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Chapter 7, Part 2

Medical Science Publication No. 4, Volume II

LEPTOSPIROSES*

LIEUTENANT COLONEL ROBERT H. YAGER, VC

Members of the spirochetal genus Leptospira comprise a group of antigenically distinct strains, globally distributed in enzootic proportions among many species of rodent as well as other mammalian populations (1). Although the infection in man is accidental, it presents a potential military hazard due to the exigencies and exactments of military personnel under combat and training conditions. The enforced departure from normal sanitary facilities, coupled with the association and exposure of troops to particular environmental conditions, may bring into play all the epidemiologic factors that make up the links in the chain of transmission of leptospires from animal to man. No consideration of leptospirosis in military personnel is possible without a basic understanding of the multiple epidemiologic characteristics that must be present before humans can be infected (2, 3).

Leptospires have been found, with rare exception, in every area of the world in which they have been sought. Generally, most strains are associated with one or more mammalian hosts; however, a particular mammalian species may serve as the primary host for a multiple number of leptospiral strains (4). The principal reservoirs involve numerous species of the rodent family and in recent years the widespread infection of domesticated animals, particularly among canine, bovine and porcine populations, has been demonstrated (5-7). Leptospires usually exhibit little or no pathogenicity for their natural rodent hosts, and even in severe infections of larger mammals their presence may be asymptomatic (1).

Of particular epidemiologic significance is the characteristic nesting ability of these organisms within the host's tissue (2). Leptospires are able to exist in the lumen of the convoluted tubules of the renal cortex, even in the presence of a large number of protective humoral antibodies. From this site they are discharged and excreted with the urine. The chronicity of leptospiruria may extend for months and in several instances has been observed to last for years in various natural hosts. The incidence of leptospirosis in the natural host varies with


*Presented 29 April 1954, to the Course on Recent Advances in Medicine and Surgery, Army Medical Service Graduate School, Walter Reed Army Medical Center, Washington, D. C.


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the species, its geographic location, and the infecting strain. The results of many surveys, conducted in diverse parts of the world, indicate that infectivity rates in excess of 50 percent are not uncommon. It is interesting to note that in several conducted surveys, the incidence of human leptospirosis could be correlated to the relative frequency of leptospirosis in the natural hosts of the regions studied. This is not always the case, as evidenced by the rare appearance of Weil's disease in the United States where the infectivity rate in rats is high (8, 9). Obviously, the hygenic status of the American populace is a significant factor which contributes to the paucity of human leptospiral infections.

The existence of leptospires in waters contaminated by the urine of host-carriers is of fundamental importance to our knowledge of the epidemiology of leptospirosis. The viability of these organisms outside their hosts depends upon the salinity and acidity of the aquatic environment (3). These organisms do not tolerate brackish water and, consequently, no known cases of leptospirosis are known to be associated with sea water. It has been demonstrated that the low frequency rate of Weil's disease in North Holland as compared to the high frequency rate in South Holland is related to the salinity of the water in the former region. The inability of leptospires to survive in water of low pH has been adequately established by different investigators (3). Epidemiologic studies in Japan, Africa and Indonesia have indicated that the difference in the prevalence of human leptospirosis in selected regions is associated with the acidity of the waters of these areas (3). In addition, leptospires have been shown to retain their viability and pathogenicity for as long as 22 days in surface waters of pH 7.0 to 8.0 (2, 3). The epidemic outbreaks of human leptospirosis have usually occurred where there has been contact with contaminated waters, and such outbreaks are made possible by the remarkable pervasiveness of leptospires.

The invasiveness of leptospires is unique with respect to the readiness and rapidity with which they penetrate mucous membranes. Upon intraperitoneal inoculation of cultures in experimental animals, leptospires appear within minutes in the circulating blood (3). The ability of these organisms to penetrate intact skin has not been conclusively demonstrated. The fact that leptospires can penetrate scarified skin has been repeatedly shown in experimental animals and has been utilized in the recovery of pathogenic strains from contaminated waters. In man infections result from the penetration of leptospires through the skin which is usually associated with those occupations where the skin is readily injured or softened by prolonged exposure to water. The nasopharyngeal, buccal and esophageal mucosa, as


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well as the conjunctival membrane, are probably the more frequent sites of entry (3).

