Comprehensive Epidemiological Insights on Leptospirosis Global Health Effects and the Risk Factors for Prevention and Control

1.1 Leptospirosis a global zoonotic health effects

A zoonotic bacterial disease, leptospirosis, affects populations with few resources the most, while it can arise in a variety of epidemiological contexts [40, 41]. Because a wide variety of mammals can retain and excrete the spirochete agent from their renal tubules, the disease has a wide geographic spread [41, 42]. Leptospirosis is predicted to be responsible for more than half a million deaths, with over a million cases reported annually [13, 14]. Costa et al.’s [41] more recent estimates indicate that leptospirosis is “among the leading zoonotic causes of morbidity and mortality”. However, according to estimates from the World Health Organization (WHO), there are five endemic cases of human leptospirosis for every 100,000 persons and 14 epidemic cases each year worldwide [43]. These disparate figures demonstrate how challenging it is to quantify the current leptospirosis burden worldwide. This is due to the lack of diagnostic facility availability, low reliability of surveillance systems and little knowledge of the disease, and these numbers are thought to be significantly underestimated [15]. Furthermore, the diagnostic tests that are currently accessible are not ideal; the best tests miss nearly 40% of patients [15]. However, due to low clinical presentation specificity and close similarities to other diseases, only one in ten infections are believed to be precisely identified [44]. Case fatality rates for leptospirosis can vary from less than 5% to more than 30%, depending on the clinical presentation and course of treatment. Young adults between the ages of 20 and 49 are more likely to contract an infection with Leptospira [41]. Males are estimated to bear 80% of the global leptospirosis burden [45]. Leptospirosis, which causes high death rates in both people and sensitive animal species, has become a major infectious zoonotic disease in the last 10 years, especially in endemic tropical locations with significant rainfall [14, 46]. The high death rate in leptospirosis is still high, attributed to a variety of poorly understood factors that may include the innate pathogenicity of some Leptospira strains or host immune-pathological responses that are genetically determined [47]. These factors also contribute to delays in diagnosis brought on by a lack of infrastructure and sufficient clinical suspicion.

In many areas where transmission is endemic, the primary burden attributed to leptospirosis life-threatening manifestations has occurred as a significant cause of acute renal injury related to Weil’s disease [41] and pulmonary hemorrhage syndrome [48]. Moreover, leptospirosis is becoming more widely acknowledged as a significant contributor to undifferentiated fever [49, 50]. Most cases of leptospirosis are misinterpreted as dengue [50, 51], or other acute febrile illness-related conditions. This has been linked to the lack of an appropriate diagnostic test [52], which leads to underreporting of cases [53, 54] and deaths [51]. The absence of trustworthy leptospirosis burden approximations has hindered attempts to build the case for investment in order to remove important obstacles, such as better diagnostics, and find efficient preventive and control strategies. Risk groups for leptospirosis include those working in sewage and abattoirs, military personnel, and people who participate in water sports and recreation, as well as those exposed to animal reservoirs or contaminated surroundings [41]. Furthermore, because of the effects of globalization and climate change, leptospirosis has become a health concern in previously unexplored areas [55, 56]. Epidemics are now known to be glowed by disasters and harsh weather [40, 41].

1.2 Socioeconomic impact of leptospirosis

In addition to the health consequences that leptospirosis might have, the relatives of the victims and society at large may also be negatively impacted financially and socially. The condition has both direct and indirect financial consequences, such as the expense of treating the acute sickness, managing long-term medical issues, causing income loss due to the illness, and maybe having an impact on one’s eventual ability to earn a living [57]. During epidemics, thousands of individuals may possibly become infected in a short period of time, placing a great deal of strain on healthcare services. The health system will be further taxed by the implementation of public health initiatives for surveillance, control, and prevention. Moreover, leptospirosis poses a risk to cattle, exacerbating financial losses. A lot of leptospirosis epidemics happen in urban slums, which are home to some of the most vulnerable and impoverished individuals on the planet. These areas also tend to have low socioeconomic resilience, insufficient access to healthcare, and few public health resources. The combination of these factors will make leptospirosis the most harmful disease to communities in terms of both health and socioeconomics, and as emerging nations become more urbanized, this situation is expected to get worse.

