ETIOLOGY

 Toxoplasmosis is a widespread disease in human beings and animals. This infection is caused by Toxoplasma gondii, recognized as a tissue coccidian.

EPIDEMIOLOGY

 T. gondii was first discovered in a North African rodent and has been observed in numerous birds and mammals worldwide, including human beings. It is a parasite of cosmopolitan distribution able to develop in a wide variety of vertebrate hosts.

Human infections are common in many parts of the world. The prevalence of infection in adults ranges from less than 10% to more than 90%; higher prevalences tend to occur at lower elevations and in latitudes closer to the equator. The highest recorded rate (93%) was in Parisian women who preferred undercooked or raw meat; a 50% rate of occurrence was documented in the children of these women. Toxoplasma infection rates vary around the world. In the United States, it’s about 10% to 15%, while rates in Europe and Brazil are much higher, around 50% to 80%. These are only estimates. Calculating exact rates is difficult because most infected people don’t have any symptoms.

Toxoplasmosis is not passed from person-to-person, except in cases of mother to child (congenital) transmission and blood transfusion or organ transplantation. People typically become infected by three principal routes of transmission:

• Foodborne

• Animal to human (zoonotic)

• Mother to child (congenital)

The definitive host is the house cat and other members of the Felidae family (Fig.1). Domestic cats are a source of the disease because oocysts are often present in their feces. Accidental ingestion of oocysts by human beings and animals, including the cat, produces a proliferative infection in the body tissues. Fecal contamination of food or water, soiled hands, inadequately cooked or infected meat, and raw milk can be major sources of human infection. The risk for infection is higher in many developing and tropical countries, especially when people eat undercooked meat, drink untreated water, or are extensively exposed to soil.

Fig1. Life cycle of Toxoplasma gondii.  (Adapted from Katz SL, Gershon AA, Wilfert CM, Krugman S editors: Infectious diseases of children, ed 9, St Louis, 1992, Mosby.)

Organ transplant recipients can become infected by receiving an organ from a Toxoplasma-positive donor. Transfusion transmitted toxoplasmosis has been associated with the use of leukocyte concentrates. Patients at risk are those receiving immunosuppressive agents or corticosteroids. Laboratory workers who handle infected blood can also acquire infection through accidental inoculation.

Transplacental Transmission

 All mammals, including human beings, can transmit the infection transplacentally. Transplacental transmission usually takes place in the course of an acute but inapparent or undiagnosed maternal infection. Evidence has shown that the number of infants born in the United States each year with congenital T. gondii infection is considerably higher than the 3000 previously estimated. It is estimated that 6 of 1000 pregnant women in the United States will acquire primary infection with Toxoplasma during a 9-month gestation. Approximately 45% of women who acquire the infection for the first time and who are not treated will give birth to congenitally infected infants. Consequently, the expected incidence of congenital toxoplasmosis is 2.7/1000 live births.

It is recommended that all pregnant women be tested for toxoplasmosis immunity. If a patient is susceptible, screening should be repeated during pregnancy and at delivery. Prevention of infection in pregnant women should be practiced to avert congenital toxoplasmosis (Box 1). To further prevent infection of the fetus, women at risk should be identified by serologic testing and pregnant women with primary infection should receive drug therapy.

Box1. Methods for Prevention of Congenital Toxoplasmosis

Seroprevalence

 Seroprevalence (antibody to T. gondii) varies considerably in the general population. It ranges from 96% in Western Europe to 10% to 40% in the United States. Of patients with acquired immunodeficiency syndrome (AIDS) who are seropositive for T. gondii, approximately 25% to 50% will develop toxoplasmic encephalitis (meningoencephalitis). In areas with a lower seroprevalence, such as the United States, the percentage of AIDS patients who develop toxoplasmic encephalitis is lower (5% to 10%).

SIGNS AND SYMPTOMS

In adults and children other than newborns, toxoplasmosis is usually asymptomatic. A generalized infection probably occurs. Although spontaneous recovery follows acute febrile disease, the organism can localize and multiply in any organ of the body or the circulatory system.

Toxoplasma can be harmful to individuals with suppressed immune systems. Toxoplasmic encephalitis in AIDS patients may result in death, even when treated (Fig. 2). Persons at risk can be identified by screening patients positive for human immunodeficiency virus (HIV) for antibody to T. gondii.

Fig2. Toxoplasmic meningoencephalitis. Shown are magnetic resonance imaging (MRI) brain scans of patients with AIDS. Arrows  indicate areas infected with toxoplasmosis.

Acquired Infection

 When seen, symptoms are frequently mild. Toxoplasmosis can simulate infectious mononucleosis, with chills, fever, headache, lymphadenopathy, and extreme fatigue. Primary infection may be promoted by immunosuppression. A chronic form of toxoplasmic lymphadenopathy exists. T. gondii presents a special problem in immunosuppressed or otherwise compromised hosts. Some of these patients have experienced reactivation of a latent toxoplasmosis. These patients have included those with Hodgkin’s and non-Hodgkin’s lymphoma, as well as recipients of organ transplants.

