Meningitis in Children - I.V. Bogadelnikov 2005

Aseptic Meningitis in Children. General Overview
Aseptic Meningitis of Fungal Etiology
Coccidioidal Meningitis

Coccidioidal meningitis is a slowly progressive disease manifested by granulomatous lesions of the Meninges and characterized by a prolonged chronic course.

Etiology. The pathogen Coccidioides immitis belongs to Molds, the main reservoir of which is soil. A characteristic property of the fungus is dimorphism, i.e., existence in 2 forms: the cultural form (in soil) and the tissue parasitic form (in the host's body). The mycelial phase of fungal reproduction is considered saprophytic or natural, and the Yeast-like phase is considered the tissue phase.

In body Tissues, the fungus appears as spherules—large, oval, or round structures 20 to 80 μm in diameter with a distinct double-contoured wall. Coccidioides immitis is considered the most virulent infectious agent among all fungal pathogens.

It grows well on standard nutrient media, forming grayish mold colonies after 7 days of incubation at 25°C.

Coccidioides immitis is resistant to ultraviolet and X-ray radiation, as well as other Physical and Chemical influences.

Epidemiology. Coccidioidomycosis is endemic to certain Regions of the Southwestern United States, Mexico, the San Joaquin Valley, Argentina, and other regions of South and Central America. According to Skin test data, more than 90% of the population in these areas have Antibodies to the pathogen. However, only 1% of primary cases progress to coccidioidal meningitis.

Sporadic outbreaks of the disease can occur anywhere. They are caused by pottery or textile products manufactured in endemic areas and exported to other countries. A corresponding susceptibility to this disease is observed in people of different races, with Filipinos, Blacks, and dark-skinned ethnic groups being the most susceptible. Factors that mediate a high probability of infection and dissemination of the pathogen include Pregnancy and glucocorticoid use. In non-endemic areas, sporadic cases of the disease are usually registered, caused by the importation of Fungi with various products. It has been proven that staying in an endemic area for just a few hours is sufficient to contract coccidioidomycosis.

The route of infection is aerosol. Susceptibility is general, high enough for the occurrence of primary foci, but low for disseminated forms of the disease.

Pathogenesis. The portal of entry for the infection is the mucous membranes of the Upper Respiratory Tract. While local resistance factors of the respiratory tract mucosa actively prevent the germination of arthrospores in the Trachea and Bronchi, their activity is sharply reduced at the alveolar level. In the affected alveolar spaces, the spherule formation phase begins. Mature spherules contain endospores; upon maturation, the spherule walls rupture, releasing endospores into the surrounding tissues, where some of them are phagocytosed by leukocytes. The fungal infection triggers an inflammatory response involving leukocytes, macrophages, and giant Cells. However, the thick fungal Cell wall and germinating spherules inhibit phagocytic activity. Defects in the cellular Immune Response facilitate the dissemination of the infectious process and The Development of secondary foci in any organ. Disseminated coccidioidomycosis typically develops in untreated cases no earlier than 6 months from the onset of the disease, presenting with Osteomyelitis, Arthritis, skin manifestations, and meningitis.

Clearance and elimination of the pathogen are mediated primarily by cellular immune responses and, to a lesser extent, by humoral ones.

Pathological anatomy. Morphological changes in coccidioidomycosis are associated with The life cycle of the pathogen. During the release of endospores from spherules, a polynuclear reaction with abscess formation develops in the surrounding tissues. As surviving endospores mature and form spherules, granulomatous tissue is formed, consisting of histiocytes, epithelioid cells, and Pirogov-Langhans or foreign-body giant cells, in whose Cytoplasm spherules are found. In the lesions, against the Background of scar tissue proliferation, abscesses containing fragments of spherule walls are detected. A granulomatous process develops on the meninges, forming numerous small granules.

Clinical presentation. The incubation period of primary coccidioidomycosis ranges from 7 to 18 days. In most cases, the primary infection is asymptomatic; some infected individuals develop a distinct Pneumonia. Meningitis typically develops 6 months to 1 year after primary infection, followed by slow progression of symptoms.

Meningitis can often be the first clinical manifestation of coccidioidomycosis, as the primary infection is asymptomatic in most cases.

The most characteristic subjective symptom of meningitis is a severe headache. Other clinical symptoms are quite variable. Fever, weakness, nuchal rigidity, mental disorders, diplopia, ataxia, and vomiting are observed. Skin lesions in the nasolabial fold area are also frequently detected.

In the CSF, monocytosis, occasionally polymorphonuclear leukocytes, elevated protein levels, and decreased glucose levels are detected.

Relapses of the disease occur frequently, usually 1-2 years after apparent recovery.

Main diagnostic criteria for coccidioidal meningitis:

1. Epidemiological history: travel to or residence in endemic areas, contact with household items manufactured in endemic areas, or products.

2. Predisposing factors (presence of immunodeficiency, use of glucocorticoids, cytostatics).

3. Onset of meningitis is gradual, occurring no earlier than 6 months to 1 year after the primary form (most commonly pulmonary).

4. Typical symptoms of meningitis include severe headache, fever, vomiting, and nuchal rigidity.

5. The disease is characterized by a prolonged course and a tendency toward late relapses.

6. The Nature of CSF changes is similar to that in Tuberculous meningitis.

Laboratory Diagnostics. Microscopic examination. Fungal mycelium is extremely rarely found in CSF and Blood. This diagnostic method is practically not used.

Bacteriological examination. Isolation and identification of the pathogen in blood cultures, CSF, and tissue biopsies is possible in no more than 30% of clinical cases. Grown cultures of Coccidioides immitis are identified by Microscopy and colony Morphology.

Serological testing. Serodiagnosis is based on the detection of Complement-fixing antibodies in the CSF. In 70% of patients, they can be detected during the very first test. As the disease progresses, antibodies are detected in virtually all patients.

Coccidioidin skin test.