1.3 Leptospirosis epidemiological insights

Leptospirosis is a zoonotic, important bacterial disease that is associated with low levels of sanitation and poverty in both rural and urban regions. Although transmission happens in both developed and developing nations, the occurrence of human infection is greater in tropical regions than in temperate ones. Since the disease is not well-known and tests are not readily available or performed quickly enough, incidence rates are underestimated. In endemic areas, infection that is asymptomatic or subclinical is frequent [58]. It is also interconnected with the locations where livestock is raised, as close contact with animals may facilitate the transmission of leptospirosis. Veterinary professionals, hunters, caregivers of wild animals, farmers, and agricultural workers who come into contact with infected animals are among the people who are affected by this occupational risk disease [59]. Leptospira strains associated with human cases are influenced by the animal reservoir in each particular area. Numerous mammals, such as domestic animals, can preserve and disperse a variety of Leptospira serovars in rural areas [60, 61].

Due to the fact that numerous species can act as reservoirs for illness and are found in tropical, subtropical, and temperate regions, leptospirosis has a complicated epidemiology [62]. Both genders and urban and rural environments report cases of the disease, with young adult males being the most affected [44, 63, 64]. Additionally, it is a significant occupational zoonosis that affects workers in the agricultural, sewage, mining, slaughterhouse, butcher, dairy, veterinary, and animal handling industries, as well as construction, kennel, military, and fishing industries [63, 64, 65]. Teams that work in occupationally exposed environments consider communities living in urban slums with inadequate sanitation to be extremely vulnerable and represent a substantial risk to occupationally exposed personnel [66, 67, 68, 69].

Leptospirosis was mostly a work-related illness in temperate, wealthy nations, linked to exposure to animals or freshwater. It is becoming more widely acknowledged that this environmental illness is linked to leisure pursuits including tramping, rafting, and other outdoor sports [60, 70]. There is evidence that the countries visited pose harm to the environment, and the number of individuals with leptospirosis cases returning from tropical vacations is rising [34, 71]. Leptospirosis is known to occur in both temperate and tropical climates. Research has revealed that the highest frequency of the illness transpired during the rainy seasons in tropical areas and late summer to early fall in temperate countries; nevertheless, the majority of the outbreaks were preceded by times of excessive rainfall where favorable conditions allow for its spread [44, 72, 73]. This is due to warm and moist weather which favors Leptospira existence, and incidences in tropical areas are almost ten times greater than those in temperate areas.

Both global warming and changes in rainfall patterns have the potential to raise the disease burden. For instance, it is a seasonal sickness that is most likely caused by climate change environment (soil or water) contamination in particular as a result of prolonged exposure to an abundance of rodent populations [74, 75, 76, 77]. In areas of moderate climate, work-related and entertaining activities (e.g. contact with polluted water or soil, contact with cattle infected with leptospirosis) are more probable to be linked with leptospirosis [77, 78]. Thus, the population biology, behaviour, or community ecology of spirochetes and their hosts are altered by environmental factors, which have a significant impact on leptospirosis transmission.

1.4 Aetiology of leptospirosis

Leptospira are tiny, helicoidal bacteria with a diameter of 0.1–0.2 μm and a length of 6–20 μm. Two periplasmic flagella are located at each pole of these hooked-ended, gram-negative spirochete bacteria. In addition to aiding in the bacterium’s survival within the host and during infection, flagella allow the bacteria to travel swiftly in viscous environments such as blood, interstitial fluid, and connective tissues [17]. Lipo-polysaccharides, proteins, lipoproteins, and lipids make up the outer membrane, while lipoproteins and transport proteins are in the double-layer inner membrane, which is tightly linked to the peptidoglycan layer [79]. It is believed that having periplasmic flagella and a corkscrew-shaped structure helps Leptospira survive over the long term in both their host and the environment [80]. Leptospira were categorized formerly based on their antigenic patterns, which were grouped into over 25 serogroups that combined serovars that were antigenically linked [58, 81], but, in more recent times, a molecular taxonomy has been reported that uses DNA relatedness to split the Leptospira genus into many species [82]. Leptospira is classified as pathogen, intermediate, or saprophyte strain. Saprophytes are normal inhabitants of many types of wet, humid, and freshwater environments. Pathogen strains can be found in nature in the renal tubules of animals and are notable for their extreme sensitivity to UV radiation, chlorine, and detergents [60, 83]. It is also believed that they are vulnerable to low temperatures and acidic environments.

