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Contrasting roles for reactive oxygen species and nitric oxide in the innate response to pulmonary infection with Streptococcus pneumoniae.

The pulmonary innate response to low-dose bacterial challenge requires functioning alveolar macrophages (AM) but also subsequent macrophage apoptosis. To address the role of reactive oxygen species (ROS) and nitric oxide (NO) in AM apoptosis, sub-clinical Streptococcus pneumoniae infection was established in gp91(phox-/-) and inducible NO synthase deficient (iNOS(-/-)) mice. Both AM apoptosis and the number of macrophages containing apoptotic bodies are reduced in iNOS(-/-) as compared to control or gp91(phox-/-) mice. iNOS(-/-) mice recruit neutrophils and generate TNF-alpha to compensate for impaired AM competence but ROS deficiency has no apparent effect on AM function in this model.

Animals↗

[Perinatal Streptococcus agalactiae infections. Clinical epidemiological study and evaluation of a prevention program].

BACKGROUND: To prove both the importance of SGB (group B streptococci) as a cause of perinatal infection and the efficacy of a prophylactic treatment in pregnant women with cervicovaginal colonization by SGB. METHODS: Retrospective study of 197 third trimester pregnant women who were carriers of SGB (155 received intrapartum prophylaxis) and of 44 patients with SGB infections during pregnancy, post-partum and neonatal periods. RESULTS: No neonatal sepsis was detected in the group of SGB carrier mothers who received antibiotic prophylaxis. In carrier pregnant women who did not receive prophylaxis, one case of neonatal sepsis by SGB was detected and a greater prevalence of intrapartum fever, and neonatal infection with negative cultures was observed. SGB was frequently isolated as a cause of early sepsis and neonatal meningitis (13 cases), intraamniotic infection (12 cases) and puerperal endometritis (8 cases). In 45% of the patients with perinatal infections by SGB, the cervicovaginal culture performed in the third trimester of pregnancy did not detect the presence of SGB. CONCLUSIONS: The administration of intrapartum ampicillin to pregnant SGB carriers permits the prevention of perinatal infections by this microorganism in a great number of patients, although the possibility of late colonization, which may not be detected during pregnancy, stil remains.

Ampicillin↗

[Tissue infections caused by group A beta hemolytic Streptococcus in a regional hospital of Talca, Chile].

BACKGROUND: A resurgence of group A beta hemolytic Streptococcus infections such as fasciitis, cellulitis and Streptococcal Toxic Syndrome has been observed recently. AIM: To study the clinical features of patients with group A beta hemolytic Streptococcus infections in a regional hospital. PATIENTS AND METHODS: Retrospective review of medical records of patients notified as having a group A beta hemolytic Streptococcus tissue infection, between 1994 and 1999. RESULTS: Twenty four patients were notified in the period as having a group A beta hemolytic Streptococcus infection and 18 (13 male, mean age 39 tears old) had tissue involvement. Eleven patients had a fasciitis (61%), six had a cellulitis (33%) and 14 patients (77%), a Streptococcal Toxic Shock Syndrome. Eight patients died during hospital stay. The infection portal of entry was identify in 13 patients (the skin in 10 and intramuscular injections in three). Decreased patients had a longer lapse of disease before admission than patients discharged alive (5(range 3h-7 days) and 2.1 (range 6h-5 days) respectively). In seven patients a quick serological test, designed for pharyngeal infections was performed and it was positive in five. Blood cultures were positive in seven patients and in 11, the germ was isolated from the lesions. CONCLUSIONS: As the early diagnosis of group A beta hemolytic Streptococcus tissue infections has a prognostic value, the population should be instructed to recognize early signs and symptoms of these infections.

Adolescent↗

Host Proteome Remodeling During Group A Streptococcus Skin Infection.

