Leptospirosis: a zoonotic disease of global importance

doi:10.1016/S1473-3099(03)00830-2

The Lancet Infectious Diseases

Volume 3, Issue 12, December 2003, Pages 757-771

https://doi.org/10.1016/S1473-3099(03)00830-2 Get rights and content

Summary

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 β—lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.

Section snippets

Microbiology and taxonomy

Leptospires are spirochetes (figure 1), a group of bacteria that diverged early in bacterial evolution.¹⁰ The family leptospiraceae includes two genera, Leptospira and Leptonema. Typically, leptospires were classified according to antigenic determinants.11, 12 More recently, a molecular classification has been described that divides the Leptospira genus into several species on the basis of DNA relatedness.13, 14, 15, 16 The reclassification of leptospires using genetic determinants provides

Microbiology

The leptospiral genome consists of two circular chromosomes¹⁷ and its entire sequence was recently established.¹⁸ The genome is large compared with the genomes of other spirochetes such as Treponema spp¹⁹ and Borrelia spp,²⁰ which indicates the ability of Leptospira spp to live within diverse environments: animal hosts and freely in the environment. Little is known about genetic exchange among the Leptospira, although lateral transfer has been suggested.²¹ Tools for genetic manipulation of

Taxonomy

The species classification of the genus Leptospira is based on DNA relatedness (table 1).13, 14, 15, 16 The genus is divided into 17 species, defined as being at least 70% DNA—related and whose related DNA sequences contain at most 5% unpaired bases (divergence).¹⁵ This classification coexists with the older serological classification in which antisera are used to establish antigenic relatedness between isolates.¹¹ Leptospiral strains are still commonly referred to by serovar (Table 1, Table 2

Epidemiology

Leptospirosis has a worldwide distribution. The incidence of human infection is higher in the tropics than in temperate regions but transmission occurs in both industrialised and developing countries. Incidence rates are underestimated due to lack of awareness of the disease and relatively inaccessible and insufficiently rapid diagnostics. Symptom—less or subclinical infection is common in endemic regions.34,35 We have seen that a surprisingly high proportion (20–30%) of patients presenting

Pathogenesis

Host infection by pathogenic Leptospira produces a diverse array of clinical manifestations ranging from subclinical infection to undifferentiated febrile illness to jaundice, renal failure, and potentially lethal pulmonary haemorrhage. Our understanding of mechanisms of leptospirosis pathogenesis is limited. Answers to the most basic questions, such as whether the outcome of infection (mild or severe disease) is due to direct pathogen effects or genetically determined host immune responses,

Clinical features

Leptospirosis has protean manifestations, and mimics the clinical presentations of many other diseases.32, 96 Consequently, mechanisms of the clinical manifestations of leptospirosis remain obscure. Typical descriptions⁹⁷ include a biphasic illness (anicteric form, figure 10) and fulminant disease (icterohaemorrhagic form, figure 11).⁹ In the biphasic illness the initial acute or septicaemic phase is characterised by bacteraemia that typically lasts about 1 week. Most of the recognised cases

General laboratory tests

Diagnosis of leptospirosis depends on simple diagnostic tests, which are often not done because of a low index of clinical suspicion. Laboratory diagnosis of leptospirosis can be made either by showing the organism or by serological tests that detect leptospiral antibodies.¹²² Several non—specific findings may include increased ESR, mild increases in transaminases, alkaline phosphatase, and bilirubin; abnormal urinanalysis showing proteinuria, pyuria, and microscopic haematuria. CSF protein may

Treatment

There remains some controversy about whether antimicrobial treatment of severe leptospirosis should even be initiated since most cases of acute leptospirosis resolve spontaneously.¹⁴⁰ However, most experts would not withhold antimicrobial treatment when clinical findings and epidemiological exposure history suggest leptospirosis.¹⁴⁰ In the case series reported from Hawaii from 1974–1998, no significant difference was seen between use and non—use of antibiotics and duration of illness.¹⁰⁰ In a

Chemoprophylaxis

In a now classic study, a clinical trial comparing doxycycline (200 mg/week) with placebo was done in Panama in 1982 involving 940 US soldiers deployed for jungle training⁹⁸ 22 cases of leptospirosis occurred in the placebo group (attack rate of 4·2%), which was significantly different from the single case in the doxycycline group (attack rate of 0·2%, p<0·001). A randomised clinical trial done on the North Andaman islands of India examined doxycycline prophylaxis against leptospirosis in

Vaccine development

Vaccines to prevent human leptospirosis are available in some countries and large—scale clinical trials have been reported from Cuba,149, 150 Russia,¹⁵¹ and China¹⁵² in non—English language journals. In Cuba, there was not a single reported side—effect in more than 100 000 people vaccinated and protection was reported to be 100%.149, 150 Only a few patients developed MAT antibodies to the serovars in the preparation,149, 150 so that in—vitro tests did not correlate with protective immunity.

