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1.
Animals (Basel) ; 11(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34827779

RESUMO

Non-typeable (NT) Staphylococcus aureus strains are associated with chronic bovine mastitis. This study investigates the impact of biofilm formation by clinical NT S. aureus on cytokine production and mammary tissue damage by using a mouse mastitis model. Mice infected with two different NT S. aureus strains with strong and weak biofilm forming potential demonstrated identical clinical symptoms (moderate), minimal inflammatory infiltrates, and tissue damage (level 1 histopathological changes) in the mammary glands. However, the S. aureus load in the mammary glands of mice and the level of pro-inflammatory cytokines (IL-1ß, IL-6, IL-12, IL-17 and IFN-γ) in serum were significantly higher (p ≤ 0.05) in those infected with the strong biofilm forming NT S. aureus strain. The level of IL-6 in sera samples of these mice was extremely high (15,479.9 ± 532 Pg/mL). Furthermore, these mice died in 24h of post infection compared to 30 h in the weak biofilm forming NT S. aureus infected group. The study demonstrates no association between the strength of PIA (polysaccharide intercellular adhesion)-dependent biofilm production by clinical NT S. aureus and mammary gland pathology in a mouse mastitis model. However, the role of biofilm in the virulence of S. aureus advancing the time of mortality in mice warrants further investigation.

2.
Cell Immunol ; 337: 42-47, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30770093

RESUMO

The resurgence of whooping cough reflects novel genetic variants of Bordetella pertussis and inadequate protection conferred by current acellular vaccines (aP). Biofilm is a source of novel vaccine candidates, including membrane protein assembly factor (BamB) and lipopolysaccharide assembly protein (LptD). Responses of BALB/c mice to candidate vaccines included IFN-γ and IL-17a production by spleen and lymph node cells, and serum IgG1 and IgG2a reactive with whole bacteria or aP. Protection was determined using bacterial cultured from lungs of vaccinated mice challenged with virulent B. pertussis. Mice vaccinated with biofilm produced efficient IFN-γ responses and more IL-17a and IgG2a than mice vaccinated with planktonic cells, aP or adjuvant alone. Vaccination with aP produced abundant IgG1 with little IgG2a. Mice vaccinated with aP plus BamB and LptD retained lower bacterial loads than mice vaccinated with aP alone. Whooping cough vaccines formulated with biofilm antigens, including BamB and LptD, may have clinical value.


Assuntos
Bordetella pertussis/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas Acelulares/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antibacterianos/sangue , Antígenos/imunologia , Biofilmes , Modelos Animais de Doenças , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon gama/imunologia , Interleucina-17/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Vacina contra Coqueluche/imunologia , Baço/imunologia , Vacinação/métodos , Coqueluche/imunologia
3.
Med Microbiol Immunol ; 207(1): 3-26, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29164393

RESUMO

Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis. Despite induction of both antibody and cell-mediated immune (CMI) responses by aP and wP vaccines, there has been resurgence of pertussis in many countries in recent years. Possible reasons hypothesised for resurgence have ranged from incompliance with the recommended vaccination programmes with the currently used aP vaccine to infection with a resurged clinical isolates characterised by mutations in the virulence factors, resulting in antigenic divergence with vaccine strain, and increased production of pertussis toxin, resulting in dampening of immune responses. While use of these vaccines provide varying degrees of protection against whooping cough, protection against infection and transmission appears to be less effective, warranting continuation of efforts in the development of an improved pertussis vaccine formulations capable of achieving this objective. Major approaches currently under evaluation for the development of an improved pertussis vaccine include identification of novel biofilm-associated antigens for incorporation in current aP vaccine formulations, development of live attenuated vaccines and discovery of novel non-toxic adjuvants capable of inducing both antibody and CMI. In this review, the potential roles of different accredited virulence factors, including novel biofilm-associated antigens, of B. pertussis in the evolution, formulation and delivery of improved pertussis vaccines, with potential to block the transmission of whooping cough in the community, are discussed.


