Meningitis in Children - I.V. Bohadelnikov 2005

Primary purulent meningitis in children. General information
Haemophilus influenzae meningitis

Meningitis caused by Haemophilus influenzae is an acute infectious disease characterized by a gradual onset of intoxication and meningeal symptoms, tending to follow a sluggish, undulating course and occurring sporadically.

Etiology. Haemophilus influenzae (the Afanasiev-Pfeiffer bacillus) is a small (0.3–0.4 × 1–1.5 µm) coccobacillary bacterium prone to pleomorphism. Some strains possess a polysaccharide capsule. The Cell wall of the outer membrane contains a lipopolysaccharide (endotoxin). Haemophilus influenzae is a facultative anaerobe that grows well in ambient air. A mandatory requirement for growth is the presence of fresh Blood in the nutrient medium. The antigenic Structure consists of capsular (5–30% of all strains) and somatic Antigens. Based on capsular antigens, all known strains are divided into 6 serotypes (a–f), and serotype transformation is possible. Serodiagnosis is performed using the agglutination reaction with type-specific polyvalent or monovalent sera.

Epidemiology. Among healthy individuals, the carriage rate of Haemophilus bacilli reaches 90%. Non-capsulated avirulent strains can be isolated from the Upper Respiratory Tract in 30–50% of children, whereas the carriage of encapsulated strains, predominantly Haemophilus influenzae type b (Hib infection), is observed in 3–5%. This pathotype represents the primary epidemiological hazard. The disease is registered exclusively in humans and, In addition to meningeal involvement, causes respiratory infections, endocarditis, abscesses, Arthritis, and Skin, nail, and eye lesions. The source of infection can be either a sick individual or a carrier of Haemophilus influenzae type b. Children aged 3 months to 6 years are most susceptible to the infection, with the peak incidence occurring in the same age group. Genetic factors determining susceptibility to the pathogen have currently been elucidated. The disease is most frequently registered among individuals of African and Spanish descent who lack the G2m(n) marker of IgG2 subclass heavy chains.

The main transmission routes are airborne droplet and contact. The highest incidence is observed in autumn and winter, with boys falling ill more frequently than girls. In terms of prevalence, this type of meningitis ranks third after meningococcal and Pneumococcal meningitis.

Meningitis most commonly occurs in infants During the first months of life, in weakened children with an unfavorable premorbid Background, during or after a recent acute respiratory infection of the nasopharynx or respiratory tract, and in patients with Rickets or hypotrophy. A direct correlation has been established between the level of Antibodies to the capsular antigens of Haemophilus influenzae type b and the risk of developing meningitis. A deficiency of these antibodies is observed in children starting from 3–24 months of age and persists up to five years of age.

Pathogenesis. The entryway for the infection is the mucous membrane of the upper respiratory tract. The main pathogenicity factors of Haemophilus influenzae type b are the capsule and pili, which impede the phagocytic uptake of Bacteria and facilitate their adhesion to the mucosa of the upper respiratory tract. Subsequently, the microbes penetrate the submucosa and induce inflammation. When pathogenicity factors are present, the bacteria can enter the lymphatic and Blood Circulation. Upon crossing the blood-Brain barrier (BBB) to the Central Nervous system (CNS), the pathogens localize and multiply in the pia and arachnoid mater, cause a blockade of the microvilli of the arachnoid membrane, and invade the Veins OF THE Cerebral Cortex. This leads to increased intracranial pressure, Impaired blood supply to the cerebral cortex, tissue Hypoxia, tissue necrosis, and cerebral dysfunction.

Clinical manifestations. In children suffering from Bronchitis, Pneumonia, or otitis media, the onset of Haemophilus meningitis is typically subacute and gradual. Against the background of a moderate Temperature elevation (37.5°–38°C), there appear somnolence, lethargy, adynamia, and a decrease in appetite. Over the following days, temperature and intoxication gradually increase, accompanied by headache and vomiting; meningeal signs are mild or indistinct, and seizures may occasionally occur. As the condition progresses, meningeal symptoms intensify, and involvement of the III, VI, and VII Cranial Nerves is possible. The Diagnosis of meningitis in these patients is established late and, as a rule, when the patient's condition has significantly deteriorated.

In previously healthy children, Influenza meningitis begins acutely with a sharp rise in body temperature to 39°–40°C, recurrent vomiting, and a rapid increase in other intoxication symptoms. Meningeal signs are pronounced from the first days of the illness, and seizures and focal symptoms may occur. However, manifestations of acute brain Swelling and edema are observed only rarely. Sometimes, the acute course of meningitis is accompanied by the appearance of a polymorphic or hemorrhagic rash (associated with septicemia), arthritis, or Osteomyelitis. Gastrointestinal disorders may occur, and in rare cases, infectious-toxic Shock may develop.

