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      Metagenomic next-generation sequencing in the diagnosis of leptospirosis presenting as severe diffuse alveolar hemorrhage: a case report and literature review

      case-report

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          Abstract

          Background

          Leptospirosis is a common infectious disease in tropical and semitropical regions, and it is typically neglected. Leptospirosis-associated acute diffuse alveolar hemorrhage is one of its fatal complications. The use of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing in the diagnosis of Leptospira interrogans infection has rarely been reported.

          Case presentation

          We present the case of a 62-year-old female who was transferred to our hospital with dyspnea, and severe hemoptysis and was supported by a tracheal intubation ventilator. Bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) reported Leptospira interrogans. A diagnosis of diffuse alveolar hemorrhage caused by leptospirosis was made. After immediately receiving antibiotics and hormone therapy, the patient achieved a complete recovery upon discharge.

          Conclusion

          Leptospirosis presenting as severe diffuse alveolar hemorrhage is rare but should be considered in the differential diagnosis. mNGS can help identify pathogens and treat them early, which can improve prognosis.

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          Most cited references18

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          Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection

          Wei Gu, Steve Miller, Charles Y. Chiu (2019)
          Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.
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            Leptospirosis: a zoonotic disease of global importance

            Ajay R Bharti, Jarlath E. Nally, Jessica Ricaldi … (2004)
            In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.
            Article 0 comments Cited 383 times – based on 0 reviews     Review now
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              Actionable diagnosis of neuroleptospirosis by next-generation sequencing.

              Erik Samayoa, Samia N Naccache, Mark J Biagtan … (2014)
              A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.
              Article 0 comments Cited 212 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chunxian Peng:
                ORCID: http://orcid.org/0000-0003-3496-5962
                springpeng1999@163.com
                Journal
                Journal ID (nlm-ta): BMC Infect Dis
                Journal ID (iso-abbrev): BMC Infect Dis
                Title: BMC Infectious Diseases
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2334
                Publication date (Electronic): 7 December 2021
                Publication date PMC-release: 7 December 2021
                Publication date Collection: 2021
                Volume: 21
                Electronic Location Identifier: 1230
                Affiliations
                GRID grid.459520.f, Department of Infectious Diseases, , The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, ; Quzhou, 324000 Zhejiang China
                Author information
                http://orcid.org/0000-0003-3496-5962
                Article
                Publisher ID: 6923
                DOI: 10.1186/s12879-021-06923-w
                PMC ID: 8650322
                PubMed ID: 34876042
                SO-VID: 24c395c2-f040-42b5-b1c0-58928a5569ba
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 1 March 2021
                Date accepted : 30 November 2021
                Categories
                Subject: Case Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: severe diffuse alveolar hemorrhage,leptospirosis,metagenomic next-generation sequencing,case report
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: severe diffuse alveolar hemorrhage, leptospirosis, metagenomic next-generation sequencing, case report

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