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1.
J Hosp Infect ; 132: 36-45, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36435307

RESUMO

BACKGROUND: Surfaces and air in healthcare facilities can be contaminated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Previously, the authors identified SARS-CoV-2 RNA on surfaces and air in their hospital during the first wave of the coronavirus disease 2019 pandemic (April 2020). AIM: To explore whether the profile of SARS-CoV-2 surface and air contamination had changed between April 2020 and January 2021. METHODS: This was a prospective, cross-sectional, observational study in a multi-site London hospital. In January 2021, surface and air samples were collected from comparable areas to those sampled in April 2020, comprising six clinical areas and a public area. SARS-CoV-2 was detected using reverse transcription polymerase chain reaction and viral culture. Sampling was also undertaken in two wards with natural ventilation alone. The ability of the prevalent variants at the time of the study to survive on dry surfaces was evaluated. FINDINGS: No viable virus was recovered from surfaces or air. Five percent (N=14) of 270 surface samples and 4% (N=1) of 27 air samples were positive for SARS-CoV-2, which was significantly lower than in April 2020 [52% (N=114) of 218 surface samples and 48% (N=13) of 27 air samples (P<0.001, Fisher's exact test)]. There was no clear difference in the proportion of surface and air samples positive for SARS-CoV-2 RNA based on the type of ventilation in the ward. All variants tested survived on dry surfaces for >72 h, with a <3-log10 reduction in viable count. CONCLUSION: This study suggests that enhanced infection prevention measures have reduced the burden of SARS-CoV-2 RNA on surfaces and air in healthcare facilities.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , RNA Viral/genética , Pandemias/prevenção & controle , Estudos Transversais , Estudos Prospectivos , Atenção à Saúde
2.
Clin Microbiol Infect ; 26(3): 381.e1-381.e6, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31357012

RESUMO

OBJECTIVES: Skin and soft tissue infections (SSTIs) are a serious health issue for military personnel. Of particular importance are those caused by methicillin-resistant Staphylococcus aureus and Panton-Valentine leucocidin (PVL)-positive S. aureus (PVL-SA), as they have been associated with outbreaks of SSTIs. A prospective observational study was conducted in Royal Marine (RM) recruits to investigate the prevalence of PVL-SA carriage and any association with SSTIs. METHODS: A total of 1012 RM recruits were followed through a 32-week training programme, with nose and throat swabs obtained at weeks 1, 6, 15 and 32. S. aureus isolates were characterized by antibiotic susceptibility testing, spa typing, presence of mecA/C and PVL genes. Retrospective review of the clinical notes for SSTI acquisition was conducted. RESULTS: S. aureus colonization decreased from Week 1 to Week 32 (41% to 26%, p < 0.0001). Of 1168 S. aureus isolates, three out of 1168 (0.3%) were MRSA and ten out of 1168 (0.9%) PVL-positive (all MSSA) and 169 out of 1168 (14.5%) were resistant to clindamycin. Isolates showed genetic diversity with 238 different spa types associated with 25 multi-locus sequence type (MLST) clonal complexes. SSTIs were seen in 35% (351/989) of recruits with 3 training days lost per recruit. SSTI acquisition rate was reduced amongst persistent carriers (p < 0.0283). CONCLUSIONS: Nose and throat carriage of MRSA and PVL-SA was low among recruits, despite a high incidence of SSTIs being reported, particularly cellulitis. Carriage strains were predominantly MSSA with a marked diversity of genotypes. Persistent nose and/or throat carriage was not associated with SSTI acquisition. Putative person-to-person transmission within troops was identified based on spa typing requiring further research to confirm and explore potential transmission routes.