Almost all mammal species are susceptible to Leptospira infection, which can result in leptospirosis. Intermediates strains can infect mammals, but they often have a lesser virulence and only cause minor illnesses. Pathogenic strains can endure extended periods of time in the environment, but their capacity to multiply outside of their live host is limited. As a response to the prolonged lack of a suitable host species, they instead occasionally display binary fission or, in other situations, group together to form a biofilm [84]. For survival, both saprophyt and pathogen Leptospira need the same kinds of nutrients and temperatures. Saprophyte strains are sometimes discovered in humans and other animals, but they usually live their whole lives in soil and water. In order to finish their life cycles, pathogenic organisms need a live object. However, leptospires’ ability to survive and thrive is mostly dependent on the temperature, pH, and moisture content of their surroundings, in addition to the vital nutrients they need to grow [85, 86]. Leptospira are assumed to be persistent and have an extended lifespan in the environment because of their ability to build biofilms with other bacteria [86].

The majority of settlements use natural water sources like rivers, streams, or subterranean aquifers to gather water, which is then stored in reservoirs for extended periods of time. It is reported worldwide as a threat to epidemics in developing nations during and after the rainy season. People in metropolitan areas are susceptible to leptospirosis when roadways flood after heavy rainfall [87, 88]. There is a significant risk of infection for farmers in rural areas who labour in rice fields [89].

1.5 Leptospirosis infection cycle and transmission

The possibility of contracting leptospirosis is via contact with contaminated environment, infected wild animals, and rodents [60, 61, 68]. Natural reservoirs for Leptospira, such as herbivores and other animals, may develop into symptomless carriers following an infection. As a result, they serve as a significant foundation for Leptospira in the environment through bacteria emissions in urine. Renal carrier state is thought to be the primary mechanism that allows leptospirosis to sustain itself in the environment [90]. The primary carriers of Leptospira are rodents, who can contaminate the environment by releasing the germs through their urine [17]. Many wild and domestic animals, such as bovine, swine, canines, and horses, can serve as reservoirs and contribute to the spread of leptospirosis, but the brown rat has been shown to be the most vital source of human infection [24]. Humans can get sick from direct contact with infected animals and Leptospira contaminated soil and water. Once ingested, the germs penetrate and enter the bloodstream and go to the organs, where they cause pathological harm.

In the past, leptospirosis was mostly thought to be an occupational illness linked to occupations including mining, sewage cleaning, raising and killing livestock, veterinary care, and military operations. With the introduction of preventive measures, the relative significance of certain occupational risks has dropped. Human infection occurs when a person comes into contact with a carrier mammal’s contaminated urine, either directly or through polluted surfaces, water, or soil [91]. Leptospirosis is primarily spread by damaged skin or mucosa when contaminated water, soil, or urine comes into contact with it [92]. Leptospira has never been shown to represent significant epidemiological sources of transmission, despite the fact that humans can excrete them into their urine for weeks, or, in rare cases, months, or longer than a year [24, 60]. In addition, the occurrence of different Leptospira serovars within a human population is influenced by the existence of reservoir animals and the serovars they carry, as well as by local environmental conditions, occupation, agronomical practices, and agricultural methods. People who live in urban areas that are characterized by high population density, poor housing quality, and inadequate cleanliness are more likely to be exposed to rats and consequently contract leptospirosis. In industrialized countries, occupational exposure, visits to endemic regions, leisure activities, and the introduction of both domestic and wild animals are the main causes of infection [24]. For example, a sero-prevalence study conducted by Schoonman and colleagues [93] revealed that, among livestock farmers, veterinary/meat inspectors, and abattoir workers, the prevalence of Leptospira spp. infection was 19.4, 18.1, and 17.1%, respectively. Additionally, subjects who reported milking cows had a significantly higher likelihood of testing positive for the infection [47].

