bubble_chart Overview

Toxoplasmosis, also known as toxoplasmic disease, is a zoonotic disease caused by Toxoplasma gondii. In humans, it is mostly a latent infection. The clinical manifestations in affected individuals are complex, and the symptoms and signs lack specificity, often leading to misdiagnosis. It primarily affects the eyes, brain, heart, liver, lymph nodes, and other organs. When pregnant women are infected, the pathogen can cross the placenta to infect the fetus, directly impacting fetal development and causing severe malformations. The risk is 10 times higher compared to uninfected pregnant women, adversely affecting eugenics and making it one of the most severe congenital infections in humans, which has garnered widespread attention. This disease is also closely related to Acquired Immune Deficiency Syndrome (AIDS).

bubble_chart Epidemiology

(1) Source of pestilence Almost all mammals and some birds can serve as reservoir hosts for Toxoplasma gondii, with varying roles in epidemiology. Cats are the most significant, followed by pigs, sheep, dogs, rats, etc. Although Toxoplasma gondii can be found in the urine, feces, saliva, and sputum of patients during the acute phase, its inability to survive long in the external environment means that, except for transmission from pregnant women to fetuses via the placenta, the significance of patients as a pestilence source is minimal.

(2) Transmission routes ① Congenital toxoplasmosis is transmitted through the placenta during pestilence. If a woman is infected for the first time during pregnancy, whether the infection is overt or latent, the fetus can be affected. However, generally, only one transmission occurs. ② Acquired toxoplasmosis is primarily transmitted orally: ingestion of food or water contaminated with infectious oocysts from cat feces, or consumption of undercooked meat, eggs, or unpasteurized milk containing cysts or pseudocysts can lead to infection. Toxoplasma gondii in the sputum or saliva of cats and dogs can enter the human body through close contact such as playing or being licked, via mucous membranes or damaged skin. Laboratory workers and those injured during autopsies can also become infected. Additionally, transmission can occur through blood transfusions and organ transplants.

(3) Susceptible populations Animal handlers, slaughterhouse workers, and medical personnel are more prone to infection. Pregnant women with new infections have a higher rate of fetal infection. Immunocompromised individuals, such as those undergoing immunosuppressive therapy, cancer patients, organ transplant recipients, and those with Acquired Immune Deficiency Syndrome, are more susceptible to the disease and often exhibit overt infections.

(4) Epidemic situation The disease is distributed worldwide, with infections in both animals and humans being extremely common. According to seroepidemiological surveys, toxoplasmosis is prevalent among domestic animals in China: the highest seropositivity rate is in cats (15.16–73%), followed by pigs, dogs, sheep, cattle, horses, etc. As for human infections, surveys in most regions of China estimate the seropositivity rate to be around 5–15%, with an average of 8.5%, significantly lower than in some Western countries, possibly due to differences in lifestyle and dietary habits.

bubble_chart Pathogen

Toxoplasma gondii belongs to the subphylum Apicomplexa, class Sporozoasida, order Eucoccidiorida, and is an intracellular protozoan parasite. Its life cycle includes five morphological forms: the trophozoite (tachyzoite); the cyst (which can survive long-term in tissues), round or oval in shape, 10–200 μm in diameter, capable of releasing bradyzoites upon rupture; the schizont; the gametocyte; and the oocyst. The first three stages involve asexual reproduction, while the latter two involve sexual reproduction. The completion of the Toxoplasma life cycle requires two hosts: in the definitive host (cats and other felids), all five forms are present; in intermediate hosts (including birds, mammals, and humans), only asexual reproduction occurs. Asexual reproduction often leads to systemic infection, whereas sexual reproduction occurs exclusively in the intestinal epithelial cells of the definitive host, causing localized infection. Oocysts are excreted in cat feces and, upon maturation, contain two sporocysts, each with four sporozoites. Under electron microscopy, the structure of sporozoites resembles that of trophozoites. When ingested by a cat, the sporozoites are released in the intestine, invade the epithelial cells of the ileum, and undergo schizogony. After the host cell ruptures, merozoites are released, invade nearby cells, and continue schizogony. Some develop into male and female gametocytes, undergo gametogony, and form oocysts, which are shed into the intestinal lumen. Under suitable temperature (24°C) and humidity conditions, the oocysts mature in about 2–4 days, are highly resistant, and can survive for over a year. If ingested by an intermediate host, sporozoites penetrate the intestinal wall upon reaching the small intestine, disseminate via blood or lymphatic circulation, and invade tissue cells, where they multiply by endodyogeny. Within cells, multiple parasites may aggregate to form pseudocysts, containing tachyzoites, which are commonly observed in acute infections. Upon host cell rupture, tachyzoites are released and invade other cells, repeating the cycle and potentially leading to host death. More commonly, however, the host develops immunity, slowing parasite proliferation and leading to cyst formation. The encysted parasites are called bradyzoites. Cysts can persist in intermediate hosts for months, years, or even a lifetime (as latent infections).

