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2.
Gut ; 72(6): 1186-1195, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35977815

RESUMEN

OBJECTIVE: Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo. DESIGN: A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer. RESULTS: The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection. CONCLUSION: The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Sobreinfección , Humanos , Ratones , Animales , Conejos , Antígenos de Hepatitis delta , Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica/prevención & control , Sobreinfección/prevención & control , Virus de la Hepatitis Delta/genética , Hepatitis B/prevención & control , Virus de la Hepatitis B/genética , Anticuerpos Antivirales , Ratones Transgénicos
3.
Londres; NICE; rev; Mar. 11, 2022. tab, ilus.
No convencional en Inglés | BIGG - guías GRADE | ID: biblio-1379308

RESUMEN

This guideline sets out an antimicrobial prescribing strategy for acute otitis media (ear infection). It aims to limit antibiotic use and reduce antimicrobial resistance. Acute otitis media can be caused by viruses or bacteria. It lasts for about a week, and most children get better in 3 days without antibiotics. Serious complications are rare. In March 2022, we reviewed the evidence and added a recommendation on eardrops containing an anaesthetic and an analgesic because a licensed preparation is now available in the UK. For more information, see update information.


Asunto(s)
Otitis Media/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Placebos/uso terapéutico , Prescripciones de Medicamentos/normas , Tabaquismo/complicaciones , Farmacorresistencia Microbiana , Sobreinfección/prevención & control , Cefalosporinas/uso terapéutico , Ibuprofeno/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Amoxicilina/uso terapéutico , Acetaminofén/uso terapéutico , Antibacterianos/uso terapéutico
4.
Comput Math Methods Med ; 2021: 9919700, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34868347

RESUMEN

In recent years, multiscale modelling approach has begun to receive an overwhelming appreciation as an appropriate technique to characterize the complexity of infectious disease systems. In this study, we develop an embedded multiscale model of paratuberculosis in ruminants at host level that integrates the within-host scale and the between-host. A key feature of embedded multiscale models developed at host level of organization of an infectious disease system is that the within-host scale and the between-host scale influence each other in a reciprocal (i.e., both) way through superinfection, that is, through repeated infection before the host recovers from the initial infectious episode. This key feature is demonstrated in this study through a multiscale model of paratuberculosis in ruminants. The results of this study, through numerical analysis of the multiscale model, show that superinfection influences the dynamics of paratuberculosis only at the start of the infection, while the MAP bacteria replication continuously influences paratuberculosis dynamics throughout the infection until the host recovers from the initial infectious episode. This is largely because the replication of MAP bacteria at the within-host scale sustains the dynamics of paratuberculosis at this scale domain. We further use the embedded multiscale model developed in this study to evaluate the comparative effectiveness of paratuberculosis health interventions that influence the disease dynamics at different scales from efficacy data.


Asunto(s)
Modelos Biológicos , Paratuberculosis/prevención & control , Rumiantes/microbiología , Animales , Número Básico de Reproducción/prevención & control , Número Básico de Reproducción/estadística & datos numéricos , Número Básico de Reproducción/veterinaria , Biología Computacional , Simulación por Computador , Enfermedades Endémicas/prevención & control , Enfermedades Endémicas/estadística & datos numéricos , Enfermedades Endémicas/veterinaria , Interacciones Microbiota-Huesped , Conceptos Matemáticos , Mycobacterium avium subsp. paratuberculosis/crecimiento & desarrollo , Mycobacterium avium subsp. paratuberculosis/patogenicidad , Paratuberculosis/microbiología , Paratuberculosis/transmisión , Sobreinfección/microbiología , Sobreinfección/prevención & control , Sobreinfección/veterinaria
5.
Viruses ; 13(7)2021 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-34372595

