Meningitis in Children - I.V. Bogadelnikov 2005

Aseptic Meningitis in Children. General Information
Aseptic Meningitis of Parasitic Etiology
Toxoplasma Meningitis

CNS lesions caused by parasites are observed in diseases such as Toxoplasmosis, malaria, amebiasis, and giardiasis. As a rule, CNS involvement in the form of meningitis or meningoencephalitis occurs in patients with severe, disseminated forms of these infections. The Nature of CSF changes can be either purulent or serous.

Among this group of meningitides in children, toxoplasmic and ornithosis meningitides are the most common.

Toxoplasmic meningitis (meningoencephalitis) is a congenital or acquired parasitic disease characterized by severe CNS damage involving the Meninges and often the Brain AND SPINAL cord parenchyma, as well as the eyes, Liver, Spleen, and other Organs.

Etiology. The CAUSATIVE AGENT OF the disease is Toxoplasma gondii, an obligate intracellular parasite that morphologically resembles an elongated orange slice. It is 4-7 µm in length, with one rounded end; when stained with Romanowsky-Giemsa, the Cytoplasm stains blue and The Nucleus red-violet. The pathogen was first isolated in 1908 by C. Nicolle and L. Manceaux in Tunisia from gundi rodents, and by A. Splendore in Brazil from rabbits. Like all parasites, Toxoplasma has a definitive host (domestic cat, lynx, jaguar, etc.) and an intermediate host (humans and many species of warm-blooded birds). Vegetative forms of Toxoplasma (endozoites) are unstable in the environment and die rapidly, within a few hours, outside the body. Toxoplasma is sensitive to high temperatures, 2% chloramine solution, 1% phenol solution, and 50% alcohol solution. Cysts and oocysts are more resistant and can survive in meat at temperatures of 4-6°C for up to a month, and in soil for over a year. The life cycle of the parasites includes sexual and asexual reproduction stages.

Epidemiology. The disease is ubiquitous. The causative agent of toxoplasmosis has been detected in more than 300 animal species and 150 bird species. Domestic cats, which are the main reservoir and source of infection, pose the greatest epidemiological hazard. About 1% of domestic cats are asymptomatic carriers and shed oocysts continuously in their feces. Children are predominantly affected, showing 100% susceptibility to toxoplasmosis. The Mechanism of transmission is fecal-oral, and the routes of transmission are foodborne, waterborne, and contact. Human infection most commonly occurs via the alimentary route through the consumption of meat, often with unwashed vegetables and fruits, less frequently via contact (through the Skin) and transplacentally (from a pregnant woman if she contracts a newly acquired infection). In rare cases, transmission can occur via Blood transfusions. A patient with toxoplasmosis is not contagious to others. The probability of contracting toxoplasmosis increases with age; the infection rate of the population in various countries ranges from 4 to 68%. Toxoplasmosis is often an opportunistic infection in AIDS.

Pathogenesis. The gastrointestinal tract is the most common portal of entry for toxoplasmosis oocysts. Parasites (sporozoites) emerge from the ingested oocysts and migrate from the intestine to regional Lymph Nodes, causing an inflammatory process. Upon reaching a certain concentration through reproduction in the lymph nodes, the parasites enter the bloodstream, where they reside within macrophages. The First stage of asexual reproduction begins in the cytoplasm of macrophages. In the later stages of asexual reproduction, the macrophages die, and the released parasites (tachyzoites) invade any nucleated Cells of the body.

The acute stage of infection is characterized by The formation of Toxoplasma clusters in affected cells; when these cells rupture, the parasites invade neighboring cells, and the cycle repeats. Parasitemia develops only in the acute stage of the disease. In the chronic process, the pathogen forms thick-walled cysts. Each cyst contains more than a hundred parasites. The parasite's life cycle is completed in The Human Body. Upon reaching a certain concentration, Toxoplasma organisms enter the bloodstream and spread throughout the body, causing damage to many organs and systems, including the CNS. Once in the CNS, Toxoplasma multiplies, involving the meninges and often the brain parenchyma in the pathological process, with The Development of inflammation in the form of necrotic foci that subsequently calcify. The immune status of the host, the route of infection, virulence, and other CHARACTERISTICS OF THE pathogen are of great importance in pathogenesis.

