What is leptospirosis?

Leptospirosis is a disease caused by bacteria (Leptospira interrogans) that produce a wide range of symptoms that may occur in phases; some patients may develop kidney or liver failure, respiratory failure, meningitis, or even death. The disease is spread by the urine of infected animals (many species, both domesticated and wild); the bacteria can survive in the water and soil for months. The disease is most common in temperate and tropical climates. The infecting bacteria occur worldwide. 

Leptospirosis is an infection caused by corkscrew-shaped bacteria called Leptospira. Signs and symptoms can range from none to mild such as headaches, muscle pains, and fevers; to severe with bleeding from the lungs ormeningitis.[4][5] If the infection causes the person to turn yellow, have kidney failure and bleeding, it is then known asWeil's disease.[5] If it causes lots of bleeding from the lungs it is known as severe pulmonary haemorrhage syndrome.[5]

Up to 13 different genetic types of Leptospira may cause disease in humans.[6] It is transmitted by both wild and domestic animals.[5] The most common animals that spread the disease are rodents.[7] It is often transmitted byanimal urine or by water or soil containing animal urine coming into contact with breaks in the skin, eyes, mouth, or nose.[4][8] In the developing world the disease most commonly occurs in farmers and poor people who live in cities.[5] In the developed world it most commonly occurs in those involved in outdoor activities in warm and wet areas of the world.[4] Diagnosis is typically by looking for antibodies against the bacteria or finding its DNA in the blood.[9]

Efforts to prevent the disease include protective equipment to prevent contact when working with potentially infected animals, washing after this contact, and reducing rodents in areas people live and work.[4] The antibioticdoxycycline, when used in an effort to prevent infection among travellers, is of unclear benefit.[4] Vaccines for animals exist for certain type of Leptospira which may decrease the risk of spread to humans.[4] Treatment if infected is with antibiotics such as: doxycycline, penicillin, or ceftriaxone.[4] Weil's disease and severe pulmonary haemorrhage syndrome result in death rates greater than 10% and 50%, respectively, even with treatment.[5]

It is estimated that seven to ten million people are infected by leptospirosis a year.[10] The number of deaths this causes is not clear.[10] The disease is most common in tropical areas of the world but may occur anywhere.[4]Outbreaks may occur in slums of the developing world.[5] The disease was first described by Weil in 1886 in Germany.[4] Animals who are infected may have no symptoms, mild symptoms, or severe symptoms.[6] Symptoms may vary by the type of animal.[6] In some animals Leptospira live in the reproductive tract, leading to transmission during mating.[11]

Signs and symptoms

Leptospiral infection in humans causes a range of symptoms, and some infected persons may have no symptoms at all. Leptospirosis is a biphasic disease that begins suddenly with fever accompanied by chills, intense headache, severe myalgia (muscle ache), abdominal pain, conjunctival suffusion (red eye), and occasionally a skin rash.[12] The symptoms appear after an incubation period of 7–12 days. The first phase (acute or septicemic phase) ends after 3–7 days of illness.[13] The disappearance of symptoms coincides with the appearance of antibodies against Leptospira and the disappearance of the bacteria from the bloodstream. The patient is asymptomatic for 3–4 days until the second phase begins with another episode of fever.[12] The hallmark of the second phase ismeningitis (inflammation of the membranes covering the brain).[14]

90 percent of cases of the disease are mild leptospirosis. The rest experience severe disease, which develops during the second stage or occurs as a single progressive illness.[15] The classic form of severe leptospirosis is known as Weil's disease, which is characterized by liver damage (causing jaundice), kidney failure, and bleeding.[16] Additionally, the heart and brain can be affected, meningitis of the outer layer of the brain, encephalitis of brain tissue with same signs and symptoms; and lung affected as the most serious and life-threatening of all leptospirosis complications. The infection is often incorrectly diagnosed due to the nonspecific symptoms.

Other severe manifestations include extreme fatigue, hearing loss, respiratory distress, and azotemia.