RESUMEN

In microbial communities, viruses compete with each other for host cells to infect. As a consequence of competition for hosts, viruses evolve inhibitory mechanisms to suppress their competitors. One such mechanism is superinfection exclusion, in which a preexisting viral infection prevents a secondary infection. The bacteriophage ΦX174 exhibits a potential superinfection inhibition mechanism (in which secondary infections are either blocked or resisted) known as the reduction effect. In this auto-inhibitory phenomenon, a plasmid containing a fragment of the ΦX174 genome confers resistance to infection among cells that were once permissive to ΦX174. Taking advantage of this plasmid system, we examine the inhibitory properties of the ΦX174 reduction effect on a range of wild ΦX174-like phages. We then assess how closely the reduction effect in the plasmid system mimics natural superinfection inhibition by carrying out phage-phage competitions in continuous culture, and we evaluate whether the overall competitive advantage can be predicted by phage fitness or by a combination of fitness and reduction effect inhibition. Our results show that viral fitness often correctly predicts the winner. However, a phage's reduction sequence also provides an advantage to the phage in some cases, modulating phage-phage competition and allowing for persistence where competitive exclusion was expected. These findings provide strong evidence for more complex dynamics than were previously thought, in which the reduction effect may inhibit fast-growing viruses, thereby helping to facilitate coexistence.


Asunto(s)
Bacteriófagos/genética , Bacteriófagos/patogenicidad , Ecología , Sobreinfección/virología , Virus/genética , ADN Viral , Evolución Molecular , Aptitud Genética , Humanos , Sobreinfección/prevención & control
6.
J Virol ; 95(21): e0126421, 2021 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-34431701

RESUMEN

Vaccination against the betaherpesvirus, human cytomegalovirus (HCMV) is a public health goal. However, HCMV has proved difficult to vaccinate against. Vaccination against single HCMV determinants has not worked, suggesting that immunity to a wider antigenic profile may be required. Live attenuated vaccines provide the best prospects for protection, but the question remains as to how to balance vaccine virulence with safety. Animal models of HCMV infection provide insights into identifying targets for virus attenuation and understanding how host immunity blocks natural, mucosal infection. Here, we evaluated the vaccine potential of a mouse cytomegalovirus (MCMV) vaccine deleted of a viral G protein-coupled receptor (GPCR), designated M33, that renders it attenuated for systemic spread. A single noninvasive olfactory ΔM33 MCMV vaccine replicated locally, but as a result of the loss of the M33 GPCR, it failed to spread systemically and was attenuated for latent infection. Vaccination did not prevent host entry of a superinfecting MCMV but spread from the mucosa was blocked. This approach to vaccine design may provide a viable alternative for a safe and effective betaherpesvirus vaccine. IMPORTANCE Human cytomegalovirus (HCMV) is the most common cause of congenital infection for which a vaccine is not yet available. Subunit vaccine candidates have failed to achieve licensure. A live HCMV vaccine may prove more efficacious, but it faces safety hurdles which include its propensity to persist and to establish latency. Understanding how pathogens infect guide rational vaccine design. However, HCMV infections are asymptomatic and thus difficult to capture. Animal models of experimental infection provide insight. Here, we investigated the vaccine potential of a mouse cytomegalovirus (MCMV) attenuated for systemic spread and latency. We used olfactory vaccination and virus challenge to mimic its natural acquisition. We provide proof of concept that a single olfactory MCMV that is deficient in systemic spread can protect against wild-type MCMV superinfection and dissemination. This approach of deleting functional counterpart genes in HCMV may provide safe and effective vaccination against congenital HCMV disease.


Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Vacunas contra Citomegalovirus/inmunología , Citomegalovirus/inmunología , Muromegalovirus/inmunología , Mucosa Olfatoria/virología , Sobreinfección/prevención & control , Sobreinfección/virología , Animales , Infecciones por Citomegalovirus/inmunología , Vacunas contra Citomegalovirus/administración & dosificación , Femenino , Inmunidad Innata , Ratones , Ratones Endogámicos BALB C , Nariz/virología , Prueba de Estudio Conceptual , Vacunación/métodos , Vacunas Atenuadas
7.
Front Immunol ; 12: 652923, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34163470

RESUMEN

Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-ß expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-ß, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-ß, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.


