Meningitis in Children - I.V. Bohadelnikov 2005

Serous meningitis in children. General overview
Serous meningitis of bacterial etiology
Leptospiral meningitis

This group of serous meningitis includes Meningitis caused by leptospires, Mycobacterium tuberculosis, and Treponema pallidum.

Leptospiral meningitis is a form of serous meningitis characterized by an acute onset, general intoxication and meningeal syndromes, as well as clinical manifestations typical of leptospirosis.

Etiology. The disease is caused by pathogens belonging to the genus Leptospira, which comprises free-living (saprophytic) and parasitic species (pathogenic to humans and animals). The reference species, L. interrogans, is represented by more than 100 serovars. Leptospires are single, spiral-shaped Cells with an average size of 7–14 × 0.1 µm, possessing a delicate Cytoplasm devoid of inclusions, and are motile with characteristic screw-like movements. In smears stained with Gram or Romanowsky-Giemsa stains, they appear pink, but they are better visualized using silver impregnation, which turns them brown or black. Leptospires are obligate aerobes with an optimal growth Temperature of +30°C; they grow in liquid and semi-liquid media supplemented with rabbit serum within 5–8 days of incubation (sometimes up to 21–25 days). In cultures, The formation of leptospiral tangles is frequently observed. Pathogenic serovars are sensitive to sunlight and high temperatures (they are destroyed within 45 minutes at a Water temperature of 45°C, and within 10 seconds at 70°C), while desiccation causes immediate death. In freshwater reservoirs, they survive from several hours to 30 days; they persist in dry soil for 2–3 hours, and in marshy soil for up to 200 days. All leptospires are susceptible to disinfectants (0.1% Hydrochloric acid solution, 0.5% phenol solution, etc.), which kill them within a few minutes.

Epidemiology. The reservoir and source of infection include various wild and domestic animals. By excreting leptospires in their urine, they contaminate open water bodies, soil, food supplies, and vegetation. Humans contract leptospires through swimming in open ponds and water bodies, consuming contaminated food, or engaging in agricultural activities. Cases of infection are also documented following direct or indirect contact with infected animals. Rodents can develop chronic forms of the disease with continuous shedding of the pathogen into the environment. A person sick with leptospirosis poses no danger to others. Experiments have also proven the ability of Blood-sucking insects and ticks to harbor (for up to 1 month) and transmit leptospires. The transmission mechanism of leptospirosis is fecal-oral. The primary route of transmission is waterborne, while contact and foodborne routes are less significant. The incidence peak of leptospirosis is observed from July to September, and the disease is distributed globally. Older children and adults are affected more frequently than others.

Pathogenesis. The portal of entry for the infection consists of damaged Skin or mucous membranes of the Nose, Mouth, eyes, or Esophagus. Combined infection (via both mucous membranes and skin) is more common. Without leaving inflammatory changes at the site of entry, leptospires initially invade regional Lymph Nodes, and subsequently enter the bloodstream, causing primary leptospiremia. Generalized leptospiremia lasts for 4–5 days from the moment of infection and is accompanied by the accumulation of the pathogen in parenchymal Organs (by days 5–6). Leptospires predominantly accumulate in The Liver and Kidneys, where active multiplication takes place. Re-entry of leptospires into the bloodstream (secondary leptospiremia) results in damage to the liver, kidneys, Adrenal Glands, Spleen, and other organs, leading to functional insufficiency. During the septic stage of the disease, leptospires can readily cross the blood-Brain barrier (BBB) into the Central Nervous system (CNS), resulting in serous meningitis and meningoencephalitis, as evidenced by their isolation from CEREBROSPINAL FLUID (CSF) between the 7th and 15th days of illness. Massive breakdown of leptospires from the end of the first to the beginning of the second week of the disease triggers the toxemic phase, which is characterized primarily by microvascular endothelial damage and The Development of multiple hemorrhages in Internal Organs and the skin. Intoxication and microcirculatory disorders lead to CNS involvement, manifesting as neurotoxicosis more frequently than as serous meningitis. Starting from the second week of the illness, specific Antibodies are produced in the body, and leptospires are cleared. Recovery confers robust and lasting Immunity.

