RESUMEN
Human norovirus was discovered more than five decades ago and is a widespread cause of outbreaks of acute gastroenteritis. There are no approved vaccines or antivirals currently available. However, norovirus inhibitors, including capsid-specific monoclonal antibodies (Mabs) and nanobodies, have recently shown promising results. Several Mabs and nanobodies were found to inhibit norovirus replication using a human intestinal enteroid (HIE) culture system and/or could block norovirus attachment to histo-blood group antigen (HBGA) co-factors. In our pursuit to develop a single broad-spectrum norovirus therapeutic, we continued our analysis and development of a cross-reactive and HBGA interfering nanobody (NB26). To improve NB26 binding capacity and therapeutic potential, we conjugated NB26 onto a human IgG Fc domain (Fc-NB26). We confirmed that Fc-NB26 cross-reacts with genetically diverse GII genotype capsid protruding (P) domains (GII.8, GII.14, GII.17, GII.24, GII.26, and GII.NA1) using a direct enzyme-linked immunosorbent assay. Furthermore, X-ray crystallography structures of these P domains and structures of other GII genotypes reveal that the NB26 binding site is largely conserved, validating its broad reactivity. We showed that Fc-NB26 has ~100-fold higher affinity toward the norovirus P domain compared to native NB26. We also found that both NB26 and Fc-NB26 neutralize human norovirus replication in the HIE culture system. Furthermore, the mode of inhibition confirmed that like NB26, Fc-NB26 caused norovirus particle disassembly and aggregation. Overall, these new findings demonstrate that structural modifications to nanobodies can improve their therapeutic potential.IMPORTANCEDeveloping vaccines and antivirals against norovirus remains a challenge, mainly due to the constant genetic and antigenic evolution. Moreover, re-infection with genetically related and/or antigenic variants is not uncommon. We further developed our leading norovirus nanobody (NB26) that indirectly interfered with norovirus binding to HBGAs, by converting NB26 into a dimeric Fc-linked Nanobody (Fc-NB26). We found that Fc-NB26 had improved binding affinity and neutralization capacity compared with native NB26. Using X-ray crystallography, we showed this nanobody engaged highly conserved capsid residues among genetically diverse noroviruses. Development of such broadly reactive potent therapeutic nanobodies delivered as a slow-releasing prophylactic could be of exceptional value for norovirus outbreaks, especially for the prevention or treatment of severe acute gastroenteritis in high-risk groups such as the young, elderly, and immunocompromised.
Asunto(s)
Infecciones por Caliciviridae , Proteínas de la Cápside , Norovirus , Anticuerpos de Dominio Único , Norovirus/genética , Norovirus/efectos de los fármacos , Norovirus/inmunología , Humanos , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/farmacología , Anticuerpos de Dominio Único/química , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/terapia , Antivirales/farmacología , Fragmentos Fc de Inmunoglobulinas/inmunología , Fragmentos Fc de Inmunoglobulinas/química , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Cápside/metabolismo , Cápside/inmunología , Antígenos de Grupos Sanguíneos/metabolismo , Replicación Viral/efectos de los fármacos , Gastroenteritis/virología , Inmunoglobulina G/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunologíaAsunto(s)
Infecciones por Caliciviridae , Trasplante de Microbiota Fecal , Norovirus , Humanos , Infecciones por Caliciviridae/terapia , Trasplante de Microbiota Fecal/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Enfermedad Crónica , Receptores de Trasplantes , Resultado del Tratamiento , Anciano , Gastroenteritis/virología , Gastroenteritis/microbiología , Gastroenteritis/terapiaRESUMEN
