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1.
Front Public Health ; 12: 1447592, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39360250

RESUMO

Rats are major reservoirs for pathogenic Leptospira, the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which "total shedding", obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally-higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for "total shedding" by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases.


Assuntos
Reservatórios de Doenças , Leptospira , Leptospirose , Zoonoses , Animais , Humanos , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/transmissão , Leptospira/isolamento & purificação , Reservatórios de Doenças/microbiologia , Brasil/epidemiologia , Ratos , Zoonoses/microbiologia , Masculino , Feminino , Adulto , Derrame de Bactérias , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , População Urbana/estatística & dados numéricos , Adolescente , Adulto Jovem
2.
ACS Infect Dis ; 10(9): 3256-3272, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39231002

RESUMO

The survival and proliferation of pathogenic Leptospira within a host are complex phenomena that require careful consideration. The ErpY-like lipoprotein, found on the outer membrane surface of Leptospira, plays a crucial role in enhancing the bacterium's pathogenicity. The rErpY-like protein, in its recombinant form, contributes significantly to spirochete virulence by interacting with various host factors, including host complement regulators. This interaction facilitates the bacterium's evasion of the host complement system, thereby augmenting its overall pathogenicity. The rErpY-like protein exhibits a robust binding affinity to soluble fibrinogen, a vital component of the host coagulation system. In this study, we demonstrate that the rErpY-like protein intervenes in the clotting process of the platelet-poor citrated plasma of bovines and humans in a concentration-dependent manner. It significantly reduces clot density, alters the viscoelastic properties of the clot, and diminishes the average clotting rate in plasma. Furthermore, the ErpY-like protein inhibits thrombin-catalyzed fibrin formation in a dose-dependent manner and exhibits saturable binding to thrombin, suggesting its significant role in leptospiral infection. These findings provide compelling evidence for the anticoagulant effect of the ErpY-like lipoprotein and its significant role in leptospiral infection.


Assuntos
Coagulação Sanguínea , Fibrinogênio , Trombina , Fibrinogênio/metabolismo , Fibrinogênio/química , Humanos , Trombina/metabolismo , Animais , Bovinos , Ligação Proteica , Leptospira/metabolismo , Leptospirose/microbiologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Lipoproteínas/metabolismo , Interações Hospedeiro-Patógeno
3.
PLoS Negl Trop Dis ; 18(9): e0012449, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39298533

RESUMO

BACKGROUND: Leptospirosis is responsible for various clinical syndromes, classically linked with fever and acute kidney injury. METHODOLOGY/PRINCIPAL FINDINGS: A prospective multicenter observational study was conducted in six health institutions in the region of Urabá, Colombia. Enrollment was based on leptospirosis-compatible clinical syndrome and a positive preliminary serological test, with PCR used to confirm the disease. Clinical data were collected using a standard questionnaire at enrollment, complemented with a review of clinical records. A total of 100 patients were enrolled, 37% (95% CI 27.0-46.9%) had a positive PCR result confirming acute leptospirosis. The most frequent symptoms in patients with a positive PCR test were headache (91.9%; 34/37), chills and sweating (80.6%; 29/37), nausea (75%; 27/37), dizziness (74.3%; 26/37), vomiting (61.1%; 22/37), congestion (56.8%; 21/37), and conjunctival suffusion (51.4%; 19/37). The frequency of clinical signs classically described in leptospirosis was low: jaundice (8.3%; 3/36) and anuria/oliguria (21.6%; 8/37). An increased neutrophile percentage was reported in 60.6% (20/33) of patients. The presence of complications was 21.6% (8/37), with pulmonary complications being the most frequent (75.0% 6/8). One confirmed case died resulting in a fatality of 2.7% (95% CI 0.5-13.8). CONCLUSIONS/SIGNIFICANCE: Leptospirosis should be considered within the differential diagnoses of an undifferentiated acute febrile syndrome. Leptospirosis presents diagnostic challenges due to limitations in both clinical and laboratory diagnosis thus it is important to improve understanding of disease presentation and identify signs and symptoms that might help differentiate it from other causes of febrile illness.


