New Insights in Leptospirosis

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 21912

Special Issue Editors


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Guest Editor
1. National Veterinary Services Laboratories, Animal and Plant Health Inspection Service (APHIS), U.S. Department of Agriculture, Ames, IA 50010, USA
2. Laboratório de Referência Nacional para Leptospirose/Centro Colaborador da Organização Mundial da Saúde para Leptospirose, Instituto Oswaldo Cruz, Rio de Janeiro 3304557, Brazil
Interests: leptospirosis; animal leptospirosis; Leptospira; animal reservoir; environment; epidemiology; One Health; diagnosis; culture; PCR; ELISA; serology and molecular typing; control; zoonoses

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Guest Editor
Spirochete Research Lab, Department of Medicine, University of Connecticut Health, 263 Farmington Avenue, Farmington, CT 06030-3715, USA
Interests: leptospirosis; leptospira; pathogenesis; virulence; animal models; vaccines; Lyme disease; Borrelia burgdorferi; transcriptional regulation; gene expression

Special Issue Information

Dear Colleagues,

Leptospirosis is a neglected zoonotic disease of global importance and has a worldwide distribution. Over 1 million people suffer acute leptospirosis each year, with an estimated 58,900 deaths. Clinical manifestations range from asymptomatic or mild flu-like illness to severe disease, such as Weil’s disease and pulmonary hemorrhagic syndrome, for which fatality rates are higher than 10% and 50%, respectively. The precise molecular mechanisms that allow leptospires to stablish infection are largely unknown. Limitations on animal models and genetic manipulation of leptospires are major reasons for the small number of virulence determinants defined to date.

The epidemiology of the disease can vary depending on the ecology of cohabiting and interacting species and relating to serovars/genospecies distribution. Regarding the high number of asymptomatic animals, the true burden of the disease could be underestimated, and it can lead to neglecting the real rate of infection in livestock and domestic animals. The study of Leptospira spp. in animals, humans, and the environment is one health approach, which represents a key tool in the understanding of the disease’s epidemiology and control. The identification of urinary shedding of leptospires in symptomatic or asymptomatic animals and effective vaccines highlight preventive veterinary measures which should be taken to prevent dissemination of the leptospires in the environment and between animals, including humans, and which can help to direct animal and public health interventions.

This Special Issue aims to address new insights in animal and human leptospirosis with broad emphasis on epidemiology, pathogenesis, clinical cases, diagnosis, vaccine development, genomics, treatment, and control to improve the awareness and understanding of veterinarians, physicians, and researchers regarding this neglected disease. Studies on knowledge about Leptospira in soil and water environments are also welcomed. We invite the submission of reviews, protocols, reports, and original research articles; submissions based on work that originates from high-burden leptospirosis countries are especially encouraged.

Dr. Camila Hamond
Dr. André Grassmann
Guest Editors

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Keywords

  • animal leptospirosis
  • human leptospirosis
  • environmental
  • epidemiology
  • pathogenesis
  • clinical cases
  • diagnosis
  • molecular and serological typing
  • vaccine
  • one health

Published Papers (8 papers)

