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1.
PLoS One ; 16(10): e0258500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644359

RESUMO

Chlamydial infections, caused by a group of obligate, intracellular, gram-negative bacteria, have health implications for animals and humans. Due to their highly infectious nature and zoonotic potential, staff at wildlife rehabilitation centers should be educated on the clinical manifestations, prevalence, and risk factors associated with Chlamydia spp. infections in raptors. The objectives of this study were to document the prevalence of chlamydial DNA shedding and anti-chlamydial antibodies in raptors admitted to five wildlife rehabilitation centers in California over a one-year period. Chlamydial prevalence was estimated in raptors for each center and potential risk factors associated with infection were evaluated, including location, species, season, and age class. Plasma samples and conjunctiva/choana/cloaca swabs were collected for serology and qPCR from a subset of 263 birds of prey, representing 18 species. Serologic assays identified both anti-C. buteonis IgM and anti-chlamydial IgY antibodies. Chlamydial DNA and anti-chlamydial antibodies were detected in 4.18% (11/263) and 3.14% (6/191) of patients, respectively. Chamydial DNA was identified in raptors from the families Accipitridae and Strigidae while anti-C.buteonis IgM was identified in birds identified in Accipitridae, Falconidae, Strigidae, and Cathartidae. Two of the chlamydial DNA positive birds (one Swainson's hawk (Buteo swainsoni) and one red-tailed hawk (Buteo jamaicensis)) were necropsied, and tissues were collected for culture. Sequencing of the cultured elementary bodies revealed a chlamydial DNA sequence with 99.97% average nucleotide identity to the recently described Chlamydia buteonis. Spatial clusters of seropositive raptors and raptors positive for chlamydial DNA were detected in northern California. Infections were most prevalent during the winter season. Furthermore, while the proportion of raptors testing positive for chlamydial DNA was similar across age classes, seroprevalence was highest in adults. This study questions the current knowledge on C. buteonis host range and highlights the importance of further studies to evaluate the diversity and epidemiology of Chlamydia spp. infecting raptor populations.


Assuntos
Doenças das Aves/epidemiologia , Infecções por Chlamydia/epidemiologia , Chlamydia/isolamento & purificação , Aves Predatórias/microbiologia , Animais , Animais Selvagens , Anticorpos Antibacterianos/sangue , Doenças das Aves/imunologia , Doenças das Aves/microbiologia , California/epidemiologia , Chlamydia/classificação , Chlamydia/genética , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Cloaca/microbiologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Imunoglobulina M/sangue , Imunoglobulinas/sangue , Filogenia , Prevalência , Centros de Reabilitação , Fatores de Risco , Análise de Sequência de DNA
2.
Nat Commun ; 12(1): 5454, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526512

RESUMO

Chlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis resulting in infertility by using a female mouse genital tract chlamydial infection model. We find the chlamydial parasitophorous vacuole protein CT135 triggers NLRP3 inflammasome activation via TLR2/MyD88 signaling as a pathogenic strategy to evade neutrophil host defense. Paradoxically, a consequence of CT135 mediated neutrophil killing results in a submucosal macrophage-associated endometritis driven by ATP/P2X7R induced NLRP3 inflammasome activation. Importantly, macrophage-associated immunopathology occurs independent of macrophage infection. We show chlamydial infection of neutrophils and epithelial cells produce elevated levels of extracellular ATP. We propose this source of ATP serves as a DAMP to activate submucosal macrophage NLRP3 inflammasome that drive damaging immunopathology. These findings offer a paradigm of sterile inflammation in infectious disease pathogenesis.


Assuntos
Infecções por Chlamydia/imunologia , Chlamydia/imunologia , Inflamação/imunologia , Células Mieloides/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Neutrófilos/imunologia , Receptores Purinérgicos P2X7/imunologia , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Chlamydia/fisiologia , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/microbiologia , Modelos Animais de Doenças , Feminino , Células HeLa , Interações Hospedeiro-Patógeno/imunologia , Humanos , Evasão da Resposta Imune/imunologia , Inflamação/metabolismo , Inflamação/microbiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/metabolismo , Células Mieloides/microbiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo
3.
Infect Immun ; 89(10): e0020521, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34227838

