RESUMO
INTRODUCTION: Aminoglycosides are vital antibiotics for treating Brucella infections, because they interfere with bacterial protein production and are often combined with other antibiotics. They are cost-effective, have fewer side effects, and can penetrate biofilms. The prevalence of brucellosis has increased in recent years, increasing the need for effective treatments. In addition, the emergence of multidrug-resistant Brucella strains has highlighted the need for an updated and comprehensive understanding of aminoglycoside resistance. This systematic review aimed to provide a comprehensive overview of the global prevalence of aminoglycoside resistance in B. melitensis and B. abortus. METHODS: A systematic search of online databases was conducted and eligible studies met certain criteria and were published in English. Quality assessment was performed using the JBI Checklist. A random-effects model was fitted to the data, and meta-regression, subgroup, and outlier/influential analyses were performed. The analysis was performed using R and the metafor package. RESULTS: The results of this systematic review and meta-analysis suggested that the average prevalence rates of streptomycin, gentamicin, and amikacin resistance were 0.027 (95% confidence interval [CI], 0.015-0.049), 0.023 (95% CI, 0.017-0.032), and 0.008 (95% CI, 0.002-0.039), respectively. The prevalence of streptomycin resistance was higher in the unidentified Brucella group than in the B. abortus and B. melitensis groups (0.234, 0.046, and 0.017, respectively; p < 0.02). The prevalence of gentamicin resistance increased over time (r = 0.064; 95% CI, 0.018 to 0.111; p = 0.007). The prevalence of resistance did not correlate with the quality score for any antibiotic. Funnel plots showed a potential asymmetry for streptomycin and gentamicin. These results suggest a low prevalence of antibiotic resistance in the studied populations. CONCLUSION: The prevalence of aminoglycoside resistance in B. melitensis and B. abortus was low. However, gentamicin resistance has increased in recent years. This review provides a comprehensive and updated understanding of aminoglycoside resistance in B. melitensis and B. abortus.
Assuntos
Aminoglicosídeos , Antibacterianos , Brucella abortus , Brucella melitensis , Brucelose , Aminoglicosídeos/farmacologia , Brucella abortus/efeitos dos fármacos , Brucella abortus/genética , Brucella abortus/isolamento & purificação , Antibacterianos/farmacologia , Brucelose/microbiologia , Brucelose/epidemiologia , Brucella melitensis/efeitos dos fármacos , Brucella melitensis/isolamento & purificação , Brucella melitensis/genética , Humanos , Prevalência , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , AnimaisRESUMO
La endocarditis bacteriana secundaria a la infección por Brucella spp., en este caso B. melitensis, como complicación de la brucelosis humana tiene una incidencia baja y, aunque es la presentación clínica con la que se asocia más frecuentemente la mortalidad, no todos los casos son letales, si son tratados oportunamente. Se describe el caso clínico de una endocarditis bacteriana por B. melitensis, diagnosticada en un adulto por el aislamiento del microorganismo en el hemocultivo. Paciente del sexo masculino, de 40 años, con antecedentes de realizar partos en el ganado bovino y consumir leche no pasteurizada. Acudió al médico por presentar durante siete días de evolución de las siguientes manifestaciones clínicas: fiebre, mialgias, artralgias, tos seca y pérdida de peso (15 kg). El hemograma informa: leucopenia, trombocitopenia y anemia; mientras que en un ecocardiograma transesofágico se observó vegetación en la válvula aórtica con una disminución de la función sistólica y en el hemocultivo se aisló B. melitensis. Debido a estos antecedentes, se inició el tratamiento antibacteriano con rifampicina, doxiciclina y gentamicina. El paciente se recuperó y tuvo una evolución clínica satisfactoria. La brucelosis es una enfermedad infrecuente. Debe considerarse en toda persona con fiebre de foco desconocido que resida en zonas endémicas o esté expuesto al cuidado de animales de granja. En esta enfermedad se impone un diagnóstico y tratamiento preciso, por ser una complicación con alta letalidad.
Bacterial endocarditis, secondary to Brucella spp. infection, in this case by B. melitensis, as a complication of human brucellosis has a low incidence. Although it is the clinical presentation most frequently associated with mortality, not all cases are lethal if timely treatment is provided. We describe a clinical case of bacterial endocarditis due to B. melitensis in a 40-year-old male patient with a history of conducting cattle deliveries and consuming unpasteurized milk, diagnosed after isolating the microorganism in blood culture. He presented with the following clinical manifestations after seven days of evolution: fever, myalgias, arthralgias, dry cough and weight loss (15 kg). The hemogram revealed leukopenia, thrombocytopenia, and anemia; while a transesophageal echocardiogram showed vegetation on the aortic valve with decreased systolic function, and B. melitensis was isolated in a blood culture. Considering this medical history, antibacterial treatment was initiated with rifampicin, doxycycline and gentamicin. The patient recovered and had satisfactory clinical evolution. Brucellosis is a rare disease. It should be considered in any person with a fever of unknown origin who lives in endemic areas or is exposed to the care of farm animals. Endocarditis is a highly lethal complication of human brucellosis; therefore, it requires a precise diagnosis and treatment.
