Severe <i>Leptospira interrogans</i> serovar Icterohaemorrhagiae infection with hepato‐renal‐pulmonary involvement treated with corticosteroids

Schulze, Marco H.; Raschel, Heribert; Langen, H.-J.; Stich, August; Tappe, Dennis

doi:10.1002/ccr3.91

Cited by 10 publications

(7 citation statements)

References 29 publications

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“…57, 58, 59 In this study, we observed an alleviation of pulmonary hemorrhage in TLR4 −/− mice, possibly due to suppression of the ‘storm’ of proinflammatory cytokine production. This suggests the potential of combining TLR4 blockade and antibiotics in the treatment of severe leptospirosis with manifestations of pulmonary hemorrhage.…”

Section: Discussionsupporting

confidence: 54%

“…There are some published cases of severe leptospirosis in which corticosteroid administration improved survival among patients, while there is still insufficient evidence to suggest the effectiveness of immunosuppressive treatments in severe leptospirosis. 57 , 58 , 59 In this study, we observed an alleviation of pulmonary hemorrhage in TLR4 −/− mice, possibly due to suppression of the ‘storm’ of proinflammatory cytokine production. This suggests the potential of combining TLR4 blockade and antibiotics in the treatment of severe leptospirosis with manifestations of pulmonary hemorrhage.…”

Section: Discussionsupporting

confidence: 54%

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A new model of self-resolving leptospirosis in mice infected with a strain of Leptospira interrogans serovar Autumnalis harboring LPS signaling only through TLR4

Xia

Sun

Fan

et al. 2017

Emerging Microbes & Infections

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Leptospirosis is an emerging worldwide zoonosis caused by pathogenic Leptospira spp. Our understanding of leptospirosis pathogenesis and host immune response remains limited, while mechanistic studies are hindered by a lack of proper animal models and immunological reagents. Here we established a murine model of acute and self-resolving leptospirosis by infecting 10-week-old C57BL/6 mice with Leptospira interrogans serovar Autumnalis strain 56606v, with characteristic manifestations including jaundice as well as subcutaneous and pulmonary bleeding, but no kidney lesions. We also verified that the lipopolysaccharide (LPS) of strain 56606v signaled through a TLR4-dependent pathway in murine bone marrow-derived macrophages (BMDMs), rather than the previously reported TLR2. In addition, upon infection with Leptospira strain 56606v, TLR4−/− C57BL/6 mice presented more severe jaundice and liver injury as well as higher bacterial loads than WT mice but milder pulmonary hemorrhaging. Molecular studies showed that leptospirosis-related bleeding coincides with the temporal kinetics of iNOS production, while jaundice and liver injury are probably due to insufficiently controlled bacterial loads in the liver. These results suggested that TLR4 is essential in mediating host leptospiral clearance and, to some extent, is associated with pulmonary and subcutaneous hemorrhage, probably through downstream inflammatory mediators, iNOS in particular. Overall, our murine model using immunocompetent mice might facilitate future studies into the pathogenesis of jaundice and bleeding in leptospirosis. Meanwhile, our study suggests the prospect of combining antibiotics and immunosuppressants in the treatment of severe leptospirosis presenting with pulmonary hemorrhage.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionsupporting

confidence: 54%

A new model of self-resolving leptospirosis in mice infected with a strain of Leptospira interrogans serovar Autumnalis harboring LPS signaling only through TLR4

Xia

Sun

Fan

et al. 2017

Emerging Microbes & Infections

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“…Leptospira interrogans is known to cause severe symptoms such as pneumonia, hepatitis and kidney failure in humans and dogs [ 45 , 46 ]. The hazardous impact of L .…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Genotype Allocation of Pathogenic Leptospira Species in Small Mammals from Various Habitat Types in Germany

et al. 2016

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Small mammals serve as most important reservoirs for Leptospira spp., the causative agents of Leptospirosis, which is one of the most neglected and widespread zoonotic diseases worldwide. The knowledge about Leptospira spp. occurring in small mammals from Germany is scarce. Thus, this study’s objectives were to investigate the occurrence of Leptospira spp. and the inherent sequence types in small mammals from three different study sites: a forest in southern Germany (site B1); a National Park in south-eastern Germany (site B2) and a renaturalised area, in eastern Germany (site S) where small mammals were captured. DNA was extracted from kidneys of small mammals and tested for Leptospira spp. by real-time PCR. Positive samples were further analysed by duplex and conventional PCRs. For 14 positive samples, multi locus sequence typing (MLST) was performed. Altogether, 1213 small mammals were captured: 216 at site B1, 456 at site B2 and 541 at site S belonging to following species: Sorex (S.) araneus, S. coronatus, Apodemus (A.) flavicollis, Myodes glareolus, Microtus (Mi.) arvalis, Crocidura russula, Arvicola terrestris, A. agrarius, Mustela nivalis, Talpa europaea, and Mi. agrestis. DNA of Leptospira spp. was detected in 6% of all small mammals. At site B1, 25 small mammals (11.6%), at site B2, 15 small mammals (3.3%) and at site S, 33 small mammals (6.1%) were positive for Leptospira spp. Overall, 54 of the positive samples were further determined as L. kirschneri, nine as L. interrogans and four as L. borgpetersenii while five real-time PCR-positive samples could not be further determined by conventional PCR. MLST results revealed focal occurrence of L. interrogans and L. kirschneri sequence type (ST) 117 while L. kirschneri ST 110 was present in small mammals at all three sites. Further, this study provides evidence for a particular host association of L. borgpetersenii to mice of the genus Apodemus.

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“…Five studies (11,12,13,14,15) on patients with a severe form of leptospirosis treated with corticosteroids have been published to date (mostly concerning patients with pulmonary haemorrhage and multiorgan failure). These patients were treated with corticosteroids in the first 12 hours since the onset of respiratory symptoms (tachypnea >30/min, dry cough, dyspnoea or haemoptysis).…”

Section: Discussionmentioning

confidence: 99%

Adjunctive treatment of leptospirosis with corticosteroids

Pavić

2020

Infektol. glas. (Online)

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Leptospirosis is one of the most globally widespread zoonosis caused by pathogenic spirochetes from genus Leptospira spp. Icteric leptospirosis is a severe form of the disease which affects 5-15% of patients with leptospirosis, is often rapidly progressive and has a high mortality rate. Early diagnosis of leptospirosis is crucial for initiation of adequate antimicrobial therapy in order to prevent the advent of complications and reduce mortality. Literature offers an increasing amount of evidence that early application of corticosteroids affects the course of the disease, prevents the onset of multiorgan failure, reduces mortality and reduces the duration of hospitalization. This paper is a case report of a patient with severe icteric leptospirosis who was treated with antimicrobial and corticosteroid therapy. The patient recovered fully, with no remaining morbidity after the severe disease.

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Severe Leptospira interrogans serovar Icterohaemorrhagiae infection with hepato‐renal‐pulmonary involvement treated with corticosteroids

Cited by 10 publications

References 29 publications

A new model of self-resolving leptospirosis in mice infected with a strain of Leptospira interrogans serovar Autumnalis harboring LPS signaling only through TLR4

A new model of self-resolving leptospirosis in mice infected with a strain of Leptospira interrogans serovar Autumnalis harboring LPS signaling only through TLR4

Prevalence and Genotype Allocation of Pathogenic Leptospira Species in Small Mammals from Various Habitat Types in Germany

Adjunctive treatment of leptospirosis with corticosteroids

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