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Research

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9 pages, 951 KiB  
Communication
Animals Exposed to Leptospira Serogroups Not Included in Bacterins in the United States and Puerto Rico
by Tammy Anderson, Camila Hamond, Andréa Haluch, Kari Toot, Jarlath E. Nally, Karen LeCount and Linda K. Schlater
Trop. Med. Infect. Dis. 2023, 8(3), 183; https://doi.org/10.3390/tropicalmed8030183 - 22 Mar 2023
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Abstract
Leptospirosis is a worldwide zoonotic disease. Pathogenic leptospires colonize the renal tubules and genital tract of animals and are excreted via urine. Transmission occurs via direct contact or through contaminated water or soil. The microscopic agglutination test (MAT) is the gold standard for [...] Read more.
Leptospirosis is a worldwide zoonotic disease. Pathogenic leptospires colonize the renal tubules and genital tract of animals and are excreted via urine. Transmission occurs via direct contact or through contaminated water or soil. The microscopic agglutination test (MAT) is the gold standard for the serodiagnosis of leptospirosis. The present study aims to evaluate animal exposure to Leptospira in the U.S. and Puerto Rico during the period 2018–2020. The presence of antibodies against pathogenic Leptospira spp. was assessed with the MAT according to the standards of the World Organisation for Animal Health. A total of 568 sera were submitted for diagnostic, surveillance, or import/export testing from the U.S. and Puerto Rico. Seropositivity (≥1:100) was 51.8% (294/568) with agglutinating antibodies found in 115 (39.1%) cattle, 84 (28.6%) exotic animals, 38 (12.9%) horses, 22 (7.5%) goats, 15 (5.1%) dogs, 11 (3.7%) swine, and 9 (3.1%) sheep. The most detected serogroups were Australis, Grippotyphosa, and Ballum. The results showed that animals were exposed to serogroups/serovars not included in commercial bacterins such as Ballum, Bratislava (only in swine vaccine), and Tarassovi. Our findings suggest that more studies should include culture and concomitant genotyping to reduce animal disease and zoonotic risk through efficacious vaccine and diagnostic strategies. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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11 pages, 1397 KiB  
Article
Effect of Demographics and Time to Sample Processing on the qPCR Detection of Pathogenic Leptospira spp. from Human Samples in the National Reference Laboratory for Leptospirosis, Brazil
by Romulo Leão Silva Neris, Mariana Cristina da Silva, Mariana da Silva Batista, Keila de Cássia Ferreira de Almeida Silva, Ilana Teruszkin Balassiano and Kátia Eliane Santos Avelar
Trop. Med. Infect. Dis. 2023, 8(3), 151; https://doi.org/10.3390/tropicalmed8030151 - 28 Feb 2023
Viewed by 1365
Abstract
Leptospirosis diagnosis by MAT requires antibody levels that are typically present only after the first week of symptoms, many days after infection. To improve testing capacity and to develop a fast and reliable solution for the diagnosis of this disease in the first [...] Read more.
Leptospirosis diagnosis by MAT requires antibody levels that are typically present only after the first week of symptoms, many days after infection. To improve testing capacity and to develop a fast and reliable solution for the diagnosis of this disease in the first few days after clinical manifestations, the National Reference Laboratory for Leptospirosis/WHO Collaborating Center in Brazil implemented a duplex molecular method by qPCR for human samples for the detection of the gene lipL32, conserved in pathogenic Leptospira spp. In this paper, we describe the overall performance of this protocol in the first 3 months as a standard routine. Detection of pathogenic Leptospira spp. DNA was similar between blood, plasma, and tissue samples, with a limit of detection as low as one cell per sample, and among 391 samples from suspected cases, 174 (44.6%) were positive. The average RNASEP1 control gene detection cycle thresholds (Ct) were 28.4 and 29.8 for positive and negative samples, respectively. The median sample collection interval from the beginning of symptoms was 3 days for positive and 4 days for negative samples, respectively. Neither age, sex, nor the time intervals between sample collection and DNA extraction significantly influenced the results. Surprisingly, positivity was related to the time between DNA extraction and the qPCR reaction. These data support the use of this routine as a diagnostic approach to strengthen the molecular detection of leptospirosis and to develop new strategies. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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14 pages, 775 KiB  
Article
Feline Susceptibility to Leptospirosis and Presence of Immunosuppressive Co-Morbidities: First European Report of L. interrogans Serogroup Australis Sequence Type 24 in a Cat and Survey of Leptospira Exposure in Outdoor Cats
