Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach

BACKGROUND Carrion's disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIVE The main aim of this study was to integrate genomic-scale data to shortlist a set of proteins that could serve as attractive targets for new antimicrobial discovery to combat B. bacilliformis. METHODS We performed a multidimensional genomic scale analysis of potential and relevant targets which includes structural druggability, metabolic analysis and essentiality criteria to select proteins with attractive features for drug discovery. FINDINGS We shortlisted seventeen relevant proteins to develop new drugs against the causative agent of Carrion's disease. Particularly, the protein products of fabI, folA, aroA, trmFO, uppP and murE genes, meet an important number of desirable features that make them attractive targets for new drug development. This data compendium is freely available as a web server (http://target.sbg.qb.fcen.uba.ar/). MAIN CONCLUSION This work represents an effort to reduce the costs in the first phases of B. bacilliformis drug discovery.

Febre do viajante associada com adenite cervical e sororreatividade para Bartonella sp em paciente brasileira, após retorno da África do Sul / Traveler's fever associated with cervical adenomegaly and antibodies for Bartonella sp in a Brazilian patient returning from South Africa

Um grande número de viajantes visita anualmente, por estudo, turismo ou trabalho o continente africano. Um caso de adenomegalia cervical e hepatoesplenomegalia associado à febre de duas semanas de duração com teste sorológico positivo para Bartonella sp em uma paciente de 22 anos do sexo feminino que retornou da África do Sul após realização de trabalho de campo com primatas em área silvestre é apresentado.

A large number of travelers visit the African continent annually for studying, tourism or business reasons. The authors report a case of cervical adenomegaly, hepatomegaly and splenomegaly associated with a two-week history of fever and seropositivity for Bartonella sp in a 22-year-old female patient who returned from South Africa after field work with primates in a wild area.

Bartonellosis: suggestive case reports in adult and pediatric patients and therapeutic issues

Cat-scratch disease warrants extensive investigation, from an epidemiological, a diagnostic, but especially a therapeutic point of view. Two suggestive episodes of Bartonella henselae-caused cat-scratch disease are reported, and discussed in the light of the most recent literature evidence. The first case occurred in a 60-year-old man, thus suggesting that it is important to maintain an elevated level of suspicion for this disease in adults as well. Both episodes were characterized by a very prolonged and complicated disease course (with the involvement of three lymph node sets in the first case), a need for lymph-node drainage, and apparently negligible activity of many antimicrobial courses, with a very slow local cure. While specific culture and molecular biology techniques proved negative (probably due to late availability of appropriate clinical specimens), indirect immunofluorescence antibody assay was positive since the first weeks of disease, and elevated levels were also fond many months after disease onset. When clinicians face patients with prominent swelling of lymph nodes draining from the upper limbs, cat-scratch disease may be suspected on the grounds of epidemiological and clinical features, with a limited systemic involvement contrasting with a prominent local disease. The significance of specific antibody temporal kinetics in the subacute disease course is still unknown. Although biomolecular assays are now available, the time elapsed from disease onset to clinical diagnosis usually hampers diagnosis, while the roles of surgical debridement and of the unpredictable activity of antimicrobial chemotherapy warrant careful investigation.

Bartonelosis (Carrion's Disease) in the pediatric population of Peru: an overview and update

Bartonellosis, or Carrion's Disease, is an endemic and reemerging disease in Peru and Ecuador. Carrion's Disease constitutes a health problem in Peru because its epidemiology has been changing, and it is affecting new areas between the highland and the jungle. During the latest outbreaks, and previously in endemic areas, the pediatric population has been the most commonly affected. In the pediatric population, the acute phase symptoms are fever, anorexia, malaise, nausea and/or vomiting. The main signs are pallor, hepatomegaly, lymphadenopathies, cardiac murmur, and jaundice. Arthralgias and weight loss have also commonly been described. The morbidity and mortality of the acute phase is variable, and it is due mainly to superimposed infections or associated respiratory, cardiovascular, neurological or gastrointestinal complications. The eruptive phase, also known as Peruvian Wart, is characterized by eruptive nodes (which commonly bleed) and arthralgias. The mortality of the eruptive phase is currently extremely low. The diagnosis is still based on blood culture and direct observation of the bacilli in a blood smear. In the chronic phase, the diagnosis is based on biopsy or serologic assays. There are nationally standardized treatments for the acute phase, which consist of ciprofloxacin, and alternatively chloramphenicol plus penicillin G. However, most of the treatments are based on evidence from reported cases. During the eruptive phase the recommended treatment is rifampin, and alternatively, azithromycin or erythromycin.