Search strategy and selection criteria

We identified relevant English language publications from 1966 onwards through Pubmed searches. Keywords used were “leptospirosis” and “leptospira”. To look for reports of human vaccine clinical trials in all languages we used keywords “vaccine”, “leptospirosis”, and “clinical trials”. We also examined reference lists of major reviews, a reference database compiled by Solomon Faine, and the compendium of references by E Ryu, Chronological references of zoonoses: leptospires and

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Cited by (1808)

Tracking potential Leptospira sources following human cases of leptospirosis: A One Health approach applied to an ecosystem in Brittany, France
2024, One Health
Pathogenic Leptospira can cause leptospirosis: a widespread, potentially fatal bacterial zoonosis whose risk is mediated by the soil and water features, animal host distributions, meaning the local ecosystem. When human cases of leptospirosis occur, it is challenging to track down their source because ecosystem-level epidemiological knowledge on Leptospira is needed. Between 2016 and 2019 in a focal riparian ecosystem, the human population experienced an outbreak and successive cases of leptospirosis attributable to L. kirschneri and L. interrogans. The epidemiological investigation was carried out using the One Health approach, as described in international health guidelines. As a first step in this process, we investigated leptospiral carriage in the main animal hosts found in the region. We sampled 143 nutrias, 17 muskrats, and 10 Norway rats using convenient trapping. DNA was extracted from their kidneys, lungs, and urine and subjected to real-time PCR (RT-PCR) targeting the Leptospira 16S rDNA and lfb1 genes. In the farms along the river's stretch of interest, we sampled serum from 439 cattle and used a microscopic agglutination test to detect the presence of antibodies against Leptospira. Urine samples were concomitantly obtained from 145 cattle and were used in two analyses: RT-PCR targeting the Leptospira 16S rDNA gene and Leptospira culturing. We found th, wt rodents were the most likely source of the L. interrogans behind the human cases. The cattle tested negative for Leptospira DNA but positive for antibodies against the serogroups implicated in the human cases. We failed to identify the potential source of the L. kirschneri responsible for several human cases of leptospirosis. Our results call for further clarification of the Leptospira maintenance community, which may comprise known maintenance hosts, such as rodents, as well as taxa not commonly considered to be maintenance hosts but that can still spread Leptospira. The resulting research network will collaboratively conduct future eco-epidemiological surveys to illuminate the leptospirosis risks faced by humans and animals within ecosystems.
Global proteome of the saprophytic strain Leptospira biflexa and comparative analysis with pathogenic strain Leptospira interrogans uncover new pathogenesis mechanisms
2024, Journal of Proteomics
Leptospira is a genus of bacteria that includes free-living saprophytic species found in water or soil, and pathogenic species, which are the etiologic agents of leptospirosis. Besides all the efforts, there are only a few proteins described as virulence factors in the pathogenic strain L. interrogans. This work aims to perform L. biflexa serovar Patoc1 strain Paris global proteome and to compare with the proteome database of pathogenic L. interrogans serovar Copenhageni strain Fiocruz L1–130. We identified a total of 2327 expressed proteins of L. biflexa by mass spectrometry. Using the Get Homologues software with the global proteome of L. biflexa and L. interrogans, we found orthologous proteins classified into conserved, low conserved, and specific proteins. Comparative bioinformatic analyses were performed to understand the biological functions of the proteins, subcellular localization, the presence of signal peptide, structural domains, and motifs using public softwares. These results lead to the selection of 182 low conserved within the saprophyte, and 176 specific proteins of L. interrogans. It is anticipated that these findings will indicate further studies to uncover virulence factors in the pathogenic strain. This work presents for the first time the global proteome of saprophytic strain L. biflexa serovar Patoc, strain Patoc1.
The comparative analysis established an array of specific proteins in pathogenic strain that will narrow down the identification of immune protective proteins that will help fight leptospirosis.
Fatal leptospirosis in endangered Barbary macaques (Macaca sylvanus) kept in captivity: Assessing the role of sympatric rodents
2024, Veterinary Microbiology
Between December 2020 and January 2021, an outbreak of acute mortality in endangered Barbary macaques (Macaca sylvanus) kept in captivity was detected in a zoo in Spain. The main findings observed in the two fatally affected animals at post-mortem evaluation were jaundice, renal tubular necrosis and interstitial nephritis. Leptospira spp. infection was confirmed by real time PCR (qPCR) in different tissues in both individuals. Analyses of secY gene from a positive individual showed 100% homology with a previously published sequence corresponding to Leptospira interrogans serovar Copenhageni. Free-living sympatric brown rats (Rattus norvegicus) from the affected zoo were also analyzed, and showed a prevalence and seroprevalence of Leptospira spp. of 18.2% (4/22; 95% CI: 2.1–34.3) and 41.9% (26/62; 95% CI: 29.7–54.2), respectively. We detected seropositive sera to five different serovars of Leptospira spp. (Copenhageni, Grippotyphosa, Pomona, Canicola and Hardjo) in the rodent population, with L. Copenhageni being the predominant one. This study describes for first time an outbreak of fatal leptospirosis in captive non-human primates in Europe. Our results show that Barbary macaques, an endangered species, are highly susceptible to Leptospira spp. infection, with sympatric wild rodents being the most likely reservoir animals involved in transmission in this outbreak. Our results suggest that rodent control could be an effective measure for minimizing exposure to Leptospira spp. in zoological collections. Given the potential implications for conservation, animal and public health, non-human primates and rodents should be included in surveillance programs for Leptospira spp. in zoos.
