الصفحة الرئيسية

من نحن

الأقسام

المجلة الطبية

موقع الوزارة

راسلنا

الأرشيف

 

Toxoplasmosis: Diagnosis and treatment

Abstract:
 

 Toxoplasmosis is a common zoonosis caused by infection with Toxoplasma gondii.

Toxoplasmosis in immunocompetent adults is usually asymptomatic or self-limited.

 However, toxoplasmosis is associated with a significant morbidity in certain patient population.

Those patients are immunocompromised patients, pregnant women, fetuses, and newborns. Furthermore, the diagnosis of toxoplasmosis in this group of patients is very critical and a challenge for physicians.

Consultation with an infectious diseases specialist and microbiologist is recommended in these situations.

In this review, there is a detailed discussion on the diagnosis of toxoplasmosis with a brief notes on treatment and prevention of toxoplasmosis.
 

Introduction:
 

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii.

Toxoplasmosis can be transmitted to humans by three principal routes.

First, humans can inadvertently ingest water or food contaminated with oocysts that cats have passed in their feces, either in a cat litter box or outdoors in soil.

This is the most common method of infection in underdeveloped and developing countries. Epidemiologic surveys have revealed that in most areas of the world, the presence of cats is the primary importance for the transmission of toxoplasmosis (1).

Second, humans can eat raw or inadequately cooked infected meat or eat uncooked foods that have come in contact with contaminated meat.

This is more common in developed countries where eating undercooked meat is common.

Third, a woman can transmit the infection to her unborn fetus.

Women infected with Toxoplasma before conceptions, with rare exceptions such as immunocompromised women or women infected shortly before conception, 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 (2).

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 AIDS or transplant patients) 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) (3).
 

Diagnosis

Acute infection is diagnosed by the isolation of T. gondii , demonstration of tachyzoites in histologic sections of tissue or cytologic preparations of body fluids, serologic tests, or by amplification of T. gondii DNA by PCR in blood or various body fluids.

 The use of serologic tests to show specific antibody to T. gondii is the primary method of diagnosis of toxoplasma infections (4).

The problem with serologic diagnosis is that there is no single test than can be used to support the diagnosis of acute or chronic infection by T. gondii. In most cases, a battery of tests is required to differentiate between acute and chronic infections (4).

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 (5) .

The most commonly used serologic tests for the diagnosis of T. gondii infection are

 

Summarized in table1.

 

There are four groups of individuals in whom the diagnosis of toxoplasmosis is most critical: pregnant women who acquire their infection during gestation, fetuses and newborns with congenital acquired infection, immunocompromised patients, and patients with chorioretinitis.

 

T. gondii infection in pregnancy:

Determining when T. gondii 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.

The diagnosis of acute T. gondii infection in most cases requires demonstration of either conversion from a negative to a positive titer or a significant rise in titers in serial serum samples obtained at least 3 weeks apart.

However, using serum titers might not helpful if considered late in the course of the patientís pregnancy because they may have reached their peak at the time the first serum sample is obtained for testing.

Initial screening of maternal serum involves testing for IgG and IgM antibodies.

The lack of both IgG and IgM antibodies essentially excludes active infection.

The presence of IgG antibodies in the absence of IgM  antibodie in the first two trimesters amost always indicate chronic maternal infection with no risk of transmission to the fetus.

 In the third trimester,  negative IgM antibodies with positive IgG antibodies is most likely consistent with chronic maternal infection but does not exclude entirely the possibility of acute infection acquired early in pregnancy.

In these cases, the use other serologic testing such as IgA or IgE antibodies may be of particular help (6). However, a positive IgM test result requires further assessment with confirmatory testing since a false-positive result for IgM can occur.

Several tests are used to help differentiate between recently acquired infection and distant infections. The IgG avidity test is one of the commonly used confirmatory testings.

 Results are based on the measurement of avidity of functional affinity of toxoplasma-specific IgG antibodies.