Assuntos
Militares , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus , Adolescente , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Vigilância em Saúde Pública , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Adulto Jovem
3.
J Hosp Infect ; 103(4): 388-394, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31220480

RESUMO

BACKGROUND: Certain Clostridium difficile ribotypes have been associated with complex disease phenotypes including recurrence and increased severity, especially the well-described hypervirulent RT027. This study aimed to determine the pattern of ribotypes causing infection and the association, if any, with severity. METHODS: All faecal samples submitted to a large diagnostic laboratory for C. difficile testing between 2011 and 2013 were subject to routine testing and culture. All C. difficile isolates were ribotyped, and associated clinical and demographic patient data were retrieved and linked to ribotyping data. RESULTS: In total, 86 distinct ribotypes were identified from 705 isolates of C. difficile. RT002 and RT015 were the most prevalent (22.5%, N=159). Only five isolates (0.7%) were hypervirulent RT027. Ninety of 450 (20%) patients with clinical information available died within 30 days of C. difficile isolation. RT220, one of the 10 most common ribotypes, was associated with elevated median C-reactive protein and significantly increased 30-day all-cause mortality compared with RT002 and RT015, and with all other ribotypes found in the study. CONCLUSIONS: A wide range of C. difficile ribotypes were responsible for C. difficile infection presentations. Although C. difficile-associated mortality has reduced in recent years, expansion of lineages associated with increased severity could herald increases in future mortality. Enhanced surveillance for emerging lineages such as RT220 that are associated with more severe disease is required, with genomic approaches to dissect pathogenicity.


Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Ribotipagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Fezes/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
4.
Clin Exp Immunol ; 197(1): 83-94, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30815853

RESUMO

Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillo-pharyngitis and outbreaks of scarlet fever, although the mechanisms by which superantigens confer advantage to Streptococcus pyogenes are unclear. S. pyogenes is an exclusively human pathogen. As the leucocyte profile of tonsil is unique, the impact of SpeA production on human tonsil cell function was investigated. Human tonsil cells from routine tonsillectomy were co-incubated with purified streptococcal superantigens or culture supernatants from isogenic streptococcal isolates, differing only in superantigen production. Tonsil cell proliferation was quantified by tritiated thymidine incorporation, and cell surface characteristics assessed by flow cytometry. Soluble mediators including immunoglobulin were measured using enzyme-linked immunosorbent assay. Tonsil T cells proliferated in response to SpeA and demonstrated typical release of proinflammatory cytokines. When cultured in the absence of superantigen, tonsil preparations released large quantities of immunoglobulin over 7 days. In contrast, marked B cell apoptosis and abrogation of total immunoglobulin (Ig)A, IgM, and IgG production occurred in the presence of SpeA and other superantigens. In SpeA-stimulated cultures, T follicular helper (Tfh) cells showed a reduction in C-X-C chemokine receptor (CXCR)5 (CD185) expression, but up-regulation of OX40 (CD134) and inducible T cell co-stimulator (ICOS) (CD278) expression. The phenotypical change in the Tfh population was associated with impaired chemotactic response to CXCL13. SpeA and other superantigens cause dysregulated tonsil immune function, driving T cells from Tfh to a proliferating phenotype, with resultant loss of B cells and immunoglobulin production, providing superantigen-producing bacteria with a probable survival advantage.


Assuntos
Proteínas de Bactérias/imunologia , Exotoxinas/imunologia , Proteínas de Membrana/imunologia , Tonsila Palatina/imunologia , Streptococcus pyogenes/imunologia , Imunidade Adaptativa , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/toxicidade , Linfócitos B/imunologia , Linfócitos B/patologia , Proteínas de Bactérias/toxicidade , Morte Celular/imunologia , Proliferação de Células , Citocinas/metabolismo , Exotoxinas/toxicidade , Humanos , Imunoglobulinas/biossíntese , Técnicas In Vitro , Ativação Linfocitária , Proteínas de Membrana/toxicidade , Tonsila Palatina/patologia , Fenótipo , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/patogenicidade , Superantígenos/imunologia , Superantígenos/toxicidade , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia
5.
J Hosp Infect ; 101(2): 120-128, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30403958