Seroprevalence of Coxiella burnetii, Leptospira interrogans serovar hardjo, and Brucella species and associated reproductive disorders in cattle in southwest Ethiopia
2024, Heliyon
In Ethiopia, Coxiella burnetii, Leptospira Hardjo, and Brucella spp are recognized as the primary factors contributing to cattle reproductive issues. A cross-sectional study was conducted in southwest Ethiopia from October 2020 to October 2021 to assess the risk of reproductive disorders associated with L. Hardjo, Coxiella burnetii, and Brucella spp. Moreover, the study aimed to identify the factors associated with reproductive disorders. Using an indirect ELISA, antibodies against these pathogens were observed in serum samples collected from 461 cattle. We employed multivariable random effect logistic regression analysis to identify potential risk factors associated with reproductive disorders in cattle. The study areas showed a prevalence of 25.16 % (95 % CI: 21.20–29.12) for cattle reproductive disorders. The presence of Leptospira Hardjo (OR = 2.9, 95 % CI: 1.17–4.02) and Coxiella burnetii (OR = 3.0, 1.49–5.94) antibodies was associated to the occurrence of cattle reproductive disorders. Seropositivity to pathogens B. abortus, C. burnetii, and L. Hardjo, along with co-infection of all three, showed association with cattle abortion. The presence of L. Hardjo seropositivity and co-infection with C. burnetii were related to dystocia in cattle. Cattle with retained fetal membranes were associated with co-infection seropositivity to these pathogens. Additionally, B. abortus seropositivity was linked to cases of repeated breeding in cattle. Age, breeding practices, and dog access to cattle showed associations with reproductive disorders, with odds ratios of 2.3 (95 % CI: 2.03–4.69), 2.9 (95 % CI: 1.83–4.82), and 6.5 (95 % CI: 1.04–2.53) respectively. This research indicates that Brucella abortus, Coxiella burnetii, and Leptospira Hardjo, which are responsible for severe zoonotic diseases, have a substantial negative impact on cattle production by causing reproductive disorders. To address the transmission of these diseases, it is essential to implement effective mitigation strategies and enhance public awareness. Additional investigation is necessary to identify and understand the factors contributing to cattle reproductive disorders in the specified area.
Enhancing leptospirosis control with nanosensing technology: A critical analysis
2024, Comparative Immunology, Microbiology and Infectious Diseases
Leptospirosis is a serious health problem in tropical areas; thus, animals shed leptospires in the environment. Humans are accidental hosts infected through exposure to contaminating bacteria in the environment. One health strategy can be applied to protect and eliminate leptospirosis because this cooperates and coordinates activities between doctors, veterinarians, and ecologists. However, conventional methods still have limitations. Therefore, the main challenges of leptospirosis control are the high sensing of detection methods to screen and control the pathogens. Interestingly, nano sensing combined with a leptospirosis detection approach can increase the sensitivity and eliminate some limitations. This article reviews nanomaterial development for an advanced leptospirosis detection method, e.g., latex beads-based agglutination test, magnetic nanoparticles enrichment, and gold-nanoparticles-based immunochromatographic assay. Thus, nanomaterials can be functionalized with biomolecules or sensing molecules utilized in various mechanisms such as biosensors. Over the last decade, many biosensors have been developed for Leptospira spp. pathogen and others. The evolution of biosensors for leptospirosis detection was designed for high efficiency and might be an alternative tool. In addition, the high-sensing fabrications are useful for leptospires screening in very low levels, for example, soil or water from the environment.
Leptospirosis seroprevalence and risk factors among slaughterhouse workers in Burkina Faso
2023, IJID Regions
The objectives of this study were to determine the seroprevalence and risk factors of leptospirosis among slaughterhouse workers in Burkina Faso.
We performed a cross-sectional survey of slaughterhouse workers from Ouagadougou and Bobo Dioulasso between March and April 2021. Blood was collected by venipuncture and serum samples were tested using enzyme-linked immunosorbent assay and microscopic agglutination test. Questionnaires were used to collect information from these workers on sociodemographic characteristics, work activities, knowledge of zoonosis, and risky behaviors.
Of the 172 subjects investigated, 28 (16.28%) were found seropositive for leptospirosis using enzyme-linked immunosorbent assay or microscopic agglutination test. The main Leptospira infecting serogroup were Mini, Autumnalis, Canicola, Copenhageni, L. mayottensis (ND), Icterohaemorrhagiae, Pyrogenes/Tarassovi (cross reaction), Panama, and Ballum. Risk factors according to multivariate analysis, included residence (P = 0.02), working at the bleeding station (P = 0.03), contact with feces and urine (P = 0.04), and the practice of agriculture outside the slaughterhouse (P = 0.05).
These findings indicate that a significant proportion of slaughterhouse workers are being exposed to pathogenic Leptospira. Public-health interventions against leptospirosis will need to target this occupational group. Proper personal protective equipment and information about the disease should be disseminated among slaughterhouses.

