Leptospirosis is a public health concern due to its global distribution, its epidemic potential, its presence in domestic animals, small mammals and the natural environment, and its high potential for human mortality, if left untreated.

Its sensitivity to environmental conditions suggests that climate change and population drift from rural to peri-urban and urban areas impact the nature of the disease and affects the magnitude and severity of outbreaks.

To date there is a lack of clarity surrounding the disease, its global burden, the dynamic relationship between animals, humans and the environment and its economic impact. With so many unanswered questions, developing control strategies, particularly in epidemic and outbreak situations, becomes extremely difficult, yet exceedingly crucial.

Distribution of leptospirosis 

Leptospirosis is a multifactorial neglected tropical infectious disease (NTD) with uneven global distribution (Goarant et al., 2016; Costa et al., 2015). Its existence results from factors such as climate, environment, and presence of reservoir hosts. It is caused by a spirochete bacteria of the genus Leptospira, found in the urine of rats and other animals (Levett, 2001). 

Endemic regions in developing countries have a high leptospirosis incidence, as in countries in Asia, Latin America, and Africa (Goarant et al., 2016). This is estimated to be responsible for around 1.03 million cases and 58,900 deaths yearly (Costa et al., 2015). Cases of the disease and high mortality rates may be more frequent in contexts with poor sanitation and housing located in areas known as the bottom of valleys (Hagan et al., 2016; Costa et al., 2015; Reis et al., 2008). In these places, the prevalence of Leptospira in rats is the highest, >80%, as is the case in Brazil, India, and the Philippines (Boey et al., 2019). Efforts are essential to ensure permanent monitoring of exposure areas and cases of the disease in sites with those characteristics, as well as carrying out frequent actions to control and prevent leptospirosis.


Leptospira Species

To date, up to 69 species of Leptospira have been validly described, with more than 40 of them being described in the last 10 years. They have been isolated from humans, animals, and environmental sources (Vincent et al., 2019; Fernandes et al., 2022; Korba et al., 2021). Leptospira species are divided into two phylogenetic groups according to their level of pathogenicity and are known as pathogenic (with two sub-clades P1 and P2, the latter corresponding to species formerly known as “intermediates”), and saprophytes (also with 2 subclades S1 and S2) (Vincent et al., 2019; Fouts et al., 2016).

The survival and adaptation of Leptospira in the environment are specific to each species (Bierque et al., 2020). Most studies carried out to date have identified the presence of Leptospira more frequently in soils (Thibeaux et al., 2018). This strengthens the existing hypothesis about the dispersal of Leptospira with resuspension particles in the soil during heavy rainfall (Thibeaux et al., 2024). Factors such as pH, salinity, temperature, and humidity influence the survival of Leptospira in the soil (Bierque et al., 2020). Furthermore, high soil humidity, the presence of nutrients such as metals and nitrate, and interactions with other microorganisms were identified as important factors for maintaining the survival of Leptospira in this type of environment (Bierque et al., 2020; Miller et al., 2021).

In water, studies have identified that Leptospira spp can continue to be virulent for weeks (André-Fontaine et al., 2015). Both saprophytic and pathogenic Leptospira species were shown to survive in waters with low or high pH (<6 to >8) and low temperature (4°C to 37°C) (Chaiwattanarungruengpaisan et al., 2020; Bierque et al., 2020).

Pathogenic Species

Leptospira species in the P1 sub-clade are known as the leading cause of leptospirosis and can cause severe forms of the disease such as Weil's disease and hemorrhagic syndrome in humans.

Some examples of pathogenic leptospires:


Recent studies have evidenced that some species in the Pathogenic P1 subclade have a low virulence (if any) in animal models, leading to distinguishing “Low-virulent” pathogenic species (Thibeaux et al., 2018). These include Leptospira kmetyi and Leptospira gomenensis among others.

Leptospira species in the P2 sub-clade were formerly described as “intermediates”. These species are considered to have moderate virulence and cannot reproduce disease in animal models, but several of them have been isolated from mammals, including humans. The first species in this group was Leptospira fainei (Perolat et al., 1998). Another well-described species in this P2 category is Leptospira licerasiae (Fouts et al. 2016).

Saprophytes

These species were isolated from the soil and water environment and do not cause leptospirosis in humans or other animals (Casanovas-Massana et al., 2018; Andre-Fontaine et al., 2015). Based on the phylogeny, they are classified into two sub-clades named S1 and S2. The S1 subclade includes the first Leptospira species described in 1914; Leptospira biflexa, (Wolbach and Binger, 1914) and Leptospira meyeri (Yasuda et al., 1987). The S2 subclade includes species described almost one century later such as Leptospira idonii (Saito et al., 2013) and others.

Life cycle and Transmission

Leptospires have a life cycle linked to the transmission of leptospirosis. Below are more details about the phases of the Leptospira life cycle.

