A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides.

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies. The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples. Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F. The overall mean percent coefficients of variation in this interlaboratory study for all five selotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 3/% for IgM, and 36% for IgA. This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines.

[Surgical treatment of severe snoring. Long-term effects]. / Operativ behandling af excessiv snorken. Langtidseffekt.

AIM: The long-term results of uvulopalapharyngoplasty (UPPP) reported by patients who had been operated for severe snoring but without clinically significant obstructive sleep apnoea were explored. METHODS: Median three years (one to eight years) after the operation follow-up results were obtained from 80 of 85 patients (94%), using a questionnaire. RESULTS: In nine patients (11%) the operation had been without any effect. Eleven patients (14%) indicated that they were completely cured of snoring. In sixty patients (75%) snoring was reduced. In about half of these the initial effect had been more pronounced than the present. About 60% of the patients felt better during daytime, were less tired or sleepy than before the operation. Slight or temporary side effects were present in 30% of the patients. Eighty percent of the patients would recommend the operation to others. CONCLUSION: This study confirms that UPPP is effective in relieving the symptoms in non-apnoeic snorers, without significant side effects. A certain reduction of the positive effect occurs during the first two years in about half of the patients. Nevertheless most patients are satisfied with the operation and would recommend it to others.

Typing of Streptococcus pneumoniae: past, present, and future.

Early works leading to the detection of the pneumococcus and eventually to the appreciation that isolates differed in agglutination and that antisera differed in their capacity to protect against pneumococcal infection in the mouse protection test are reviewed. Studies by researchers from Europe, South Africa, and the United States over nearly five decades led to the introduction of serum therapy. Rapid typing methods thus became very important, and type-specific serum therapy generated a dramatic decrease in the number of deaths from pneumococcal pneumonia. Just before the introduction of sulfonamides and, shortly thereafter, penicillin, the use of horse sera was replaced by the use of rabbit sera for a number of reasons. The present methods of typing comprise the capsular reaction test, latex- and coagglutination, and capillary precipitation, to name the most important; these use a large variety of antisera. Newer methods include the use of DNA probes and DNA sequence-based subtyping.

Does bismuth subgallate have haemostatic effects in tonsillectomy?

Previous studies have shown that bismuth subgallate added to gauze swabs in tonsillectomy reduces the time to achieve haemostasis and probably reduces the risk of postoperative haemorrhage. All these studies have used bismuth subgallate in combination with adrenaline. In this randomised clinical study we investigated the effect of bismuth subgallate alone. A total of 204 patients were randomised into two groups. One hundred and six patients had swabs with bismuth subgallate. In the control group (n = 98), plain swabs were used. Operating time time to achieve haemostasis, peroperative blood loss, and incidence of postoperative haemorrhages were recorded. There were no significant differences between the two groups. We conclude that the evidence for using bismuth subgallate as a haemostatic agent in tonsillectomy is weak. The effect observed in previous studies can probably be ascribed to the effect of adrenaline.

Incidence of invasive pneumococcal disease and distribution of capsular types of pneumococci in Denmark, 1989-94.

During the period 1989-94, 4620 strains of Streptococcus pneumoniae (4063 from blood and 557 from cerebrospinal fluid), from cases of invasive disease in Denmark, were received for capsular typing and penicillin susceptibility testing. During the study period the incidence of bacteraemic pneumococcal disease increased from 10 to 18 cases per 100000 inhabitants per year. The highest rates were seen in the very young, age less than 5 years (23/100000/year, in 1994), and in the elderly, age greater than 60 years (55/100000/year, in 1994). The annual number of cases of meningitis did not vary. Overall, 92% (93% blood, 87% CSF) of isolates and 94% of all childhood isolates belonged to the 23 vaccine types. The capsular types occurring most commonly among the 4123 pneumococcal strains from adults were types 1, 4, 14, 6A + 6B, 7F, 9V, 3, 12F, and 8 (in order of frequency). The ten most frequently occurring types from children (6A + 6B, 18C, 14, 1, 7F, 19F, 9V, 4, and 23F) covered 84% of the cases of bacteraemia and meningitis. Reduced susceptibility to penicillin was rare (< 1%).

High rate of nasopharyngeal carriage of potential pathogens among children in Greenland: results of a clinical survey of middle-ear disease.