RESUMO

Chlamydia is known to both ascend to the upper genital tract and spread to the gastrointestinal tract following intravaginal inoculation. Gastrointestinal Chlamydia was recently reported to promote chlamydial pathogenicity in the genital tract since mice intravaginally inoculated with an attenuated Chlamydia strain, which alone failed to develop pathology in the genital tract, were restored to develop hydrosalpinx by intragastric coinoculation with wild-type Chlamydia. Gastrointestinal Chlamydia promoted hydrosalpinx via an indirect mechanism since Chlamydia in the gut did not directly spread to the genital tract lumen. In the current study, we further investigated the role of CD8+ T cells in the promotion of hydrosalpinx by gastrointestinal Chlamydia. First, we confirmed that intragastric coinoculation with wild-type Chlamydia promoted hydrosalpinx in mice that were inoculated with an attenuated Chlamydia strain in the genital tract 1 week earlier. Second, the promotion of hydrosalpinx by intragastrically coinoculated Chlamydia was blocked by depleting CD8+ T cells. Third, adoptive transfer of gastrointestinal Chlamydia-induced CD8+ T cells was sufficient for promoting hydrosalpinx in mice that were intravaginally inoculated with an attenuated Chlamydia strain. These observations have demonstrated that CD8+ T cells induced by gastrointestinal Chlamydia are both necessary and sufficient for promoting hydrosalpinx in the genital tract. The study has laid a foundation for further revealing the mechanisms by which Chlamydia-induced T lymphocyte responses (as a 2nd hit) promote hydrosalpinx in mice with genital Chlamydia-triggered tubal injury (as a 1st hit), a continuing effort in testing the two-hit hypothesis as a chlamydial pathogenic mechanism.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Chlamydia/imunologia , Chlamydia/patogenicidade , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Genitália Feminina/imunologia , Infecções do Sistema Genital/imunologia , Transferência Adotiva/métodos , Animais , Linfócitos T CD8-Positivos/microbiologia , Linhagem Celular Tumoral , Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Modelos Animais de Doenças , Feminino , Genitália Feminina/microbiologia , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos CBA , Infecções do Sistema Genital/microbiologia
5.
Methods Mol Biol ; 2183: 19-28, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959238

RESUMO

Chlamydia trachomatis is one of the most prevalent sexually transmitted infectious agents in the world and the leading cause of infectious blindness. The role of antibodies in the prevention and clearance of infection is still not fully understood, but the analysis of the immunoglobulin response to novel vaccine candidates is an important part of many of these studies. In this chapter, we describe a novel method to identify and isolate Chlamydia-specific memory B cells by fluorescence-activated cell sorting (FACS) using fluorescently labeled whole bacteria from cryopreserved human PBMC samples. This method allows for live single cells to be sorted for cell culture, in vitro assays, single-cell RNA sequencing, and cloning of paired heavy and light chains for recombinant monoclonal antibody production.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Especificidade de Anticorpos/imunologia , Antígenos de Bactérias/imunologia , Chlamydia/imunologia , Sondas Moleculares , Anticorpos Antibacterianos/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Vacinas Bacterianas/imunologia , Criopreservação , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Memória Imunológica , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo
6.
Comp Immunol Microbiol Infect Dis ; 73: 101557, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33065404

RESUMO

Chlamydiosis is caused by an obligate intracellular gram-negative bacterium of the genus Chlamydophila which is a zoonotic pathogen. The objectives of the study were to identify the seroprevalence of antibodies against Chlamydophila abortus in dromedary camel herds from four districts in eastern Algeria, as well as to estimate the association between seroprevalence and certain factors present at the animal and herd levels. Blood samples were collected from a random sample of animals within each of 82 camel herds. Serum samples were subjected to a C. abortus ELISA test, and association between the presence of antibodies and potential risk factors was estimated. Animal and herd seroprevalence were 2.5 % and 15.8 %, respectively, indicating substantial exposure of camels to C. abortus in the four districts studied. Age, breed, and sex did not influence seroprevalence in tested animals. Based on the univariate analysis, contact with sheep and goats, contact with other camel herds, and histories of abortion were major risk factors for infection. By using multivariate analysis, contact of camels with sheep and goats and with others camel herds, through shared grazing or watering points, were important factors for transmission of chlamydiosis with an odds ratio of 3.3 and 9.4, respectively. At the herd level the introduction of purchased animals was the major risk factor. This baseline information will be highly useful for launching C. abortus control programs in the region and potentially elsewhere.