Reservoir host: pathogenic leptospires have one or more preferred reservoir hosts, infected animals carrying the bacteria (Adler, 2009; Levett, 2001). These hosts can include mammals such as rodents, dogs, cattle, and pigs. Humans are known as accidental and terminal hosts. The main reservoir is the synanthropic rodents of the species Rattus norvegicus (rat or sewer rat), Rattus rattus (roof rat or black rat), and Mus musculus (mouse or catite) (Brasil, 2010). Reservoir hosts harbor the bacteria in their kidneys and can eliminate it in the urine. The intraspecific Leptospira transmission process in rats is not entirely known to us. However, a study using mathematical modeling and eco-epidemiology of urban leptospirosis suggests transmission through breastfeeding (Oliveira et al., 2016) and greater chances of transporting L. interrogans by bite wounds of rats (Minter et al., 2019).

Eliminating urine into the environment: reservoir hosts eliminate leptospires (bacteria) in urine, contaminating the surrounding environment, including fresh water, moist soil, and mud (Ko et al., 2009).


Survival in the environment: leptospires can survive, especially in aquatic environments, for weeks to months, depending on environmental conditions. Depending on specific factors, they can remain infectious during this period (Ko et al., 2009).


Human or animal exposure: exposure to Leptospira occurs through direct skin contact with contaminated water and soil or indirect contact with reservoir animals. Although less frequent, one of the forms of animal transmission can occur through rat bites (Minter et al., 2019).


Infection: when penetrating the human body through injured skin or mucous membranes, the bacteria spreads through the blood and affects tissues and organs, such as kidneys, liver, and lungs, and, depending on the severity, can lead to death. In humans, the incubation period can last approximately 7 to 14 days once the infection has occurred (Levett, 2001).


Disease (recovery or death): Leptospira can cause leptospirosis when infecting the host. Clinical manifestations can be mild or nonspecific, which corresponds to approximately 90%-95% of cases (Haake et al., 2015; Levett, 2001), or severe (Weil's disease and hemorrhagic syndrome) which affects approximately 10 % to 15% of cases, with a fatality rate of 10% to 50%, depending on the clinical manifestation of the disease (Goarant et al., 2016). Although uncommon, there is recent evidence in China of a case of a patient, a rural farmer, with intracranial arterial disease caused by leptospirosis (Zhu et al., 2022).


There are still no predictive models that determine which patients with leptospirosis may develop a severe case of the disease. Therefore, there is a need for studies that can focus on identifying biomarkers of this severity to contribute to the prevention of these cases of the disease (Rajapakse et al., 2022).

Diagnosis

Early diagnosis of leptospirosis is essential for more effective treatment of the disease. There are different methods currently available. Furthermore, differential diagnosis is essential to rule out diseases with signs and symptoms similar to leptospirosis, such as dengue fever and malaria (Brasil, 2010; Ko et al., 2009).

Clinical examination and gathering information about the patient's history of recent exposure to areas with risk factors for the disease, such as contact with soil, water, and infected animals, is also essential for subsequent confirmation by specific methods (Brasil, 2010).

Know about the diagnostic methods used to diagnose leptospirosis (Haake et al., 2015; Brasil, 2010; Levett, 2001):








In addition to the conventional methods presented, Peripheral blood Metagenomic Next-generation Sequencing (mNGS) has been used as a complementary approach in the differential diagnosis of Leptospira. There are reports that this method has contributed to the accurate detection of Leptospira DNA in the early stages of infection (Dai et al., 2023).


Prevention

Preventing leptospirosis helps reduce the risk of contracting the disease, especially in its severe stages. It involves measures related to the source of infection, transmission routes, people susceptible to the disease, control of reservoirs, protection of exposed workers, care for the hygienic and sanitary conditions of the population, and the use of corrective measures in the environment. Common risk factors for leptospirosis infection include working outdoors in areas with water, recreational activities in water, certain types of agriculture, and interactions with rodents (Bierque et al., 2020; Ko et al., 2009).

Here are some recommended measures to prevent leptospirosis (Haake et al, 2015; Faine et al., 1999):

Contact with contaminated water and soil:

Avoid swimming in water that may be contaminated, especially in areas with a history of leptospirosis cases.

Avoid direct unprotected contact with flood water, mud, or damp soil, as these environments may contain leptospires.

Wear suitable high-protection footwear when walking in potentially contaminated areas.

Use personal protective clothing (boots and gloves) and avoid contact with animals that are hosts of the disease, such as rodents.

Good hygiene practices: wash your hands with soap and water after contact with animals, soil, or water suspected of contamination. Avoid contact with mouth, nose, and eyes.

Animal vaccination: vaccinate pets (dogs and cats) and cattle and horses against leptospirosis.

Human vaccination: there are reports on the immunization of individuals in high-risk occupations and places of floods and epidemics in countries such as Japan, China, Cuba, and Paris (Adler et al., 2009).

Rodent and cat control: keep the environment free of food or other attractant reservoir hosts, such as rodents. Construction of housing that makes it difficult for rodents to enter. Reducing stray cat populations may also help lessen the burden of leptospirosis, as they can become reservoirs if they hunt infected rodents.

Health education: awareness and knowledge about the risks of leptospirosis and the situations that can contribute to exposure to the disease's risk factors.

Protect yourself with PPE: working in areas that pose risks, such as agriculture, sanitation, and animal husbandry, requires appropriate personal protective equipment.

Chemoprophylaxis: used in cases where exposure was unavoidable.

Measures aimed at preventing and mitigating floods can also contribute to reducing the incidence of leptospirosis.