RESUMO

BACKGROUND: The incidence of Escherichia coli bacteraemia in England is increasing amid concern regarding the roles of antimicrobial resistance and nosocomial acquisition on burden of disease. AIM: To determine the relative contributions of hospital-onset E. coli bloodstream infection and specific E. coli antimicrobial resistance patterns to the burden and severity of E. coli bacteraemia in West London. METHODS: Patient and antimicrobial susceptibility data were collected for all cases of E. coli bacteraemia between 2011 and 2015. Multivariable logistic regression was used to determine the association between the category of infection (hospital or community-onset) and length of stay, intensive care unit admission, and 30-day all-cause mortality. FINDINGS: E. coli bacteraemia incidence increased by 76% during the study period, predominantly due to community-onset cases. Resistance to quinolones, third-generation cephalosporins, and aminoglycosides also increased over the study period, occurring in both community- and hospital-onset cases. Hospital-onset and non-susceptibility to either quinolones or third-generation cephalosporins were significant risk factors for prolonged length of stay, as was older age. Rates of mortality were 7% and 12% at 7 and 30 days, respectively. Older age, a higher comorbidity score, and bacteraemia caused by strains resistant to three antibiotic classes were all significant risk factors for mortality at 30 days. CONCLUSION: Multidrug resistance, increased age, and comorbidities were the main drivers of adverse outcome. The rise in E. coli bacteraemia was predominantly driven by community-onset infections, and initiatives to prevent community-onset cases should be a major focus to reduce the quantitative burden of E. coli infection.


Assuntos
Bacteriemia/epidemiologia , Farmacorresistência Bacteriana , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Feminino , Humanos , Incidência , Tempo de Internação , Londres/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
6.
BJOG ; 126(1): 44-53, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30070056

RESUMO

OBJECTIVE: We describe cases of invasive group A Streptococcus (iGAS) in mothers or neonates and assess management according to national guidelines, which recommend administering antibiotics to both mother and neonate if either develops iGAS infection within 28 days of birth and investigation of clusters in maternity units. DESIGN: Cross-sectional retrospective study. SETTING AND POPULATION: Notified confirmed iGAS cases in either mothers or neonates with onset within 28 days of birth in London and the South East of England between 2010 and 2016 METHOD: Review of public health records of notified cases. MAIN OUTCOME MEASURES: Incidence and onset time of iGAS in postpartum mothers and babies, proportion given prophylaxis, maternity unit clusters within 6 months. RESULTS: We identified 134 maternal and 21 neonatal confirmed iGAS infections. The incidence (in 100 000 person years) of iGAS in women within 28 days postpartum was 109 (95% CI 90-127) compared with 1.3 in other females aged 15-44. For neonates the incidence was 1.5 (95% CI 9-23). The median onset time was 2 days postpartum [interquartile range (IQR) 0-5 days] for mothers and 12 days (IQR 7-15 days) for neonates. All eligible mothers and most (109, 89%) eligible neonates received chemoprophylaxis. Of 20 clusters (59 cases of GAS and iGAS) in maternity units, two clusters involved possible transmission. However, in 6 of 15 clusters, GAS isolates were not saved for comparison even after relevant guidance was issued. CONCLUSIONS: iGAS infection remains a potential postpartum risk. Prophylaxis among neonates and storage of isolates from maternity cases can be improved. TWEETABLE ABSTRACT: Are public health guidelines being followed in the management of mothers and their newborns to reduce the risk of iGAS infection?


