwashed fruits or vegetables). Third, a woman can transmit the infection to her unborn fetus.

Women infected with Toxoplasma before conception, with rare exceptions, do not transmit the infection to their fetuses. Women infected with Toxoplasma after conception (i.e., during pregnancy) can transmit the infection across the placenta to their fetuses. Maternal infections early in pregnancy are less likely to be transmitted to the fetus than infections later in pregnancy, but early fetal infections, when they do occur, are more likely than later infections to be severe (25). An estimated one half of untreated maternal infections are transmitted to the fetus.

The classic triad of signs suggestive of congenital toxoplasmosis include chorioretinitis, intracranial calcifications, and hydrocephalus. However, most infants infected in utero are born with no obvious signs of toxoplasmosis on routine examination, but many develop learning and visual disabilities later in life (26,27). If untreated, congenital toxoplasmosis can be associated with severe and even fatal disease (28).

The severity of Toxoplasma infections is correlated with the immune status of the infected person. Toxoplasmosis in immunocompetent adolescents or adults is generally mild or unapparent. Mild infections can result in lymphadenopathy, fever, fatigue, and malaise, all of which usually resolve within weeks to months without specific treatment. However, infection in immunocompromised persons can be severe. Immunosuppression caused by AIDS or therapies for malignancies, transplants, or lymphoproliferative disorders can result in reactivation of preexisting latent Toxoplasma infections. Reactivation most often involves the central nervous system, and symptoms can include meningoencephalitis or symptoms of a mass lesion.

RECOMMENDATIONS FOR PREVENTION

• To prevent toxoplasmosis and other foodborne illnesses, food should be cooked to safe temperatures. A food thermometer should be used to measure the internal temperature of cooked meat to ensure that meat is cooked all the way through. Beef, lamb, and veal roasts and steaks should be cooked to at least 145 F, and pork, ground meat, and wild game should be cooked to 160 F before eating. Whole poultry should be cooked to 180 F in the thigh to ensure doneness.
• Fruits and vegetables should be peeled or thoroughly washed before eating.
• Cutting boards, dishes, counters, utensils, and hands should always be washed with hot soapy water after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables.
• Pregnant women should wear gloves when gardening and during any contact with soil or sand because cat waste might be in soil or sand. After gardening or contact with soil or sand, wash hands thoroughly.
• Pregnant women should avoid changing cat litter if possible. If no one else is available to change the cat litter, use gloves, then wash hands thoroughly. Change the litter box daily because Toxoplasma oocysts require several days to become infectious. Pregnant women should be encouraged to keep their cats inside and not adopt or handle stray cats. Cats should be fed only canned or dried commercial food or well-cooked table food, not raw or undercooked meats.
• Health education for women of childbearing age should include information about meat-related and soilborne toxoplasmosis prevention. Health-care providers should educate pregnant women at their first prenatal visit about food hygiene and prevention of exposure to cat feces.
• Health-care providers who care for pregnant women should be educated about two potential problems associated with Toxoplasma serology tests. First, no assay exists that can determine precisely when initial Toxoplasma infection occurred. Second, in populations with a low incidence of Toxoplasma infection, such as in the United States, a substantial proportion of the positive IgM test results will probably be false positive.
• The government and the meat industry should continue efforts to reduce Toxoplasma in meat.

RESEARCH AGENDA

NWTPCT Recommendations for Research

Experts who participated in NWTPCT considered several issues regarding prevention of this disease. These issues included the need to improve estimates of the burden of toxoplasmosis and immunodiagnostics for the disease and to determine the applicability of national toxoplasmosis screening for newborns. Participants discussed current knowledge about these issues, gaps in current knowledge, and needs for future research.

Improving Estimates of the Burden of Toxoplasmosis

In their recommendations, NWTPCT participants emphasized the importance of obtaining more complete and accurate data regarding the incidence of new infections and the number of cases by mode of transmission. Participants recommended that CDC obtain population-based data regarding the incidence of and risk factors for toxoplasmosis. In addition, participants recommended the use of existing private data systems (e.g., those of health-maintenance organizations and managed-care systems) for surveillance and research, and development of techniques that would enable tracing the source of individual infections to foodborne, catborne, or soilborne transmission.

Improving Immunodiagnostics for Toxoplasma

NWTPCT participants recommended that additional efforts were needed to develop more accurate screening diagnostic tests and improved confirmatory tests. NWTPCT participants also emphasized that resources should be identified to increase current capacity to provide reference diagnostic services in the United States.