Assuntos
Humanos , Masculino , Adulto , Gentamicinas/uso terapêutico , Brucella melitensis/patogenicidade , Endocardite Bacteriana/complicaçõesRESUMO
Brucellosis is a zoonosis caused by Brucella; B. melitensis is the most prevalent species in goats and humans. Previously, three B. melitensis peptides, rBtuB-Hia-FlgK showed antigen-specific immune responses in rodent models. The goal of this study was to evaluate the goat Th1/Th2 immune response to B. melitensis peptides. Twenty-eight animals were separated into four groups and were immunized with the rBtuB-Hia-FlgK peptides cocktail, adjuvant, PBS and Rev-1 vaccine, respectively. Peripheral blood samples were collected on days 0, 15, and 80 post-inoculation. The CD4+ and CD8+ T cells proliferation, and cytokine production of the Th-1 (IL-2, IL-12, TNF-α, and IFN-γ) and Th-2 profiles (IL-4, IL-5, and IL-10) were evaluated. An increase of CD4+/CD8+ at 15 days post-vaccination was observed and continued until the 80th. In addition, the IFN-γ, TNF-α, and IL-2 mRNA expression were typically induced by the 15th day, but only IFN-γ levels were observed at day 80 post-immunization. Brucella pathogenesis is distinguished by the presence of a large amount of Th-1 cytokines. Although a reduced amount of IFN-γ in the culture supernatant was accurately detected compared with Rev-1 after 15 days, it could be influenced by the sampling schedule, as a higher cytokine production might be induced as early as the first-week post-vaccination. The results indicate that rBtuB-Hia-FlgK induced an immune response similar to the Rev-1 vaccine. The possible use of inert molecules with the unique ability to typically induce cellular response similar to attenuated vaccine represents an attractive option that should not be ruled out.
Assuntos
Vacina contra Brucelose , Brucella melitensis , Brucelose , Doenças das Cabras , Humanos , Animais , Camundongos , Interleucina-2 , Cabras , Fator de Necrose Tumoral alfa , Brucelose/veterinária , Peptídeos , Imunidade Celular , Citocinas , Camundongos Endogâmicos BALB C , Doenças das Cabras/prevenção & controleRESUMO
Brucella melitensis and Brucella ovis are the primary etiological agents of brucellosis in small domestic ruminants. B. melitensis was first isolated in 1887 by David Bruce in Malta Island from spleens of four soldiers, while B. ovis was originally isolated in Australia and New Zealand in early 1950's from ovine abortion and rams epididymitis. Today, both agents are distributed worldwide: B. melitensis remains endemic and associated with an extensive negative impact on the productivity of flocks in -some regions, and B. ovis is still present in most sheep-raising regions in the world. Despite being species of the same bacterial genus, B. melitensis and B. ovis have extensive differences in their cultural and biochemical characteristics (smooth vs. rough colonial phases, serum and CO2 dependence for in vitro growth, carbohydrate metabolism), host preference (female goat and sheep vs. rams), the outcome of infection (abortion vs. epididymitis), and their zoonotic potential. Some of these differences can be explained at the bacterial genomic level, but the role of the host genome in promoting or preventing interaction with pathogens is largely unknown. Diagnostic techniques and measures to prevent and control brucellosis in small ruminants vary, with B. melitensis having more available tools for detection and prevention than B. ovis. This review summarizes and analyzes current available information on: (1) the similarities and differences between these two etiological agents of brucellosis in small ruminants, (2) the outcomes after their interaction with different preferred hosts and current diagnostic methodologies, (3) the prevention and control measures, and (4) alerting animal producers about the disease and raise awareness in the research community for future innovative activities.
RESUMO
Brucellosis is a zoonotic disease widespread almost all over the world, representing a significant economic and public health problem. Brucella melitensis, B. suis and B. abortus are considered the most pathogenic species for humans. The most virulent species, B. melitensis is endemic in many parts of the world, particularly the biovar 3 in the Mediterranean and Eastern Europe. Some Latin American countries are seriously affected by biovar 1, especially Mexico, Peru and northern Argentina. Furthermore, while Brazil is considered free of this etiologic agent, one recurrent question is whether this infection really does not occur in Brazil or there is a lack of research/data on the subject. To answer this question, this study aims to investigate the occurrence of antibodies against smooth Brucella in goats and sheep in the states of Sergipe, Paraíba, Ceará and Paraíba. All samples were screened by the Rose Bengal test (RBT). The complement fixation (CFT) and the fluorescence polarization (FPT) tests were used as confirmatory tests. There were no positive samples in the confirmatory tests (both CFT and FPT). We, therefore, conclude that this result reinforces the previous knowledge regarding the exotic status of B. melitensis infection in Brazil.