Assuntos
Anticorpos Antibacterianos/sangue , Camelus , Infecções por Chlamydia/veterinária , Chlamydia , Argélia/epidemiologia , Animais , Chlamydia/imunologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Masculino , Fatores de Risco , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Ovinos
7.
Pathog Dis ; 78(6)2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32804203

RESUMO

Chlamydia suis intestinal infection of single-animal experimental groups of gnotobiotic newborn piglets was previously reported to cause severe, temporary small intestinal epithelium damage. We investigated archived intestinal samples for pro-inflammatory nuclear factor kappa B (NF-κB) activation, Interleukin (IL)-6 and IL-8 production and immune cell influx. Samples were collected 2, 4 and 7 days post-inoculation with C. suis strain S45/6 or mock inoculum (control). Increased nuclear localization of epithelial NF-κB, representative of activation, in the jejunum and ileum of C. suis-infected animals, compared to uninfected controls, began by 2 days post-infection (dpi) and persisted through 7 dpi. Infected animals showed increased production of IL-8, peaking at 2 dpi, compared to controls. Infection-mediated CD45-positive immune cell influx into the jejunal lamina propria peaked at 7 dpi, when epithelial damage was largely resolved. Activation of NF-κB appears to be a key early event in the innate response of the unprimed porcine immune system challenged with C. suis. This results in an acute phase, coinciding with the most severe clinical symptoms, diarrhea and weight loss. Immune cells recruited shortly after infection remain present in the lamina propria during the recovery phase, which is characterized by reduced chlamydial shedding and restored intestinal epithelium integrity.


Assuntos
Infecções por Chlamydia/veterinária , Chlamydia/imunologia , Mucosa Intestinal/imunologia , NF-kappa B/metabolismo , Doenças dos Suínos/microbiologia , Animais , Infecções por Chlamydia/imunologia , Diarreia/microbiologia , Fezes/microbiologia , Vida Livre de Germes , Interações Hospedeiro-Patógeno , Imunidade Celular , Imuno-Histoquímica , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Intestinal/microbiologia , Modelos Animais , Suínos , Doenças dos Suínos/imunologia
8.
Nanomedicine ; 29: 102257, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32610072

RESUMO

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.


Assuntos
Imunidade Adaptativa/genética , Proteínas da Membrana Bacteriana Externa/genética , Nanopartículas/química , Vacinas/imunologia , Imunidade Adaptativa/imunologia , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Antígenos CD4/química , Antígenos CD4/imunologia , Chlamydia/genética , Chlamydia/imunologia , Chlamydia/patogenicidade , Células Dendríticas/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Receptores de Hialuronatos/química , Receptores de Hialuronatos/imunologia , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Selectina L/química , Selectina L/imunologia , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Linfócitos T/imunologia , Vacinas/genética
9.
Sci Rep ; 10(1): 10152, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576914

RESUMO

Chlamydia infection and disease are endemic in free-ranging koalas. Antibiotics remain the front line treatment for Chlamydia in koalas, despite their rates of treatment failure and adverse gut dysbiosis outcomes. A Chlamydia vaccine for koalas has shown promise for replacing antibiotic treatment in mild ocular Chlamydia disease. In more severe disease presentations that require antibiotic intervention, the effect of vaccinating during antibiotic use is not currently known. This study investigated whether a productive immune response could be induced by vaccinating koalas during antibiotic treatment for Chlamydia-induced cystitis. Plasma IgG antibody levels against the C. pecorum major outer membrane protein (MOMP) dropped during antibiotic treatment in both vaccinated and unvaccinated koalas. Post-treatment, IgG levels recovered. The IgG antibodies from naturally-infected, vaccinated koalas recognised a greater proportion of the MOMP protein compared to their naturally-infected, unvaccinated counterparts. Furthermore, peripheral blood mononuclear cell gene expression revealed an up-regulation in genes related to neutrophil degranulation in vaccinated koalas during the first month post-vaccination. These findings show that vaccination of koalas while they are being treated with antibiotics for cystitis can result in the generation of a productive immune response, in the form of increased and expanded IgG production and host response through neutrophil degranulation.