Group A Streptococcus (Streptococcus pyogenes, GAS) is a bacterial pathogen that commonly causes local infections in humans and can lead to invasive diseases. GAS infections trigger complex host immune and tissue responses, yet how these processes are coordinated over time and across different tissues remains poorly understood. To explore the spectrum of GAS infection, we examined responses in a skin infection model at multiple proteome levels, characterizing local and distant tissues with variable infection responses. We map changes in canonical innate and adaptive immune signaling while uncovering new mechanisms in the context of skin infection. We uncover the robust and time-dependent expression of one family of proteins, chitinase-like proteins, that coincides with immune cell infiltration of local tissues. Because immunomodulatory networks are tightly regulated through post-translational modifications, we integrated global proteomic data with cytokine signaling and key phosphoproteome changes. This analysis revealed correlations between mTOR and kinase signaling pathways that diverge at local and systemic tissues. Our systems-based approach provides a rigorous evaluation of a GAS skin infection, characterizing host proteome remodeling across experimental groups and individual mice.

Animals↗

Invasive Streptococcus iniae infections outside North America.

Streptococcus iniae, a fish pathogen causing infections in aquaculture farms worldwide, has only been reported to cause human infections in North America. In this article, we report the first two cases of invasive S. iniae infections in two Chinese patients outside North America. While the first patient presented with bacteremic cellulitis, which is the most common presentation in previous cases, the second patient represents the first recognized case of S. iniae osteomyelitis. Both S. iniae strains isolated from the two patients were either misidentified or unidentified by three commercial systems and were only identified by 16S rRNA gene sequencing. Since no currently available commercial system for bacterial identification includes S. iniae in its database, 16S rRNA gene sequencing is the most practical and reliable method to identify the bacterium at the moment. In contrast to the distinct genetic profile described previously in clinical isolates from Canada, the present two isolates and a clinical isolate from a Canadian patient were found to be genetically unrelated, as demonstrated by pulsed-field gel electrophoresis. Morphologically, colonies of both isolates were also larger, more beta-hemolytic and mucoid, which differ from the usual morphotype described for S. iniae. Owing to their habit of cooking and eating fresh fish, the Asian population is strongly associated with S. iniae infections. As a result of the difficulty in making microbiological diagnosis in patients with cellulitis and the problem of identification in most clinical microbiology laboratories, the prevalence of S. iniae infections, especially in the Asian population, may have been under-estimated.

Adult↗

The molecular basis of Streptococcus equi infection and disease.

Streptococcus equi is the aetiological agent of strangles, one of the most prevalent diseases of the horse. The animal suffering and economic burden associated with this disease necessitate effective treatment. Current antibiotic therapy is often ineffective and thus recent attention has focused on vaccine development. A systematic understanding of S. equi virulence, leading to the identification of targets to which protective immunity can be directed, is a prerequisite of the development of such a vaccine. Here, the virulence factors of S. equi are reviewed.

Animals↗

Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice.

The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B. Serotype 6B is known to give a more protracted infection when injected intraperitoneally into susceptible mice than more virulent serotypes like type 4. PMII was administered i.p. either once 3 days before challenge or once to thrice from 3 to 48 h after challenge. The number of bacteria in blood and the mouse survival rate were recorded. Pre-challenge administration of PMII and also lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective effect against S. pneumoniae type 6B infection. However, injection of PMII after establishment of the infection in NIH/OlaHsd mice had no effect. The data demonstrate that, firstly, the polysaccharide fraction PMII from P. major protects against pneumococcal infection in mice when administered systemically prechallenge, and secondly that the protective effect is owing to stimulation of the innate and not the adaptive immune system.

Animals↗

The role of the molecular laboratory in the investigation of Streptococcus pneumoniae infections.

