A closer look at leptospirosis (Part 1)

Tropical Storm Ondoy’s heavy rains on Sept. 24, caused massive flooding in the Philippines’ National Capital Region and its nearby provinces Rizal and Laguna. A major leptopspirosis outbreak followed.

As of Oct. 26, the statistics gathered by the Department of Health showed 2,158 cases, including 167 deaths, a threefold increase from the 769 cases monitored by the health department nationwide for the whole of 2008. According to the information available from Gideon (Global Infectious Disease & Epidemiology Network), 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 fatal).

Leptospirosis is a serious bacterial zoonosis, present in man and mammals in most countries of the world, with particular impact in under-developed countries. In major outbreaks, it is commonly transmitted in floodwaters tainted by the urine of rats and other animals; patients are infected by swallowing or by absorbing contaminated water through cuts in the skin. In developed countries, one of the main risks of infection may now be from animals imported from countries and regions where leptospirosis is endemic. The disease in animals is OIE-listed. In the United States, leptospirosis is no longer a reportable disease: according to the CDC, 100 to 200 cases are identified annually with about 50% of cases occurring in Hawaii. The largest recorded outbreak in the continental United States, affecting 110 patients in a group of 775 exposed people who participated in triathlons, that included swimming in a lake, occurred in June and July 1998. Although incidence in the United States is relatively low, leptospirosis is considered to be one of the three most widespread zoonotic disease in the world.

Etiology

Leptospirosis is caused by various species of Leptospira, a spirochete in the family Leptospiraceae, order Spirochaetales. The classification of this organism is complex. The basic taxon of these organisms is the serovar, which is identified on the basis of cross-absorption agglutination reactions with specific antisera.

Before 1989, all of the pathogenic isolates belonged to the species Leptospira interrogans, which contained more than 200 serovars in 23 serogroups. More recently, the genus Leptospira has been reclassified into 16 or more species. Pathogenic serovars are now found in the species Leptospira interrogans, L. noguchii, L. santarosai, L. meyeri, L. borgpetersenii, L. kirschneri, L. weilii, L. inadai, L. fainei and L. alexanderi. The new classification system can be confusing because both pathogenic and non-pathogenic serovars and serogroups occur in the same species and a single serovar or serogroup can occur within multiple species. In clinical laboratories, the older serogroup/serovar classification is often still used.

Geographic distribution

Leptospira species are found worldwide; however, the predominant serovars vary by geographic region. Only relatively small numbers of serovars are endemic in any geographic location and these tend to be maintained in specific species hosts. The most common serovars in the United States are L. canicola, grippotyphosa, hardjo, icterohaemorrhagiae and pomona.

Leptospirosis can be transmitted either directly between hosts or indirectly in the environment. Leptospira spp. can be ingested in contaminated food or water, spread in aerosolized urine or water, or transmitted by direct contact with the skin. The organisms usually enter the body through mucous membranes or abraded skin. They may also be able to penetrate intact skin that has been immersed for a long time in water. Leptospira spp. are excreted in the urine and can be found in aborted or stillborn fetuses, as well as in normal fetuses or vaginal discharges after calving. They can be isolated from the male reproductive organs. Infections from rodent bites and after laboratory accidents have been recorded. Human-to-human transmission is rare – reportedly transmitted during sexual intercourse and by breast feeding.

Leptospira spp. do not multiply outside the host. In the environment, they require high humidity for survival and are killed by dehydration or temperatures greater than 50¡C. They can remain viable for a few to many weeks or months in contaminated soil and for several weeks in cattle slurry. They can remain viable in water for several months under laboratory conditions, but do not survive as well in river water under natural conditions.

Infection reservoir

A wide variety of animal species, primarily mammals, may serve as sources of human infection. The most important in this context are considered to be:

• small mammal species, notably feral and peridomestic rodents (rats, mice, voles, etc.) and insectivores (shrews and hedgehogs);
• domestic animals (cattle, pigs, dogs, more rarely sheep, goats, horses and buffaloes).

Rodents have been recognized to be the most important and widely distributed reservoirs of leptospiral infection. An animal is definitely a carrier of leptospira only if the organism can be cultured from it, particularly from the urine or the kidney. As animals may carry leptospirae in their kidneys and shed them with their urine, caution is always necessary in handling animals, and they should be considered potential sources of infection until proven otherwise.

All mammals appear to be susceptible to at least one species of Leptospira. Infections with leptospirae are maintained within a population of natural maintenance hosts by vertical and horizontal transmission. Such a population of a natural animal host species forms the infection reservoir.

The natural maintenance host ensures the continuous circulation of a particular leptospiral serovar in a geographical area (natural focus) without the need for other, incidental hosts to be involved. Natural maintenance hosts may carry a particular strain of Leptospira in their kidneys and shed them with their urine for long periods, and sometimes for the lifespan of the animal. Many Leptospira strains appear to be so well adapted to their natural hosts that the infection remains subclinical. In each specific area, the risk of human infection will vary depending on the chance of direct or indirect contact with the urine of one of the maintenance hosts. In addition to these long-term maintenance hosts, any infected animal can be a source of infection to other individuals of its own kind or to other species, including humans.

Infections in humans

Human infections vary from asymptomatic to severe. Many cases are mild or asymptomatic, and go unrecognized. Some serovars tend to be associated more often with some syndromes (eg, severe disease is often associated with serovar icterohaemorrhagiae). However, any serovar can cause any syndrome.

The incubation period in humans is usually seven to 12 days, with a range of two to 29 days. The disease is usually biphasic; the first, septicemic phase, lasts for approximately four to nine days, typically followed by a one to three day of improvement period that is followed by the second, "immune" phase, during which the patient becomes ill again. This phase may last 30 days or more but does not develop in all patients.

Two forms of disease, icteric and anicteric, are seen. Most infections are of the anicteric form, typically associated with aseptic meningitis. Deaths are rare in the typical anicteric form; however, a syndrome of fatal pulmonary hemorrhage, without jaundice, has recently been reported.

The icteric form is more severe. It occurs in 5% to 10% of all patients, is often rapidly progressive and may be associated with multiorgan failure. The most commonly involved organ systems are the liver, kidneys and CNS. In the icteric form, there may be no improvement between the septicemic and immune phases. Acute renal failure occurs in 16% to 40% of cases. Some patients also have pulmonary symptoms. Cardiac involvement can result in congestive heart failure, myocarditis and pericarditis. Hemorrhages may also be seen; severe gastrointestinal bleeding, adrenal or subarachnoid hemorrhage, and pulmonary hemorrhages can occur. Convalescence from the icteric form may take one to two months. Hepatic disease is rarely the cause of death. Most patients also recover kidney function. Anterior uveitis occurs up to a year after recovery in 2% to 10% of cases, but most of these patients recover full vision.

The second part of this review will address animal leptospirosis, diagnostic methods, prevention and control measures.

Bharti A, et al. Leptospirosis: A zoonotic disease of global importance (A review). Lancet Infect Dis. 2003;3:757–771.

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.