Rabbit hemorrhagic disease virus (RHDV) can cause fatal fulminant hepatitis, which is very similar to human acute liver failure. The aim of this study was to investigate whether adipose-derived stem cells (ADSCs) could alleviate RHDV2-induced liver injury in rabbits. Twenty 50-day-old rabbits were divided randomly into two groups (RHDV2 group, ADSCs + RHDV2 group). Starting from the 1st day, two groups of rabbits were given 0.5 ml of viral suspensions by subcutaneous injection in the neck. Meanwhile, the ADSCs + RHDV2 group was injected with ADSCs cell suspension (1.5 × 107 cells/ml) via a marginal ear vein, and the RHDV2 group was injected with an equal amount of saline via a marginal ear vein. At the end of the 48 h experiment, the animals were euthanized and gross hepatic changes were observed before liver specimens were collected. Histopathological analysis was performed using hematoxylin-eosin (HE), periodic acid schiff (PAS) and Masson's trichrome staining. For RHDV2 affected rabbits, HE staining demonstrated disorganized hepatic cords, loss of cellular detail, and severe cytoplasmic vacuolation within hepatocytes. Glycogen was not observed with PAS staining, and Masson's Trichrome staining showed increased hepatic collagen deposition. For rabbits treated with ADSCs at the time of inoculation, hepatic pathological changes were significantly less severe, liver glycogen synthesis was increased, and collagen fiber deposition was decreased. For RHDV2 affected rabbits, Tunel and immunofluorescence staining showed that the number of apoptotic cells, TGF-ß, and MMP-9 protein expression increased. And that in the ADSC treated group there was less hepatocyte apoptosis. In addition, RHDV2 induces liver inflammation and promotes the expression of IL-1ß, IL-6, and TNF-α. In rabbits administered ADSCs at time of inoculation, the expression of inflammatory factors in liver tissue decreased significantly. Our experiments show that ADSCs can protect rabbits from liver injury by RHDV2 and reduce the pathological and inflammatory response of liver. However, the specific protective mechanism needs further study.
Asunto(s)
Tejido Adiposo , Virus de la Enfermedad Hemorrágica del Conejo , Animales , Conejos , Virus de la Enfermedad Hemorrágica del Conejo/fisiología , Tejido Adiposo/citología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/terapia , Hígado/patología , Trasplante de Células Madre/métodos , Células Madre , Apoptosis , Masculino , Distribución AleatoriaRESUMEN
Acute liver failure (ALF) is a rare and severe disease, which, despite continuous advances in medicine, is still characterized by high mortality (65-85%). Very often, a liver transplant is the only effective treatment for ALF. Despite the implementation of prophylactic vaccinations in the world, the viral background of ALF is still a problem and leads to many deaths. Depending on the cause of ALF, it is sometimes possible to reverse this condition with appropriate therapies, which is why the search for effective antiviral agents seems to be a very desirable direction of research. Defensins, which are our natural antimicrobial peptides, have a very high potential to be used as therapeutic agents for infectious liver diseases. Previous studies on the expression of human defensins have shown that increased expression of human α and ß-defensins in HCV and HBV infections is associated with a better response to treatment. Unfortunately, conducting clinical trials for ALF is very difficult due to the severity of the disease and the low incidence, therefore animal models are important for the development of new therapeutic strategies. One of the best animal models that has real reference to research on acute liver failure (ALF) is rabbit hemorrhagic disease in rabbits caused by the Lagovirus europaeus virus. So far, there have been no studies on the potential of defensins in rabbits infected with Lagovirus europaeus virus.
Asunto(s)
Defensinas , Modelos Animales de Enfermedad , Virus de la Enfermedad Hemorrágica del Conejo , Fallo Hepático Agudo , Conejos , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/virología , Defensinas/uso terapéutico , Animales , Infecciones por Caliciviridae/terapiaRESUMEN
Norovirus is generally an acute infection causing symptoms such as diarrhea, nausea, and vomiting lasting for 24-48 hours. However, for immunocompromised patients, norovirus gastroenteritis can last for several years and result in villous atrophy and lead to severe malnutrition, dehydration, electrolyte imbalance and continuous viral shedding. Several treatment strategies have been suggested in case reports: nitazoxanide, ribavirin and enterally administered immunoglobulin with varying results. Favipiravir is also suggested but not tested on humans, highlighting the need for further research.
Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Gastroenteritis/terapia , Diarrea , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/terapia , Huésped InmunocomprometidoRESUMEN
Knowledge of the epidemiology of sporadic acute gastroenteritis (AGE) in the United States is limited. During September 2016-September 2017, we surveyed Kaiser Permanente Northwest members in Oregon and Washington, USA, to collect data on the 30-day prevalence of dually defined AGE and diarrhea disease and related health-seeking behavior; from a subset of participants, we obtained a stool specimen. Using the iterative proportional fitting algorithm with raked weights, we generated AGE prevalence and annualized rate estimates. We detected norovirus, rotavirus, astrovirus, and sapovirus from submitted stool specimens through real-time quantitative reverse transcription PCR (qRT-PCR). We estimated a 30-day prevalence of 10.4% for AGE and 7.6% for diarrhea only; annual rates were 1.27 cases/person/year for AGE and 0.92 cases/person/year for diarrhea only. Of those with AGE, 19% sought medical care. Almost one quarter (22.4%) of stool specimens from those reporting AGE tested positive for ≥1 viral pathogen, compared with 8.2% from those without AGE.
Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Rotavirus , Humanos , Estados Unidos/epidemiología , Lactante , Niño , Incidencia , Heces , Gastroenteritis/epidemiología , Gastroenteritis/terapia , Diarrea/epidemiología , Aceptación de la Atención de Salud , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/terapiaRESUMEN
Since the first clinical description in 1952, immunoglobulin replacement therapy remains the mainstay of treatment of patients with X-linked agammaglobulinemia (XLA). However, this therapy only replaces IgG isotype and does not compensate for the loss of Bruton tyrosine kinase in non-B-lymphocytes. Patients may still therefore develop complications despite current standard of care. Here, we describe an XLA patient with persistent chronic norovirus infection, refractory to treatment and causing intestinal failure. The patient underwent haematopoietic stem cell transplantation, curing XLA and allowed clearance of norovirus prior to humoral immunoreconstitution, suggesting non-humoral immunodeficiency in these patients.
Asunto(s)
Agammaglobulinemia/terapia , Infecciones por Caliciviridae/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Trasplante de Células Madre Hematopoyéticas , Insuficiencia Intestinal/terapia , Norovirus , Niño , Humanos , MasculinoRESUMEN
Human sapoviruses (HuSaVs) cause acute gastroenteritis similar to human noroviruses. Although HuSaVs were discovered four decades ago, no HuSaV has been grown in vitro, which has significantly impeded the understanding of viral biology and the development of antiviral strategies. In this study, we identified two susceptible human cell lines, that originated from testis and duodenum, that support HuSaV replication and found that replication requires bile acids. HuSaVs replicated more efficiently in the duodenum cell line, and viral RNA levels increased up to â¼6 log10-fold. We also detected double-stranded RNA, viral nonstructural and structural proteins in the cell cultures, and intact HuSaV particles. We confirmed the infectivity of progeny viruses released into the cell culture supernatants by passaging. These results indicate the successful growth of HuSaVs in vitro. Additionally, we determined the minimum infectious dose and tested the sensitivities of HuSaV GI.1 and GII.3 to heat and ultraviolet treatments. This system is inexpensive, scalable, and reproducible in different laboratories, and can be used to investigate mechanisms of HuSaV replication and to evaluate antivirals and/or disinfection methods for HuSaVs.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Medios de Cultivo/metabolismo , Sapovirus/fisiología , Cultivo de Virus/métodos , Replicación Viral , Infecciones por Caliciviridae/terapia , Infecciones por Caliciviridae/virología , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Células Epiteliales , Heces/virología , Gastroenteritis/terapia , Gastroenteritis/virología , Humanos , Sapovirus/aislamiento & purificaciónRESUMEN
Human noroviruses (HuNoVs) are a main cause of acute gastroenteritis worldwide. They are frequently involved in foodborne and waterborne outbreaks. Environmental transmission of the virus depends on two main factors: the ability of viral particles to remain infectious and their adhesion capacity onto different surfaces. Until recently, adhesion of viral particles to food matrices was mainly investigated by considering non-specific interactions (e.g. electrostatic, hydrophobic) and there was only limited information about infectious HuNoVs because of the absence of a reliable in vitro HuNoV cultivation system. Many HuNoV strains have now been described as having specific binding interactions with human Histo-Blood Group Antigens (HBGAs) and non-HBGA ligands found in food and the environment. Relevant approaches to the in vitro replication of HuNoVs were also proposed recently. On the basis of the available literature data, this review discusses the opportunities to use this new knowledge to obtain a better understanding of HuNoV transmission to human populations and better evaluate the hazard posed by HuNoVs in foodstuffs and the environment.
