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REVIEW ARTICLES

Received: July 8^th 2015

Accepted: September 10^th 2015

Current review of the epidemiology of leptospirosis

Marco Torres-Castro,^a Silvia Hernández-Betancourt,^b Piedad Agudelo-Flórez,^c Esteban Arroyave-Sierra,^c Jorge Zavala-Castro,^a Fernando I. Puerto^a

^aLaboratorio de Enfermedades Emergentes y Reemergentes, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, México

^bDepartamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Mérida, Yucatán, México

^cFacultad de Medicina, Universidad CES, Medellín, Antioquia, Colombia.

Communication with: Marco Torres-Castro

Telephones: (999) 924 5809; 924 5755

Email: antonio.torres@correo.uady.mx

Spirochete bacteria Leptospira spp. is the causative agent of leptospirosis, antropozoonotic endemic disease in many parts of the world, mainly in underdeveloped countries with high levels of poverty. Its incidence and prevalence rates are higher and important in human populations living in tropical and subtropical climates. Leptospira spp. , is capable of infecting more than 160 species of domestic and wild mammals, including human beings, causing various and nonspecific clinical manifestations that make the diagnosis of the disease rarely accurate. In Mexico, the first reports of leptospirosis dating from 1920 and is now considered a matter of public and animal health, mainly for the economic losses it generates. The aim of this paper is to present a review in Spanish, containing the most important aspects in the epidemiology of leptospirosis, to serve as a starting point for students and researchers who are interested about this endemic disease in Mexico.

Keywords: Leptospira; Leptospirosis; Epidemiology; Review

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The bacterium Leptospira spp. is the causative agent of leptospirosis, an anthropozoonosis with cases around the world, occurring most frequently in tropical or subtropical climates. Besides humans, it affects different domestic and wild mammals. Synanthropic rodents are the main reservoirs, because they do not develop clinical manifestations and host various pathogenic serovars that reproduce in their renal tubules, encouraged by the alkaline pH of their urine, the main route of transmission to humans and susceptible animals.¹

Leptospirosis is classified as an emerging disease due to the more than 500,000 annual cases in humans with a mortality rate exceeding 10%.² The World Health Organization (WHO) classifies it as a neglected tropical disease, estimating an incidence of 5.1 cases/100,000 people in endemic areas and 14 cases/100,000 people in epidemics.³

Several studies conclude that the increase in the prevalence and incidence of leptospirosis is related to the poor living, occupational, and hygiene conditions of human populations, changing climactic factors, and the presence of reservoirs and/or hosts.⁴ In Mexico, leptospirosis is significant because of its negative impact on public and animal health, especially in economic terms.⁵

Etiologic agent, species, and serovars

Leptospirosis is caused by spirochete bacteria belonging to the order Spirochaetales, the family Leptospiraceae, genus Leptospira.⁶ In past decades the classification of this genus included two groups differentiated by their antigenic determinants, biochemical behavior, infectivity, growth in culture, nutritional needs, and other phenotypic properties: Leptospira interrogans sensu lato (with over 250 serovars) and Leptospira biflexa sensu lato (with 60 serovars), the first pathogen and the second non-pathogen, with bacteria isolated in the environment.⁷

Currently, the classification of the genus Leptospira comprises 21 species (characterized by the phylogenetic analysis of gene 16S rRNA and its pathogenicity) divided into three types:

1. Seven saprophytic species: L. biflexa, L. wolbachii, L. meyeri, L. vanthielii, L. terpstrae, L. yanagawae and L. idonii;
2. Nine pathogenic species: L. interrogans, L. kirschneri, L. borgpetersenii, L. santarosai, L. noguchii, L. weilii, L. alexanderi, L. kmetyi and L. alstoni;
3. Five intermediate species: L. inadai, L. broomii, L. fainei, L. wolffii and L. licerasiae.