During an acute infection, IgG antibodies bind antigen weakly (low avidity).

However, in chronic infection the affinity of IgG anibodies increases progressively over weeks to months (high avidity) (7). The currently available avidity tests are helpful primarily in excluding that a patientís infection occurred within the prior 3-5 months.

This is most helpful in pregnant women in their first months of gestation who have positive test result for both IgG and IgM antibodies.

A pregnant woman in her first trimester with high avidity test result indicates the acute infection was not acquired in the preceding 3 months and therefore the fetus is at no risk of getting infected (8). It should be noted that low avidity test result doesnít indicate recently acquired infection.

Avidity IgG testing should not be used alone as a definitive test for decision making.

It should be used with other serologic tests.

These tests are ELISA for IgM, IgA, IgE, IgG and the differential agglutination test (7).

When the diagnosis of acute acquired T. gondii infection during pregnancy has been established, diagnostic efforts should focus on determining whether the fetus has been infected.

However, these confirmatory tests might be available in resources poor countries with high prevalence of toxoplasmosis.

In this situation, knowing the serologic status of the patient at first prenatal examination in early pregnancy might be helpful to differentiate between infection before and during gestation.

A screening program for toxoplasmosis in all pregnant women can be implemented to institute preventive measures for seronegative women and to ensure early diagnosis and treatment of infection acquired during pregnancy.

All women who become pregnant should be serologically screened in the first prenatal examination during her first trimester, if found to be negative initially, should be tested again during the second and third trimesters.

In addition, women are educated about prevention methods during pregnancy.

Women with Toxoplasma infections are treated as soon as infection is detected (9).

Congenital toxoplasmosis in the fetus:

 

Prenatal diagnosis of fetal infection is recommended when a diagnosis of acute infection is established or highly suspected in a pregnant woman.

Prenatal diagnosis of congenital toxoplasmosis is based on ultrasonography and amniocentesis.

PCR on amniotic fluid for the detection of T. gondii-specific DNA performed at 18 week of gestation or later is more sensitive, more rapid, and safer than conventional diagnostic procedures involving fetal blood sampling.

Amniotic fluid should be tested by PCR in all cases with serologic test results diagnostic of or highly suggestive of acute acquired infection during pregnancy and if there is evidence of fetal damage by ultrasound examination such as hydrocephalus or calcifications (10).

Congenital toxoplasmosis in the newborn:

 

Serologic diagnosis of congenital toxoplasmosis in the newborn is most commonly made by demonstration of serum IgM or IgA Toxoplasma gondii antibodies in the infant.

 The serologic diagnosis can not be made by demonstration of IgG antibodies in the newborn because of maternal IgG antibodies are passively transferred in utero to the fetus.

 However, transmission of maternal IgM and/or IgA antibodies can occur during the birth process. Therefore, serum samples obtained from peripheral blood and not from the umbilical cords are preferred.

Furthermore, positive results for IgM and IgA antibodies in the newborn must be confirmed by repeat testing at 2-4 days of life in the case of IgM antibodies and at 10 days of life for IgA antibodies (11). Occasionally, some newborn with congenital toxoplasmosis may be negative for IgM and/or IgA antibodies during the newborn period.

In this case, a monthly measurement of infant IgG antibodies should be performed for 6 months or longer to determine if IgG antibodies are due maternal transfer of antibodies or to the infantís own immune response to the infection (12). Studies using the Western blot techniques, with IgG and IgM mother-infant pairs, have shown that maternal and infant sera may recognize different T. gondii antigens when the infant is congenitally infected.

 However, it should be emphasized that Western blot method should be used in a combination with other serologic testing.

Overall, the combination of Western blots with conventional serologic tests can detect 94% of congenitally infected infants in the first 3 months of life (7).

PCR of cerebrospinal fluid, whole blood, and urine can also be used to diagnose congenital toxoplasmosis in the newborn (6).