The water ecology of leptospires, coupled with their ready penetration of injured skin and mucosal surfaces, demonstrates the potential sources of infection in stagnant pools, slow-moving streams, swamps, wet trenches, etc., in an enzootic or epizootic area of leptospirosis, particularly in view of the marked susceptibility of human beings to these infections. Sex and age are not determining factors in the incidence of these diseases in man, and seasonal factors are important only insofar as they are related to the occurrences of floods and abundant rainfall. Epidemiologic surveys suggest that certain occupational or recreational practices afford greater opportunities for infection than the naturally occurring events previously mentioned.

The medical significance of leptospirosis in military history cannot be fully appreciated since the Weil's disease syndrome was not described until 1886, and the etiologic agent of the disease was not recognized and isolated until 1916 by Inado and Ido in Japan (10). Since the medical records of many campaigns, including the American Civil War, contain descriptions of febrile disease outbreaks accompanied by jaundice, it is quite possible that some cases were due to leptospirosis. The military significance of this disease was definitely established by Uhlenhuth and Fromme (11) in World War I, while working in a field laboratory in France. They observed the disease in German troops engaged in trench warfare. These and other reports of leptospirosis in the German Army in 1915 were followed by similar reports among British troops the following year by Stokes, Ryle and coworkers (12). It was along the Ypres sector in Flanders that some of the bloodiest fighting in World War I took place, and the battle that began as a series of offenses and counteroffenses in 1915 bogged down to a trench war that was characterized by violent activity but little change of position. In these sodden, rat-infested trenches a hundred cases of leptospirosis among British soldiers were observed (13). Scattered outbreaks were also reported in the French and Belgian armies along the Western front. Various European investigators confirmed the observation of Miyajima and other Japanese workers by demonstrating the significance of leptospires in the urine of rats trapped in areas where human leptospirosis had occurred. The disease was also reported among Italian and Canadian forces in Northern Italy.

It would be difficult, if not impossible, to give an accurate appraisal of the incidence of leptospirosis among military personnel in World War II. This war was fought on so many fronts, and under such conditions as to make laboratory confirmation of sporadic cases un-


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feasible. However, an outbreak of leptospirosis with at least 100 clinical cases was reported among British troops on the Normandy beachhead near Caen (14).

One of the most notable outbreaks of leptospirosis occurred among the American soldiers stationed on the military reservation of Fort Bragg, North Carolina, in 1942, and again in 1943 and 1944 (15). It is significant that in this instance the diagnosis of leptospirosis was made in retrospect some 8 years following its last occurrence and that the infecting serotype was L. autumnalis, not previously reported in the United States.

Data obtained from Medical Statistics Division of the Office of The Surgeon General indicate that a total of 115 cases of Weil's disease occurred in the United States Army in all theaters from 1942 to 1945 (16). This figure represents only cases of clinically diagnosed spirochetal jaundice (Weil's disease) and does not include cases of leptospirosis manifested in other clinical forms. There is ample evidence to support the view that more cases of leptospirosis occurred in the United States Army during World War II than the records indicate. Obviously an accurate estimate can never be obtained.

Numerous other instances of outbreaks of leptospirosis are recorded among troops both in war and in peace. An outbreak of aseptic meningitis among American soldiers on Okinawa in 1949 was diagnosed as leptospirosis in retrospect several years later (17). This outbreak as well as other epidemics have occurred among troops who swam and bathed in slow-moving streams and ponds. More recently, leptospirosis has been implicated as one of the most serious infectious disease problems in units fighting in Malaya (18). Injection rates up to 10 percent have been experienced among jungle patrols forced into close contact with an environment contaminated with leptospires.