Assuntos
Febre , Leptospirose , Humanos , Leptospirose/diagnóstico , Leptospirose/complicações , Leptospirose/epidemiologia , Colômbia/epidemiologia , Masculino , Feminino , Adulto , Estudos Prospectivos , Febre/etiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Criança , Leptospira/isolamento & purificação , Leptospira/genética , Reação em Cadeia da Polimerase
4.
PLoS One ; 19(9): e0311040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39325783

RESUMO

Heme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant. Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses. HemKR is a TCS present in both saprophytic and pathogenic Leptospira species, involved in the control of heme metabolism. However, the molecular means by which HemKR is switched on/off in a signal-dependent way, are still unknown. Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. Using the saprophytic species Leptospira biflexa as a model, we now show that 5-aminolevulinic acid (ALA) triggers the shutdown of the HemKR pathway in live cells, and does so by stimulating the phosphatase activity of HemK towards phosphorylated HemR. Phospho~HemR dephosphorylation leads to differential expression of multiple genes, including of heme metabolism and transport systems. Besides the heme-biosynthetic genes hemA and the catabolic hmuO, which we had previously reported as phospho~HemR targets, we now extend the regulon identifying additional genes. Finally, we discover that HemR inactivation brings about an iron-deficit tolerant phenotype, synergistically with iron-responsive signaling systems. Future studies with pathogenic Leptospira will be able to confirm whether such tolerance to iron deprivation is conserved among Leptospira spp., in which case HemKR could play a vital role during infection where available iron is scarce. In sum, HemKR responds to abundance of porphyrin metabolites by shutting down and controlling heme homeostasis, while also contributing to integrate the regulation of heme and iron metabolism in the L. biflexa spirochete model.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Heme , Ferro , Leptospira , Transdução de Sinais , Heme/metabolismo , Leptospira/metabolismo , Leptospira/genética , Ferro/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ácido Aminolevulínico/metabolismo , Fosforilação
5.
Indian J Med Microbiol ; 51: 100698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39094972

RESUMO

INTRODUCTION: Leptospirosis and dengue are two significant public health concerns in tropical and subtropical regions, often resulting in severe forms of disease and fatality. This study addresses the pressing public health issues of leptospirosis and dengue in the Dakshina Kannada district of Karnataka, India. Both diseases pose significant health risks and are relatively understudied in this region, making it essential to investigate their prevalence and clinical presentations for targeted healthcare planning. AIM: The primary aim is to determine the frequency of leptospirosis and dengue among febrile illness cases to understand the epidemiological patterns and assess co-infection rates in Dakshina Kannada. METHOD: Between 2020 and 2021, serum samples suspected of leptospirosis were tested using IgM ELISA (n = 1629) and the Microscopic Agglutination Test (MAT) (n = 92) for leptospirosis, while dengue was tested using NS1Ag and IgM antibodies ELISA (n = 1415). Data were collected through medical records and patient interviews. Seasonal trends, gender, and age distributions were analyzed. RESULT: The study found a significant prevalence of leptospirosis (21 %) and dengue (10 %) among febrile illness cases in the study area, with a 1.3 % co-infection rate. Clinically, fever was common to both diseases, but leptospirosis also frequently exhibited symptoms such as abdominal pain, myalgia, and jaundice. MAT screening revealed a predominance of anti-leptospiral antibodies against the Djasiman, Pyrogenes, Hurstbridge, Hebdomadis, and Grippotyphosa serogroups in Dakshina Kannada. CONCLUSION: The study highlights the urgent need for focused public health interventions, improved diagnostic tools, and targeted epidemiological studies to manage these diseases. The findings underscore the necessity of enhancing diagnostic capabilities and public health awareness, particularly considering the significant health risks posed by leptospirosis and dengue in the region.


Assuntos
Coinfecção , Dengue , Leptospirose , Leptospirose/epidemiologia , Humanos , Dengue/epidemiologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Índia/epidemiologia , Adulto Jovem , Criança , Prevalência , Pré-Escolar , Febre/epidemiologia , Idoso , Leptospira/imunologia , Lactente , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática , Imunoglobulina M/sangue
6.
Vet Res Commun ; 48(5): 3461-3468, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153112

RESUMO

Leptospirosis is a worldwide re-emerging zoonotic disease. The study was conducted to estimate the Seroprevalence of canine leptospirosis in a total of 450 dogs, from a total of 97 puppies and 353 adult dogs selected for examination Sampling, started from January to December 2023 in District Kasur in the province Punjab of the country Pakistan. Leptospira IgG ELISA kit manufactured by DRG Instruments GmbH, Germany was used for the screening of canine Leptospira antibodies. Out of 450 tested dogs, 183 dogs (40.67%) were tested positive for Leptospira antibody for the screening of Leptospira antibodies. The estimated Seroprevalence of leptospirosis in various age groups of dogs, were 23.7% (23/97) and 45.3% (160/353), in puppies and adults, respectively (P < 0.05). It was found that out of the sampled dogs, a total of 35/127 (27.6%), 29/100 (29%), 73/130 (56.2%), and 46/93 (49.5%) dogs were tested seropositive for Leptospira antibodies in winter, spring, summer and fall, respectively (P < 0.05).