Finally, evaluation of infants with suspected congenital toxoplasmosis always should include ophthalmologic examination, radiologic examination for detection o cerebral calcifications, and examination of cerebrospinal fluid (6).

 

T. gondii infection in immunocompromised patient:

Reactivation of chronic infection is the most common source of toxoplasmosis in immunocompromised patients such as patients with AIDS, malignancy, and organ transplantation.

 Routine screening of these patients for T. gondii IgG antibodies should be as an initial assessment. Patient with negative IgG antibodies should be instructed on prevention of infection.

 Patient with positive IgG antibodies are at high risk of reactivation.

Post-transplant serology frequently is not helpful in the diagnosis of toxoplasmosis in patients who have undergone organ transplantation and knowing the pre-transplant serology status might be helpful. A definitive diagnosis of toxoplasmosis in immunocompromised patients relies on histologic demonstration of the parasite or on detection of T. gondii DNA by PCR (4).

Ocular toxoplasmosis:

In most cases, toxoplasma chorioretinitis is diagnosed by ophthalmologic examination, and empiric therapy against T. gondii is often initiated based on clinical findings and serologic test result.

However, in cases of unclear diagnosis or inadequate clinical response to empiric therapy, other diagnostic tests such as abnormal T. gondii antibody response in ocular fluid, histopathologic examination, and PCR of vitreous or aqueous fluids should be used (13). 

Treatment

Treatment of toxoplasmosis in immunocompetent persons other than pregnant women is generally not indicated unless symptoms are severe or persistent.

In immunocompromised persons, treatment usually consists of pyrimethamine,sulfadiazine, and folinic acid.

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 (14).

Treatment of acute infection during pregnancy has been associated with an approximately 50% reduction in fetal infection (15). Treatment options for toxoplasmosis are summarized in table2.

 

RECOMMENDATIONS FOR PREVENTION

  • To prevent toxoplasmosis and other foodborne illnesses, food should be cooked to safe temperatures.

  • 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. Pregnant women should be encouraged to keep their cats inside and not adopt or handle stray cats. 

  • 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.

  • The government and the meat industry should continue efforts to reduce Toxoplasma in meat.

    References:

  1.  Dubey J. Toxoplasmosis. J Am Vet Med Assoc 1994; 205: 1593-1598.

  2.  Holliman RE. Congenital toxoplasmosis: prevention, screening and treatment. J Hosp Infect 1995; 30(suppl):179-90.

  3. Hill D, Dubey JP. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect 2002; 8:634-640.

  4. Montoya JG. Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. J Infect Dis 2002; 185:S73-82.

  5. Wilson M, McAuley JB. Toxoplasma. In: Murray P, ed. Manual of clinical microbiology. 7th ed. Washington, DC: ASM Press, 1999:1374-82.

  6. Remington JS, McLeod R, Thulliez P, et al. Toxoplasmosis. In: Remington JS, Klein JD, eds. Infectious diseases of the fetus and newborn infant. 4th ed. Philadelphia, PA: WB Saunders, 2001:205-346.

  7. Remington J, Thulliez P, Montoya J. Recent developments for diagnosis of Toxoplasmosis. J Clin Microbiol 2004; 42:941-945.

  8. Hedman K, Lapalainen M, Sepalla I, Makela O. Recent primary toxoplasma infection indicated by a low avidity of specific IgG. J Infect Dis 1989; 159:736739.

  9. Aspock H, Pollak A. Prevention of prenatal toxoplasmosis by serological screening of pregnant women in Austria. Scand J Infect Dis 1992; 24(suppl 84):32-8.

  10. Hohlfeld P, Daffos F, Costa J, et al. Prenatal diagnosis of congenital toxoplasmosis with polymerase-chain-reaction test on amniotic fluid. N Eng J Med 1994; 331:695-699.

  11. Stepick-Biek P, Thulliez P, Araujo FG, et al. IgA antibodies for diagnosis of acute congenital and acquired toxoplasmosis. J Infect Dis 1990; 162:270-273.