Assuntos
Antibacterianos/uso terapêutico , Formação de Anticorpos , Vacinas Bacterianas/imunologia , Infecções por Chlamydia , Chlamydia/imunologia , Cistite/microbiologia , Cistite/terapia , Imunoglobulina G/sangue , Phascolarctidae/imunologia , Vacinação , Animais , Antibacterianos/efeitos adversos , Proteínas da Membrana Bacteriana Externa/imunologia , Degranulação Celular/genética , Cistite/imunologia , Feminino , Masculino , Neutrófilos/imunologia , Neutrófilos/fisiologia
10.
Expert Rev Vaccines ; 18(12): 1323-1337, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31773996

RESUMO

Background: Vaccine-development research is proliferating making it difficult to determine the most promising vaccine candidates. Exemplary of this problem is vaccine development against Chlamydia, a pathogen of global public health and financial importance.Methods: We systematically extracted data from studies that included chlamydial load or host immune parameter measurements, estimating 4,453 standardized effect sizes between control and chlamydial immunization experimental groups.Results: Chlamydial immunization studies most often used (78%) laboratory mouse models. Depending on chlamydial species, single and multiple recombinant protein, viral and bacterial vectors, dendritic transfer, and dead whole pathogen were most effective at reducing chlamydial load. Immunization-driven decrease in chlamydial load was associated with increases in IFNg, IgA, IgG1, and IgG2a. Using data from individual studies, the magnitude of IgA and IgG2a increase was correlated with chlamydial load reduction. IFNg also showed this pattern for C. trachomatis, but not for C. muridarum. We also reveal the chlamydial vaccine development field to be highly bias toward studies showing these effects, limiting lessons learned from negative results.Conclusions: Most murine immunizations against Chlamydia reduced chlamydial load and increased host immune parameters. These methods are novel for vaccine development and are critical in identifying trends where large quantities of literature exist.


Assuntos
Vacinas Bacterianas/imunologia , Vacinas Bacterianas/isolamento & purificação , Infecções por Chlamydia/prevenção & controle , Chlamydia/imunologia , Desenvolvimento de Medicamentos/métodos , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Vacinas Bacterianas/administração & dosagem , Modelos Animais de Doenças , Desenvolvimento de Medicamentos/tendências , Interferon gama/metabolismo , Camundongos , Resultado do Tratamento
11.
Vaccine ; 37(36): 5428-5438, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31375438

RESUMO

MIP and CPAF from Chlamydia have been shown to be effective in inducing immune responses important in clearing chlamydial infections. This study evaluates the protection conferred by MIP and CPAF as novel vaccines in pregnant C. abortus challenged ewes. Fifty C. abortus sero-negative sheep were randomly allocated into 5 groups of 10 according to the treatment they were to receive (1) 100 µg of MBP-MIP (2) 100 µg CPAF (3) 50 µg MBP-MIP and 50 µg CPAF (4) Tris-buffer (negative control) (5) Enzovax (positive control). Booster inoculations were administered 3 weeks after primary inoculations. Blood samples were taken pre-vaccination and weekly for 5 weeks. Five months after vaccination the ewes were mated. Pregnant ewes were then challenged on day 90 of gestation. Blood samples taken at four time-points post challenge were analysed for IFNγ levels, TNFα and IL-10 expression and anti-chlamydial antibody levels. Vaginal swabs, placental and foetal tissue and bacterial shedding were analysed using qPCR to quantify levels of C. abortus. Enzovax was 100% effective with no abortions occurring. The MIP/CPAF combined vaccine offered the greatest protection of the novel vaccines with 67% of ewes giving birth to one or more live lambs equating to a 50% vaccine efficacy rate. MIP and CPAF administered singly did not confer protection. Enzovax and MIP/CPAF vaccinated ewes had longer gestations and lambs with higher birth weights than negative control ewes. Aborting ewes shed higher numbers of C. abortus than ewes that had live lambs, all vaccinated ewes demonstrated lower levels of bacterial shedding than negative control ewes with Enzovax ewes shedding significantly fewer bacteria. Ewes that went on to abort had significantly higher levels of IFNγ and IL-10 at day 35 post challenge and significantly higher levels of anti-chlamydial antibodies at 24 h post lambing compared to ewes that had live lambs.


