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1.
Virology ; 597: 110155, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38943783

RESUMEN

The increasing prevalence of drug-resistant Escherichia coli (E. coli) resulting from the excessive utilization of antibiotics necessitates the immediate exploration of alternative approaches to counteract pathogenic E. coli. Phages, with their unique antibacterial mechanisms, are considered promising candidates for treating bacterial infections. Herein, we isolated a lytic Escherichia phage Tequatrovirus YZ2 (phage YZ2), which belongs to the genus Tequatrovirus. The genome of phage YZ2 consists of 168,356 base pairs with a G + C content of 35.34% and 269 putative open reading frames (ORFs). Of these, 146 ORFs have been annotated as functional proteins associated with nucleotide metabolism, structure, transcription, DNA replication, translation, and lysis. In the mouse model of a skin wound infected by E. coli, phage YZ2 therapy significantly promoted the wound healing. Furthermore, histopathological analysis revealed reductions in IL-1ß and TNF-α and increased VEGF levels, indicating the potential of phages as effective antimicrobial agents against E. coli infection.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Genoma Viral , Infección de Heridas , Animales , Escherichia coli/virología , Escherichia coli/genética , Ratones , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infección de Heridas/microbiología , Infección de Heridas/virología , Infección de Heridas/tratamiento farmacológico , Sistemas de Lectura Abierta , Colifagos/genética , Colifagos/fisiología , Terapia de Fagos , Modelos Animales de Enfermedad , Cicatrización de Heridas , Composición de Base , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo
2.
J Virol ; 95(21): e0133821, 2021 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-34379501

RESUMEN

Herpes simplex virus 1 (HSV-1) enters its human host via the skin and mucosa. The open question is how the virus invades this highly protective tissue in vivo to approach its receptors in the epidermis and initiate infection. Here, we performed ex vivo infection studies in human skin to investigate how susceptible the epidermis and dermis are to HSV-1 and whether wounding facilitates viral invasion. Upon ex vivo infection of complete skin, only sample edges with integrity loss demonstrated infected cells. After removal of the dermis, HSV-1 efficiently invaded the basal layer of the epidermis and, from there, gained access to suprabasal layers. This finding supports a high susceptibility of all epidermal layers which correlated with the surface expression of the receptors nectin-1 and herpesvirus entry mediator (HVEM). In contrast, only single infected cells were detected in the separated dermis, where minor expression of the receptors was found. Interestingly, after wounding, nearly no infection of the epidermis was observed via the skin surface. However, if the wounding of the skin samples led to breaks through the dermis, HSV-1 infected mainly keratinocytes via the damaged dermal layer. The application of latex beads revealed only occasional entry via the wounded dermis; however, it facilitated penetration via the wounded skin surface. Thus, we suggest that although the wounded human skin surface allows particle penetration, the skin still provides barriers that prevent HSV-1 from reaching its receptors. IMPORTANCE The human pathogen herpes simplex virus 1 (HSV-1) invades its host via the skin and mucosa, which leads to primary infection of the epithelium. As the various epithelial barriers effectively protect the tissue against viral invasion, successful infection most likely depends on tissue damage. We addressed the initial invasion process in human skin by ex vivo infection to understand how HSV-1 overcomes physical skin barriers and reaches its receptors to enter skin cells. Our results demonstrate that intact skin samples allow viral access only from the edges, while the epidermis is highly susceptible once the basal epidermal layer serves as an initial entry portal. Surprisingly, mechanical wounding did not facilitate HSV-1 entry via the skin surface, although latex beads still penetrated via the lesions. Our results imply that successful invasion of HSV-1 depends on how well the virus can reach its receptors, which was not accomplished by skin lesions under ex vivo conditions.


