Epidemiology of Leptospira sp. Infection: Current Status, Insights and Future Prospects

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Parasitology".

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 15423

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Special Issue Information

Dear Colleagues,

Leptospirosis is an emerging zoonosis, especially in subtropical and tropical regions. The etiologic agent belongs to the order Spirochaetales, family Leptospiraceae and genus Leptospira. It affects several animal species causing great economic losses in livestock, and the negative effects of the disease on the productive and reproductive indices of ruminants are well known, causing abortion, repetition of estrus, the birth of weak animals, stillbirth and decreased production of milk, in addition to being an important public health concern.

Leptospires are shed and maintained in the environment by several hosts, such as wild, domestic and synanthropic animals, with rodents being the main reservoirs. The disease is complex, including the natural environment, asymptomatic reservoirs and susceptible hosts. Domestic animals can get infected and act as sources of infection for other animals or humans, and the main transmission routes are direct or indirect contact with urine, placenta, vaginal fluid, venereal contact, and intrauterine infection, contributing to the endemism of the disease. Disease control becomes complex as multiple hosts can act as asymptomatic carriers or develop mild or severe disease. Humans are most commonly infected through occupational, recreational, or domestic contact with the urine of carrier animals, either directly or through contaminated water or soil.

This Special Issue aims to address the current status, insights and future prospects on the epidemiology of Leptospira sp. infection, with a broad emphasis on the relevant aspects such as a deeper understanding of the biodiversity of strains that can lead to infections in both humans and animals, molecular epidemiology, improvement of diagnostic methods, and new epidemiological insights. We invite the submission of reviews and original research articles.

We look forward to receiving your contributions.

Dr. Sérgio Santos De Azevedo
Guest Editor

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Keywords

  • Leptospira sp.
  • leptospirosis
  • epidemiology
  • control
  • environment
  • diagnosis

Published Papers (8 papers)

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Editorial

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3 pages, 196 KiB  
Editorial
Epidemiology of Leptospira sp. Infection: Current Status, Insights and Future Prospects
by Sérgio Santos de Azevedo
Microorganisms 2024, 12(1), 22; https://doi.org/10.3390/microorganisms12010022 - 22 Dec 2023
Viewed by 778
Abstract
In recent decades, the scientific community has been faced with an increased risk of emerging or re-emerging zoonotic diseases, such as leptospirosis, mainly originating from anthropic actions [...] Full article