All too frequently the reported incidence of leptospirosis may vary with the general awareness of the disease, and unless adequate laboratory support is available, many cases of leptospirosis, other than those that exhibit the symptoms of classical Weil's disease, may be overlooked. Army area laboratories and medical general laboratories are currently prepared to render serologic diagnoses of leptospirosis. These units are supplied with three sonic-vibrated complement-fixing antigens with a sufficiently broad spectrum to detect leptospiral antibodies, regardless of the infecting strain (19). Standard Kolmer qualitative technics are employed in examining paired undiluted sera from suspected cases. The paired sera should consist of one specimen drawn during the acute phase of the disease and another drawn the tenth day or after. Since no information can be obtained as to the infecting serotype on the basis of a positive complement fixation test, such sera should be forwarded to the Army Medical Service Graduate


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School where the agglutination-lysis test is employed to confirm diagnosis and identify the etiologic serotype. A battery of selected distinct leptospiral serotypes are employed in our laboratory since it has been determined, on the basis of cross-agglutination studies, that such a combination of antigens is essential in detecting an antibody response to any leptospiral serotype known to exist in the world (19).

Numerous technics have been described for the detection of leptospires in blood, cerebrospinal fluid, urine and tissue emulsion. We have found that the direct dark-field examination of such material is unreliable in itself. Too often artifacts resembling leptospires in size and behavior are present, which may lead to a false-positive diagnosis. Conversely, the spirochetes may be present in such small numbers as to be undetectable, leading to a false-negative result. Leptospiral isolation attempts are best made by the direct culturing into appropriate laboratory media of patients' blood or cerebrospinal fluid during the first week of disease and by the subsequent microscopic examination of the cultures at 2-week intervals (20). Cultures are considered negative only after no leptospires are detected after 4 weeks of incubation at 30° C. The leptospiruric phase of the disease commences usually about the fourteenth day, and the organisms may be isolated from urine by inoculating freshly voided or catheterized specimens into small hamsters or guinea pigs and culturing their heart's blood 4 to 6 days post-inoculation. The same procedures are then followed in handling these cultures as those used in the cultivation and identification of direct isolations. Any leptospiral isolations made in Army Medical Service units are forwarded to the Army Medical Service Graduate School for definitive typing.

Almost all of the work done on leptospirosis in the Far Eastern Theater was done by the Japanese, and there is no paucity of information concerning this disease in their home islands. The early work done by Inado and Ido has already been mentioned. Kitaoka has described the existence of eight leptospiral strains in Japan and Okinawa (21). In addition to Weil's disease, seven-day fever (Nanukayami) is widespread in Japan, and its etiologic agent is L. hebdomadis. So-called autumnal fever (Akiyami) has as it etiologic agent L. autumnalis, a strain closely related to the leptospires of Fort Bragg fever.

With the exception of the outbreak of leptospirosis on Okinawa in 1949, few cases have been recorded among military personnel in the Far Eastern Theater of Operation since the end of World War II. The hazards of schistosomiasis in Japan and Okinawa, the military regulations placing fresh water lakes and streams off limits in endemic areas, can be considered as an important factor in reducing the potentiality of leptospirosis.


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Prior to 1951 little was known or at least recorded about the incidence of leptospirosis in Korea. No cases of human leptospirosis had been reported, and there were no data available regarding surveys to determine possible animal host carriers of the organism. Less than a year after the outbreak of the Korean conflict there appeared among United Nations forces a malady previously unknown to the Western world. It was the disease now described as hemorrhagic fever. Early reports, based on the detection of leptospira-like organisms in the blood of those with acute clinical cases, created a sharper interest in leptospirosis in that country. Although it was subsequently demonstrated that hemorrhagic fever is not a leptospirosis, the interest created by these early but erroneous reports lead to leptospiral surveys of rodents trapped in Korea (22).