Determining the Applicability of National Toxoplasmosis Screening for Newborns

Research is under way to determine the need for national toxoplasmosis screening of newborn infants in the United States (See Exhibit). NWTPCT participants identified the need for cost-effectiveness studies to enable comparison of the benefits of expanded testing in the United States and the costs of such testing.

CDC Priorities

The Food Safety Initiative has enabled CDC to increase support for activities related to prevention of toxoplasmosis, with a special emphasis on preventing congenital toxoplasmosis. The NWTPCT has helped CDC to identify high-priority activities and to form important partnerships with other groups with similar goals.

CDC is engaged in several activities to improve the ability to measure the burden of toxoplasmosis in the United States and to provide a baseline against which the impact of future prevention efforts can be measured. Epidemiologic staff are analyzing Toxoplasma IgG seroprevalence in samples collected in the nationally representative NHANES III (1) and preparing a document to disseminate the results. Plans are under way to conduct serologic testing of samples obtained as part of NHANES 2000 to evaluate trends in the prevalence of Toxoplasma infection and to assess the occurrence of acute Toxoplasma infections. In addition, CDC staff will examine national hospital discharge data and national death certificate data to monitor the annual number of cases of and deaths caused by toxoplasmosis, the proportion of toxoplasmosis associated with congenital infection, and the proportion associated with HIV infection. Other possible activities include a) examination of surveillance data (obtained from both educational and medical records) for multiple developmental disabilities (e.g., mental retardation, cerebral palsy, and hearing and vision impairment) and evidence of positive Toxoplasma tests and b) the designation by state health departments of congenital toxoplasmosis as a reportable infection.

CDC is supporting a cost-effectiveness analysis of the New England Newborn Screening Program to provide background information for states considering newborn toxoplasmosis screening and reporting. One state has already received funding from CDC through the Emerging Infections Program and has begun toxoplasmosis-related activities. Minnesota is conducting active surveillance for toxoplasmosis using laboratories, ophthalmologists, infection-control practitioners, and other clinicians.

CDC is conducting research on the genetic variation of Toxoplasma to develop tools that would enable molecular epidemiologic studies (e.g., to determine whether different strains have different characteristics and are more infectious or pathogenic for humans). The results of this research might help investigators describe the source and spread of Toxoplasma in outbreaks and differentiate between foodborne and cat feces or soilborne Toxoplasma infections. In addition, through FoodNet, CDC is querying laboratories in eight states about their diagnostic practices for toxoplasmosis.

To help evaluate the accuracy of future commercial Toxoplasma antibody test kits, CDC created a Toxoplasma serum panel that contains known positive and negative sera. FDA now requires that any new commercial Toxoplasma test kit perform adequately based on results obtained using this panel. The panel is available for purchase through the CDC Technology Transfer Office.

The American College of Obstetricians and Gynecologists, with assistance from CDC, is conducting a national survey of obstetricians to assess their knowledge about congenital toxoplasmosis and interpretation of related laboratory tests. The results of the survey will be used to identify ways to educate health-care providers about diagnosis and clinical management of pregnant women with suspected Toxoplasma infections.

To help educate women about toxoplasmosis prevention, CDC has published a pamphlet entitled "Attention Pregnant Women: What You Can Do to Keep Germs from Harming You and Your Baby," which discusses, among other infections, toxoplasmosis and ways to minimize the risk for infection during pregnancy. The pamphlet is available by mail (CDC, National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases, Respiratory Diseases Branch, MS C-23, 1600 Clifton Rd. N.E., Atlanta, GA 30333), fax ([404] 639-3970), or on the Internet at <http://www.cdc.gov/ncidod/diseases>.

CONCLUSION

Many cases of congenital toxoplasmosis in the United States can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and, if primary prevention fails and congenital infection occurs, to reduce the severity of infection in newborns. CDC is involved in efforts to improve measurement of the burden of toxoplasmosis in the United States, evaluate current prevention programs, train health-care providers, and educate women about toxoplasmosis. These efforts should allow CDC and state and local health departments to better monitor and reduce the impact of toxoplasmosis on pregnant women and their newborn infants.

References

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16. Weigel RM, Dubey JP, Siegel AM, et al. Prevalence of antibodies to Toxoplasma gondii in swine in Illinois in 1992. J Am Vet Med Assoc 1995;206:1747-51.
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* A separate effort at CDC deals with the prevention of opportunistic infections. Toxoplasmosis can be a serious opportunistic infection in persons with AIDS, and specific recommendations regarding how to prevent it have been published (4). Therefore, toxoplasmosis in persons with AIDS is not the primary focus of this report.