bubble_chart Pathological Changes

Toxoplasma gondii differs from most other intracellular Chinese Taxillus Herb pathogens in that it can infect almost all types of cells. After entering the bloodstream from the site of invasion, T. gondii spreads throughout the body and rapidly infiltrates mononuclear-macrophage cells as well as various organ or tissue cells of the host, where it proliferates until the cells burst. The released protozoa (tachyzoites) can then invade neighboring cells, repeating this cycle endlessly, leading to focal necrosis of local tissues and inflammatory reactions in surrounding tissues. This constitutes the fundamental pathological change during the acute phase. If the patient's immune function is normal, specific immunity can quickly develop to eliminate T. gondii, resulting in latent infection. The protozoa may also form cysts in the body, remaining dormant for long periods. Once the host's immune function declines, the bradyzoites within the cysts break out, causing relapse. If the patient has impaired immune function, the protozoa proliferate extensively, causing systemic disseminated damage. T. gondii can also act as an antigen, triggering allergic reactions and forming granulomatous inflammation. Additionally, the focal damage caused by T. gondii can lead to severe secondary sexually transmitted disease changes, such as microthrombosis, local tissue infarction, surrounded by hemorrhage and inflammatory cells, which may eventually form cavities or calcify over time.

T. gondii can invade various organs or tissues, with the most commonly affected sites being the central nervous system, eyes, lymph nodes, heart, lungs, liver, and muscles.

bubble_chart Clinical Manifestations

It is generally divided into congenital and acquired types, with both being predominantly asymptomatic infections. Clinical symptoms are mostly caused by recent acute infections or the activation of latent lesions.

(1) Congenital Toxoplasmosis: Mostly caused by pregnant women contracting acute toxoplasmosis (often asymptomatic) during pregnancy. There is an inherent correlation between whether the pregnant woman shows symptoms and the risk of fetal infection. Prospective studies indicate that the incidence and severity of congenital infection are related to the timing of maternal infection: Pregnant women infected with toxoplasmosis in the early stages of pregnancy, if untreated, can lead to 10–25% congenital infections, resulting in spontaneous late abortion, dead fetus, premature labor, and severe neonatal infections. Infections during the intermediate stage [second trimester] and late stage [third trimester] of pregnancy can cause fetal infections in 30–50% (of which 72–79% may be asymptomatic) and 60–65% (of which 89–100% may be asymptomatic), respectively. If infected pregnant women receive treatment, the incidence of congenital infection can be reduced by about 60%.

The clinical manifestations of congenital toxoplasmosis vary. Most infants are asymptomatic at birth, but some may develop retinochoroiditis, strabismus, blindness, epilepsy, psychomotor or intellectual retardation months or years after birth. Infants with symptoms at birth may exhibit the following clinical manifestations in various combinations: retinochoroiditis; hydrocephalus or microcephaly or anencephaly, intracranial calcification, accompanied by spina bifida, meningocele, harelip cleft palate; adrenal agenesis, bilateral polycystic kidneys; conjoined twins; spasms, psychomotor disorders; lymphadenopathy, hepatosplenomegaly, fever, jaundice, rash, etc.

(2) Acquired Toxoplasmosis: The severity of the condition varies, ranging from subclinical to fulminant infections. It can be localized or systemic: ① Localized infections are most commonly lymphadenitis, accounting for about 90%. It often affects the neck or armpit. The lymph nodes are firm, vary in size (generally not exceeding cm), are non-tender, and do not suppurate. It may be accompanied by low-grade fever, headache, sore throat, myalgia, lack of strength, etc. When the retroperitoneal or mesenteric lymph nodes are involved, abdominal pain may occur. The clinical presentation may mimic infectious mononucleosis or cytomegalovirus infection, but toxoplasmosis likely accounts for less than 1% of mononucleosis-like syndromes. Less common manifestations include myocarditis, pericarditis, hepatitis, polymyositis, myositis, pleuritis, peritonitis, etc. Retinochoroiditis is extremely rare. ② Systemic infections are more common in immunocompromised individuals (such as Acquired Immune Deficiency Syndrome, organ transplant recipients, malignancies, primarily Hodgkin's disease, lymphoma, etc.) and laboratory personnel. They often present with significant systemic symptoms, such as high fever, maculopapular rash, myalgia, arthralgia, headache, vomiting, delirium, and complications such as encephalitis, myocarditis, pneumonia, hepatitis, gastroenteritis, etc.

