Background & objectives: The biological spectrum of leptospirosis ranges from acute undifferentiated febrile illness to severe fatal syndrome or a combination of syndromes. Diagnosis on clinical ...grounds alone is difficult and depends on laboratory support. However, no confirmatory tests are available, which is rapid and can be performed with minimum facilities available. The objectives of this study were to evaluate the diagnostic utility, accuracy and reproducibility of a rapid real time-PCR based method (TruenatTM) for early diagnosis of leptospirosis, and its usage in low resource settings.
Methods: The Truenat™ test was performed using plasma sample collected from confirmed patients and controls. DNA was extracted from plasma samples and the reaction was performed as per the manufacturer's instructions. Leptospiral isolates were also used to assess the performance using different serovars.
Results: Evaluation of the Truenat™ test with RT-PCR as the gold standard showed that Truenat™ had a sensitivity of 97.4 per cent and a specificity of 98.6 per cent. The overall agreement with RT-PCR was 98.2 per cent.
Interpretation & conclusions: Our results showed that the test would be a useful tool for early diagnosis of leptospirosis in settings with minimal facilities and the test results could be obtained within an hour. This indicates that a specific therapy can be instituted during the early phase of the disease even at peripheral healthcare facilities as well during the outbreaks.
Leptospirosis is a worldwide re-emerging zoonosis caused by pathogenic Leptospira spp. All vertebrate species can be infected; humans are sensitive hosts whereas other species, such as rodents, may ...become long-term renal carrier reservoirs. Upon infection, innate immune responses are initiated by recognition of Microbial Associated Molecular Patterns (MAMPs) by Pattern Recognition Receptors (PRRs). Among MAMPs, the lipopolysaccharide (LPS) is recognized by the Toll-Like-Receptor 4 (TLR4) and activates both the MyD88-dependent pathway at the plasma membrane and the TRIF-dependent pathway after TLR4 internalization. We previously showed that leptospiral LPS is not recognized by the human-TLR4, whereas it signals through mouse-TLR4 (mTLR4), which mediates mouse resistance to acute leptospirosis. However, although resistant, mice are known to be chronically infected by leptospires. Interestingly, the leptospiral LPS has low endotoxicity in mouse cells and is an agonist of TLR2, the sensor for bacterial lipoproteins. Here, we investigated the signaling properties of the leptospiral LPS in mouse macrophages. Using confocal microscopy and flow cytometry, we showed that the LPS of L. interrogans did not induce internalization of mTLR4, unlike the LPS of Escherichia coli. Consequently, the LPS failed to induce the production of the TRIF-dependent nitric oxide and RANTES, both important antimicrobial responses. Using shorter LPS and LPS devoid of TLR2 activity, we further found this mTLR4-TRIF escape to be dependent on both the co-purifying lipoproteins and the full-length O antigen. Furthermore, our data suggest that the O antigen could alter the binding of the leptospiral LPS to the co-receptor CD14 that is essential for TLR4-TRIF activation. Overall, we describe here a novel leptospiral immune escape mechanism from mouse macrophages and hypothesize that the LPS altered signaling could contribute to the stealthiness and chronicity of the leptospires in mice.
Leptospirosis is a zoonotic disease with a worldwide distribution affecting most mammalian species. Clinical leptospirosis is common in dogs but appears to be rare in cats. Both dogs and cats, ...however, can shed leptospires in the urine. This is problematic as it can lead to exposure of humans. The control of leptospirosis, therefore, is important not only from an animal but also from a public health perspective. The aim of this consensus statement is to raise awareness of leptospirosis and to outline the current knowledge on the epidemiology, clinical features, diagnostic tools, prevention and treatment measures relevant to canine and feline leptospirosis in Europe.
Letter to the Editor Lilenbaum, Walter; Narduche, Lorena; Ana Paula Loureiro ...
Journal of veterinary internal medicine,
11/2014, Letnik:
28, Številka:
6
Journal Article
Leptospira and leptospirosis Adler, Ben; de la Peña Moctezuma, Alejandro
Veterinary microbiology,
01/2010, Letnik:
140, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Leptospirosis is the most wide spread zoonosis worldwide; it is present in all continents except Antarctica and evidence for the carriage of
Leptospira has been found in virtually all mammalian ...species examined. Humans most commonly become infected through occupational, recreational, or domestic contact with the urine of carrier animals, either directly or via contaminated water or soil. Leptospires are thin, helical bacteria classified into at least 12 pathogenic and 4 saprophytic species, with more than 250 pathogenic serovars. Immunity following infection is generally, but not exclusively, mediated by antibody against leptospiral LPS and restricted to antigenically related serovars. Vaccines currently available consist of killed whole cell bacterins which are used widely in animals, but less so in humans. Current work with recombinant protein antigens shows promise for the development of vaccines based on defined protective antigens. The cellular and molecular basis for virulence remains poorly understood, but comparative genomics of pathogenic and saprophytic species suggests that
Leptospira expresses unique virulence determinants. However, the recent development of defined mutagenesis systems for
Leptospira heralds the potential for gaining a much improved understanding of pathogenesis in leptospirosis.
Leptospirosis is a zoonotic disease that has emerged as an important cause of morbidity and mortality among impoverished populations. One hundred years after the discovery of the causative ...spirochaetal agent, little is understood about Leptospira spp. pathogenesis, which in turn has hampered the development of new intervention strategies to address this neglected disease. However, the recent availability of complete genome sequences for Leptospira spp. and the discovery of genetic tools for their transformation have led to important insights into the biology of these pathogens and their pathogenesis. We discuss the life cycle of the bacterium, the recent advances in our understanding and the implications for the future prevention of leptospirosis.
Globally, leptospirosis poses an increasing public health problem, as evidenced by markedly increasing incidence rates and multiple outbreaks in all continents. Yet, the disease is severely neglected ...and hence, its global burden is largely unknown. The estimated incidence of about half a million severe human cases annually is probably an underestimation while the burden for animal health is unknown. It is anticipated that current international initiatives will assess the global burden of leptospirosis, while mathematical modelling of transmission dynamics will allow the identification and testing of appropriate intervention and outbreak response measures within the coming years.
Pathogenic leptospires are the bacterial agents of leptospirosis, which is an emerging zoonotic disease that affects animals and humans worldwide. The success of leptospires as pathogens is explained ...by their spiral shape and endoflagellar motility (which enable these spirochetes to rapidly cross connective tissues and barriers), as well as by their ability to escape or hijack the host immune system. However, the basic biology and virulence factors of leptospires remain poorly characterized. In this Review, we discuss the recent advances in our understanding of the epidemiology, taxonomy, genomics and the molecular basis of virulence in leptospires, and how these properties contribute to the mechanism of pathogenesis of leptospirosis.
This report offers a consensus opinion on the diagnosis, epidemiology, treatment, and prevention of leptospirosis in dogs, an important zoonosis. Clinical signs of leptospirosis in dogs relate to ...development of renal disease, hepatic disease, uveitis, and pulmonary hemorrhage. Disease may follow periods of high rainfall, and can occur in dogs roaming in proximity to water sources, farm animals, or wildlife, or dogs residing in suburban environments. Diagnosis is based on acute and convalescent phase antibody titers by the microscopic agglutination test (MAT), with or without use of polymerase chain reaction assays. There is considerable interlaboratory variation in MAT results, and the MAT does not accurately predict the infecting serogroup. The recommended treatment for optimal clearance of the organism from renal tubules is doxycycline, 5 mg/kg PO q12h, for 14 days. Annual vaccination can prevent leptospirosis caused by serovars included in the vaccine and is recommended for dogs at risk of infection.
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