A brucelose é uma das doenças de caráter zoonótico mais difundidas no mundo, representando um grande problema econômico e de saúde pública. A Brucella melitensis, a B. suis e a B. abortus são consideradas as mais patogênicas espécies para humanos. A espécie apontada como a mais virulenta é a B. melitensis, endêmica em várias partes do mundo, particularmente o biovar 3 na região do Mediterrâneo e na Europa Oriental. Alguns países da América Latina são seriamente afetados pelo biovar 1, especialmente México, Peru e norte da Argentina. O Brasil é considerado livre desse agente etiológico, porém sempre há o questionamento se a infecção não ocorre ou se falta pesquisa. Diante dessa questão, o objetivo deste trabalho foi investigar a ocorrência de anticorpos contra amostras lisas de Brucella em caprinos e ovinos dos estados de Sergipe, Bahia, Ceará e Paraíba. Todas as amostras foram submetidas triagem pelo teste do antígeno acidificado tamponado (AAT). Como testes confirmatórios, utilizou-se a reação de fixação de complemento (RFC) e também o teste de polarização fluorescente (TPF). Nenhuma amostra foi positiva nos testes confirmatórios (RFC e TPF). Esse resultado comprova que a infecção por B. melitensis é exótica no Brasil.
Assuntos
Animais , Brucelose/epidemiologia , Cabras/microbiologia , Ovinos/microbiologia , Brucella melitensis/isolamento & purificação , Polarização de Fluorescência/veterináriaRESUMO
Brucella melitensis is the main cause of human brucellosis worldwide and is considered the most virulent and neurotropic species. In Mexico, this species is considered endemic, being reported since the first decade of the 20th century. Here we present a case of subacute transverse myelitis with the isolation and identification of B. melitensis as the causative agent of Neurobrucellosis in a female patient from the coastal state of Guerrero, Mexico.
Assuntos
Brucella melitensis/isolamento & purificação , Brucelose/diagnóstico , Mielite Transversa/diagnóstico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Brucelose/complicações , Brucelose/tratamento farmacológico , Ceftriaxona/administração & dosagem , Ceftriaxona/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Infusões Intravenosas , Mielite Transversa/complicações , Mielite Transversa/tratamento farmacológicoRESUMO
Resumen La brucelosis, principal zoonosis a nivel mundial tiene alta prevalencia en varios países de Latinoamérica. Se asocia con la exposición a ganado infectado por distintas especies del género Brucella. B. melitensis la más virulenta para el humano, causa con frecuencia complicaciones de predominio osteoarticular. En Colombia se cree que la infección por B. melitensis es una entidad ausente, a pesar de su plausibilidad biológica en nuestro contexto; sin embargo, son escasos los estudios sobre su ocurrencia y mínimo el índice de sospecha de la enfermedad, por lo cual creemos está subdiagnosticada. Presentamos el primer caso confirmado de brucelosis por B. melitensis en Colombia en una joven embarazada, con diagnóstico incidental, en quien el análisis retrospectivo de su cuadro clínico alertó sobre puntos clave que pueden impactar en el diagnóstico y tratamiento oportuno de la enfermedad. Se plantean preguntas de prevalencia real de esta entidad en Colombia.
Summary Brucellosis, the principal zoonoses globally is highly prevalent in different countries of Latin America. It is associated with the exposition of livestock infected with different Brucella species, being B. melitensis the most virulent for humans, and frequently causing osteoarticular complications. In Colombia it is believed that B. melitensis infection is an absent entity, despite its biological plausibility in our context; however, there are few studies on its occurrence and a minimum index of suspicion of the disease, which is why we believe it is underdiagnosed. We present the first confirmed case of brucellosis by B. melitensis in Colombia diagnosed in a young pregnant patient, with an incidental diagnosis, in whom a retrospective analysis of her clinical outcome warned of key points that may impact on the diagnosis and timely treatment of the disease. We present several questions surrounding the real prevalence of this entity in Colombia.
Assuntos
Humanos , Feminino , Gravidez , Adolescente , Brucelose , Zoonoses , Brucella melitensis , Brucella , Etnicidade , Colômbia , Gado , InfecçõesRESUMO
[This corrects the article DOI: 10.3389/fvets.2019.00175.].
RESUMO
Members of the genus Brucella cluster in two phylogenetic groups: classical and non-classical species. The former group is composed of Brucella species that cause disease in mammals, including humans. A Brucella species, labeled as Brucella sp. BCCN84.3, was isolated from the testes of a Saint Bernard dog suffering orchiepididymitis, in Costa Rica. Following standard microbiological methods, the bacterium was first defined as "Brucella melitensis biovar 2." Further molecular typing, identified the strain as an atypical "Brucella suis." Distinctive Brucella sp. BCCN84.3 markers, absent in other Brucella species and strains, were revealed by fatty acid methyl ester analysis, high resolution melting PCR and omp25 and omp2a/omp2b gene diversity. Analysis of multiple loci variable number of tandem repeats and whole genome sequencing demonstrated that this isolate was different from the currently described Brucella species. The smooth Brucella sp. BCCN84.3 clusters together with the classical Brucella clade and displays all the genes required for virulence. Brucella sp. BCCN84.3 is a species nova taxonomical entity displaying pathogenicity; therefore, relevant for differential diagnoses in the context of brucellosis. Considering the debate on the Brucella species concept, there is a need to describe the extant taxonomical entities of these pathogens in order to understand the dispersion and evolution.
