Leptospirosis is a febrile (fever) disease caused primarily by infection with the bacterium Leptospira interrogans, but also by other bacteria within the genus Leptospira. It can be transmitted to humans by animals.
The German physician Adolf Weil (1848–1916) first described the disease in 1886. It was later observed in 1907 from a slice of renal tissue during a post mortem procedure.
An infection by the bacterium Leptospira interrogans goes by different names in different regions. Alternate names for leptospirosis include mud fever, canefield fever, Rat Catcher's Yellows, seven-day fever, swamp fever, cane cutter's fever, rice field fever, Stuttgart disease, Swineherd's disease, and Fort Bragg fever. More severe cases of leptospirosis are called Weil's syndrome or icterohemorrhagic fever.
Leptospirosis is called a zoonosis because it is a disease of animals that can be transmitted to humans by various wild animals such as rats, opossums, raccoons, foxes, and skunks. It can be a very serious problem in the livestock industry. Leptospira bacteria have been found in dogs, rats, livestock, mice, voles, rabbits, hedgehogs, skunks, possums, frogs, fish, snakes, and certain birds and insects. Infected animals pass the bacteria in their urine for months, or even years. In the United States, rats and dogs are more commonly linked with human leptospirosis than other animals. Domesticated animals such as dogs and livestock can also carry and transmit the disease. Humans may also acquire the disease through soil or water infected by such animals. This rare disease and contagious infection can range from very mild and symptomless to a more serious, even life–threatening form, that may be associated with kidney (renal) failure.
Humans are considered accidental hosts and become infected with Leptospira interrogans by coming into contact with urine from infected animals. Transmission of the organism occurs through direct contact with urine, or through contact with soil, water, or plants that have been contaminated by animal urine. Leptospira interrogans can survive for as long as six months outdoors under favorable conditions. Leptospira bacteria can enter the body through cuts or other skin damage or through mucous membranes (such as the inside of the mouth and nose). Researchers believe that the bacteria may be able to pass through intact skin, although evidence for this hypothesis has not been obtained.
Once past the skin barrier, bacteria enter the blood stream and rapidly spread throughout the body. The infection causes damage to the inner lining of blood vessels. The liver, kidneys, heart, lungs, central nervous system, and eyes may be affected.
There are two stages in the disease process. The first stage is during the active Leptospira infection and is called the bacteremic or septicemic phase. The bacteremic phase lasts from three to seven days and presents as typical flu–like symptoms. During this phase, bacteria can be found in the patient's blood and cerebrospinal fluid. The second stage, or immune phase, takes place either immediately after the bacteremic stage or after a one to three day symptom-free period. The immune phase can last up to one month. During the immune phase, symptoms are milder but meningitis (inflammation of spinal cord and brain tissues) is common. Bacteria can be isolated only from the urine during this second phase.
Leptospirosis occurs all over the world, especially in temperate or tropical climates. It is considered an occupational hazard for many people who work outdoors or with animals, such as farmers, fish and meat processing workers, miners and sewer workers. Leptospirosis has also been associated with outdoor sports, such as swimming, wading, kayaking, and rafting in contaminated lakes and rivers. High–risk activities also include care of pets (especially dogs), raising of livestock, hunting and trapping.
The disease is relatively rare in humans. Leptospirosis is usually found in tropical and subtropical areas, especially around stagnant or slow–moving waters, but can be present anywhere worldwide. It is also more likely to be a problem during the months of July through October and February through March. The infection is often transmitted to humans after they have drunk water contaminated with animal urine. It can also be contracted through such contamination of breaks in the skin and through mucous membranes such as the eyes.
Leptospirosis is rarely found in the continental part of the United States. However, when it is present in the United States, it is most often located in the state of Hawaii. According to the Centers for Disease Control and Prevention (CDC), between 100 and 200 cases of leptospirosis are reported in the United States each year. In addition, nearly 75% of cases of leptospirosis in North America occur in males. Further, about 50% of cases happen in Hawaii, followed by the southern Atlantic, Gulf, and Pacific coastal states. However, because of the nonspecific symptoms of leptospirosis, it is believed that the occurrence in the United States is actually much higher. Leptospirosis occurs year–round in North America, but about half of the cases take place between July and October.
Leptospirosis is caused primarily by an infection with the bacterium Leptospira interrogans. Bacteria are spread through contact with urine from infected animals.
Symptoms of Leptospira infection appear within two to 26 days following exposure to the bacteria, with 10 days being the average number of days. Because the symptoms can be nonspecific, most people who have antibodies to Leptospira do not remember having had an illness. Eighty-five to 90% of the cases are not serious and clear up on their own. Symptoms of the first stage of leptospirosis last three to seven days and include:
Following the first stage of disease, a brief symptomfree period ensues for most patients. The symptoms of the second stage vary in each patient. Most patients have a low-grade fever, headache, vomiting, and rash. Aseptic meningitis is common in the second stage, symptoms of which include headache and photosensitivity (sensitivity of the eye to light). Leptospira can affect the eyes and make them cloudy and yellow to orange colored. Vision may be blurred.
Ten percent of the persons infected with Leptospira develop a serious disease called Weil's syndrome. The symptoms of Weil's syndrome are more severe than those described above and there is no distinction between the first and second stages of disease. The hallmark of Weil's syndrome is liver, kidney, and blood vessel disease. The signs of severe disease are apparent after 3–7 days of illness. In addition to those listed above, symptoms of Weil's syndrome include jaundice (yellow skin and eyes), decreased or no urine output, hypotension (low blood pressure), rash, anemia (decreased number of red blood cells), shock, and severe mental status changes. Red spots on the skin, “blood shot” eyes, and bloody sputum signal that blood vessel damage and hemorrhage have occurred.
