Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. It is widely parasitized in nucleated cells of humans and animals. The clinical manifestations of the disease are complex, and the signs and symptoms are not specific enough to cause misdiagnosis, mainly affecting the eyes, brain, heart, liver and lymph nodes. Toxoplasma gondii is one of the important pathogens that cause embryonic malformations during intrauterine infection during pregnancy. It is also an important pathogen causing opportunistic infections in immunodeficient patients.
I. The life history of Toxoplasma gondii can be divided into two stages of asexual reproduction
1. Developmental stage in the intermediate host: The intermediate host is infected by swallowing oocysts, slow colonies or tachyzoites. After entering the digestive tract, Toxoplasma gondii quickly reaches various tissues and organs via lymph and blood, actively invades nucleated cells or is engulfed by phagocytes and develops and multiplies into tachyzoites in their cells. After the host cells rupture, the tachyzoites enter new cells and continue to develop and proliferate. When some tachyzoites invade the host brain, eye, skeletal muscle and other tissue cells, they become slow-growing retarded proliferators and secrete some substances to form a vesicle wall, which becomes an independent capsule after bursting the host cell. The capsule can exist in the intermediate host for months, years, or even for life. When the immune function of the host is reduced, toxoplasmosis can appear again.
2. Developmental stages in the end-host: After the oocysts, encysts and pseudocysts are swallowed by the feline, the ascospores, tachyzoites and bradyzoites are released, and the tachyzoites and bradyzoites reproduce asexually in the feline. The oocysts develop and proliferate in the epithelial cells of the intestinal mucosa of the final host small intestine, forming lysosomes. After cell rupture, the lysosomes escape, invade nearby cells, and continue to proliferate. After several generations of proliferation, some of them develop into male and female gametophytes, which proliferate as gametes, and the male and female gametophytes unite to form conidia and finally develop into oocysts. After maturation, the oocysts are removed from the host intestinal epithelium and fall into the intestinal lumen, where they are excreted in the feces. The oocysts mature in a suitable temperature (24°C) and humidity environment in about 2-4 days and contain 2 sporangia, each with 4 ascospores, which are infectious, resistant and can survive for more than 1 year.
II. Epidemiology
Toxoplasmosis is a global epidemic. China is a low-infection area, with an infection rate of 0.09% to 34%, but it shows an increasing trend year by year. According to the survey, the existence of this disease has been confirmed in almost all provinces, cities and autonomous regions in China. The infection rate of normal population is less than 10%; the infection rate of special population such as tumor patients, psychiatric patients, infants and children with congenital defects, immunosuppressed or immunodeficient patients is higher.
Toxoplasmosis is a zoonotic protozoan disease. Among domestic animals, it is the most harmful to pigs and sheep, especially pigs, and can cause epidemic outbreaks.
1.Infectious source According to the pathogenic investigation, 141 species of mammals are confirmed to have Toxoplasma gondii, but for human, livestock and poultry are the important infectious source of toxoplasmosis, especially cats and felines infected with Toxoplasma gondii, which are important in the transmission of the disease.
The former means that the disease develops when the host is immunocompromised and can be transmitted to the fetus via the placenta in the mother’s womb; the latter means that the infection is mainly oral after birth and can be acquired by eating uncooked meat, eggs, milk, etc. containing Toxoplasma gondii. The latter is mainly transmitted by mouth after birth and can be acquired by ingesting uncooked meat, eggs and milk. In addition, contact with soil and water contaminated by oocysts is also an important route. Blood transfusion and organ transplantation are important routes of medical transmission. Arthropods carrying oocysts also have some transmission significance.
3.Population susceptibility Humans are generally susceptible to Toxoplasma gondii. Especially fetuses, infants and children, tumors and AIDS patients. Long-term application of immunosuppressants and immunodeficient people may cause the rekindling of latent infection and the appearance of symptoms. Occupation, lifestyle, economic level, dietary habits, hygiene, and cultural quality are closely related to Toxoplasma gondii infection.
Animal breeders, slaughterers, meat processing workers and Toxoplasma gondii laboratory researchers are all susceptible groups; in addition, the disease also has certain ethnic distribution characteristics, and ethnic minorities are more seriously affected by toxoplasmosis than Han Chinese, which may be related to certain living and eating habits and hygiene conditions of ethnic minorities.