Why then, was leptospirosis not reported among United Nations personnel engaged in the Korean incident? Laboratory support was available in Japan and the United States for confirmation of any sporadic cases that might have occurred. It was definitely established that leptospirosis is enzootic in Korean rodents, as in rodents elsewhere.

One might still consider the possibility that leptospirosis did occur in Korea, and in keeping with its protean nature was classified as a fever of unknown origin. Confirmation, in either sense, could be obtained by screening all such available sera from Korea. There is reason to believe, on the basis of past experience, that a few such cases might prove to be leptospirosis. Probably of greater significance in regard to the paucity of leptospirosis in Korea were the overall standards of military sanitation in our Army. The prevention of the transmission of leptospira from infected rodent urine to man was made possible by the routine chlorination of drinking water, strict mess hall sanitation in permanent and semipermanent installations, and by the methods used to protect rations for front line units during all stages of processing, shipping and utilization.

The intensive effort to curtail rodent population, because of their possible epidemiologic importance in hemorrhagic fever, probably is a factor in at least reducing the leptospiral contamination of streams, marshy areas and rice paddies. The climate of Korea cannot be described as being favorable for the prolonged survival of leptospires in the free state. Korea has been described as being either all dust or all mud. A dry spell may end with a torrential rain, followed by a rapid runoff of surface water, quick drying up of streams and ditches, and then a repetition of the cycle. Under such conditions leptospira would suffer the fate of either being dessicated or washed into the sea.

Consideration must also be given to the nature of the conflict that was fought in Korea. Troop movements were generally made by


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road, even in the forward areas, and not by wading through rice paddies and streams, such as the jungle patrols encountered in Malaya. The forward observation bunkers of Korea were placed mainly in elevated, better drained positions than the trenches in Flanders, where men were pinned down for long periods of time in the mire of these trenches.

In summary, leptospirosis has been a major problem of preventive medicine in military history, and will remain so as long as wars are fought with large masses of men forced into intimate contact with the earth and its animal population.

On the basis of experience gained in Korea and in other conflicts, the chief weapons at our disposal in the control of leptospirosis are:

1. Strict adherence to the basic principles of military sanitation with particular emphasis on chlorination of water, protection of food from contamination, rodent control and water discipline.

2. Constant awareness of its potentiality and an understanding of the basic epidemiologic mechanisms involved.

3. Adequate and readily available laboratory support to military units in all parts of the world.

References

1. Gsell, O.: Leptospirosen. Medizinischer Verlag Hans Huber, Bern, 1952.

2. Walch-Sorgdrager, B.: Leptospirosis. League of Nations Bull. of the World Health Organ. 8 : 143-386, 1939.

3. Van Thiel, P. H.: The Leptospirosis. Universitaire pers Leiden, 1948.

4. Gsell, O.: Epidemiology of the Leptospirosis. Symposium on the Leptospiroses. Med. Sci. Pub. No. 1 : 34-56, U. S. Government Printing Office, Washington, 1953.

5. Rosenberg, B. L.: Canicola Fever. Review, with report of two new cases. Am. J. Med. 11 : 75-91, 1951.

6. Wolff, J. W., and Bohlander, H.: Bovine Leptospirosis. A survey of the epidemiology and serology and an investigation on the possible occurrence in bovines in the Netherlands. Doc de Med. Geog. et Tropien. 4 : 257-265, 1952.

7. Sippel, W. L., and Atwood, M. G.: Leptospirosis in Swine. Symposium on the Leptospiroses. Med. Sci. Pub. No. 1 : 143-151, U. S. Government Printing Office, Washington, 1953.

8. Larsen, Carl L.: The Public Health Significance of the Leptospirosis. Symposium on the Leptospiroses. Med. Sci. Pub. No. 1 : 14-24, U. S. Government Printing Office, Washington, 1953.

9. Li, H. Y., and Davis, D. E.: The Prevalence of Carriers of Leptospira and Salmonella in Norway Rats of Baltimore. Am. J. Hyg. 56 : 90-100, 1952.

10. Inada, R., Ido, Y., Koki, R., