Leptospirosis is a
blood infection
Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. Blood is normally a sterile environment, so the detection of micro ...
caused by the bacteria ''
Leptospira
''Leptospira'' ( grc, leptos, italics=yes, 'fine, thin' and la, spira, links=no, 'coil') is a genus of spirochaete bacteria, including a small number of pathogenic and saprophytic species. ''Leptospira'' was first observed in 1907 in kidney ti ...
''.
Signs and symptoms can range from none to mild (
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s,
muscle pains
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another lik ...
, and
fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
s) to severe (
bleeding in the lungs or
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
).
Weil's disease, the acute, severe form of leptospirosis, causes the infected individual to become
jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
d (skin and eyes become yellow), develop
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, and bleed.
[ Bleeding from the lungs associated with leptospirosis is known as severe pulmonary haemorrhage syndrome.]
More than ten genetic types of ''Leptospira'' cause disease in humans. Both wild and domestic animals can spread the disease, most commonly rodent
Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...
s. The bacteria are spread to humans through animal urine
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
, or water and soil contaminated with animal urine, coming into contact with the eyes
Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conve ...
, mouth, nose or breaks in the skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
. In developing countries, the disease occurs most commonly in farmers and low-income people who live in areas with poor sanitation. In developed countries, it occurs during heavy downpours and is a risk to sewage
Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater that is produced by a community of people. It is typically transported through a sewer system. Sewage consists of wastewater discharged from residenc ...
workers and those involved in outdoor activities in warm and wet areas. Diagnosis is typically by testing for antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against the bacteria or finding bacterial DNA in the blood.
Efforts to prevent the disease include protective equipment to block contact when working with potentially infected animals, washing after contact, and reducing rodents in areas where people live and work. The antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
doxycycline
Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
is effective in preventing leptospirosis infection. Human vaccines are of limited usefulness; vaccines for other animals are more widely available. Treatment when infected is with antibiotics such as doxycycline, penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
, or ceftriaxone
Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint ...
. The overall risk of death is 5–10%. However, when the lungs are involved, the risk of death increases to the range of 50–70%.
It is estimated that one million severe cases of leptospirosis occur every year, causing about 58,900 deaths. The disease is most common in tropical
The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in
the Southern Hemisphere at S. The tropics are also referred to ...
areas of the world but may occur anywhere. Outbreaks
In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
may arise after heavy rainfall. The disease was first described by physician Adolf Weil in 1886 in Germany. Infected animals may have no, mild or severe symptoms. These may vary by the type of animal.[ In some animals ''Leptospira'' live in the reproductive tract, leading to transmission during mating.]
Signs and symptoms
The symptoms of leptospirosis usually appear one to two weeks after infection, but the incubation period
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...
can be as long as a month. The illness is biphasic
Biphasic, meaning having two phases, may refer to:
* Phase (matter)
In the physical sciences, a phase is a region of space (a thermodynamic system), throughout which all physical properties of a material are essentially uniform. Examples ...
in a majority of symptomatic cases. Symptoms of the first phase (acute or leptospiremic phase) last five to seven days. In the second phase (immune phase), the symptoms resolve as antibodies against the bacteria are produced. Additional symptoms develop in the second phase. The phases of illness may not be distinct, especially in patients with severe illness. 90% of those infected experience mild symptoms while 10% experience severe leptospirosis.
Leptospiral infection in humans causes a range of symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s, though some infected persons may have none. The disease begins suddenly with fever accompanied by chills, intense headache, severe muscle aches and abdominal pain. A headache brought on by leptospirosis causes throbbing pain and is characteristically located at the head's bilateral temporal or frontal
Front may refer to:
Arts, entertainment, and media Films
* ''The Front'' (1943 film), a 1943 Soviet drama film
* ''The Front'', 1976 film
Music
* The Front (band), an American rock band signed to Columbia Records and active in the 1980s and e ...
regions. The person could also have pain behind the eyes and a sensitivity to light. Muscle pain usually involves the calf muscle
The triceps surae consists of two muscles located at the calf – the two-headed gastrocnemius and the soleus. These muscles both insert into the calcaneus, the bone of the heel of the human foot, and form the major part of the muscle of the ...
and the lower back. The most characteristic feature of leptospirosis is the conjunctival suffusion
Conjunctival suffusion is an eye finding occurring early in leptospirosis, which is caused by ''Leptospira interrogans''. Conjunctival suffusion is characterized by redness of the conjunctiva that resembles conjunctivitis, but it does not invo ...
(conjunctivitis
Conjunctivitis, also known as pink eye, is inflammation of the conjunctiva, outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may ...
without exudate) which is rarely found in other febrile
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
illnesses. Other characteristic findings on the eye include subconjunctival bleeding
Subconjunctival bleeding, also known as subconjunctival hemorrhage or subconjunctival haemorrhage, is bleeding from a small blood vessel over the whites of the eye. It results in a red spot in the white of the eye. There is generally little to no ...
and jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
. A rash is rarely found in leptospirosis. When one is found alternative diagnoses such as dengue fever
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characterist ...
and chikungunya fever should be considered. Dry cough is observed in 20–57% of people with leptospirosis. Thus, this clinical feature can mislead a doctor to diagnose the disease as a respiratory illness. Additionally, gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
symptoms such as nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting, abdominal pain, and diarrhoea frequently occur. Vomiting and diarrhea may contribute to dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
. The abdominal pain can be due to acalculous cholecystitis or inflammation of the pancreas. Rarely, the lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
, liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, and spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . may be enlarged and palpable.