Ocular toxoplasmosis is mostly congenital, and acquired cases may result from the activation of latent congenital lesions. Clinically, it presents with blurred vision, blind spots, photophobia, pain, tearing, central vision loss, etc., with few systemic symptoms. Vision improves after inflammation subsides, but often does not fully recover. Vitreous opacity may occur.

bubble_chart Auxiliary Examination

(1) Pathogen Examination

1. Direct Microscopy: Take patient's blood, bone marrow, cerebrospinal fluid, pleural ascites, sputum, bronchoalveolar lavage fluid, aqueous humor, amniotic fluid, etc., to make smears, or take lymph nodes, muscles, liver, placenta, and other biopsy sections for Wright or Giemsa staining microscopy to find trophozoites or cysts, but the positive rate is not high. Direct immunofluorescence can also be used to examine Toxoplasma in tissues.

2. Animal Inoculation or Tissue Culture: Take the test fluid or tissue suspension and inoculate it into the abdominal cavity of mice to induce infection and find the pathogen. If the first-generation inoculation is negative, blind passage should be performed three times. Alternatively, tissue (monkey kidney or pig kidney cells) culture can be used to isolate and identify Toxoplasma.

3. DNA Hybridization Technology: Domestic scholars first applied ³²P-labeled probes containing Toxoplasma-specific DNA sequences to perform molecular hybridization with patient peripheral blood cells or tissue DNA, showing specific hybridization bands or spots as positive reactions. Both specificity and sensitivity are high. In addition, polymerase chain reaction (PCR) has also been established domestically to diagnose this disease, and compared with probe hybridization, animal inoculation, and immunological examination methods, it demonstrates high specificity, sensitivity, and speed.

(2) Immunological Examination

1. Antibody Detection: The antigens used mainly include soluble antigens (cytoplasmic antigens) and membrane antigens of tachyzoites. Antibodies to the former appear earlier (detected by dye test, indirect immunofluorescence test), while antibodies to the latter appear later (detected by indirect hemagglutination test, etc.). Using multiple methods simultaneously can complement each other and improve detection rates. Since Toxoplasma can persist in human cells for a long time, antibody detection generally cannot distinguish between current or past infections. Judgment can be made based on antibody titers and their kinetic changes. Commonly used detection methods include:

(1) Dye Test (Sabin-Feldman DT): Detects IgG antibodies. Positive results appear 1–2 weeks after infection, antibody titers peak at 3–5 weeks, then gradually decline and can persist for years. A titer of 1: positive suggests latent infection; 1:256 indicates active infection; 1:1024 indicates acute infection. The drawback is the need for live parasites for operation.

(2) Indirect Fluorescent Antibody Test (IFAT): Detects IgM and IgG antibodies. It has advantages such as sensitivity, specificity, speed, and good reproducibility, and is largely consistent with DT. However, false positives may occur if rheumatoid factor or antinuclear antibodies are present. A serum antibody titer of 1:64 indicates past infection; the rest are the same as DT.

(3) Indirect Hemagglutination Test (IHA): The method is simple. It has a high concordance rate with DT results. However, it usually turns positive about one month after infection. Interpretation is the same as IFAT. Poor reproducibility and unstable sensitized red blood cells are its drawbacks.

(4) Enzyme-Linked Immunosorbent Assay (ELISA): Can detect IgM and IgG antibodies. It has advantages such as high sensitivity and strong specificity. It can also be used for antigen identification. In recent years, based on ELISA, many new methods have been developed, such as SPA-ELISA; PPA-ELISA, where horseradish peroxidase-labeled SPA replaces enzyme-labeled secondary antibodies for ELISA detection; ABG ELISA; DIG-ELISA; DDT-ELISA; and McAb-ELISA, which are more sensitive and specific.

(5) Radioimmunoassay (RIA): Has high sensitivity and specificity.

2. Antigen Detection: This involves using immunological methods to detect pathogens (tachyzoites or cysts) within host cells, as well as metabolic or lysed products (circulating antigens) in serum and body fluids. It is a reliable method for early diagnosis and confirmation. Domestic and foreign scholars have established McAb-ELISA and sandwich ELISA methods using McAb and polyclonal antibodies to detect circulating antigens in the serum of acute patients, with a sensitivity capable of detecting antigens at 0.4μg/ml in serum.