Assuntos
Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Infecções Estreptocócicas/epidemiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Auditoria Clínica , Estudos Transversais , Diagnóstico Precoce , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Londres/epidemiologia , Período Pós-Parto , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/prevenção & controle , Adulto Jovem
7.
J Antimicrob Chemother ; 74(4): 1108-1115, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590545

RESUMO

BACKGROUND: Infection diagnosis can be challenging, relying on clinical judgement and non-specific markers of infection. We evaluated a supervised machine learning (SML) algorithm for diagnosing bacterial infection using routinely available blood parameters on presentation to hospital. METHODS: An SML algorithm was developed to classify cases into infection versus no infection using microbiology records and six available blood parameters (C-reactive protein, white cell count, bilirubin, creatinine, ALT and alkaline phosphatase) from 160203 individuals. A cohort of patients admitted to hospital over a 6 month period had their admission blood parameters prospectively inputted into the SML algorithm. They were prospectively followed up from admission to classify those who fulfilled clinical case criteria for a community-acquired bacterial infection within 72 h of admission using a pre-determined definition. Predictive ability was assessed using receiver operating characteristics (ROC) with cut-off values for optimal sensitivity and specificity explored. RESULTS: One hundred and four individuals were included prospectively. The median (range) cohort age was 65 (21-98) years. The majority were female (56/104; 54%). Thirty-six (35%) were diagnosed with infection in the first 72 h of admission. Overall, 44/104 (42%) individuals had microbiological investigations performed. Treatment was prescribed for 33/36 (92%) of infected individuals and 4/68 (6%) of those with no identifiable bacterial infection. Mean (SD) likelihood estimates for those with and without infection were significantly different. The infection group had a likelihood of 0.80 (0.09) and the non-infection group 0.50 (0.29) (P < 0.01; 95% CI: 0.20-0.40). ROC AUC was 0.84 (95% CI: 0.76-0.91). CONCLUSIONS: An SML algorithm was able to diagnose infection in individuals presenting to hospital using routinely available blood parameters.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Infecções/diagnóstico , Admissão do Paciente , Aprendizado de Máquina Supervisionado , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores , Tomada de Decisão Clínica , Estudos de Coortes , Testes Diagnósticos de Rotina/métodos , Gerenciamento Clínico , Feminino , Seguimentos , Testes Hematológicos , Humanos , Infecções/epidemiologia , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Adulto Jovem
8.
Virulence ; 9(1): 1074-1084, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30052105

RESUMO

Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected.


Assuntos
Contusões/microbiologia , Linfonodos/microbiologia , Músculos/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/fisiologia , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Regulação Bacteriana da Expressão Gênica , Humanos , Camundongos , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Virulência
9.
BMC Microbiol ; 18(1): 60, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921240

RESUMO

BACKGROUND: The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models. RESULTS: Using clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues. CONCLUSION: Development of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes.


Assuntos
Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/genética , Proteínas Luminescentes/metabolismo , Infecções Respiratórias/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/patogenicidade , Animais , Modelos Animais de Doenças , Feminino , Aptidão Genética , Humanos , Medições Luminescentes , Proteínas Luminescentes/genética , Camundongos , Óperon , Streptococcus pyogenes/genética
10.
J Infect ; 74(6): 585-589, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28344116

RESUMO

AIMS: A prospective observational study was conducted in Royal Marines (RM) recruits to investigate throat carriage of group A Streptococcus (GAS) and incidence of soft tissue infections. METHODS: 1012 RM recruits were followed through a 32-week training programme, with throat swabs being obtained in weeks 1, 6, 15, and 32. Alongside a separate cohort of 46 RM Young Officers (YO) undergoing training were sampled in parallel. RESULTS: Carriage of group A Streptococcus was detected in only 5/1012 (0.49%) recruits at the beginning of training and remained low throughout training. There was no association between GAS carriage and development of soft tissue infection. There was no carriage of GAS in the smaller YO cohort at the start of training, (0/46). At week 6, a surge in GAS carriage was detected in 8/46 (17%) YO, that could be ascribed to a cluster of GAS genotype emm83. CONCLUSIONS: Asymptomatic GAS carriage is very infrequent among young adults in England and this should be borne in mind when considering the relevance of a positive throat swab result in symptomatic patients or outbreaks. Despite low prevalence, there is however potential for GAS to rapidly and transiently disseminate among adults during outbreaks.


Assuntos
Infecções Assintomáticas/epidemiologia , Portador Sadio/epidemiologia , Militares , Faringe/microbiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação , Adolescente , Adulto , Portador Sadio/microbiologia , Surtos de Doenças , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Adulto Jovem
12.
Epidemiol Infect ; 143(8): 1719-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25262779

RESUMO

The objective of this study was to estimate the direct financial costs of hospital care for management of invasive group A streptococcal (GAS) infections using hospital records for cases diagnosed in England. We linked laboratory-confirmed cases (n = 3696) identified through national surveillance to hospital episode statistics and reimbursement codes. From these codes we estimated the direct hospital costs of admissions. Almost all notified invasive GAS cases (92% of 3696) were successfully matched to a primary hospital admission. Of these, secondary admissions (within 30 days of primary admission) were further identified for 593 (17%). After exclusion of nosocomial cases (12%), the median costs of primary and secondary hospital admissions were estimated by subgroup analysis as £1984-£2212 per case, totalling £4·43-£6·34 million per year in England. With adjustment for unmatched cases this equated to £4·84-£6·93 million per year. Adults aged 16-64 years accounted for 48% of costs but only 40% of cases, largely due to an increased number of surgical procedures. The direct costs of hospital admissions for invasive GAS infection are substantial. These estimated costs will contribute to a full assessment of the total economic burden of invasive GAS infection as a means to assess potential savings through prevention measures.


Assuntos
Cuidados Críticos/economia , Fasciite Necrosante/economia , Custos Hospitalares , Hospitalização/economia , Pneumonia Bacteriana/economia , Sepse/economia , Infecções dos Tecidos Moles/economia , Infecções Estreptocócicas/economia , Streptococcus pyogenes , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Inglaterra/epidemiologia , Fasciite Necrosante/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/epidemiologia , Sepse/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estreptocócicas/epidemiologia , Adulto Jovem
13.
Clin Exp Immunol ; 173(1): 84-91, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23607659

RESUMO

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.


Assuntos
Antraz/sangue , Antígenos de Bactérias/farmacologia , Toxinas Bacterianas/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Receptores de Superfície Celular/biossíntese , Dermatopatias Bacterianas/sangue , Antraz/genética , Vacinas contra Antraz/farmacologia , Antígenos de Bactérias/metabolismo , Estudos de Coortes , Convalescença , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunização Secundária , Interferon gama/biossíntese , Interferon gama/genética , Leucócitos Mononucleares/metabolismo , Proteínas dos Microfilamentos , Proteínas de Neoplasias/genética , Receptores de Superfície Celular/genética , Dermatopatias Bacterianas/genética , Turquia , Reino Unido , Vacinação
14.
J R Coll Physicians Edinb ; 41(4): 339-46, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22184573

RESUMO

Despite global efforts to reduce maternal mortality, maternal deaths from bacterial sepsis have actually risen in the UK. The group A streptococcus, also known as Streptococcus pyogenes, is the leading cause of infection-related death in pregnancy and the puerperium. Many clinicians remain unaware of the risks posed to this particular group of otherwise fit, healthy patients despite the fact that S. pyogenes has been the leading infective cause of puerperal deaths since records began. S. pyogenes has a specific but unexplained predilection for the recently pregnant woman, and has an attributable mortality greater than many other invasive bacteria. Here, the epidemiology, aetiology, and management of severe peripartum sepsis are discussed, as are potential approaches to reduce risks. While fundamental changes in healthcare access can lead to dramatic reductions in maternal deaths in developing countries, an improvement in maternal sepsis deaths in the UK will require heightened awareness among both hospital and community-based clinical staff.