There will be a resolution of symptoms for one to three days. The immune phase starts after this and can last from four to 30 days and can be anything from brain to kidney complications. The hallmark of the second phase is inflammation of the membranes covering the brain. Signs and symptoms of meningitis include severe headache and neck stiffness. Kidney involvement is associated with reduced or absent urine output.
The classic form of severe leptospirosis, known as Weil's disease, is characterised by liver damage (causing jaundice), kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, and bleeding, which happens in 5–10% of those infected. Lung and brain damage can also occur. For those with signs of inflammation of membranes covering the brain and the brain itself, altered level of consciousness
An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment.
A mildly depressed level of consciousn ...
can happen. A variety of neurological problems such as paralysis of half of the body, complete inflammation of a whole horizontal section of spinal cord, and muscle weakness due to immune damage of the nerves supplying the muscles are the complications. Signs of bleeding such as non-traumatic bruises at , non-traumatic bruises more than , nose bleeding
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
, blackish stools due to bleeding in the stomach, vomiting blood
Hematemesis is the vomiting of blood. It is always an important sign. It can be confused with hemoptysis (coughing up blood) or epistaxis (nosebleed), which are more common. The source is generally the upper gastrointestinal tract, typically abo ...
and bleeding from the lungs can also be found. Prolongation of prothrombin time
The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...
in coagulation testing
Blood clotting tests are the tests used for diagnostics of the hemostasis system.
Coagulometer is the medical laboratory analyzer used for testing of the hemostasis system. Modern coagulometers realize different methods of activation and observatio ...
is associated with severe bleeding manifestation. However, low platelet count is not associated with severe bleeding. Pulmonary haemorrhage is alveolar haemorrhage (bleeding into the alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
of the lungs) leading to massive coughing up of blood, and causing acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...
, where the risk of death is more than 50%. Rarely, inflammation of the heart muscles, inflammation of membranes covering the heart, abnormalities in the heart's natural pacemaker and abnormal heart rhythms may occur.
Cause
Bacteria
Leptospirosis is caused by spirochaete
A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...
bacteria that belong to the genus
Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
''Leptospira
''Leptospira'' ( grc, leptos, italics=yes, 'fine, thin' and la, spira, links=no, 'coil') is a genus of spirochaete bacteria, including a small number of pathogenic and saprophytic species. ''Leptospira'' was first observed in 1907 in kidney ti ...
'', which are aerobic
Aerobic means "requiring air," in which "air" usually means oxygen.
Aerobic may also refer to
* Aerobic exercise, prolonged exercise of moderate intensity
* Aerobics, a form of aerobic exercise
* Aerobic respiration, the aerobic process of cel ...
, right-handed
In human biology, handedness is an individual's preferential use of one hand, known as the dominant hand, due to it being stronger, faster or more dextrous. The other hand, comparatively often the weaker, less dextrous or simply less subjecti ...
helical
Helical may refer to:
* Helix, the mathematical concept for the shape
* Helical engine, a proposed spacecraft propulsion drive
* Helical spring, a coilspring
* Helical plc, a British property company, once a maker of steel bar stock
* Helicoil
A t ...
,[ and 6–20 ]micrometer Micrometer can mean:
* Micrometer (device), used for accurate measurements by means of a calibrated screw
* American spelling of micrometre
The micrometre ( international spelling as used by the International Bureau of Weights and Measures; ...
s long. Like Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
bacteria, ''Leptospira'' have an outer membrane studded with lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
(LPS) on the surface, an inner membrane and a layer of peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...
cell wall. However, unlike Gram-negative bacteria, the peptidoglycan layer in ''Leptospira'' lies closer to the inner than the outer membrane. This results in a fluid outer membrane loosely associated with the cell wall. In addition, ''Leptospira'' have a flagellum
A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates.
A microorganism may have f ...
located in the periplasm
The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found that ...
, associated with corkscrew style movement. Chemoreceptor
A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...
s at the poles of the bacteria sense various substrates and change the direction of its movement.[ The bacteria are traditionally visualised using ]dark-field microscopy
Dark-field microscopy (also called dark-ground microscopy) describes microscopy methods, in both light and electron microscopy, which exclude the unscattered beam from the image. As a result, the field around the specimen (i.e., where there is ...
without staining.
A total of 66 species of ''Leptospira'' has been identified. Based on their genomic sequence, they are divided into two clade
A clade (), also known as a monophyletic group or natural group, is a group of organisms that are monophyletic – that is, composed of a common ancestor and all its lineal descendants – on a phylogenetic tree. Rather than the English term, ...
s and four subclades: P1, P2, S1, and S2. The 19 members of the P1 subclade include the 8 species that can cause severe disease in humans: '' L. alexanderi'', '' L. borgpetersenii'', '' L. interrogans'', '' L. kirschneri'', ''L. mayottensis'', '' L. noguchii'', ''L. santarosai'', and '' L. weilii.''[ The P2 clade comprises 21 species that may cause mild disease in humans. The remaining 26 species comprise the S1 and S2 subclades, which include "saprophytes" known to consume decaying matter (]saprotrophic nutrition
Saprotrophic nutrition or lysotrophic nutrition is a process of chemoheterotrophic extracellular digestion involved in the processing of decayed (dead or waste) organic matter. It occurs in saprotrophs, and is most often associated with fungi ( ...
).[ Pathogenic ''Leptospira'' do not multiply in the environment. ''Leptospira'' require high humidity for survival but can remain alive in environments such as stagnant water or contaminated soil. The bacterium can be killed by temperatures of and can be inactivated by 70% ]ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
, 1% sodium hypochlorite
Sodium hypochlorite (commonly known in a dilute solution as bleach) is an Inorganic chemistry, inorganic chemical compound with the chemical formula, formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may ...
, formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
, detergents and acids.
''Leptospira'' are also classified based on their serovar. The diverse sugar composition of the lipopolysaccharide on the surface of the bacteria is responsible for the antigenic difference between serovars.[ About 300 pathogenic serovars of ''Leptospira'' are recognised. Antigenically related serovars (belonging to the same serogroup) may belong to different species because of ]horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
of LPS biosynthetic genes between different species. Currently, the cross agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
absorption test and DNA-DNA hybridisation are used to classify ''Leptospira'' species, but are time consuming. Therefore, total genomic sequencing could potentially replace these two methods as the new gold standard of classifying ''Leptospira'' species.[
]
Transmission
The bacteria can be found in ponds, rivers, puddles, sewers, agricultural fields and moist soil. Pathogenic ''Leptospira'' have been found in the form of aquatic biofilms
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular po ...
, which may aid survival in the environment.
The number of cases of leptospirosis is directly related to the amount of rainfall, making the disease seasonal in temperate climates and year-round in tropical climates. The risk of contracting leptospirosis depends upon the risk of disease carriage in the community and the frequency of exposure. In rural areas, farming and animal husbandry are the major risk factors for contracting leptospirosis. Poor housing and inadequate sanitation also increase the risk of infection. In tropical and semi-tropical areas, the disease often becomes widespread after heavy rains or after flooding.
''Leptospira'' are found mostly in mammals. However, reptiles and cold-blooded animals such as frogs, snakes, turtles, and toads have been shown to have the infection. Whether there are reservoirs of human infection is unknown. Rats, mice, and moles are important primary hosts, but other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, swine, raccoons, opossums, and skunks can also carry the disease. In Africa, a number of wildlife hosts have been identified as carriers, including the banded mongoose
The banded mongoose (''Mungos mungo'') is a mongoose species native from the Sahel to Southern Africa. It lives in savannas, open forests and grasslands and feeds primarily on beetles and millipedes. Mongooses use various types of dens for shel ...
, Egyptian fox, Rusa deer
The Javan rusa or Sunda sambar (''Rusa timorensis'') is a deer native to Indonesia and East Timor. Introduced populations exist in a wide variety of locations in the Southern Hemisphere.
Taxonomy
Seven subspecies of the Javan rusa are recognis ...
, and shrews
Shrews (family Soricidae) are small mole-like mammals classified in the order Eulipotyphla. True shrews are not to be confused with treeshrews, otter shrews, elephant shrews, West Indies shrews, or marsupial shrews, which belong to different ...
. There are various mechanisms whereby animals can infect each other. Dogs may lick the urine of an infected animal off the grass or soil
Soil, also commonly referred to as earth or dirt, is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Some scientific definitions distinguish ''dirt'' from ''soil'' by restricting the former te ...
, or drink from an infected puddle. House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house. Leptospirosis can also be transmitted via the semen of infected animals. The duration of bacteria being consistently present in animal urine may persist for years.
Humans are the accidental host of ''Leptospira''. Humans become infected through contact with water or moist soil that contains urine from infected animals. The bacteria enter through cuts, abrasions, ingestion of contaminated food, or contact with mucous membrane
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
of the body (e.g. mouth, nose, and eyes). Occupations at risk of contracting leptospirosis include farmers, fishermen, garbage collectors and sewage workers. The disease is also related to adventure tourism
Adventure travel is a type of niche tourism, involving exploration or travel with a certain degree of risk (real or perceived), and which may require special skills and physical exertion. In the United States, adventure tourism has grown in r ...
and recreational activities. It is common among water-sports enthusiasts in specific areas, including triathlon
A triathlon is an endurance multisport race consisting of Swimming (sport), swimming, Cycle sport, cycling, and running over various distances. Triathletes compete for fastest overall completion time, racing each segment sequentially with the t ...
s, water rafting
Rafting and whitewater rafting are recreational outdoor activities which use an inflatable raft to navigate a river or other body of water. This is often done on whitewater or different degrees of rough water. Dealing with risk is often a ...
, canoeing
Canoeing is an activity which involves paddling a canoe with a single-bladed paddle. Common meanings of the term are limited to when the canoeing is the central purpose of the activity. Broader meanings include when it is combined with other acti ...
and swimming, as prolonged immersion in water promotes the entry of the bacteria. However, ''Leptospira'' are unlikely to penetrate intact skin. The disease is not known to spread between humans, and bacterial dissemination in recovery period is extremely rare in humans. Once humans are infected, bacterial shedding from the kidneys usually persists for up to 60 days.
Rarely, leptospirosis can be transmitted through an organ transplant. Infection through the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
during pregnancy is also possible. It can cause miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
and infection in infant
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
s. Leptospirosis transmission through eating raw meat of wildlife animals have also been reported (e.g. psychiatric patients with allotriophagy).
Pathogenesis
When animals ingest the bacteria, they circulate in the bloodstream, then lodge themselves into the kidneys through the glomerulular or peritubular capillaries
In the renal system, peritubular capillaries are tiny blood vessels, supplied by the efferent arteriole, that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron. Peritubular capillaries s ...
. The bacteria then pass into the lumens of the renal tubules
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
and colonise the brush border
A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and their ...
and proximal convoluted tubule
The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...
. This causes the continuous shedding of bacteria in the urine without the animal experiencing significant ill effects. This relationship between the animal and the bacteria is known as a commensal relationship
Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism (biology), mutualism, in which both o ...
