Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia.

This study investigated the causes of invasive bacterial infections in children aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.

Rapid HLA-DQB1 genotyping for four alleles in the assessment of risk for IDDM in the Finnish population. The Childhood Diabetes in Finland (DiMe) Study Group.

OBJECTIVE: To study the effectiveness of MHC genotyping in the assessment of risk for IDDM based on the identification of alleles that are significantly associated with risk for IDDM (DQB1 *0302 and *0201) and protection from it (DQB1 *0602/*0603 and *0301). RESEARCH DESIGN AND METHODS: A long series of 649 index cases of IDDM, together with their healthy siblings and 756 healthy blood donors, was collected in Finland. The samples were analyzed using a large-scale assay procedure that was developed for rapid screening purposes. The method utilizes time-resolved fluorometry to detect the hybridization of lanthanide-labeled allele-specific oligonucleotide probes with amplified gene product. RESULTS: A total of 61.9% of IDDM index cases had high risk (DQB1 *0201/*0302) or moderate risk (DQB1 *0302/x [x meaning DQB1 *0302 or a nondefined allele]) genotypes compared with 14.3% of the reference population. In patients and control subjects, the frequencies of low risk genotypes were 28.0 and 22.1%, respectively, and those of decreased risk genotypes, 10.0 and 63.6%. The relative risk of a *0201/*0302 genotype was 53.5 (31.1-92.8) compared with the decreased risk genotypes (63.6% of controls). The graded risk estimation was equally efficient in assessing the risk of IDDM in siblings of child with IDDM. CONCLUSION: The near-automatic typing procedure developed is attractive for large-scale screening projects, such as diabetes prevention and intervention trials.

Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life.

BACKGROUND: Timely information on the bacteriology of primary, noncomplicated acute otitis media (AOM) may today be needed more than ever, because of the increasing antimicrobial resistance of its major bacterial causes and because of the potential of new pneumococcal and other bacterial vaccines for prevention of AOM. METHODS: The study followed 329 children from 2 to 24 months of age at scheduled healthy visits and sick visits at the study clinic. Whenever AOM was diagnosed during the follow-up, myringotomy was performed and middle ear fluid was aspirated for bacterial culture. RESULTS: At least one middle ear fluid sample was available from 772 AOM events; Streptococcus pneumoniae (Pnc) was isolated in 201 (26%), Moraxella catarrhalis (Mc) in 177 (23%) and Haemophilus influenzae (Hi) in 174 events (23%). The incidence of Pnc AOM peaked at 12 months of age, whereas the incidence of Mc AOM showed the first peak at 6 months and Hi AOM at 20 months. Pnc AOM showed less prominent seasonality in occurrence than Mc and Hi AOM. Hi was a rare cause of the first 2 AOM episodes (13%) but became increasingly common from the third episode on (32% on average). CONCLUSIONS: Pnc, Mc and Hi were almost equally common findings in AOM. Pnc seems to be the most pathogenic of these three, the role of Mc is increasing and Hi is clearly associated with recurrent AOM.

Establishing a laboratory for surveillance of invasive bacterial infections in a tertiary care government hospital in a rural province in the Philippines.

A clinical bacteriologic laboratory was established in a tertiary care government hospital in The Philippines, where expert bacteriologic laboratories do not usually exist at this level of health care. The laboratory was jointly established by the Research Institute for Tropical Medicine (RITM) (Manila, The Philippines) and the National Public Health Institute (KTL) (Helsinki, Finland). The laboratory was planned, its personnel were trained, and its functioning was continuously supported by the RITM and KTL. The following aspects were of utmost importance in establishing the laboratory and launching its work: 1) the support of the RITM bacteriologic laboratory, with back-up and consultations from KTL; 2) creation and maintenance of personal contacts between clinicians and laboratory staff with an emphasis on clinical relevance and rapid reporting of laboratory results; 3) the consideration of the quality aspects of the work from the start; and 4) keen follow-up of the bacteriologic results and their clinical significance and use, of practical laboratory work, and of quality assurance aspects. In the first two years of its operation, the laboratory identified Streptococcus pneumoniae and Haemophilus influenzae as the most important causes of severe pneumonia, sepsis or meningitis in children less than two years of age, and Salmonella typhi as the most frequent significant isolate from the blood cultures, being found most often in school age children and young adults.