Assuntos
Infecções por Chlamydia/imunologia , Infecções por Chlamydia/prevenção & controle , Chlamydia/imunologia , Chlamydia/patogenicidade , Endopeptidases/imunologia , Vacinação/métodos , Aborto Animal/prevenção & controle , Animais , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Endopeptidases/metabolismo , Feminino , Gravidez , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/prevenção & controle
12.
Lancet Infect Dis ; 19(10): 1091-1100, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31416692

RESUMO

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 µg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 µg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Vacinas Bacterianas/imunologia , Infecções por Chlamydia/prevenção & controle , Chlamydia/imunologia , Imunogenicidade da Vacina , Lipossomos/administração & dosagem , Vacinação/métodos , Administração Intranasal , Adulto , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/uso terapêutico , Infecções por Chlamydia/microbiologia , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Esquemas de Imunização , Injeções Intramusculares , Londres , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
13.
Vet Immunol Immunopathol ; 213: 109887, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307668

RESUMO

Chlamydia abortus produces ovine enzootic abortion (OEA). Symptoms are not observed until the organism colonises the placenta, eventually causing abortion. Infected animals become carriers and will shed the organism in the following oestruses. This process suggests that sex hormones might play an important role in the physiopathology of OEA, affecting the success of chlamydial clearance and also jeopardising the effectiveness of vaccination. However, the mechanisms through which sex hormones are involved in chlamydial pathogenicity remain unclear. The aim of this study, therefore, was to determine the effect of progesterone on the immune response against C. abortus and on the protection conferred by an experimental inactivated vaccine in sheep. Eighteen sheep were ovariectomised and divided into four groups: vaccinated and progesterone-treated (V-PG), vaccinated and non-treated (V-NT), non-vaccinated and non-treated (NV-NT) and non-vaccinated and progesterone-treated sheep (NV-PG). Animals from both PG groups were treated with commercial medroxyprogesterone acetate impregnated intravaginal sponges before and during the vaccination (V-PG) or just before challenge (NV-PG). The animals from both V groups were subcutaneously immunised with an experimental inactivated vaccine, which was seen to confer high protection in previous studies. All sheep were challenged intratracheally with C. abortus strain AB7 and were sacrificed on day 8 post-infection. Morbidity was measured as the variation in rectal temperature and samples of sera were collected for antibody and cytokine (IFN-γ and IL-10) analysis by commercial ELISA. In addition, lung and lymph node samples were collected for chlamydial detection by qPCR and for histopathological and immunohistochemical analyses. Sheep from the V-PG group showed less severe or no lesions and lower morbidity than the other groups. They also had the highest abundance of regulatory T-cells. The sheep from V-NT also manifested high antibody levels against C. abortus and less severe lesions than those observed in non-vaccinated sheep, which showed high morbidity, low antibody levels and severe lesions, especially in NV-NT. These results confirm the effectiveness of the experimental vaccine employed and suggest that progesterone could enhance the effect.


Assuntos
Vacinas Bacterianas/uso terapêutico , Infecções por Chlamydia/veterinária , Imunidade Humoral , Progesterona/administração & dosagem , Doenças dos Ovinos/imunologia , Aborto Animal/imunologia , Aborto Animal/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ovinos , Doenças dos Ovinos/microbiologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
14.
Pathog Dis ; 77(3)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201421

RESUMO

Serological assays can be used to investigate the population burden of infection and potentially sequelae from Chlamydia. We investigated the PGP3 ELISA as a sero-epidemiological tool for infection or sub-fertility in Australian and Samoan women. The PGP3 ELISA absorbance levels were compared between groups of women with infertility, fertile, and current chlamydial infections. In the Australian groups, women with chlamydial tubal factor infertility had significantly higher absorbance levels in the PGP3 ELISA compared to fertile women (P < 0.0001), but not when compared to women with current chlamydial infection (P = 0.44). In the Samoan study, where the prevalence of chlamydial infections is much higher there were significant differences in the PGP3 ELISA absorbance levels between chlamydial sub-fertile women and fertile women (P = 0.003). There was no difference between chlamydial sub-fertile women and women with a current infection (P = 0.829). The results support that the PGP3 assay is effective for sero-epidemiological analysis of burden of infection, but not for evaluation of chlamydial pathological sequelae such as infertility.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Chlamydia/diagnóstico , Chlamydia/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Monitoramento Epidemiológico , Testes Sorológicos/métodos , Adolescente , Adulto , Austrália/epidemiologia , Infecções por Chlamydia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Samoa/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem
15.
PLoS One ; 14(1): e0210245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615687

RESUMO

Chlamydia pecorum is responsible for causing ocular infection and disease which can lead to blindness in koalas (Phascolarctos cinereus). Antibiotics are the current treatment for chlamydial infection and disease in koalas, however, they can be detrimental for the koala's gastrointestinal tract microbiota and in severe cases, can lead to dysbiosis and death. In this study, we evaluated the therapeutic effects provided by a recombinant chlamydial major outer membrane protein (MOMP) vaccine on ocular disease in koalas. Koalas with ocular disease (unilateral or bilateral) were vaccinated and assessed for six weeks, evaluating any changes to the conjunctival tissue and discharge. Samples were collected pre- and post-vaccination to evaluate both humoral and cell-mediated immune responses. We further assessed the infecting C. pecorum genotype, host MHC class II alleles and presence of koala retrovirus type (KoRV-B). Our results clearly showed an improvement in the clinical ocular disease state of all seven koalas, post-vaccination. We observed increases in ocular mucosal IgA antibodies to whole C. pecorum elementary bodies, post-vaccination. We found that systemic cell-mediated immune responses to interferon-γ, interleukin-6 and interleukin-17A were not significantly predictive of ocular disease in koalas. Interestingly, one koala did not have as positive a clinical response (in one eye primarily) and this koala was infected with a C. pecorum genotype (E') that was not used as part of the vaccine formula (MOMP genotypes A, F and G). The predominant MHC class II alleles identified were DAb*19, DAb*21 and DBb*05, with no two koalas identified with the same genetic sequence. Additionally, KoRV-B, which is associated with chlamydial disease outcome, was identified in two (29%) ocular diseased koalas, which still produced vaccine-induced immune responses and clinical ocular improvements post-vaccination. Our findings show promise for the use of a recombinant chlamydial MOMP vaccine for the therapeutic treatment of ocular disease in koalas.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/administração & dosagem , Infecções por Chlamydia/veterinária , Chlamydia/imunologia , Oftalmopatias/prevenção & controle , Phascolarctidae/imunologia , Proteínas Recombinantes/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Chlamydia/genética , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/prevenção & controle , Oftalmopatias/epidemiologia , Oftalmopatias/microbiologia , Feminino , Masculino , Phascolarctidae/microbiologia , Vacinação
16.
Vaccine ; 37(50): 7419-7426, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29680200

RESUMO

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women's reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N. gonorrhoeae infections occur annually and the greatest disease burden is carried by low- and middle-income countries (LMIC). Current control measures are clearly inadequate and threatened by the rapid emergence of antibiotic resistance. The gonococcus now holds the status of "super-bug" as there is currently no single reliable monotherapy for empirical treatment of gonorrhea. The problem of antibiotic resistance has elevated treatment costs and necessitated the establishment of large surveillance programs to track the spread of resistant strains. Here we review the need for a gonorrhea vaccine with respect to global disease burden and related socioeconomic and treatment costs, with an emphasis on the impact of gonorrhea on women and newborns. We also highlight the challenge of estimating the impact of a gonorrhea vaccine due to the need for more data on the burden of gonococcal pelvic inflammatory disease and related sequelae and of gonorrhea-associated adverse pregnancy outcomes and the problem of empirical diagnosis and treatment of STIs in LMIC. There is also a lack of clinical and basic science research in the area of gonococcal/chlamydia coinfection, which occurs in a high percentage of individuals with gonorrhea and should be considered when testing the efficacy of gonorrhea vaccines. Finally, we review recent research that suggests a gonorrhea vaccine is feasible and discuss challenges and research gaps in gonorrhea vaccine development.


Assuntos
Vacinas Bacterianas/biossíntese , Infecções por Chlamydia/prevenção & controle , Gonorreia/prevenção & controle , Doença Inflamatória Pélvica/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Antibacterianos/farmacologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/economia , Chlamydia/efeitos dos fármacos , Chlamydia/imunologia , Chlamydia/patogenicidade , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Coinfecção , Farmacorresistência Bacteriana Múltipla , Feminino , Gonorreia/epidemiologia , Gonorreia/imunologia , Gonorreia/microbiologia , Humanos , Masculino , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/imunologia , Neisseria gonorrhoeae/patogenicidade , Doença Inflamatória Pélvica/epidemiologia , Doença Inflamatória Pélvica/imunologia , Doença Inflamatória Pélvica/microbiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/microbiologia , Saúde Pública/economia , Saúde Pública/estatística & dados numéricos , Fatores Socioeconômicos
17.
Sex Transm Dis ; 46(3): 153-158, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30383619