The importance of infections with Streptococcus pneumoniae is being increasingly recognized. This has been emphasised by the emergence and international dissemination of penicillin-resistant strains. These factors challenge modern microbiologists to use molecular tools to speed the process of the diagnosis of S pneumoniae at each of the stages: rapid diagnosis, culture identification, and typing. The polymerase chain reaction (PCR) has been used to amplify a number of different targets for primary diagnosis of pneumonia, meningitis, otitis media, and bacteraemia. This may provide a rapid diagnosis in patients who have been partially treated with antibiotics and increase the diagnostic yield in clinical trials of antimicrobial agents and new vaccines. A new development is the use of PCR to rapidly determine penicillin susceptibility. Several different experimental protocols are reviewed. In the past serotyping using the capsule swelling, or Quellung reaction was the only typing method available. Recent insight into epidemiology and population genetics of S pneumoniae has shown that this technique is inadequate to study the transmission of this organism. New molecular typing techniques have been developed including Field version gel electrophoresis, ribotyping, restriction fragment end labeling, BOX PCR, and random amplification of polymorphic DNA. As these methods become available to clinicians, they will gain more understanding of the way in which this organism interacts with human populations.

Bacterial Typing Techniques↗

Critical role of Valpha14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection.

The present study was designed to elucidate the role of Valpha14(+) NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jalpha281 gene-disrupted mice (Jalpha281KO mice) that lacked this lymphocyte subset. In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild-type (WT) mice. The proportion of Valpha14(+) NKT cells, detected by an alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramer, increased in thelung after S. pneumoniae infection. This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)-1, which was produced in the early phaseof infection in WT mice. In the lungs of Jalpha281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice. In support of this finding, macrophage inflammatory protein (MIP)-2 and TNF-alpha synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jalpha281KO mice, compared to WT mice. In addition, treatment of mice with alpha-GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of Valpha14(+) NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.

Animals↗

Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae.

Intranasal infection of mice with certain strains of capsular group 19 Streptococcus pneumoniae can result in focal pneumonia in the absence of bacteremia. Using this model of murine pneumonia, we demonstrated that immunization with recombinant forms of either pneumococcal surface protein A (PspA) or PdB (a genetically detoxified derivative of pneumolysin) elicited significant protection against focal pulmonary infection. This may be the first demonstration that a proposed vaccine antigen can protect against pneumococcal pneumonia. The best protection was obtained by immunizing mice with a mixture of PspA and PdB, indicating that the protection elicited by these antigens can complement each other. This result is in agreement with previous studies that used pneumococcal sepsis and nasal colonization models and demonstrate that the best protein vaccines for prevention of infection may be those that include more than one protection-eliciting pneumococcal protein.

Administration, Intranasal↗

Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in transgenic mice.

C-reactive protein (CRP) is an acute phase protein with a well known association with infection and other inflammatory conditions. Studies with use of purified CRP in in vitro assays provided early evidence that CRP has antibacterial activity. Subsequently it was shown that passively administered human CRP can protect mice from lethal infection with Streptococcus pneumoniae. In this study, we extend these observations to an in vivo model of host resistance by using human CRP transgenic mice. CRP transgenic mice experimentally infected with S. pneumoniae lived longer and had significantly lower mortality than their nontransgenic littermates. This increased resistance to infection was associated with q 10- to 400-fold reduction of bacteremia. Furthermore, male transgenics exhibited longer survival time than females, and this difference could be attributed to increased expression of CRP by males, which was mediated by testosterone. This study provides the first unequivocal evidence that CRP plays an important role in vivo in host defense against pneumococcal infections, and shows that sex hormones can affect expression of the human CRP transgene in mice.

Animals↗

[Streptococcus suis infection--clinical manifestations].