Invasive bacterial infections of children in a rural province in the central Philippines.

The etiology of invasive bacterial infections was studied among 956 Filipino children less than five years old who fulfilled the World Health Organization criteria for severe or very severe pneumonia or had suspected meningitis or sepsis. The most common invasive infections were due to Streptococcus pneumoniae (12 [1.3%]) and Haemophilus influenzae (12 [1.3%]); including four cases of pneumococcal meningitis and 11 cases of H. influenzae meningitis. Type 1 was the most common (six of the 12 isolates) of the pneumococcal serotypes. Serotypes/groups 1, 6, 14, and 23 accounted for 91.7% of the invasive isolates. The majority of the H. influenzae strains from blood (10 out of 10) and cerebrospinal fluid (6 out of 7) were type b. Almost all of the invasive S. pneumoniae (9 out of 12) and H. influenzae (11 out of 12) infections were seen before one year of age, which stresses the need to investigate early immunization of children for H. influenzae type b and S. pneumoniae, as well as maternal immunization to maximize the potential of immunoprophylaxis.

Evaluation of gene-technological and conventional methods in the identification of Streptococcus pneumoniae.

To find reliable methods able to identify the "difficult" Streptococcus pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe) were evaluated. Selected isolates of suspected pneumococci, sent for confirmation of identification and for serotyping, were classified into four groups based on their optochin sensitivity and capsule reaction. All isolates in Group 1, which consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains, were positive in the Ply-PCR and AccuProbe tests. In Group 2, which consisted of 25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates were positive in the Ply-PCR test, and 23 were positive in the AccuProbe test. In Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the AccuProbe test, and 11 of these 12 strains were positive in both tests. In Group 4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates, 15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe test. As a conclusion, the Ply-PCR and AccuProbe tests identified similarly typical optochin-sensitive pneumococci, but gave partly controversial results about atypical pneumococci. Thus, they did not reliably help in the identification of suspected pneumococcal isolates lacking the conventional characteristics of pneumococcus.

Recurrent meningococcal meningitis due to partial complement defects and poor anti-meningococcal antibody response.

An otherwise healthy young man had three episodes of meningococcal meningitis within three years. The last episode was caused by group A, and occurred four weeks after the patient received group A vaccine, thus representing one of the very few failures of this vaccine. The specific susceptibility to meningococcal infections was connected with half-normal levels of several components of the complement system (C3, C4, C9, factor B, properdin), and reduced antibody responses to group A and group C meningococcal polysaccharides, but not to several other polysaccharide or protein antigens.

Negative pressure tympanograms in children less than 2 years of age--different bacterial findings in otitis media by tympanometric results.

OBJECTIVE: The interpretation of negative pressure tympanograms as indicators of the presence of middle ear fluid has been ambiguous. Our purpose was to assess the occurrence and implications of negative pressure tympanograms and to study their association with bacterial pathogens in otitis media. METHODS: Altogether 329 infants were enrolled at a well-baby clinic for the Finnish Otitis Media Cohort Study, a longitudinal prospective cohort study. The children were closely followed in a special study clinic from 2 to 24 months of age for respiratory diseases, especially acute otitis media. Children were examined at the study clinic with tympanometry and pneumatic otoscopy whenever visiting the study clinic for respiratory disease. Myringotomy with aspiration was performed if middle ear fluid was suspected in otoscopy. Occurrence of middle ear fluid in ears with negative pressure tympanograms (less than -100 daPa) was assessed. Nested case control design matched by visit type (acute or follow-up visit) and month of visit was used for analysis of association of bacterial pathogens and tympanometric results. RESULTS: Middle ear fluid was encountered in 15% of ears with negative tympanometric peak pressure, a lower proportion than described previously. In otitis media with a negative tympanometric peak pressure, 71% of bacterial cultures remained negative for the main pathogens, compared to 36% in matched controls (P<0.001). Especially Streptococcus pneumoniae but also Haemophilus influenzae were rarely found in samples from negative pressure ears. Moraxella catarrhalis was equally often found. CONCLUSIONS: Negative pressure tympanogram is a poor indicator for the presence of middle ear fluid. Furthermore, if otitis media is diagnosed with negative tympanometric peak pressure negative middle ear bacterial culture for the main pathogens is highly probable. Expectant follow-up might be more appropriate than routine antibiotic treatment.