by Elisa Mazzotta, Gabrita De Zan, Monia Cocchi, Maria Beatrice Boniotti, Cristina Bertasio, Tommaso Furlanello, Laura Lucchese, Letizia Ceglie, Laura Bellinati and Alda Natale
Trop. Med. Infect. Dis. 2023, 8(1), 54; https://doi.org/10.3390/tropicalmed8010054 - 10 Jan 2023
Cited by 3 | Viewed by 3652
Abstract
Leptospirosis is one of the most widespread zoonotic diseases and can infect both humans and animals worldwide. The role of the cat as a susceptible host and potential environmental reservoir of Leptospira is still not well understood, due to the lack of obvious [...] Read more.
Leptospirosis is one of the most widespread zoonotic diseases and can infect both humans and animals worldwide. The role of the cat as a susceptible host and potential environmental reservoir of Leptospira is still not well understood, due to the lack of obvious clinical signs associated with Leptospira spp. infection in this species. This study aims to describe the first European detection of Leptospira interrogans serogroup Australis ST 24 in a young outdoor cat with a severe comorbidity (feline panleukopenia virus). In addition, the results of a preliminary study conducted in 2014–2016 are presented (RC IZSVE 16/12), which reports an investigation of Leptospira exposure of outdoor cats in Northeast Italy by means of serological investigation and molecular evaluation of urine. The animals included in the survey are part of samples collected during active and passive surveillance (diagnostic samples). The study reported a seroprevalence of 10.5% among outdoor cats and the serogroups identified were Grippotyphosa, Icterohaemorrhagiae, Bratislava, Canicola and Ballum. Symptomatic cats reported high MAT titres (ranging from 1:800 to 1:1600) towards antigens belonging to the serovars Grippotyphosa (1:800), Bratislava (1:1600), Icterohaemorrhagiae (1:200) and Copenhageni (1:200–1:800). In one subject, urine tested positive for Leptospira PCR. Cats with high antibody titres for Leptospira and/or positivity on molecular test suffered from immunosuppressive comorbidities (feline immunodeficiency virus and feline leukaemia virus; feline herpesvirus and lymphoma; hyperthyroidism). The overall prevalence of serum antibodies against Leptospira found in free-ranging cats (10.53%, 95% CI: 4.35–16.70%) and the identification of L. interrogans ST 24 in a young cat with immunosuppressive disease (feline panleukopenia virus) suggest the possibility of natural resistance to clinical leptospirosis in healthy cats. In a One Health perspective, further studies are needed to better define the pathogenesis of leptospirosis in cats and their epidemiological role as environmental sentinels or possible carriers of pathogenic Leptospira. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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14 pages, 1921 KiB  
Article
A New Recombinant Multiepitope Chimeric Protein of Leptospira interrogans Is a Promising Marker for the Serodiagnosis of Leptospirosis
by Luis G. V. Fernandes, Kátia E. S. Avelar, Eliete C. Romero, Marcos B. Heinemann, Karin Kirchgatter and Ana L. T. O. Nascimento
Trop. Med. Infect. Dis. 2022, 7(11), 362; https://doi.org/10.3390/tropicalmed7110362 - 09 Nov 2022
Cited by 2 | Viewed by 1935
Abstract
The zoonotic disease leptospirosis is caused by pathogenic species of the genus Leptospira and was recently included in the list of Neglected Diseases by the World Health Organization. Leptospirosis burden is estimated to have over a million human cases and cause 60 thousand [...] Read more.
The zoonotic disease leptospirosis is caused by pathogenic species of the genus Leptospira and was recently included in the list of Neglected Diseases by the World Health Organization. Leptospirosis burden is estimated to have over a million human cases and cause 60 thousand deaths annually, in addition to its economic impact and veterinary concern. The microscopic agglutination test (MAT), recommended by the World Health Organization, exhibits reduced sensitivity at the beginning of the disease, in addition to being technically difficult. New recombinant antigens are being pursued for rapid and specific serodiagnostic tests, especially in the initial phase of the disease, and chimeric multiepitope proteins are a strategy with a great potential to be implemented in serology. Based on previous subproteomic results, we designed a synthetic construct comprising 10 conserved leptospiral surface antigens, and the recombinant protein was purified and evaluated regarding its diagnostic potential. The protein termed rChi2 was recognized by antibodies in serum from patients both at the onset (MAT−) and in the convalescent (MAT+) phase in 75 and 82% of responders, respectively. In addition, rChi2 immunization in hamsters elicited a strong humoral response, and anti-rChi2 antibodies recognized several immobilized intact Leptospira species, validating its potential as an early, broad, and cross-reactive diagnostic test. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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12 pages, 3433 KiB  
Article