RESUMO
Brucellosis is an infectious disease that affects practically all species of mammals, including human, and is a major zoonosis worldwide. Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in phagocytic and nonphagocytic cells such as trophoblast and epithelial cells. Among the six recognized species of the genus Brucella, Brucella melitensis is the main etiological agent involved in goat brucellosis and is also the most pathogenic for human. It causes significant losses in livestock production as a result of abortions, metritis, infertility, and birth of weak animals. Outer membrane proteins (OMPs) are exposed on the bacterial surface and are in contact with cells and effectors of the host immune response, whereby they could be important virulence factors of Brucella species. To evaluate this hypothesis, the gene encoding for the major outer membrane protein Omp31 was amplified, cloned into pUC18 plasmid, and inactivated by inserting a kanamycin cassette, rendering pLVM31 plasmid which was transformed into B. melitensis wild-type strain to obtain LVM31 mutant strain. The Outer membrane (OM) properties of the mutant strain were compared with B. melitensis Bm133 wild-type and B. melitensis Rev1 vaccine strains, in assessing its susceptibility to polymyxin B, sodium deoxycholate, and nonimmune serum. The mutant strain was assessed in vitro with survival assays in murine macrophages J774.A1 and HeLa cells. Our results demonstrate that LVM31 mutant is more susceptible to polymyxin B, sodium deoxycholate, and nonimmune serum than control strains; moreover, Omp31 mutation caused a decrease in the internalization and a significant decrease in the intracellular survival compared with the reference strains in both cell lines. These results allow us to conclude that Omp31 is important for maintaining OM integrity, but also it is necessary for bacterial internalization, establishment and development of an optimal replication niche, and essential for survival and intracellular multiplication.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Brucella melitensis/patogenicidade , Brucelose/patologia , Macrófagos/microbiologia , Animais , Brucella melitensis/genética , Brucella melitensis/metabolismo , Brucelose/microbiologia , Linhagem Celular Tumoral , Ácido Desoxicólico/farmacologia , Células HeLa , Humanos , Macrófagos/imunologia , Camundongos , Testes de Sensibilidade Microbiana , Mutação/genética , Plasmídeos/genética , Polimixina B/farmacologia , Fatores de Virulência/metabolismoRESUMO
Se realizó un estudio epidemiológico de brucelosis en 516 majadas caprinas o mixtas (caprinos/ovinos) de las 3 regiones agroecológicas de la provincia de Formosa, Argentina. Mediante las pruebas de aglutinación en placa con antígeno tamponado y de fijación del complemento en suero se estudiaron un total de 25.401 caprinos y 2.453 ovinos. Además, se realizaron cultivos bacteriológicos y PCR en muestras de leche de cabras de 3 majadas con brucelosis y abortos recientes. Se detectó brucelosis en 4 de los 9 departamentos de la provincia, la prevalencia global fue del 2 % y la intrapredial varió entre el 1 y el 40%. La proporción de majadas positivas fue del 3,6, el 12 y el 36 % para las regiones este, centro y oeste, respectivamente. Se aisló Brucella melitensis bv. 1 de cabras por primera vez en la provincia. La PCR amplificó fragmentos esperados de 827 pb correspondiente al gen omp2ab (Brucella spp.) y de 731 pb correspondiente al inserto IS711 (B. melitensis). La detección de anticuerpos en ovinos que cohabitan con caprinos sugiere que las infecciones habrían sido causadas por B. melitensis, lo que constituye un riesgo adicional para la salud pública. Los programas de control y erradicación de la brucelosis deberían considerar las majadas mixtas como una sola unidad epidemiológica. Los resultados indican que la brucelosis por B. melitensis bv. 1 es altamente endémica en las regiones centro y oeste de la provincia de Formosa.
An epidemiological study of brucellosis was carried out in 516 goats and mixed flocks (goat/sheep) from the three agro-ecological regions of Formosa province, Argentina. Serum samples from a total of 25401 goats and 2453 sheeps were analyzed using buffered plate agglutination test (BPAT) and complement fixation test (CFT). Bacteriological and PCR analyses on milk samples from goats in three flocks with a history of brucellosis and recent abortions were also performed. Brucellosis was detected in four of the nine departments of the province with an overall prevalence of 2 % and an intra-flock prevalence ranging between 1 % and 40 %. The proportion of infected flocks was 3.6 %, 12 % and 36 % for the eastern, central and western regions, respectively. Brucella melitensis bv. 1 was isolated efrom goats for the first time in the province. The expected fragments of 827 bp from the omp2ab gene (Brucella spp.) and 731 bp from the insert IS711 (B. melitensis) were amplified by PCR. Detection of antibodies by BPAT and FCT in sheep cohabiting with goats suggests that infections could have been caused by B. melitensis, posing an additional risk to public health. Control and eradication programs for brucellosis should consider mixed flocks as a single epidemiological unit. The results indicate that brucellosis by B. melitensis bv1 is highly endemic in the central and western regions of Formosa province.