Exhibit

Screening Programs for Pregnant Women

France

In France, a screening program was implemented in 1976 to detect and treat Toxoplasma infection during pregnancy. The goal of this program is to institute preventive measures for seronegative women and to ensure early diagnosis and treatment of infection acquired during pregnancy. Since the beginning of the program, premarital and prenatal medical examinations for Toxoplasma antibodies have been performed. Premarital examinations are conducted to distinguish previously infected women from women who have not been previously infected. When a previously uninfected woman becomes pregnant, testing is conducted at her first prenatal examination during her first trimester and at six additional examinations conducted monthly during her second and third trimesters. In addition, women are educated about prevention methods during pregnancy (29). If these screening tests detect evidence of acute infection during pregnancy, treatment for the woman is initiated with spiramycin. If infection in the fetus is confirmed through fetal blood sampling and amniocentesis, pyrimethamine and sulfadiazine or sulfadoxine is added to the regimen (30-32).

Even though coverage of the French program has been incomplete, the program has been associated with a decline in the incidence of congenital infection, as well as a decline in severe disease detected at birth. The proportion of the decline specifically attributable to the program or to the general decline in Europe in rates of seropositivity is difficult to determine because no unscreened group of women exists for comparison.

Austria

Austria implemented a toxoplasmosis screening program in 1975. Nearly all women who become pregnant are serologically screened early in pregnancy and, if found to be negative initially, are tested again during the second and third trimesters. Women with Toxoplasma infections are treated as soon as infection is detected. Although seropositivity rates among pregnant Austrian women have declined from approximately 50.0% during the late 1970s to 36.7% during the early 1990s, the incidence of congenital Toxoplasma infection has declined even more, from 50-70 cases per 10,000 births before the program to 1 per 10,000 births during the early 1990s (33). As with the French program, the lack of an unscreened comparison group precludes determining the proportion of the decline attributable to the screening program, and lack of cost figures precludes cost-effectiveness analyses.

European Research Network on Congenital Toxoplasmosis

The European Research Network on Congenital Toxoplasmosis was established in 1993 and has sponsored several studies regarding public health interventions for congenital toxoplasmosis. Most recently, a multicenter study was conducted to evaluate the effectiveness of toxoplasmosis treatment administered during pregnancy in preventing transmission of maternal infection to the fetus. Pregnant women who visited one of five European university medical centers for prenatal care were screened for Toxoplasma antibodies at their first prenatal visit. Women who were seronegative were retested at least once every trimester in two centers and monthly in the other centers, until the birth of the infant. For women who seroconverted during pregnancy, prenatal antibiotic treatment was started, and their infants were followed for 1 year after birth. Treatment regimens consisted of spiramycin or a combination of pyrimethamine and sulfadiazine. If prenatal infection was confirmed with amniocentesis or cordocentesis, women were treated with pyrimethamine and sulfadiazine or sulfadoxine. Of women who screened positive and did not receive prenatal therapy, transmission from mother to infant occurred in 72% of the mother-infant pairs; of women who received prenatal therapy, transmission occurred in 39% of the mother-infant pairs. In addition, 20% of the untreated mothers gave birth to infants with severe sequelae, and 3.5% of the treated mothers gave birth to infants with severe sequelae. Furthermore, the earlier antibiotics were administered after infection, the less likely sequelae were detected in the infant (34).

Finland

From January 1988 through June 1989, a cost-benefit analysis of Toxoplasma screening during pregnancy was conducted in a prospective study in Finland. The study compared costs of screening alternatives for primary infections during pregnancy with the costs of no screening. With screening, the annual costs of congenital toxoplasmosis were $95 US per pregnancy; without screening, annual costs were $128 US per pregnancy. Furthermore, screening along with health education was more beneficial than health education alone (35). The study findings suggest screening is beneficial in countries with low incidence of congenital toxoplasmosis, such as Finland. The findings of other studies suggest screening programs can also be beneficial in areas with high incidences of congenital toxoplasmosis (30,36,37).

NWTPCT's Assessment

Although the findings of the European studies suggest Toxoplasma screening programs of women of childbearing age can prevent cases of congenital toxoplasmosis, several concerns could limit support for such programs in the United States. NWTPCT participants identified the need for cost-effectiveness studies to enable comparison of the benefits of expanded testing in the United States, the costs of such testing, and the unintended adverse consequences that might accompany such testing (e.g., inappropriately treating women with false-positive test results).

