Subtractive proteomics and immunoinformatics approaches to explore Bartonella bacilliformis proteome (virulence factors) to design B and T cell multi-epitope subunit vaccine.

Bartonella bacilliformis a gram-negative facultative aerobe responsible for the Carrion's disease widely distributed in Ecuador, Peru, and Colombia with a high mortality rate when no specific treatment is received. B bacilliformis is transmitted by Sand fly (Lutzomyia verrucarum) to healthy individuals. Immunoinformatic and subtractive proteomics approaches were employed in this study to prioritize the best candidates for vaccine designing. These approaches resulted in five vaccine candidates, flagellar biosynthetic protein (Uniprot ID: A1UTU1), heme exporter protein C (UniProt ID: A1UU82), Cytochrome c-type biogenesis protein (Uniprot ID: A1URZ7), Hemin ABC transporter (Uniprot ID: A1US20) and Phosphatidate cytidylyltransferase (Uniprot ID: A1USE3). The mentioned proteins are antigenic and essential for pathogen survival. A range of immune-informatics tools was applied for the prediction of B and T cell epitopes for the vaccine candidate proteins. In-silico vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 4. TLR-4 agonist 50S ribosomal protein L7/L12 (UniproKB ID; P9WHE3) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-4 docked complex, MD simulations were performed. The final vaccine was back-translated and cloned in Eschericia coli to attain the maximal expression of the vaccine protein. The maximal expression was ensured, and the CAI score of 0.96 was reported. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against B bacilliformis associated infections.

Carrion's disease: more than a neglected disease.

Infections with Bartonella bacilliformis result in Carrion's disease in humans. In the first phase of infection, the pathogen causes a hemolytic fever ("Oroya fever") with case-fatality rates as high as ~90% in untreated patients, followed by a chronical phase resulting in angiogenic skin lesions ("verruga peruana"). Bartonella bacilliformis is endemic to South American Andean valleys and is transmitted via sand flies (Lutzomyia spp.). Humans are the only known reservoir for this old disease and therefore no animal infection model is available. In the present review, we provide the current knowledge on B. bacilliformis and its pathogenicity factors, vectors, possible unknown reservoirs, established and potential infection models and immunological aspects of the disease.

Bartonella bacilliformis: a systematic review of the literature to guide the research agenda for elimination.

BACKGROUND: Carrion's disease affects small Andean communities in Peru, Colombia and Ecuador and is characterized by two distinct disease manifestations: an abrupt acute bacteraemic illness (Oroya fever) and an indolent cutaneous eruptive condition (verruga Peruana). Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Despite being an ancient disease that has affected populations since pre-Inca times, research in this area has been limited and diagnostic and treatment guidelines are based on very low evidence reports. The apparently limited geographical distribution and ecology of Bartonella bacilliformis may present an opportunity for disease elimination if a clear understanding of the epidemiology and optimal case and outbreak management can be gained. METHODS: All available databases were searched for English and Spanish language articles on Carrion's disease. In addition, experts in the field were consulted for recent un-published work and conference papers. The highest level evidence studies in the fields of diagnostics, treatment, vector control and epidemiology were critically reviewed and allocated a level of evidence, using the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines. RESULTS: A total of 44 studies were considered to be of sufficient quality to be included in the analysis. The majority of these were level 4 or 5 (low quality) evidence and based on small sample sizes. Few studies had been carried out in endemic areas. CONCLUSIONS: Current approaches to the diagnosis and management of Carrion's disease are based on small retrospective or observational studies and expert opinion. Few studies take a public health perspective or examine vector control and prevention. High quality studies performed in endemic areas are required to define optimal diagnostic and treatment strategies.

Persistence of Bartonella spp. stealth pathogens: from subclinical infections to vasoproliferative tumor formation.

Bartonella spp. are facultative intracellular bacteria that typically cause a long-lasting intraerythrocytic bacteremia in their mammalian reservoir hosts, thereby favoring transmission by blood-sucking arthropods. In most cases, natural reservoir host infections are subclinical and the relapsing intraerythrocytic bacteremia may last weeks, months, or even years. In this review, we will follow the infection cycle of Bartonella spp. in a reservoir host, which typically starts with an intradermal inoculation of bacteria that are superficially scratched into the skin from arthropod feces and terminates with the pathogen exit by the blood-sucking arthropod. The current knowledge of bacterial countermeasures against mammalian immune response will be presented for each critical step of the pathogenesis. The prevailing models of the still-enigmatic primary niche and the anatomical location where bacteria reside, persist, and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia will also be critically discussed. The review will end up with a discussion of the ability of Bartonella spp., namely Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis, to induce tumor-like vascular deformations in humans having compromised immune response such as in patients with AIDS.

