A closer look at leptospirosis (Part 2)

Last month’s Part 1 of the leptospirosis review, which addressed the etiology, geographic distribution, transmission, infection reservoir and infection in humans, included some information on the recent leptospirosis epidemic in flooded territories of the Philippines. As of Oct. 26, 2,158 cases – including 167 deaths – were recorded. On Nov. 16, WHO reported that the number of cases increased to 3,382 individuals, with an estimate of 249 deaths. To compare, during all of 2008, 769 cases were reported throughout the Philippines.

The Filipino government and the humanitarian community had distributed leptospirosis prophylaxis to nearly 338,000 individuals in the National Capital Region as of Nov. 16. This has become the world’s second largest leptospirosis epidemic on record, the largest being the 2008 Sri Lanka post-flooding outbreak (4,500 cases, of which 1,150 reportedly were fatal).

The WHO-coordinated Global Outbreak Alert and Response Network (GOARN), a pool of experts on permanent standby to identify, respond and assist with disease outbreaks around the world, presented in mid-November the results from its three-week technical assessment of the leptospirosis situation in the Philippines. It reported that the GOARN lab continued the testing of leptospirosis samples from infected patients in the Philippines to determine the particular disease strain. According to the GOARN experts, the testing requires significant time and effort due to the fragility of the samples and the complicated nature of the disease.

Infections in animals

All mammals appear to be susceptible to at least one species of Leptospira. Disease is rare in cats and less common in sheep than cattle.

Serovars associated with disease in cattle include L. hardjo, L. pomona, L. grippotyphosa, L. canicola and L. icterohaemorrhagiae. In sheep and goats, serovars associated with disease include L. hardjo, L. pomona, L. grippotyphosa and L. ballum. Serovars associated with disease in pigs include L. pomona, L. grippotyphosa, L. bratislava, L. canicola, L. icterohaemorrhagiae, L. tarassovi and L. muenchen. Serovars associated with disease in horses include L. hardjo, L. pomona, L. canicola, L. icterohaemorrhagiae and L. sejroe. In dogs, the serovars associated with the disease include L. pomona, L. grippotyphosa, L. canicola, L. icterohaemorrhagiae, L. pyrogenes, L. paidjan, L. tarassovi, L. ballum and L. bratislava.

The risk of infection is highest in hunting dogs, show dogs and dogs with access to water such as ponds. The severity of disease is affected by the dog’s age, previous leptospirosis vaccinations and the serovar, route of exposure and dose of organisms.

The primary reservoir hosts for most Leptospira serovars are wild mammals, particularly rodents. Reservoir hosts among domestic animals include cattle, pigs, sheep and dogs.

The specific reservoir hosts vary with the serovar and the geographic region. Disease in reservoir hosts is more likely to be asymptomatic, mild or chronic. Reservoir hosts include:

• Rats serogroups: L. icterohaemorrhagiae and L. ballum;
• Mice serogroup: L. ballum;
• Cattle serovars: L. hardjo, L. grippotyphosa and L. pomona;
• Sheep serovars: L. hardjo and L. pomona;
• Pigs serovars: L. pomona, L. tarassovi and L. bratislava
• Dogs serovars: L. canicola and L. bataviae.

The incubation period is four to 12 days in dogs. Abortions usually occur three to 10 weeks after infection in cattle and 15 to 30 days after infection in pigs.

Clinical signs

Leptospira infections may be asymptomatic, mild or severe and acute or chronic. The clinical signs are often related to kidney disease, liver disease or reproductive dysfunction. Chronically-infected animals are often asymptomatic.

In cattle, acute leptospirosis occurs mainly in calves. The symptoms may include fever, anorexia, conjunctivitis, diarrhea and, in severe cases, jaundice, hemoglobinuria, anemia, pneumonia or signs of meningitis. Some calves may die within three to five days. The clinical signs vary with the serovar. Infections with serovar L. hardjo, for example, are not usually associated with hemolytic anemia. In adult cattle, the most prominent signs of infection are abortions, decreased fertility or decreased milk yield. Some serovars also cause increased neonatal mortality; others can cause sudden agalactia or decreased milk production; the milk may be thick, yellow and blood-tinged but there is typically little evidence of mammary inflammation.