Asunto(s)
Infecciones por Escherichia coli/veterinaria , Ligilactobacillus salivarius/inmunología , Probióticos/administración & dosificación , Infecciones por Rotavirus/veterinaria , Sobreinfección/veterinaria , Porcinos/inmunología , Alimentación Animal/microbiología , Animales , Modelos Animales de Enfermedad , Escherichia coli Enterotoxigénica/inmunología , Escherichia coli Enterotoxigénica/patogenicidad , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/prevención & control , Femenino , Inmunidad Innata , Mucosa Intestinal/microbiología , Ratones , Poli I-C/administración & dosificación , Poli I-C/inmunología , Rotavirus/inmunología , Rotavirus/patogenicidad , Infecciones por Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , Sobreinfección/inmunología , Sobreinfección/microbiología , Sobreinfección/prevención & control , Porcinos/microbiología , Undaria/inmunología , Destete
9.
J Theor Biol ; 484: 110014, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31557473

RESUMEN

Superinfection exclusion is a phenomenon whereby the co-infection of a host with a secondary pathogen is prevented due to a current infection by another closely-related pathogenic strain. We construct a novel vector-host mathematical model for two pathogens that exhibit superinfection exclusion and simultaneously account for vaccination strategies against them. We then derive the conditions under which an endemic disease will prevent the establishment of another through the action of superinfection exclusion and show that vaccination against the endemic strain can enable the previously suppressed strain to invade the population. Through appropriate parameterisation of the model for dengue and yellow fever we find that superinfection exclusion alone is unlikely to explain the absence of yellow fever in many regions where dengue is endemic, and that the rollout of the recently licensed dengue vaccine, Dengvaxia, is unlikely to enable the establishment of Yellow Fever in regions where it has previously been absent.


Asunto(s)
Dengue , Modelos Biológicos , Sobreinfección , Fiebre Amarilla , Animales , Dengue/prevención & control , Vectores de Enfermedades , Humanos , Sobreinfección/prevención & control , Vacunación/estadística & datos numéricos , Fiebre Amarilla/prevención & control
10.
Vaccine ; 38(4): 859-867, 2020 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-31718898

RESUMEN

Clinical and historical data underscore the ability of influenza viruses to ally with Staphylococcus aureus and predispose the host for secondary bacterial pneumonia, which is a leading cause of influenza-associated mortality. This is fundamental because no vaccine for S. aureus is available and the number of antibiotic-resistant strains is alarmingly rising. Hence, this leaves influenza vaccination the only strategy to prevent postinfluenza staphylococcal infections. In the present work, we assessed the off-target effects of a Tnms42 insect cell-expressed BEI-treated Gag-VLP preparation expressing the HA of A/Puerto Rico/8/1934 (H1N1) in preventing S. aureus superinfection in mice pre-infected with a homologous or heterologous H1N1 viral challenge strain. Our results demonstrate that matched anti-hemagglutinin immunity elicited by a VLP preparation may suffice to prevent morbidity and mortality caused by lethal secondary bacterial infection. This effect was observed even when employing a single low antigen dose of 50 ng HA per animal. However, induction of anti-hemagglutinin immunity alone was not helpful in inhibiting heterologous viral replication and subsequent bacterial infection. Our results indicate the potential of the VLP vaccine approach in terms of immunogenicity but suggest that anti-HA immunity should not be considered as the sole preventive method for combatting influenza and postinfluenza bacterial infections.


Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Infecciones Estafilocócicas/prevención & control , Vacunas de Partículas Similares a Virus/administración & dosificación , Animales , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/complicaciones , Insectos , Ratones , Ratones Endogámicos BALB C , Sobreinfección/prevención & control , Vacunación , Vacunas de Partículas Similares a Virus/inmunología , Replicación Viral/inmunología
11.
Hum Vaccin Immunother ; 15(9): 2009-2012, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31121112

RESUMEN

When we reconsider the virology and history of the Spanish Influenza Pandemic, the science of 2018 provides us with tools which did not exist at the time. Two such tools come to mind. The first lies in the field of 'gain of function' experiments. A potential pandemic virus, such as influenza A (H5N1), can be deliberately mutated in the laboratory in order to change its virulence and spreadability. Key mutations can then be identified. A second tool lies in phylogenetics, combined with molecular clock analysis. It shows that the 1918 pandemic virus first emerged in the years 1915-1916. We have revisited the literature published in Europe and the United States, and the notes left by physicians who lived at the time. In this, we have followed the words of the late Alfred Crosby: who wrote that "contemporary documentary evidence from qualified physicians" is the key to understanding where and how the first outbreaks occurred. In our view, the scientists working in Europe fulfill Crosby's requirement for contemporary evidence of origin. Elsewhere, Crosby also suggested that "the physicians of 1918 were participants in the greatest failure of medical science in the twentieth century". Ours is a different approach. We point to individual pathologists in the United States and in France, who strove to construct the first universal vaccines against influenza. Their efforts were not misdirected, because the ultimate cause of death in nearly all cases flowed from superinfections with respiratory bacteria.


Asunto(s)
Infecciones Bacterianas/mortalidad , Coinfección/mortalidad , Coinfección/prevención & control , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Personal Militar , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/prevención & control , Coinfección/microbiología , Europa (Continente)/epidemiología , Personal de Salud , Historia del Siglo XX , Humanos , Gripe Humana/historia , Pandemias/historia , Sobreinfección/epidemiología , Sobreinfección/microbiología , Sobreinfección/prevención & control , Estados Unidos/epidemiología , Virología
12.
Pathog Dis ; 76(8)2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30321322

RESUMEN

Chlamydia trachomatis/HSV-2 vaginal co-infections are seen clinically, suggesting that these sexually transmitted pathogens may interact. We previously established an intravaginal Chlamydia muridarum/HSV-2 super-infection model and observed that chlamydial pre-infection protects mice from a subsequent lethal HSV-2 challenge. However, the mechanism of protection remains unknown. The type I interferon, IFN-ß, binds to the type I interferon receptor (IFNR), elicits a host cellular antiviral response and inhibits HSV replication in vitro and in vivo. Previous studies have demonstrated that C. muridarum infection stimulates genital tract (GT) IFN-ß production; therefore, we hypothesized that chlamydial pre-infection protects mice from HSV-2 challenge via the IFN-ß/IFNR-induced antiviral response. To test this prediction, we quantified IFN-ß levels in vaginal swab samples. Detection of IFN-ß in C. muridarum singly infected, but not in mock-infected animals, prompted the use of the super-infection model in IFNR knockout (IFNR-/-) mice. We observed that C. muridarum pre-infection reduces HSV-2-induced mortality by 40% in wild-type mice and by 60% IFNR-/- mice. Severity of HSV-2 disease symptoms and viral shedding was also similarly reduced by C. muridarum pre-infection. These data indicate that, while chlamydial infection induces GT production of IFN-ß, type I IFN-induced antiviral responses are likely not required for the observed protective effect.


Asunto(s)
Infecciones por Chlamydia/complicaciones , Herpes Genital/prevención & control , Receptor de Interferón alfa y beta/metabolismo , Sobreinfección/prevención & control , Animales , Chlamydia muridarum/inmunología , Modelos Animales de Enfermedad , Femenino , Herpesvirus Humano 2/inmunología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Vagina/inmunología
13.
Ital J Pediatr ; 44(1): 112, 2018 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-30257691

