Recent studies in leptospirosis
Pharmakis, Thomas Liberty
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The leptospiral infections from the aspects of the characteristics of the aetiologic agents, pathogenicity, immunity, diagnosis, treatment and epidemiology have been discussed. The type organism (Leptospira icterohaemorrhagiae) which belongs to the order Spirochaetales and family Treponemataceae is a strikingly flexible, motile microorganism measuring seven to fourteen microns in length with exceptionally long forms measuring from thirty to forty microns due to delayed transverse fission. The organisms are finely coiled with regular spirals measuring 0.45 to 0.5 micron in amplitude, and 0.3 micron in depth. There are one of more undulations throughout the entire length and the body culminates in finely pointed ends. The organism may be demonstrated as a fine tapering filament which may assume the forms of semicircles, figures-of-eight, and S-shapes from a liquid culture medium, and serpentine, undulating or bent forms from a semi-solid medium. The leptospira may be stained by Giemsa's or Fontana's silver impregnation methods. The leptospi rae are morphologically undistinguishable. They are facultative aerobes and require one or more of the thermolabile factors in the serum of rabbits, horses, guinea-pigs or humans for growth. Optimal growth occurs at a pH of 7.2 and a temperature range from thirty to thirty-seven degrees Centigrade. The pathogenic leptospirae live exclusively on proteins. Optimum growth requires a period of seven days to reach its peak in contrast to twenty-four hours for most of the other microorganisms. The media in use today are either liquid or semi-solid that contain a 10 per cent concentration of suitable animal serum and are buffered to a pH of 7.2. Examples of these are Schuffner's liquid and Chang's (1947) semi-solid media. Studies of the antigenicity of the leptospirae show that they may arbitrarily be placed into two groups. The first group is called the Cosmopolitan group, which includes Leptospira icterohaemorrhagiae, Leptospira canicola, and Leptospira grippotyphosa. The second group is called the Far East Group, which includes Leptospira auturnnalis, Leptospira hebidomadis, and Leptospira febrilis (Leptospira pyrogenes). The organisms are all antigenically related since they show varying degrees of antigen-antibody reactions in their heterologous antisera. One species of leptospirae (Leptospira piflexa) is unique in its non-pathogenicity, simple growth requirements, and distinct antigenicity. The pathogenicity of the two groups of leptospirae depends upon the species (and even strains) in question and the host infected. The wild rat (Rattus species) is an asymptomatic host of the organisms. The organisms attack the liver, kidneys, and capillaries causing icterus, uremia, and haemorrhage in the susceptible host. Guinea-pigs, hamsters, and young albino mice (Mus musculus) are susceptible hosts to Leptospira icterohaemorrhagiae, and Leptospira canicola. They may be used as test animals for diagnosis of these agents. Lepto-spira canicola and Leptospira grippotyphosa, and the miscellaneous leptospirae of Asia seldom show icterus or the severe symptoms t hat the other leptospiral agents demonstrate in man and test animals. In leptospiral infections, the aetiological agent may be demonstrated in the blood during the primary toxemic stage. The organisms are found in the liver and kidneys in the secondary stage. This stage is manifested by icterus, hemorrhage into the subcutaneous tissues, and uremia. Postmortarn examination shows hemorrhages of the internal organs. Agglutinins may be demonstrated in the tertiary stage (seventh to twentieth day of infection), and can be detected in incr easing titers for weeks thereafter. Lasting immunity is established after an attack, and agglutinins have been detected as long as twenty years after the initial infection. The diagnostic agglutinin titer is 1:300 and may run as high as 1:30,000. Diagnosis of a leptospiral infection is confirmed by darkfield examination or culture of the blood during the primary stage. Inoculation of emulsions of kidney or liver from infected hosts into test animals will reproduce the disease. Antibodies may be detected during convalescent and latent periods. Effective treatment must be started before the onset of icterus for the best therapeutic response. Serum therapy has been used experimentally to protect guinea-pigs, hamsters and young white mice (Mus musculus) from infection. Penicillin in concentrations of 0.4 u/ml. has been shown to have a leptospiristatic effect on the organisms in vitro. Leptospira icterohaemorrhagiae has been shown to have a sensitivity variance to 0.1 - 70.5 u./ml. of penicillin when tested in vitro. Leptospira grippotyphosa was found to be sensitive to 0.25 u./ml., Leptospira canicola to 0.5 u./ml., and Leptospira bataviae to 0.1 u./ml. when tested in vitro. Guinea-pigs have been effectively treated against Leptospira icterohaemorrhagiae when 1500 units of penicillin a day was given early and in maintained doses. General treatment consists of intravenous fluids and the administration of agents that will ameliorate the symptoms. Leptospirosis is endemic in Japan, Holland, South Central Europe, England, and in parts of the United States. The disease prevails in groups that are in proximity to the infective agents. Lepta-spira canicola infects dogs and those who are closely associated with dogs, i.e., veterinarians, and dog owners. Weil' s disease is seen in persons who are in proximity to infected rats. Leptospira grippotyphosa and Leptospira hebdomadis are neted among field workers who contact the disease from infective soil. Wild rats (Rattus species) have been shown to be infected with Leptospira icterohaemorrhagia in incidences of ten to thirty per cent from surveys conducted in Japan, Holland, England, and some of the major cities in the United States. Prophylactic measures should include rat proofing and extermination. Occupational groups should wear gloves to protect themselves from leptospirae-containing urine. Field workers should protect their feet with boots. Rat excreta may be sterilized with sodium hypochlorite 1:64. Health education should be stressed in endemic areas.
Thesis (M.A.)--Boston University
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