bubble_chart Overview

Toxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii, widely distributed around the world and posing a serious threat to human and animal health. Congenital infection is far more severe than acquired infection, and this infection is systemic, primarily manifested as systemic infectious toxic symptoms and lesions in multiple organs such as the central nervous system and eyes.

bubble_chart Epidemiology

Due to different routes of pestilence, there are two types: congenital and acquired. When a pregnant mother is infected, Toxoplasma gondii can be transmitted to the fetus through the placenta, leading to congenital toxoplasmosis. Acquired toxoplasmosis refers to infection acquired from the surrounding environment after birth. It can occur by consuming raw meat, eggs, or dairy products from livestock or poultry containing cysts, or by ingesting water, food, or hands contaminated with oocysts. Direct contact with infected animals (whose saliva, urine, or feces contain Toxoplasma gondii), such as through licking, being bitten, or during slaughter, can also lead to direct infection. Additionally, blood transfusion or organ transplantation can also cause pestilence, though these are secondary routes.

Toxoplasmosis is widely distributed globally, with an infection rate of approximately 25-50%. In some European and American countries, the rate can exceed 50%. In China, the infection rate ranges from 1.87% to 38.2%. A 1989 report from the Department of Pediatrics at Jiangxi Medical College indicated that the antibody positivity rate among healthy children was 10% in rural areas and 5% in urban areas. This parasite can be stained using Giemsa or Wright's methods.

bubble_chart Pathogen

The pathogen of this disease is the protozoan Toxoplasma gondii. It is named after the shape of its trophozoite. Cats and felines serve as its definitive hosts and sources of pestilence, while intermediate hosts include humans and animal hosts other than cats and felines, encompassing all mammals, birds, fish, and various domestic animals and poultry.

Toxoplasma has five different forms in its life cycle: trophozoite, cyst, schizont, gametocyte, and oocyst. The trophozoite is banana-shaped or crescent-shaped, measuring about 4-7μm in length and 2-4μm in width. All five forms are present in the definitive host, while only the trophozoite and cyst forms are found in intermediate hosts. The most significant forms in the transmission of Toxoplasma are the oocyst and cyst, followed by the trophozoite. The source of pestilence is mainly animal pestilence, which occurs only under special circumstances.

bubble_chart Pathogenesis

In the early stages of infection, Toxoplasma gondii disseminates to various organs and tissues throughout the body, causing corresponding pathological changes. In the advanced stage of infection, the body gradually produces specific antibodies against Toxoplasma gondii, and the parasite forms cysts within the tissues, leading to the gradual stabilization of the existing lesions. The condition of toxoplasmosis depends on the outcome of the interaction between the pathogen and the host. After invading the human body, some individuals do not develop symptoms, representing a latent infection, with only a minority showing clinical manifestations. In patients with latent infection or stabilized lesions, a decline in immune function (or treatment with immunosuppressive agents) can lead to the reactivation of the disease.

After the pathogen proliferates within host cells, it causes cellular degeneration and swelling, leading to cell rupture and the release of Toxoplasma, which then invades other cells. This cycle repeats, causing damage to tissues and organs, primarily manifested as necrotic foci due to vascular occlusion and inflammatory cell infiltration in the surrounding tissues. These are the fundamental pathological changes. The lesions are caused by the trophozoites, while cysts generally do not induce inflammation. The common sites of lesions include the brain, eyes, lymph nodes, heart, lungs, liver, spleen, and muscles.

bubble_chart Clinical Manifestations

Early fetal infection during pregnancy can lead to late abortion or malformations (the incidence of fetal malformations in pregnant women with toxoplasmosis in Beijing is 2% to 4.3%). Late stage [third stage] infection can cause premature labor or stillbirth, or result in the delivered infant showing clinical manifestations of the disease. If toxoplasmosis infection occurs close to childbirth, the baby may be born healthy but develop clinical symptoms several weeks later. If the fetus receives a certain amount of antibodies from the mother during the fetal period, the newborn may have some immunity to the disease after birth, but it is still insufficient to prevent the onset, and the course of the disease is often prolonged. The main symptoms are as follows:

1. Systemic manifestations: Systemic infection is more common in newborns, often due to the rapid proliferation of Toxoplasma in various organs, directly destroying cells infected by Chinese Taxillus Herb. Common symptoms include fever, anemia, vomiting, cyanosis, edema, maculopapular rash, body cavity effusion, hepatosplenomegaly, jaundice, myocarditis, and lymphadenopathy. Death can often occur rapidly. The so-called neonatal toxoplasmosis syndrome is mainly characterized by anemia, jaundice, and hepatosplenomegaly.

2. Central nervous system manifestations: Hydrocephalus, brain calcification, and various brain malformations are the main symptoms. These manifest as meningoencephalitis, encephalitis, or meningitis. Common symptoms include spasms, limb rigidity, cranial nerve paralysis, and motor and consciousness disorders. The cerebrospinal fluid appears yellow, with increased lymphocytes and protein. In the advanced stage, brain calcification occurs at the center of the lesion. In some cases, debris from necrotic brain tissue may detach and enter the lateral ventricle, circulating with the cerebrospinal fluid, causing obstruction of the cerebral aqueduct or lesions on the walls of the cerebral aqueduct, leading to obstructive hydrocephalus. If the lesion is localized, it may cause epilepsy. Death may occur within days or weeks of onset. If improvement occurs, sequelae such as spasms, intellectual disability, and chorioretinitis may remain.