, and the animal is known as a reservoir host.
Humans are the accidental host of ''Leptospira''. The pathogenesis of leptospirosis remains poorly understood despite research efforts. The bacteria enter the human body through either breaches in the skin or the mucous membrane, then into the bloodstream. The bacteria later attach to the endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
cells of the blood vessels and extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
(complex network of proteins and carbohydrates present between cells). The bacteria use their flagella for moving between cell layers. They bind to cells such as fibroblasts, macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, endothelial cells, and kidney epithelial cells. They also bind to several human proteins such as complement proteins, thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
, fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...
, and plasminogen
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
using surface leptospiral immunoglobulin-like (Lig) proteins such as LigB and LipL32, whose genes are found in all pathogenic species.
Through innate immune system, endothelial cells of the capillaries in the human body are activated by the presence of these bacteria. The endothelial cells produce cytokines
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
and antimicrobial peptides against the bacteria. These products regulate the coagulation cascade
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism ...
and movements of white blood cells.[ Macrophages presented in humans are able to engulf ''Leptospira''. However, ''Leptospira'' are able to reside and proliferate in the cytoplasmic matrix after being ingested by macrophages.][ Those with severe leptospirosis can experience a high level of cytokines such as ]interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene.
In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...
, tumor necrosis factor alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...
(TNF-α), and interleukin 10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 ...
. The high level of cytokines causes sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
-like symptoms which is life-threatening instead of helping to fight against the infection. Those who have a high risk of sepsis during a leptospirosis infection are found to have the HLA-DQ6
HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 a ...
genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
, possibly due to superantigen activation, which damages bodily organs.
''Leptospira'' LPS only activates toll-like receptor 2
Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the ''TLR2'' gene. TLR2 has also been designated as CD282 (cluster of differentiation 282). TLR2 is one of the toll-like receptors and plays a role in the immune ...
(TLR2) in monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s in humans. The lipid A molecule of the bacteria is not recognised by human TLR4
Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...
receptors. Therefore, the lack of ''Leptospira'' recognition by TLR4 receptors probably contributes to the leptospirosis disease process in humans.[
Although there are various mechanisms in the human body to fight against the bacteria, ''Leptospira'' is well adapted to such an inflammatory condition created by it. In the bloodstream, it can activate host plasminogen to become ]plasmin
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
that breaks down extracellular matrix, degrades fibrin clots and complemental proteins (C3b
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apopto ...
and C5) to avoid opsonisation. It can also recruit complement regulators such as Factor H
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at typical concentrations of 200–300 micrograms ...
, C4b-binding protein, factor H-like binding protein, and vitronectin
Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene.
Vitronectin binds to integrin alpha-V beta-3 and thus promotes ...
to prevent the activation of membrane attack complex
The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector ...
on its surface. It also secretes protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s to degrade complement proteins such as C3. It can bind to thrombin that decreases the fibrin formation. Reduced fibrin formation increases the risk of bleeding.[ ''Leptospira'' also secretes ]sphingomyelinase
Sphingomyelin phosphodiesterase (EC 3.1.4.12, also known as neutral sphingomyelinase, sphingomyelinase, or SMase; systematic name sphingomyelin cholinephosphohydrolase) is a hydrolase enzyme that is involved in sphingolipid metabolism reactions. ...
and haemolysin
Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acqu ...
that target red blood cells.
''Leptospira'' spreads rapidly to all organs through the bloodstream.[ They mainly affect the liver. They invade spaces between ]hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
s, causing apoptosis. The damaged hepatocytes and hepatocyte intercellular junctions cause leakage of bile into the bloodstream, causing elevated levels of bilirubin
Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...
, resulting in jaundice. Congested liver sinusoid
A liver sinusoid is a type of capillary known as a sinusoidal capillary, discontinuous capillary or sinusoid, that is similar to a fenestrated capillary, having discontinuous endothelium that serves as a location for mixing of the oxygen-rich blo ...
s and perisinusoidal space
The perisinusoidal space (or space of Disse) is a location in the liver between a hepatocyte and a sinusoid. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the ...
s have been reported. Meanwhile, in the lungs, petechiae or frank bleeding
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
can be found at the alveolar septum Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* Mam ...
and spaces between alveoli. ''Leptospira'' secretes toxins that cause mild to severe kidney failure or interstitial nephritis
Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules ...
. The kidney failure can recover completely or lead to atrophy and fibrosis
Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
. Rarely, inflammation of the heart muscles, coronary arteries, and aorta
The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...
are found.
Diagnosis
Laboratory tests
For those who are infected, a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
may show a high white cell count and a low platelet count. When a low haemoglobin count is present together with a low white cell count and thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
, bone marrow suppression
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity ( leukocytes), carrying oxygen ( erythrocytes), and/or those responsible for normal blood clotting ...
should be considered. Erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
and C-reactive protein
C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...
may also be elevated.
The kidneys are commonly involved in leptospirosis. Blood urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
and creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an importa ...
levels will be elevated. Leptospirosis increases potassium excretion in urine, which leads to a low potassium level and a low sodium level in the blood. Urinalysis may reveal the presence of protein, white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, and microscopic haematuria
Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
. Because the bacteria settle in the kidneys, urine cultures will be positive for leptospirosis starting after the second week of illness until 30 days of infection.
For those with liver involvement, transaminase
Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α- keto acid. They are important in the synthesis of amino acids, which form proteins.