Assuntos
Animais , Feminino , Masculino , Gravidez , Doenças dos Ovinos/epidemiologia , Brucelose/veterinária , Doenças das Cabras/epidemiologia , Brucella melitensis/isolamento & purificação , Argentina/epidemiologia , Doenças dos Ovinos/microbiologia , Doenças dos Ovinos/transmissão , Brucelose/microbiologia , Brucelose/transmissão , Brucelose/epidemiologia , Cabras/microbiologia , Ovinos/microbiologia , Doenças das Cabras/microbiologia , Doenças das Cabras/transmissão , Estudos Soroepidemiológicos , Prevalência , Técnicas de Tipagem Bacteriana , Brucella melitensis/imunologia , Aborto Animal/etiologia , Aborto Animal/microbiologia , Leite/microbiologia , Geografia Médica , Criação de Animais Domésticos/métodos , Anticorpos Antibacterianos/sangueRESUMO
An epidemiological study of brucellosis was carried out in 516 goats and mixed flocks (goat/sheep) from the three agro-ecological regions of Formosa province, Argentina. Serum samples from a total of 25401 goats and 2453 sheeps were analyzed using buffered plate agglutination test (BPAT) and complement fixation test (CFT). Bacteriological and PCR analyses on milk samples from goats in three flocks with a history of brucellosis and recent abortions were also performed. Brucellosis was detected in four of the nine departments of the province with an overall prevalence of 2% and an intra-flock prevalence ranging between 1% and 40%. The proportion of infected flocks was 3.6%, 12% and 36% for the eastern, central and western regions, respectively. Brucella melitensis bv. 1 was isolated efrom goats for the first time in the province. The expected fragments of 827bp from the omp2ab gene (Brucella spp.) and 731bp from the insert IS711 (B. melitensis) were amplified by PCR. Detection of antibodies by BPAT and FCT in sheep cohabiting with goats suggests that infections could have been caused by B. melitensis, posing an additional risk to public health. Control and eradication programs for brucellosis should consider mixed flocks as a single epidemiological unit. The results indicate that brucellosis by B. melitensis bv1 is highly endemic in the central and western regions of Formosa province.
Assuntos
Brucella melitensis/isolamento & purificação , Brucelose/veterinária , Doenças das Cabras/epidemiologia , Doenças dos Ovinos/epidemiologia , Aborto Animal/etiologia , Aborto Animal/microbiologia , Criação de Animais Domésticos/métodos , Animais , Anticorpos Antibacterianos/sangue , Argentina/epidemiologia , Técnicas de Tipagem Bacteriana , Brucella melitensis/imunologia , Brucelose/epidemiologia , Brucelose/microbiologia , Brucelose/transmissão , Feminino , Geografia Médica , Doenças das Cabras/microbiologia , Doenças das Cabras/transmissão , Cabras/microbiologia , Masculino , Leite/microbiologia , Gravidez , Prevalência , Estudos Soroepidemiológicos , Ovinos/microbiologia , Doenças dos Ovinos/microbiologia , Doenças dos Ovinos/transmissãoRESUMO
Brucellosis is an endemic disease in small-scale goat husbandry systems in Mexico. It is a zoonosis and the economic consequences can be large, although estimates are not available for the Mexican goat sector. Our objective was to conduct a financial analysis of brucellosis control in a prominent dairy goat production area of the Bajío region, Mexico. We used three models: (1) a brucellosis transmission model at village flock level (n=1000 head), (2) a flock growth model at smallholder flock level (n=23 head) using output of model 1 and (3) cost-benefit analysis of several brucellosis control scenarios based on output of model 2. Scenarios consisted of test-and-slaughter or vaccination or a combination of both compared to the base situation (no control). The average net present values (NPV) of using vaccination over a 5-year period was 3.8 US$ (90% CI: 1.3-6.6) and 20 US$ (90% CI: 11.3-28.6) over a 10-year period per goat. The average benefit-cost ratios over a 5-year period and 10-year period were 4.3 US$ (90% CI: 2.2-6.9) and 12.3 US$ (90% CI: 7.5-17.3) per goat, respectively. For the total dairy goat population (38,462 head) of the study area (the Bajío of Jalisco and Michoacán) the NPV's over a 5-year and 10-year period were 0.15 million US$ and 0.8 million US$. However, brucellosis prevalence was predicted to remain relatively high at about 12%. Control scenarios with test-and-slaughter predicted to reduce brucellosis prevalence to less than 3%, but this produced a negative NPV over a 5-year period ranging from -31.6 to -11.1 US$ and from -31.1 to 7.5 US$ over a 10-year period. A brucellosis control campaign based on vaccination with full coverage is economically profitable for the goat dairy sector of the region although smallholders would need financial support in case test-and-slaughter is applied to reduce the prevalence more quickly.