Assuntos
Antígenos de Bactérias/imunologia , Bordetella pertussis/imunologia , Transmissão de Doença Infecciosa/prevenção & controle , Vacina contra Coqueluche/imunologia , Fatores de Virulência/imunologia , Coqueluche/prevenção & controle , Bordetella pertussis/patogenicidade , Descoberta de Drogas/tendências , Humanos , Vacina contra Coqueluche/isolamento & purificação , Coqueluche/epidemiologia
4.
Biofouling ; 32(9): 1141-1152, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27669900

RESUMO

Whooping cough caused by Bordetella pertussis is increasing in several countries despite high vaccine coverage. One potential reason for the resurgence is the emergence of genetic variants of the bacterium. Biofilm formation has recently been associated with the pathogenesis of B. pertussis. Biofilm formation of 21 Western Australian B. pertussis clinical isolates was investigated. All isolates formed thicker biofilms than the reference vaccine strain Tohama I while retaining susceptibility to ampicillin, erythromycin, azithromycin and streptomycin. When two biofilm-forming clinical isolates were compared with Tohama I, minimum bactericidal concentrations of antimicrobial agents increased. Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis revealed significant differences in protein expression in B. pertussis biofilms, providing an opportunity for identification of novel biofilm-associated antigens for incorporation in current pertussis vaccines to improve their protective efficacy. The study also highlights the importance of determining antibiograms for biofilms to formulate improved antimicrobial therapeutic regimens.

5.
BMC Infect Dis ; 14: 408, 2014 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-25047665

RESUMO

BACKGROUND: Cervical cancer is the most common female cancer in Bhutan, the first low/middle-income country to implement a national human papillomavirus (HPV) vaccination programme. METHODS: To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2,505 women aged 18-69 years from the general population, and biopsies from 211 cervical intraepithelial neoplasia grade 3 (CIN3) and 112 invasive cervical cancer (ICC) cases. Samples were tested for HPV using GP5+/6+ PCR. RESULTS: Among the general population, HPV prevalence was 26%, being highest (33%) in women ≤24 years, but remaining above 15% in all age-groups. Determinants of HPV included age, marital status, and number of sexual partners. Among the eight percent with cytological abnormalities, 24 CIN3 and 4 ICC were histologically confirmed. Even after additional testing with a sensitive E7 PCR, no infections with vaccine-targeted HPV types were detected in the few vaccinated women (n = 34) compared to 6% prevalence in unvaccinated women of similar age (p = 0 · 215). CONCLUSION: Based upon type-specific prevalence among biopsies, at least 70% of ICC in Bhutan are theoretically preventable by HPV16/18 vaccination, but screening programmes should be expanded among older women, who have an important underlying burden of CIN3 and ICC.


Assuntos
Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Adolescente , Adulto , Idoso , Butão/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Prevalência , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
6.
Helicobacter ; 19(1): 69-73, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24102940

RESUMO

BACKGROUND: Bhutan is small mountainous country bordering India and China and consists of four geographic regions, west, east, central, and south. The epidemiology of Helicobacter pylori infection and risk factors associated with in Bhutan are not previously studied. The World Health Organization reported the incidence of stomach cancer to be very high in Bhutan. AIM: We conducted a cross-sectional study to determine the seroepidemiologic pattern of H. pylori among Bhutanese from the four regions with emphasis on water source and household sanitation. METHODS: Between June and November 2012, blood samples from patients with complaints of dyspepsia were collected after obtaining an informed consent. Demographic information, occupation, family size living in the same household, consumption of betel nut, and aspects of household environment including type of latrines, source of drinking water were collected. All serum samples were tested for H. pylori immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA) using MAGIWELL ELISA kit from United Biotech, USA. RESULTS: Two hundred and forty-four patients between 17 and 75 years of age participated in the study, of them, 102 were men, and the mean age was 38 (±14.2) years. The overall prevalence of H. pylori among patients was 86% with no difference between men and women (90 vs 83%, respectively, p = .12). The prevalence was almost identical among all age groups: 81% at 17-20, 84% at 20-29, 93% at 30-39, 82% at 40-49, 87% at 50-59, and 82% at ≥60 years (p = .51). H. pylori prevalence was lower in the southern region of Bhutan (78%) compared with the central region (97%) (OR = 8.6; 95% CI = 1.1-55; p = .02), eastern region (91%) (OR = 2.7; 95% CI = 1.1-7.2, p = .004) or the western region (83%) (OR = 1.4, 95% CI = 0.8-3.1, p = .07). The prevalence of H. pylori was significantly lower among household with less than 4 persons living in the same household. Source of drinking water, type of occupation, type of latrines, or consumption of betel nut showed no association with H. pylori prevalence. Logistic regression analysis revealed that residing region was the only significant variable. CONCLUSIONS: The high prevalence of antibodies to H. pylori among patients and in all groups could contribute to the high incident rate of gastric cancer in Bhutan. Crowded living condition and the residing region contribute to the variation of the prevalence of the infection. The lowest prevalence in southern part of the country could be due to the difference in the ethnicity as most of its population is of Indian and Nepal origin. Further data regarding H. pylori in Bhutan are critical to developing surveillance and prevention strategies for gastric cancer.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Butão/epidemiologia , Estudos Transversais , Aglomeração , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Topografia Médica , Adulto Jovem
7.
BMC Infect Dis ; 13: 35, 2013 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-23347339