Function and mechanism
An amino acid ...
s and direct bilirubin are elevated in liver function test
Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
s. The Icterohaemorrhagiae serogroup is associated with jaundice and elevated bilirubin levels. Hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
contributes to jaundice. A feature of leptospirosis is acute haemolytic anaemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
and conjugated hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
. Abnormal serum amylase
An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...
and lipase levels (associated with pancreatitis) are found in those who are admitted to hospital due to leptospirosis. Impaired kidney function with creatinine clearance
Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.
Functions of a healthy kidney include maintaining a person's fluid ...
less than 50 ml/min is associated with elevated pancreatic enzymes.
For those with severe headache who show signs of meningitis, a lumbar puncture
Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...
can be attempted. If infected, cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
(CSF) examination shows lymphocytic
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of gnathostomata, most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated immunity, cell-mediated, cytotoxicity, cytotoxic innate imm ...
predominance with a cell count of about 500/mm3, protein between 50 and 100 mg/ml and normal glucose levels. These findings are consistent with aseptic meningitis
Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, my ...
.
Serological tests
Rapid detection of ''Leptospira'' can be done by quantifying the IgM antibodies using an enzyme-linked immunosorbent assay (ELISA). Typically, ''L. biflexa'' antigen is used to detect the IgM antibodies. This test can quickly determine the diagnosis and help in early treatment. However, the test specificity depends upon the type of antigen used and the presence of antibodies from previous infections. The presence of other diseases such as Epstein–Barr virus
The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.
It is b ...
infection, viral hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
, and cytomegalovirus infection can cause false-positive results. Other rapid screening tests have been developed such as dipsticks, latex
Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latexes are found in nature, but synthetic latexes are common as well.
In nature, latex is found as a milky fluid found in 10% of all flowering plants (angiosperms ...
and slide agglutination tests.
The microscopic agglutination test (MAT) is the reference test for the diagnosis of leptospirosis. MAT is a test where serial dilutions of patient sera are mixed with different serovars of ''Leptospira''. The mixture is then examined under a dark field microscope to look for agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
. The highest dilution where 50% agglutination occurs is the result. MAT titres of 1:100 to 1:800 are diagnostic of leptospirosis. A fourfold or greater rise in titre of two sera taken at symptoms' onset and three to 10 days of disease onset confirms the diagnosis. During the acute phase of the disease, MAT is not specific in detecting a serotype of ''Leptospira'' because of cross-reactivity between the serovars. In the convalescent phase, MAT is more specific in detecting the serovar types. MAT requires a panel of live antigens and requires laborious work.
Molecular tests
Leptospiral DNA can be amplified by using polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) from serum, urine, aqueous humour
The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the poster ...
, CSF, and autopsy specimens. It detects the presence of bacteria faster than MAT during the first few days of infection without waiting for the appearance of antibodies. As PCR detects the presence of leptospiral DNA in the blood it is useful even when the bacteria is killed by antibiotics.
Imaging
In those who have lung involvement, a chest X-ray may demonstrate diffuse alveolar opacities.
Diagnostic criteria
In 1982, the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) proposed the Faine's criteria for the diagnosis of leptospirosis. It consists of three parts: A (clinical findings), B (epidemiological factors), and C (lab findings and bacteriological data). Since the original Faine's criteria only included culture and MAT in part C, which is difficult and complex to perform, the modified Faine's criteria was proposed in 2004 to include ELISA and slide agglutination tests which are easier to perform. In 2012, modified Faine's criteria (with amendment) was proposed to include shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
and coughing up blood in the diagnosis. In 2013, India recommended modified Faine's criteria in the diagnosis of leptospirosis.
Prevention
Rates of leptospirosis can be reduced by improving housing, infrastructure, and sanitation standards. Rodent abatement efforts and flood mitigation projects can also help to prevent it. Proper use of personal protective equipment
Personal protective equipment (PPE) is protective clothing, helmets, goggles, or other garments or equipment designed to protect the wearer's body from injury or infection. The hazards addressed by protective equipment include physical, elec ...
(PPE) by people who have a high risk of occupational exposure can prevent leptospirosis infections in most cases.
There is no human vaccine suitable for worldwide use. Only a few countries such as Cuba, Japan, France, and China have approved the use of inactivated vaccines with limited protective effects. Side effects such as nausea, injection site redness and swelling have been reported after the vaccine was injected. Since the immunity induced by one ''Leptospira''serovar is only protective against that specific one, trivalent
In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with other atoms when it forms chemical compounds or molecules.
Description
The combining capacity, or affinity of an ...
vaccines have been developed. However, they do not confer long-lasting immunity to humans or animals.[ Vaccines for other animals are more widely available.]
Doxycycline
Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
is given once a week as a prophylaxis
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
and is effective in reducing the rate of leptospirosis infections amongst high-risk individuals in flood-prone areas. In one study, it reduced the number of leptospirosis cases in military personnel undergoing exercises in the jungles. In another study, it reduced the number of symptomatic cases after exposure to leptospirosis under heavy rainfall in endemic
Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found elsew ...
areas.
Treatment
Most leptospiral cases resolve spontaneously. Early initiation of antibiotics may prevent the progression to severe disease. Therefore, in resource-limited settings, antibiotics can be started once leptospirosis is suspected after history taking and examination.
For mild leptospirosis, antibiotic recommendations such as doxycycline, azithromycin
Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
, ampicillin
Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...
and amoxicillin
Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
were based solely on ''in vitro'' testing. In 2001, the WHO recommended oral doxycycline (2 mg/kg up to 100 mg every 12 hours) for five to seven days for those with mild leptospirosis. Tetracycline
Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis.
Common side effects in ...