Screening Programs for Newborns

Denmark

During June 1992August 1996, researchers in Denmark conducted a newborn screening study for toxoplasmosis. The primary goal of this study was to determine the feasibility of screening newborn infants for congenital toxoplasmosis in an area with low prevalence; in Denmark, the seroprevalence of antibodies to Toxoplasma among women during this study was 28% (38,39). Approximately 90,000 infants were screened for Toxoplasma-specific IgG antibodies 5-10 days after birth. Infants born to mothers who seroconverted during pregnancy were subsequently examined physically and serologically for 1 year; for those with confirmed congenital infections, treatment was initiated with courses of pyrimethamine and sulfadiazine, alternating with spiramycin (38). During 1996, serum levels of Toxoplasma-specific IgM antibodies were also determined. The IgM test conducted within 10 days of birth resulted in a false-positive rate of 0.2 per 1,000 with no false-negatives. Results from this study indicated that a newborn screening program using a Toxoplasma-specific IgM antibody test exclusively could identify approximately 75% of infections in infants born to untreated mothers. In addition, the low rates of false-positives and false-negatives suggested this method would be feasible in large-scale newborn screening programs in areas with low seroprevalence rates of toxoplasmosis.

United States

In the United States, the New England Newborn Screening Program tests newborn "filter-paper" specimens from all infants born in Massachusetts and New Hampshire for congenital toxoplasmosis by using a Toxoplasma-specific IgM antibody assay. If IgM antibodies are detected, an extensive clinical evaluation is performed, and a 1-year treatment regimen is initiated with a combination therapy of pyrimethamine and sulfa-diazine (11). During 1986-1992, a total of 52 of the 635,000 infants screened had confirmed congenital infections; 50 appeared normal on routine neonatal examination and had toxoplasmosis diagnosed through screening alone. After more intensive examination, 19 (40%) of the 48 evaluated infants who appeared normal on routine examination had evidence of retinal or central nervous system disease. Treatment was provided for these infants, and compliance with therapy was observed. After 1 year of treatment, only one (2.2%) of 46 children had a neurologic deficit, and four (10.3%) of 39 had eye lesions that could have developed after birth. The findings of this program demonstrated that screening newborns for congenital toxoplasmosis is feasible in the United States. The laboratory and personnel costs of screening approximately 100,000 infants per year for Toxoplasma infection and following those who were infected totaled $220,000 or approximately $30,000 per infant identified. Costs were relatively low because the system used by the program to collect and process specimens was the same one already used for screening newborns for eight other diseases. On the basis of these preliminary cost estimates, this screening program appears to be a favorable alternative, considering the financial and social costs associated with raising a visually or mentally impaired child (40).

NWTPCT's Assessment

NWTPCT participants recognized the benefits of these newborn screening programs and discussed ways to evaluate the New England program to determine the benefit of using it as a model for developing additional programs in other areas of the United States. One specific recommendation was for CDC to support a detailed, cost- effectiveness evaluation of the program.

Education Programs for Women

The third approach to preventing toxoplasmosis focuses on educating women of childbearing age about minimizing their risk for infection with Toxoplasma. Education interventions assume that increased knowledge results in awareness, which consequently results in changes in risky behavior and declines in infection rates. Messages emphasize the importance of avoiding eating raw or undercooked meat, handling raw meat safely, and washing hands after gardening or changing cat litter boxes (37).

Canada

A study conducted as part of prenatal classes at Canadian public health agencies evaluated the effect of a 10-minute teaching session on three behaviors: practices associated with cleaning the cat litter box and limiting the cat's diet to cooked food; safe food-handling practices; and handwashing after exposure to cat feces, garden soil, or raw meats. Among women in the classes, behavior improved regarding practices associated with cats; however, behavior regarding food-handling practices remained unchanged. In addition, improvement occurred in handwashing practices but only among professional women (41).

Belgium

During 1979-1986, a Belgium study assessed the effectiveness of educational sessions held in hospital settings. Baseline data were collected during 1979-1982, when no education measures were in effect. During 1983-1986, education sessions were provided to pregnant women. Although the intervention was associated with a 34% decrease in seroconversion rates, the decrease was not statistically significant (42).

NWTPCT's Assessment

NWTPCT participants considered education programs to be a potentially powerful intervention because of their low cost and because pregnant women were highly motivated to protect the health of their babies. However, participants emphasized that the impact of educational programs was difficult to evaluate because of the limited number of comparative studies a) conducted with rigorous scientific methodology and b) of sufficient size to enable calculation of the effectiveness of the intervention compared with its cost.