Asunto(s)
Herpes Simple/virología , Herpesvirus Humano 1/fisiología , Nectinas/metabolismo , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Piel/virología , Internalización del Virus , Infección de Heridas/virología , Dermis/virología , Epidermis/virología , Interacciones Microbiota-Huesped , Humanos , Queratinocitos/virología
3.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34360986

RESUMEN

Human Cytomegalovirus (HCMV) may cause severe infections in transplant recipients. HCMV-replication can be limited by HCMV-specific antibody responses. The impact of the antibody-dependent cellular phagocytosis (ADCP) on inhibition of HCMV-replication in natural infections has not been clarified. Therefore, we investigated the HCMV-specific ADCP response in a study cohort of lung-transplant recipients (LTRs) with different donor (D) and recipient (R) HCMV-serostatus. Follow-up plasma samples from 39 non/low-viremic and 36 highly viremic (>1000 HCMV copies/mL plasma) LTRs were collected for one (R+ LTRs) or two (D+/R- LTRs) years post-transplantation. The HCMV-specific ADCP responses were assessed by focal expansion assays (FEA) and flow-cytometry. In all LTRs, ADCP responses were detected against HCMV-infected cells and cell-free virions. When measured in fibroblasts as well as with cell-free virus, the HCMV-specific ADPC response was higher in LTRs than in HCMV-seropositive healthy controls. In D+/R- LTRs, a significant ADCP response developed over time after the receipt of an HCMV positive lung, and a level of <19 IE+ cells/focus in the FEA on fibroblasts was associated with further protection from high-level viremia. Taken together, a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection.


Asunto(s)
Infecciones por Citomegalovirus/inmunología , Inmunoglobulina G/inmunología , Trasplante de Pulmón/efectos adversos , Fagocitosis , Infección de Heridas/inmunología , Células Cultivadas , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células THP-1 , Carga Viral , Infección de Heridas/etiología , Infección de Heridas/virología
4.
Artículo en Inglés | MEDLINE | ID: mdl-29963501

RESUMEN

Biofilm formation in wounds is considered a major barrier to successful treatment, and has been associated with the transition of wounds to a chronic non-healing state. Here, we present a novel laboratory model of wound biofilm formation using ex-vivo porcine skin and a custom burn wound array device. The model supports high-throughput studies of biofilm formation and is compatible with a range of established methods for monitoring bacterial growth, biofilm formation, and gene expression. We demonstrate the use of this model by evaluating the potential for bacteriophage to control biofilm formation by Staphylococcus aureus, and for population density dependant expression of S. aureus virulence factors (regulated by the Accessory Gene Regulator, agr) to signal clinically relevant wound infection. Enumeration of colony forming units and metabolic activity using the XTT assay, confirmed growth of bacteria in wounds and showed a significant reduction in viable cells after phage treatment. Confocal laser scanning microscopy confirmed the growth of biofilms in wounds, and showed phage treatment could significantly reduce the formation of these communities. Evaluation of agr activity by qRT-PCR showed an increase in activity during growth in wound models for most strains. Activation of a prototype infection-responsive dressing designed to provide a visual signal of wound infection, was related to increased agr activity. In all assays, excellent reproducibility was observed between replicates using this model.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Quemaduras/microbiología , Piel/lesiones , Staphylococcus aureus/crecimiento & desarrollo , Infección de Heridas/prevención & control , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Quemaduras/patología , Quemaduras/veterinaria , Humanos , Terapia de Fagos/veterinaria , Reproducibilidad de los Resultados , Piel/patología , Infecciones Estafilocócicas/patología , Infecciones Estafilocócicas/terapia , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/virología , Staphylococcus aureus/patogenicidad , Staphylococcus aureus/fisiología , Staphylococcus aureus/virología , Porcinos , Transactivadores/genética , Transactivadores/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/fisiología , Infección de Heridas/terapia , Infección de Heridas/veterinaria , Infección de Heridas/virología
5.
Am J Dermatopathol ; 40(4): 295-298, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28937438

RESUMEN

We present a rare case of cutaneous cytomegalovirus (CMV) infection in a nonimmunocompromised patient. A 74-year-old woman with a history of diabetes presented with an ulcer on the right lateral tibia that occurred at the site of a nerve core biopsy. Subsequent biopsy of the ulcer edge showed granulation tissue with neutrophilic inflammation. The patient underwent extensive antibiotic treatment for possible infection with weekly wound care. However, the ulceration persisted and enlarged. A repeat biopsy 1 year later showed superficial and deep mixed inflammation with an associated vasculitis. On close examination, endothelial and eccrine ducts cells showed characteristic CMV viral cytopathic changes with positivity on CMV immunohistochemical stain. Although the patient was started on valganciclovir, the ulceration did not resolve with treatment and slightly enlarged. Treatment modalities included dapsone, prednisone, weekly wound care, wound vacuum, and eventually a skin graft of the ulcer site. This case highlights the presence of CMV infection in a cutaneous ulceration in a relatively immunocompetent patient, and the lack of response to treatment raises the question whether CMV was causative, partially contributory, or simply an innocent bystander.


Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Úlcera Cutánea/virología , Infección de Heridas/virología , Anciano , Biopsia , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Úlcera Cutánea/terapia , Infección de Heridas/terapia
6.
PLoS One ; 12(7): e0179245, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28719657

RESUMEN

Multi-drug resistance has become a major problem for the treatment of pathogenic bacterial infections. The use of bacteriophages is an attractive approach to overcome the problem of drug resistance in several pathogens that cause fatal diseases. Our study aimed to isolate multi drug resistant bacteria from patients with septic wounds and then isolate and apply bacteriophages in vitro as alternative therapeutic agents. Pus samples were aseptically collected from Rajiv Gandhi Institute of Medical Science (RIMS), Kadapa, A.P., and samples were analyzed by gram staining, evaluating morphological characteristics, and biochemical methods. MDR-bacterial strains were collected using the Kirby-Bauer disk diffusion method against a variety of antibiotics. Bacteriophages were collected and tested in vitro for lytic activity against MDR-bacterial isolates. Analysis of the pus swab samples revealed that the most of the isolates detected had Pseudomonas aeruginosa as the predominant bacterium, followed by Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Our results suggested that gram-negative bacteria were more predominant than gram-positive bacteria in septic wounds; most of these isolates were resistant to ampicillin, amoxicillin, penicillin, vancomycin and tetracycline. All the gram-positive isolates (100%) were multi-drug resistant, whereas 86% of the gram-negative isolates had a drug resistant nature. Further bacteriophages isolated from sewage demonstrated perfect lytic activity against the multi-drug resistant bacteria causing septic wounds. In vitro analysis of the isolated bacteriophages demonstrated perfect lysis against the corresponding MDR-bacteria, and these isolated phages may be promising as a first choice for prophylaxis against wound sepsis, Moreover, phage therapy does not enhance multi-drug resistance in bacteria and could work simultaneously on a wide variety of MDR-bacteria when used in a bacteriophage cocktail. Hence, our results suggest that these bacteriophages could be potential therapeutic options for treating septic wounds caused by P. aeruginosa, S. aureus, K. pneumoniae and E. coli.


Asunto(s)
Bacteriófagos/fisiología , Farmacorresistencia Bacteriana Múltiple , Sepsis/terapia , Sepsis/virología , Infección de Heridas/terapia , Infección de Heridas/virología , Adolescente , Adulto , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Sepsis/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Adulto Joven
7.
PLoS One ; 12(7): e0182121, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28750102

RESUMEN

Bacteriophages could be used along with burn wound care products to enhance antimicrobial pressure during treatment. However, some of the components of the topical antimicrobials that are traditionally used for the prevention and treatment of burn wound infection might affect the activity of phages. Therefore, it is imperative to determine the counteraction of therapeutic phage preparations by burn wound care products before application in patients. Five phages, representatives of two morphological families (Myoviridae and Podoviridae) and active against 3 common bacterial burn wound pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus) were tested against 13 different products commonly used in the treatment of burn wounds. The inactivation of the phages was quite variable for different phages and different products. Majority of the anti-infective products affected phage activity negatively either immediately or in the course of time, although impact was not always significant. Products with high acidity had the most adverse effect on phages. Our findings demonstrate that during combined treatment the choice of phages and wound care products must be carefully defined in advance.