, ampicillin, and amoxicillin can also be used in such cases. However, in areas where rickettsia
''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The term "ricke ...
and leptospirosis are both endemic, azithromycin and doxycycline are the drugs of choice.
Based on a 1988 study, intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
(IV) benzylpenicillin
Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...
(also known as penicillin G) is recommended for the treatment of severe leptospirosis. Intravenous benzylpenicillin (30 mg/kg up to 1.2 g every six hours) is used for five to seven days. Amoxicillin, ampicillin, and erythromycin may also be used for severe cases. Ceftriaxone
Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint ...
(1 g IV every 24 hours for seven days) is also effective for severe leptospirosis. Cefotaxime
Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urin ...
(1 g IV every six hours for seven days) and doxycycline (200 mg initially followed by 100 mg IV every 12 hours for seven days) are equally effective as benzylpenicillin (1.5 million units IV every six hours for seven days). Therefore, there is no evidence on differences in death reduction when benzylpenicillin is compared with ceftriaxone or cefotaxime. Another study conducted in 2007 also showed no difference in efficacy between doxycycline (200 mg initially followed by 100 mg orally every 12 hours for seven days) or azithromycin (2 g on day one followed by 1 g daily for two more days) for suspected leptospirosis. There was no difference in the resolution of fever and azithromycin is better tolerated than doxycycline.
Outpatients are given doxycycline or azithromycin. Doxycycline can shorten the duration of leptospirosis by two days, improve symptoms, and prevent the shedding of organisms in their urine. Azithromycin and amoxicillin are given to pregnant women and children. Rarely, a Jarisch–Herxheimer reaction
A Jarisch–Herxheimer reaction is a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. Efficacious antimicrobial therapy results in lysis (destruction) of bacterial cel ...
can develop in the first few hours after antibiotic administration. However, according to a meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
done in 2012, the benefit of antibiotics in the treatment of leptospirosis was unclear although the use of antibiotics may reduce the duration of illness by two to four days. Another meta-analysis done in 2013 reached a similar conclusion.
For those with severe leptospirosis, including potassium wasting with high kidney output dysfunction, intravenous hydration and potassium supplements can prevent dehydration and hypokalemia
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
. When acute kidney failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are cla ...
occurs, early initiation of haemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatini ...
or peritoneal dialysis
Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...
can help to improve survival. For those with respiratory failure, tracheal intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic catheter, tube into the vertebrate trachea, trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer ce ...
with low tidal volume
Tidal volume (symbol VT or TV) is the volume of air moved into or out of the lungs during a normal breath. In a healthy, young human adult, tidal volume is approximately 500 ml per inspiration or 7 ml/kg of body mass.
Mechanical vent ...
improves survival rates.
Corticosteroids have been proposed to suppress inflammation in leptospirosis because ''Leptospira'' infection can induce the release of chemical signals which promote inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
of blood vessels in the lungs. However, there is insufficient evidence to determine whether the use of corticosteroids is beneficial.
Prognosis
The overall risk of death for leptospirosis is 5–10%. For those with jaundice, the case fatality can increase up to 15%. For those infected who present with confusion and neurological signs, there is a high risk of death. Other factors that increase the risk of death include reduced urine output, age more than 36 years, and respiratory failure. With proper care, most of those infected will recover completely. Those with acute kidney failure may develop persistent mild kidney impairment after they recover. In those with severe lung involvement, the risk of death is 50–70%. Thirty percent of people with acute leptospirosis complained of long-lasting symptoms characterised by weakness, muscle pain, and headaches.
Eye complications
Eye problems can occur in 10% of those who recovered from leptospirosis in the range from two weeks to a few years post-infection. Most commonly, eye complications can occur at six months after the infection. This is due to the immune privilege
Certain sites of the mammalian body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Tissue grafts are normally recognised as foreign antigen by the body and ...
of the eye which protects it from immunological damage during the initial phase of leptospiral infection. These complications can range from mild anterior uveitis to severe panuveitis (which involves all three vascular layers of the eye). The uveitis is more commonly happen in young to a middle-aged man and those working in agricultural farming. In up to 80% of those infected, ''Leptospira'' DNA can be found in the aqueous humour of the eye. Eye problems usually have a good prognosis following treatment or they are self-limiting. In anterior uveitis, only topical steroids and mydriatics (an agent that causes dilation of the pupil) are needed while in panuveitis, it requires periocular corticosteroids. Leptospiral uveitis is characterised by hypopyon, rapidly maturing cataract, free floating vitreous membranes, disc hyperemia and retinal vasculitis.
Epidemiology
It is estimated that one million severe cases of leptospirosis occur annually, with 58,900 deaths. Severe cases account for 5–15% of all leptospirosis cases.[ Leptospirosis is found in both urban and rural areas in ]tropical
The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in
the Southern Hemisphere at S. The tropics are also referred to ...
, subtropical
The subtropical zones or subtropics are geographical zone, geographical and Köppen climate classification, climate zones to the Northern Hemisphere, north and Southern Hemisphere, south of the tropics. Geographically part of the Geographical z ...
, and temperate
In geography, the temperate climates of Earth occur in the middle latitudes (23.5° to 66.5° N/S of Equator), which span between the tropics and the polar regions of Earth. These zones generally have wider temperature ranges throughout t ...
regions. The global health burden for leptospirosis can be measured by disability-adjusted life year
The disability-adjusted life year (DALY) is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death. It was developed in the 1990s as a way of comparing the overall health and life ex ...
(DALY). The score is 42 per 100,000 people per year, which is more than other diseases such as rabies
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, vi ...
and filariasis
Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases.
These ...
.