Nasopharyngeal and middle-ear colonization with bacteria and viruses, including Mycoplasma pneumoniae and chlamydiae, was investigated in a survey of 54 children with acute otitis media (AOM) and 201 control children without AOM in Greenland. In total, 98% with AOM and 91% without AOM carried potentially pathogenic bacteria in the nasopharynx. Two or more potentially pathogenic species were carried by 78% with AOM and 57% without AOM. Haemophilus influenzae was found in 92% and 77%, respectively, but only Streptococcus pneumoniae was found significantly more often in the nasopharynx of children with AOM than in age-matched controls (P < .03). The two species were found in 22 of 24 ear-discharge specimens. Nine children (three with AOM) had chlamydiae in the nasopharynx, and seven of them reported rhinitis. Enteroviruses or rhinoviruses were detected in 23 nasopharyngeal specimens from 39 children with AOM, in 13 such specimens from 39 children without AOM (P = .040), and in 4 of 14 ear-discharge specimens. The potentially pathogenic load in the nasopharynx was massive, suggesting an association with the high prevalence of otitis media among children in Greenland.

[An outbreak of Streptococcus pyogenes infections in institutions for the mentally retarded in Greater Copenhagen 1995]. / Et udbrud af infektioner med Streptococcus pyogenes på institutioner for psykisk udviklingshaemmede i Storkøbenhavn 1995.

The largest reported outbreak of infections due to Streptococcus pyogenes, M-type 18, in recent years is described. Ninety persons at institutions for mentally retarded (73% residents) had infections due to the epidemic strain. Pharyngitis and scarlatina were the most common infections. Six patients died, five having a streptococcal toxic shock syndrome. During the outbreak an intensive surveillance was carried out together with improved infection control measures and prompt culturing of residents and employees before antimicrobial treatment. The primary outbreak was confined but a secondary outbreak could not be prevented. This was probably due to difficulties in implementing proper isolation precautions in this setting.

Distribution of capsular types and antibiotic susceptibility of invasive Streptococcus pneumoniae isolated from aborigines in central Australia.

Streptococcus pneumoniae strains isolated from 203 episodes of invasive disease in central Australian Aborigines were studied. Capsular types from children aged 0 to 4 years (n = 89) belonged most commonly to types 14, 6B, 9V, 4, 18C, and 19F, which together accounted for 67% of the pediatric strains. In adults (n = 98), types 1, 7F, 3, 4, 12F, and 8 contributed 68% of the isolates. Of 114 pneumococci from patients 5 years and older, 102 (89.5%) were types represented in the 23-valent pneumococcal polysaccharide vaccine. The MICs of five antibiotics were determined for 201 strains by using the E-Test (AB Biodisk). No chloramphenicol or ceftriaxone resistance was found, but 46 strains (22.9%) showed diminished susceptibility to one or more of the drugs penicillin, erythromycin, and trimethoprim-sulfamethoxazole. Penicillin resistance occurred in 15.4% of all isolates tested but only within the intermediate range (0.1 to 1.0 microgram/ml). Resistance to trimethoprimsulfamethoxazole affected 13.9% of the pneumococci tested. All type 23F and most type 19F organisms were resistant to one or more antibiotics. Resistance was significantly more common in pediatric isolates than in those from adults (chi 2(1) = 14.1; P < 0.001).

Rapid emergence of penicillin-resistant pneumococci in Hong Kong.

The prevalence of penicillin resistance in Streptococcus pneumoniae isolated at the Prince of Wales Hospital, Hong Kong, rose from 6.6% of sputum isolates in the first quarter of 1993 to 55.8% of isolates in the second quarter of 1995. Most of the isolates were also resistant to co-trimoxazole, tetracycline, choramphenicol and erythromycin. Type 19F was the most common capsular type in 1993-1994, comprising 40.0% of typed isolates in this period. Type 23F emerged in 1995 as the predominant type, making up 62.2% of typed isolates in the first 2 quarters of 1995. A high population density and excessive community use of antibiotics are likely to be factors promoting the rapid emergence of multiply-resistant pneumococci in Hong Kong.

Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in healthy children and in children at increased risk of pneumococcal infection.