1.6 Pathogenesis and clinical sign

Despite decades of study on leptospirosis, understanding mechanisms of leptospirosis pathogenesis is limited [94]. For example, the cause of the severity or mildness of an infection, whether caused by the pathogen directly or by host immune responses that are genetically defined, is yet unclear [95, 96]. However, the emergence of genetic manipulation instruments and the release of genome sequences from saprophytic and pathogenic Leptospira have recently provided new information about the biology and pathophysiology of this significant agent [97]. Leptospira’s motility and capacity to float through viscous liquids are two virulence mechanisms [98]. The preliminary contagion and the spread of organisms from the site of entrance to end-organ damage locations, including the lung, liver, kidney, eye, and brain, are likely critical processes involving motility. Among the Leptospira genome sequence, there are 4768 predicted genes, at least 50 of which are related to motility [99]. After entering a new host, Leptospira reach the kidneys through the hematogenous route, passing glomeruli or peritubular capillaries. They overrun the brush boundary of the proximal tubule, which is where urine is excreted, when they penetrate the renal tubular lumen [24]. Pathogenic Leptospira can inflict local or systemic harm if it enters the bloodstream. Variations in severity are related to patient age, health state, inoculum size, and serovars [17].

Leptospira incubation lasts approximately 10 days, and the illness manifests 5–14 days following the bacteria’s introduction [100]. A wide range of events may be involved in the acute and chronic infection processes of humans and reservoir hosts, according to the widely varying clinical presentations of Leptospira infection [101]. Leptospira spread quickly and multiplied in the bloodstream during the early phase (3–7 days), after which they went to the kidney, liver, spleen, and other organs [17]. Pathogenic Leptospira infection in hosts results in a wide range of clinical symptoms, including subclinical infection, undifferentiated febrile illness, jaundice, renal failure, and possibly fatal pulmonary hemorrhage [24]. On the other hand, conjunctival suffusion is thought to be a distinctive clinical feature of the early stages of leptospirosis [17]. The proximal renal tubules of carrier animals continue to be colonized, which sustains leptospirosis. An animal that is afflicted may not show any symptoms and may secrete infectious organisms in its urine for the whole of its life [102, 103].

The clinical course of leptospirosis can be split into two phases: the acute phase, marked by flu-like symptoms that are milder, and the chronic phase, which has more severe clinical indications, including renal failure and pulmonary diffuse hemorrhage [100, 104]. In certain instances, the infection may not cause any symptoms. The majority of individuals infected with the pathogen either exhibit few symptoms, such as fever, headache, myalgia, nausea, vomiting, malaise, and conjunctival hyperaemia, or none at all [105]. However, as one of the many potential causes of acute fevers in medical settings, patients experience around 7 days of fever, photophobia, headache, arthralgia, chills, diaphoresis, asthenia, cough, nausea, vomiting, and muscle discomfort that can all manifest during the acute phase of the leptospirosis stage. These symptoms are similar to those of other illnesses like dengue and influenza, which cause misdiagnosis and underreporting of leptospirosis cases worldwide. If treatment is not received, serious forms may develop, resulting in serious pulmonary hemorrhage, liver damage, and renal damage [104]. Leptospirosis motility is likely significant for both the initial infection and the spread of the organisms from the point of entry to end-organ damage sites, including the liver, kidney, brain, lung, and eye [106]. It has been demonstrated that virulent Leptospira strains have a chemotaxis toward haemoglobin [107]. Leptospira also has a variety of putative virulence factors, including phospholipase, sphingomyelinase, and haemolytic activities, which are consistent with their projected capacity to move through host tissues [108].

According to estimates [17], between 10 and 15% of tainted individual’s exhibit major clinical signs, which are more frequent in the late phase (after the first week of infection). However, occasionally, even in the early stages, very severe signs are noted. Weil’s syndrome is the term for the characteristic symptom of the severe form of leptospirosis. Chronic interstitial nephritis, pancreatitis, anemia, splenomegaly, jaundice, renal failure, myocarditis, and pulmonary hemorrhage are among the conditions that these patients may experience [109]. Interstitial nephritis is the key pathological change detected in most cases of patients [110]. According to Ferrer et al. [111], experimental mouse models of Leptospira outer membrane proteins (OMPs) cause local inflammation by stimulating renal cells to produce pro-inflammatory cytokines. Furthermore, one of the most alarming side effects of leptospirosis is severe pulmonary hemorrhage syndrome (SPHS), which is characterized by cough, dyspnoea, haemoptysis, and dense pulmonary hemorrhage as its primary symptoms. About half of the patients with SPHS pass away as a result of these problems [112]. Leptospirosis in cattle is a reproductive disease that is widely known. The main features of this illness include poor offspring’s birth and abortions occurring at any time during a pregnancy. There have been reports of nursing cows’ milk tainted with blood. Conversely, the most typical sign is a silent, on-going infection associated with recurrent estruses and the loss of embryos. Due to their capacity to colonize and bear in the genital tracts of afflicted cows and bulls, serovars Hardjo and Guaricura are more closely linked with the chronic reproductive type of disease. It is becoming well-acknowledged that the main sign of leptospirosis affecting cattle is this genital manifestation of the disease [113, 114, 115].