RESUMO

BACKGROUND: Knowledge on antimicrobial drug resistance and genetic characteristics of Neisseria gonorrhoeae isolates circulating in India, Pakistan, and Bhutan is sorely lacking. In this paper, we describe the prevalence of antimicrobial resistance and molecular characteristics of N. gonorrhoeae isolates from India, Pakistan, and Bhutan in 2007-2011. METHODS: Antimicrobial susceptibility and ß-lactamase production were tested for 65 N. gonorrhoeae isolates from India (n=40), Pakistan (n=18) and Bhutan (n=7) using Etest methodology (eight antimicrobials) and nitrocefin solution, respectively. Resistance determinants, i.e. penA, mtrR, porB1b, gyrA, and parC, were sequenced. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology. RESULTS: The highest resistance level was observed for ciprofloxacin (94%), followed by penicillin G (68%), erythromycin (62%), tetracycline (55%), and azithromycin (7.7%). All the isolates were susceptible to ceftriaxone, cefixime, and spectinomycin. Thirty-four (52%) of the isolates were producing ß-lactamase. No penA mosaic alleles or A501-altered alleles of penicillin-binding protein 2 were identified. Forty-nine NG-MAST STs were identified, of which 42 STs have not been previously described worldwide. CONCLUSIONS: Based on this study, ceftriaxone, cefixime, and spectinomycin can be used as an empirical first-line therapy for gonorrhoea in India, Pakistan, and Bhutan, whereas ciprofloxacin, penicillin G, tetracycline, erythromycin, and azithromycin should not be. It is imperative to strengthen the laboratory infrastructure in this region, as well as to expand the phenotypic and genetic surveillance of antimicrobial resistance, emergence of new resistance, particularly, to extended-spectrum cephalosporins, and molecular epidemiology.


Assuntos
Antibacterianos/farmacologia , Gonorreia/epidemiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Alelos , Butão/epidemiologia , Farmacorresistência Bacteriana/genética , Feminino , Genes Bacterianos , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/isolamento & purificação , Paquistão/epidemiologia
8.
Microb Drug Resist ; 17(1): 109-19, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21117966

RESUMO

A total of 83 Acinetobacter baumannii isolates from patients attending a tertiary care university hospital in Thailand were investigated for their clonal relatedness, antimicrobial susceptibility profiles, and integron carriage. Susceptibility profiles showed that 56 (67%) of these isolates exhibited multiple drug resistance (MDR). Pulsed-field gel electrophoresis (PFGE) showed that 73% of these resistant isolates were clustered into three predominant PFGE types: 6, 7, and 36. This suggested that the high number of isolates exhibiting MDR phenotypes observed in the hospital is, to some extent, due to the spread of these three resistant clones. Class 1 integrase genes were detected in all MDR isolates belonging to PFGE type 6, most MDR isolates belonging to PFGE type 7 and none of the isolates belonging to PFGE type 36. Five different class 1 gene cassette arrays, dfrA1-orfC, bla(IMP-14)-aac6', aacA4- catB8-aadA1, aacC1-orfX-orfX'-aadA1a, and aacC1-orfX-orfX-orfX'-aadA1a, were identified, of which the bla(IMP-14)-aac6' array has only been found in Thai isolates. Two isolates identified in this study carried a class 2 integrase gene with a 2.2 kb cassette array containing aadA1-sat-dfrA1.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Clonagem Molecular , Farmacorresistência Bacteriana Múltipla/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Hospitais Universitários , Humanos , Lactente , Integrases/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tailândia/epidemiologia , Adulto Jovem
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