Assuntos
Criação de Animais Domésticos/economia , Brucelose/veterinária , Doenças das Cabras/economia , Doenças das Cabras/prevenção & controle , Criação de Animais Domésticos/métodos , Animais , Vacinas Bacterianas/economia , Brucelose/economia , Brucelose/epidemiologia , Brucelose/prevenção & controle , Brucelose/transmissão , Controle de Doenças Transmissíveis/economia , Controle de Doenças Transmissíveis/métodos , Simulação por Computador , Análise Custo-Benefício , Doenças das Cabras/epidemiologia , Doenças das Cabras/transmissão , Cabras , México/epidemiologia , Vacinação/veterináriaRESUMO
El objetivo de la investigación fue realizar un estudio descriptivo de la ocurrencia de brucelosis humana en Colombia entre 2000 y 2012, y con base en estudios previos conocer la prevalencia e incidencia de la enfermedad, las limitaciones para el diagnóstico oportuno y el reconocimiento de la enfermedad por el sistema laboral colombiano. La investigación se basó en la búsqueda y análisis de la información publicada en artículos relacionados con brucelosis humana entre 2000 y 2012 en Colombia. En esta investigación se incluyó una fase de recopilación de información y entrevistas no estructuradas a representantes de programas de control de brucelosis y a profesionales expertos. Se analizaron 17 trabajos de brucelosis humana realizados en el personal a riesgo en plantas de beneficio, expendedores y vacunadores del programa de brucelosis animal, en los cuales se reportaron 10 estudios con prevalencias entre 0,14% y 10,4% y 7 con seropositividad. En estos se encontró alguna información pertinente a las limitaciones del diagnóstico y se evidenció el poco conocimiento de la comunidad médica frente a la enfermedad. En Colombia no hay una política clara respecto a esta zoonosis de riesgo ocupacional. Solo se menciona la brucelosis en el Decreto 2566 de 2009, en la cual se adopta la nueva tabla de enfermedades profesionales. Se concluye que la brucelosis humana en Colombia es una enfermedad subdiagnosticada y, por lo tanto, subnotificada, ya que no existe un sistema de notificación obligatoria.
This research aims to conduct a descriptive study of the occurrence of human brucellosis in Colombia between 2000 and 2012, and, based on previous studies, to determine the prevalence and incidence of the disease, and the limitations for its timely diagnosis and recognition by the Colombian labor system. The research consisted of searching for and analyzing articles on human brucellosis published between 2000 and 2012 in Colombia. It included a phase of information gathering and unstructured interviews with representatives of brucellosis control programs and experienced professionals. We analyzed 17 studies of human brucellosis cases in personnel at risk in slaughterhouses, retailers and vaccinators for animal brucellosis programs: 10 of them reported prevalences between 0.14% and 10.4%, and seven evidenced seropositivity. Information revealed the limitations of the diagnosis, and it demonstrated the little knowledge of the medical community about this disease. In Colombia, there is no clear policy regarding this occupational zoonosis. Brucellosis is mentioned only in Decree 2566 of 2009, in which the new table of occupational diseases is established. The paper concludes that human brucellosis in Colombia is an underdiagnosed, and therefore underreported, disease since there is no mandatory reporting system on the subject.
O objetivo da pesquisa foi realizar um estudo descritivo da ocorrência de brucelose humana na Colômbia entre 2000 e 2012, e com base em estudos prévios conhecer a prevalência e incidência da doença, as limitações para o diagnóstico oportuno e o reconhecimento da doença pelo sistema laboral colombiano. A pesquisa se baseou na busca e análise da informação publicada em artigos relacionados com brucelose humana entre 2000 e 2012 na Colômbia. Nesta pesquisa se incluiu uma fase de recopilação de informação e entrevistas não estruturadas às representantes de programas de controle de brucelose e a profissionais especialistas. Analisaram-se 17 trabalhos de brucelose humana realizados no pessoal a risco em plantas de benefício, vendedores e vacinadores do programa de brucelose animal, nos quais se reportaram 10 estudos com prevalências entre 0,14% e 10,4% e 7 com soro positividade. Nestes se encontrou alguma informação pertinente às limitações do diagnóstico e se evidenciou o pouco conhecimento da comunidade médica frente na doença. Na Colômbia não há uma política clara em relação com esta zoonose de risco ocupacional. Solo se menciona a brucelose no Decreto 2566 de 2009, na qual se adota a nova tabela de doenças profissionais. Conclui-se que a brucelose humana na Colômbia é uma doença subdiagnosticada e, portanto, subnotificada, já que não existe um sistema de notificação obrigatória.
RESUMO
Some of the mechanisms underlying the invasion and intracellular survival of B. melitensis are still unknown, including the role of a subfamily of NUDIX enzymes, which have been described in other bacterial species as invasins and are present in Brucella spp. We have generated a mutation in the coding gene of one of these proteins, the invA gene (BMEI0215) of B. melitensis strain 133, to understand its role in virulence. HeLa cell invasion results showed that mutant strain survival was decreased 5-fold compared with that of the parental strain at 2 h pi (P<0.001). In a goat macrophage infection assay, mutant strain replication was 8-fold less than in the parental strain at 24 h pi (P<0.001); yet, at 48 h pi, no significant differences in intracellular replication were observed. Additionally, colocalization of the invA mutant with calregulin was significantly lower at 24 h pi compared with that of the parental strain. Furthermore, the mutant strain exhibited a low level of colocalization with cathepsin D, which was similar to the parental strain colocalization at 24 h pi. In vivo infection results demonstrated that spleen colonization was significantly lower with the mutant than with the parental strain. The immune response, measured in terms of antibody switching and IFN-γ transcription, was similar for Rev1 and infection with the mutant, although it was lower than the immune response elicited by the parental strain. Consequently, these results indicate that the invA gene is important during invasion but not for intracellular replication. Additionally, mutation of the invA gene results in in vivo attenuation.