Also, based on their homology and antigenic structure, more than 320 serovars have been identified, mainly belonging to pathogenic species.⁸ 

Pathogenic serovars have the ability to colonize the organs of affected individuals, mainly kidneys, liver and lungs. In addition, they subsist and remain infective in various media such as wet soil, rivers, lakes, stagnant water, marshes, and mud. They have also been isolated in organ meats, milk, and cold cuts.⁹ In contrast, they are sensitive to acidity, drying, freezing, variations in pH (deactivating in pH less than six or more than eight), and pasteurization.^10,11 Acidic urine, antiseptics, and disinfectants do not allow their survival, and they are sensitive to several antibiotics, including penicillin.⁹

Morphological, cellular, and molecular characteristics

Leptospires are strict aerobic bacteria with oxidase enzymes, catalase, and peroxidase.¹⁰ Their shape is generally helical, they are rolled clockwise, and have a slight curvature at one or both ends, characteristic of pathogenic Leptospira. Their mobility, which is caused by axial fibrils inserted into a protuberance at the end of the cytoplasmic body, varies depending on where they are cultivated. Its diameter is about 0.25 μm and its length is 6-25 μm. Display in histological sections is done with silver impregnation or by immunoperoxidase or immunofluorescence. These bacteria grow slowly in liquid or solid media supplemented with fatty acids, vitamins B1 and B12, and nitrogen sources. Fletcher, Kortoff, Schüffner, and EMJH media are the most used for cultivation.¹²

Leptospira spp. has developed common surface structures in Gram-positive (+) and Gram-negative (-) bacteria: the double membrane and the presence of lipopolysaccharides (LPS) are characteristic of Gram-negative bacteria, while the association between the cytoplasmic membrane and the murein of the cell wall is part of Gram-positive bacteria.⁷ However, due to the formation of its cell wall and the structure of the LPS (major antigens), it is considered Gram-negative.⁹

Molecular tools have been able to decode the complete genome of different species of Leptospira: it consists of two circular chromosomes and is longer compared to other spirochetes like Treponema spp. and Borrelia spp.^1,8 Each chromosome has a guanine and cytosine content between 35-41% and a size of 3.9-4.6 Mb.^6,8

Epidemiology

Leptospira spp. is able to infect humans and more than 160 species of domestic and wild mammals,^7,12 although its circulation has also been reported in reptiles, birds, and amphibians.¹³  

Human and/or animal leptospirosis is present on every continent (except Antarctica) and island, so it is presumably the most globally distributed zoonosis.¹² Its incidence is greater in rural populations in tropical and subtropical climates and flood areas, presenting peaks from June to November.⁴ Moreover, a minimal number of cases are diagnosed in arid or desert climates and in developed nations, usually in people who have traveled to endemic countries.⁸ Some studies agree that leptospirosis represents 20-40% of the febrile disease of unknown etiology in humans. Also in endemic countries about 10% of hospital admissions may be attributable to this infection.¹⁴

Leptospirosis in Mexico

The first report of this disease in Mexico was in Merida, Yucatan, in the year of 1920, during an alleged outbreak of yellow fever.¹⁵ In subsequent years, serosurveys appeared identifying seropositive patients in Campeche, Tabasco, Veracruz, Tamaulipas, Colima, and Mexico City (DF).^16-18 However, interest in delimiting the true extent of the disease in the country began in the nineties: Gavaldón et al.¹⁹ conducted a study on 206 blood donors against seven serovars of L. interrogans, finding a 7% seropositivity. Also, from 1990 to 1995, researchers at the Instituto Nacional de Diagnóstico y Referencia Epidemiológicas (INDRE) at the Secretaría de Salud (SSA), examined 446 samples from patients with probable diagnosis of leptospirosis, finding gammaglobulins against serogroups of L. interrogans in 46% of cases.¹⁰

Historically, the prevalence and incidence of human leptospirosis in Mexico have been variable due to the use of different laboratories and tests, as well as discrepancies in the values ​​and criteria for the interpretation of results.²⁰ In 1998, INDRE collected 119 positive cases distributed mainly in Mexico City, Hidalgo, and Guerrero.²¹ In the period 2003-2008, the national infection rate was 0.6-2.1 cases/10,000.²² In 2010, the incidence also varied from 0.5-10 cases/10,000 inhabitants, with 483 new cases accumulating in Tabasco, Baja California Sur, Colima, and Campeche. In 2012, SSA through the Dirección General de Epidemiología (DGE) confirmed 481 positive cases of human leptospirosis, the State of Tabasco being the most affected with 255 patients.²³

Natural reservoirs

Different mammals are involved in the transmission cycle of leptospirosis; however, the most important are the natural reservoirs, small wild or synanthropic mammals belonging to the order of rodents,⁶ which maintain a commensal relationship with spirochetes (transferring it to their young in utero or in the neonatal period),⁷ and which ensure the circulation of pathogenic serovars in certain geographical areas without needing accidental hosts involved.¹³ The synanthropic genera Rattus and Mus have been identified as the major disseminators of Leptospira spp. ,²⁴ due to their remarkable ability to shed bacteria in their urine. Quantifications made experimentally in the urine of infected rats have revealed concentrations of 100 million bacteria/ml.²⁵ Another factor that extends or limits the participation of reservoirs in the transmission cycle is the average life expectancy, since the greater longevity, the greater the opportunity to disseminate viable spirochetes.²⁶