Assuntos
Doenças do Cão , Leptospirose , Animais , Leptospirose/veterinária , Leptospirose/epidemiologia , Leptospirose/sangue , Cães , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Doenças do Cão/sangue , Estudos Soroepidemiológicos , Masculino , Feminino , Paquistão/epidemiologia , Leptospira/imunologia , Análise Espaço-Temporal , Anticorpos Antibacterianos/sangue , Estações do Ano
7.
mBio ; 15(9): e0151624, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39136471

RESUMO

Leptospirosis, caused by pathogenic bacteria from the genus Leptospira, is a global zoonosis responsible for more than one million human cases and 60,000 deaths annually. The disease also affects many domestic animal species. Historically, genetic manipulation of Leptospira has been difficult to perform, resulting in limited knowledge on pathogenic mechanisms of disease and the identification of virulence factors. The application of CRISPR/Cas9 and its variations have helped fill these gaps but the generation of knockout mutants remains challenging because double-strand breaks (DSBs) inflicted by Cas9 nuclease are lethal to Leptospira cells. The novel CRISPR prime editing (PE) strategy is the first precise genome-editing technology that allows deletions, insertions, and base substitutions without introducing DSBs. This revolutionary technique utilizes a nickase Cas9 that cleaves a single strand of DNA, coupled with an engineered reverse transcriptase and a modified single-guide RNA (termed prime editing guide RNA) containing an extended 3' end with the desired edits. We demonstrate the application of CRISPR-PE in both saprophytic and pathogenic Leptospira from multiple species and serovars by introducing deletions or insertions into target DNA with a remarkable precision of just one nucleotide. Additionally, we demonstrate the ability to genetically manipulate Leptospira borgpetersenii, a prevalent pathogenic species of humans, domestic cattle, and wildlife animals. Rapid plasmid loss by mutated strains in liquid culture allows for the generation of knockout strains without selective markers, which can be readily used to elucidate virulence factors and develop optimized bacterin and/or live vaccines against leptospirosis.IMPORTANCELeptospirosis is a geographically widespread bacterial zoonosis. Genetic manipulation of pathogenic Leptospira spp. has been laborious and difficult to perform, limiting our ability to understand how leptospires cause disease. The application of the CRISPR/Cas9 system to Leptospira enhanced our ability to generate knockdown and knockout mutants; however, the latter remains challenging. Here, we demonstrate the application of the CRISPR prime editing technique in Leptospira, allowing the generation of knockout mutants in several pathogenic species, with mutations comprising just a single nucleotide resolution. Notably, we generated a mutant in the Leptospira borgpetersenii background, a prevalent pathogenic species of humans and cattle. Our application of this method opens new avenues for studying pathogenic mechanisms of Leptospira and the identification of virulence factors across multiple species. These methods can also be used to facilitate the generation of marker-less knockout strains for updated and improved bacterin and/or live vaccines.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Leptospira , Leptospira/genética , Leptospira/patogenicidade , Edição de Genes/métodos , Leptospirose/microbiologia , Animais , Mutação , Humanos
8.
Acta Trop ; 258: 107361, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39154698

RESUMO

Leptospirosis is a zoonotic disease with significant global impact and a challenging diagnosis. The utilization of adequately validated rapid tests is relevant for the opportune identification of the disease and for reduction in fatality rates. The present study analyzes the accuracy and reliability of the Dual Path Platform (DPP) assay -produced in Brazil by the Oswaldo Cruz Foundation (Fiocruz)- for diagnosing leptospirosis. Firstly, a serological panel was constructed in the Brazilian Reference Laboratory for Leptospirosis using samples routinely handled by reference laboratories of six Brazilian states. It consisted of 150 positive (according to MAT and IgM-ELISA) and 250 negative samples for leptospirosis. Subsequently, the panel samples were distributed to the reference laboratories for the performance of DPP assays in triplicate. Different measures were used in the assessment of diagnostic quality. Predictive values were estimated for different pre-test probability settings. Sensitivities varied between 67.33 % and 74.00 % and specificities between 93.20 % and 98.40 % in the states, and there were adequate agreements between them. Accuracies were lower for the samples of patients with less than 7 days of symptoms. In contexts of prevalence values up to around 25 %, positive and negative predictive values were around 90 %. However, in situations of high pre-test probabilities, NPVs were low. This study improves understanding of the use of DPP in diagnosing leptospirosis, particularly its application in healthcare settings. As long as the time of symptoms onset and clinical and epidemiological contexts are adequately considered for the interpretation of results, DPP is a valid option to be used in the leptospirosis diagnostic routine.