RESUMEN

BACKGROUND: Viral respiratory infections may promote bacterial super-infection decreasing the host immune response efficiency. However, using a mice model we recently demonstrated that preventive treatment with the bacterial extract OM-85 reduces the susceptibility to a secondary Streptococcus (S.) pneumoniae infection after influenza virus (I.V.) challenge. METHODS: To better characterize the efficacy of OM-85 against S. pneumoniae super-infection, a post-hoc analysis was conducted, comparing efficacy (survival) and morbidity signs (clinical score, body temperature and weight loss) in the OM-85 and the control (BLANC) groups of mice after: a) I.V. infection; b) primary S. pneumoniae infection and c) post-I.V. S. pneumoniae super-infection. RESULTS: After a sublethal I.V. dose, all mice stayed alive at day 5 and no differences in morbidity signs were detected between the OM-85 and the BLANC groups. However, OM-85 pretreatment led to a significantly reduction of the viral load in the lung on day 5 post viral infection and, on day 10, reduced neutrophilic inflammation while increasing influenza-specific CD8 + T-cell proportion in the airways. Conversely to viral infection, exposure to S. pneumoniae induced a dramatic reduction of survival, with no mice surviving on day 3 post infection in the BLANC group, whereas a partial protective effect was observed in OM-85 pre-treated mice (20% of mice surviving at day 3, and 10% at day 4 and 5). The morbidity data substantiated the survival results. Interestingly, in the "super-infection" study, when mice were exposed to a sublethal I.V. dose followed by a secondary S. pneumoniae infection, all mice died by day 4 in the BLANC group. In contrast, in the OM-85 treated group, the survival rate was 70% at day 4 and still 50% at day 5, with positive effects on the clinical scores and on the body temperature already detectable at days 1 and 2. CONCLUSIONS: The efficacy of OM-85 pre-treatment against S. pneumoniae super-infection reflects a strong and immediate immune reaction from the host, an event that can be explained in part by a "non-specific" activation of the immune system, a positive "immune effect" of the general OM-85- induced immune response against I.V.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Extractos Celulares/farmacología , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones Neumocócicas/prevención & control , Sobreinfección/prevención & control , Inmunidad Adaptativa , Animales , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T CD8-positivos/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Pulmón/virología , Ratones Endogámicos BALB C , Neutrófilos/metabolismo , Streptococcus pneumoniae/inmunología , Carga Viral/efectos de los fármacos
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 108(3): 209-220, abr. 2017. tab, ilus
Artículo en Español | IBECS | ID: ibc-161636

RESUMEN

La radioterapia es una técnica de uso creciente en el campo de la oncología. Debido al alto recambio celular cutáneo, la radiación ionizante afecta colateralmente a la piel y encontramos de forma frecuente dermatosis inflamatorias asociadas a radioterapia. Algunos de estos cuadros, como la radiodermitis o el fenómeno de recall, son bien conocidos por el dermatólogo. Es importante reconocer otros cuadros cutáneos asociados a radioterapia que aparecen de forma menos frecuente y que en muchas ocasiones son infradiagnosticados


Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often expressed in inflammatory reactions. Some of these reactions-radiodermatitis and recall phenomenon, for example-are very familiar to dermatologists. Other, less common radiotherapy-associated skin conditions are often underdiagnosed but must also be recognized


Asunto(s)
Humanos , Masculino , Femenino , Enfermedades de la Piel/complicaciones , Radiodermatitis/complicaciones , Radioterapia/efectos adversos , Corticoesteroides/uso terapéutico , Ácido Hialurónico/uso terapéutico , Cisplatino/uso terapéutico , Enfermedades de la Piel/clasificación , Sobreinfección/prevención & control , Sobreinfección/terapia , Calidad de Vida , Amifostina/uso terapéutico , Hiperqueratosis Epidermolítica/complicaciones , Pentoxifilina/uso terapéutico , Vitamina E/uso terapéutico , Liquen Plano/complicaciones
15.
Virus Res ; 233: 51-59, 2017 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-28279802