The serovars circulating in humans or animals rely heavily on the variety of reservoirs present, which is confirmed by the fact that the highest infection rates with different serovars are reported in areas with a high number of rodents. Similarly, the larger the reservoir population, the more common is inter- and intra-species transmission.^1,26

Accidental hosts

Hosts are animals that are infected by chance with leptospira for which they do not represent a natural reservoir, but are able to excrete spirochetes in their urine for months or years, so they are also known as temporary carriers.¹² Infection in them is acquired mainly through indirect contact from environmental contamination with urine from positive reservoirs. Potentially any vertebrate animal can be considered susceptible to infection and become an accidental host.²⁷ 

Carrier animals are often domestic species (Table I). Meanwhile, wildlife plays a dual role in the transmission cycle of Leptospira spp. , as they can be considered a reservoir of wild serovars and a source of interspecies infection, or even a susceptible host by contact with domestic serovars.²⁸

The seroconversion or infection rates of accidental hosts vary from 2-46% depending on the serovar or species involved.²⁹ Similarly, based on the conditions of the region where the study is done, the serovars identified may change.^5,11,27

Environmental and anthropogenic factors

Leptospirosis’ cycle of infection is strongly influenced by the environmental and anthropogenic factors present, the current population of reservoirs and hosts, and the diversity of serovars prevalent; so the interaction between these factors outlines the creation of outbreaks and epidemics.¹⁴

The most important environmental factors in the transmission dynamics of Leptospira spp. are: temperature, humidity, and rainfall, which act in synergy with anthropogenic variables such as population density, type of housing, drinking water sanitation programs, waste management, land use, deforestation, and environmental degradation.³⁰ This synergy results in variation in rates of prevalence and incidence of leptospirosis among nations, and even between regions within countries- which is the particular situation in Latin America, where leptospirosis is the most significant zoonotic disease.⁴ Another anthropogenic factor contributing to the dynamics of infection is the introduction of carrier animals other than serovars endemic into a region.²⁶

Research shows that the key to understanding the epidemiology of leptospirosis is in climatic elements, particularly rainfall.^6,30 The Intergovernmental Panel on Climate Change (IPCC) warns that the increase in rainfall in the tropics has raised the risk of transmission of Leptospira spp. through contamination of water sources consumed by positive rodent populations. Evidence of this, are epidemics and outbreaks in Guyana, India, Kenya, Laos, New Caledonia, and Thailand, which also highlights the connection between the disease, climatic elements, poverty, and poor health.³

Transmission in humans

The transmission cycle of leptospirosis begins with the presence of reservoirs and hosts carrying bacteria in their renal tubules, which are excreted in urine (leptospiruria) contaminating water, soil, plants, pastures, food, etc., where they remain viable until they infect new susceptible hosts.^29,31,32 Leptospiruria in reservoirs is more intense, constant, and prolonged than in the host, which is low-intensity, intermittent, and brief.³³

Infection in humans usually occurs by accidental exposure to urine containing spirochetes or by contact with some contaminated medium.³⁰ The other documented pathways are: contact with secretions, tissues and/or blood of positive individuals,¹ inhaling aerosols,¹¹ and ingesting unhygienic food.³² The infection is also transmitted by the bite of positive animals.⁷

Indirect transmission between humans has occasionally been seen because the acid pH of human urine limits the survival of spirochetes.²⁰ In this context, there are studies that prove that human beings are responsible for the circulation of Leptospira spp. in particular ecosystems, due to the excretion of spirochetes over weeks or months.³⁴ A case of transmission via direct sexual contact³² has been documented, and another probable case via ingestion of breast milk.³⁵

Leptospirosis in humans can also be acquired through recreational or occupational activities, or exposure in laboratories. Therefore, work is a major risk factor because it usually occurs in workers in contact with animals, their products and/or byproducts,⁴ or those working in wet soil and/or semi-flooded areas.³¹ In Europe, the infection is associated with inappropriate living with pets, especially dogs, cattle, and swine.³ Other factors that carry a higher risk of transmission are: improper disposal of garbage and sewage, contact with irrigation or waste water,³⁴ walking barefoot on unpaved and/or flooded streets,²⁰ and sharing housing with reservoirs or hosts.²⁴

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