Occurrences of antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion and serum during the course of acute otitis media.

The occurrence of IgG, IgM and IgA class antibodies against a type-specific capsular polysaccharide of Streptococcus pneumoniae (Pn) and against a whole cell antigen of Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) was studied using the ELISA method on middle ear effusion (MEE) samples of 85 patients and paired serum samples of 40 patients during the course of acute otitis media (AOM). Although specific antibodies to all of these three bacteria appeared in MEE during the course of an AOM episode, antibodies against the infecting bacteria of that particular AOM episode were more often prominent. The antibodies were also detectable in the MEE without simultaneous presence in the serum. The middle ear infection was prolonged more often if specific antibodies to the infecting bacterium could not be detected in the MEE obtained at the beginning of the AOM attack. The present study indicates that AOM caused by Pn, Hi or Br may induce both a systemic and a local production of specific antibodies against the causative organisms during the course of otitis media. The occurrence of such antibodies in MEE seems to play a major role in the resolution of AOM.

Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media.

Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question.

Branhamella catarrhalis in acute otitis media.

A total of 5217 middle ear fluid (MEF) samples obtained from 1203 children with otitis media, aged 3 months to 6 years, were studied for the presence of Branhamella catarrhalis (Br) between Oct. 1977 and Sept. 1981. Br grew in 10.2% of 3497 MEFs of acute otitis media (AOM), with almost the same frequency in the very first and subsequent attacks. During the first 4 years of life the percentage did not vary much; among older children it seemed to decrease. The overall prevalence of Br in AOM did not change during the study period. Br alone grew in 72.4% of acute MEFs with Br; with other bacteria the respective figure was 82.9% (p less than 0.001). Acute attacks with bilateral Br were found in 22.8% of attacks with Br. In 1720 non-acute MEFs obtained at postacute control visits, Br was isolated in only 7.0%. The proportion of beta-lactamase-producing strains among the 2419 otitis-Br strains tested in two laboratories of the two study regions showed an increase from 27.1% and 21.1% in 1980 to 57.6% and 38.6% in 1983, respectively (p less than 0.001).

Haemophilus influenzae in acute otitis media.

We studied the occurrence of Haemophilus influenzae (Hi) in 2625 middle ear fluid (MEF) specimens obtained from 523 children with otitis media, aged 3 months to 6 years, between October 1977 and May 1979. In clinically acute cases 12.3% of the MEFs grew Hi; 6.3% (13/206) of the strains were of type b and 4.9% (10/206) were beta-lactamase producing. In the very first acute case of a child 8.0% (21/263) of the MEFs grew Hi, but in acute recurrences it was cultured in 17.0% (184/1082) (p less than 0.001). In non-acute persistent MEFs obtained during control visits Hi was found in no less than 21.7% (198/913); as many as 12.6% (25/198) of them were beta-lactamase producing. Both of these figures, but not the proportion of type b strains (8.6%), were significantly (p less than 0.001 and p less than 0.01, respectively) greater than in clinically acute MEFs. Hi was grown in 13.1% of the acute MEFs taken from children less than 4 years old, but in only 8.6% of the older children (p less than 0.05). The annual survey of all the 1816 Hi strains isolated from the MEFs of acute or subacute cases of otitis media in one laboratory in 1976-81 showed the proportion of beta-lactamase producing strains of all Hi strains to be gradually increasing from 8.0% (17/212) in 1976 to 15.2% (16/105) in 1981 (p less than 0.05).