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ReviewLeptospirosis: a zoonotic disease of global importance

Summary

Section snippets

Microbiology and taxonomy

Microbiology

Taxonomy

Epidemiology

Pathogenesis

Clinical features

General laboratory tests

Treatment

Chemoprophylaxis

Vaccine development

Search strategy and selection criteria

FEMS Microbiol Lett

Zentralbl Bakteriol Mikrobiol Hyg [A]

Trans R Soc Trop Med Hyg

Lancet

FEMS Microbiol Lett

Exp Toxicol Pathol

Exp Pathol

Am J Ophthalmol

Vet Immunol Immunopathol

Vaccine

FEMS Microbiol Lett

Exp Toxicol Pathol

Leptospirosis

Curr Opin Infect Dis

Epidemic leptospirosis associated with pulmonary haemorrhage—Nicaragua, 1995

J Infect Dis

Pulmonary manifestations of leptospirosis

Rev Infect Dis

Leptospirosis presenting as a haemorrhagic fever in a traveller from Africa

Med J Aust

Leptospirosis presenting as haemorrhagic fever in visitor to Africa

Lancet

Outbreak of leptospirosis among triathlon participants and community residents in Springfield, Illinois, 1998

Clin Infect Dis

Leptospirosis, water sports, and chemoprophylaxis

Clin Infect Dis

Active surveillance and risk factors for leptospirosis in Hawaii

Am J Trop Med Hyg

Sporadic urban leptospirosis

Ann Intern Med

Phylogenetic analysis of the spirochetes

J Bacteriol

Typing leptospira from the perspective of a reference laboratory

Acta Leiden

Deoxyribonucleic acid relatedness between serogroups and serovars in the family Leptospiraceae with proposals for seven new Leptospira species

Int J Syst Bacteriol

Genetic characterization of pathogenic Leptospira species by DNA hybridization

Int J Syst Bacteriol

Further determination of DNA relatedness between serogroups and serovars in the family Leptospiraceae with a proposal for Leptospira alexanderi sp nov and four new Leptospira genomospecies

Int J Syst Bacteriol

Leptospira fainei sp nov, isolated from pigs in Australia

Int J Syst Bacteriol

Leptospira genomics

Electrophoresis

Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing

Nature

Complete genome sequence of Treponema pallidum, the syphilis spirochete

Science

Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.

Nature

The LE1 bacteriophage replicates as a plasmid within Leptospira biflexa: construction of an L biflexa-Escherichia coli shuttle vecto

J Bacteriol

Spirochaetal lipoproteins and pathogenesis

Microbiology

Determination by means of electron microscopy of morphological criteria of value for classification of some spirochetes, in particular treponemes

Acta Pathol Microbiol Scand

Genetics of motility and chemotaxis of a fascinating group of bacteria: The spirochetes

Annu Rev Genet

Bovine leptospirosis: a serological and clinical study

Vet Rec

Leptospira and leptospirosis

Nutrition of Leptospira pomona and growth of 13 other serotypes: fractionation of oleic albumin complex and a medium of bovine albumin and polysorbate 80

Am J Vet Res

Nutrition of Leptospira pomona and growth of 13 other serotypes: a serum-free medium employing oleic albumin complex

Am J Vet Res

Metabolism of leptospires II. The action of 8-azaguanine

Review
Leptospirosis: a zoonotic disease of global importance