Pathological anatomy. In generalized acute acquired toxoplasmosis, the brain is affected to a lesser extent than in the congenital form. Inflammatory changes of a focal nature are noted in the form of calcifications and focal necrosis, most pronounced in the periventricular Regions of the brain. The resulting necrotic foci are small, and glial proliferation is diffuse or focal. Perivascular glial mononuclear infiltrates are found in the brain parenchyma. Involvement of the meninges is accompanied by the spread of inflammation along the CSF pathways, leading to the development of ependymitis and Hydrocephalus.

Generalized intrauterine toxoplasmosis is characterized by the presence of necrosis, calcifications, and clusters of parasites in the brain.

Specific Changes in the CNS in toxoplasmosis are not inflammatory granules, but foci of necrosis and calcification, with the presence of free forms of Toxoplasma, pseudocysts, and cysts in these areas (A.P. Kazantsev, 1985).

Clinical presentation. Based on the route of infection, two main forms of toxoplasmosis in children are distinguished: acquired and congenital. Most cases of acquired toxoplasmosis are asymptomatic. The Nature of the disease manifestations is largely influenced by the general state of the body, reactivity, and immune status. Only in severe cases, under exceptional circumstances, is CNS involvement observed, with the development of meningoencephalitis and damage to other organs, leading to Pneumonia, endocarditis, chorioretinitis, and others.

CNS involvement in children is more commonly observed in the congenital form of toxoplasmosis.

Congenital toxoplasmic meningitis (meningoencephalitis). When a pregnant woman is infected, the pathogen penetrates the fetus through the Placenta. As a result of infection, the fetus either dies or is born with Clinical symptoms of acute congenital toxoplasmosis, manifested by intoxication, jaundice, damage to the liver, spleen, lymph nodes, and CNS. If fetal infection occurred in the first trimester of Pregnancy, Disorders of the CNS and other organs are more pronounced than when the fetus is infected in late pregnancy.

Congenital toxoplasmic meningitis (meningoencephalitis) begins acutely with a body Temperature rise to 39°-40°C, severe headache, repeated vomiting, loss of consciousness, cranial nerve involvement, the appearance of meningeal signs, and cerebral disorders. Paresis and paralysis of the limbs and aphasia develop. Mental disorders often occur. Sometimes meningitis takes a subacute course, slowly progressing as meningoencephalitis with predominant involvement of the periventricular zone. It manifests as a severe condition of the child from the first days of life. Pronounced symptoms of intoxication, general cerebral, and focal manifestations are present: high body temperature, vomiting, seizures or limb tremors, paralysis, paresis, and cranial nerve involvement. With the progression of the disease, a fatal outcome quickly occurs. Sometimes the pathological process becomes chronic, with the slow development of such signs of CNS damage as mental and physical developmental delay, speech and motor function disorders, the appearance of pathological Reflexes, and increased Muscle tone. Hydrocephalus or microcephaly with oligophrenia develops, as well as severe irreversible eye changes in the form of microphthalmia, chorioretinitis, and optic atrophy. Deafness may occur.

Other clinical manifestations of toxoplasmosis that are important for the etiological Diagnosis of meningitis include generalized lymphadenopathy, myositis, mesadenitis, hepatomegaly, and chorioretinitis. Calcifications in the brain can be detected radiographically or by computed tomography. In the CSF, pleocytosis is in the range of 100-1000 cells per 1 µL with a predominance of lymphocytes, the protein content reaches 5 g/L, and xanthochromia may be present. Detection of Toxoplasma in the CSF and positive serological tests are decisive in establishing the diagnosis.