Asunto(s)
Bacteriófagos/fisiología , Quemaduras/virología , Infección de Heridas/virología , Antiinfecciosos/química , Concentración de Iones de Hidrógeno
8.
Burns ; 43(5): 987-992, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28420570

RESUMEN

OBJECTIVE: Burn-related immunosuppression can promote human herpesviridae infections. However, the effect of these infections on morbidity and mortality after pediatric burn injuries is unclear. METHODS: We retrospectively analyzed pediatric patients with burns ≥10% of the total body surface area (TBSA) who were admitted between 2010 and 2015. On clinical suspicion of a viral infection, antiviral therapy was initiated. Viral infection was confirmed via Tzanck smear, viral culture, and/or PCR. Study endpoints were mortality, days of antiviral agent administration, type of viral test used, type of viral infection, and length of hospitalization. RESULTS: Of the 613 patients were analyzed, 28 presented with clinically diagnosed viral infections. The use of Tzanck smears decreased over the past 5 years, whereas PCR and viral cultures have become standard. Patients with viral infections had significantly larger burns (53±15% vs. 38±18%, p<0.001); however, length of stay per TBSA burn was comparable (0.5±0.4 vs. 0.6±0.2, p=0.211). The most commonly detected herpesviridae was herpes simplex virus 1. Two patients died due to sepsis, which was accompanied by HSV infection. The mortality rate among all patients (2.7%) was comparable to that in the infected group (7.1%, p=0.898). Acyclovir was given systemically for 9±8days (N=76) and/or topically for 9±9days for HSV (N=39, combination of both N=33). Ganciclovir was prescribed in three cases for CMV. CONCLUSIONS: Viral infections occur more commonly in patients suffering from larger burns, and HSV infections can contribute to mortality.


Asunto(s)
Quemaduras/virología , Infecciones por Herpesviridae , Herpesviridae/aislamiento & purificación , Infección de Heridas/virología , Adolescente , Antivirales/uso terapéutico , Quemaduras/mortalidad , Quemaduras/terapia , Niño , Preescolar , Femenino , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/etiología , Humanos , Lactante , Masculino , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Factores de Riesgo , Sepsis/virología , Virología/métodos , Infección de Heridas/diagnóstico , Infección de Heridas/tratamiento farmacológico
9.
Antimicrob Agents Chemother ; 60(10): 5806-16, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27431214

RESUMEN

Multidrug-resistant bacterial pathogens are an increasing threat to public health, and lytic bacteriophages have reemerged as a potential therapeutic option. In this work, we isolated and assembled a five-member cocktail of wild phages against Acinetobacter baumannii and demonstrated therapeutic efficacy in a mouse full-thickness dorsal infected wound model. The cocktail lowers the bioburden in the wound, prevents the spread of infection and necrosis to surrounding tissue, and decreases infection-associated morbidity. Interestingly, this effective cocktail is composed of four phages that do not kill the parent strain of the infection and one phage that simply delays bacterial growth in vitro via a strong but incomplete selection event. The cocktail here appears to function in a combinatorial manner, as one constituent phage targets capsulated A. baumannii bacteria and selects for loss of receptor, shifting the population to an uncapsulated state that is then sensitized to the remaining four phages in the cocktail. Additionally, capsule is a known virulence factor for A. baumannii, and we demonstrated that the emergent uncapsulated bacteria are avirulent in a Galleria mellonella model. These results highlight the importance of anticipating population changes during phage therapy and designing intelligent cocktails to control emergent strains, as well as the benefits of using phages that target virulence factors. Because of the efficacy of this cocktail isolated from a limited environmental pool, we have established a pipeline for developing new phage therapeutics against additional clinically relevant multidrug-resistant pathogens by using environmental phages sourced from around the globe.


Asunto(s)
Infecciones por Acinetobacter/terapia , Acinetobacter baumannii/virología , Bacteriófagos , Infección de Heridas/terapia , Infecciones por Acinetobacter/virología , Acinetobacter baumannii/química , Acinetobacter baumannii/patogenicidad , Animales , Farmacorresistencia Bacteriana Múltiple , Femenino , Ratones Endogámicos BALB C , Mariposas Nocturnas/microbiología , Aguas del Alcantarillado/virología , Espectrometría Raman , Infección de Heridas/virología
10.
PLoS Med ; 12(4): e1001820, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25919012

RESUMEN

BACKGROUND: A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. METHODS AND FINDINGS: HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment. CONCLUSION: Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.