The disease is observed persistently in parts of Asia, Oceania, the Caribbean, Latin America and Africa. Antarctica
Antarctica () is Earth's southernmost and least-populated continent. Situated almost entirely south of the Antarctic Circle and surrounded by the Southern Ocean, it contains the geographic South Pole. Antarctica is the fifth-largest contine ...
is the only place not affected by leptospirosis. In the United States, there were 100 to 150 leptospirosis cases annually. In 1994, leptospirosis ceased to be a notifiable disease in the United States except in 36 states/territories where it is prevalent such as Hawaii, Texas, California, and Puerto Rico. About 50% of the reported cases occurred in Puerto Rico. In January 2013, leptospirosis was reinstated as a nationally notifiable disease in the United States. Research on epidemiology of leptospirosis in high-risk groups and risk factors is limited in India.
The global rates of leptospirosis have been underestimated because most affected countries lack notification or notification is not mandatory. Distinguishing clinical signs of leptospirosis from other diseases and lack of laboratory diagnostic services are other problems. The socioeconomic status of many of the world's population is closely tied to malnutrition; subsequent lack of micronutrients
Micronutrients are essential dietary elements required by organisms in varying quantities throughout life to orchestrate a range of physiological functions to maintain health. Micronutrient requirements differ between organisms; for example, huma ...
may lead to increased risk of infection and death due to leptospirosis infection. Micronutrients such as iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
, calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
, and magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
represent important areas for future research.
History
The disease was first described by Adolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice, and nephritis
Nephritis is inflammation of the kidneys and may involve the glomeruli, tubules, or interstitial tissue surrounding the glomeruli and tubules. It is one of several different types of nephropathy.
Types
* Glomerulonephritis is inflammation of th ...
." Before Weil's description, the disease was known as "rice field jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
" in ancient Chinese text, "autumn fever", "seven-day fever", and "''nanukayami'' fever" in Japan; in Europe and Australia, the disease was associated with certain occupations and given names such as "cane-cutter's disease", "swine-herd's disease", and "''Schlammfieber''" (mud fever). It has been known historically as "black jaundice", or "dairy farm fever" in New Zealand. Leptospirosis was postulated as the cause of an epidemic among Native Americans along the coast of what is now New England
New England is a region comprising six states in the Northeastern United States: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont. It is bordered by the state of New York to the west and by the Canadian provinces ...
during 1616–19. The disease was most likely brought to the New World
The term ''New World'' is often used to mean the majority of Earth's Western Hemisphere, specifically the Americas."America." ''The Oxford Companion to the English Language'' (). McArthur, Tom, ed., 1992. New York: Oxford University Press, p. 3 ...
by Europeans.
''Leptospira'' was first observed in 1907 in a post mortem
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any dis ...
kidney tissue slice by Arthur Stimson using silver deposition staining technique. He called the organism ''Spirocheta interrogans'' because the bacteria resembled a question mark. In 1908, a Japanese research group led by Ryukichi Inada
was a Japanese physician, a prominent academic, and bacteriologist researcher. He was the discoverer of the Weil's disease pathogen. In addition to his life's work in early 20th-century Japanese medical education, he was a pioneer in Japanese ...
and Yutaka Ito first identified this bacterium as the causative agent of leptospirosis and noted its presence in rats in 1916. Japanese coal mine workers frequently contracted leptospirosis. In Japan, the organism was named ''Spirocheta icterohaemorrhagiae''. The Japanese group also experimented with the first leptospiral immunisation studies in guinea pigs. They demonstrated that by injecting the infected guinea pig
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus ''Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ani ...
s with sera from convalescent humans or goats, passive immunity Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when hi ...
could be provided to the guinea pigs. In 1917, the Japanese group discovered rats as the carriers of leptospirosis. Unaware of the Japanese group's work, two German groups independently and almost simultaneously published their first demonstration of transmitting leptospiral infection in guinea pigs in October 1915. They named the organism ''Spirochaeta nodosa'' and ''Spirochaeta Icterogenes'' respectively.
Leptospirosis was subsequently recognised as a disease of all mammalian species. In 1933, Dutch workers reported the isolation of ''Leptospira canicola'' which specifically infects dogs. In 1940, the strain that specifically infects cattle was first reported in Russia. In 1942, soldiers at Fort Bragg
Fort Bragg is a military installation of the United States Army in North Carolina, and is one of the largest military installations in the world by population, with around 54,000 military personnel. The military reservation is located within Cum ...
, North Carolina
North Carolina () is a state in the Southeastern region of the United States. The state is the 28th largest and 9th-most populous of the United States. It is bordered by Virginia to the north, the Atlantic Ocean to the east, Georgia and So ...
, were recorded to have an infectious disease which caused a rash over their shinbone
The tibia (; ), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outside of the tibia); it connects ...
s. This disease was later known to be caused by leptospirosis. By the 1950s, the number of serovars that infected various mammals had expanded significantly. In the 1980s, leptospirosis was recognised as a veterinary disease of major economic importance.
In 1982, there were about 200 serovars of ''Leptospira'' available for classification. The International Committee on Systematic Bacteriology The International Committee on Systematics of Prokaryotes (ICSP), formerly the International Committee on Systematic Bacteriology (ICSB), is the body that oversees the nomenclature of prokaryotes, determines the rules by which prokaryotes are named ...