Assuntos
Bacteriemia , Mortalidade Materna , Período Periparto , Complicações na Gravidez , Streptococcus pyogenes , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/terapia , Feminino , Humanos , Gravidez , Complicações na Gravidez/mortalidade , Competência Profissional , Reino Unido/epidemiologia
16.
Br J Pharmacol ; 154(4): 864-71, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18536738

RESUMO

BACKGROUND AND PURPOSE: Lung epithelial cells express pattern recognition receptors, which react to bacteria. We have evaluated the effect of Gram-positive and Gram-negative bacteria on interleukin-8 (CXCL8) release from epithelial cells and the integrity of the epithelial barrier. EXPERIMENTAL APPROACH: Primary cultures of human airway epithelial cells and the epithelial cell line A549 were used, and CXCL8 release was measured after exposure to Gram-negative or Gram-positive bacteria. Epithelial barrier function was assessed in monolayer cultures of A549 cells. RESULTS: Gram-positive bacteria Staphylococcus aureus or Streptococcus pneumoniae, induced release of CXCL8 from human airway epithelial cells. These bacteria also disrupted barrier function in A549 cells, an effect mimicked by CXCL8 and blocked by specific binding antibodies to CXCL8. Gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa induced greater release of CXCL8 than Gram-positive bacteria. However, Gram-negative bacteria did not affect epithelial barrier function directly, but prevented disruption induced by Gram-positive bacteria. These effects of Gram-negative bacteria on barrier function were mimicked by FK565, an agonist of the nucleotide-binding oligomerization domain 1 (NOD1) receptor, but not by the Toll-like receptor (TLR) 4 agonist bacterial lipopolysaccharide. Neither the Gram-negative bacteria nor FK565 blocked CXCL8 release. CONCLUSIONS: These data show differential functional responses induced by Gram-negative and Gram-positive bacteria in human lung epithelial cells. The NOD1 receptors may have a role in preventing disruption of the epithelial barrier in lung, during inflammatory states.


Assuntos
Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Interleucina-8/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Humanos , Pulmão/citologia , Pulmão/metabolismo , Pulmão/microbiologia , Proteína Adaptadora de Sinalização NOD1/metabolismo , Receptor 4 Toll-Like/metabolismo
17.
J Pathol ; 214(2): 211-23, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18161754

RESUMO

Sepsis, the systemic inflammatory response to infection, is considered the major cause of death among critically ill patients in the developed world. While there is a general view that this reflects contributions from both the pathogen and the host with respect to an inappropriate inflammatory response, there is a lack of agreement as to the key immune mechanisms. This has been reflected in the diverse range of immunotherapies tested in clinical trials, often with rather marginal effects. The case has been made for a pathogenic role of excessive immunity, the so-called 'cytokine storm', and for a role of too little immunity through immune paralysis. Apoptosis is implicated as a key mechanism in both this immune paralysis and the multi-organ failure that is a feature of severe sepsis. A number of polymorphisms have been implicated in susceptibility to sepsis, including cytokine genes, HLA class II and caspase-12. In this review we focus in particular on the role of group A streptococci in severe sepsis. Here the effect of bacterial superantigens appears to be a correlate of inflammatory activation, although the precise evolutionary role of the superantigens remains unclear.


Assuntos
Sepse/imunologia , Reação de Fase Aguda/imunologia , Animais , Coagulação Sanguínea , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Humanos , Imunidade Inata , Mediadores da Inflamação/fisiologia , Sepse/sangue , Superantígenos/imunologia
18.
Br J Pharmacol ; 153(3): 536-43, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18059323

RESUMO

BACKGROUND AND PURPOSE: Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smokers are more prone to infections. This has been associated with a suppression of the immune system by smoke. However, it is not clear how cigarette smoke affects the ability of immune cells to sense pathogens. Cigarette smoke contains a large number of molecules which may mediate responses on immune cells and of these, nicotine and oxidants have both been identified as inhibitory for the sensing of bacterial lipopolysaccharide (LPS). Nitric oxide synthase (NOS) and tumour necrosis factor (TNF)-alpha are both induced in macrophages on stimulation with Gram negative bacteria or LPS. EXPERIMENTAL APPROACH: We used murine macrophages stimulated with whole heat-killed bacteria or LPS. We measured output of NO (as nitrite) and TNFalpha, NOS protein by Western blotting and cellular oxidant stress. KEY RESULTS: Cigarette smoke extract suppressed the ability of murine macrophages to release NO, but not TNFalpha in response to whole bacteria. Cigarette smoke extract also inhibited nitric oxide synthase II protein expression in response to LPS. The effects of cigarette smoke extract on nitrite formation stimulated by LPS were unaffected by inhibition of nicotinic receptors with alpha-bungarotoxin (100 units ml(-1)). However, the effects of cigarette smoke extract on LPS-induced nitrite formation were mimicked by hydrogen peroxide and reversed by the anti-oxidants N-acetyl cysteine and glutathione. CONCLUSIONS AND IMPLICATIONS: We suggest that cigarette smoke exerts its immunosuppressive effects through an oxidant-dependent and not a nicotine-dependent mechanism.


Assuntos
Bactérias Gram-Negativas/metabolismo , Macrófagos/efeitos dos fármacos , Nicotiana/efeitos adversos , Fumaça/efeitos adversos , Animais , Western Blotting , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Nicotina/efeitos adversos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
J Infect ; 54(5): 422-6, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17116332

RESUMO

OBJECTIVES: Injecting drug users (IDU) represent an increasing proportion of patients with invasive group A streptococcal (GAS) disease. Our aims were to characterise the clinical presentation and strains causing GAS bacteremia in IDU from a single UK city (Brighton and Hove), and to compare this patient group with non-drug users (non-DU) with GAS bacteremia. METHODS: Consecutive GAS blood culture isolates from twenty-two IDU and twenty-two non-DU presenting to the city hospital were studied. Clinical features, strain emm typing and superantigen toxin genotyping were investigated. RESULTS: GAS invasive disease presented differently in IDU compared to non-DU with a predominance of injection site abscesses and lower mortality in IDU. GAS strains from IDU were predominantly emm82 and emm83 types, which are uncommon in the UK and emm82 strains appeared clonal. The non-DU GAS strains demonstrated a broader range of emm types including most frequently emm1 and emm89. There was no major difference in superantigen gene profile between the isolate groups. CONCLUSION: The distinct presentation of invasive GAS disease in IDU compared with non-DU was associated with distinct emm types, a predominance of abscesses, and low mortality, although the small numbers preclude definitive conclusions. Further study is required to establish if these findings reflect strain differences or epidemiological differences in colonisation patterns and injecting practice.


Assuntos
Bacteriemia , Hospitais Urbanos , Infecções Estreptocócicas , Streptococcus pyogenes/classificação , Abuso de Substâncias por Via Intravenosa/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/classificação , Antígenos de Bactérias/genética , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/patologia , Proteínas da Membrana Bacteriana Externa/classificação , Proteínas da Membrana Bacteriana Externa/genética , Técnicas de Tipagem Bacteriana , Sangue/microbiologia , Proteínas de Transporte/classificação , Proteínas de Transporte/genética , Criança , Pré-Escolar , Meios de Cultura , Genótipo , Humanos , Lactente , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/mortalidade , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/isolamento & purificação , Abuso de Substâncias por Via Intravenosa/mortalidade , Superantígenos/genética , Reino Unido/epidemiologia
20.
Clin Lab Haematol ; 28(6): 423-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17105498

RESUMO

Although cystic fibrosis (CF) is common, the diagnosis (and subsequent treatment) may be delayed if the presentation is atypical. We present three cases of children with CF who presented with haematological abnormalities. In all cases, they underwent extensive and invasive investigations prior to the diagnosis.


Assuntos
Anemia/etiologia , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Suor/química , Anemia/diagnóstico , Exame de Medula Óssea , Cloretos/análise , Fibrose Cística/genética , Análise Mutacional de DNA , Diagnóstico Diferencial , Insuficiência de Crescimento/etiologia , Feminino , Humanos , Lactente , Masculino
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