(Leptospirosis) Weil’s disease, an infection associated with jaundice and caused by invasion with Leptospira icterohaemorrhagiae, was the first leptospiral infection to be recognized in man. It was not long before it was discovered that the rat is the natural host and that the mode of spread is by contact with rat’s urine containing the organism, which can penetrate the skin or mucosae.
(Leptospirosis) Subsequently over 100 serotypes of leptospires have been identified, many of which have been shown to cause disease in man. The natural hosts of most of these types are small wild rodents, but some may also occur in animals such as dogs and pigs. In Britain only two serotypes, namely L. icterohaemorrhagiae and L. canicola, have been shown to cause human disease, but other serotypes have been isolated from wild rodents. The spread of these infections is usually by contamination with infected animal urine, and fish cleaners, farm-workers, veterinarians and vagrants are those most at risk; immersion in canals or stagnant water may also result in sporadic infection and in such instances the disease may present as lymphocytic meningitis due, probably, to the entrance of the leptospires through the conjunctivae. (Leptospirosis) Infections due to leptospires other than L. icterohaemorrhagiae are not often associated with jaundice and diagnosis frequently involves differentiation from other causes of pyrexia of unknown origin. The first step is to establish whether or not antibody to leptospiral antigen is present and this may be rapidly carried out in most laboratories. The isolation and identification of the causative organism from body fluids such as blood or urine is more difficult and time consuming.
Pathology. In patients dying from laptospirosis, there has usually been a combination of hepatic, renal and cardiac failure. The changes in the liver are non-specific; in severe cases, there may be centrilobular and even massive necrosis. Oedema and inflammatory exudate lead to intralobular biliary stasis. In the kidneys, the glomeruli are usually spared, but the tubules are affected and contain haemoglobin and myoglobin casts. The main findings in the myocardium are focal haemorrhages, interstitial oedema and cellular infiltration. A similar picture is seen in skeletal muscle. If meningitis is present, there is thickening of the meninges due to inflammatory exudate.
Clinical Features.(Leptospirosis)(Leptospirosis) The average incubation period is 10 days, the range being 4 to 21 days. An unknown, but significantly high proportion of infections are subclinical or may cause a mild undiagnosed fever. In the more severe infections the first or septicaemic phase lasts about a week. Usually the clinical illness begins abruptly with headache, severe myalgia, pyrexia, conjunctival suffusion, anorexia and vomiting. Infrequently, there are skin rashes or petechiae and enlargement of the liver and spleen.
In the second phase, sometimes termed the toxic or immune phase, leptospiral antibodies appear in the blood. The temperature falls by lysis and is usually normal for two or three days. In the majority of patients, there is further pyrexia for a few days and transient meningism followed by prompt recovery. In other cases, during this phase, hepatitis, tubular necrosis, myocarditis and meningitis may occur. The cause of these serious complications is uncertain but cell damage from immune complexes is a possible explanation.
Hepatitis is indicated by epigastric pain and tenderness in the right upper quadrant of the abdomen and the appearance of jaundice, usually accompanied by dark urine. There may or may not be pallor of the stools. In severe cases, jaundice deepens, there is marked anorexia and vomiting and there is a haemorrhagic tendency. The patient may worsen and show all the features of acute massive liver necrosis. Renal tubular necrosis may lead to acute renal failure. Myocarditis is suggested by tachycardia, fall in blood pressure and cardiac enlargement. The development of profound hypotension, arrhythmias and cardiac failure are ominous signs. Meningitis causes severe headache, neck stiffness and a positive Kernig’s sign. Haemorrhagic pneumonia and iritis are infrequent complications.
By the third and fourth week of the illness, the majority of patients enter the third or convalescent phase. The average case has a post-infective debility which gradually improves. When there has been serious involvement of the liver, kidneys and heart, mortality is in the region of 15% to 20%. Those who recover, do so completely. There is gradual clearing of jaundice, the urine output improves with regression of uraemia, the blood pressure rises, the heart returns to normal size and any signs of cardiac failure disappear. During the third phase, the case untreated with penicillin may show a temporary return of muscle pain with pyrexia (secondary fever). The reason for this is not known.
(Leptospirosis) Laboratory Data. Most patients with leptospirosis show a polymorphonuclear leucocytosis. When there is liver involvement, the liver function tests indicate a mild hepatocellular jaundice with and intrahepatic obstructive element; bilirubin and urobilinogen are present in the urine. In patients with renal failure the urine contains protein, red blood cells and cellular and granular casts; in severe cases the rise in blood urea is progressive. In myocarditis there is electrocardiographic evidence of conduction disturbances and arrhythmias. Meningitis is characterized by an increase of lymphocytes in the cerebrospinal fluid with little or no rise in protein; xanthochromia may be observed in the jaundiced patient. Apart from the few patients developing severe haemorrhagic pneumonia, scattered opacities’ probably due to haemorrhage are seen on radiography of the chest in 10 to 20% of cases.
The diagnosis is made by culturing the organism from the blood in the first week or from the urine in the second and third weeks. Alternatively, blood or urine specimens may be inoculated into a guinea-pig. From the second week onwards, specific leptospiral antibodies in rising titre may be demonstrated in the blood. The serum antibody titres may not however reach diagnostic levels in those cases treated promptly.