Acute anterior uveitis and HLA-B27 in families.

To determine the hereditary pattern of acute anterior uveitis (AAU) 12 families with 2 cases of AAU in each family were given a routine eye examination which included serological determination of HLA antigens. Members of four families underwent x-ray examination of the lumbosacral spine. Of the 23 cases with AAU examined, 19 had the antigen B27. The genes determining B27 and a2 were inherited together in 14 instances and the gene determining Cwl in 10 of these 14. The lymphocytes of the HLA identical siblings of the three families studied by the mixed lymphocyte culture test did not react against each other. Sacroilities was seen in 62.5% of cases with familial AAU and in 58.6% of their relatives. It is concluded that HLA-B27 is linked with genes predisposing the carrier to familial AAU, which is closely related to the rheumatic group of diseases.

Efficacy of pneumococcal vaccination against recurrent otitis media. Preliminary results of a field trial in Finland.

For this study, 781 children, and 3 to 83 months, after presenting with acute otitis media, were immunized with either 14-valent pneumococcal or Haemophilus influenzae type b capsular polysaccharide vaccine. The vaccines were tolerated well. Antibody responses to the 14 pneumococcal polysaccharide types, measured by radioimmunoassay, were fair to good and increased with age, with the exception of types 1, 6 and 12 to which the responses were generally poor. During the follow-up of 1-17 months, average 13 months, 45 vaccine type (except type 6) pneumococcal recurrences were met among 456 pneumococcal-vaccinated and 45 among 288 H. influenzae-vaccinated children, at least six months old (P < .05). The corresponding protective efficacy by the pneumococcal vaccine was 37%, for the first six months, 51% (P < .01). No protection by the pneumococcal vaccine was seen against group 6 pneumococci, nor among 19 infants under six months of age. Nonvaccine type pneumococcal ad H. influenzae recurrences did not significantly concentrate in either of the vaccination groups. Thus, it seems that parenteral immunization of children can reduce the recurrence rate of otitis media caused by pneumococci of types (except type 6) present in the vaccine.

Blood culture confirmed typhoid fever in a provincial hospital in the Philippines.

Epidemiological features of blood culture confirmed typhoid fever and antibiotic sensitivity of isolated Salmonella typhi strains were investigated in Bohol Province in Central Philippines from where no earlier information of these was avialable. Typhoid fever is endemic elsewhere in the Philippines (eg Metropolitan Manila and surroundings) where also multidrug resistant S. typhi strains have been detected. A laboratory for surveillance of invasive bacterial infections was established in a tertiary care government hospital, in Bohol, Central Philippines, in 1994. Patients with suspected typhoid fever or other serious infection were managed and blood cultures from them were taken according to clinicians' judgment. Blood cultures were processed and the isolated bacteria identified using generally accepted methods. S. typhi and other Salmonella isolates were identified using commercial antisera. Patient data were collected from hospital records. Of a total of 4,699 blood cultures done during a period of 3 3/4 years, 1,530 (32%) were requested for suspected typhoid fever. S. typhi was the most common pathogen isolated from 422 patients (8.9%), followed by S. paratyphi A from 55 patients (1%). Most patients were young adults (43%) and school age children (28%). Male:female ratio was 1.5:1. Among the 422 patients, there were 9 (2%) deaths due to typhoid fever, all with complications. All S. typhi isolates were sensitive to chloramphenicol, cotrimoxazole, and ampicillin. Our observation on blood culture confirmed typhoid fever demonstrates its importance as a major infectious disease in Bohol and gives a sound basis for treatment of typhoid patients and for further clinical and epidemiologic studies of typhoid fever and for following antibiotic sensitivity of S. typhi in Bohol and elsewhere in the Philippines.