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Pharmalicensing
is a division of
UTEK Europe Ltd
UTEK Corporation
Articles

Pharmalicensing brings you advice, commentary and analysis from industry experts.

A Tour around Leptospirosis

Prepared on 13 August 2004, Derrick Garwood, Freelance Medical Writer and Editor

Britain's rats are currently enjoying a somewhat pampered existence, and their numbers are increasing accordingly – not surprising when a single pair can produce a colony of 2,000 within a year. Today the UK plays host to more than 60 million of them. The causes of their proliferation include mild winters, a cutback in expenditure on pest control and the increased discarding of junk food in the street. One reason this population explosion is important is that feral rats are the main animal reservoir for Leptospira interrogans, the causative organism of leptospirosis, which is occasionally fatal. About 30 cases occur each year in Britain. Warnings about rat numbers were issued by the National Pest Technicians Association as long ago as November 2000, a year after high concentrations of the bacteria were found at stations on Glasgow's subway system.

Leptospira interrogans is a flexible, spiral-shaped, Gram-negative spirochaete with internal flagella (see this scanning electron micrograph) . There are more than 200 serovars, classified according to cell surface antigens, of which Icterohaemorrhagiae is most frequently associated with severe infection. Long chain fatty acids are this pathogen's sole major energy source, and it is unique in being able to grow at temperatures as low as 11°C to 13°C.

Infection predominantly occurs via contact with rat urine, or water containing it, either by ingestion or through broken skin. The bacterium is unable to survive for more than an hour unless immersed in water or urine, and does not multiply once it has left the host. Thus leptospirosis is relatively difficult to catch, but swimming, canoeing, fishing, sailing, windsurfing or water-skiing in fresh water – and caving – are associated with a high risk. The precautions which should be taken to minimise the chances of infection are covered extensively here.

Brief details about the disease can be found (buried amongst a profusion of advertisements!) at this site. Most cases are not severe and comprise two phases: during the first phase the patient experiences fever, chills, muscle and abdominal pain, and severe headache. After one to three days of improvement, these symptoms re-appear during the second phase, along with eye pain, rash and enlarged lymph glands. As explained about halfway down this page, the first phase coincides with bacteraemia. Once antileptospiral antibodies appear, the acute phase subsides and bacteria can no longer be isolated from the blood. The second phase of the disease corresponds with the host's immunological response, when the bacteria are rapidly eliminated from all tissues except the brain, eyes and kidneys. Those in the brain and eyes do not proliferate, but in the kidney they multiply and are shed in the urine. A photograph of an infected kidney can be seen here, and a kidney section showing an inflammatory cell infiltrate and the damage to tubular epithelial cells here.

The severe form of leptospirosis is termed Weil's Syndrome and may be fatal in 5% of cases. Characteristic features are mental involvement, low blood pressure, fever, and renal and hepatic dysfunction. The disease-causing mechanism is not known, but the contrast between the level of functional impairment and the scarcity of histological lesions suggests that most damage occurs at the subcellular level.

A notably comprehensive account of leptospirosis is available on the emedicine site, which also has some interesting facts. This disease is the most common zoonosis in the world, and also glories in the wonderfully attractive name of 'swamp fever'. At least 160 mammalian species can be affected. Approximately 90% of human patients have the mild anicteric (without jaundice) form of the disease, and many (77%) have an intense headache during the second phase which is poorly controlled by analgesics and often heralds the onset of aseptic meningitis.

The most common ocular complication is subconjunctival haemorrhage (an extreme example is shown here). Uveitis (inflammation of the iris, ciliary body or choroid) may occur at any stage of the disease and is usually classified by the part of the eye that is affected; the signs and symptoms of the different categories are described in the Merck Manual.

In severe cases of leptospirosis, liver involvement may lead to jaundice, with its yellow coloration of the skin, eyes and mucous membranes that results from an accumulation of bilirubin, a product of the breakdown of red blood cells. The condition is outlined briefly at this site and the photograph of an eye leaves little doubt about the diagnosis. Much more information about jaundice is available here, including the significance of whether the excess bilirubin is in the conjugated (and therefore water-soluble) or unconjugated form.

Renal symptoms such as pyuria, haematuria and oliguria are seen in 50% of patients. Acute tubular necrosis may occur in sufferers from Weil's Syndrome as a result of hypovolaemia and decreased renal perfusion, and those with severe jaundice are more likely to develop acute renal failure. This is defined as a precipitous and significant (>50%) decrease in the glomerular filtration rate. It constitutes a medical emergency, may require dialysis, and has a significant mortality rate. For all you want to know on the topic, surf to this site.

Finally, the good news is that most patients with leptospirosis recover and those with hepatic symptoms and renal failure have a good chance of regaining normal function. The mild form of the disease is treated with doxycycline, ampicillin or amoxicillin, and the severe form with penicillin G. Obviously prevention is better than cure, but balancing the risk of infection against the pleasure derived from water-based pastimes is not an easy task...

This tour was submitted by Derrick Garwood, a Freelance Medical Writer and Editor whose contact details can be found in our directory of freelancers.

If you have any comments on this article, please feel free to email Derrick or let us know.

To make any comments on this article, or to ask a question of the author, please contact the publisher. If you would like to submit an article please subscribe to our PL Intelligence service.

The opinions expressed in the articles published in this section do not necessarily reflect those of Pharmalicensing or UTEK Corporation. No actions including proposals to or agreements with other companies should be taken by any reader without obtaining specific business or legal advice. Neither the publisher nor the authors accept any liability for any actions or activities undertaken by any reader or other third party as a consequence of these articles or for any errors or omissions therein.

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