III. Pathogenesis and pathological changes
Toxoplasma gondii infection can be either dominant or recessive, and is closely related to the immune status of the host. People with normal immune function are mostly asymptomatic after infection, but those with impaired or defective immune function and congenital infection often have severe symptoms. Infection in pregnant women can cause miscarriage, premature birth and even stillbirth. AIDS patients can often lead to serious complications and even death. Previous studies have suggested that T lymphocytes play a key role in fighting infection. However, recent studies have found that B lymphocytes also play a role that cannot be ignored. Therefore, it is important to strengthen the immunity of susceptible individuals.
Unlike most other intracellular parasitic pathogens, Toxoplasma gondii can infect almost all types of cells. Toxoplasma gondii enters the bloodstream from the invasion site and then spreads throughout the body and rapidly enters monocytes-macrophages as well as various organs or tissue cells of the host to multiply until the cells swell up and the escaped tachyzoites can invade neighboring cells, and so on repeatedly, causing focal necrosis of local tissues and inflammatory reaction of surrounding tissues, which is the basic lesion in the acute stage. If the patient’s immune function is normal, specific immunity can be produced rapidly to clear Toxoplasma gondii and form a hidden infection; the protozoa can also form a capsule in the body and incubate for a long time, once the body’s immune function is reduced, the tachyzoa in the capsule will break the capsule and escape, causing recurrence. If the immune function of the patient is impaired, the worms will multiply and cause generalized damage. Toxoplasma gondii can also act as an antigen, causing allergic reactions and granuloma-like lesions. In addition, focal damage caused by Toxoplasma gondii can lead to severe secondary lesions, such as small thrombosis, local tissue infarction surrounded by hemorrhagic and inflammatory cells, and the formation of cavities or calcifications over time.
Toxoplasma gondii can attack a variety of organs or tissues, with the most common sites of lesions being the central nervous system, eyes, lymph nodes, heart, lungs, liver and muscles.
Histopathological examination often shows typical follicular hyperplasia in the lymph nodes, focal damage with mononuclear cell infiltration and irregular concentrations of cytoplasmically eosinophilic, dense tissue phagocytes. Granulocytic infiltration and abscess formation are rarely seen.
IV. Clinical manifestations
There are two general categories: congenital and acquired, both with occult infection. Clinical symptoms are mostly caused by recent acute infection or activation of underlying lesions.
1.Congenital toxoplasmosis
Congenital toxoplasmosis can be transmitted to the fetus through the placenta when a pregnant woman is infected with Toxoplasma gondii without treatment. The incidence and severity of congenital infection is related to the early and late infection time of pregnant women: early pregnancy infection causes low rate of fetal congenital infection, but the condition is serious. The incidence of congenital Toxoplasma gondii infection in late pregnancy is high, but the disease is mild. The clinical manifestations of congenital toxoplasmosis are complex and varied. Premature birth, miscarriage or stillbirth may occur during pregnancy. After birth, a variety of congenital malformations may occur, including hydrocephalus, microcephaly, spina bifida, microphthalmia, anophthalmia, cleft harelip and palate, etc. Psychomotor disorders due to toxoplasma encephalopathy may include mental retardation, epilepsy, myotonia, spasticity and paralysis; ocular lesions are more common, including chorioretinitis, ocular muscle paralysis, iridocyclitis, cataract, optic neuritis and optic nerve atrophy, etc. In addition, after birth, children with toxoplasmosis may have Fever, rash, pneumonia, hepatosplenomegaly, jaundice, etc. Pregnant women with Toxoplasma gondii infection may also have increased pregnancy complications, such as weak contractions, excessive postpartum bleeding, incomplete uterine regeneration, and endometritis. If infected pregnant women can receive treatment, the incidence of congenital infection can be reduced by about 60%.
2.Acquired toxoplasmosis
Acquired toxoplasmosis is more complex, with varying severity, ranging from subclinical to fulminant infection, and is related to the soundness of immune function.