The latent form of toxoplasmosis can be one of the causes of brain damage in HIV-infected children at the stage of AIDS-related complex, when the activation of the opportunistic infection occurs. In this case, Toxoplasma begins to develop inside Neurons, followed by the formation of inflammatory foci. Clinically, this manifests as the development of necrotizing encephalitis, brain abscesses, or severe generalized forms of the disease. In meningoencephalitis, severe headaches, somnolence, epileptiform seizures, meningeal signs, focal neurological symptoms, and cognitive decline are noted. These CNS changes are often combined with hepatolienal syndrome, pneumonia, myocarditis, lymphadenopathy, and chorioretinitis.

Toxoplasmic meningoencephalitis is detected in 50% of AIDS patients, accounting for up to 90% of all deaths from toxoplasmosis.

A diagnostic criterion confirming the diagnosis of toxoplasmic meningoencephalitis in patients at the stage of AIDS-related complex is the detection of intracranial calcifications using radiography, computed tomography, or nuclear magnetic Resonance. Serological tests are of little informative value because positive reactions only indicate the presence of infection but do not reflect The activity of the process. Furthermore, in AIDS, the antibody titer is sharply reduced.

Main diagnostic criteria for toxoplasmic meningitis (meningoencephalitis):

1. Epidemiological history: the disease develops during intrauterine fetal infection or against the Background of generalization of a chronic or latent form of toxoplasmosis.

2. Infants and children in the first months of life are more commonly affected; older children are rarely affected.

3. An acute onset of the disease is characteristic of meningoencephalitis, while a subacute onset is typical for meningitis.

4. Neurological symptoms develop at the peak of clinical manifestations of toxoplasmosis and are characterized by A wide variety of symptoms and a lack of Specificity.

5. In severe cases, loss of consciousness, mental disorders, and speech impairment are possible.

6. For etiological diagnosis, it is necessary to consider the presence of generalized lymphadenopathy, myositis, mesadenitis, chorioretinitis, and brain calcifications detected radiographically.

7. The detection of Toxoplasma in the CSF and positive serological tests are crucial for establishing an etiological diagnosis.

Laboratory diagnosis. A complete blood count (especially in the chronic form) may reveal leukopenia and neutropenia, relative monocytosis, and a normal ESR.

Microscopic examination. If toxoplasmosis is suspected, blood, CSF, lymph node aspirate, remnants of fetal membranes, as well as biopsy and autopsy Materials are examined. Smears and sections are stained using Romanowsky-Giemsa or Wright's stains. Detection of Toxoplasma in brain tissue specimens is performed using Electron Cell/15.html">Microscopy or various immunofluorescence Methods.

Microscopy results should be interpreted with caution, as it is necessary to differentiate acute infection from latent and chronic forms.

Bioassay. White mice are inoculated parenterally with blood from individuals suspected of harboring Toxoplasma, which helps detect the acute form of the disease through microscopic examination of tissue samples from the infected animals. This method is of the highest diagnostic value.

Serological testing:

a) Ig detection. Antibodies to Toxoplasma appear in the Cytology/cytology/16.html">Early stages of the disease and are detected using CFT, IHA, and latex agglutination tests. Their presence is used to diagnose congenital toxoplasmosis, as Ig do not cross the placenta, and their detection in newborns indicates active infection. Antibody titers in these tests of 1:80 or higher indicate the presence of toxoplasmosis.

These tests are relatively non-specific, difficult to standardize, and are not widely used in infants and immunocompromised patients.

b) Ig detection. The production of antibodies of this Class peaks at weeks 4-8. Typical antibody titers are 1:1000 or higher. The indirect immunofluorescence assay (IFA) is the most widely used method.

Currently, ELISA and RIA Methods based on the detection of Ig class antibodies have been developed. They are particularly widely used in infants and immunocompromised patients.

The toxoplasmin skin test is the most accessible diagnostic method. The test becomes positive from the 4th week of the disease and remains so for many years. A positive result only indicates a past infection and points to The Need for a more thorough evaluation.

CSF examination. In the development of meningitis (meningoencephalitis), the CSF is examined, showing pleocytosis ranging from 100 to 1000 cells/μL with a predominance of over 50% lymphocytes, elevated protein content (up to 5 g/L), and potential xanthochromia. The detection of Toxoplasma in the CSF is crucial for establishing an etiological diagnosis.