In swine, clinical leptospirosis is most often characterized by reproductive signs, including late-term abortions, infertility, stillbirths, mummified or macerated fetuses and increased neonatal mortality. Subclinical infections are common. In piglets, there may be fever, anorexia, depression, diarrhea, jaundice, hemoglobinuria and gastrointestinal disorders, as well as signs of meningitis.

In horses, many infections are subclinical. Ocular disease is the most common syndrome. During the acute phase, ocular signs may include fever, photophobia, conjunctivitis, miosis and iritis. Periodic ophthalmia may be sequelae of acute infections. In the chronic phase, there may be anterior and posterior adhesions of the eye, a turbid vitreous body, cataracts, uveitis and other ocular abnormalities.

Canine leptospirosis is clinically highly variable. Some infections are asymptomatic or mild, while others are severe or fatal. The initial signs are usually nonspecific and may include fever, depression, anorexia, stiffness, myalgia, shivering and weakness. The mucus membranes are often injected. These symptoms may be followed by signs of kidney disease, including anuria, hematuria, polyuria, vomiting, dehydration and oral ulceration. Hemorrhagic syndromes occur in some dogs; some die peracutely without clinical signs. Chronic kidney disease can be a sequela.

In dogs, the serovar L. icterohaemorrhagiae usually causes fever, hemorrhage, anemia and jaundice. L. grippotyphosa tends to cause severe acute kidney failure and/or chronic active hepatitis. Dogs infected with serovar L. pomona are often asymptomatic and chronic carriers; serovar L. canicola often causes chronic interstitial nephritis.

Leptospira spp. are shed in the urine of acutely infected animals. Chronic carriers may excrete them for months or years. In addition, organisms can be found in aborted or stillborn fetuses, as well as in normal fetuses or vaginal discharges after calving. Rarely, leptospira is transmitted through rodent bites.

Leptospirosis can be diagnosed by culture, detection of antigens or nucleic acids, or serology. The location of the organisms varies with the form of the disease. In acute infections, Leptospira may be found in the blood, milk, and cerebrospinal, thoracic or peritoneal fluids. During chronic infections, they are sometimes found in the urine. The liver, lung, brain and kidney are collected at necropsy from acute cases, and the kidney and genital tract are tested in chronic cases. Organisms can also be found in the body fluids or tissues of aborted fetuses.

Leptospira species can be cultured on a variety of media but are fastidious and grow slowly on primary isolation. Special transport media may be required for shipment to the laboratory. Depending on the serovar, culture may take up to 13 to 26 weeks. Identification to the species, serogroup and serovar level is done by reference laboratories, using genetic and immunologic techniques. Leptospira can also be identified in clinical samples by immunofluorescence and immunhistochemical staining, as well as DNA probes and polymerase chain reaction techniques. Silver staining is sometimes useful as an adjunct technique. Antigen- detection techniques include enzyme-linked immunosorbent assays.

Serology is also used for diagnosis. Paired acute and convalescent samples are preferred from most animals, but a single positive sample from an aborted fetus is diagnostic.

Herd tests are often used in ruminants. The most commonly used serological tests are the microscopic agglutination test and ELISAs. Serovar-specific ELISAs are available in veterinary medicine, and cross-reactions are less common in animals than in humans.

A milk ELISA can detect antibodies in samples from individual cows or in bulk milk. Titers may become undetectable in chronically-infected dogs that are still shedding organisms.

Prevention

Leptospirosis vaccines are available for pigs, cattle and dogs. Although the vaccines prevent disease, they do not completely prevent infection or the shedding of the organisms.

Immunity is largely serovar specific: vaccines are protective only against the included serovars or closely related serovars. Prophylactic treatment of exposed animals with antibiotics can also prevent disease.

Sanitation and preventing contact with contaminated environments or infected wildlife, particularly rodents, can decrease infection. Animals should not be allowed to drink from or enter contaminated water. Good sanitation can reduce the risk of infection in kennels and in areas where livestock are bred or give birth.

In cattle, control measures include vaccination, isolation and treatment of infected animals, rodent control, prevention of contact with wildlife, sheep and pigs, and prevention of access to contaminated bodies of water.

Preventive treatment of animals with streptomycine before their export or to their introduction into other herds has been practiced by many countries as a standard requirement.

To read Part 1 of this column, click here.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.