Childhood Haemophilus influenzae type b meningitis in Russia.
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Biomedical subjects
Publications and source records attributed to M O Volkova.
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Pneumococcal meningitis in St. Petersburg in the period 1985-1991 occurred in 1.7-2.3 children per 100,000 annually. The most common serotypes among pneumococcal strains isolated from patients with meningitis were 19, 1, 6, 15, and 2, whereas, among the capsulated strains isolated from carriers, type 3 predominated. Only one third of strains from cases of meningitis were highly virulent for mice (types 1, 2, 3). Hyaluronidase was produced by all the 39 studied strains, 22 (84.6 +/- 7.1%) out of 26 strains from patients with otitis media, and only by 15 (11.5 +/- 2.8%) out of 130 strains isolated from carriers. Non-capsulated strains lacked this enzyme. Results of intranasal inoculation of pneumococcal strains with different hyaluronidase activity and addition of exogenous hyaluronidase to strains which did not produce the enzyme confirm the hypothesis that this enzyme plays an important role in bacterial dissemination and breaching of the blood brain barrier by pneumococci. It was concluded that high hyaluronidase activity, presence of capsule, and pneumolysin or serotype (1, 2, and 19) despite hyaluronidase titer, are the most important factors contributing to the development of pneumococcal meningitis. The role of the mouse toxic factor is unclear.
In 1985-1989 the etiological structure of acute bacterial meningitides (ABM) in children was studied in 4 largest industrial cities in different regions of the European part of the former USSR, as well as in 2 industrial cities of western Siberia. Due to the common methodological approach used in all investigations, comparable data were obtained in all cities. These investigations revealed that meningococci caused 53.0-86.7% of all cases of ABM in children, which corresponded to moderately increased morbidity rate in meningococcal infection (3.9-11.0 cases per 100,000 of the population, mostly 5.0-7.0 cases) in these cities with its progressive decrease during 3-4 years of observation. The gradual change of meningococci from group A, prevailing in the '70s and early '80s, to group B and in some cases the appearance of group C meningococci, accompanied by a decrease in morbidity rate, were noted. In St. Petersburg the indices of ABM morbidity in children aged up to 5 years for 1987 and 1988, caused by Haemophilus influenzae (0.74 and 4.13) and pneumococci (3.23 and 4.86), could be calculated. A great number of ABM cases of unclear etiology (15.9-33.3%) suggests that the number of ABM cases caused by these two infective agents was underestimated.
The pneumococcal origin of purulent otitis was diagnosed in 74 (35 percent) of 211 children, in whom acute respiratory viral diseases or purulent otitis were previously diagnosed, by a combination of indirect immunofluorescence, cytobacterioscopic and culture methods. Use of indirect immunofluorescence and of special medium for isolation of atypical forms of the agent (L-forms and unbalanced growth forms) helped diagnose pneumococcal otitis in 47 (22.3 percent) more patients.
The biological properties of 97 S. pneumoniae strains isolated from 92 children with purulent meningitides, meningoencephalitides, pneumonia and otitis, hospitalized at the Leningrad Research Institute of Childhood Infections, were studied. The data obtained in this investigation were indicative of the formation of atypical forms of pneumococci (R-forms, unbalanced growth forms and L-forms) in all clinical forms of pneumococcal infection in children. In purulent meningitides and meningoencephalitides serovars 1 and 6, in pneumonia serovars 1, 3 and 6 and in otitis serovars 6 and 19 played the leading role. The determination of sensitivity to antibiotics showed that the forms under study retained high sensitivity to a number of antibiotics. The appearance of strains resistant to benzylopenicillin was registered. (10%). The isolated strains either possessed low virulence or were avirulent in bioassay on white mice.
The analysis of morphological, clinical and bacteriological data on 31 deceased children with pneumococcal meningoencephalitis is presented. The lesions observed at early and late stages of the disease are characterized in detail and the tendency of pneumococcal meningoencephalitis to a chronic course in the presence of the viable pathogen is shown. The majority of pneumococcal meningoencephalitides were proved to develop primarily, and in their pathogenesis significant role is played by the lesions of hematoencephalic barrier caused by respiratory viruses. High lethality and frequency of severe residual changes in the children with pneumococcal meningoencephalitis are due to early lesions of choroid plexuses and brain matter. In the experiment on 18 rabbits with their suboccipital challenge with 3 different pneumococcal strains, the influence of the biological properties of the pathogen on the clinical and morphological features of the illness is shown.
The complex clinico-laboratory examination of 92 children aged 3-14 years with the localized form of stomatopharyngeal diphtheria and toxigenic C. diphtheriae (TCD) carrier state was carried out. The children were hospitalized in the clinic of drop infections during the period of 1996-1998. The hydrophobic properties, adhesive, lysozyme, antilysozyme and DNAase activities of 92 TCD strains, as well as the levels of the specific and nonspecific immunity of the macroorganism, were studied. The study revealed that the character of the infectious process in TCD carrier state was determined by the degree of the colonization activity of the infective agent. Direct correlation between the time of the persistence of TCD in the body and their hydrophobic properties, adhesive and antilysozyme activities (with r = 0.89-0.93) was established. The duration of TCD carrier state was found to be inversely related to the electrophysiological state of epithelial cells of the mucosa, the level of humoral specific antibacterial immunity and the content of local antidiphtheria IgA.
The hyaluronidase activity of pneumococcal strains isolated from 39 patients with purulent meningitis, 26 patients with acute internal otitis and 130 healthy carriers was studied. All strains isolated from patients with purulent meningitis and meningoencephalitis and 84.6% of strains isolated in cases of otitis were found to have hyaluronidase, while in healthy children hyaluronidase-synthesizing strains were detected only in 11.5% of cases. Hyaluronidase titers in pneumococcal strains isolated from patients with meningitis and meningoencephalitis were significantly higher than in strains causing purulent otitis. At the same time strains with high hyaluronidase titers were also isolated from 7% of healthy carriers. Noncapsular pneumococcal strains had no hyaluronidase. The average value of the reverse correlation between hyaluronidase activity and the virulence of strains for mice was established. Hyaluronidase activity did not correlate with different serotypes of pneumococcal strains. The intranasal administration of hyaluronidase in high titers (> or = 1:8) to mice and rats led to the penetration of the infective agent through the hematoencephalic barrier of the animals and to their death from generalized pneumococcal infection. The role of hyaluronidase as the invasiveness factor of pneumococci was confirmed in experiments on the intranasal infection of mice with low active strains mixed with the preparation of exogenous hyaluronidase.
The adhesive capacity of 425 S.pneumoniae strains (S- and R-forms) isolated from children with various clinical forms of pneumococcal infection was studied with the use of the epithelium of oral cavity as a model. The strains isolated from patients with meningitis and otitis appeared to be less adhesive than the strains isolated from mucous membrane of respiratory tracts. In all clinical forms of infections the adhesive capacity of S.pneumoniae S-forms was significantly lower than that of R-forms. The hyaluronidase activity and the adhesive capacity of S.pneumoniae strains were found to be inversely related.
Pneumococcal meningitis was registered in St. Petersburg in 1985-1991, morbidity rate being 1.7-2.3 cases per 100,000 children, including 7.4-19.8 cases among children under 1 year. Two thirds of the pneumococcal strains isolated in cases of meningitis belonged to serovars 19, 1, 6, 15 and 2. The comparative study of pneumococcal strains revealed that the presence of capsules, pneumolysin, high hyaluronidase activity or belonging to serovars 1 and 2 (irrespective of their hyaluronidase titers) were the most important factors contributing to the development of generalized infection. The role of such a factor as virulence for mice is not yet clear.