Participants in the National Workshop on Toxoplasmosis: Preventing Congenital Toxoplasmosis

Professor Horst Aspöck
Department of Medical Parasitology
Clinical Institute of Hygiene
Kinderspitalgasse 15
A-1095 Vienna, Austria

Sue Binder, M.D.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-22
4770 Buford Highway
Atlanta, Georgia 30341

Kenneth Boyer, M.D.
Department of Pediatrics
Rush Presbyterian/St. Luke's Medical Center
1653 W. Congress Parkway
Chicago, Illinois 60612

Steve Crutchfield, Ph.D
U.S. Department of Agriculture
Room N 3077
1800 M Street N.W.
Washington, D.C. 20036-5831

Alfred DeMaria, Jr., M.D.
State Laboratory Institute
305 South Street
Jamaica Plain, Massachusetts 02130

Vance Dietz, M.D.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-22
4770 Buford Highway
Atlanta, Georgia 30341

J.P. Dubey, Ph.D.
Zoonotic Diseases Laboratory
U.S. Department of Agriculture
Barc-East Bldg. 1040
Beltsville, Maryland 20705

Roger Eaton, Ph.D.
NE Newborn Screening Program
University of Massachusetts Medical School
305 South Street
Jamaica Plain, Massachusetts 02130

Ruth Etzel, M.D.
U.S. Department of Agriculture
Room 3718 Franklin Court
1400 Independence Avenue, S.W.
Washington, D.C. 20250-3700

Jack Frenkel, M.D.
1252 Vallecita Drive
Sante Fe, NM 87501-8803

Ronald Gibbs, M.D.
Department of Ob/Gyn
University of Colorado Health Sciences Center
4200 E. Ninth Avenue, Campus Box B-198
Denver, Colorado 80262

Ruth Gilbert, M.D.
Department of Epidemiology and Public Health
Institute of Child Health
30 Guilford Street
London WC1 N 1EH, United Kingdom

Carol Herman, M.S.
OSB, Center for Devices & Radiological Health
Food and Drug Administration, HFZ-510
1350 Piccard Drive
Rockville, Maryland 20850

Peter Hotez, M.D.
Yale University School of Medicine
507 LEPH; 60 College Street
New Haven, Connecticut 06520

Dennis Juranek, D.V.M.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-22
4770 Buford Highway
Atlanta, Georgia 30341

Ruth Lynfield, M.D.
Acute Disease Epidemiology Section
Minnesota Department of Health
717 Delaware Street, S.E.
Minneapolis, Minnesota 55440-9441

James McAuley, M.D.
Westside Center for Disease Control
2160 W. Ogden Avenue
Chicago, Illinois 60612

Rima McLeod, M.D.
The University of Chicago
939 E. 57th Street (VSC, MC 2114)
Chicago, Illinois 60637

Martin Meltzer, Ph.D.
Office of the Director
National Center for Infectious Diseases
CDC, MS C-12
1600 Clifton Road, N.E.
Atlanta, Georgia 30333

Marilyn Mets, M.D.
Children's Memorial Hospital
Division of Ophthalmology
2300 Children's Plaza/Box 70
Chicago, Illinois 60614

Thomas Navin, M.D.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-22
4770 Buford Highway
Atlanta, Georgia 30341

Eskild Petersen, M.D.
Laboratory of Parasitology
Statens Serum Institute
Artillerivej 5
DK-2300 Copenhagen S Denmark

Jack Remington, M.D.
Research Institute
Palo Alto Medical Foundation
860 Bryant Street
Palo Alto, California 94301

Rigoberto Roca, M.D.
Center for Drug Evaluation & Research
Food and Drug Administration, HFD-590
5600 Fishers Lane
Rockville, Maryland 20857

Peter Schantz, V.M.D.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-22
4770 Buford Highway
Atlanta, Georgia 30341

Jack Schlater, D.V.M.
National Veterinary Services Laboratories
1800 Dayton Avenue
Ames, Iowa 50010

L. David Sibley, Ph.D.
Washington University School of Medicine
660 S. Euclid Avenue, Campus Box 8230
St. Louis, Missouri 63110-1093

Kirk Smith, D.V.M.
Acute Disease Epidemiology
MN Department of Health
717 Delaware Street, N.E.
Minneapolis, Minnesota 55414

Philippe Thulliez, M.D.
Laboratoire de la Toxoplasmose
Institut de Puériculture
26 Boulevard Brune
F-75014 Paris
France

Ralph Timperi, M.P.H.
State Laboratory Institute
Massachusetts Department of Health
305 South Street
Jamaica Plain, Massachusetts 02130-3597

Marianna Wilson, M.S.
Division of Parasitic Diseases
National Center for Infectious Diseases
CDC, MS F-13
4770 Buford Highway
Atlanta, Georgia 30341

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