Assuntos
Anticorpos Antibacterianos , Leptospirose , Sensibilidade e Especificidade , Humanos , Anticorpos Antibacterianos/sangue , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina M/sangue , Leptospira/isolamento & purificação , Leptospira/imunologia , Leptospirose/sangue , Leptospirose/diagnóstico , Leptospirose/imunologia , Leptospirose/microbiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Testes Sorológicos/métodos
9.
Res Vet Sci ; 178: 105342, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39146598

RESUMO

Leptospirosis is a zoonotic disease whose transmission is linked to multiple factors involving the interface between animals, humans, and the environment. This disease is of great importance for public health, as it profoundly affects the health aspects of the population and animals. Considering the importance of non-human primates in this epidemiological chain, the objective of this research was to conduct a systematic literature review with meta-analysis, providing information on leptospirosis in non-human primates (NHPs) and an update on the infection situation in Brazil and other countries. Thus, a search was performed in five databases, initially finding 3332 studies, of which 32 met the eligibility criteria and were used for the systematic review. According to them, the most prevalent serogroup in non-human primates was Icterohaemorrhagiae, which is adapted to rodents as primary hosts. A wide distribution of the infection was found in the regions of both wild and captive animals. Through meta-analysis, the seroprevalence rate of leptospirosis in non-human primates was 27.21% (CI 17.97-38.95%). Cochran's Q test (p < 0.01) identified heterogeneity between studies, classified as high by the Higgins and Thompson test (I2 = 92.4%). Therefore, seroepidemiological and Leptospira isolation studies in non-human primates are important to investigate and monitor the suspected impact of these species as maintainers or transmitters of the pathogen to humans and other wild and domestic animals, in addition to demonstrating the need for standardization related to control and prevention measures.


Assuntos
Leptospirose , Primatas , Animais , Leptospira/imunologia , Leptospira/isolamento & purificação , Leptospirose/sangue , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/veterinária , Doenças dos Macacos/sangue , Doenças dos Macacos/epidemiologia , Doenças dos Macacos/microbiologia , Doenças dos Macacos/transmissão , Primatas/microbiologia , Estudos Soroepidemiológicos , Zoonoses/sangue , Zoonoses/epidemiologia , Zoonoses/microbiologia , Zoonoses/transmissão , Humanos
10.
J Vet Intern Med ; 38(5): 2729-2738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39194176

RESUMO

BACKGROUND: Reports of leptospirosis in horses are limited. OBJECTIVES: To describe the clinical and diagnostic findings of acute systemic leptospirosis in horses. ANIMALS: Eleven client-owned horses presented to an equine hospital because of acute onset of disease between 2015 and 2023. METHODS: Retrospective case series. Horses diagnosed with leptospirosis by 1 or more of urine PCR, serologic microscopic agglutination test (MAT), and histopathology. RESULTS: Common clinical signs included lethargy (10), anorexia (10), fever (9), tachypnea (9), abnormal lung sounds (9), and epistaxis (6). Acute kidney injury was present in all cases. Evidence of pulmonary hemorrhage and liver disease was found in 8 (73%) and 6 (55%) horses, respectively. In 6 (55%) horses, kidneys, lungs, and liver were affected. Urine quantitative polymerase chain reaction for detection of pathogenic Leptospira spp. was positive in 6 (55%) cases. On serology Leptospira interrogans serovar Australis, Autumnalis, and Bratislava accounted for 86% of all titers ≥1 : 800. Overall case fatality rate was 4/11 (36%). Main findings on necropsy were tubular necrosis, interstitial nephritis, hemorrhage in the alveoli, pulmonary edema, periportal hepatitis and necrosis, cholestasis, and cholangitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Leptospirosis should be considered as a differential diagnosis in horses with evidence of acute systemic inflammation and acute renal injury, epistaxis, or hepatic disease. For increased likelihood of identifying positive cases, both MAT serology and urine PCR should be performed.