Pathological anatomy. Histological examination of the brain in deceased patients reveals significant circulatory disturbances with predominant damage to the microvasculature. These changes manifest as hemorrhages, edema of the brain tissue and Meninges, focal cerebral hemorrhages, as well as dystrophic alterations accompanied by foci of necrobiosis and necrosis (E.P. Bernasovska et al., 1989).

Clinical Features. The incubation period of leptospirosis averages 6–14 days, with a range of 3 to 30 days.

Clinical manifestations of leptospirosis vary widely. Leptospiral meningitis develops in 10–20% of patients. In typical cases, the disease follows a biphasic course: initially, fever, chills, myalgia, and headache persist for 3–6 days. Following an asymptomatic interval lasting 1 to 3 days, the second (immune) phase begins, during which meningitis manifests against the backdrop of recurring initial symptoms. The meningeal syndrome is characterized by intensified headaches, dizziness, nausea, and vomiting. With the development of meningitis, the patient's general condition deteriorates significantly; cutaneous hyperesthesia and photophobia appear, and nuchal rigidity along with Kernig's and Brudzinski's signs can be elicited. The meningeal syndrome persists for a prolonged period, typically 20–30 days. Concurrently with meningitis, renal and hepatic dysfunction sometimes develops.

Leptospiral meningoencephalitis is characterized by mild Facial Nerve paresis, anisocoria, convergence insufficiency, sluggish pupillary Reflexes, and other symptoms combined with the meningeal syndrome. Pathological reflexes—such as Babinski, Gordon, and Rossolimo signs—may also be present. Upon lumbar puncture, the CSF emerges under pressure and appears turbid. Pleocytosis ranges from 100 to 500 cells per 1 µL, initially neutrophilic and subsequently lymphocytic. Protein content is elevated, while glucose and chloride levels remain within normal limits.

Main diagnostic criteria for leptospiral meningitis:

1. Epidemiological history: animal contact, swimming in freshwater bodies, higher incidence among older children, and summer-autumn seasonality.

2. Meningeal syndrome developing on the 6th–8th day of illness, most frequently at the peak of the fever.

3. Presence of typical Clinical symptoms of leptospirosis, such as acute onset, Muscle pain, characteristic appearance, frequently polymorphic rash (including hemorrhagic), jaundice, and hepatomegaly.

4. CSF findings characteristic of serous meningitis.

5. Definitive confirmation of the etiology via bacterioscopic detection of leptospires in the blood and CSF.

Laboratory Diagnostics. Complete blood count reveals neutrophilic leukocytosis, a left shift with immature forms and myelocytes, aneosinophilia, early and significant elevation of the ERYTHROCYTE SEDIMENTATION RATE (ESR up to 50 mm/h), and anemia.

Microscopic examination. Direct Cell/15.html">Microscopy is performed on a blood smear prepared by the "hanging drop" method (During the first week of illness) or urine sediment (from the second week onwards), which may reveal leptospires.

Bacteriological examination. During the febrile period, blood, urine, and CSF cultures are inoculated onto standard nutrient media. Guinea pigs are also inoculated with the same material, followed by the detection of leptospires in urine or Tissues using silver nitrate staining.

Serological testing: a) detection of antibodies using the microscopic agglutination-lysis test with live leptospiral cultures, with a diagnostic titer of 1:100–1:200;

b) determination of antibody titers via the indirect hemagglutination assay (IHA) using formalinized erythrocytes sensitized with leptospiral Antigens, with a diagnostic titer of 1:80.

Other Methods. Enzyme-linked immunosorbent assay (ELISA) and immunodiffusion are considered promising diagnostic methods.