RESUMO

INTRODUCTION: Gonorrhea and chlamydia (GC/CT) testing falls below recommended rates for people living with HIV (PLWH) in routine care. Despite evidence that homelessness and unstable housing (HUH) negatively impacts clinical outcomes for PLWH, little is known about GC/CT screening for HUH-PLWH in routine care. METHODS: Using an observational cohort of PLWH establishing care at a large publicly funded HIV clinic in San Francisco between February 2013 and December 2014 and with at least 1 primary care visit (PCV) before February 2016, we assessed GC/CT testing for HUH (staying outdoors, in shelters, in vehicles, or in places not made for habitation in the last year) compared with stably housed patients. We calculated (1) the odds of having GC/CT screening at a PCV using logistic regression with random effects to handle intrasubject correlations and (2) the percent of time enrolled in clinical care in which patients had any GC/CT testing ("time in coverage") based on 180-day periods and using linear regression modeling. RESULTS: Of 323 patients, mean age was 43 years, 92% were male, 52% were non-Latino white, and 46% were HUH. Homeless and unstably housed PLWH had 0.66 odds of GC/CT screening at a PCV than did stably housed patients (95% confidence interval, 0.44-0.99; P = 0.043). Time in coverage showed no difference by housing status (regression coefficient, -0.93; 95% confidence interval, -8.02 to 6.16; P = 0.80). CONCLUSIONS: Homeless and unstably housed PLWH had 34% lower odds of GC/CT screening at a PCV, demonstrating a disparity in routine care provision, but similar time in coverage. More research is needed to effectively increase GC/CT screening among HUH-PLWH.


Assuntos
Infecções por Chlamydia/diagnóstico , Gonorreia/diagnóstico , Infecções por HIV/patologia , Disparidades em Assistência à Saúde , Habitação , Programas de Rastreamento/métodos , Atenção Primária à Saúde , Adulto , Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Feminino , Seguimentos , Gonorreia/microbiologia , Pessoas em Situação de Rua , Humanos , Masculino , Pessoa de Meia-Idade , Neisseria gonorrhoeae/imunologia , Estudos Retrospectivos , São Francisco , Fatores Socioeconômicos
18.
Vector Borne Zoonotic Dis ; 18(12): 677-682, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30251925

RESUMO

Chlamydia suis is a swine pathogen that causes economic losses due to reproductive failure. Recently, C. suis has been detected in human eyes. However, knowledge of the zoonotic potential is still limited. C. suis infections in swine could present a risk for public health because (1) tetracycline-resistant C. suis strains are emerging in the pork industry, (2) tetracycline resistance gene transfers in vitro from C. suis to the human pathogen Chlamydia trachomatis and as previously demonstrated, (3) C. suis and C. trachomatis can be both present in the human eye. Pig farmers were sampled during a seminar in West-Flanders. Conjunctival swabs for detection of C. suis and C. trachomatis and for the detection of mucosal antibodies against C. suis and C. trachomatis were collected. The farmers completed a questionnaire designed to assess information on the following: (1) the health status of their pigs, (2) administration of veterinary drugs, (3) their professional and nonprofessional activities, (4) general health status, (5) smoking habits, (6) use of medication, (7) allergies, and (8) clinical signs/history. Thirty-three on 40 (82.5%) farmers participated. None of the conjunctival swabs contained C. trachomatis DNA and mucosal antibodies against C. trachomatis were not detected. Six of 33 (18.2%) farmers had C. suis DNA in their eyes and 22 of 33 (67%) swabs contained C. suis-specific mucosal antibodies. The older the farmer, higher the chance of finding C. suis antibodies in the eye. There was a significant correlation between the presence of conjunctivitis in the pigs and the occurrence of C. suis DNA in the eye of their owner. This study shows that C. suis may transfer from pigs to the human eye as specific mucosal antibodies were detected in conjunctivae of pig farmers. Veterinarians, general practitioners, and occupational physicians should be aware of the zoonotic potential of C. suis.


