Medicación sin prescripción veterinaria en animales de compañía en Lima, Perú (2020)

The aim of this the study was to describe the reasons related to the medication of pets without veterinary prescription among clients of veterinary services in Metropolitan Lima, Peru in 2020. A descriptive cross-sectional observational study was developed that collected information through virtual surveys. In total, 408 clients were surveyed, of which 22.3% (91/408) mentioned consulting other media before visiting the veterinarian when their animal showed any signs of illness and 34.8% (142/408) mentioned having offered medicines without a veterinary prescription. The drugs that were used most frequently were analgesics / anti-inflammatories (32.4%, 46/142), antiparasitic (23.3%, 33/142) and antibiotics (19.0%, 27/142). Moreover, 87.7% (126/142) of the respondents who administered medication to their pets without a prescription, had the perception that this practice could have negative consequences on their animal. Of the total respondents, 62.5% (255/408) did not know or mentioned not having heard about “antimicrobial resistance”. It is concluded that in Metropolitan Lima there is the practice of medication for animals without a veterinary prescription and this requires the development of sensitization and awareness campaigns so that these practices do not affect animal health and welfare and public health.El objetivo del estudio fue describir las razones relacionadas a la medicación de animales de compañía sin prescripción veterinaria entre clientes de servicios veterinarios en la ciudad de Lima, Perú en 2020. Se desarrolló un estudio transversal descriptivo que recolectó información a través de encuestas virtuales. Se encuestaron a 408 clientes, de los cuales el 22.3% (91/408) mencionó consultar otros medios antes de visitar al médico veterinario cuando su animal mostraba algún signo de enfermedad y el 34.8% (142/408) mencionó haber ofrecido medicamentos sin prescripción veterinaria. Los fármacos que fueron utilizados con mayor frecuencia fueron analgésicos/antinflamatorios (32.4%, 46/142), antiparasitarios (23.3%, 33/142) y antibióticos (19.0%, 27/142). El 87.7% (126/142) de los encuestados que administraban medicamentos a sus animales de compañía sin receta médica tenía la percepción de que dicha práctica podría producir consecuencias negativas en su animal. Del total de encuestados, el 62.5% (255/408) no conocía o mencionaba no haber escuchado acerca de “resistencia antimicrobiana”. Se concluye que en Lima Metropolitana existe la práctica de medicación a los animales sin prescripción veterinaria, por lo que requiere el desarrollo de campañas de sensibilización y concienciación a fin de que estas prácticas no afecten la salud y bienestar animal y la salud pública

The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis

Published onlineJournal ArticleThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene. RESULTS: In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several Tfp genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type. CONCLUSIONS: This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model

Characterization of the outer membrane proteome of Francisella noatunensis subsp. orientalis

Aims The aims of the current study were to characterise the outer membrane proteins (OMPs) of Francisella noatunensis subsp. orientalis (Fno) STIR‐GUS‐F2f7, and identify proteins recognised by sera from tilapia, Oreochromis niloticus, (L) that survived experimental challenge with Fno. Methods and Results The composition of the OMPs of a virulent strain of Fno (STIR‐GUS‐ F2f7), isolated from diseased red Nile tilapia in UK, was examined. The sarcosine‐insoluble OMP fraction was screened with tilapia hyper‐immune sera by western blot analysis following separation of the proteins by 1D SDS‐PAGE. Liquid chromatography‐electrospray ionisation‐tandem mass spectrometry (LC‐ESI‐MS/MS) was used to identify the various proteins present in the OMP profile. Two hundred and thirty‐nine proteins were identified, of which 44 were found in the immunogenic band recognised by the tilapia hyperimmune serum. In silico analysis was performed to predict the function and location of the OMPs identified by MS. Conclusions Using a powerful proteomic‐based approach in conjugation with western immunoblotting, proteins comprising the outer membrane fraction of Fno STIR‐GUS‐F2f7 were identified, catalogued and screened for immune recognition by tilapia sera. Significance and Impact of the study The current study is the first report on the characterisation of Fno OMPs. The findings here provide preliminary data on bacterial surface proteins that exist in direct contact with the host's immune defences during infection and offer an insight into the pathogenesis of Fno

Identification of Genes Contributing to the Virulence of Francisella tularensis SCHU S4 in a Mouse Intradermal Infection Model

Background: Francisella tularensis is a highly virulent human pathogen. The most virulent strains belong to subspecies tularensis and these strains cause a sometimes fatal disease. Despite an intense recent research effort, there is very limited information available that explains the unique features of subspecies tularensis strains that distinguish them from other F. tularensis strains and that explain their high virulence. Here we report the use of targeted mutagenesis to investigate the roles of various genes or pathways for the virulence of strain SCHU S4, the type strain of subspecies tularensis. Methodology/Principal Findings: The virulence of SCHU S4 mutants was assessed by following the outcome of infection after intradermal administration of graded doses of bacteria. By this route, the LD\u2085\u2080 of the SCHU S4 strain is one CFU. The virulence of 20 in-frame deletion mutants and 37 transposon mutants was assessed. A majority of the mutants did not show increased prolonged time to death, among them notably \u394pyrB and \u394recA. Of the remaining, mutations in six unique targets, tolC, rep, FTT0609, FTT1149c, ahpC, and hfq resulted in significantly prolonged time to death and mutations in nine targets, rplA, wbtI, iglB, iglD, purL, purF, ggt, kdtA, and glpX, led to marked attenuation with an LD\u2085\u2080 of >10\ub3 CFU. In fact, the latter seven mutants showed very marked attenuation with an LD\u2085\u2080 of 6510\u2077 CFU. Conclusions/Significance: The results demonstrate that the characterization of targeted mutants yielded important information about essential virulence determinants that will help to identify the so far little understood extreme virulence of F. tularensis subspecies tularensis.Peer reviewed: YesNRC publication: Ye

Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11bhigh/CD11cmed/autofluorescencelow DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria (∼75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment

Microarray Analysis of Human Monocytes Infected with Francisella tularensis Identifies New Targets of Host Response Subversion

Francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. In order to help understand the mechanisms by which this occurs, we performed Affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent Type A Schu S4 strain. Results showed that expression of several host response genes were reduced such as those associated with interferon signaling, Toll-like receptor signaling, autophagy and phagocytosis. When compared to microarrays from monocytes infected with the less virulent F. tularensis subsp. novicida, we found qualitative differences and also a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes in the Schu S4 strain. Notably, the PI3K / Akt1 pathway appeared specifically down-regulated following Schu S4 infection and a concomitantly lower cytokine response was observed. This study identifies several new factors potentially important in host cell subversion by the virulent Type A F. tularensis that may serve as novel targets for drug discovery

Temporal differences of onset between primary skin lesions and regional lymph node lesions for tularemia in Japan: a clinicopathologic and immunohistochemical study of 19 skin cases and 54 lymph node cases

For tularemia, a zoonosis caused by the gram-negative coccobacillus Francisella tularensis, research of the relation between skin lesions and lymph node lesions has not been reported in the literature. This report describes skin lesions and lymph node lesions and their mutual relation over time for tularemia in Japan. Around the second day after infection (DAI), a subcutaneous abscess was observed (abscess form). Hand and finger skin ulcers formed during the second to the fourth week. Subcutaneous and dermal granulomas were observed with adjacent monocytoid B lymphocytes (MBLs) (abscess–granulomatous form). From the sixth week, large granulomas with central homogeneous lesions emerged diffusely (granulomatous form). On 2–14 DAI, F. tularensis antigen in skin lesions was detected in abscesses. During 7–12 DAI, abscesses with adjacent MBLs appeared without epithelioid granuloma (abscess form) in regional lymph nodes. During the second to fifth week, granulomas appeared with necrosis (abscess–granulomatous form). After the sixth week, large granulomas with a central homogeneous lesion (granulomatous form) appeared. F. tularensis antigen in lymph node lesions was observed in the abscess on 7–92 DAI. Apparently, F. tularensis penetrates the finger skin immediately after contact with infected hares. Subsequently, the primary lesion gradually transfers from skin to regional lymph nodes. The regional lymph node lesions induced by skin lesion are designated as dermatopathic lymphadenopathy. This study revealed temporal differences of onset among the skin and lymph node lesions

Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis

<p>Abstract</p> <p>Background</p> <p>After infecting a mammalian host, the facultative intracellular bacterium, <it>Francisella tularensis</it>, encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection.</p> <p>Results</p> <p>Microarray analysis of <it>F. tularensis </it>LVS shifted from 26°C (environmental) to 37°C (mammalian) showed ~11% of this bacterium's genes were differentially-regulated. Importantly, 40% of the protein-coding genes that were induced at 37°C have been previously implicated in virulence or intracellular growth of <it>Francisella </it>in other studies, associating the bacterial response to this temperature shift with pathogenesis. Forty-four percent of the genes induced at 37°C encode proteins of unknown function, suggesting novel <it>Francisella </it>virulence traits are regulated by mammalian temperature. To explore this possibility, we generated two mutants of loci induced at 37°C [FTL_1581 and FTL_1664 (<it>deoB</it>)]. The FTL_1581 mutant was attenuated in a chicken embryo infection model, which was likely attributable to a defect in survival within macrophages. FTL_1581 encodes a novel hypothetical protein that we suggest naming <it>t</it>emperature-<it>i</it>nduced, <it>v</it>irulence-associated locus <it>A</it>, <it>tivA</it>. Interestingly, the <it>deoB </it>mutant showed diminished entry into mammalian cells compared to wild-type LVS, including primary human macrophages and dendritic cells, the macrophage-like RAW 264.7 line, and non-phagocytic HEK-293 cells. This is the first study identifying a <it>Francisella </it>gene that contributes to uptake into both phagocytic and non-phagocytic host cells.</p> <p>Conclusion</p> <p>Our results provide new insight into mechanisms of <it>Francisella </it>virulence regulation and pathogenesis. <it>F. tularensis </it>LVS undergoes considerable gene expression changes in response to mammalian body temperature. This temperature shift is important for the regulation of genes that are critical for the pathogenesis of <it>Francisella</it>. Importantly, the compilation of temperature-regulated genes also defines a rich collection of novel candidate virulence determinants, including <it>tivA </it>(FTL_1581). An analysis of <it>tivA </it>and <it>deoB </it>(FTL_1664) revealed that these genes contribute to intracellular survival and entry into mammalian cells, respectively.</p