Assuntos
Doenças dos Cavalos , Leptospirose , Animais , Cavalos , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/patologia , Doenças dos Cavalos/diagnóstico , Leptospirose/veterinária , Leptospirose/diagnóstico , Leptospirose/patologia , Estudos Retrospectivos , Masculino , Feminino , Leptospira/isolamento & purificação , Doença Aguda
11.
Eur J Clin Microbiol Infect Dis ; 43(10): 1959-1968, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39093525

RESUMO

PURPOSE: The current diagnostic methods for leptospirosis diagnosis are technically complex and expensive, with limited applicability to specialized laboratories. Furthermore, they lack diagnostic accuracy in the acute stage of the disease, which coincides with a period when antibiotics are highly effective. New simple and accurate tests are mandatory to decentralize and improve diagnosis. Here, we introduced a new lateral flow immunoassay (Lepto-LF) for human leptospirosis. METHODS: We conducted a double-blinded assay using 104 serum samples from patients with confirmed or discarded diagnosis for leptospirosis. The diagnostic performance of Lepto-LF was estimated across different ranges of days from onset of symptoms (dpo), considering the diagnostic algorithm as reference standard. Additionally, it was compared with the screening methods enzyme-linked immunosorbent assay (IgM-ELISA) and the slide agglutination test using temperature-resistant antigen (SATR). RESULTS: Lepto-LF exhibited perfect diagnostic performance with a Youden´s index J = 1 from 6 dpo in the acute phase. IgM-ELISA gave slightly lower accuracy with J = 0.91 and 95.5% of both sensitivity and specificity; while SATR showed a markedly inferior yield (J = 0.41, sensitivity = 95.5%, specificity = 45.5%). The performances remained consistent in the convalescence phase of the disease (> 10 dpo). CONCLUSION: Lepto-LF was found to be a reliable test for simple, rapid and early diagnosis of leptospirosis, resulting a promising tool for decentralizing leptospirosis diagnosis and enabling timely treatment of patients. In addition, Lepto-LF may be employed as confirmatory test, especially in remote areas and vulnerable contexts where the standard MAT is not available.


Assuntos
Anticorpos Antibacterianos , Ensaio de Imunoadsorção Enzimática , Leptospirose , Sensibilidade e Especificidade , Humanos , Leptospirose/diagnóstico , Leptospirose/sangue , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , Imunoensaio/normas , Leptospira/imunologia , Leptospira/isolamento & purificação , Imunoglobulina M/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Método Duplo-Cego , Testes de Aglutinação/métodos , Adulto Jovem
12.
J Med Case Rep ; 18(1): 370, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39107781

RESUMO

BACKGROUND: Both dengue and Leptospira infections are endemic to tropical and subtropical regions, with their prevalence increasing in recent decades. Coinfection with these pathogens presents significant diagnostic challenges for clinicians due to overlapping clinical manifestations and laboratory findings. This case report aims to elucidate two clinical scenarios where the coinfection of dengue and leptospirosis complicates the disease course, creating a diagnostic conundrum. CASE PRESENTATION: We present the clinical scenarios of two Bangladeshi males, aged 25 and 35 years, who were admitted to our hospital with acute febrile illness. The first patient exhibited hepatic and renal involvement, while the second presented with symptoms initially suggestive of meningoencephalitis. Both cases were initially managed under the presumption of dengue infection based on positive serology. However, further evaluation revealed coinfection with Leptospira, complicating the disease course. Both patients received appropriate treatment for dengue and antibacterial therapy for leptospirosis, ultimately resulting in their recovery. CONCLUSION: These case scenarios underscore the critical importance for clinicians in regions where dengue and Leptospira are endemic to consider both diseases when evaluating patients presenting with acute febrile illness.


Assuntos
Antibacterianos , Coinfecção , Dengue , Leptospirose , Humanos , Dengue/complicações , Dengue/diagnóstico , Masculino , Leptospirose/complicações , Leptospirose/diagnóstico , Leptospirose/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Febre/etiologia , Leptospira/isolamento & purificação , Resultado do Tratamento
13.
Prev Vet Med ; 231: 106301, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121516