RESUMEN

Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections. Influenza virus A (H3N2) is a major pathogen that causes secondary bacterial infections and inflammation that lead to pneumonia. The herbal medicine Echinacea purpurea, on the other hand, has been widely used to prevent and treat viral respiratory infections, and recent clinical data suggest that it may prevent secondary infection complications as well. We investigated the role of standardized E. purpurea (Echinaforce® extract or EF) on H3N2-induced adhesion of live nontypeable Haemophilus influenzae (NTHi) and Staphylococcus aureus, along with the expression of bacterial receptors, intracellular adhesion molecule-1 (ICAM-1), fibronectin, and platelet activating factor receptor (PAFr), by BEAS-2B cells. Inflammatory processes were investigated by determining the cellular expression of IL-6 and IL-8 and the involvement of Toll-like receptor (TLR-4) and NFκB p65. We found that influenza virus A infection increased the adhesion of H. influenzae and S. aureus to bronchial epithelial cells via upregulated expression of the ICAM-1 receptor and, to some extent, of fibronectin and PAFr. Echinaforce (EF) significantly reduced the expression of ICAM-1, fibronectin, and PAFr and consequently the adhesion of both bacterial strains. EF also effectively prevented the super-expression of inflammatory cytokines by suppressing the expression of NFκB and possibly TLR-4. These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammation super-stimulation (cytokine storms).


Asunto(s)
Antiinfecciosos/farmacología , Echinacea/química , Células Epiteliales/efectos de los fármacos , Sobreinfección/prevención & control , Receptor Toll-Like 4/antagonistas & inhibidores , Factor de Transcripción ReIA/antagonistas & inhibidores , Línea Celular , Coinfección , Células Epiteliales/citología , Células Epiteliales/microbiología , Células Epiteliales/virología , Fibronectinas/genética , Fibronectinas/inmunología , Regulación de la Expresión Génica , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/crecimiento & desarrollo , Haemophilus influenzae/patogenicidad , Interacciones Huésped-Patógeno , Humanos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/crecimiento & desarrollo , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Pulmón/citología , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/virología , Extractos Vegetales/farmacología , Glicoproteínas de Membrana Plaquetaria/genética , Glicoproteínas de Membrana Plaquetaria/inmunología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/inmunología , Transducción de Señal , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/patogenicidad , Sobreinfección/microbiología , Sobreinfección/virología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/inmunología
16.
Arch Virol ; 162(5): 1211-1221, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28110425

RESUMEN

Many studies have revealed a protective effect of infection of an individual with an immunodeficiency virus against subsequent infection with a heterologous strain. However, the extent of protection against superinfection conferred by the first infection and the biological consequences of superinfection are not well understood. Here, we report that a rhesus monkey model of mucosal superinfection was established to investigate the protective immune response. Protection against superinfection was shown to correlate with the extent of the polyfunctionality of CD4+ effector memory T cells, whereas neutralizing antibody responses did not protect against superinfection in this model. Notably, immunodeficiency-virus-associated effector memory T-cell responses might significantly contribute to the suppression of virus superinfection. This provides a potential theoretical basis for the development of an HIV/AIDS vaccine.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Sobreinfección/inmunología , Sobreinfección/virología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Modelos Animales de Enfermedad , Femenino , Macaca mulatta , Masculino , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Sobreinfección/prevención & control , Carga Viral
17.
BMJ Open ; 7(1): e013268, 2017 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-28115333

RESUMEN

INTRODUCTION: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Neutropenia/complicaciones , Inhibidores de beta-Lactamasas/uso terapéutico , beta-Lactamas/uso terapéutico , Adolescente , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sobreinfección/prevención & control
18.
Virology ; 499: 331-339, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27743959

RESUMEN

Superinfection exclusion (SIE) is a phenomenon in which a primary viral infection restricts a secondary infection with the same or closely related virus. Previously we showed that SIE by Citrus tristeza virus (CTV) occurs only between isolates of the same virus genotype. This work, however, was done using single genotype-containing isolates, while most field citrus trees harbor complex populations composed of different virus genotypes. Here we examined SIE in plants simultaneously infected with several CTV genotypes. The experiments showed that exclusion of a secondary infection by a CTV variant was triggered by the presence of another variant of the same genotype in the primary population, even under the conditions of its low-level accumulation, and was not affected by co-occurrence of additional heterologous genotypes. The same rule appeared to be in effect when SIE by mixed populations was tested in a series of different citrus varieties.