's subcommittee on taxonomy of ''Leptospira'' proposed classifying these serovars into two big groups: ''L. interrogans'' containing pathogenic serovars and ''L. biflexa'' containing saprophytic serovars. In 1979, the leptospiral family of ''Leptospiraceae'' was proposed. In the same year, ''Leptospira illini'' was reclassified as the new genus ''Leptonema''. In 2002, "Lepthangamushi syndrome" was coined to describe a series of overlapping symptoms of leptospirosis with Hantavirus hemorrhagic fever with renal syndrome
Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by species of hantaviruses. It is also known as Korean hemorrhagic fever and epidemic hemorrhagic fever. It is found in Europe, Asia, and A ...
, and scrub typhus
Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite '' Orientia tsutsugamushi'', a Gram-negative α-proteobacterium of family Rickettsiaceae first isolated and identified in 1930 in Japan.[Orientia tsutsugamushi
''Orientia tsutsugamushi'' (from Japanese ''tsutsuga'' meaning "illness", and ''mushi'' meaning "insect") is a mite-borne bacterium belonging to the family Rickettsiaceae and is responsible for a disease called scrub typhus in humans. It is a ...]
''. In 2005, ''Leptospira parva'' was classified as ''Turneriella''. With DNA-DNA hybridisation technology, ''L. interrogans'' was divided into seven species. More ''Leptospira'' species have been discovered since then. The WHO established the Leptospirosis Burden Epidemiology Reference Group (LERG) to review the latest disease epidemiological data of leptospirosis, formulate a disease transmission model, and identify gaps in knowledge and research. The first meeting was convened in 2009. In 2011, LERG estimated that the global yearly rate of leptospirosis is five to 14 cases per 100,000 population.
Other animals
Infected animals can have no, mild, or severe symptoms; the presenting symptoms may vary by the type of animal. In some animals the bacteria live in the reproductive tract, leading to transmission during mating.
Animals also present with similar clinical features when compared to humans. Clinical signs can appear in 5–15 days in dogs. The incubation period can be prolonged in cats. Leptospirosis can cause abortions after 2–12 weeks in cattle, and 1–4 weeks of infection in pigs. The illness tends to be milder in reservoir hosts. The most commonly affected organs are the kidneys, liver, and reproductive system, but other organs can be affected. In dogs, the acute clinical signs include fever, loss of appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
, shivering, muscle pain, weakness, and urinary symptoms. Vomiting, diarrhea, and abdominal pain may also present. Petechiae and ecchymoses may be seen on mucous membranes. Bleeding from the lungs may also be seen in dogs. In chronic presentations, the affected dog may have no symptoms. In animals that have died of leptospirosis, their kidneys may be swollen with grey and white spots, mottling
Mottle is a pattern of irregular marks, spots, streaks, blotches or patches of different shades or colours. It is commonly used to describe the surface of plants or the skin of animals. In plants, mottling usually consists of yellowish spots o ...
, or scarring. Their liver may be enlarged with areas of cell death
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as d ...
. Petechiae and ecchymoses may be found in various organs. Inflammation of the blood vessels, inflammation of the heart, meningeal layers covering the brain and spinal cord, and uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
are also possible. Equine recurrent uveitis
Equine recurrent uveitis (ERU) – also known as moon blindness, recurrent iridocyclitis, or periodic ophthalmia – is an acute, nongranulomatous inflammation of the uveal tract of the eye, occurring commonly in horses of all breeds, w ...
(ERU) is the most common disease associated with ''Leptospira'' infection in horses in North America and may lead to blindness. ERU is an autoimmune disease involving antibodies against ''Leptospira'' proteins LruA and LruB cross-reacting with eye proteins. Live ''Leptospira'' can be recovered from the aqueous or vitreous fluid of many horses with ''Leptospira''-associated ERU. Risk of death or disability in infected animals varies depending upon the species and age of the animals. In adult pigs and cattle, reproductive signs are the most common signs of leptospirosis. Up to 40% of cows may have a spontaneous abortion. Younger animals usually develop more severe disease. About 80% of dogs can survive with treatment, but the survival rate is reduced if the lungs are involved.
ELISA and microscopic agglutination tests are most commonly used to diagnose leptospirosis in animals. The bacteria can be detected in blood, urine, and milk or liver, kidney, or other tissue samples by using immunofluorescence or immunohistochemical
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...
or polymerase chain reaction techniques. Silver staining or immunogold silver staining is used to detect ''Leptospira'' in tissue sections. The organisms stain poorly with Gram stain
In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish ...
. Dark-field microscopy can be used to detect ''Leptospira'' in body fluids, but it is neither sensitive nor specific in detecting the organism. A positive culture for leptospirosis is definitive, but the availability is limited, and culture results can take 13–26 weeks for a result, limiting its utility. Paired acute and convalescent samples are preferred for serological diagnosis of leptospirosis in animals. A positive serological sample from an aborted fetus is also diagnostic of leptospirosis.
Various antibiotics such as doxycycline, penicillins, dihydrostreptomycin, and streptomycin
Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, ''Mycobacterium avium'' complex, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever. Fo ...
have been used to treat leptospirosis in animals. Fluid therapy, blood transfusion, and respiratory support may be required in severe disease. For horses with ERU, the primary treatment is with anti-inflammatory drugs.
Leptospirosis vaccines are available for animals such as pigs, dogs, cattle, sheep, and goats. Vaccines for cattle usually contain ''Leptospira'' serovar Hardjo and Pomona, for dogs, the vaccines usually contain serovar Icterohaemorrhagiae and Canicola. Vaccines containing multiple serovars do not work for cattle as well as vaccines containing a single serovar, yet the multivalent vaccines continue to be sold. Isolation of infected animals and prophylactic antibiotics are also effective in preventing leptospirosis transmission between animals. Environmental control and sanitation also reduce transmission rates.
References
External links
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