RESUMO

Leptospirosis is an anthropozoonosis of economic and public health importance, caused by bacteria of the genus Leptospira. Horses are deemed important in its transmission chain due to their proximity to humans, and because the species is often asymptomatic, making these animals potential silent reservoirs. In this context, the objectives of this study were to determine the prevalence of seropositive horses for Leptospira spp., and to identify the presence of Leptospira spp. serogroups and antibody titers, the occurrence of areas with higher density of infection cases and demographic characteristics associated with seropositivity in the states of Paraíba (PB), Pernambuco (PE), Rio Grande do Norte (RN) and Ceará (CE), in the Northeast region of Brazil, during rainy (May and June) and dry (October and November) seasons from 2017 to 2019. Using the microscopic agglutination test (MAT), 1152 equine serum samples from 225 municipalities were analyzed. Anti-Leptospira antibodies were detected in 23.9 % (95 % CI= 21.4 - 26.3 %) of the samples in the three-year period, with a frequency of 30.4 % (95 % CI= 26.7 - 34.2 %) during the rainy period (with greater emphasis on the Ballum serogroup) and 17.4 % (95 % CI= 14.3 - 20.5 %) in the dry period (with greater emphasis on the Sejroe serogroup). Age of horses ≥ 6 years (6-10 years, 11-15 years and ≥ 16 years), rainy season, and animal belonging to Pernambuco state were factors with higher seropositivities. Regarding spatial distribution, a higher percentage of seropositive animals was observed in Pernambuco (P < 0.05), in interstate border areas, and large urban centers, with a spatial cluster detected in the dry season of 2018 with relative risk of 2.8 (P = 0.049) times higher in municipalities within the cluster. It is suggested that measures for controlling rodents and contact with wild animals in equine farming, both in rainy and dry periods, combined with care regarding the use of pastures shared with cattle and the adoption of immunoprophylaxis are important in preventing and controlling leptospirosis in horses in the Northeast region of Brazil.


Assuntos
Doenças dos Cavalos , Leptospira , Leptospirose , Estações do Ano , Animais , Cavalos , Leptospirose/veterinária , Leptospirose/epidemiologia , Leptospirose/microbiologia , Brasil/epidemiologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/microbiologia , Leptospira/isolamento & purificação , Leptospira/imunologia , Estudos Soroepidemiológicos , Prevalência , Masculino , Feminino , Anticorpos Antibacterianos/sangue , Análise Espacial , Sorogrupo
14.
BMC Vet Res ; 20(1): 348, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113014

RESUMO

BACKGROUND: Leptospiraceae comprise a diverse family of spirochetal bacteria, of which many are involved in infectious diseases of animals and humans. Local leptospiral diversity in domestic animals is often poorly understood. Here we describe the incidental detection of Leptospira (L.) licerasiae in an Austrian pig. CASE PRESENTATION: During an experiment to characterize the pathogenesis of L. interrogans serovar Icterohaemorrhagiae in pigs, cultivation of a urine sample from a non-challenged contact pig resulted in growth of a spirochetal bacterium that tested negative for pathogenic Leptospira (LipL32 gene). PCR, Sanger sequencing and standard serotyping further confirmed that the recovered isolate was clearly different from the challenge strain L. interrogans serovar Icterohaemorrhagiae used in the animal experiment. Whole genome sequencing revealed that the isolate belongs to the species L. licerasiae, a tropical member of the Leptospiraceae, with no prior record of detection in Europe. CONCLUSIONS: This is the first report describing the occurrence of L. licerasiae in Europe. Since L. licerasiae is considered to have intermediate pathogenicity, it will be important to follow the geographical distribution of this species and its pathogenic and zoonotic potential in more detail.


Assuntos
Leptospira , Leptospirose , Doenças dos Suínos , Animais , Suínos , Leptospirose/veterinária , Leptospirose/microbiologia , Leptospira/isolamento & purificação , Leptospira/genética , Doenças dos Suínos/microbiologia , Áustria
15.
Am J Trop Med Hyg ; 111(4): 856-864, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39106850

RESUMO

Leptospirosis, a bacterial infection transmitted through contact with infected animals or contaminated water sources, imposes a substantial health burden in Colombia. Since 2007, the National Institute of Health (INS) has mandated the notification and confirmation of all suspected leptospirosis cases. This passive surveillance program employs the microscopic agglutination test (MAT) on serum samples to ascertain confirmed cases of leptospirosis infection. However, the absence of a robust surveillance system has hindered our comprehensive understanding of the morbidity, mortality, geographical distribution, species/serovars, and strains responsible for severe disease. Our study aimed to provide an epidemiological overview of MAT-confirmed human leptospirosis cases reported over 6 years (2015-2020) in Colombia. In addition, we offer insights into the status of leptospirosis in the country, focusing on risk factors and proposing potential improvements for diagnosis and disease management. During the 6-year surveillance period, the laboratory at the INS received 3,535 serum samples from suspected human leptospirosis cases, with 880 (25%) confirmed through MAT. The incidence of leptospirosis was calculated at 1.9 cases per 100,000 people, with a higher prevalence among men (82.1%). Furthermore, 54 (6.1%) deaths were confirmed as leptospirosis, and cases were documented across nearly all regions of Colombia. Our findings emphasize the urgent need to strengthen leptospirosis laboratory surveillance, implement effective prevention measures, and enhance diagnostic capabilities in Colombia. The analysis conducted in this study provides the groundwork for estimating the impact of leptospirosis and raises awareness of its significance in public health.


