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1.
PLoS Negl Trop Dis ; 14(3): e0008197, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32203511

RESUMO

BACKGROUND: Leptospirosis, commonly known as rat-urine disease, is a global but endemic zoonotic disease in the tropics. Despite the historical report of leptospirosis in Malaysia, the information on human-infecting species is limited. Determining the circulating species is important to understand its epidemiology, thereby to strategize appropriate control measures through public health interventions, diagnostics, therapeutics and vaccine development. METHODOLOGY/PRINCIPLE FINDINGS: We investigated the human-infecting Leptospira species in blood and serum samples collected from clinically suspected leptospirosis patients admitted to three tertiary care hospitals in Malaysia. From a total of 165 patients, 92 (56%) were confirmed cases of leptospirosis through Microscopic Agglutination Test (MAT) (n = 43; 47%), Polymerase Chain Reaction (PCR) (n = 63; 68%) or both MAT and PCR (n = 14; 15%). The infecting Leptospira spp., determined by partial 16S rDNA (rrs) gene sequencing revealed two pathogenic species namely Leptospira interrogans (n = 44, 70%) and Leptospira kirschneri (n = 17, 27%) and one intermediate species Leptospira wolffii (n = 2, 3%). Multilocus sequence typing (MLST) identified an isolate of L. interrogans as a novel sequence type (ST 265), suggesting that this human-infecting strain has a unique genetic profile different from similar species isolated from rodents so far. CONCLUSIONS/SIGNIFICANCE: Leptospira interrogans and Leptospira kirschneri were identified as the dominant Leptospira species causing human leptospirosis in Central Malaysia. The existence of novel clinically important ST 265 (infecting human), that is different from rodent L. interrogans strains cautions reservoir(s) of these Leptospira lineages are yet to be identified.


Assuntos
Leptospira interrogans/isolamento & purificação , Leptospira/classificação , Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , Adulto , Testes de Aglutinação , Animais , Feminino , Genes Bacterianos/genética , Humanos , Leptospira/genética , Leptospira/patogenicidade , Leptospira interrogans/genética , Leptospira interrogans/patogenicidade , Leptospirose/sangue , Leptospirose/urina , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Doenças dos Roedores , Roedores , Análise de Sequência de DNA , Testes Sorológicos , Adulto Jovem , Zoonoses
2.
PLoS One ; 15(2): e0228577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074117

RESUMO

Knowledge on the possible sources of human leptospirosis, other than rats, is currently lacking. To assess the distribution pattern of exposure and infection by Leptospira serogroups in the two main semi-aquatic rodents of Western France, coypus (Myocastor coypus) and muskrats (Ondatra zibethicus), results of micro-agglutination testing and renal tissue PCR were used. In coypus, the apparent prevalence was 11% (n = 524, CI95% = [9% - 14%]), seroprevalence was 42% (n = 590, CI95% = [38% - 46%]), and the predominant serogroup was Australis (84%). In muskrats, the apparent prevalence was 33% (n = 274, CI95% = [27% - 39%]), seroprevalence was 57% (n = 305, CI95% = [52% - 63%]), and the predominant serogroup was Grippotyphosa (47%). Muskrats should therefore be considered an important source of Grippotyphosa infection in humans and domestic animals exposed in this part of France.


Assuntos
Arvicolinae/microbiologia , Portador Sadio/microbiologia , Leptospira/patogenicidade , Animais , Anticorpos Antibacterianos/sangue , Arvicolinae/sangue , Arvicolinae/imunologia , Portador Sadio/sangue , Portador Sadio/imunologia , Clima , Ecossistema , Rim/microbiologia , Leptospira/imunologia
3.
PLoS One ; 15(1): e0227055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31986154

RESUMO

BACKGROUND: Leptospirosis, caused by pathogenic Leptospira, is a zoonosis of global distribution. This infectious disease is mainly transmitted by indirect exposure to urine of asymptomatic animals via the environment. As human cases generally occur after heavy rain, an emerging hypothesis suggests that rainfall re-suspend leptospires together with soil particles. Bacteria are then carried to surface water, where humans get exposed. It is currently assumed that pathogenic leptospires can survive in the environment but do not multiply. However, little is known on their capacity to survive in a soil and freshwater environment. METHODS: We conducted a systematic review on Leptospira and leptospirosis in the environment in order to collect current knowledge on the lifestyle of Leptospira in soil and water. In total, 86 scientific articles retrieved from online databases or institutional libraries were included in this study. PRINCIPALS FINDINGS/SIGNIFICANCE: This work identified evidence of survival of Leptospira in the environment but major gaps remain about the survival of virulent species associated with human and animal diseases. Studies providing quantitative data on Leptospira in soil and water are a very recent trend, but must be interpreted with caution because of the uncertainty in the species identification. Several studies mentioned the presence of Leptospira in soils more frequently than in waters, supporting the hypothesis of the soil habitat and dispersion of Leptospira with re-suspended soil particles during heavy rain. In a near future, the growing use of high throughput sequencing will offer new opportunities to improve our understanding of the habitat of Leptospira in the environment. This better insight into the risk of leptospirosis will allow implementing efficient control measures and prevention for the human and animal populations exposed.


Assuntos
Leptospira/patogenicidade , Microbiologia do Solo , Microbiologia da Água , Animais , Humanos , Leptospirose/transmissão
4.
PLoS Negl Trop Dis ; 13(11): e0007789, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31675378

RESUMO

Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (ß-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of ß-glucan against Leptospira infection in hamsters. First, ß-glucan was administered 24 h prior to, during and after infection. The results showed that ß-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of ß-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1ß and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1ß and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, ß-glucan was administered 5 days prior to infection. ß-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that ß-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1ß and IL-6) in vitro, indicating that ß-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of ß-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Leptospirose/imunologia , Leptospirose/prevenção & controle , beta-Glucanas/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Cricetinae , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade Inata/efeitos dos fármacos , Interleucina-1beta/metabolismo , Leptospira/crescimento & desenvolvimento , Leptospira/imunologia , Leptospira/patogenicidade , Leptospira interrogans/crescimento & desenvolvimento , Leptospira interrogans/imunologia , Leptospirose/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor 2 Toll-Like/metabolismo , beta-Glucanas/administração & dosagem
5.
Braz J Microbiol ; 50(4): 1129-1132, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359352

RESUMO

To assess the virulence of leptospires from the serogroup Sejroe (from ruminants), hamsters were tested against 12 strains. Three Guaricura strains induced severe lethal disease, in contrast to the Hardjo strains. Although with the preliminary outcomes, this finding may be useful for the control of bovine leptospirosis in the Americas, where Guaricura is prevalent.


Assuntos
Doenças dos Bovinos/microbiologia , Leptospira/isolamento & purificação , Leptospira/patogenicidade , Leptospirose/veterinária , Animais , Bovinos , Cricetinae , Feminino , Leptospira/classificação , Leptospira/genética , Leptospirose/microbiologia , Mesocricetus , Sorogrupo , Virulência
6.
PLoS One ; 14(6): e0210688, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170263

RESUMO

Leptospira spp. are re-emerging zoonotic pathogens. Previous research has found that Blanding's turtles (Emydoidea blandingii) experimentally infected with Leptospira interrogans shed leptospires in their urine, suggesting that they could play a role in transmitting pathogen within an aquatic ecosystem. This study investigated whether a population of wild Blanding's turtles known to be exposed to Leptospira spp. actively shed the pathogen under natural conditions. Blood samples were collected for serologic testing and to assess the health of the turtles. Free catch urine was collected for polymerase chain reaction (PCR) testing. All turtles were seropositive for Leptospira spp. and 73.5% (25/34) of the urine samples were PCR positive. All animals appeared clinically healthy and showed no apparent signs of disease. This study confirms that wild Blanding's turtles can actively shed Leptospira spp. in their urine and suggests that they may play a role in the epidemiology of this disease in habitats in which they reside.


Assuntos
Leptospira/patogenicidade , Leptospirose/transmissão , Tartarugas/microbiologia , Animais , Sangue/microbiologia , Ecossistema , Leptospira/fisiologia , Leptospirose/sangue , Leptospirose/urina , Tartarugas/sangue , Tartarugas/urina , Urina/microbiologia
8.
PLoS Negl Trop Dis ; 13(5): e0007270, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31120895

RESUMO

The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the natural environment contaminated with the urine of a wide range of reservoir animals. Soils and surface waters also host a high diversity of non-pathogenic Leptospira and species for which the virulence status is not clearly established. The genus Leptospira is currently divided into 35 species classified into three phylogenetic clusters, which supposedly correlate with the virulence of the bacteria. In this study, a total of 90 Leptospira strains isolated from different environments worldwide including Japan, Malaysia, New Caledonia, Algeria, mainland France, and the island of Mayotte in the Indian Ocean were sequenced. A comparison of average nucleotide identity (ANI) values of genomes of the 90 isolates and representative genomes of known species revealed 30 new Leptospira species. These data also supported the existence of two clades and 4 subclades. To avoid classification that strongly implies assumption on the virulence status of the lineages, we called them P1, P2, S1, S2. One of these subclades has not yet been described and is composed of Leptospira idonii and 4 novel species that are phylogenetically related to the saprophytes. We then investigated genome diversity and evolutionary relationships among members of the genus Leptospira by studying the pangenome and core gene sets. Our data enable the identification of genome features, genes and domains that are important for each subclade, thereby laying the foundation for refining the classification of this complex bacterial genus. We also shed light on atypical genomic features of a group of species that includes the species often associated with human infection, suggesting a specific and ongoing evolution of this group of species that will require more attention. In conclusion, we have uncovered a massive species diversity and revealed a novel subclade in environmental samples collected worldwide and we have redefined the classification of species in the genus. The implication of several new potentially infectious Leptospira species for human and animal health remains to be determined but our data also provide new insights into the emergence of virulence in the pathogenic species.


Assuntos
Evolução Molecular , Genoma Bacteriano , Leptospira/classificação , Leptospira/patogenicidade , Leptospirose/microbiologia , Animais , Ásia , Genômica , Humanos , Leptospira/genética , Leptospira/isolamento & purificação , Filogenia , Virulência , Zoonoses/microbiologia
9.
Microbes Infect ; 21(8-9): 377-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923000

RESUMO

Several pathogens including Gram-negative bacteria hijack complement regulators to escape host's innate response. Pathogenic Leptospira species bind Factor H, C4b binding protein and vitronectin from the complement system. We evaluated the ability of low passage (LP) and culture-attenuated (CA) pathogenic strains of Leptospira, to bind Factor H. We used LOCaS46 (Leptospira interrogans sv Canicola), LOVe30 (L. interrogans sv Icterohaemorrhagiae) and MOCA45 (L. santarosai sv Tarassovi), and ten high passage strains of Leptospira [used in the microscopic agglutination test (MAT)]. Afterwards, we assessed their survival in normal human serum (NHS). Interestingly, the ability in binding Factor H was higher for LOCaS46 and LOVe30 LP strains, than for the respective CA strains suggesting that the ability of evading the alternative complement pathway is lost after culture attenuation. Accordingly, the level of mRNA expression of the Factor H binding proteins, LigA, LigB and Lsa23 was higher in these LP strains than in the corresponding CA strains. Unexpectedly, no difference in Factor H binding and surviving was observed between LP and CA MOCA45 strains. The high passage MAT-reference strains showed variation in Factor H binding ability, but, in most cases, the ability for capturing Factor H by Leptospira strains correlated with their survival in NHS.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Regulação Bacteriana da Expressão Gênica , Leptospira/imunologia , Leptospira/patogenicidade , Proteínas de Transporte/genética , Fator H do Complemento/metabolismo , Humanos , Evasão da Resposta Imune/genética , Leptospira/genética , Leptospirose/microbiologia , Viabilidade Microbiana/genética , Viabilidade Microbiana/imunologia , Ligação Proteica , RNA Mensageiro/genética
10.
In. The University of the West Indies, Faculty of Medical Sciences. Faculty of Medical Sciences, Research Day. St. Augustine, Caribbean Medical Journal, March 21, 2019. .
Não convencional em Inglês | MedCarib | ID: biblio-1026242