Several patients have enlarged nodes, and in addition to enlarged superficial lymph nodes, they may also have. The present is more complex, whether soundness related, hepatosplenomegaly, jaundice, etc. and atrophy and other spasms and paralysis; eye lesions are mostly seen as hydrocephalus, microcephaly, spina bifida, microphthalmia, anophthalmia, cleft harelip and palate, etc.1. Acquired toxoplasmosis with normal immune function 80% to 90% are occult infection or cervical lymph node enlargement. 10% to 20% of patients have clinical symptoms, manifested as chills, fever, headache, myalgia, pharyngitis, rash, hepatosplenomegaly, generalized lymph node enlargement, in addition to superficial In addition to superficial lymph node enlargement, mediastinal, retroperitoneal or mesenteric lymph node enlargement may also be involved, and abdominal pain may be present when the abdominal lymph nodes are enlarged. Chorioretinitis may also occur.
The course of the disease is benign and self-limiting in most patients, usually weeks to months and rarely more than a year. Most lymphadenopathy resolves spontaneously, with a few patients becoming chronic. In rare cases, pneumonia, acute respiratory distress syndrome, myocarditis, pericarditis, polymyositis, hepatitis, and encephalitis may develop.
Immunodeficient acquired toxoplasmosis Patients with immunodeficiency such as AIDS, organ transplantation, Hodgkin’s disease, lymphoma, etc. infected with Toxoplasma gondii or relapse of latent infection may have significant systemic symptoms such as high fever, maculopapular rash, myalgia, arthralgia, headache, vomiting, delirium, etc. K may occur with disseminated and severe multi-organ infection.
V. Central nervous system Toxoplasma gondii infection
1, focal encephalopathy: manifested as intracerebral occupying lesions, such as headache, hemiparesis, epilepsy, visual impairment, delirium, etc.
2.Diffuse encephalopathy: less common, but rapid onset and development. There is delirium with signs of meningeal irritation and other meningoencephalitis.
3, myelitis: seen in AIDS patients with Toxoplasma gondii infection. There may be motor and sensory impairment of one or more limbs.
2. Pulmonary toxoplasmosis: Most often seen in patients with advanced AIDS. There is prolonged fever, cough and difficulty in breathing.
3.Ocular toxoplasmosis: mainly manifests as chorioretinitis. There is vision loss, visual distortion, etc.
4.Other toxoplasmosis: hypopituitarism, uremia; abdominal pain, diarrhea, ascites and acute liver failure, etc.
VI. Laboratory tests
Total peripheral blood leukocyte count is usually within the normal range or mildly increased. Lymphocytes can be increased, but the percentage of increase is usually not more than 10%, and abnormal lymphocytes can be seen. In Toxoplasma gondii encephalopathy, the typical cerebrospinal fluid shows an increased total leukocyte count, predominantly monocytes; increased protein, normal sugar, and decreased chloride. The cerebrospinal fluid centrifugal Jimsa staining sometimes reveals tachyzoites.
1, pathogenic tests Pathogenic tests are less commonly used in clinical practice because of their complexity, low detection rate, and invasive nature. Direct microscopic examination of blood, bone marrow, cerebrospinal fluid, lymph nodes, muscle, liver and spleen, placenta and other tissues inside and outside the cells can find tachyzoites, pseudocapsules or slow proliferation can be diagnosed, but the positive rate is not high. Animal inoculation or tissue culture can be used for the identification of Toxoplasma gondii. Currently, polymerase reaction (PCR) and real-time quantitative PCR methods can be used to diagnose the disease with high specificity and sensitivity.
2.Immunological test Immunological test is simple and rapid, with high sensitivity and specificity, so it is most widely used in clinical practice.
(1) Serum-specific antibody test: IgM antibody can appear on day 5-7 after Toxoplasma gondii infection, and a positive IgM or a 4-fold increase in IgG within 2 weeks can lead to an early diagnosis of the presenting infection. Commonly used detection methods include Sabin-Feldman staining test (Sabin-Feldman, SFDT), indirect fluorescent antibody test (IFA), indirect hemagglutination test (IHA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). Among them, ELISA has high sensitivity and specificity, and is widely used in clinical applications.
(2) Serum circulating antigen test: ELISA is commonly used to detect Toxoplasma circulating antigen in serum, which has high sensitivity and specificity and can be used as a reliable method for early diagnosis and confirmation.
(3) Intradermal test: The intracutaneous test is performed on the peritoneal fluid of infected mice or chicken embryo fluid. It is generally positive only 4~18 months after infection and can be used only for epidemiological investigation.