Assuntos
Leptospirose , Humanos , Leptospirose/epidemiologia , Leptospirose/diagnóstico , Leptospirose/sangue , Colômbia/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Idoso , Testes de Aglutinação , Pré-Escolar , Incidência , Leptospira/isolamento & purificação , Fatores de Risco , Prevalência , Lactente
16.
Indian J Med Microbiol ; 51: 100689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39067858

RESUMO

Leptospirosis, an underdiagnosed zoonotic disease in India, was studied retrospectively in Madhya Pradesh, Central India. Between 2018 and 2019, 2617 samples from patients with hepatitis-related symptoms were collected. Of these, 518 tested negative for hepatitis and other tropical viral diseases under the VRDL project were analyzed for leptospira IgM using ELISA. 68 (13.12%) were positive for leptospirosis. Common symptoms included fever (97.45%) and jaundice (42.27%), with renal involvement in 30.88% of cases. Higher incidence was observed in the 31-60 age group, especially during monsoon and post-monsoon seasons. The study highlights the need for increased clinician awareness and inclusion of leptospirosis in screening panels to differentiate tropical illnesses in India.


Assuntos
Imunoglobulina M , Leptospira , Leptospirose , Leptospirose/epidemiologia , Leptospirose/diagnóstico , Humanos , Índia/epidemiologia , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Leptospira/imunologia , Adolescente , Adulto Jovem , Imunoglobulina M/sangue , Criança , Incidência , Anticorpos Antibacterianos/sangue , Pré-Escolar , Idoso , Estações do Ano , Efeitos Psicossociais da Doença , Ensaio de Imunoadsorção Enzimática , Febre/epidemiologia , Icterícia/etiologia
17.
Am J Trop Med Hyg ; 111(2): 237-245, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-38955193

RESUMO

Leptospirosis is a neglected zoonosis for which investigations assessing host-pathogen interaction are scarce. The aim of this study was to compare the severity and bacterial species involved in human cases of leptospirosis on Reunion and Mayotte islands, territories located in the southwest Indian Ocean that have recorded high human leptospirosis incidence but display fairly distinct epidemiological situations. A retrospective multicentric study including all patients over 18 years of age from Mayotte or Reunion with proven leptospirosis was conducted from January 2018 to April 2020. This study collected demographic, geographical, clinical, and biological data. Overall, 490 patients were included, 222 on Mayotte and 268 on Reunion. More patients were hospitalized on Reunion (n = 215, 80%) compared with Mayotte (n = 102, 46%). Severe disease was more common on Reunion (n = 75, 28%) than on Mayotte (n = 22, 10%). The dominant Leptospira species on Reunion was Leptospira interrogans (79%) followed by Leptospira borgpetersenii (21%), contrasting with the epidemiological situation on Mayotte where L. interrogans was found in only a minority of patients (10%). The high frequency of severe cases on Reunion could be explained not only by higher comorbidities but also by the higher occurrence of L. interrogans infections compared with Mayotte. Finally, the distribution of cases linked to L. borgpetersenii was found almost exclusively on the west coast of Reunion, raising the potential role of a ruminant reservoir.


Assuntos
Leptospira , Leptospirose , Leptospirose/epidemiologia , Leptospirose/microbiologia , Humanos , Reunião/epidemiologia , Leptospira/isolamento & purificação , Feminino , Adulto , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Comores/epidemiologia , Leptospira interrogans/isolamento & purificação , Adulto Jovem , Adolescente , Idoso , Animais
18.
J Appl Microbiol ; 135(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39020252