INTRODUCTION: Streptococcus suis is a bacterium causing a disease in pigs and rarely in humans. This zoonosis is mostly found as a sporadic disease in individuals that were in contact with the affected or infected pigs: farmers, veterinarians and workers engaged in fresh pork processing. It is assumed that the bacterium enters the body through a cut abrasion in the skin. Initially, the condition resembles a flu, followed by signs of bacteriemia and sepsis. The most frequent clinical manifestation of Streptococcus suis infection is meningitis, leading to hearing loss in over 75% of patients, and subsequent arthritis, endophtalmitis, endocarditis and pneumonia. Toxic shock syndrome with hemorhagic manifestations rarely develops. MATERIAL AND METHODS: This study included five male patients aged 22 to 63 years treated in the Intensive Care Unit of the Institute of Infectious and Tropical Diseases in Belgrade, due to Streptococcus suis infection. The aim of this study was to point to the existence of this bacteria in our environment, to describe clinical manifestations of the disease and to point out the importance of its prevention. RESULTS: All patients had epidemiological evidence of being in contact with pork meat. There were no data about diseased pigs. The estimated incubation period was 4 to 8 days. All patients had meningeal signs. Clinical symptoms included shivering, fever, vomiting, headache, malaise, vertigo and tinitus. Three patients presented with alerterd level of awarrness. Four patients developed very severe bilateral hearing impairment, whereas one endophtalmtis and one developed endocarditis. The cerebrospinal fluid (CSF) was opalescent in four patients, and only one patient presented with clear CSF. CSF examination showed typical changes characteristic for bacterial meningitis. Streptoccocus suis was isolated in CSF in all patients, and in one patient the bacteria was isolated in blood as well. All patients underwent treatement with II and III generation cephalosporins and one with one aminoglycosides. All patients were cured, but 4 of them developed sequelae like permanent sensorineural deafness and mild ataxia. CONCLUSIONS: Streptococcus suis infection is present as a zoonosis in pigs, while humans are contracted occasionaly, most frequently related to occupational risk. In cases with bacterial meningitis with sepsis and hearing loss, Streptococcus suis infections must be suspected. Effective prevention requires collaboration between epidemiologists, veterinarians and human medicine physicians.

Adult↗

Pathologic findings of experimentally induced Streptococcus uberis infection in the mammary gland of cows.

Twenty-five quarters of 12 dairy cows, 3 to 8 years old, with a bacteriologic history of freedom from infection with Streptococcus uberis were inoculated via the teat canal with S uberis (23 quarters) or sterile medium (2 quarters). The cows were sent to slaughter 1, 3, or 6 days later. Acute inflammatory response involving accumulation of large numbers of polymorphonuclear, neutrophilic leukocytes (neutrophils) in the secretory acini was recognized after 24 hours in infected cows. After 6 days, the neutrophil response was still evident, but infiltration of septa by lymphocytes, septal edema, extensive vacuolation of secretory cells, focal necrosis of alveoli, small outgrowths of the secretory and ductular epithelium, and widespread hypertrophy of the ductular epithelium also were recognized. Early stages of involution and fibrosis also were evident at that stage. Streptococci were identified by immunoperoxidase labeling, free or phagocytosed, in macrophages; in the alveolar lumina, adherent to damaged secretory or ductular epithelium; in the subepithelium and septal tissue; and in lymphatic vessels and lymph nodes. The importance of the macrophage as the primary phagocytic cell is highlighted, and doubt is cast on the value of the exuberant neutrophil response by the host in defense of the gland.

Animals↗

Streptococcus milleri infection of a hepatopulmonary hydatid cyst.

A case of hepatopulmonary hydatid disease in a Cypriot who presented with pyogenic infection with Streptococcus milleri is described. Although hydatid disease and pyogenic liver abscess are both rare in the UK, an underlying echinococcal pathology should be suspected in any patient from an area endemic for hydatid who presents with a pyogenic hepatic or hepatopulmonary abscess.

Echinococcosis, Hepatic↗

Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections.

CONTEXT: Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites. Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown. OBJECTIVE: To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States. DESIGN, SETTING, AND PATIENTS: Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states. Patients were 15,923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002. MAIN OUTCOME MEASURES: Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences. RESULTS: Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks. Due to these declines, 14,730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999. Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval [CI], 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4). Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002. By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses. CONCLUSION: Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease.

Adolescent↗