Research

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15 pages, 1845 KiB  
Article
First Report on Leptospira Species Isolated from Patients in Slovenia
by Eva Ružić-Sabljić, Daša Podgoršek, Katja Strašek Smrdel, Andraž Celar Šturm, Mateja Logar, Andrea Pavlović, Tatjana Remec, Zvonko Baklan, Emil Pal and Tjaša Cerar Kišek
Microorganisms 2023, 11(11), 2739; https://doi.org/10.3390/microorganisms11112739 - 9 Nov 2023
Viewed by 812
Abstract
Leptospirosis is an important worldwide zoonosis, and it has also been reported in Slovenia. The cultivation of Leptospira from human material is difficult. Despite that, we successfully isolated 12 human Leptospira strains isolated from patients between 2002 and 2020 and used various methods [...] Read more.
Leptospirosis is an important worldwide zoonosis, and it has also been reported in Slovenia. The cultivation of Leptospira from human material is difficult. Despite that, we successfully isolated 12 human Leptospira strains isolated from patients between 2002 and 2020 and used various methods for the phenotypic and genotypic characterization of the strains, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) using our own MALDI-TOF data library, melting temperature analysis of the amplified lfb1 gene, determination of Leptospira serogroups using rabbit immune sera, NotI-RFLP of the whole Leptospira genome, multilocus sequence typing (MLST) of seven housekeeping genes, and whole-genome sequencing (WGS)-based typing. We confirmed the presence of four pathogenic Leptospira species (L. kirschneri, L. interrogans, L. borgpetersenii, and L. santarosai) and three serogroups: Grippotyphosa, Icterohaemorrhagiae, and Sejroe. MALDI-TOF identified three of seven isolates at the species level and four isolates at the genus level. Serovars of 8 of the 10 strains were determined using NotI-RFLP. MLST showed that the clinical isolates belonged to sequence types ST17, ST110, and ST155. WGS confirmed the analysis of Leptospira strains using conventional methods. In addition, WGS provided better taxonomic resolution for isolate DDA 10944/10. Full article
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9 pages, 311 KiB  
Article
Strong Evidence of the Role of Donkeys in the Epidemiology of Leptospira spp. in Semiarid Conditions
by Davidianne de Andrade Morais, Bruno Cesar Nunes, Rafael Rodrigues Soares, Murilo Duarte de Oliveira, Diego Figueiredo da Costa, Hosaneide Gomes de Araújo, João Pessoa Araújo Júnior, Camila Dantas Malossi, Maria Luana Cristiny Rodrigues Silva, Sérgio Santos de Azevedo and Clebert José Alves
Microorganisms 2023, 11(7), 1853; https://doi.org/10.3390/microorganisms11071853 - 22 Jul 2023
Viewed by 973
Abstract
Donkeys (Equus asinus) are historically known for their close relationship to humanity, which raises the need to study zoonotic diseases that affect them. In this perspective, leptospirosis stands out as a disease with an economic and public health impact, and its [...] Read more.
Donkeys (Equus asinus) are historically known for their close relationship to humanity, which raises the need to study zoonotic diseases that affect them. In this perspective, leptospirosis stands out as a disease with an economic and public health impact, and its occurrence is facilitated in times of higher rainfall indexes, especially in large urban centers. In view of the scarcity of information about leptospirosis in donkeys, the objective of this study was to detect the presence of Leptospira spp. and anti-leptospiral antibodies in donkeys rescued by a zoonosis center located in the Caatiga biome, Brazilian semiarid region. Overall, 30 donkeys of both sexes, aged between 4 months and 15 years, were used, from which 64 serum samples were collected and submitted to the microscopic agglutination test (MAT). In addition, 64 samples of urine, vaginal and preputial fluid, in duplicates, were subjected to the polymerase chain reaction (PCR) and microbiological. Sixteen (53.3%) animals tested positive in at least one diagnostic test, 12 (40%) of which were positive at MAT and seven (23.3%) in the molecular and bacteriological detection (urine, vaginal, and preputial fluid samples). This is the first report identifying donkeys infected with Leptospira spp. by molecular and bacteriological diagnosis in Brazil, and the first in the world to detect this agent in their genital fluids. The study also shows that donkeys are commonly exposed to leptospires in the Caatinga biome, and this constitutes a One Health-based concern, demonstrating the importance of broad studies where large numbers of humans and animals coexist when investigating zoonotic infections and when planning and implementing control measures for donkeys-associated leptospirosis. Full article
26 pages, 1824 KiB  
Article
DNA Capture and Enrichment: A Culture-Independent Approach for Characterizing the Genomic Diversity of Pathogenic Leptospira Species