Assuntos
Proteínas de Bactérias/metabolismo , Brucella melitensis/enzimologia , Brucelose/microbiologia , Animais , Proteínas de Bactérias/genética , Brucella melitensis/genética , Brucella melitensis/patogenicidade , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , VirulênciaRESUMO
The treatment of brucellosis is still problematic, because of high rates of treatment failure or relapses. As the microorganism is an intracellular pathogen, treatment requires combined regimens. However, limited existing data on in vitro combinations are avaliable for Brucellae. The aim of this study was to investigate the in vitro efficacy of various traditional and new antibiotic combinations against 16 Brucella melitensis strains. The combination effect of antimicrobial agents was evaluated by E-test synergy method to obtain a fractional inhibitory concentration (FIC) index. Co-Trimoxazole (SXT) and moxifloxocin (MXF) exhibited the lowest MIC, while Rifampin (RIF) had the highest MIC in the study. Combinations with RIF showed the best synergistic activity (100 percent of RIF-tetracycline (TET), and 87.5 percent of RIF-SXT). Synergistic activity was also detected at seven (43.7 percent) of ciprofloxocin (CIP)-SXT, four (25 percent) of TET-MXF, and two (12.5 percent) of TET-SXT combinations. The combinations that demonstrated additivity were TET-SXT, CIP-SXT and TET-MXF. Antagonism was observed only with the TET-Streptomycin (STR) combination in three strains (18.8 percent). Further work including randomized controlled clinical trials is required to fully evaluate the usefulness of these data.
O tratamento da brucelose é problemático devido à alta freqüência de tratamentos mal sucedidos e recidivas. Por tratar-se de um patógeno intracelular, o tratamento requer procedimentos combinados. Entretanto, existem poucos dados sobre combinações in vitro para Brucellae. O objetivo deste trabalho foi investigar a eficiência de vários tratamentos tradicionais e novas combinações de antibióticos contra 16 isolados de Brucella melitensis. O efeito combinado foi avaliado através do método do E-test para obtenção do FIC (índice de concentração inibitória fracional). Co-trimoxazol (SXT) e moxifloxocina (MXF) apresentaram o MIC mais baixo, enquanto rifampicina (RIF) apresentou o MIC mais alto. Combinações com RIF mostraram a melhor atividade sinergística (100 por cento para RIF-tetraciclina e 87,5 por cento para RIF-SXT). Atividade sinergística foi também detectada para sete (43,7 por cento) combinações de ciprofloxacina (CIP-STX), quatro (25 por cento) de TET-MXF e duas (12,5 por cento) de TET-SXT. As combinações que apresentaram efeito aditivo foram TET-SXT, CIP-SXT e TET-MXF. Antagonismo foi observado somente para a combinação TET-estreptomicina (STR) em três isolados (18,8 por cento). Mais pesquisas utilizando ensaios clínicos randomizados controlados são necessárias para avaliar a utilidade desses dados.
Assuntos
Humanos , Antibacterianos , Brucelose , Brucella melitensis/isolamento & purificação , Técnicas In Vitro , Técnicas e Procedimentos Diagnósticos , Sinergismo Farmacológico , Metodologia como Assunto , MétodosRESUMO
The treatment of brucellosis is still problematic, because of high rates of treatment failure or relapses. As the microorganism is an intracellular pathogen, treatment requires combined regimens. However, limited existing data on in vitro combinations are avaliable for Brucellae. The aim of this study was to investigate the in vitro efficacy of various traditional and new antibiotic combinations against 16 Brucella melitensis strains. The combination effect of antimicrobial agents was evaluated by E-test synergy method to obtain a fractional inhibitory concentration (FIC) index. Co-Trimoxazole (SXT) and moxifloxocin (MXF) exhibited the lowest MIC, while Rifampin (RIF) had the highest MIC in the study. Combinations with RIF showed the best synergistic activity (100% of RIF-tetracycline (TET), and 87.5% of RIF-SXT). Synergistic activity was also detected at seven (43.7%) of ciprofloxocin (CIP)-SXT, four (25%) of TET-MXF, and two (12.5%) of TET-SXT combinations. The combinations that demonstrated additivity were TET-SXT, CIP-SXT and TET-MXF. Antagonism was observed only with the TET-Streptomycin (STR) combination in three strains (18.8%). Further work including randomized controlled clinical trials is required to fully evaluate the usefulness of these data.