Asunto(s)
Antígenos de Grupos Sanguíneos/metabolismo , Infecciones por Caliciviridae/metabolismo , Gastroenteritis/metabolismo , Norovirus/metabolismo , Animales , Antígenos de Grupos Sanguíneos/genética , Infecciones por Caliciviridae/terapia , Infecciones por Caliciviridae/transmisión , Infecciones por Caliciviridae/virología , Gastroenteritis/genética , Gastroenteritis/terapia , Gastroenteritis/virología , Humanos , Norovirus/genética , Norovirus/aislamiento & purificación , Norovirus/fisiología , Unión Proteica , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: After the introduction of rotavirus vaccines into immunization schedules, noroviruses account for the majority of acute gastrointestinal infections. The aim of the study was to assess the clinical presentation in immunocompromised and immunocompetent children with hospital- and community-acquired norovirus gastroenteritis. MATERIAL AND METHODS: We retrospectively reviewed clinical records of children with noroviral gastroenteritis, hospitalized in the Pediatric Hospital, Medical University of Warsaw, between 2015 and 2018. Acute gastrointestinal tract symptoms and confirmed etiology of noroviral infection were inclusion criteria. The analysis was performed in the subgroups of immunocompetent and immunocompromised patients, during community-acquired and nosocomial infections. RESULTS: A total of 57 children with median age 1.5 year (IQR: 0.7-4.0) were recruited. The majority of patients were immunocompetent (87.7%), and nosocomial infections were predominant (56.1%). Gastrointestinal symptoms included nausea, vomiting and diarrhoea (in approximately 85%), while systemic manifestations such as fever and malaise where observed in only ». Routine laboratory tests were normal in most of the patients. An analysis in the subgroups revealed statistically significant differences in blood pH and serum electrolyte levels - acidosis and electrolyte disturbances were statistically significantly more common in immunocompromised vs immunocompetent patients (p<0.05). CONCLUSIONS: More frequently the clinical presentation includes gastrointestinal symptoms with no differences between immunocompromised and immunocompetent hosts. The median laboratory values were normal in generally healthy children; disturbances were observed only in children with immunodeficiencies. Therefore, prophylactic measures are of particular importance in the latter group, which is especially sensitive to severe and nosocomial infections.
Asunto(s)
Infecciones por Caliciviridae/terapia , Infecciones Comunitarias Adquiridas/terapia , Infección Hospitalaria/terapia , Infecciones por Caliciviridae/epidemiología , Niño , Preescolar , Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Masculino , NorovirusRESUMEN
Human norovirus frequently causes outbreaks of acute gastroenteritis. Although discovered more than five decades ago, antiviral development has, until recently, been hampered by the lack of a reliable human norovirus cell culture system. Nevertheless, a lot of pathogenesis studies were accomplished using murine norovirus (MNV), which can be grown routinely in cell culture. In this study, we analyzed a sizeable library of nanobodies that were raised against the murine norovirus virion with the main purpose of developing nanobody-based inhibitors. We discovered two types of neutralizing nanobodies and analyzed the inhibition mechanisms using X-ray crystallography, cryo-electron microscopy (cryo-EM), and cell culture techniques. The first type bound on the top region of the protruding (P) domain. Interestingly, this nanobody binding region closely overlapped the MNV receptor-binding site and collectively shared numerous P domain-binding residues. In addition, we showed that these nanobodies competed with the soluble receptor, and this action blocked virion attachment to cultured cells. The second type bound at a dimeric interface on the lower side of the P dimer. We discovered that these nanobodies disrupted a structural change in the capsid associated with binding cofactors (i.e., metal cations/bile acid). Indeed, we found that capsids underwent major conformational changes following addition of Mg2+ or Ca2+ Ultimately, these nanobodies directly obstructed a structural modification reserved for a postreceptor attachment stage. Altogether, our new data show that nanobody-based inhibition could occur by blocking functional and structural capsid properties.IMPORTANCE This research discovered and analyzed two different types of MNV-neutralizing nanobodies. The top-binding nanobodies sterically inhibited the receptor-binding site, whereas the dimeric-binding nanobodies interfered with a structural modification associated with cofactor binding. Moreover, we found that the capsid contained a number of vulnerable regions that were essential for viral replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for cofactor/receptor-binding functions. Blocking these capsid-binding events with nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific nanobody binding epitopes were comparable to human norovirus-specific nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals.