3. Ocular lesions: Ocular lesions are relatively common, primarily affecting the retina, and occasionally the entire eye, leading to reduced eye size, deformity, and blindness. This usually occurs in both eyes.

Latent congenital toxoplasmosis is also common, accounting for about 80% of cases. There may be no symptoms at birth, but Toxoplasma cysts may be present in the nervous system or choroid retina, and neurological or chorioretinal symptoms may appear months, years, or even in adulthood.

bubble_chart Auxiliary Examination

1. Methylene Blue Staining Test: Positive results can be observed as early as 10 to 14 days post-infection, with the titer peaking between the 3rd to 5th week and potentially lasting for several months to years. A low titer generally indicates chronic or past infection. Antibodies acquired from the mother disappear within 3 to 6 months after birth. Therefore, antibody levels can be retested in children older than 4 months; a persistently high titer suggests an active infection.

2. Indirect Immunofluorescence Assay: This test measures anti-Toxoplasma IgG antibodies, with the timing and duration of the response similar to the Methylene Blue Staining Test.

3. IgM-Immunofluorescence Assay: A modified version of the indirect immunofluorescence assay, it yields positive results as early as 5 to 6 days post-infection and can remain positive for 3 to 6 months, making it suitable for early diagnosis. Due to the large molecular size of IgM, maternal IgM generally does not cross the placenta. Therefore, the presence of anti-Toxoplasma IgM in a newborn's serum may indicate a diagnosis of congenital toxoplasmosis.

4. Direct Agglutination Test: Primarily used to detect anti-Toxoplasma IgM, a titer of 1:16 is considered positive. Positive results can be detected 5 to 6 days post-infection.

5. Enzyme-Linked Immunosorbent Assay (ELISA) and Soluble Antigen-Fluorescent Antibody Technique: These methods are simple and rapid. ELISA is particularly suitable for large-scale screening due to its satisfactory sensitivity and specificity. The fluorescent antibody technique requires only a single dilution to determine antibody levels, with sensitivity comparable to that of immunofluorescence assays.

In some countries, serological testing is a mandatory premarital screening requirement. For example, in Paris, France (1985), etiological and serological tests were conducted on fetal blood from pregnant women at 20 to 26 weeks, with positive cases leading to induced late abortion.

bubble_chart Diagnosis

When the disease is suspected based on clinical features, the following laboratory tests can be applied to establish a diagnosis by identifying protozoa in the patient's body fluids or lesion tissues. Smears of the patient's blood, bone marrow, lymph puncture fluid, or cerebrospinal fluid sediment may reveal protozoa when stained with Giemsa or Wright's stain, although the positive rate is not high. Pathological biopsy of living tissue or animal inoculation tests can also be performed. Additionally, serological tests to detect an increase in antibody levels are simpler than the aforementioned methods, with higher sensitivity and specificity. This is currently the most commonly used method.

bubble_chart Treatment Measures

The prognosis of congenital toxoplasmosis is relatively severe, and treatment is necessary regardless of the presence or absence of symptoms. Acquired infections also require treatment if symptoms are present. Patients with toxoplasmic eye disease should be treated with corticosteroids concurrently.

Currently, there are three drugs with certain efficacy:

1. Sulfadiazine and pyrimethamine combination - Can be used together during the acute phase. Sulfadiazine 50-150mg/kg per day, divided into 4 oral doses, and pyrimethamine 1mg/kg per day, divided into 2 oral doses. After 2-4 days, reduce the dose by half, with a maximum daily dose not exceeding 25mg. The combined treatment course is about 2-4 weeks. Pyrimethamine is excreted very slowly and can easily cause toxicity, leading to folic acid deficiency and bone marrow suppression. Therefore, folic acid 5mg orally, three times a day, or folinic acid 5mg intramuscularly, twice a week, should be administered during treatment, and yeast tablets can be given orally to reduce toxic reactions.

2. Spiramycin - Has anti-toxoplasma effects and can pass through the placenta. Pregnant women can take 3g orally per day, with the concentration in umbilical cord blood being 3-5 times higher. It is believed that the use of spiramycin can reduce fetal congenital infection by 50-70%. This Yaodui has no adverse effects on the fetus and is suitable for treatment during pregnancy. The treatment method often alternates with sulfadiazine and pyrimethamine, with a course of 20-30 days. Congenital toxoplasmosis requires 2-4 courses of pyrimethamine-sulfadiazine, with a one-month interval between courses, during which spiramycin is used, with a dose of 100mg/kg per day. Medication can be stopped after one year of age and resumed during acute episodes.

Recently, there have been reports that the compound formula of co-trimoxazole is particularly effective against intracellular toxoplasma and easily passes through the placenta, with better efficacy for fetal toxoplasma infection than spiramycin. Its toxicity to humans is significantly lower than that of pyrimethamine-sulfonamides.

For toxoplasmic chorioretinitis, pyrimethamine-sulfadiazine should be used first for 20-30 days, followed by spiramycin combined with corticosteroid prednisone at 1-2mg/kg per day until the inflammatory lesions are absorbed, gradually reducing the dose to discontinuation to avoid clinical rebound.

bubble_chart Prevention

Prevention should be implemented for immunodeficient children and seronegative pregnant women. The main measures include proper management of human and animal feces to prevent food contamination by oocysts, avoiding consumption of undercooked meat, eggs, dairy products, and washing hands before meals. Early serological testing for antibodies in pregnant women can alert seronegative pregnant women to take preventive measures seriously to protect the fetus from infection. If the fetus is already infected, termination of pregnancy may be considered.