by Nathan E. Stone, Ryelan F. McDonough, Camila Hamond, Karen LeCount, Joseph D. Busch, Katherine L. Dirsmith, Sarai Rivera-Garcia, Fred Soltero, Laura M. Arnold, Zachary Weiner, Renee L. Galloway, Linda K. Schlater, Jarlath E. Nally, Jason W. Sahl and David M. Wagner
Microorganisms 2023, 11(5), 1282; https://doi.org/10.3390/microorganisms11051282 - 14 May 2023
Cited by 3 | Viewed by 1659
Abstract
Because they are difficult to culture, obtaining genomic information from Leptospira spp. is challenging, hindering the overall understanding of leptospirosis. We designed and validated a culture-independent DNA capture and enrichment system for obtaining Leptospira genomic information from complex human and animal samples. It [...] Read more.
Because they are difficult to culture, obtaining genomic information from Leptospira spp. is challenging, hindering the overall understanding of leptospirosis. We designed and validated a culture-independent DNA capture and enrichment system for obtaining Leptospira genomic information from complex human and animal samples. It can be utilized with a variety of complex sample types and diverse species as it was designed using the pan-genome of all known pathogenic Leptospira spp. This system significantly increases the proportion of Leptospira DNA contained within DNA extracts obtained from complex samples, oftentimes reaching >95% even when some estimated starting proportions were <1%. Sequencing enriched extracts results in genomic coverage similar to sequenced isolates, thereby enabling enriched complex extracts to be analyzed together with whole genome sequences from isolates, which facilitates robust species identification and high-resolution genotyping. The system is flexible and can be readily updated when new genomic information becomes available. Implementation of this DNA capture and enrichment system will improve efforts to obtain genomic data from unculturable Leptospira-positive human and animal samples. This, in turn, will lead to a better understanding of the overall genomic diversity and gene content of Leptospira spp. that cause leptospirosis, aiding epidemiology and the development of improved diagnostics and vaccines. Full article
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12 pages, 1252 KiB  
Article
Serological and Molecular Evidence of Pathogenic Leptospira spp. in Stray Dogs and Cats of Sicily (South Italy), 2017–2021
by Francesca Grippi, Vincenza Cannella, Giusi Macaluso, Valeria Blanda, Giovanni Emmolo, Francesco Santangelo, Domenico Vicari, Paola Galluzzo, Carmela Sciacca, Rosalia D’Agostino, Ilenia Giacchino, Cristina Bertasio, Mario D’Incau, Annalisa Guercio and Alessandra Torina
Microorganisms 2023, 11(2), 385; https://doi.org/10.3390/microorganisms11020385 - 2 Feb 2023
Cited by 5 | Viewed by 1582
Abstract
Leptospirosis is a zoonosis of public health concern. Its prevalence in stray animals in the South of Italy is unknown. This study aimed to investigate Leptospira spp. prevalence in 1009 stray animals. Out of them, 749 were alive animals, including 358 dogs (316 [...] Read more.
Leptospirosis is a zoonosis of public health concern. Its prevalence in stray animals in the South of Italy is unknown. This study aimed to investigate Leptospira spp. prevalence in 1009 stray animals. Out of them, 749 were alive animals, including 358 dogs (316 from Palermo and 42 from Ragusa) and 391 cats (359 from Palermo and 32 from Ragusa), and 260 were corpses (216 dogs and 44 cats) randomly collected in Sicily. Dogs and cats underwent a serological screening by Microscopic Agglutination Test and a molecular investigation by Real-Time PCR targeting lipL32. Corpses were subjected to Real-Time PCR. Serological analyses showed a prevalence of 1.12% (4/358) for dogs and 0.26% (1/391) for cats, with the only positive cat coming from Palermo. Serogroup Icterohaemorrhagiae serovar Icterohaemorrhagiae or Copenhageni, followed by Canicola and Bratislava, were the most spread among dogs, while the serological positive cat reacted with Hardjo serogroup. Two urine (2/32, 6.25%) and one blood (1/391, 0.26%) samples of cats, all from Ragusa, were positive at Real-Time PCR for pathogenic Leptospira spp. Sequencing analyses showed the presence of L. interrogans serogroup Icterohaemorrhagiae serovar Icterohaemorrhagiae or Copenhageni in one of the positive urine samples and in the positive blood sample. Analyses on corpses showed a prevalence of 1.85% (4/216) in Sicilian dog kidney samples, while all corpses of cats resulted in negative. Genotyping analysis showed a genetic relatedness between cat and human isolates. Results show Leptospira spp. circulation among Sicilian stray animals. The genetic relatedness between cat and human isolates suggests a possible common infection source. Full article
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Review