VII. Diagnosis
1. Congenital toxoplasmosis: The clinical manifestations of this disease are complex and difficult to diagnose. If the clinical appearance of chorioretinitis, hydrocephalus, microcephaly, intracranial calcification, etc. should be considered the possibility of the disease. Definitive diagnosis depends on pathogenetic examination. Serological examination is the most commonly used diagnostic method. In the acute phase, IgM can be positive within a week. If the initial test is positive for IgM and negative for IgG, a repeat test 2 weeks later is positive for both IgM and IgG, this diagnosis is supported. Because direct contact with felines is not required for Toxoplasma gondii infection, it is important to emphasize that a history of cat contact is not necessary. However, the diagnosis of toxoplasmosis cannot depend on any one test due to sensitivity and specificity issues. High-risk groups (e.g., pregnant women, immunocompromised individuals) require multiple serological testing methods for further diagnosis.
2. Acquired toxoplasmosis: Toxoplasma gondii lymphadenitis can be diagnosed in immunocompetent hosts with acute lymphadenopathy and positive IgM by serologic ELISA and positive IgM and IgG after 2 weeks, except for negative IgM and IgG. If the serological ELISA results are suspicious, further serological tests or PCR for Toxoplasma gondii DNA may be performed to confirm the diagnosis. If ocular lesions are clinically present, Toxoplasma gondii antibodies from relevant intraocular samples will be required to confirm the diagnosis.
Most AIDS patients with Toxoplasma gondii may present with multiple, dense lesions in the brain parenchyma with edema. CT or MRI should be performed if there are clinical symptoms such as headache and neck stiffness; MRI is more sensitive than CT, and SPECT and PET can differentiate brain lymphoma from infection (including Toxoplasma gondii infection). If necessary, craniotomy or stereotactic brain biopsy can be performed.
Since Toxoplasma gondii in AIDS patients is a recurrence of latent infection, patients already have IgG antibodies in their body, but not IgM antibodies, and less than 1/3 of patients have elevated antibody titers, antibody negativity cannot exclude toxoplasmosis. Therefore, once a patient with AIDS has the following 3 points: CD4+ cell count <0.1×109/L, positive IgG on serology, and typical brain imaging, the patient can be diagnosed as suspicious and receive empirical treatment. If the 3 diagnostic points cannot be met simultaneously, brain biopsy or other diagnostic tests are required.
VIII. Differential diagnosis
Congenital toxoplasmosis should be differentiated from other diseases in the TORCH syndrome. In addition, it should be differentiated from congenital syphilis, etc.
Toxoplasma gondii lymphadenitis should be differentiated from lymph node tuberculosis, bacterial lymphadenitis and lymphoma.
Acute toxoplasmosis with systemic symptoms should be differentiated from EBV or cytomegalovirus infection, sepsis, cat scratch fever, rabbit fever, brucellosis, etc.
Toxoplasmosis in the central nervous system should be differentiated from viral, bacterial, tuberculous and fungal meningitis, encephalitis and meningoencephalitis, etc.
Treatment
1.Toxoplasma gondii treatment targets
(1) Immunocompetent patients with Toxoplasma gondii who have severe symptoms and important organ involvement, such as cerebral toxoplasmosis and ocular toxoplasmosis;
(2) Immunocompetent patients with dominant and recessive Toxoplasma gondii infection.
(3) Children with congenital toxoplasmosis.
(4) Pregnant women with recent Toxoplasma gondii infection whose serological test has changed from negative to positive.
IX. Prevention
Toxoplasmosis is widely prevalent and both humans and animals are susceptible. Active measures should be taken for its transmission and immunoprophylaxis.
1. Pay attention to dietary hygiene, fully cook meat and separate raw from cooked.
2. Cats should be domesticated to avoid infection and transmission from the digestive tract through contaminated food.
3, pay attention to daily hygiene, pet owners, wash hands carefully after contact with animal excrement.
4. Pregnant women should avoid contact with cats and their feces during pregnancy. Monitor closely for Toxoplasma IgM and IgG, and if necessary, take amniotic fluid for immunological examination. If there is evidence of acute infection, consider whether to terminate the pregnancy.
5. Regularly monitor Toxoplasma gondii infection in key high-risk groups such as AIDS patients; practice good hygiene and dietary habits, do not eat raw food, undercooked meat, eggs and milk, and do not drink raw water.
6.For agricultural and livestock producers, fur processors, slaughterers, meat processors, laboratory animal breeders and users, etc., should strengthen the training of prevention knowledge.