Splenectomized children as well as those suffering from nephrotic syndrome or recurrent asthmatic bronchitis have an increased susceptibility to systemic pneumococcal infections compared to healthy children. To determine the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPV), 119 children (21 healthy, 26 splenectomized children, 48 with nephrotic syndrome and 24 with recurrent asthmatic bronchitis), aged 2-18 years, received one subcutaneous injection of a 23-valent PPV. Anti-capsular antibodies (Ab) to types 6B, 9V, 14, 18C, 19F and 23F were measured by ELISA before and 4 weeks after immunization. In all cases the adverse reactions were mild and transient, consisting of local pain and/or erythema or swelling in 41% and fever above 38.5 degrees C in 2% of the children. The healthy children responded well to vaccination with a mean fold increase (FI) of 2.6 in postvaccination Ab titers compared to prevaccination titers. The combined geometric mean Ab concentrations in the high-risk children were significantly lower than those of healthy children both before and after vaccination. However, the combined geometric mean FI were not significantly different between high-risk and healthy children. These results indicate that PPV is immunogenic and safe in high-risk as well as in healthy Korean children.

Improved vaccination response during ranitidine treatment, and increased plasma histamine concentrations, in patients with B cell chronic lymphocytic leukemia.

Patients with B cell chronic lymphocytic leukemia (B-CLL) have decreased capacity to mount relevant antibody responses upon immunization, and development of hypogammaglobulinemia is part of the natural history of the disease. We investigated the influence of histamine type-2 (H2) receptor blockade by ranitidine on the in vivo antibody production in B-CLL patients following vaccination. Anti-polysaccharide antibodies in B-CLL patients, vaccinated with a tetanus-toxoid conjugated vaccine against Haemophilus influenzae type-B (Hib), reached long-term protective levels in more than 90% of B-CLL patients randomized to ranitidine treatment, as compared to 43% of the untreated patients (P = 0.024). No difference in the response to vaccination against influenza virus types A and B protein could be detected between the two groups. Plasma histamine levels were 2-fold to 20-fold higher in 23 out of 31 B-CLL patients, compared to normal controls, and these levels showed a significant positive correlation to disease duration. These findings indicate the possibility of improving in vivo antibody production against a highly relevant pathogen in B-CLL patients by histamine type-2 receptor blockade, and the combined finding of an immune-stimulatory effect of ranitidine and increased plasma histamine levels, strongly suggests the involvement of histamine in the pathogenesis of B-CLL immunodeficiency.

Six newly recognized types of Streptococcus pneumoniae.

The serological properties of six new pneumococcal capsular types are described. A table listing all 90 pneumococcal types and their cross-reactions is included.

Incidence, capsular types, and antibiotic susceptibility of invasive Streptococcus pneumoniae in Sweden.

The number of reported cases of invasive pneumococcal infections in Sweden increased more than threefold from 1988 through 1992. We studied the capsular types and the antibiotic susceptibility of 619 pneumococcal strains isolated from blood or CSF at 18 Swedish microbiological laboratories in 1987 and in 1992. These strains belonged to 35 of the 84 recognized capsular types. We noted a remarkable increase in the prevalence of invasive infections with type 14 from 1987 (8.2%) to 1992 (18%) (P = .001), which correspond to a sevenfold increase in absolute numbers. The most prominent increase in infections was seen among elderly people; in 1992, type 14 accounted for 22.5% of the isolates from infected persons who were >64 years of age. The majority of the strains were susceptible to all antibiotics tested. However, there was a significant increase in trimethoprim-sulfamethoxazole resistance from 1.4% in 1987 to 7.1% in 1992. Nine multiresistant isolates (1.5%) were found.

Capsular types and antimicrobial resistance of Streptococcus pneumoniae isolated in Korea.

The capsular types and the MICs of penicillin G and other antimicrobial agents were determined for 89 isolates of Streptococcus pneumoniae. MICs of penicillin G ranged from 0.015 to 2 mg/l, with 29% and 48% of the isolates exhibiting intermediate resistance and complete resistance, respectively. All isolates were susceptible to teicoplanin and vancomycin, but 81% and 43% of the penicillin G-resistant strains were intermediately resistant to cefotaxime and imipenem, respectively. Strains belonged to 16 different capsular types: 73% belonged to types 19F and 23F, and 97% of strains belonging to these two types exhibited either intermediate or complete resistance to penicillin G.