Asunto(s)
Circuncisión Masculina , Infecciones por VIH/transmisión , VIH-1 , Pene , Carga Viral , Infección de Heridas/virología , Heridas y Lesiones/virología , Adulto , Antivirales/uso terapéutico , Femenino , Infecciones por VIH/etiología , Infecciones por VIH/virología , Humanos , Masculino , Pene/cirugía , Pene/virología , Prevalencia , Estudios Prospectivos , Autoinforme , Uganda/epidemiología , Infección de Heridas/complicaciones
11.
Microb Drug Resist ; 21(2): 171-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25411824

RESUMEN

Acinetobacter baumannii, a substantial nosocomial pathogen, has developed resistance to almost all available antimicrobial drugs. Bacteriophage therapy is a possible alternative treatment for multidrug-resistant (MDR) bacterial infections. In this study, we have successfully isolated bacteriophage active against clinical strains of A. baumannii by enrichment from hospital sewage sludge using representatives of those strains. The bacteriophage isolated against A. baumannii formed plaques against beta-lactamases producing strains of A. baumannii. The utility of bacteriophage specific for A. baumannii to resolve wound infection in uncontrolled diabetic rats was evaluated. Five groups of uncontrolled diabetic rats were used. Group I was noninfected (Control), Group II was infected with MDR A. baumannii and challenged with bacteriophage, Group III was infected with MDR A. baumannii, Group IV was infected with MDR A. baumannii and challenged with antibiotic colistin, and Group V consisted of noninfected rats and sprayed with phage (Phage control). A significant decrease in infection, period of epithelization, and wound contraction was observed in the phage-challenged group when compared with antibiotic-treated uncontrolled diabetic rats and the control group. To conclude the study, new insights are provided into the biology of the broad host range of A. baumannii phage, demonstrating that A. baumannii phage has prospects for the treatment of infections caused by the MDR A. baumannii.


Asunto(s)
Infecciones por Acinetobacter/terapia , Infecciones por Acinetobacter/virología , Acinetobacter baumannii/virología , Bacteriófagos/metabolismo , Diabetes Mellitus Experimental/virología , Infección de Heridas/terapia , Infección de Heridas/virología , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/metabolismo , Animales , Antibacterianos/farmacología , Colistina/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/terapia , Infección Hospitalaria/virología , Diabetes Mellitus Experimental/microbiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Ratas , Ratas Wistar , Infección de Heridas/microbiología , beta-Lactamasas/metabolismo
12.
Pediatr Emerg Care ; 29(10): 1119-21;quiz 1122-4, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24084614

RESUMEN

There is overwhelming evidence that the 4-dose vaccine schedule as part of postexposure prophylaxis to prevent human rabies for previously unvaccinated persons, as recommended by the Advisory Committee on Immunization Practices, United States in 2009, is safe and effective. When used appropriately with timely wound care and administration of human rabies immune globulin, the administration of 4 doses of vaccine on days 0, 3, 7, and 14 is likely to induce an adequate,long-lasting antibody response that is able to neutralize rabies virus and prevent disease in exposed patients. There has been no change in the recommended regimen for pre-exposure prophylaxis and for postexposure prophylaxis of previously vaccinated persons or for immunosuppressed patients.


Asunto(s)
Inmunoterapia Activa/métodos , Vacunas Antirrábicas/uso terapéutico , Rabia/prevención & control , Animales , Animales Salvajes/virología , Mordeduras y Picaduras/complicaciones , Mordeduras y Picaduras/terapia , Mordeduras y Picaduras/virología , Esquema de Medicación , Humanos , Huésped Inmunocomprometido , Guías de Práctica Clínica como Asunto , Rabia/transmisión , Vacunas Antirrábicas/administración & dosificación , Vacunación , Infección de Heridas/terapia , Infección de Heridas/virología
13.
Wound Repair Regen ; 20(4): 592-600, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22713157