Bartonelosis (fiebre de la Oroya o verruga peruana): reporte de un caso-revisión de la literatura / Bartonellosis(Oroya fever or verruga paruana): a case report and literature review

Se presenta un caso típico de verruga peruana atendido en el Servicio de Dermatología del Hospital Alberto Sabogal Sologuren, y a raíz de ello revisamos esta interesante enfermedad emergente mundial. La bartonelosis humana al principio fue asociada básicamente a la especie Bartonella bacilliformis, pero hoy en día se han descubierto hasta 18 Bartonellas que afectan al humano y a varios animales domésticos. La Bartonella bacilliformis es una parásito bacteriano intracelular 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. Aunque las infecciones que involucran especies de Bartonella, tales como Bartonella henselae quintan, ocurren en todo el mundo, la enfermedad de Carrión es endémica únicamente en Sudamérica. Las infecciones por B. bacilliformis son un problema de salud en numerosas áreas rurales de Sudamérica y para los viajeros que visitan estas regiones montañosas de Perú, Ecuador y Colombia. La Lutzomya verrucarum es el principal vector para la transmisión de la bacteria al ser humano; la hembra del mosquito transmite el patógeno durante su alimentación nocturna de sangre humana. Presumiblemente el insecto se alimenta de la 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.

Estudio clínico de 145 casos de bartonellosis en el Hospital Nacional cayetano Heredia: 1969-1992 / Clinic study of 145 cases of bartonellosis in Hospital Nacional Cayetano Heredia: 1969-1992

El estudio de 145 casos con bartonellosis (68 en fase aguda y 77 en fase eruptiva), demuestra que un 50 por ciento (34/68) de los pacientes en fase aguda eran residentes nativos de zonas endémicas, lo que revela su susceptibilidad a la adquisición de la Bartonellosis. Lugares principales de adquisición de la Bartonellosis son: 60.6 por ciento Ancash, 30.3 por ciento Lima, 3.4 por ciento Amazonas, 2.7 por ciento Cajamarca, 2 por ciento Huancavelica (probable nueva zona de bartonellosis). Los síntomas en la fase aguda en orden de importancia son: fiebre, palidez, hiporexia, decaimiento general, debilidad, postración, cefalea; en los pacientes en fase eruptiva: sangrado de las verrugas, fiebre, malestar general, artralgias. Signos importantes en los pacientes en fase aguda son: 97 por ciento palidez, 91.2 por ciento de regular a mal estado general, 82 por ciento hepatomegalia, 79.1 por ciento fiebre, 75.2 por ciento de regular a mal estado nutricional, 77.9 por ciento soplo sistólico, 71.6 por ciento ictericia, 70.1 por ciento linfoadenomegalia. Otros signos destacados en la evolución son: 29.4 por ciento edema pretibial, 26.4 por ciento somnolemcia, 22 por ciento mialgias, 16.4 por ciento derrame pericárdico, 14.7 por ciento fondo de ojo anormal (la gran mayoría con retinopatía hemorrágica), 10.2 por ciento convulsiones. Un hallazgo interesante es la positividad en el frotis sanguíneo y el aislamiento de Bartonella bacilliformis en la sangre del 13 por ciento (2/15) de pacientes en fase eruptiva. En los pacientes agudos, el promedio del hematocrito inicial ht(i) fue de 17.21 por ciento, un 61 por ciento presentó leucocitosis inicial y sólo el 17.2 por ciento tuvo linfopenia, no se tuvieron casos de leucopenia. El 60 por ciento tuvo incremento de bilirrubina total, predominando el incremento de la bilirrubina directa sobre la indirecta. La serología antibartonella practicada a sólo 21 de los pacientes, tuvo una sensibilidad de 95.2 por ciento para Elisa y 100 por ciento para Western blot. Un 36.7 por ciento de los pacientes en fase aguda presenta complicación infecciosa, predominando la bacteriana con 8 casos, 5 a Salmonella no tífica, 1 a Shigella dysenteriae, 1 a Enterobacter sp, 1 a Estafilococo aureus; 2 pacientes con Salmonella typhi. Le siguió en forma importante, la complicación parasitaria con 5 casos de probable reactivación de toxoplasmosis y 1 caso con histeoplasmosis diseminada (descrita pro primera vez). Los pacientes en fase aguda que se complic