Features of the clinical course. The course of meningitis caused by Haemophilus influenzae type b is more frequently sluggish, undulating, and chronic, characterized by irregular fever and prolonged meningeal symptoms. However, acute septic forms with a fatal outcome on the 2nd–3rd day of the illness are possible. Another specific feature of this meningitis is the potential development of intracranial hypotension syndrome as early as the first hour of the disease. It typically arises against a backdrop of dehydration symptoms: sharpened facial features, decreased tissue turgor, loss of skin elasticity, dark circles under the eyes, yellowish skin discoloration, and a sunken anterior fontanelle. In such cases, meningeal symptoms are absent, marked muscular hypotonia is present, and deep tendon Reflexes are brisk. Upon lumbar puncture, the CEREBROSPINAL FLUID is turbid and greenish, dripping slowly; in some cases, it can only be obtained by aspiration with a syringe, which must be performed without fail. When performing ventricular puncture, one should account for the possibility of ventricular collapse (brain ventricle collapse). Cerebrospinal fluid hypotension may also develop on the 3rd–4th day of Treatment As a result of administering massive doses of benzylpenicillin or as a consequence of excessive dehydration (A.P. Zinchenko, 1986). The mortality rate among patients with influenza meningitis is 14.3%, while 41.8% of survivors exhibit severe long-term sequelae such as decortication, Hydrocephalus, tetra- or hemiparesis, Hearing loss, optic atrophy, and intracranial Hypertension, among others (A.A. Demina, 1999).

Main diagnostic criteria for meningitis caused by Haemophilus influenzae:

1. Epidemiological history: contact with a patient or a carrier of the Haemophilus bacillus, airborne droplet or contact transmission routes, predominant incidence in children aged 6 months to 3 years, and autumn-winter seasonality.

2. The Development of meningitis is frequently preceded by otitis, eustachitis, sinusitis, or bronchitis.

3. The onset of the disease is usually gradual, featuring a sluggish prodrome and catarrhal phenomena, followed by a slow yet progressive increase in body temperature, intoxication, and meningeal syndrome.

4. Less commonly, Haemophilus meningitis begins acutely with high fever, rapid escalation of intoxication symptoms, and pronounced meningeal and focal signs.

5. A characteristically sluggish, chronic, undulating course with irregular fever, prolonged manifestation of meningeal syndrome, and the development of early cerebrospinal fluid hypotension.

6. Characteristic inflammatory changes in peripheral blood and cerebrospinal fluid (CSF).

Laboratory Diagnostics. Complete blood count. Peripheral blood analysis reveals leukocytosis with neutrophilia and a left shift in the band neutrophil count, although a normal blood picture may also occur.

CSF examination. The cerebrospinal fluid is turbid, sometimes milky white, with a marked increase in protein content. Pleocytosis ranges widely, averaging 300–900 Cells per 1 µL, with a predominance of neutrophils. Occasionally, pleocytosis may be lymphocytic. Of great differential diagnostic value is the dissociation between a relatively mild pleocytosis and a high degree of CSF turbidity (the turbidity is caused by a massive load of pathogens—Haemophilus bacilli—which can be detected via bacterioscopic examination)

(T.M. Zubik et al., 1991). Protein levels are elevated up to 1.5–3.0 g/L. In prolonged meningitis, glucose levels gradually decrease. A distinctive feature of Haemophilus meningitis is the slow clearance of the cerebrospinal fluid, which can be delayed for up to 50–60 days, even under adequate antibacterial therapy.

Bacteriological examinations. Sputum, blood, and CSF are cultured on enrichment media such as blood Agar, chocolate agar, and Mueller-Hinton agar. This is followed by bacterioscopy (revealing gram-negative coccobacilli and bacilli) and biochemical identification of the isolated microbes. A specific feature of Haemophilus influenzae is its inability to ferment sugars (except for glucose).

Serological testing. Various serological assays are widely employed to identify the pathogen in clinical specimens (V.I. Pokrovsky, O.K. Pozdeev, 1999):

a) CSF sediment is mixed with a specific anti-serum. A positive reaction with gram-negative pleomorphic bacilli in the sediment confirms Haemophilus influenzae infection;

b) fluorescently labeled specific antibodies bind to capsular antigens of Haemophilus influenzae, enabling their detection in the CSF;

c) countercurrent Immunoelectrophoresis of the CSF allows the detection of microbial polysaccharide antigens. The formation of a precipitation line proves the etiological role of Haemophilus influenzae in the onset of meningitis.

Other diagnostic Methods.

a) Analysis of the requirement for X and V factors. To this end, CSF or blood is cultured on chocolate agar at 37⁰ C under microaerophilic conditions (a candle jar or CO incubator). When culturing, the growth factor requirements of the isolates are investigated using the following methods:

(1) Direct method. Material presumably containing Haemophilus influenzae is streaked onto The surface of the nutrient medium to obtain confluent growth. Paper strips soaked in X and V factors are placed on the agar surface. Bacterial growth around the strips, but not in other areas of the medium, confirms the assumption that they belong to the species Haemophilus influenzae.

(2) Satellite colony test. Used for the identification of the influenza bacillus. Test samples are inoculated onto blood agar, and certain areas of the medium are seeded with Staphylococcus aureus, which, as it grows, hemolyzes the blood and releases X and V factors. Haemophilus influenzae can be found in small satellite colonies surrounding the Staphylococcus aureus colonies.

e) Porphyrin test. Determines The ability to synthesize -aminolevulinic acid and reveals the requirement for the X factor. When studying the X factor requirement of an unknown bacterial species, the material is inoculated onto a solid medium, and commercial discs impregnated with aminolevulinic acid are applied to its surface (similar to the antibiotic disc method). After 24 hours of incubation, the culture is irradiated with UV light (Wood's lamp). If the grown microorganisms are X-independent, a brick-red fluorescence is observed.