Etiologia of Bacterial Meningitis in Children of the Ryazan Region

A retrospective analysis of 23 cases of bacterial meningitis (BM) in children in 2016-2019 was carried out. The examined patients were not vaccinated against H. Influenzae type B and S. pneumoniae. The dominant pathogens of BM were H. Influenzae (52.2%), S. pneumoniae (8.7%), N. meningitidis (4.3%). BM caused by H. Influenza was characterized by a wave-like course with complications, which required correction of antibiotic therapy (ABT). This indicates the feasibility of vaccinating of the children against hemophilic infection.

Acute bacterial meningitis (BM) remains a serious global health threat with high mortality and morbidity, despite advances in antibiotic therapy and modern vaccination strategies. Children are particularly vulnerable to ABM because of their relatively immature immune systems, particularly their impaired immunity to the polysaccharide capsule of bacteria commonly associated with ABM. It has been estimated that over 75% of all cases of ABM occur in children under 5 years of age, and it is one of the most common life-threatening infections in children worldwide. The WHO estimates that about 170 000 deaths occur annually from the disease worldwide; the case fatality rate can be as high as 50% if not treated [1]. The estimated median risk of at least one major or minor sequel from ABM after hospital discharge is 19.9%. Adverse outcome varies with age group, geographic location and the infecting organism. In middle- and low-income countries, ABM remains the fourth leading cause of disability [2]. Even with early diagnosis and adequate treatment 15% of patients die, as a rule, within 24 and 48 hours after the onset of the first symptoms [3]. Annually more than 4000 cases of BM in children and 500 deaths were registered in USA in 2003-2007 years [4]. Annually incidence of BM in Russia is 8.22 cases per 100 thousand population [4]. Most cases of BM are associated with opportunistic flora (S. agalactiae B, E. col, and L monocytogenes) in newborns and S. Pneumoniae, N. meningitides and H. influenzae in children and adolescent. [5,6]. Vaccination of the children against N. meningitides and H. influenza are not mandatory. Becose prevalence of BM by these pathogenes in children is higher. But during 2004-2007 yars among pathogens of BM in children were identyfed only in 38% cases. N. meningitides was a main pathogens (24%) and in isolated cases it was H. influenza and S. aureus.

To study of the clinical and etiological features of cases of the bacterial meningitis in children of the Ryazan region in 2016-2019 years.

A retrospective analysis of medical documentations of 23 patients (17 boys and 23 girls) with BM was made. The children treated in Ryazan City Hospital (average age – 2.3 year old). 

All patient with BM were admitted to infectious hospital for emergency indications. More than half of patients were delivered from regional hospitals (52.1%) and 30.1% from home by ambulance. The gender-age structure of patients presents in table (Table 1).

The majority of sick children admitted to the hospital on 2nd day of the disease (8/34.7%); 5 (21.7%) patients – on the 3rd and 6 (26.1%) – on 4th days of disease and only one patient admitted in 1st day of sick. In 30.4 % the pathogens failed to isolate. The most prevalent pathogens caused bacterial meningitis was H. influenzae (12 cases, 52.2 %). Two patients was isolated N. meningitides (8.7%), S. pneumonia in 1 case (4.3 %) and S. agalactiae in 1 child (4.3%). All patient have typical complaints and clinic of bacterial meningitis. It was febril fiver in 1st day of the deases. The fiver was poorly controlled by antipyretics. Most children had repeated woming with not food intake (82.6%), headache (86.9%), and hyperesthesia (82.6%) (Figure 1).

Figure 1: Rate of pathogens that caused bacterial meningitis in children in Ryazan region (2016-2019 years).

Table 1: The gender-age structure of patients with BM.

Different neurological symptoms were in exanimated patients: 7 children had convulsions (30.3%), monotonous cry – in 5 (21.7%), psikhomotor agitation – in 8 (34.7%), photophobia – in 1 (4,3%). Cerebral, meningeal and intoxication symptoms prevaleted in the clinic of disease (Table 2).