Bartonelosis (Fiebre de la Oroyao verruga peruana) ¿Enfermedad ocupacional? / No disponible

La Bartonella bacilliformis es un parásito bacterianointracelular facultativo de los eritrocitos humanos y de las células endoteliales. La enfermedad de Carrión, fiebre de La Oroya y Verruga Peruana son todos términos que describen las consecuencias patológicas de la infección humana por Bartonella bacilliformis. (1)Aunque las infecciones que involucran especies deBartonella, tales como Bartonella henselae y Bartonellaquintana, ocurren en todo el mundo, la enfermedad deCarrión es endémica únicamente en Sudamérica. (14)Las infecciones por B. bacilliformis son un problemade salud en numerosas áreas rurales de Sudamérica y paralos viajeros que visitan esas regiones. Se han reportadobrotes de bartonelosis en las regiones montañosas de Perú, Ecuador y Colombia. (1)La Lutzomyia verrucarum es el principal vector para latransmisión de la bacteria al ser humano; la hembra delmosquito transmite el patógeno durante su alimentaciónnocturna de sangre humana. Presumiblemente el insecto sealimenta de sangre de un individuo infectado y disemina el patógeno por medio de su saliva durante la siguiente ingesta de sangre. La bacteria no es contagiosa entre humanos.(1)Presentamos un enfoque laboral de la enfermedad entrabajadores que realizan desplazamientos continuos azonas endémicas y analizamos sus posibles consecuencias

Bartonella bacilliformis is a facultative intracellularbacterial parasite of human erythrocytes and endotelialcells. Carrion’s disease, Oroya fever and Peruvian wart are all terms describing the pathological consequences ofhuman infection with Bartonella bacilliformis. (1) Although infections involving the Bartonella species, such as Bartonella henselae and Bartonella Quintana occur worldwide, Carrion’s disease is uniquely endemic to South America.(14)Bartonella baciliformis infections are a health problemin many rural areas of South America and to travellers who visit these regions.Outbreaks of Bartonellosis have been reported in themountainous regions of Peru, Ecuador and Colombia.(1)The Lutzomyia verrucarum is the main vector fortransmission of the bacteria to humans. The female sandfly transmits the pathogen during nocturnal blood feeding on humans. Presumably the insects feed on the blood of an infected individual and spread the pathogen via saliva during a subsequent meal.The bacterium is not transmitted from person to person.(1)Let's sense beforehand a labour approach of the diseasein workers who realize constant displacements to endemiczones and we analyze your possible consequences

La enfermedad de Carrión, dos siglos después / Carrión disease: two century later

No disponible

Enfermedades producidas por Bartonella spp / Diseases produced by Bartonella

Las bacterias del género Bartonella son responsables de un amplio grupo de enfermedades infecciosas emergentes y reemergentes. Las manifestaciones clínicas varían en dependencia de la especie de Bartonella y de la situación inmunológica del paciente. En las infecciones por Bartonella spp. no existe un tratamiento universalizado, por lo que debe adaptarse a la situación clínica de cada paciente. Al ser responsables de cuadros clínicos potencialmente graves (endocarditis, bacteriemias prolongadas, angiomatosis bacilar, enfermedad de Carrión, etc.), la sospecha clínica, la rapidez con que se realice el diagnóstico y el inicio precoz del tratamiento puede conducir a una evolución favorable (AU)

The genus Bartonella is cause of a broad number of emerging and re-emerging infectious diseases. Clinical manifestations depend on the implicated Bartonella sp. and the immunity of the host. Because there is not a universal therapy for this infection, treatment should be chosen individually. Bartonella sp. is responsible of potentially serious clinical pictures (endocarditis, chronic bacteremia, bacillary angiomatosis, Carrion's disease, etc.), so clinical suspicion, a quickly diagnosis and an early treatment provide a better resolution (AU)