RESUMEN

Cell specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy for tissue repair and regeneration. Adeno-associated virus serotype 2 (AAV2/2) mediated gene transfer to the skin results in stable transgene expression in the muscle fascicles of the panniculus carnosus in mice, with minimal gene transfer to the dermal or epidermal elements. We hypothesized that pseudotyped AAV vectors may have a unique and characteristic tropism and transduction efficiency profile for specific cells in the cutaneous wounds. We compared transduction efficiencies of cells in the epidermis, cells in the dermis, and the fascicles of the panniculus carnosus by AAV2/2 and three pseudotyped AAV vectors, AAV2/5, AAV2/7, and AAV2/8 in a murine excisional wound model. AAV2/5 and AAV2/8 result in significantly enhanced transduction of cells both in the epidermis and the dermis compared to AAV2/2. AAV2/5 transduces both the basilar and supra-basilar keratinocytes. In contrast, AAV2/8 transduces mainly supra-basilar keratinocytes. Both AAV2/7 and AAV2/8 result in more efficient gene transfer to the muscular panniculus carnosus compared to AAV2/2. The capsid of the different pseudotyped AAV vectors produces distinct tropism and efficiency profiles in the murine wound healing model. Both AAV2/5 and AAV2/8 administration result in significantly enhanced gene transfer. To further characterize cell specific transduction and tropism profiles of the AAV pseudotyped vectors, we performed in vitro experiments using human and mouse primary dermal fibroblasts. Our data demonstrate that pseudotyping strategy confers a differential transduction of dermal fibroblasts, with higher transduction of both human and murine cells by AAV2/5 and AAV2/8 at early and later time points. At later time points, AAV2/2 demonstrates increased transduction. Interestingly, AAV2/8 appears to be more efficacious in transducing human cells as compared to AAV2/5. The pseudotype-specific pattern of transduction and tropism observed both in vivo and in vitro suggests that choice of AAV vectors should be based on the desired target cell and the timing of transgene expression in wound healing for gene transfer therapy in dermal wounds.


Asunto(s)
Dependovirus/fisiología , Vectores Genéticos , Infecciones por Parvoviridae/genética , Tropismo Viral , Cicatrización de Heridas , Infección de Heridas/genética , Animales , Dependovirus/aislamiento & purificación , Modelos Animales de Enfermedad , Técnicas de Transferencia de Gen , Vectores Genéticos/aislamiento & purificación , Queratinocitos/inmunología , Queratinocitos/patología , Ratones , Ratones Endogámicos C57BL , Infecciones por Parvoviridae/inmunología , Infecciones por Parvoviridae/patología , Infecciones por Parvoviridae/fisiopatología , Transducción Genética , Infección de Heridas/patología , Infección de Heridas/fisiopatología , Infección de Heridas/virología
14.
J Burn Care Res ; 32(3): 358-62, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21427598

RESUMEN

Both cosmetic facial resurfacing and facial burns cause an injury to the dermal layer of the skin. This injury renders the patient susceptible to primary herpes simplex virus (HSV) infection or, more commonly, to HSV reactivation. This in turn can lead to bacterial superinfection, possibly resulting in scarring and systemic dissemination in the immunosuppressed burn patient. HSV reactivation rates have been reported to be up to 50% in cosmetic procedures without acyclovir prophylaxis and up to 25% in patients with burn injury. Currently, acyclovir prophylaxis is a common practice in facial resurfacing, but no such recommendations have been issued for patients with burn injury. HSV usually presents in a febrile burn patient between the first and third postburn weeks as a cluster of small, umbilicated vesicles or vesicopustules on an erythematous base found within or around the margins of healing partial-thickness wounds. Diagnosis is confirmed through viral culture from the base of an unroofed vesicle, and treatment is begun with intravenous acyclovir. Antiviral prophylaxis should be strongly considered for HSV infection prevention in patients with major burn injury, particularly with burns involving the face. Acyclovir is the primary drug of choice, and contact precautions should be practiced. High suspicion levels and alertness to this entity can help prompt diagnosis and timely treatment while alleviating late complications.


Asunto(s)
Aciclovir/uso terapéutico , Quemaduras/tratamiento farmacológico , Traumatismos Faciales/tratamiento farmacológico , Herpes Simple/prevención & control , Premedicación , Infección de Heridas/prevención & control , Antivirales/uso terapéutico , Quemaduras/complicaciones , Quemaduras/virología , Traumatismos Faciales/complicaciones , Traumatismos Faciales/virología , Femenino , Herpes Simple/tratamiento farmacológico , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Prevención Primaria/métodos , Pronóstico , Medición de Riesgo , Resultado del Tratamiento , Infección de Heridas/etiología , Infección de Heridas/virología
15.
Med Mal Infect ; 41(3): 115-22, 2011 Mar.
Artículo en Francés | MEDLINE | ID: mdl-21144685

RESUMEN

Decorative tattooing is made by introducing exogenous pigments and/or dyes into the dermis to permanently mark the body for decorative or other reasons. Unfortunately, this procedure is not harmless and various complications may occur including the potential inoculation of virulent microorganisms in the dermis. Cutaneous infections usually develop within days to weeks after the procedure and may include: pyogenic infections (staphylococcus, streptococcus, Pseudomonas aeruginosa, etc.), but also atypical bacteria (commensal mycobacteria, tuberculosis, leprosy, etc.), viral infections (molluscum contagiosum, verruca vulgaris, herpes, etc.), and also fungal and parasitic infections. This review focuses on dermatological infections occurring on tattoos and their management.


Asunto(s)
Enfermedades Cutáneas Infecciosas/etiología , Tatuaje/efectos adversos , Adulto , Conducta Ceremonial , Niño , Dermatomicosis/etiología , Dermatomicosis/microbiología , Dermatomicosis/transmisión , Contaminación de Equipos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agujas/microbiología , Piel/microbiología , Piel/virología , Enfermedades Cutáneas Bacterianas/etiología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/transmisión , Enfermedades Cutáneas Infecciosas/transmisión , Enfermedades Cutáneas Parasitarias/etiología , Enfermedades Cutáneas Parasitarias/parasitología , Enfermedades Cutáneas Parasitarias/transmisión , Enfermedades Cutáneas Virales/etiología , Enfermedades Cutáneas Virales/transmisión , Enfermedades Cutáneas Virales/virología , Infección de Heridas/microbiología , Infección de Heridas/parasitología , Infección de Heridas/virología , Adulto Joven
16.
Biomedica ; 29(2): 191-203, 2009 Jun.
Artículo en Español | MEDLINE | ID: mdl-20128344

RESUMEN

Human rabies encephalitis by a vampire bat bite in an urban area of Colombia A case of rabies encephalitis is presented in a teenaged male, which developed four months after a bat bite in the urban area of Floridablanca, Santander Province, Colombia. The complex clinical manifestations prevented the confirmation of an antemortem diagnosis, principally because of the lengthy incubation period and the absence of other similar urban cases. Despite application of several therapies, including the Milwaukee protocol, the patient died 19 days after hospital admission. The autopsy revealed a necrotic, acute, pan-encephalitis of rabies virus etiology. The test of direct immunofluorescence in brain tissue was positive, as well as the biologic test in mice. Serological tests indicated it to be an antigenic variant type 3, whose main reservoir is the hematophagous vampire bat, Desmodus rotundus. This is probably the first case of bat-induced rabies reported in an urban community of Colombia and one of the few in Latin America. Although rabies encephalitis by a bat bite is rare, the case serves as a notice to health authorities and to the medical community to be alert to this risk.


Asunto(s)
Mordeduras y Picaduras/virología , Quirópteros/virología , Errores Diagnósticos , Reservorios de Enfermedades , Encefalitis Viral/virología , Virus de la Rabia/aislamiento & purificación , Rabia/transmisión , Adolescente , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Animales , Mordeduras y Picaduras/complicaciones , Colombia/epidemiología , Contraindicaciones , Dengue/diagnóstico , Encefalitis Viral/epidemiología , Encefalitis Viral/etiología , Encefalitis Viral/patología , Resultado Fatal , Traumatismos de la Mano/virología , Humanos , América Latina/epidemiología , Masculino , Ratones , Intoxicación/diagnóstico , Rabia/diagnóstico , Rabia/epidemiología , Rabia/patología , Rabia/virología , Virus de la Rabia/inmunología , Tonsilitis/diagnóstico , Salud Urbana , Infección de Heridas/virología
17.
Antimicrob Agents Chemother ; 49(3): 1220-1, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15728933

RESUMEN

In a rabbit model of wound infection caused by Staphylococcus aureus, 2 x 10(9) PFU of staphylococcal phage prevented abscess formation in rabbits when it was injected simultaneously with S. aureus (8 x 10(7) CFU) into the same subcutaneous site. Phage multiplied in the tissues. Phages might be a valuable prophylaxis against staphylococcal infection.