Pathogenesis and Genomic Analysis of a Virulent Leptospira Interrogans Serovar Copenhageni Isolated from a Dog with Lethal Infection
by Natasha Rodrigues de Oliveira, Frederico Schmitt Kremer, Risciela Salardi Alves de Brito, Rosimeri Zamboni, Odir Antônio Dellagostin and Sérgio Jorge
Trop. Med. Infect. Dis. 2022, 7(11), 333; https://doi.org/10.3390/tropicalmed7110333 - 28 Oct 2022
Cited by 1 | Viewed by 1564
Abstract
Dogs are highly susceptible to leptospirosis and are a public health concern due to their important role as a source of spreading disease, particularly in urban settings. In this study, we present the pathogenesis, serological characterization, and complete genome sequencing of a virulent [...] Read more.
Dogs are highly susceptible to leptospirosis and are a public health concern due to their important role as a source of spreading disease, particularly in urban settings. In this study, we present the pathogenesis, serological characterization, and complete genome sequencing of a virulent Brazilian strain (NEG7) of L. interrogans serovar Copenhageni isolated from the urine of a dog that died due to acute leptospirosis. Clinical investigation showed that the dog was presented with icteric mucous membranes, weakness, dehydration, anorexia, and kidney and liver failures. Necropsy followed by histopathological evaluation revealed lesions compatible with liver and kidney leptospirosis. The leptospires recovered from the urine were further characterized by genome analysis, which confirmed that the isolate belonged to L. interrogans serogroup icterohaemorrhagiae serovar Copenhageni. Multiple bioinformatics tools were used to characterize the genomic features, and comparisons with other available Copenhageni strains were performed. Characterization based on absence of an INDEL in the gene lic12008, associated with phylogenetic and ANI (99.99% identity) analyses, confirmed the genetic relatedness of the isolate with L. interrogans serovar Copenhageni. A better understanding of the diversity of the pathogenic Leptospira isolates could help in identifying genotypes responsible for severe infections. Moreover, it can be used to develop control and prevention strategies for Leptospira serovars associated with particular animal reservoirs. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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11 pages, 954 KiB  
Article
The Efficacy of Vaccination in the Prevention of Renal and Genital Leptospirosis in Experimentally Infected Sheep
by Gabriel Martins, Bruna Guadelupe, Luiza Aymée, Mario Felipe Alvarez Balaro, Pedro Henrique Pinto, Maria Isabel Nogueira Di Azevedo, Felipe Zandonadi Brandão and Walter Lilenbaum
Trop. Med. Infect. Dis. 2022, 7(10), 321; https://doi.org/10.3390/tropicalmed7100321 - 21 Oct 2022
Cited by 4 | Viewed by 1646
Abstract
(1) Background: Leptospirosis, mainly determined by strains belonging to serogroup Sejroe, has a direct impact on the reproductive efficiency of ruminants, such as sheep. In Brazil, Leptospira santarosai serovar Guaricura, known to be able to chronically colonize the uterine environment, is of special [...] Read more.
(1) Background: Leptospirosis, mainly determined by strains belonging to serogroup Sejroe, has a direct impact on the reproductive efficiency of ruminants, such as sheep. In Brazil, Leptospira santarosai serovar Guaricura, known to be able to chronically colonize the uterine environment, is of special note. Although vaccination minimizes the effects of acute disease, whether or not it can protect from renal colonization remains controversial, and its effects on the genital tract are unknown. In this context, the present study aims to investigate the efficacy of vaccination in the prevention of experimental genital leptospirosis. (2) Methods: Eighteen sheep were divided into three groups: one vaccinated with a polyvalent commercial bacterin, one vaccinated with an autologous bacterin, and one unvaccinated. After 14 days, the sheep were experimentally challenged with 108 leptospires (L. santarosai, serogroup Sejroe, serovar Guaricura, strain FV52) intraperitoneally. Serology and colonization of the urinary and genital tracts were carried out monthly by PCR for 210 days in all animals. (3) Results: Vaccination significantly elicited antibody titers with a predominance of agglutinins against serogroup Sejroe. Both urinary and genital infections were confirmed by PCR. Positivity in urine PCR was absent after D120, while genital infection persisted until the end of the study. Serological results and the finding that vaccination did not avoid renal colonization align with previous studies. Despite vaccination, Leptospira established chronic and asymptomatic colonization of the genital tract until D210, an outstanding finding that remains to be fully understood in its mechanisms. (4) Conclusions: This is the first study conducted to analyze the effects of vaccination in the prevention of genital leptospirosis. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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Review