Asunto(s)
Citrus/virología , Closterovirus/fisiología , Enfermedades de las Plantas/virología , Sobreinfección/prevención & control , Closterovirus/genética , Genotipo , ARN Viral/genética , ARN Viral/metabolismo , Sobreinfección/virología
19.
J Infect Dis ; 213(12): 1876-85, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-26908732

RESUMEN

BACKGROUND: Most preclinical studies assess vaccine effectiveness in single-pathogen infection models. This is unrealistic given that humans are continuously exposed to different commensals and pathogens in sequential and mixed infections. Accordingly, complications from secondary bacterial infection are a leading cause of influenza-associated morbidity and mortality. New vaccination strategies are needed to control infections on simultaneous fronts. METHODS: We compared different anti-influenza vaccines for their protective potential in a model of viral infection with bacterial superinfection. Mice were immunized with H1N1/A/California/7/2009 subunit vaccines, formulated with different adjuvants inducing either T-helper type 1 (Th1) (MF59 plus CpG)-, Th1/2 (MF59)-, or Th17 (LTK63)-prone immune responses and were sequentially challenged with mouse-adapted influenza virus H1N1/A/Puerto Rico/8/1934 and Staphylococcus aureus USA300, a clonotype emerging as a leading contributor in postinfluenza pneumonia in humans. RESULTS: Unadjuvanted vaccine controlled single viral infection, yet mice had considerable morbidity from viral disease and bacterial superinfection. In contrast, all adjuvanted vaccines efficiently protected mice in both conditions. Interestingly, the Th1-inducing formulation was superior to Th1/2 or Th17 inducers. CONCLUSIONS: Our studies should help us better understand how differential immunity to influenza skews immune responses toward coinfecting bacteria and discover novel modes to prevent bacterial superinfections in the lungs of persons with influenza.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/inmunología , Sobreinfección/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Animales , Toxinas Bacterianas/administración & dosificación , Enterotoxinas/administración & dosificación , Proteínas de Escherichia coli/administración & dosificación , Femenino , Humanos , Inmunización , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/complicaciones , Gripe Humana/microbiología , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/administración & dosificación , Polisorbatos/administración & dosificación , Organismos Libres de Patógenos Específicos , Escualeno/administración & dosificación , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/microbiología , Sobreinfección/microbiología
20.
Pediatr Dermatol ; 32(6): e307-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26584702

RESUMEN

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA), featuring large, ulcerative, necrotic skin plaques, high fever, and other systemic symptoms, is a rare disorder of unknown etiology. No randomized controlled trials have established treatment guidelines and multiple modalities are often employed, making it difficult to assess the efficacy of any single agent. We report two cases of this condition in which treatment with methotrexate plus antibiotic treatment for superinfection led to rapid improvement.


Asunto(s)
Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Metotrexato/administración & dosificación , Pitiriasis Liquenoide/diagnóstico , Pitiriasis Liquenoide/tratamiento farmacológico , Sobreinfección/prevención & control , Biopsia con Aguja , Cefalexina/administración & dosificación , Niño , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Exantema/diagnóstico , Exantema/etiología , Fiebre/diagnóstico , Fiebre/etiología , Estudios de Seguimiento , Hospitalización , Humanos , Inmunohistoquímica , Masculino , Enfermedades Raras , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Sobreinfección/tratamiento farmacológico , Resultado del Tratamiento
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