The disease progressed with toxicosis deferent severity. Fifteen patients have febrile fever (65.2%), in 5 children it was hectic (21.7%), in 3-subfebrile one. Cataral inflammation of appear respiratory tract had 3 patients (13.0%), respiratory disorders (tachypnea or bradipnea, shallow breathing, decrees of saturation) had 6 children (26.0%). Most of patients have changes in blood analysis: 14 patients (60.7%) had leukocytosis, 5 patients (21.7%) had leukopenia. The disease was accompanied by infectious toxicities of varying severity in all patients. Fifteen patients (65.2%) had febrile fever, 5 (21.7%) – hectic fever and 3 (13.0%) patient had sub febrile fever. Catarrhal inflammation of ??? upper respiratory tract had 3 (13.04%) patients. Hemodynamic disorders (tendency to tachycardia or bradycardia, hypertension, hypotension, microcirculation disorder, decreased CVP) were recorded in 13 (56.5%) children. Changes the blood analysis: 14 (60.7%) patients had leukocytosis, in 5 (21.7%) cases was leukopenia. There was a shift in the leukocyte formula to the left in most cases: to stab neutrophils – in 14 (60.7%) patients, to young forms of neutrophils - in 2 (8.7%) ones. Only 1 (4.3%) patient had not changes in the leukocyte formula. An increase in ESR had all patients. All the patients had of changes of cerebrospinal fluid (CSF), it was colorless, cloudy. CSF was flowing out in frequent drops in 13 (56.5%) patients; leaked out under high pressure (jet) in 7 (30.4%). Most of the examined (82.6%) had neutrophil pleocytosis. The protein content varied within wide limits – from 0.2 to 1.056 g/l. Globulin reactions (Pandey, Nonne-Apelt’s) were sharply positive in all cases (++++). Third-generation cephalosporin, such as ceftriaxone or cefotaxime, was as first-line, empiric therapy for BM. The median of ABT was 17 days (min=8; max=15). Antibiotics were used for the longest time in the treatment of BM caused by H. Influenza (21.3±1.2 days). In cases of BM of pneumococcal and meningococcal etiology, the average of course of therapy was 15.3±1.2 and 12.0±1.2 days, respectively. Against the background of the treatment, the timing of fever relief varied from 1 to 15 (min=3.5; max=12) days. General cerebral symptoms leveled off on days 2-16 (Me=4 [2.5; 8]), meningeal symptoms – on days 2-13 of therapy (Me=6 [3; 8]). The condition was assessed as moderate in 18 people (78.3%) on the 7th day of therapy. Sanitation of CSF was occurred on the 5-15th day (Me=11 [9; 15.5]), but it was prolonged to 15-20 days in 3 (13.0%) patients. BM caused by S. pneumonia was verified in 2 children (aged 3 months and 1 year old). These children were not vaccinated against this infection due to parental refusal. According to the epidemiological history, patients had family contact with adults with symptoms of catarrhal inflammation of upper respiratory tract for 3-5 days before the disease. These cases had a typical acute start of the disease, which began with febrile fever, vomiting, anorexia, lethargy. Symptoms of intoxication were prevailed (fever, pallor of the skin with a marble tint without elements of rash), positive meningeal symptoms (Lessazh, Brudzinsky’s, bulging of the fontanelle), general cerebral symptoms (impaired consciousness to stupor) were presented. The patients had grade 2-3 anemia, leukocytosis with neutrophilia, and ESR acceleration in blood analysis. One of the patients required ABT correction during treatment. Ceftriaxone in combination with ampicillin/sulbactam was prescribed as starting drugs, but on 6 day of therapy ABT was corrected on meropenem, on 13 day – ceftazidime. These patients had of febrile fever for 13 days, then to sub febrile – up to 14-15 days against the background of treatment. Consciousness returned to normal on the 1st day in a one-year-old patient, and on the 6th day of the disease in a child aged 3 months. Meningeal symptoms were cropped on 3-5 days. Despite a single etiological factor, the outcome of the disease was different: a one-year-old patient was discharged on the 22 day with a satisfactory recovery, but a child of 3 months old on the 23 day he was transferred to the neurological clinic for further rehabilitation measures in connection with the formation of residual changes in the central nervous system (he had symptoms of delayed statokinetic development and focal symptoms). Rate of BM caused by H. influenza was 52.2%. These were toddlers unvaccinated against Hib-infection due to parental refusal (10 cases, 83.3%) and for health reasons (2 cases, 16.6%). There was family contact with adults or older children with symptoms of catarrhal inflammation of upper respiratory tract on 3-7 days before the disease in all cases. All patients had acute onset of the disease with febrile fiver; 9 (75.0%) patients had severe intoxication, 4 (33.3%) had sinusitis, 2 (16.6%) children had acute otitis media. Bright cerebral symptoms were detected in 9 patients (75.0%), Kerning’s symptom – in 5 (41.6%) children; the rigidity of the occipital muscles – in 8 (66.6%); Brudzinsky's symptom – Iin 4 (33.3%) patients. Classical meningeal pose was detected in 1 (8.3%) child. All patients had anemia of 2-3 degrees of severity, leukocytosis with neutrophil, increased ESR.

BM caused by H. Influenza was characterized by an undulating course of the disease. The duration of the febrile fever period varied from 2 to 15 days (Me=9 [7.8; 12]), cerebral symptoms were stopped from 3 to 7 days (Me=5 [3.5; 4.5]), meningeal symptoms – from 3 to 13 days (Me=8 [5; 10.25]). The period of treatment in hospital ranged from 20 to 40 days (Me=23 [20.8; 24.8]).

H. Influenza was sensitive to unprotected and protected aminopenicillins, third-generation cephalosporin in 83.3%. Ceftriaxone used as a starting antibiotic in 5 (41.6%) patients (immunotherapy – in 3, combination with vancomycin – in 2 cases), 6 (50%) patients – penicillin with ceftriaxone/sulbactam, in 2 (16.6%) cases – cefepime. In the prevailing number of patients (92.0%), ABT was corrected due to the lack of positive dynamics, which may indicate a different sensitivity of the bacteria in vivo and in vitro. To achieve sanitation of the cerebrospinal fluid repeated correction of ABT was required in 11 (91.6%) patients. The time of CSF sanitation varied from 9 to 25 days (Me=15 [10.8; 17.3]).

The study was demonstrated an improvement in the quality of bacteriological diagnostics of BM in children and a change in the etiological structure of BM. BM was more often diagnosed in toddlers and manifested by the symptoms of meningeal, cerebral and intoxication syndromes. H. Influenzae was detected in 52.2% of BM in 2016-2019 years. Patients with BM caused by H. Influenzae had long course of the disease, repeated correction of ABT, had of complications. It was indicates the advisability of vaccinating children against hemophilic infection

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