Assuntos
Infecções por Chlamydia/microbiologia , Chlamydia , Olho/microbiologia , Doenças dos Suínos/microbiologia , Animais , Anticorpos Antibacterianos/isolamento & purificação , Chlamydia/genética , Chlamydia/imunologia , DNA Bacteriano/isolamento & purificação , Fazendeiros , Humanos , Suínos , Zoonoses
19.
Schweiz Arch Tierheilkd ; 160(7-8): 475-480, 2018 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-29989555

RESUMO

INTRODUCTION: In a farrowing farm 2 first parity sows aborted on day 95 and day 110 of gestation due to an infection with leptospira and chlamydia. The double infection was diagnosed by PCR examination of abortion material. Serum samples of both sows and additional 8 sows taken three weeks after abortions were sent to two different labs for serological examination for antibodies against leptospira and chlamydia using a microagglutination test and a complement fixation test, respectively. In both labs the tests for antibodies against chlamydia were negative. Titers against diverse leptospira serovars varied between both labs and were low, so that they were not indicative for the involvement of the two pathogens regarding abortion. This case report indicates the diagnostic difficulties of direct and indirect detection methods for leptospira and chlamydia to assess the impact of these pathogens on observed reproductive failure.


Assuntos
Aborto Animal/microbiologia , Infecções por Chlamydia/veterinária , Leptospirose/veterinária , Doenças dos Suínos/diagnóstico , Testes de Aglutinação , Animais , Anticorpos Antibacterianos/sangue , Chlamydia/imunologia , Infecções por Chlamydia/sangue , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/veterinária , Testes de Fixação de Complemento , Feminino , Leptospira/imunologia , Leptospirose/sangue , Leptospirose/diagnóstico , Leptospirose/microbiologia , Reação em Cadeia da Polimerase , Gravidez , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/microbiologia
20.
Vaccine ; 36(25): 3593-3598, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29759381

RESUMO

BACKGROUND: The live, temperature-attenuated vaccine strain 1B of Chlamydia abortus, the aetiological agent of ovine enzootic abortion (OEA), has been implicated in cases of vaccine breakdown. The aim of this study was to understand the nature of this attenuation through sequencing of the vaccine parent strain (AB7) and the derived mutant strains 1B and 1H, as well as to clarify the role of the vaccine strain in causing disease through comparative whole genome analysis. METHODS: Whole genome sequencing was performed on: vaccine parent strain AB7; N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced temperature attenuated mutant strain 1B grown from the commercial live vaccines Cevac Chlamydia and Enzovax; strain 1H a reverted NTG mutant; and 5 strains isolated from cases of OEA originating from animals from the original vaccine safety trial (2 strains) or from vaccinated ewes or ewes exposed to vaccinated animals (3 strains). RESULTS: We confirmed that AB7 is in a different lineage from the reference strain S26/3. The genome of vaccine strain 1B contains ten single nucleotide polymorphisms (SNPs) created by the NTG treatment, which are identical to those found in strain 1H. The strains from OEA cases also cluster phylogenetically very tightly with these vaccine strains. CONCLUSIONS: The results show that C. abortus vaccine strain 1B has an identical genome sequence to the non-attenuated "reverted mutant" strain 1H. Thus, the protection of the 1B vaccine is unlikely to be due to the NTG induced SNPs and is more likely caused by the administration of high doses of C. abortus elementary bodies that stimulate protective immunity. Vaccine-identical strains were also isolated from cases of disease, as well as strains which had acquired 1-3 SNPs, including an animal that had not been vaccinated with either of the commercial live OEA vaccines, indicating that the 1B vaccine strain may be circulating and causing disease.


Assuntos
Aborto Animal/imunologia , Vacinas Bacterianas/genética , Infecções por Chlamydia/veterinária , Chlamydia/efeitos dos fármacos , Genoma Bacteriano , Doenças dos Ovinos/imunologia , Aborto Animal/microbiologia , Animais , Vacinas Bacterianas/efeitos adversos , Vacinas Bacterianas/imunologia , Chlamydia/classificação , Chlamydia/genética , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Feminino , Metilnitronitrosoguanidina/farmacologia , Mutagênicos/farmacologia , Filogenia , Polimorfismo de Nucleotídeo Único , Gravidez , Análise de Sequência de DNA , Ovinos , Doenças dos Ovinos/microbiologia , Vacinas Atenuadas , Sequenciamento Completo do Genoma
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