Asunto(s)
Infecciones por Caliciviridae/terapia , Norovirus/genética , Anticuerpos de Dominio Único/farmacología , Sitios de Unión/genética , Cápside/metabolismo , Proteínas de la Cápside/metabolismo , Microscopía por Crioelectrón/métodos , Cristalografía por Rayos X/métodos , Epítopos/metabolismo , Gastroenteritis/metabolismo , Norovirus/inmunología , Norovirus/patogenicidad , Unión Proteica/genética , Conformación Proteica , Dominios Proteicos/genética , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/metabolismo , Virión/metabolismoRESUMEN
BACKGROUND: Chronic norovirus infection in immunocompromised patients can be severe, and presently there is no effective treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the treatment of many viral infections, and this could represent a novel treatment approach for chronic norovirus infection. Hence, we sought to generate human norovirus-specific T cells (NSTs) that can recognize different viral sequences. METHODS: Norovirus-specific T cells were generated from peripheral blood of healthy donors by stimulation with overlapping peptide libraries spanning the entire coding sequence of the norovirus genome. RESULTS: We successfully generated T cells targeting multiple norovirus antigens with a mean 4.2 ± 0.5-fold expansion after 10 days. Norovirus-specific T cells comprised both CD4+ and CD8+ T cells that expressed markers for central memory and effector memory phenotype with minimal expression of coinhibitory molecules, and they were polyfunctional based on cytokine production. We identified novel CD4- and CD8-restricted immunodominant epitopes within NS6 and VP1 antigens. Furthermore, NSTs showed a high degree of cross-reactivity to multiple variant epitopes from clinical isolates. CONCLUSIONS: Our findings identify immunodominant human norovirus T-cell epitopes and demonstrate that it is feasible to generate potent NSTs from third-party donors for use in antiviral immunotherapy.
Asunto(s)
Traslado Adoptivo/métodos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Caliciviridae/terapia , Reacciones Cruzadas/inmunología , Norovirus/inmunología , Donantes de Tejidos , Secuencia de Aminoácidos , Antígenos Virales/inmunología , Infecciones por Caliciviridae/virología , Técnicas de Cultivo de Célula/métodos , Células Cultivadas , Epítopos de Linfocito T/inmunología , Estudios de Factibilidad , Voluntarios Sanos , Humanos , Huésped Inmunocomprometido , Epítopos Inmunodominantes/inmunología , Norovirus/genéticaRESUMEN
Feline calicivirus (FCV) causes upper respiratory tract infections in felines and threatens the health of wild and domestic felines. Clinically, specific drugs to treat FCV have not yet been developed. Here, IgG was extracted from inactivated FCV-immunized horse sera. Equine F(ab')2 fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. In our study, equine immunoglobulin F(ab')2 fragments showed efficient neutralizing activity in vitro against FCV and had therapeutic and prophylactic effects in FCV-infected cats. The anti-FCV-specific F(ab')2 fragment can significantly alleviate the clinical symptoms of FCV-infected cats and reduce the viral loads of the trachea, lung and spleen. These results indicate that the F(ab')2 fragment prepared from inactivated FCV-immunized horses may be used as a prophylactic and therapeutic agent for diseases caused by FCV.