1.7 Diagnosis and treatment

In endemic areas, leptospirosis infection has a very broad spectrum, which might complicate diagnosis and is frequently asymptomatic or symptomless [68]. As a result, the disease is not as well-known as it could be, and diagnosis is not provided quickly enough or with sufficient accessibility. Leptospirosis is diagnosed depending on the temporal stage of the disease and the sample’s availability. Laboratory techniques such as microscope evaluation, culture, molecular approaches, serology, and animal inoculation are employed to detect Leptospira [116]. Bacterial culture is the gold-standard diagnostic technique, but due to financial and technological constraints, it is not widely used. Nonetheless, epidemiologic investigations of animal strains infecting a particular area need the isolation and genetic characterization of isolates [117, 118]. Thus, an immunoglobulin M (IgM) serological screening approach on a herd level with usually enzyme-linked immune-sorbent assay (ELISA), or MAT may identify suspect herds, but culturing, immunofluorescence, or, preferentially, polymerase chain reaction (PCR) assay is required for a definitive diagnosis in acute phase leptospirosis [91]. Although urine is primary and has been extensively used as a sample, recent studies have demonstrated the usefulness of cervicovaginal mucus for the diagnosis of genital infection. The mortality rate can be significantly decreased by starting antimicrobial medication early and receiving supportive therapy right away [91]. Thus, early detection is essential to lower the severity and rate of disease progression since fast treatment reduces mortality. Leptospira has not shown to have acquired antibiotic resistance, despite slight variations in antibiotic susceptibility among isolates so far [119]. Amoxicillin (or penicillin), tetracycline, or ceftriaxone, doxycycline, streptomycin, and erythromycin are used to treat leptospirosis [60, 72, 120, 121]. Early antibiotic therapy has been shown to reduce the risk of severe disease in both the individual and the population, as well as to reduce the severity and fatality rates and save costs for the healthcare system [60]. Prompt presumptive antibiotic treatment is also advised by the WHO, citing the empirical advantage of starting it prior to the fifth day of illness [72]. The requirements for supportive care, including intensive care, will vary depending on the severity of leptospirosis. The majority of cases of severe leptospirosis will necessitate some kind of supportive care, including intensive care. Hemodynamic instability is often evident in the presentation, necessitating the use of vasoactive medications and intravenous therapy, which will also be employed to administer medication and balance correction. Corticosteroids are occasionally utilized because patients often appear with a septic shock, and some degree of excessive inflammatory response is reported [122].

1.8 Prevention and control measures

The adoption of vaccination is highly recommended since it is the least expensive control strategy and is crucial for the management of leptospirosis [123]. Vaccinating both humans and animals helps prevent leptospirosis. Its effectiveness varies, and research has shown that commercial vaccinations are ineffective at preventing kidney colonization [124]. The effectiveness of the control methods differs depending on the strain of infection. Despite cross-reactivity, some vaccinations may provide protection against serovars, unlike those used to manufacture them [125]. However, their potential serotype dependence and inability to elicit an immunological response against other serovars were noted by Sonrier et al. [126]. Furthermore, the creation of vaccines is hampered by the genetic and phenotypic variety of infective Leptospira [127].

