Leptospirosis

G. B. VAN NESS AND C. A. MANTHEI.

LEPTOSPIROSIS was first described as a disease of man. Leptospira, which cause it, once were considered the cause of yellow fever, because jaundice occurs in both diseases. When mosquito-transmitted virus was found to be the cause of yellow fever, interest in Leptospira declined. Leptospirosis is a problem where carriers of the infection are found. The chance of spreading the disease is increased if animals have access to contaminated water.

Leptospira differ from other causes of infectious disease. They are parasites that have no surface covering.

They have freely moving ends with no flagella. They move by a corkscrew motion of the ends of the cell. They have been confused with true viruses because of their resistance to bacterial stains, failure to grow on the standard laboratory media, filter-ability, and growth in embryonated eggs. Leptospira can be readily demonstrated by using Giemsa's stain and silver preparations or by outlining the organisms with India ink. The motility of Leptospira as seen through the dark-field microscope is the most reliable means of differentiating them from protoplasmic strands and other artifacts.

Leptospira are separated into serotypes by serological tests, because size, biochemical activity, and the nutrient requirements are not reliable means of identification. Detailed studies are necessary to identify them. Because specific antiserums and known serotypes must be maintained in the laboratory for comparison, laboratory centers primarily interested in leptospirosis have been set up.

The extent of leptospirosis and the number of animal species affected in the United States are not known. Leptospira are found most commonly in rodents, from which infection can spread to man or domestic animals.

Weil's disease in man is due to Leptospira carried by the Norway rat. Harvest fever, ricefield fever, and mud fever are other leptospiral infections transmitted from mice and moles to man. Dogs may become infected from rodents, particularly rats, and cattle in the United States have antibodies in their blood for Leptospira sejroe, roe, an organism found in field mice.

Two serotypes commonly produce infection in domestic animals in this country. L. canicola occurs in dogs and can be transmitted to man and cattle. L. Pomona is found in swine and cattle, and infection may occur in horses and men. Carriers disseminate Leptospira through the urine. Animals can become infected by splashed urine and by eating and drinking contaminated feed and water. The Leptospira usually gain entrance to the body through abrasions of the skin and the mucous membranes of the mouth, nose, and eyes.

IN CATTLE, leptospirosis can vary from a mild to a severe infection, which may be followed by death. Fever and loss of appetite may last for several days and usually do not recur, although infection is still present. Discoloration of the urine with blood may vary from a mild pink to deep red or almost black. Anemia may occur as a result of loss of blood. Milk production drops or ceases. The milk becomes yellowish and like colostrum and may be tinged with blood. The udder may become flaccid or hardened, but not inflamed. The return to normal production may take several weeks.

Abortions may occur at any stage of pregnancy, but they usually occur in the last one-third. Full-term calves may be dead or weak. The afterbirth and the umbilical cord are often enlarged and edematous. Stunting of young animals, unthriftiness, and debility are symptoms of chronic leptospirosis.

The most frequent cause of bovine leptospirosis is L. Pomona, but two other serotypes have been associated with the disease of cattle in this country.

IN SWINE, leptospirosis is not a new problem. Early investigators encountered an organism like Leptospira in their study of hog cholera, which is caused by a virus. Leptospirosis, however, was first reported in the United States in 1952.

Symptoms in hogs may vary from mild icterus and slow gains in weight to pronounced nervous and digestive disturbances. Poor appetite, fever, frequent urination, mild conjunctivitis, weakness of the hind legs, stiffness, and drowsiness occur in varying degrees in infected herds. Leptospirosis may be responsible for serious losses from abortions and death of newborn pigs. Icterus and anemia may lead to condemnation of slaughtered hogs. The most common cause of the disease in swine is L. Pomona.

IN SHEEP AND GOATS, leptospirosis resembles leptospirosis in cows.

Information regarding the disease of these animals in the United States is limited, but the development of jaundice should suggest the presence of leptospirosis.

CANINE INFECTION is widespread. Many cases are accompanied by visible disease. Muscular stiffness, thirst, vomiting, dehydration, weakness, and constipation or bloody diarrhea are seen.

Most cases develop uremic symptoms, with a foul or an ammoniacal breath, icterus, tucked-in abdomen, and arched back.

Infected dogs may shed large numbers of Leptospira in the urine.

IN THE HORSE, general symptoms of leptospirosis may be lacking, but an eye condition may be a prominent feature. It has been suggested that the condition called periodic ophthalmia in horses is due entirely to leptospirosis.