Reactivation of cerebral toxoplasmosis is not uncommon in patients with AIDS, in whom toxoplasmic meningoencephali tis is almost always a reactivation of a preexisting latent infection, most often occurring when the total CD4 count falls below 100 × 10⁹/L. T. gondii–seropositive, HIV-infected patients may develop toxoplasmic encephalitis because of the following: (1) genetic susceptibility in the human immune response to T. gondii; (2) subtle differences in patients’ immunocompromised status; (3) differences in the virulence of individual strains of T. gondii; (4) possible recurrent infections with different strains; and (5) variable coinfections with other opportunistic pathogens.

Congenital Infection

 Toxoplasma can be harmful to fetuses whose mothers become infected during pregnancy. Congenital toxoplasmosis can result in central nervous system (CNS) malformation or prenatal mortality. In infants who are serologically positive at birth, many fail to display neurologic, ophthalmic, or generalized illness at birth. Toxoplasmosis acquired in utero can result in blindness, encephalomyelitis, mental retardation, convulsions, and death in infected neonates.

In as many as 75% of congenitally infected newborns not serologically diagnosed at birth, the disease remains dormant, only to be discovered when other symptoms become apparent, such as chorioretinitis, unilateral blindness, and severe neuro logic sequelae.

IMMUNOLOGIC MANIFESTATIONS

 Both clinical and laboratory findings in toxoplasmosis resemble those of infectious mononucleosis. An increased number of variant lymphocytes can be seen on a peripheral blood smear.

The diagnosis can be established serologically by detecting a marked elevation of Toxoplasma antibodies. Antibodies are demonstrable within the first 2 weeks after infection, rising to high levels early in the infection and then falling slightly, but persisting at an elevated level for many months before declining to low levels after many years. The best evidence for current infection is a significant change on two appropriately timed specimens (paired acute and convalescent specimens), in which both tests are done in the same laboratory at the same time.

If a significant level of T. gondii immunoglobulin M (IgM) antibody is detected, it may indicate a current or recent infection. The presence of IgM to T. gondii in an adult indicates an infection, but low levels of IgM antibodies occasionally may persist for more than 12 months after infection. The Centers for Disease Control and Prevention (CDC) recommends that any equivocal or positive result should be retested using a different assay from another reference laboratory specializing in toxoplasmosis testing.

DIAGNOSTIC EVALUATION

 The diagnosis of toxoplasmosis is typically made by serologic testing. A test that measures immunoglobulin G (IgG) is used to determine whether a person has been infected. If it is necessary to try to estimate the time of infection, which is of particular importance for pregnant women, a test that measures IgM is also used along with other tests, such as an avidity test.

Diagnosis can be made by direct observation of the parasite in stained tissue sections, cerebrospinal fluid (CSF), or other biopsy material. These techniques are used less frequently because of the difficulty of obtaining these specimens.

Parasites can also be isolated from blood or other body flu ids (e.g., CSF) but this process can be difficult and requires considerable time. Molecular techniques that can detect the parasite’s DNA in the amniotic fluid can be useful in cases of possible mother to child (congenital) transmission.

The diagnosis of toxoplasmosis can be established by the following:

• Serologic tests (Table 1)

• Polymerase chain reaction (PCR)

• Indirect fluorescent antibody (IFA)

• Isolation of the organism

Table1. Serologic Evaluation of Toxoplasmosis

Serologic Tests

The mainstay of diagnosis of T. gondii infection is serologic testing. A relatively high proportion of people have antibodies to T. gondii, which makes interpretation of serologic test results difficult. Assays for different isotypes of antibodies have been developed to support the diagnosis of an acute or chronic T. gondii infection.

For the detection of IgM antibodies to T. gondii, a variety of procedures are available—IFA, automated enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay for IgM and IgG antibodies.

IgM Antibodies

The IgM assay was widely used in the past, but this is not recommended for routine use in adults because it may yield frequent false-positive or false-negative results, particularly in pregnant women, immunocompromised patients, and patients from areas in which Toxoplasma infection is highly endemic. IgM antibodies tend to appear earlier and decline more rapidly than IgG antibodies. Persistently elevated IgM-specific antibody titers after the initial infection can lead to false-positive results and difficulty in interpreting these tests.

In patients with recently acquired infection, IgM T. gondii antibodies are detected initially and, in most cases, these titers become negative within a few months. In some patients, however, positive IgM T. gondii–specific titers can be observed during the chronic stage of the infection. IgM antibodies have been reported to persist as long as 12 years after the acute infection. However, their persistence does not seem to be clinically relevant and these patients should be considered chronically infected.

Clinicians should be cautious when using IgM antibody levels in prenatal screening. Any positive result in a pregnant patient confirmed positive by a second reference laboratory should be evaluated by amniocentesis and PCR testing for T. gondii. A negative result does not rule out the presence of PCR inhibitors in the patient specimen or T. gondii DNA concentrations below the level of detection of the assay.

The U.S. Food and Drug Administration (FDA) has recommended that sera with positive IgM test results obtained at nonreference laboratories should be sent to a Toxoplasma reference laboratory. After IgM-positive sera undergo confirmatory testing, the results are interpreted as the following: (1) a recently acquired infection; (2) an infection acquired in the past; or (3) a false-positive result.

IgG Antibodies

IgG antibodies appear 1 to 2 weeks after the initial infection, peak after about 6 to 8 weeks, decline gradually over the next 1 to 2 years and, in some cases, persist for life.

Sabin-Feldman Dye Test. IgG antibodies are primarily measured by the Sabin-Feldman dye test (DT), considered the gold standard. The DT is a sensitive and specific neutralization test in which live organisms are lysed in the presence of complement and the patient’s IgG T. gondii–specific antibody. IgG antibodies usually appear within 1 to 2 weeks of the infection, peak within 1 to 2 months, fall at variable rates, and usually persist for life. The titer does not correlate with the severity of illness. This test is available mainly in reference laboratories.

A negative test result practically rules out prior T. gondii exposure—unless the patient is hypogammaglobulinemic. In a small number of patients, IgG antibodies might not be detected within 2 to 3 weeks after initial exposure to the parasite. Rare cases of toxoplasmic chorioretinitis and toxoplasmic encephalitis have been documented in immunocompromised patients negative for T. gondii–specific IgG antibodies.

IFA Test. This test uses killed organisms as a substrate, with patient serum assayed for activity against them. IFA is used widely because it measures the same antibodies as the Sabin Feldman DT and results parallel DT results. False-positive results may occur with sera that contain antinuclear antibodies; false-negative results may occur when using sera from patients with low titers of IgG antibody.

Avidity Test. The functional affinity of specific IgG antibodies is initially low after primary antigenic challenge and increases during subsequent weeks and months. Protein-denaturing reagents are used to dissociate the antibody-antigen complex. The avidity result is determined using the ratios of antibody titration curves of urea-treated and untreated serum.

The avidity test can be used as an additional confirmatory diagnostic tool in patients with a positive or equivocal IgM test or with an acute or equivocal pattern in the differential agglutination test (AC/HS test). Its highest value is observed when laboratory test results reveal high–IgG avidity antibodies and the serum is obtained during the time window of exclusion of acute infection for a particular method (range, 12 to 16 weeks). Low– or equivocal–IgG avidity antibody results should not be interpreted as diagnostic of recently acquired infection. These low- or equivocal-avidity antibodies can persist for months to 1 year or longer.

Studies of the avidity of IgG in pregnant women who have seroconverted during gestation have shown that women with high-avidity test results are infected with T. gondii at least 3 to 5 months earlier (time to conversion from low- to high-avidity antibodies varies with the method used). Because low-avidity antibodies may persist for many months, their presence does not necessarily indicate recently acquired infection.

Polymerase Chain Reaction

PCR amplification is used to detect T. gondii DNA in body fluids and tissues. The PCR assay can be used to detect the presence or absence of T. gondii DNA in fresh or frozen biopsy tissue, CSF, amniotic fluid, serum, or plasma. A negative result does not rule out the presence of PCR inhibitors in the specimen or T. gondii DNA concentrations below the level of detection by the assay.

A PCR test performed on amniotic fluid has revolutionized the diagnosis of fetal T. gondii infection by enabling an early diagnosis to be made, which avoids the use of more invasive procedures on the fetus.

Histologic Diagnosis

 Demonstration of tachyzoites in tissue sections or smears of body fluid (e.g., CSF, amniotic fluid, bronchoalveolar lavage fluid) establishes the diagnosis of the acute infection. The immunoperoxidase method is applicable to unfixed or formalin fixed paraffin-embedded tissue sections.

A rapid and technically simple method is the detection of T. gondii in air-dried, Wright-Giemsa–stained slides of centrifuged (e.g., cytocentrifuged) sediment of CSF or of brain aspirate, or in impression smears of biopsy tissue. Multiple tissue cysts near an inflammatory necrotic lesion indicate acute infection or reactivation of latent infection.

Cell Culture

 Detection of T. gondii in the blood may represent a major advance in the diagnosis of toxoplasmosis in patients with AIDS. A cell culture method for the growth of T. gondii has been developed using monocytes. After 4 days, parasites in the culture are revealed by immunofluorescence with an anti-P30 monoclonal antibody. A quantitative and qualitative analysis by cytofluorometry can then be performed on the cultured cells.

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على الكوكب الأحمر.. ناسا تعثر على "قبعة الساحرة"

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مواضيع ذات صلة

Babesiosis

Toxoplasmosis (Toxoplasma gondii)

علاج الليشمانيا

ليشمانيا الاغشية المخاطية Mucocutaneous leishmaniasis

الليشمانيا الجلدية Cutaneous leishmaniasis

الليشمانيا الحشوية Visceral leishmaniasis

البنية المستدقة (التركيب الفوقي) لطفيليات اللشمانيا leishmania Ultrastructure of

دورة حياة الليشمانيا

جنس الليشمانيا Genus Leishmania

المشعرة المهبلية Trichomonas vaginalis

المشعرة البشرية Trichomonas hominis

جيارديا لامبليا Giardia lamblia