Leptospirosis can be diagnosed and treated by doctors who specialize in infectious diseases. During the bacteremic phase of the disease, the symptoms are relatively nonspecific. This often causes an initial misdiagnosis because many diseases have similar symptoms to leptospirosis. The later symptoms of jaundice and kidney failure together with the bacteremic phase symptoms suggest leptospirosis. Blood samples will be tested to look for antibodies to Leptospira interrogans. Blood samples taken over a period of a few days would show an increase in the number of antibodies. Isolating Leptospira bacteria from blood, cerebrospinal fluid (performed by spinal tap), and urine samples is diagnostic of leptospirosis. Tests for white blood cell count and creatine kinase may also be performed. It may take six weeks for Leptospira to grow in laboratory media. Most insurance companies cover the diagnosis and treatment of this infection.
Several diagnostic tests for leptospirosis have been devised that are more accurate as well as faster than standard cultures. One test uses flow cytometry light scatter analysis; this method can evaluate a sample of infected serum in as little as 90 minutes.
A second technique is an IgM-enzyme-linked immunosorbent assay (ELISA), which detects the presence of IgM antibodies to L. interrogans in blood serum samples.
Leptospirosis is treated with antibiotics (such as tetracycline or chloramphenicol), penicillin (Bicillin, Wycillin), doxycycline (Monodox, Vibramycin), or erythromycin (E-mycin, Ery-Tab). However, many doctors prefer to treat patients with ceftriaxone, which is easier to use than intravenous penicillin. Ciprofloxacin may be combined with other drugs in caring for patients who develop uveitis. It is generally agreed that antibiotic treatment during the first few days of illness is helpful. However, leptospirosis is often not diagnosed until the later stages of illness. The benefit of antibiotic treatment in the later stages of disease, however, is controversial. A rare complication of antibiotic therapy for leptospirosis is the occurrence of the Jarisch–Herxheimer reaction, which is characterized by fever, chills, headache, and muscle pain.
Patients with severe illness require hospitalization for treatment and monitoring. Medication or other treatment for pain, fever, vomiting, fluid loss, bleeding, mental changes, and low blood pressure may be provided. Patients with kidney failure require hemodialysis to remove waste products from the blood.
Leptospirosis is becoming an emerging global public health issue because of its increasing incidence in both developing and developed countries. A number of leptospirosis outbreaks have occurred in various regions such as Nicaragua, Brazil and India. Some outbreaks were due to natural calamities such as cyclone and floods that contaminated water supplies. Although most countries apply the basic principles of prevention such as source reduction, environmental sanitation, more hygienic work–related and personal practices, international monitoring efforts are being organized.
The World Health Organisation (WHO) has recommended standards and strategies for the surveillance, prevention and control of communicable diseases, developed by the WHO Emerging Diseases and Pandemic Response Department (EPR), in collaboration with the Department Food Safety and Zoonoses (FOS), for major zoonoses involving livestock.
The majority of patients infected with Leptospira interrogans experience a complete recovery when treated promptly. Ten percent of patients develop eye inflammation (uveitis) up to one year after the illness. Other complications include excessive bleeding, meningitis, and Jarisch-Herxheimer reaction. In the United States, about one out of every 100 patients die from leptospirosis. Death is usually caused by kidney failure, but has also been caused by myocarditis (inflammation of heart tissue), septic shock (reduced blood flow to the organs because of the bacterial infection), organ failure, and/or poorly functioning lungs. Mortality is highest in patients over 60 years of age.
Persons who are at an extremely high risk (such as soldiers training in wetlands) can be pretreated with 200 milligrams (mg) of doxycycline once a week. As of the early 2010s, no vaccine is available to prevent leptospirosis in humans, although similar vaccines have been formulated by veterinarians for dogs, swine, cattle, and other animals.
There are many ways to decrease the chances of being infected by Leptospira. These include:
See also Globalization and emerging diseases ; Zoonoses .
Russell, Jesse, and Ronald Cohn. Leptospirosis. Great Malvern, UK: Book on Demand Ltd., 2012.
World Health Organization. Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. Geneva, Switzerland: WHO Press, 2003.
Del Carlo Bernardi, F., et al. “Immune receptors and adhesion molecules in human pulmonary leptospirosis.” Human Pathology 43, no. 10 (October 2012): 1601–1610.
Dellagostin, O. A., et al. “Recombinant vaccines against leptospirosis.” Human Vaccines 7, no. 11 (November 2011): 1215–1224.
Sarkar, J., et al. “Leptospirosis: a re–emerging infection.” Asian Pacific Journal of Tropical Medicine 5, no. 6 (June 2012): 500–502.
Turhan, V. and O. Sezer. “Leptospirosis as a still unknown and underappreciated disease.” International Journal of Preventive Medicine 3, no. 8 (August 2012): 591–592.
“Leptospirosis.” Centers for Disease Control. January 13, 2012. http://www.cdc.gov/leptospirosis/
“Leptospirosis.” Medline Plus, 27 September 2012. http://www.nlm.nih.gov/medlineplus/ency/article/001376.htm
American Veterinary Medical Association (AVMA), 1931 North Meacham Rd., Suite 100, Schaumburg, IL, 60173–4360, (800) 248-2862, Fax: (847) 925-1329, http://www.avma.org .
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, (800) 232-4636, email@example.com, http://www.cdc.gov .
International Leptospirosis Society, Faculty of Medicine, Nursing and Health Sciences, Monash University Victoria, Australia, 3800, +61 3 9905 4301, Fax: +61 3 9905 4302, firstname.lastname@example.org, http://www.med.monash.edu.au/microbiology/staff/adler/ ils.html.
Belinda Rowland, PhD
Rebecca J. Frey, PhD