Bacteriologic epidemiology of Hemophilus influenzae type b strains causing invasive infections in Finland

Consecutive Hemophilus influenzae type b (Hib) isolates (333 total) from children with invasive disease in Finland in 1985-1986 were analyzed. All belonged to the common genetic clusters described in the USA and Europe. However, detailed typing demonstrated some characteristics unique to Hib strains in Finland. Of the isolates, 86% belonged to one of four distinct patterns according to the combination of outer membrane protein subtype, biotype, and lipopolysaccharide serotype: 1-I-1 (25%), 1-II-9 (8%), and 1c-I-1 (18%). Pattern 1-II-9 has not been previously reported; it was most commonly found in the most densely populated area of Finland and among children cared for outside the home. Multilocus enzyme electrophoresis revealed that 87% of isolates with the pattern 1c-I-1 belonged to the electrophoretic type 21.8, which is seldom recovered from patients with invasive Hib disease in other countries.     

Trends and geographical variation in invasive pneumococcal infections in Finland

We evaluated regional variation and trends in invasive pneumococcal infections (IPI) in Finland by using data from national, population-based laboratory surveillance and number of blood and cerebrospinal fluid (CSF) cultures performed by all microbiology laboratories during 1995-2002. The overall annualized IPI incidence was 10.6/100,000 (range by region, 7.9 15.1): 9.9 for bacteraemias (range 7.3-14.2) and 0.6 for meningitis (range 0.4-1.1). The rate in children aged <5 y was 23.5/100,000. Regional pneumococcal bacteraemia rates were correlated with blood culture sampling rates (p =0.015), but meningitis rates did not correlate with CSF culture rates. During 1995-2002, the overall annual IPI rate increased by 35.1%, from 8.2 to 11.5/100,000 (p<0.001). The annual blood culturing rate increased by 29.6% (p=0.015 for the correlation with IPI rate). Temporal increase and higher regional IPI rates were significantly associated with higher blood culturing rates. Pneumococcal serotypes included in the 7- and 10-valent conjugate vaccines caused 69.8% and 85.2% of IPIs among children aged <5 y and 49.5% and 59.3% in adults, respectively. The true incidence of pneumococcal bacteraemia in Finland may be higher than previously estimated. Introduction of universal childhood pneumococcal conjugate immunization would provide substantial health benefits to Finnish children and adults.     

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n = 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics.     

Antimicrobial susceptibility of invasive group B streptococcal isolates from south-west Sweden 1988-2001

The antibiotic susceptibility of 297 invasive isolates of group B streptococci (GBS) to a panel of 12 antibiotics was analysed using the E-test. The isolates (from 123 neonates and 174 adults) were collected from south-west Sweden during the 2 periods 1988-1997 and 1998-2001. The breakpoints of the Clinical and Laboratory Standards Institute were used. All isolates were sensitive to cefotaxime, meropenem, linezolid, vancomycin, moxifloxacin and quinupristin-dalfopristin. Two strains displayed a slightly decreased susceptibility to penicillin G (MIC 0.25 microg/ml) also when tested by the broth dilution method. Two per cent were resistant to erythromycin and 1% to clindamycin. Strains with intermediate sensitivity to erythromycin and clindamycin increased over the 2 study periods. 68% were resistant to doxycycline, and the resistance rate for doxycycline increased over the 2 study periods. No strain was resistant to trimethoprim-sulfamethoxazole. Serotype V dominated among strains with intermediate susceptibility to erythromycin and clindamycin. There were no other relationships between serotypes and decreased sensitivity to any agent. There were no significant differences in susceptibility to any agent tested between strains isolated from neonates and adults. In conclusion, penicillins remain the drug of choice in the region but with the increasing rates of intermediate susceptibility to both erythromycin and clindamycin, antibiotic sensitivity analysis should be performed on the GBS isolates from penicillin-allergic patients.     

Identification of a high-virulence clone of type III Streptococcus agalactiae (group B Streptococcus) causing invasive neonatal disease

Chromosomal genotypes of 128 isolates of six serotypes (Ia, Ib, Ic, II, Ic/II, and III) of Streptococcus agalactiae (group B Streptococcus) recovered predominantly from human infants in the United States were characterized by an analysis of electrophoretically demonstrable allelic profiles at 11 metabolic enzyme loci. Nineteen distinctive electrophoretic types (ETs), representing multilocus clonal genotypes, were identified. Mean genetic diversity per locus among ETs of isolates of the same serotype was, on average, nearly equal to that in all 19 ETs. Cluster analysis of the ETs revealed two primary phylogenetic divisions at a genetic distance of 0.65. A single clone (ET 1) represented by 40 isolates expressing type III antigen formed division I. Division II was composed of 18 ETs in three major lineages diverging from one another at distances greater than 0.35 and included strains of all six antigenic classes. The type III organisms in division I produce more extracellular neuraminidase and apparently are more virulent than the type III strains in division II, which are related to strains of other serotypes that cause disease much less frequently. The existence of this unusually virulent clone accounts, in major part, for the high morbidity and mortality associated with infection by type III organisms.     

Severe group B streptococcal eye infections in adults

Group B beta-haemolytic streptococci have not been described as causing invasive eye infection in adults. Our observation of 10 such infections in nine patients indicates that persons with damaged ocular surfaces are especially vulnerable.     

Immunoprophylaxis and immunotherapy of neonatal group B streptococcal infections

Summary With emphasis on work from our laboratory, this paper briefly reviews previous studies which have established the basis for immunity to group B streptococcal infections. Quantitative data are presented on the concentration of antibody to the type-specific polysaccharides of group B streptococci in normal adults and infected infants, the protective level in experimental animals, and the influence of prematurity on transplacental passage of antibody. The role of the polymorphonuclear leukocyte in immunity to group B streptococcal infections is critical as supported byin vitro andin vivo experiments as well as clinical observations. Strategies for prevention include antimicrobial chemoprophylaxis and active immunization. Alternative approaches to adjunctive therapy such as administration of specific immune globulin, polymorphonuclear leukocytes, and exchange transfusions are discussed.

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Immunprophylaxe und Immuntherapie von Neugeboreneninfektionen mit Streptokokken der Gruppe B

Zusammenfassung In der vorliegenden Arbeit wird — mit Schwerpunkt auf eigene Laboruntersuchungen — eine kurze Übersicht über die grundlegenden Arbeiten zur Immunität von Infektionen mit Streptokokken der Gruppe B gegeben. Zur Antikörperkonzentration typenspezifischer Polysaccharide von Streptokokken der Gruppe B bei normalen Erwachsenen und infizierten Säuglingen, protektiven Antikörperspiegeln bei Laboratoriumstieren sowie zum Einfluß der Frühgeburtlichkeit auf die transplazentare Passage von Antikörpern werden quantitative Daten vorgestellt. WieIn vitro-undIn vivo-Studien sowie klinische Beobachtungen zeigten, spielen die polymorphkernigen Leukozyten für die Immunität von Infektionen mit Streptokokken der Gruppe B eine entscheidende Rolle. Präventivmaßnahmen schließen die antimikrobielle Chemoprophylaxe und die aktive Immunisierung ein. Als alternative Zusatzmaßnahmen werden Gabe von spezifischem Immunglobulin, polymorphkernigen Leukozyten und Austauschtransfusion diskutiert.

     

Community-acquired invasive group A beta-hemolytic streptococcal infections in Zuni Indians.

BACKGROUND--Outbreaks of invasive group A beta-hemolytic streptococcal (GABS) infections have recently been reported. We observed a high incidence of invasive GABS disease among Native Americans at a small rural community hospital between 1982 and 1991. METHODS--A retrospective chart review was performed, and all cases of invasive GABS disease were studied for their clinical features. RESULTS--Sixteen cases of invasive GABS infection were identified during the 10-year study period. The rate of invasive GABS infection was 13.3 cases per 100,000 population per year. Mortality was 25%. Nearly half of the patients presented with systemic signs of sepsis without any obvious source of infection. CONCLUSIONS--Our experience documents a high rate of invasive GABS infections in a defined Native American population. To determine whether this population has a unique susceptibility to GABS disease requires further study.     

Serotypes and polyacrylamide gel electrophoresis types among disease-associated isolates of group B Neisseria meningitidis in Spain, 1976-1979

A high annual incidence of meningococcal meningitis and septicemia occurred in Spain from 1976 through 1980 with a peak of 19 cases per 100,000 population in 1979. Approximately 80% were caused by group B Neisseria meningitidis. Studies were undertaken to determine the distribution of groups, outer membrane protein serotypes and polyacrylamide gel electrophoresis (PAGE) types among 338 disease-associated group B isolates from six regions of Spain. The related serotypes 1, 8, and 15 accounted for 38% (129 of 338) of the isolates. Serotype 2, the major disease type in the United States, was responsible for 14% (48 of 338) of the disease in Spain and was prevalent in only one region. Forty-three percent (146 of 338) were nonserotypable. The predominant PAGE type among the nonserotypable strains was PAGE type IV (79%). These studies demonstrate the necessity of surveillance for selection of suitable serotypes to be included in protective group B meningococcal vaccines.     