RESUMO

Objective: To determine the immune response of dogs by measuring the levels of cytokines tumour necrosis factor (TNF) α, interleukin (IL)-4 and interferon (IFN) γ pre- and post-vaccination with a locally produced killed whole-celled Leptospira vaccine. Design and Methodology: Three separate vaccine-challenge experiments involving 21 beagle dogs were conducted. Study 1 (duration of immunity), used 6 vaccinated and 3 non-vaccinated (control) dogs. Vaccination was done at 12 and 16 weeks of age and challenged at 12 months of age with 1-2.5 x 108 live Leptospira. Study 2 (onset of immunity) also contained the same number of dogs as study 1. Vaccination was done at 12 and 16 weeks of age and challenged at 18 weeks of age. Study 3 (onset of immunity study), as study 2, used 4 vaccinated and two control dogs but challenged with 1-2.5 X 109 live Leptospira. Blood samples were collected to measure the levels of TNF α, IL-4 and IFN γ in dogs 2 days pre-challenge and daily thereafter until day 7 post-challenge. Results: For cytokine TNF α, pre-challenge levels for Study 1, 2 and 3 were 0.0000, 0.0755 and 0.0705 pg/ml which increased to a maximum post-challenge level of 49.05 pg/ml, 0.47 pg/ml and 1.667pg/ml respectively. For cytokine IL-4 and IFN γ the level increased from 0.00 pg/ml to a maximum post-challenge level of 52.67 pg/ml, 243.34 pg/ml and 989.14 pg/ml; and 281.91 pg/ml, 1223.85 pg/ ml and 1778.95 pg/ml respectively. Conclusion: The locally produced Leptospira vaccine induced immune response post-challenge with live Leptospira.


Assuntos
Animais , Cães , Leptospira/patogenicidade , Trinidad e Tobago , Região do Caribe/etnologia
11.
Transbound Emerg Dis ; 66(3): 1195-1201, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30703279

RESUMO

Leptospirosis is a common worldwide bacterial zoonosis and has been studied in One Health approaches. Small mammals are described as the most important maintenance reservoirs of several pathogens in nature, including leptospires. The aim of this study was to identify infection by leptospires among small mammals on the Atlantic forest biome and evaluate their potential as carriers of these spirochetes. A total of 153 small mammals belonging to orders Rodentia and Didelphimorphia (distributed on 17 genera and 22 species) were captured. Blood and kidney samples were collected from animals and a conventional PCR targeted on lipL32 gene was conducted on renal tissues. Species identification was performed in eight samples by sequencing of rrs gene. A total of 28% of the animals presented lipL32 PCR-positive, and four pathogenic Leptospira species (L. interrogans, L. borgpetersenii, L. santarosai and L. noguchii) were identified. This study highlights the role of small mammals as carriers of leptospires on the Atlantic Forest representing a potential source of pathogenic Leptospira spp infection for both humans and domestic animals.


Assuntos
Ecossistema , Leptospira/isolamento & purificação , Leptospirose/veterinária , Gambás/microbiologia , Roedores/microbiologia , Animais , Florestas , Humanos , Leptospira/patogenicidade , Leptospirose/epidemiologia , Leptospirose/microbiologia , Zoonoses
12.
J Infect Dis ; 219(6): 996-1006, 2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30299510

RESUMO

BACKGROUND: Leptospirosis, caused by spirochetes of the genus Leptospira, is one of the most widespread zoonoses worldwide. Efficient diagnostic methods for early diagnosis of leptospirosis are still lacking, and acute disease presents with nonspecific symptomatology and is often misdiagnosed. The leptospires pathogenic processes and virulence mechanisms remain virtually unknown. In severe infections, hemostatic impairment is frequently observed, and pathophysiological complications often develop when the host response is modulated by the pathogen. The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and potent inducer of vascular leakage. RESULTS: In this study, we found that leptospires and their secreted products induce the release of HBP from stimulated neutrophils through a controlled degranulation mechanism. We acknowledged 2 leptospiral proteins as able to induce HBP degranulation. These findings have clinical implications, as high levels of HBP were detected in serum from patients with leptospirosis, especially at the early phase of the disease. CONCLUSION: In conclusion, we describe a new mechanism by which the leptospirosis pathophysiological complications may arise, such as vascular leakage and edema formation. We also propose HBP as a new early screening biomarker for human leptospirosis.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Proteínas de Bactérias/sangue , Leptospira/patogenicidade , Leptospirose/sangue , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Bactérias/farmacologia , Biomarcadores/sangue , Proteínas Sanguíneas/farmacologia , Interações Hospedeiro-Patógeno , Humanos , Leptospira/metabolismo , Leptospirose/diagnóstico , Leptospirose/fisiopatologia , Camundongos Endogâmicos BALB C , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Proteínas Recombinantes/farmacologia
13.
Microb Pathog ; 126: 134-137, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30394297

RESUMO

Leptospirosis is an important zoonotic disease and, in urban areas, rodents are considered the main reservoir of Leptospira to human hosts. It has been described that capybaras, the world largest rodent, also harbor and shed leptospires by urine. Although not virulent to their hosts, strains of rodent origin are virulent for the hamster. In this context we aim to investigate the virulence of Leptospira kirschneri strains of serogroup Icterohaemorrhagiae recovered from capybaras in Brazil in the hamster model. Five isolates of Leptospira recovered from asymptomatic capybaras were submitted to virulence tests following the suggested protocols and the 3Rs policy for experimental science. Briefly, 1 ml of 1 × 108 leptospires was inoculated intraperitoneally four times in one hamster for each strain. Four days after inoculation, a blood sample was collected via the gingival route for confirmation of blood culture infection. The infected animals were kept isolated in microisolators to observe clinical signs and monitored daily till day 21 post-inoculation. None strain caused acute disease in hamsters but were able to colonize their kidneys. The present study demonstrated that although Icterohaemorrhagiae strains are often reported as virulent, not all strains of that serogroup are indeed aggressive. Concluding, we report that strains of L. kirschneri serogroup Icterohaemorrhagiae recovered from healthy capybaras presented an atypical virulence to the hamster model, what reinforces that virulence is an intrinsic strains characteristic.


Assuntos
Leptospira/patogenicidade , Leptospirose/microbiologia , Roedores/microbiologia , Animais , Brasil , Cricetinae , Modelos Animais de Doenças , Feminino , Gengiva/microbiologia , Rim/microbiologia , Rim/patologia , Leptospirose/veterinária , Virulência
14.
Arq. Inst. Biol ; 86: e0582018, 2019.
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, VETINDEX, SESSP-IPPROD, Sec. Est. Saúde SP | ID: biblio-1009484

RESUMO

Among the diseases that affect equines, bacterial diseases play an important role from a health and economic point of view, especially leptospirosis and brucellosis. The study aimed to provide information on the occurrence of anti-Leptospira spp. and anti-Brucella abortus antibodies in donkeys of São Paulo state. We found a frequency of 62.4% (53/85) antibodies against Leptospira spp. The donkeys were not seropositive for Brucella spp.(AU)


Entre as doenças que acometem os equídeos, as enfermidades bacterianas assumem um papel importante do ponto de vista sanitário e econômico, destacando-se a leptospirose e a brucelose. O estudo teve como objetivo fornecer informações sobre a ocorrência de anticorpos anti-Leptospira spp. e anti-Brucella abortus em jumentos no estado de São Paulo. Estimou-se que 62,4% (53/85) dos animais apresentavam anticorpos anti-Leptospira spp. Os jumentos estudados não foram sororreagentes contra a Brucella spp.(AU)


Assuntos
Animais , Infecções Bacterianas , Brucelose , Equidae , Leptospirose , Brucella , Testes Sorológicos/métodos , Leptospira/patogenicidade
15.
Am J Trop Med Hyg ; 99(6): 1366-1368, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30298813

RESUMO

Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few historical differential diagnoses were malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in "constrained settings." Achille Kelsch (1841-1911) synthesized available military data and epidemiological perspectives to define "epidemic jaundice" as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil's disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.


Assuntos
Surtos de Doenças/história , Icterícia/diagnóstico , Leptospira/patogenicidade , Leptospirose/diagnóstico , Doença de Weil/diagnóstico , Diagnóstico Diferencial , Reservatórios de Doenças , Europa (Continente)/epidemiologia , História do Século XIX , História do Século XX , Humanos , Icterícia/epidemiologia , Icterícia/história , Icterícia/microbiologia , Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/história , Leptospirose/microbiologia , Microbiologia do Solo , Doença de Weil/epidemiologia , Doença de Weil/história , Doença de Weil/microbiologia
16.
Bull Math Biol ; 80(11): 2978-3001, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30242634

RESUMO

In this paper, we propose control strategies for multigroup epidemic models. We use compartmental [Formula: see text] models to study the dynamics of n host groups sharing the same source of infection in addition to the transmission among members of the same group. In particular, we consider a model for infectious diseases with free-living pathogens in the environment and a metapopulation model with a central patch. We give the detailed derivation of the target reproduction number under three public health interventions and provide the corresponding biological insights. Moreover, using the next-generation approach, we calculate the basic reproduction numbers associated with subsystems of our models and determine algebraic connections to the target reproduction number of the complete model. The analysis presented here illustrates that understanding the topological structure of the infection process and partitioning it into simple cycles is useful to design and evaluate the control strategies.


Assuntos
Doenças Transmissíveis/epidemiologia , Epidemias/prevenção & controle , Modelos Biológicos , Animais , Derrame de Bactérias , Número Básico de Reprodução/estatística & dados numéricos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Doenças Transmissíveis/transmissão , Simulação por Computador , Reservatórios de Doenças/estatística & dados numéricos , Microbiologia Ambiental , Interações entre Hospedeiro e Microrganismos , Interações Hospedeiro-Patógeno , Humanos , Leptospira/patogenicidade , Leptospirose/epidemiologia , Leptospirose/prevenção & controle , Leptospirose/transmissão , Conceitos Matemáticos , Fatores de Risco
18.
PLoS Negl Trop Dis ; 12(7): e0006621, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29979677

RESUMO

Leptospirosis is a bacterial zoonosis, caused by Leptospira spp., that leads to significant morbidity and mortality worldwide. Despite considerable advances, much is yet to be discovered about disease pathogenicity. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune response has been described following a variety of bacterial infections. The current study examined the microtranscriptome of macrophages J774A.1 following an 8h infection with virulent, attenuated and saprophyte strains of Leptospira. Microarray analysis revealed that 29 miRNAs were misregulated following leptospiral infection compared to control macrophages in a strain and virulence-specific manner. Pathway analysis for targets of these differentially expressed miRNAs suggests that several processes involved in immune response could be regulated by miRNAs. Our data provides the first evidence that host miRNAs are regulated by Leptospira infection in macrophages. A number of the identified miRNA targets participate in key immune response processes. We suggest that post-transcriptional regulation by miRNAs may play a role in host response to infection in leptospirosis.


Assuntos
Leptospira/fisiologia , Leptospirose/genética , Macrófagos/microbiologia , Transcriptoma , Animais , Cricetinae , Humanos , Leptospira/classificação , Leptospira/genética , Leptospira/patogenicidade , Leptospirose/metabolismo , Leptospirose/microbiologia , Macrófagos/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Filogenia , Virulência
19.
Artigo em Inglês | MEDLINE | ID: mdl-29974037

RESUMO

Leptospirosis is a neglected tropical zoonosis caused by pathogenic spirochetes of the genus Leptospira. Infected reservoir animals, typically mice and rats, are asymptomatic, carry the pathogen in their renal tubules, and shed pathogenic spirochetes in their urine, contaminating the environment. Humans are accidental hosts of pathogenic Leptospira. Most human infections are mild or asymptomatic. However, 10% of human leptospirosis cases develop into severe forms, including high leptospiremia, multi-organ injuries, and a dramatically increased mortality rate, which can relate to a sepsis-like phenotype. During infection, the triggering of the inflammatory response, especially through the production of cytokines, is essential for the early elimination of pathogens. However, uncontrolled cytokine production can result in a cytokine storm process, followed by a state of immunoparalysis, which can lead to sepsis and associated organ failures. In this review, the involvement of cytokine storm and subsequent immunoparalysis in the development of severe leptospirosis in susceptible hosts will be discussed. The potential contribution of major pro-inflammatory cytokines in the development of tissue lesions and systemic inflammatory response, as well as the role of anti-inflammatory cytokines in contributing to the onset of a deleterious immunosuppressive cascade will also be examined. Data from studies comparing susceptible and resistant mouse models will be included. Lastly, a concise discussion on the use of cytokines for therapeutic purposes or as biomarkers of leptospirosis severity will be provided.


Assuntos
Citocinas/metabolismo , Leptospira/imunologia , Leptospirose/imunologia , Leptospirose/metabolismo , Imunidade Adaptativa/imunologia , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Leptospira/patogenicidade , Camundongos , Ratos
20.
Microbiol Spectr ; 6(4)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30027885

RESUMO

Leptospira, Brucella, and Borrelia are major agents of zoonotic disease, causing high morbidity and, in some cases, significant mortality in humans. For all three genera, prompt diagnosis and appropriate antimicrobial therapy are required to prevent the development of chronic, debilitating illness. Leptospira spp. are intrinsically resistant to several antimicrobial classes; however, there is little evidence in the literature for development of acquired resistance to antimicrobial agents used for clinical treatment of acute leptospirosis. For Brucella infections, there are numerous reports of relapses following therapy, but it is unclear whether this is due to sequestration within infected sites (e.g., bone) or the development of acquired resistance. Brucella have maintained their susceptibility to doxycycline and rifampicin, which in combination remain the most common treatments of brucellosis in humans. In vitro induced point mutations are described as imparting resistance to rifampicin (rpoB) and fluoroquinolones (gyrA). The clinical significance of these mutations is unclear. For Borrelia burgdorferi, although acquired resistance to some antimicrobial agents has been described, resistance due to bacterial persister cells surviving in the presence of antimicrobial, with no apparent increase in the MIC of the organism, have been recently described. Of the remaining veterinary fastidious pathogens, Lawsonia intracellularis is the most interesting from an antimicrobial resistance perspective because it can only be grown in cell culture, making in vitro susceptibility testing challenging. MIC testing has been undertaken on a small number of isolates, and some differences in susceptibility to macrolides have been demonstrated between isolates obtained from different regions.


Assuntos
Antibacterianos/uso terapêutico , Brucella/efeitos dos fármacos , Brucelose/veterinária , Farmacorresistência Bacteriana/efeitos dos fármacos , Leptospira/efeitos dos fármacos , Leptospirose/veterinária , Zoonoses/tratamento farmacológico , Animais , Borrelia burgdorferi/efeitos dos fármacos , Brucella/genética , Brucella/patogenicidade , Brucelose/tratamento farmacológico , Infecções por Desulfovibrionaceae/tratamento farmacológico , Farmacorresistência Bacteriana/genética , Humanos , Lawsonia (Bactéria)/efeitos dos fármacos , Leptospira/patogenicidade , Leptospirose/tratamento farmacológico , Leptospirose/genética , Testes de Sensibilidade Microbiana , Mutação Puntual , Zoonoses/microbiologia
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