  12. Guerina NG, Hsu H-W, Meissner H, et al. Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. N Engl J Med 1994; 330:1858-63.

  13. Montoya JG Parmley S, Liesenfeld O, et al. Use of the polymerase chain reaction for diagnosis of ocular toxoplasmosis. Ophthalmology 1999; 106:1554-1563.

  14. Kasper LH. Toxoplasma infection. In: Fauci AS, Isselbacher KJ, Wilson JD, eds. Harrison's principles of internal medicine. 14th Ed. New York: McGraw-Hill, Health Professions Division, 1998:1197-202.

  15. Desmonts G, Courvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. N Engl J Med 1974; 290:1110-6.

 

Table1. The most commonly used serologic tests for the diagnosis of Toxoplasma gondii infections.
Serologic test                                                Comments
IgG antibodies based tests
Sabin-Feldman Dye test                            The reference serologic test for other methods

                                                                     A negative test result rules out prior exposure 

                                                                     to T. gondii.

   Indirect Fluorescent Antibody test            Its titers tend to parallel Dye test titers.

                                                                      Antinuclear antibodies can cause false-

                                                                      positive result.

 Agglutination test                                      It is accurate, simple, inexpensive, and

                                                                      excellent for screening purposes.

                                                                      It should not be used for the measurement of

                                                                      IgM antibodies because of false-negative test result.
ELISA                                                        The most widely used test.

 IgG Avidity test                                          It helps to differentiate between recently acquired

                                                                       infection and distant infection.

                                                                       High avidity indicates an infection at least in the

                                                                       previous 3 to 5 months.

 

IgM antibodies based tests

 Indirect Fluorescent Antibody test            Antinuclear antibodies and rheumatoid factor can

                                                                      cause false-positive result.

  ELISA                                                        The double sandwich test is the most widely used

                                                                       test to show IgM antibodies in adults, fetuses, and

                                                                       newborns.

 Immunosorbent Agglutination Assay         It is simple and can be used for diagnosis of

                                                                       congenital infection.

IgA ELISA                                                     It is helpful in the diagnosis of congenital infection

                                                                       in the newborn.

IgE ELISA                                                      It helpful for the diagnosis of acute and congenital

                                                                        infections.

                                                                        It is less sensitive than IgM and IgA for neonatal

                                                                        diagnosis of congenital toxoplasmosis. However, it

                                                                       of the three immunoglobulins increased the

                                                                       diagnostic yield of congenital infection.                                                       


Table2. Treatment options for Toxoplasmosis.
 
Immunocompetent patients

 Lymphadenitis                                           No requirement for treatment unless symptoms

                                                                     are severe and persistent.

Infection acquired by either                       Should always be treated as for active chorioretinitis

laboratory accident or blood                         

transfusion

Active chorioretinitis, meningitis              Pyrimethamine(50-100mg orally twice aday on 1st

                                                                     day, followed by 25-50mg aday)

                                                                     PLUS

                                                                     Sulfadiazine(1-1.5 gm orally 4 times aday)

                                                                     PLUS

                                                                     Folinic acid (10mg orally a day)

                                                                     PLUS

                                                                     Prednisone 1mg/kg in 2 divided doses.

Pregnant Women

Acute infection acquired                            Spiramycin 1gm orally 3 times aday.

during gestation                                         It should be continued for the entire pregnancy even

                                                                      if amniotic fluid PCR is negative.

Amniotic fluid PCR-positive                      Pyrimethamine+sulfadiazine+folinic acid

result at 18 weeks of gestation                    The same doses as immunocompetent patients.

 or later
Immunocompromised patients                      Pyrimethamine(200mg orally once followed by 75-

                                                                      100mg/day)

                                                                      PLUS

                                                                      Sulfadiazine(1-1.5gm orally every 6 hours)

                                                                      PLUS

                                                                      Folinic acid(10-15mg/day)   

 

 

 

  وزارة الصحة - مركز المعلومات - قسم النشر الالكتروني - 2005