High dose corticosteroids in severe leptospirosis: a systematic review

Rodrigo, Chaturaka; Silva, Nipun Lakshitha de; Goonaratne, Ravindi; Samarasekara, Keshinie; Wijesinghe, Indika; Parththipan, Balasundaram; Rajapakse, Senaka

doi:10.1093/trstmh/tru148

Cited by 57 publications

(44 citation statements)

References 31 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%

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%

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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“…7 Renal support in the form of dialysis is often required, although there are few studies addressing the role of dialysis in leptospirosis. There is currently no firm evidence regarding the place of immunological therapy, such as corticosteroids 8 or immunoglobulins.…”

Section: Management Of Leptospirosismentioning

confidence: 99%

Leptospirosis: challenges in diagnosis, and predictors of severity

Rajapakse

Fernando

Niloofa

et al. 2017

J of Cey Coll of Phy

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“…This has led to recent reports of novel approaches to treatment including the use of inhaled nitric oxide and desmopressin (17,18). Although the benefits of corticosteroids in the treatment of ARDS are known, evidence for use of corticosteroids in pulmonary leptospirosis is confined to occasional case reports or small studies (19). Neither of these options were used in our case.…”

Section: Discussionmentioning

confidence: 93%

Acute Respiratory Distress Syndrome Manifested by Leptospirosis Successfully Teated by Extracorporeal Membrane Oxygenation (ECMO)

Liao

Ben

et al. 2015

Intern. Med.

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Leptospirosis is recognized as a zoonotic disease that is emerging worldwide. Severe manifestations are associated with high morbidity and mortality rates and may therefore pose an important risk to public health, especially in certain high prevalence areas like Taiwan. The severe pulmonary form of leptospirosis is a lesser known entity and is characterized by intra-alveolar hemorrhage and can lead to acute respiratory failure with resistant hypoxemia, which leads to high mortality rates despite maximally invasive mechanical ventilation and adequate treatment. We herein present a case of severe leptospirosis complicated by massive pulmonary hemorrhage, which was successfully managed by extra corporeal membrane oxygenation.

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High dose corticosteroids in severe leptospirosis: a systematic review

Cited by 57 publications

References 31 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

Leptospirosis: challenges in diagnosis, and predictors of severity

Acute Respiratory Distress Syndrome Manifested by Leptospirosis Successfully Teated by Extracorporeal Membrane Oxygenation (ECMO)

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