Cause

Scanning electron micrograph of a number of Leptospira sp. bacteria atop a 0.1 µm polycarbonate filter

Leptospirosis is caused by spirochaete bacteria belonging to the genus Leptospira. 21 species of Leptospira have been identified.[6] 13 species cause disease or have been detected in human cases.[6][17]

Leptospira are also classified based on their serovar. About 250 pathogenic serovars of Leptospira are recognized. The diverse sugar composition of the lipopolysaccharide on the surface of the spirochete is responsible for the antigenic difference between serovars. Antigenically related serovars are grouped into 24 serogroups, which are identified using the microscopic agglutination test (MAT). A given serogroup is often found in more than one species, suggesting that the LPS genes that determine the serovar are exchanged between species.[17]

The traditional serologic system currently seems more useful from a diagnostic and epidemiologic standpoint—but this may change with further development and spread of technologies like polymerase chain reaction (PCR).

Transmission

Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as the urine is still moist. Although Leptospira has been detected in reptiles and birds, only mammals are able to transmit the bacteria to humans and other animals.[18] Rats, mice, and moles are important primary hosts—but a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, opossums, skunks, and certain marine mammals carry and transmit the disease as secondary hosts. In Africa, the banded mongoose has been identified as a carrier of the pathogen, likely in addition to other African wildlife hosts.[19] Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle.

House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house. The type of habitats most likely to carry infective bacteria are muddy riverbanks, ditches, gullies, and muddy livestock rearing areas where there is regular passage of wild or farm mammals. The incidence of leptospirosis correlates directly with the amount of rainfall, making it seasonal in temperate climates and year-round in tropical climates. Leptospirosis also transmits via the semen of infected animals.[20]

Humans become infected through contact with water, food, or soil that contains urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact. The disease is not known to spread between humans, and bacterial dissemination in convalescence is extremely rare in humans. Leptospirosis is common among water-sport enthusiasts in specific areas, as prolonged immersion in water promotes the entry of the bacteria. Surfers and whitewater paddlers[21] are at especially high risk in areas that have been shown to contain the bacteria, and can contract the disease by swallowingcontaminated water, splashing contaminated water into their eyes or nose, or exposing open wounds to infected water.[22]

At risk occupations

Occupations at risk include veterinarians, slaughterhouse workers, farmers, sewer maintenance workers, waste disposal facility workers, and people who work on derelict buildings.[23] Slaughterhouse workers can contract the disease through contact with infected blood or body fluids. Rowers, kayakers and canoeists also sometimes contract the disease.[24] It was once mostly work related but is now often also related to adventure tourism and recreational activities.[5]

Diagnosis

Kidney tissue, using a silver stainingtechnique, revealing the presence ofLeptospira bacteria

On infection the microorganism can be found in blood and cerebrospinal fluid (CSF) for the first 7 to 10 days (invoking serologically identifiable reactions) and then moving to the kidneys. After 7 to 10 days the microorganism can be found in fresh urine. Hence, early diagnostic efforts include testing a serum or blood sample serologically with a panel of different strains.

Kidney function tests (blood urea nitrogen and creatinine) as well as blood tests for liver functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are relatively mild. These levels may be normal, even in children with jaundice.

Diagnosis of leptospirosis is confirmed with tests such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). The MAT (microscopic agglutination test), a serological test, is considered the gold standard in diagnosing leptospirosis. As a large panel of different leptospira must be subcultured frequently, which is both laborious and expensive, it is underused, especially in developing countries.

Differential diagnosis list for leptospirosis is very large due to diverse symptomatics. For forms with middle to high severity, the list includes dengue fever and other hemorrhagic fevers, hepatitis of various etiologies, viral meningitis, malaria, and typhoid fever. Light forms should be distinguished from influenza and other related viral diseases. Specific tests are a must for proper diagnosis of leptospirosis.

Under circumstances of limited access (e.g., developing countries) to specific diagnostic means, close attention must be paid to the medical history of the patient. Factors such as certain dwelling areas, seasonality, contact with stagnant contaminated water (bathing, swimming, working on flooded meadows, etc.) or rodents in the medical history support the leptospirosis hypothesis and serve as indications for specific tests (if available).

Leptospira can be cultured in Ellinghausen-McCullough-Johnson-Harris medium (EMJH), which is incubated at 28 to 30 °C.[25] The median time to positivity is three weeks with a maximum of three months. This makes culture techniques useless for diagnostic purposes, but is commonly used in research.