Asunto(s)
Infecciones por Caliciviridae/terapia , Enfermedades de los Gatos/terapia , Caballos/inmunología , Inmunización Pasiva , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Animales , Anticuerpos Antivirales/inmunología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/virología , Calicivirus Felino/inmunología , Enfermedades de los Gatos/virología , Gatos , Femenino , Inmunoglobulina G/inmunología , Pulmón/virología , Bazo/virología , Tráquea/virología , Vacunas ViralesRESUMEN
Acute Viral Gastroenteritis: Viruses Other Than Norovirus Abstract. Norovirus is the leading cause of acute viral gastroenteritis. Norovirus is highly contagious, thus outbreaks of norovirus in hospitals and long-term care facilities are feared. Usually, stool samples of patients with a potentially viral gastroenteritis are first checked for the presence of norovirus. In recent years, sapovirus and astrovirus were increasingly reported as cause of acute gastroenteritis. Outbreaks of acute viral gastroenteritis caused by sapovirus or astrovirus are hardly distinguishable from those caused by norovirus because of a similar clinical presentation. Molecular analyses of stool specimen are needed for accurate diagnosis of the viral cause of acute gastroenteritis. It is worth to further investigate stool samples of patients suspected of acute viral gastroenteritis not only for norovirus, but also for sapovirus and astrovirus.
Asunto(s)
Infecciones por Astroviridae , Infecciones por Caliciviridae , Gastroenteritis , Sapovirus , Infecciones por Astroviridae/diagnóstico , Infecciones por Astroviridae/terapia , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/terapia , Gastroenteritis/diagnóstico , Gastroenteritis/terapia , Gastroenteritis/virología , HumanosRESUMEN
The main causative agents of feline upper respiratory tract disease (FURTD) are feline herpesvirus-1 (FHV-1) and feline calicivirus (FCV). These viral infections are common, especially in multiple cat households. Severely affected cats often need to be hospitalized. Intensive symptomatic therapy is important in the management of cats with FURTD. The use of antiviral drugs is limited in cats, as they are often ineffective or toxic when given systemically. Antiviral drugs are, therefore, mainly used locally for the treatment of FHV-1-associated eye changes. Famciclovir, however, is an effective drug for systemic therapy in cats with FHV-1-related clinical signs. For FCV, only few antiviral drugs are available. In a controlled study, the use of immunoglobulins in cats with FHV-1 and/or FCV infection reduced clinical signs of FURTD significantly faster.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Calicivirus Felino , Enfermedades de los Gatos/terapia , Infecciones por Herpesviridae/veterinaria , Infecciones del Sistema Respiratorio/veterinaria , Varicellovirus , Enfermedad Aguda , Animales , Antivirales/uso terapéutico , Infecciones por Caliciviridae/terapia , Infecciones por Caliciviridae/virología , Enfermedades de los Gatos/virología , Gatos , Infecciones por Herpesviridae/terapia , Infecciones por Herpesviridae/virología , Infecciones del Sistema Respiratorio/terapia , Infecciones del Sistema Respiratorio/virologíaRESUMEN
Neutropenic diets were adopted as a way to decrease the infection risks in immunocompromised individuals, but these diets result in significant restrictions in the variety and types of foods an individual may consume. We used a controlled before-and-after study design in consecutive pediatric and young adult patients who underwent hematopoietic stem cell transplant at our center between January 1, 2014, and December 31, 2014. From January through June, all patients were placed on a traditional neutropenic diet; on July 1, we liberalized the bone marrow transplant (BMT) diet to a modified BMT diet. We compared the incidence of bloodstream infections in the first 100 days post-transplant, incidence of norovirus in the first 100 days, total parenteral nutrition days through day 100, incidence of grade 3 to 4 graft-versus-host disease at day 100, gastrointestinal graft-versus-host disease (any stage), and 100-day overall survival. In addition, we administered an investigator-created survey to evaluate food cravings, nausea, diet limitations, and subjective quality of life. In total, 102 patients underwent hematopoietic stem cell transplant during the study period. Forty-nine (48%) received the neutropenic diet and 53 (52%) the BMT diet. Other than more males receiving the neutropenic diet (67% versus 47%, Pâ¯=â¯0.05), there were no statistical demographic and outcome differences between the 2 groups. Additionally, 46 subjects (45%) completed the investigator-created questionnaire. There was no difference in the perceived food cravings, nausea, diet limitations, and subjective quality of life between the 2 cohorts. These data demonstrate noninferiority of the modified BMT diet over the traditional neutropenic diet. We believe the food safety-based diet offers a greater variety of food, which may assist in the transition to a normal diet.