O tratamento da brucelose é problemático devido à alta freqüência de tratamentos mal sucedidos e recidivas. Por tratar-se de um patógeno intracelular, o tratamento requer procedimentos combinados. Entretanto, existem poucos dados sobre combinações in vitro para Brucellae. O objetivo deste trabalho foi investigar a eficiência de vários tratamentos tradicionais e novas combinações de antibióticos contra 16 isolados de Brucella melitensis. O efeito combinado foi avaliado através do método do E-test para obtenção do FIC (índice de concentração inibitória fracional). Co-trimoxazol (SXT) e moxifloxocina (MXF) apresentaram o MIC mais baixo, enquanto rifampicina (RIF) apresentou o MIC mais alto. Combinações com RIF mostraram a melhor atividade sinergística (100% para RIF-tetraciclina e 87,5% para RIF-SXT). Atividade sinergística foi também detectada para sete (43,7%) combinações de ciprofloxacina (CIP-STX), quatro (25%) de TET-MXF e duas (12,5%) de TET-SXT. As combinações que apresentaram efeito aditivo foram TET-SXT, CIP-SXT e TET-MXF. Antagonismo foi observado somente para a combinação TET-estreptomicina (STR) em três isolados (18,8%). Mais pesquisas utilizando ensaios clínicos randomizados controlados são necessárias para avaliar a utilidade desses dados.
RESUMO
The treatment of brucellosis is still problematic, because of high rates of treatment failure or relapses. As the microorganism is an intracellular pathogen, treatment requires combined regimens. However, limited existing data on in vitro combinations are avaliable for Brucellae. The aim of this study was to investigate the in vitro efficacy of various traditional and new antibiotic combinations against 16 Brucella melitensis strains. The combination effect of antimicrobial agents was evaluated by E-test synergy method to obtain a fractional inhibitory concentration (FIC) index. Co-Trimoxazole (SXT) and moxifloxocin (MXF) exhibited the lowest MIC, while Rifampin (RIF) had the highest MIC in the study. Combinations with RIF showed the best synergistic activity (100% of RIF-tetracycline (TET), and 87.5% of RIF-SXT). Synergistic activity was also detected at seven (43.7%) of ciprofloxocin (CIP)-SXT, four (25%) of TET-MXF, and two (12.5%) of TET-SXT combinations. The combinations that demonstrated additivity were TET-SXT, CIP-SXT and TET-MXF. Antagonism was observed only with the TET-Streptomycin (STR) combination in three strains (18.8%). Further work including randomized controlled clinical trials is required to fully evaluate the usefulness of these data.
RESUMO
The treatment of brucellosis is still problematic, because of high rates of treatment failure or relapses. As the microorganism is an intracellular pathogen, treatment requires combined regimens. However, limited existing data on in vitro combinations are avaliable for Brucellae. The aim of this study was to investigate the in vitro efficacy of various traditional and new antibiotic combinations against 16 Brucella melitensis strains. The combination effect of antimicrobial agents was evaluated by E-test synergy method to obtain a fractional inhibitory concentration (FIC) index. Co-Trimoxazole (SXT) and moxifloxocin (MXF) exhibited the lowest MIC, while Rifampin (RIF) had the highest MIC in the study. Combinations with RIF showed the best synergistic activity (100% of RIF-tetracycline (TET), and 87.5% of RIF-SXT). Synergistic activity was also detected at seven (43.7%) of ciprofloxocin (CIP)-SXT, four (25%) of TET-MXF, and two (12.5%) of TET-SXT combinations. The combinations that demonstrated additivity were TET-SXT, CIP-SXT and TET-MXF. Antagonism was observed only with the TET-Streptomycin (STR) combination in three strains (18.8%). Further work including randomized controlled clinical trials is required to fully evaluate the usefulness of these data.
O tratamento da brucelose é problemático devido à alta freqüência de tratamentos mal sucedidos e recidivas. Por tratar-se de um patógeno intracelular, o tratamento requer procedimentos combinados. Entretanto, existem poucos dados sobre combinações in vitro para Brucellae. O objetivo deste trabalho foi investigar a eficiência de vários tratamentos tradicionais e novas combinações de antibióticos contra 16 isolados de Brucella melitensis. O efeito combinado foi avaliado através do método do E-test para obtenção do FIC (índice de concentração inibitória fracional). Co-trimoxazol (SXT) e moxifloxocina (MXF) apresentaram o MIC mais baixo, enquanto rifampicina (RIF) apresentou o MIC mais alto. Combinações com RIF mostraram a melhor atividade sinergística (100% para RIF-tetraciclina e 87,5% para RIF-SXT). Atividade sinergística foi também detectada para sete (43,7%) combinações de ciprofloxacina (CIP-STX), quatro (25%) de TET-MXF e duas (12,5%) de TET-SXT. As combinações que apresentaram efeito aditivo foram TET-SXT, CIP-SXT e TET-MXF. Antagonismo foi observado somente para a combinação TET-estreptomicina (STR) em três isolados (18,8%). Mais pesquisas utilizando ensaios clínicos randomizados controlados são necessárias para avaliar a utilidade desses dados.