Asunto(s)
Absceso/prevención & control , Infecciones Estafilocócicas/prevención & control , Fagos de Staphylococcus , Infección de Heridas/prevención & control , Absceso/microbiología , Absceso/virología , Animales , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Conejos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/virología , Infección de Heridas/microbiología , Infección de Heridas/virología
19.
Med Mal Infect ; 34(12): 551-60, 2004 Dec.
Artículo en Francés | MEDLINE | ID: mdl-15603930

RESUMEN

Twenty people died of rabies in France between 1970 and 2003 (compared to 55,000 yearly worldwide), 80% on returning from Africa. Dogs were the contaminating animals in 90% of the cases and children were the most common victims. The last instance of rabies in a native French animal was reported in 1998. However the illegal importation of animals still poses a risk. The disease is transmitted by saliva, even before the appearance of clinical symptoms, through a bite, scratch, or licks of mucous membranes or broken skin. Person-to-person transmission has only been observed in cases of grafts (cornea). The mean incubation time of 1 to 3 months is long enough to allow passive immunization and vaccination. After its onset, the disease presents as encephalitis or a paralytic syndrome the outcome of which is always fatal. Clinical diagnosis may be difficult in the early stages of the disease. If rabies is suspected, the National Reference Centre is responsible for the sampling and proper transportation of these samples so as to ensure assessment results within 5 days. If stringent hygiene rules are complied to, there is no risk of contamination for those in close contact. Vaccination, which is performed in official rabies centers, is only performed after a diagnosis based on laboratory evidence, and solely for exposed persons or those for whom a reliable history cannot be established (children under 6 years). Prevention is based on information. People traveling abroad, particularly to Africa, are warned not to approach unknown animals (especially dogs) nor to try to import them, and are advised to comply with vaccinal recommendations for travelers, particularly for toddlers.


Asunto(s)
Rabia/epidemiología , Adolescente , África , Anciano , Animales , Manejo de Caso , Niño , Preescolar , Enfermedades de los Perros/transmisión , Enfermedades de los Perros/virología , Perros/virología , Resultado Fatal , Femenino , Francia/epidemiología , Humanos , Inmunización Pasiva , India , Masculino , México , Persona de Mediana Edad , Personal de Hospital , ARN Viral/aislamiento & purificación , Rabia/diagnóstico , Rabia/terapia , Rabia/transmisión , Rabia/veterinaria , Rabia/virología , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/uso terapéutico , Virus de la Rabia/aislamiento & purificación , Saliva/virología , Convulsiones/etiología , Piel/lesiones , Trasplante/efectos adversos , Viaje , Vacunación , Infección de Heridas/virología
20.
Arch Pediatr ; 11(4): 335-9, 2004 Apr.
Artículo en Francés | MEDLINE | ID: mdl-15051092

RESUMEN

UNLABELLED: Although human cowpox virus infection is rare nowadays, an animal reservoir of this virus still exists. The general course of cowpox virus infections is usually benign but the diagnosis is difficult and often late. CASE REPORT: An 11-year-old boy, owner of two cats, presented with an infected sacral wound lesion associated with fever and lymph nodes. The wound became necrotic and other cutaneous and mucous membrane lesions developed secondarily. Blood tests did not show hyperleukocytosis or a systemic inflammatory response. Concurrently one of the cats was examined by a veterinary because of multifocal cutaneous lesions. Evocative skin biopsy specimens from the animal and, secondarily from the patient, allowed the identification of orthopoxvirus. Evolution was slowly favourable under symptomatic treatment. CONCLUSION: Poxviruses are responsible for many animal and human diseases, the most famous of them being smallpox which today is considered eradicated. Vaccination against smallpox is no longer performed since 1977. Whether the arrest of vaccinations against smallpox may induce the apparition of other poxviruses infections or alter their clinical expression is an open question.


Asunto(s)
Virus de la Viruela Vacuna/patogenicidad , Viruela Vacuna/patología , Infección de Heridas/virología , Animales , Gatos , Niño , Viruela Vacuna/terapia , Viruela Vacuna/transmisión , Viruela Vacuna/veterinaria , Fiebre/etiología , Humanos , Masculino , Necrosis , Sacro , Zoonosis
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