(3) Intradermal Test The antigen is prepared from the peritoneal fluid of infected mice or the fluid of chicken embryos. It often results in a delayed, subcutaneous nodular bacterin reaction. This method can be used for epidemiological investigations but is currently not widely applied.

bubble_chart Diagnosis

The clinical manifestations of this disease are complex, making diagnosis difficult. When encountering certain clinical presentations, such as chorioretinitis, hydrocephalus, microcephaly, cerebral calcification, etc., the possibility of this disease should be considered. Confirmation relies on laboratory tests.

Congenital toxoplasmosis should be differentiated from other diseases in the TORCH syndrome (rubella, cytomegalovirus infection, herpes simplex, and toxoplasmosis). Additionally, it needs to be distinguished from syphilis, listeriosis, or other bacterial and infectious encephalopathies, as well as fetal erythroblastosis, sepsis, infectious mononucleosis, subcutaneous lymph nodes, etc. The diagnosis primarily depends on etiological and immunological examinations.

bubble_chart Treatment Measures

(1) Pathogenic Treatment Most drugs used to treat this disease have strong activity against trophozoites, but are ineffective against cysts, except for azithromycin and atovaquone, which may have some effect.

1. Pyrimethamine and Sulfadiazine (SD) These have a synergistic effect against Toxoplasma. The adult dose of pyrimethamine is 100mg divided into two doses on the first day, followed by 1mg/kg per day (maximum 50mg); for young children, the dose is 2mg/kg per day, and newborns may take the medication every 3–4 days. Concurrently, folinic acid 10–20mg/day is administered to reduce toxic reactions. The adult dose of SD is 4–6g/day, and for infants, 100–150mg/kg, divided into four doses. Treatment duration: one month for immunocompetent patients with acute infection, appropriately extended for immunocompromised patients, and AIDS patients should receive maintenance doses long-term. SMZ-TMP can replace SD. Pyrimethamine can also be combined with clindamycin, with the latter’s dose being 0.6g for adults every 6 hours, orally or intravenously.

2. Spiramycin The adult dose is 2–3g/day, and for children, 50–100mg/kg, divided into four doses. Suitable for pregnant patients, as pyrimethamine may be teratogenic; thus, it is contraindicated in the first four months of pregnancy, and spiramycin can be used instead. Ocular toxoplasmosis can also be treated with spiramycin. If lesions involve the retinal macula and optic nerve head, short-term corticosteroids may be added.

3. Others: Pyrimethamine combined with azithromycin (1.2–1.5g/day), clarithromycin (1g every 12 hours), dapsone (300mg/day), roxithromycin, etc., has been trialed in treating AIDS patients with toxoplasmic encephalitis with some efficacy. Additionally, various drug combinations, including clarithromycin and DS; azithromycin and SD; atovaquone and SD; clarithromycin and minocycline; as well as sweet wormwood extract and pentamidine, have shown satisfactory results in animal experimental infections, but their effects on human infections remain to be determined.

(2) Supportive Therapy Measures to enhance immune function may be adopted, such as administering recombinant IFN-γ, IL-α, or LAK cells. For ocular toxoplasmosis and toxoplasmic encephalitis, corticosteroids may be used to prevent or treat cerebral edema, etc.

bubble_chart Prognosis

It depends on the host's immune function status and the affected organs. Severe congenital infections often have a poor prognosis. In adults with immune dysfunction (such as Acquired Immune Deficiency Syndrome, malignant tumors, organ transplants, etc.), toxoplasmosis tends to become systemic and also has a poor prognosis. The prognosis for simple lymphadenopathy is good. Ocular toxoplasmosis often recurs.

bubble_chart Prevention

(1) Control the source of pestilence: Control diseased cats. Pregnant women should undergo serological testing. Those infected in the early stage of pregnancy [first stage] should undergo artificial late abortion, while those infected in the middle or late stage [third stage] should receive treatment. Blood donors with positive serological tests for Toxoplasma antibodies should not donate blood. Organ transplant recipients with positive serum antibodies should also not be used.

(2) Cut off the route of pestilence: Avoid close contact with cats, dogs, etc., and prevent cat feces from contaminating food, drinking water, and feed. Do not eat raw or undercooked meat, raw milk, raw eggs, etc. Strengthen health education, improve environmental hygiene, and maintain personal hygiene.