According to Pereira et al. [18], Cuba is the only country in Latin America where people are routinely immunized against Leptospira. Inactivated vaccinations are typically given to domestic animals. It is also used on populations of susceptible people in numerous other nations. But they are not employed everywhere because of unpleasant effects on humans, a lack of cross-protection, and a short duration of immunity [127]. Mostly, the leptospirosis vaccine schedule typically calls for six-month intervals, with the vaccination window falling preferably before the breeding service season, which starts in the early spring when environmental contamination is at its peak [105]. Sejroe strain infections, on the other hand, are impossible to completely eradicate; instead, on-going vigilance and a programme centred on lowering reproductive issues and the ensuing financial risks are necessary [128]. Incidental infections can be managed more readily. The other leptospirosis control techniques are designed to reduce the incidence of clinical disease by implementing integrated actions in many parts of the transmission chain [62, 129].

2.1 Biological characteristics of Leptospira as a major challenge

The mechanism of cell aggregation as an endurance technique for leptospires was detected by Trueba et al. [131]. Through the mechanism of cell aggregation, the bacteria can accumulate nutrients and enzymes from the lysing cells, which can help them, survive hard conditions, such as low temperatures or nutrient-poor environments [86, 132]. Leptospira have a double-membrane that is similar to that of gram-negative bacteria due to the presence of lipopolysaccharide (LPS), and their cytoplasmic membrane closely resembles the envelope architecture of Gram-positive bacteria due to the tight interaction of the peptidoglycan cell wall [80]. On the other hand, Leptospira shares a thin peptidoglycan cell wall with other gram-negative bacteria. As noted by Miyamoto-Shinohara et al. [133], the thickness of the cell walls surely affects the survival rate of bacteria. LPS is another characteristic of Leptospira species. By keeping water within the cells, LPS aids in the survival of bacteria in the desiccant environment [134, 135]. For instance, to avoid ice forming inside the cells and moisture build-up during the storage of dried culture, all water must be completely removed from the cell. Accordingly, LPS prevents water molecules from being extracted from inside the cells during the freeze-drying procedure [133]. Because of their meticulous nature, Leptospira spp. are difficult to isolate, propagate, and store [136].

2.2 Diagnostic challenges

Leptospirosis in humans is frequently misdiagnosed and disregarded as the source of fever or generalized sickness. Since it can mimic many other infectious diseases, including dengue, malaria, hepatitis, pneumonia, and meningitis, misdiagnosis is widespread due to its varied symptoms and non-specific presentations. Other illnesses such as haemorrhagic fevers, Q fever, scrub typhus, yellow fever, and rickettsia infections may be included in the differential diagnosis, depending on the patient’s geographic location [137, 138, 139, 140]. Following natural catastrophes, infectious disease epidemics are frequent [138, 139, 140]. Concurrent outbreaks of various pathogens can pose diagnostic hurdles, especially if laboratory facilities are limited. The clinical ramifications of misdiagnosis or delayed diagnosis are noteworthy, as the reduction of morbidity and death associated with early treatment of certain infections like leptospirosis, malaria, and meningitis is imperative. Furthermore, misdiagnosis can cause significant delays in the application of therapies specific to a given disease, giving epidemics the opportunity to “escape.” Following flooding, food- and water-borne diseases are frequent, and some of them might be challenging to distinguish clinically from leptospirosis [89].

Diagnosis is based on laboratory results. However, the clinical appearance of leptospirosis is unclear, and the laboratory diagnosis of leptospirosis is often challenging. The polymerase chain reaction (PCR), which is infrequent in high-endemic areas, is the only sensitive and specific diagnostic that is accurate during the acute phase of the disease [141, 142]. Micro-agglutination testing (MAT), a serological reference approach, is only accessible in Ref. laboratories. Leptospirosis may be mistaken for malaria, influenza, dengue, scrub or murine typhus, spotted fevers, and a variety of other potential viral, parasitic, or bacterial diseases in tropical environments where there are many potential causes for acute fevers [60]. Among hundreds of cases of influenza, dengue, or yellow fever, leptospirosis may be the cause of a few severe cases of fever. As leptospirosis lacks a pathognomonic sign or symptom, samples should be sent to a laboratory for biological study, and the epidemiological perspective should be used to raise suspicions [60, 118]. It has been possible to detect motile, helical-shaped Leptospira bacilli directly in blood or urine; however, this method has been shown to have low sensitivity and is difficult to determine specificity due to the bacteria’s small diameter [44]. Therefore, caution should be exercised while using this technique. These days, genes specific to pathogenic Leptospira are targeted by nucleic acid amplification techniques using a matrix of blood, urine, or cerebrospinal fluid. In order to effectively control this potentially fatal zoonosis, an efficient surveillance system that tracks disease trends must be developed.