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14 pages, 1941 KiB  
Review
Comparison of the PF07598-Encoded Virulence-Modifying Proteins of L. interrogans and L. borgpetersenii
by Dielson S. Vieira, Reetika Chaurasia and Joseph M. Vinetz
Trop. Med. Infect. Dis. 2023, 8(1), 14; https://doi.org/10.3390/tropicalmed8010014 - 26 Dec 2022
Cited by 3 | Viewed by 3187
Abstract
Leptospirosis is an emerging infectious disease, with increasing frequency and severity of outbreaks, a changing epidemiology of populations at risk, and the emergence of new strains, serovars, serogroups, and species. Virulence-modifying (VM) proteins encoded by the PF07598 gene family are hypothesized to be [...] Read more.
Leptospirosis is an emerging infectious disease, with increasing frequency and severity of outbreaks, a changing epidemiology of populations at risk, and the emergence of new strains, serovars, serogroups, and species. Virulence-modifying (VM) proteins encoded by the PF07598 gene family are hypothesized to be Leptospira-secreted exotoxins that mediate the molecular and cellular pathogenesis of severe and fatal leptospirosis. If confirmed experimentally, this concept could revolutionize the treatment, diagnosis, prognosis, and vaccine-mediated prevention of leptospirosis by enabling a novel array of targeted interventions. VM proteins, as with other bacterial-secreted protein exotoxins, mediate their virulence effects by attaching to eukaryotic cells, competing with other microorganisms for limited resources in environmental niches, directly intoxicating target cells, and disrupting their function in the mammalian host. In contrast with the most pathogenic group of Lept ospira, particularly L. interrogans, whose genomes contain 12–15 PF07598 paralogs, strains of the livestock and human pathogen L. borgpetersenii have two PF07598 paralogs. Given the possible non-environmentally mediated transmission of some L. borgpetersenii strains and the much smaller number of VM proteins in this species, their role in infection and disease may well differ from other leptospiral species. Comparison of VM proteins from different clades of pathogenic Leptospira may deepen our understanding of leptospirosis’s pathogenesis, leading to novel approaches to ameliorating Leptospira infection in humans and animals. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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15 pages, 562 KiB  
Review
Potential Drivers for the Re-Emergence of Canine Leptospirosis in the United States and Canada
by Amanda M. Smith, Jason W. Stull and George E. Moore
Trop. Med. Infect. Dis. 2022, 7(11), 377; https://doi.org/10.3390/tropicalmed7110377 - 14 Nov 2022
Cited by 8 | Viewed by 4773
Abstract
Canine leptospirosis is an important zoonotic disease in many countries. This review examines potential drivers for increased diagnoses of canine leptospirosis in the United States and Canada, using the epidemiologic triad of agent-environment-host as a template. Leptospira spp. are classified into more than [...] Read more.
Canine leptospirosis is an important zoonotic disease in many countries. This review examines potential drivers for increased diagnoses of canine leptospirosis in the United States and Canada, using the epidemiologic triad of agent-environment-host as a template. Leptospira spp. are classified into more than 250 serovars, but in many laboratories only 6 are routinely tested for in serologic agglutination tests of canine sera. Leptospiral infections in dogs may potentially go undetected with unemployed or currently employed diagnostic methods. Disease transmission from infected reservoir hosts usually occurs via urine-contaminated environmental sources such as water. Direct contact between infected and susceptible individuals, environmental factors such as climate changes in temperature and/or rainfall, and increasing number and urbanization of reservoir hosts may greatly increase dog exposure risks. A dog’s lifestyle may influence exposure risk to leptospirosis, but vaccination based on proper identification of circulating serogroups dramatically reduces post-exposure infections. Regrettably, resistance to vaccination by veterinarians and dog owners leaves a large number of dogs at risk for this zoonotic disease. Full article
(This article belongs to the Special Issue New Insights in Leptospirosis)
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