Chlamydia pneumoniae infections in Norway 1981-87 earlier diagnosed as ornithosis

Ornithosis has been a notifiable disease in Norway since 1957. During an outbreak of respiratory disease in 1981-82, described as ornithosis, contact with birds was stated in only 50% of the cases, suggesting that the infection was spread by interhuman transmission. A similar outbreak occurred in the western part of Norway in 1987. Serum specimens from altogether 260 patients, collected during the outbreaks in 1981-82 and in 1987, were investigated for antibodies against Chlamydia pneumoniae (strain TWAR). Evidence of recent infection with C. pneumoniae was found in 67.7% of the cases. The results indicate that the increased incidence of ornithosis in 1981-82 and in 1987 was due mainly to C. pneumoniae infections.     

Risk factors in early-onset neonatal group B streptococcal infections

Summary Newborn infants with early-onset disease due to group B beta hemolytic streptococcus were studied over a 40-month period. Clinical presentations included asymptomatic bacteremia, mild transient illness, respiratory distress, meningitis, and overwhelming sepsis. Chronologically, 18 were ill at birth; 10 became ill after a symptom-free period; and four were asymptomatic. Sixty-six percent of the cases weighed less than 2500 grams, and 56% were born to mothers whose amniotic membranes were ruptured for over 20 hours. All 15 of the deaths occurred in low birth weight infants who were critically ill from birth. A review of 128 consecutive deliveries of infants weighing under 2000 grams revealed 28 cases with prolonged ruptured membranes, and three of these 28 infants developed group B streptococcal infection. The infant of the colonized gravid woman in premature labor or with prolonged ruptured membranes is clearly at risk, and these results suggest that the management of early-onset disease should begin prior to delivery.

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Risikofaktoren bei früh ausbrechender Neonatalinfektionen durch Streptokokken der Gruppe B

Zusammenfassung Neugeborene mit früh ausbrechender Erkrankung durch betahämolytische Streptokokken der Gruppe B wurden über einen Zeitraum von 40 Monaten untersucht. Die klinischen Bilder umfaßten asymptomatische Bakteriämie, leichte passagere Erkrankung, Atemnot-Syndrom, Meningitis und dramatische Sepsis. Chronologisch waren 18 Neugeborene zum Zeitpunkt der Geburt krank, 10 erkrankten nach einem symptomfreien Zeitabschnitt und vier waren asymptomatisch. In 66% der Fälle lag das Körpergewicht unter 2500 Gramm und bei 56% der Neugeborenen war der Blasensprung vor mehr als 20 Stunden erfolgt. Alle 15 Todesfälle traten bei Kindern mit geringem Geburtsgewicht auf, deren Zustand von Geburt an kritisch war. Eine Überprüfung von 128 aufeinanderfolgenden Geburten mit einem Körpergewicht von weniger als 2000 Gramm ergab 28 Fälle von vorzeitigem Blasensprung und drei dieser 28 Neugeborenen entwickelten eine Infektion durch Streptokokken der Gruppe B. Für das Kind der bakteriell besiedelten Schwangeren im Stadium der Frühgeburt oder mit vorzeitigem Blasensprung besteht eindeutiges Risiko, und diese Ergebnisse weisen darauf hin, daß die Behandlung der früh ausbrechenden Erkrankung vor der Entbindung eingeleitet werden sollte.

     

Large-scale questionnaire surveillance concerning invasive infections with group C and G streptococci

A large-scale questionnaire surveillance was conducted regarding the onset of invasive infections with beta-hemolytic group C (GCS) and group G (GGS) streptococci from clinical specimens that are normally aseptic and the backgrounds of these cases. The surveillance period of the questionnaire was 8 months from January to August 2005. Completed questionnaires were received from the clinical laboratories of 193 medical institutions. One hundred two clinical laboratories (52.8%) had isolated these beta-hemolytic streptococci. Of all the isolates, GCS and GGS accounted for 25 and 216 cases, respectively, or a ratio of almost 1:10. Isolates from blood cultures accounted for half the number of all isolates, followed by isolates from atretic pus or joint fluid. The isolates gradually became more prevalent from patients in their 40s, and peaked in patients in their 70s. The most prevalent disorder, described in 184 cases, was suppurative disease followed by (in descending order), bacteremia, sepsis, arthritis purulenta and cellulitis. A small number of patients had developed with streptococcal toxic shock syndrome, empyema or meningitis. Most of the patients had an underlying disease, such as diabetes mellitus, malignancy or cerebrovascular disease (in descending order). We conclude from the above findings that background factors in patients as well as identification of the pathogen should be made public when GCS or GGS is isolated from normally aseptic clinical specimens.