Our understanding of the disease will grow with the use of these data, but improving veterinary and public health surveillance and reporting will require more laboratory space and the resolution of diagnostic hurdles by scientists. To full-fill monitoring needs and prevent and reduce leptospirosis epidemics, a collaborative, multidisciplinary One Health approach is required [8]. Early detection of animal sickness could be used to detect environmental pollution and initiate preventive actions to lower the risk of leptospirosis infection in humans [54]. Reducing the opportunities for wild animals to engage with domestic and companion animals, utilizing potable water, immunizing livestock and companion animals, and donning water-proof protection gear and footwear when near potentially polluted water are all possible ways to prevent infection. To determine whether an activity poses a risk of infection for their pet, to learn about infection signs, and to take protective measures in case their pet becomes ill, pet owners should consult with their veterinarian [136].

Organizations dedicated to public and animal health should think about doing educational outreach in places that have recently seen infections in humans or animals, that occasionally flood, and that include recreational water areas or events that could potentially spread the disease. As was previously noted, leptospirosis is primarily found in tropical and subtropical areas, where there are several potential causes of acute fevers. In situations where a hospital has limited space, patient triage may be necessary, particularly in critical care units. This is especially prevalent in two scenarios: either in conjunction with an on-going (usually viral) outbreak or during large-scale leptospirosis outbreaks that follow cyclones [143]. In this specific case of concurrent dengue fevers, leptospirosis should receive extra attention due to its challenging differential diagnosis and the possibility of co-infections [60]. Leptospirosis should receive extra attention in this specific setting of concurrent dengue fevers due to its challenging differential diagnosis, especially given the possibility of co-infections [60]. To find biological indicators with a prognostic value for severity, several clinical investigations involving leptospirosis patients have been carried out. Validated prognostic markers for leptospirosis are still up for debate, despite certain cohorts demonstrating significant differences.

2.3 Animal reservoirs

Animals are traditionally categorized as susceptible or maintenance hosts. Susceptible hosts typically experience a variable-severity illness after infection, which may even be fatal. Within a few weeks, the recuperating hosts will completely eradicate the Leptospira from their bodies. After contagion, vulnerable hosts usually show a course of sickness with a range of severity; sometimes, it may be fatal. The illness varies in severity. Within weeks, the recovered hosts will totally clear their bodies from the Leptospira. With rare exceptions, the maintenance hosts will likely neither acquire nor exhibit any mild clinical symptoms, and they will also likely rid their bodies of Leptospira with the exception of the kidneys, where they will likely continue to grow and persist in the proximal renal tubules for several months.

Preservation host populations are called “reservoirs” for leptospirosis. Among the various Leptospira, different serovars with frequent host associations cattle with the serogroup Hardjo; dogs and canines with the serogroup Canicola; mice with the serogroup Ballum; rats with the serogroup Icterohaemorrhagiae are common. Recent research on the Rattus norvegicus model leptospirosis reservoir has also revealed evidence of Leptospira in the breast tissue and milk of females with long-term infections. Even though it has already been suggested that leptospirosis can spread through breastfeeding [144]. Conditions for the Leptospira strains implicated in individuals’ cases are determined by the animal reservoir in a particular setting. Many mammals in rural areas, such as domestic animals like pigs, cattle, dogs, sheep, and goats, preserve and disperse a variety of Leptospira serovars. Conversely, in typical urban and peri-urban leptospirosis, the main reservoir is rats (mainly Rattus norvegicus) bearing the serogroup Icterohaemorrhagiae. As “vectors,” domestic dogs may, for example, be seen wandering in areas where they come into contact with soil, water, or wild or feral creatures. Within days to weeks, they may become infected and start to excrete leptospires in their urine, even in close proximity to their owners.

2.4 Environmental drivers of leptospirosis

Notwithstanding the prevalence and range of leptospirosis, there are still a great deal of unanswered questions regarding the dynamics of the disease’s transmission and the catalysts for epidemics. However, several environmental risk factors for illness or outbreaks have been found by epidemiological investigations, and these factors vary depending on the ecological area. Urbanization and climate change are probably going to have an impact on a lot of these variables.