RESUMO

AIMS: Currently, immunoinformatic approaches have shown promise in rapidly and cost-effectively identifying new antigens from the Leptospira proteome. Chimeric multiepitope proteins offer a strategy with significant potential for implementation in diagnosis and vaccines development. METHODS AND RESULTS: In this study, we detail the immunoinformatic analyses and design of a new recombinant chimeric protein constructed with epitopes identified from the sequences of ErpY-like and LemA proteins, previously identified as potential antigens for controlling leptospirosis. We expressed the chimeric protein using Escherichia coli heterologous systems, evaluated its antigenicity using serum from naturally infected patients, and its immunogenicity in mice as an animal model, with Freund as an adjuvant. The resulting recombinant chimeric protein, named rErpY-LemA, was successfully expressed and purified using a prokaryotic system, with an expected mass of 35 kDa. Serologic assays using serum samples from naturally infected patients demonstrated recognition of the chimera protein by antibodies present in sera. Animals immunized with the chimera exhibited a significant IgG antibody response from the 7th day (P < 0.001), persisting until day 49 of experimentation, with a titer of 1:12,800 (P < 0.05). Notably, significant production of IgA, IgM, and IgG subclasses was observed in animals immunized with the chimera. CONCLUSIONS: These results highlight the promising role of immunoinformatics in rapidly identifying antigens and the potential of chimeric multiepitope proteins in developing effective strategies for leptospirosis control.


Assuntos
Antígenos de Bactérias , Leptospirose , Proteínas Recombinantes de Fusão , Leptospirose/imunologia , Leptospirose/prevenção & controle , Animais , Camundongos , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Humanos , Anticorpos Antibacterianos/sangue , Leptospira/imunologia , Leptospira/genética , Biologia Computacional , Epitopos/imunologia , Epitopos/genética , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Escherichia coli/genética , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética
19.
Emerg Infect Dis ; 30(8): 1514-1522, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043385

RESUMO

Leptospirosis is a common but underdiagnosed zoonosis. We conducted a 1-year prospective study in La Guaira State, Venezuela, analyzing 71 hospitalized patients who had possible leptospirosis and sampling local rodents and dairy cows. Leptospira rrs gene PCR test results were positive in blood or urine samples from 37/71 patients. Leptospira spp. were isolated from cultured blood or urine samples of 36/71 patients; 29 had L. interrogans, 3 L. noguchii, and 4 L. venezuelensis. Conjunctival suffusion was the most distinguishing clinical sign, many patients had liver involvement, and 8/30 patients with L. interrogans infections died. The Leptospira spp. found in humans were also isolated from local rodents; L. interrogans and L. venezuelensis were isolated from cows on a nearby, rodent-infested farm. Phylogenetic clustering of L. venezuelensis isolates suggested a recently expanded outbreak strain spread by rodents. Increased awareness of leptospirosis prevalence and rapid diagnostic tests are needed to improve patient outcomes.


Assuntos
Surtos de Doenças , Leptospira , Leptospirose , Filogenia , Roedores , Animais , Leptospirose/epidemiologia , Leptospirose/veterinária , Leptospirose/microbiologia , Leptospirose/diagnóstico , Humanos , Venezuela/epidemiologia , Bovinos , Leptospira/genética , Leptospira/isolamento & purificação , Leptospira/classificação , Feminino , Roedores/microbiologia , Adulto , Masculino , Pessoa de Meia-Idade , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/epidemiologia , Adolescente , Leptospira interrogans/genética , Leptospira interrogans/isolamento & purificação , Leptospira interrogans/classificação , Adulto Jovem , Estudos Prospectivos , Criança , Idoso , Doenças Endêmicas , Zoonoses/epidemiologia , Zoonoses/microbiologia , Pré-Escolar
20.
Hum Immunol ; 85(5): 110835, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38972268

RESUMO

Leptospirosis (LTPS) is a bacterial infection that affects humans, often with mild or no symptoms. It is estimated that approximately 10 % of patients with LTPS may experience multi-organ dysfunction, including renal abnormalities. In regions where LTPS is widespread, a considerable number of instances involving acute kidney injury (AKI) and chronic kidney disease (CKD) of unknown etiology (CKDu) have been reported. Additionally, studies have shown a correlation between kidney graft dysfunction in patients with stable kidney transplants after LTPS. These findings indicate that exposure to LTPS may increase the likelihood of kidney transplantation due to the onset of both acute and chronic kidney injuries. Simultaneously, it poses a potential risk to the stability of kidney grafts. Unfortunately, there is limited scientific literature addressing this issue, making it difficult to determine the negative impact that LTPS may have, such as its role as a risk factor for the need of kidney transplantation or as a threat to individuals who have undergone kidney transplants. This study aims to shed light on the immune mechanisms triggered during LTPS infection and their importance in both kidney damage and allograft dysfunction.


Assuntos
Transplante de Rim , Leptospirose , Humanos , Transplante de Rim/efeitos adversos , Leptospirose/imunologia , Fatores de Risco , Injúria Renal Aguda/etiologia , Leptospira/imunologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/imunologia , Suscetibilidade a Doenças , Rim
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