Asunto(s)
Dieta , Inocuidad de los Alimentos , Enfermedad Injerto contra Huésped/terapia , Neutropenia/terapia , Adolescente , Adulto , Aloinjertos , Infecciones por Caliciviridae/etiología , Infecciones por Caliciviridae/mortalidad , Infecciones por Caliciviridae/terapia , Niño , Preescolar , Estudios Controlados Antes y Después , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas , Humanos , Incidencia , Masculino , Neutropenia/etiología , Neutropenia/mortalidad , Norovirus , Calidad de Vida , Tasa de Supervivencia , Adulto JovenRESUMEN
Discovered in the 1970s, human noroviruses (NoV) are the leading cause of foodborne disease and gastroenteritis outbreaks worldwide. NoV affect people of all ages. In children less than 5 years old, despite rotavirus remains the main enteropathogen responsible for viral gastroenteritis, NoV become the first etiological virus in countries where the rotavirus vaccine was introduced. Treatment of viral gastroenteritis is symptomatic. The key element in front of NoV infection is limiting their transmission. A rapid NoV detection during outbreak is important in the aim to rapidly implement hygiene measures to limit the size of the outbreak. Prevention of NoV infections relies on the use of adequate hand hygiene measures and disinfection of contaminated environmental surfaces. In face of an acute gastroenteritis outbreak, the early NoV identification with rapid laboratory tests or molecular biology methods is needed in the aim to implement as soon as possible hygiene measures to limit the size of the NoV outbreak. Due to antigenically diverse NoV strains and the lack of long term immunity, the development of an effective vaccine is difficult.
Découverts dans les années 1970, les norovirus humains (NoV) sont reconnus comme les principaux agents pathogènes responsables de toxi-infections d'origine alimentaire et d'épidémies de gastro-entérites au niveau mondial. Ils infectent toutes les tranches d'âge. Chez les enfants de moins de 5 ans, bien que le rotavirus reste actuellement la première cause de gastro-entérites virales, force est de constater que les NoV sont en passe d'en devenir la première cause dans les pays où la vaccination contre le rotavirus a été introduite. Le traitement des gastro-entérites virales est symptomatique. L'élément clé face aux infections à NoV est de limiter leur transmission. La prévention des infections à NoV repose principalement sur l'application de mesures d'hygiène des mains adéquates et la désinfection de l'environnement contaminé. Lors des épidémies de gastro-entérites aiguës, l'identification précoce des NoV par des méthodes de laboratoire rapides ou de biologie moléculaire est primordiale afin de mettre en place rapidement les mesures d'hygiène permettant de limiter leur propagation. La diversité antigénique des NoV et le manque d'immunité protectrice à long terme rendent la mise au point de vaccins difficile.
Asunto(s)
Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/transmisión , Norovirus/patogenicidad , Animales , Infecciones por Caliciviridae/terapia , Control de Enfermedades Transmisibles , Vectores de Enfermedades , Enfermedades Transmitidas por los Alimentos/virología , Gastroenteritis/virología , Humanos , ZoonosisAsunto(s)
Infecciones por Caliciviridae/virología , Síndrome Hemolítico-Urémico/virología , Trasplante de Riñón/efectos adversos , Infecciones Oportunistas/virología , Adulto , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/terapia , Progresión de la Enfermedad , Resultado Fatal , Femenino , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/inmunología , Síndrome Hemolítico-Urémico/terapia , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/terapia , Resultado del TratamientoRESUMEN
The diagnosis, treatment, and prevention of infectious diseases in older adults in long-term care facilities (LTCFs), particularly nursing facilities, remains a challenge for all health providers who care for this population. This review provides updated information on the currently most important challenges of infectious diseases in LTCFs. With the increasing prescribing of antibiotics in older adults, particularly in LTCFs, the topic of antibiotic stewardship is presented in this review. Following this discussion, salient points on clinical relevance, clinical presentation, diagnostic approach, therapy, and prevention are discussed for skin and soft tissue infections, infectious diarrhea (Clostridium difficile and norovirus infections), bacterial pneumonia, and urinary tract infection, as well as some of the newer approaches to preventive interventions in the LTCF setting.