The eyes are frequently affected in leptospirosis. The mucous lining of the eyelid and the white of the eyeball are reddened, and the blood vessels are enlarged. The eyeball itself can become involved. The anterior chamber of the eye can be the site of leptospiral multiplication. Hemorrhage may occur from weakened blood vessels. More permanent injury may develop.

DIAGNOSIS of leptospirosis is made by isolating the organism or by the testing of serum for the presence of antibodies produced by the infection. A definite diagnosis can be made only by demonstration of the causative organism. It is hard to do that because only a few Leptospira usually are found in the blood and because of the difficulty of separating Leptospira from the contaminating organisms in the urine. After death, Leptospira tend to be destroyed by decomposition of tissue. Most isolations are made from susceptible laboratory animals that have been injected with tissue from suspected cases.

A tentative diagnosis can be made with the serological tests on two or more serum samples, taken periodically from the time of onset of disease. To make the tests, it is desirable to have a stock-culture collection of known Leptospira. Thirty or more serotypes are now recognized, and new ones may be found.

Workers with leptospirosis in livestock in the United States must consider the possibility of infection with at least these five serotypes: Leptospira Pomona, L. icterohaemorrhagiae, L. grippotyphosa, L. canicola, and L. sejroe.

THE AGGLUTINATION-LYSIS TEST generally is considered the standard test for the detection of leptospirosis. Its chief advantage is that the serotype involved usually can be identified. When live cultures of Leptospira are mixed with dilutions of serum from animals affected with a similar serotype, they are clumped together and lysed, so that the mixture is freed of organisms. Even very high dilutions of sera of recovered animals may have this property, and it can persist for several years after the infection occurred. The test is read by the use of the dark-field microscope. Some of the clumps of organisms are large enough to be seen with the unaided eye. The number of organisms must be sufficient to make the reading of the test relatively easy. Experience in interpretation is necessary, as Leptospira have the peculiar property of tangling themselves into masses, brought about by changes not associated with infection. Agglutinated Leptospira lose their individual cellular identity before lysis and become granular masses. Because living organisms are employed, care must be taken by laboratory workers to prevent exposure of themselves and others.

The complement-fixation test is a reliable means of detecting leptospiral infections employing Leptospira that have been washed and killed, egg-propagated Leptospira, or Leptospira cultures that have been sonic vibrated. The complement-fixation reaction may not persist so long as the agglutination-lysis reaction. The complement-fixation test is also less specific in identifying the serotype causing the infection.

Plate and tube macroscopic agglutination tests, which make use of killed Leptospira, have been described by several investigators. The main advantages of these tests are the safety (as compared with the live antigens used in the agglutination-lysis test) and the greater serotype specificity over that of the complement-fixation test.

Also, they have the most practical application under average diagnostic laboratory conditions. The greatest disadvantage is production of amounts of uniform antigens economically.

Most efforts to treat animals affected with leptospirosis have been for the purpose of alleviating symptoms. Various antibiotics have been employed,and of these Terramycin and dihydrostreptomycin appear to be of value in reducing urinary discharge of organisms.

Vaccination for leptospirosis was in the experimental stage in 1956. The experimental results have been promising, but the natural course of the disease in outbreaks is frequently followed by a disappearance of symptoms without the use of any corrective measures.

Control of leptospirosis is hampered by a lack of fundamental knowledge of the disease. For example, any successful program must depend on a source of Leptospira-free replacements and identification of the carrier animals. Because Leptospira transfer readily in large, closely confined herds, isolation into small units has a tendency to reduce the chance of spread. Damp, low ground and slow streams and ponds favor spread of the infection.

The application of serological tests on a herd basis, repeated at regular intervals, will indicate the extent of infection in the herd. Practical segregation and sanitary measures for the individual farm should be applied when indicated. The idea that all the animals exposed to infection become immune is a dangerous one, because it does not take into account that some become carriers of the causative agent.

The meaning of leptospirosis to the health of the community cannot be disregarded. Persons who have contact with infected animals and contaminated materials may contract the disease. Streams draining from infected premises may carry the organisms for several miles and be a potential source of infection.

G. B. VAN NESS has been engaged in research on animal diseases in the Animal Disease and Parasite Research Branch, at Beltsville, Md., since 1953.

C. A. MANTHEI became head of the Bacterial and Mycotic Diseases Section of the Animal Disease and Parasite Research Branch in 1954. He has been engaged in animal disease research since 1938.