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15 pages, 1571 KiB  
Review
Molecular Diagnosis as an Alternative for Public Health Surveillance of Leptospirosis in Colombia
by Margarita Arboleda, Mariana Mejía-Torres, Maritza Posada, Nicaela Restrepo, Paola Ríos-Tapias, Luis Alberto Rivera-Pedroza, David Calle, Miryan M. Sánchez-Jiménez, Katerine Marín and Piedad Agudelo-Flórez
Microorganisms 2023, 11(11), 2759; https://doi.org/10.3390/microorganisms11112759 - 13 Nov 2023
Viewed by 1249
Abstract
Leptospirosis represents a public health problem in Colombia. However, the underreporting of the disease is an unfortunate reality, with a clear trend towards a decrease in cases since 2019, when the guidelines for its confirmatory diagnosis changed with the requirement of two paired [...] Read more.
Leptospirosis represents a public health problem in Colombia. However, the underreporting of the disease is an unfortunate reality, with a clear trend towards a decrease in cases since 2019, when the guidelines for its confirmatory diagnosis changed with the requirement of two paired samples. The purpose of this review is to highlight the importance of leptospirosis. While the access to rapid diagnosis is available at practically all levels of care for dengue and malaria, leptospirosis—a doubly neglected disease—deserves recognition as a serious public health problem in Colombia. In this manner, it is proposed that molecular tests are a viable diagnostic alternative that can improve the targeted treatment of the patient and the timeliness of data and case reporting to SIVIGILA, and reduce the underreporting of the disease. Taking advantage of the strengthened technological infrastructure derived from the SARS-CoV-2 pandemic for molecular diagnosis in Colombia, with a network of 227 laboratories distributed throughout the national territory, with an installed capacity for PCR testing, it is proposed that molecular diagnosis can be used as an alternative for early diagnosis. This would allow case confirmation through the public health network in Colombia, and, together with the microagglutination (MAT) technique, the epidemiological surveillance of this disease in this country would be strengthened. Full article
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16 pages, 624 KiB  
Review
Leptospira Status in Sweden during the Past Century, Neglected and Re-Emerging?
by Tanja M. Strand, Eva Olsson Engvall, Elina Lahti, Marika Hjertqvist and Åke Lundkvist
Microorganisms 2023, 11(8), 1991; https://doi.org/10.3390/microorganisms11081991 - 2 Aug 2023
Viewed by 984
Abstract
We compiled data on notified cases of leptospirosis in animals and humans in Sweden. Published studies on leptospirosis in humans and animals from the beginning of the 20th century onwards are summarized. During the Second World War, hundreds of leptospirosis cases in humans [...] Read more.
We compiled data on notified cases of leptospirosis in animals and humans in Sweden. Published studies on leptospirosis in humans and animals from the beginning of the 20th century onwards are summarized. During the Second World War, hundreds of leptospirosis cases in humans were reported in Sweden, but since then, there have been only a few severe cases. Surveillance of leptospirosis in domestic animals demonstrates that the pathogen is still occurring. The occurrence of Leptospira in humans and animals in the other Nordic countries resembles that in Sweden. Leptospirosis is an underdiagnosed and underreported disease globally, both in animals and humans, partly due to the lack of simple, rapid diagnostic tools but possibly also due to the lack of awareness among physicians, veterinarians and nurses. Traditionally, leptospirosis has been mostly diagnosed by serology, but development of molecular methodshas improved the capability for correct diagnosis. As of today, leptospirosis is regarded as a relatively uncommon disease in the Nordic countries, but in some other countries, it is considered a neglected zoonosis or a (re-)emerging disease that may become more common in the future. Possible factors that could contribute to an increase in incidence are discussed in this review. Active surveillance of humans and domestic and wild animals and stringent rodent control in society and animal farms are of outmost importance for prevention. Full article
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16 pages, 1472 KiB  
Review
Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase
by Cassiano Felippe Gonçalves-de-Albuquerque, Carolina Medina Coeli da Cunha, Léo Victor Grimaldi de Castro, Caroline de Azevedo Martins, Marcos Roberto Colombo Barnese, Patrícia Burth and Mauricio Younes-Ibrahim
Microorganisms 2023, 11(7), 1695; https://doi.org/10.3390/microorganisms11071695 - 29 Jun 2023
Cited by 3 | Viewed by 6069
Abstract
Inada and Ido identified Leptospira sp. as the pathogen responsible for Weil’s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism’s interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated [...] Read more.
Inada and Ido identified Leptospira sp. as the pathogen responsible for Weil’s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism’s interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated and purified, the complexity of the molecular interactions between these components and the host and the molecular mechanisms responsible for the systemic dysfunctions still needs to be fully unveiled. Leptospirosis affects virtually all animal species. Its cellular pathophysiology must involve a ubiquitous cellular mechanism in all eukaryotes. Na/K-ATPase is the molecular target of the leptospiral endotoxin (glycolipoprotein—GLP). Na/K-ATPase dysfunctions on different types of cells give rise to the organ disorders manifested in leptospirosis. Concomitantly, the development of a peculiar metabolic disorder characterized by dyslipidemia, with increased levels of circulating free fatty acids and an imbalance in the fatty acid/albumin molar ratio, triggers events of cellular lipotoxicity. Synergistically, multiple molecular stimuli are prompted during the infection, activating inflammasomes and Na/K-ATPase signalosome, leading to pro-inflammatory and metabolic alterations during leptospirosis. Leptospirosis involves diverse molecular mechanisms and alteration in patient inflammatory and metabolic status. Nonetheless, Na/K-ATPase is critical in the disease, and it is targeted by GLP, its components, and other molecules, such as fatty acids, that inhibit or trigger intracellular signaling through this enzyme. Herein, we overview the role of Na/K-ATPase during leptospirosis infection as a potential therapeutic target or an indicator of disease severity. Full article
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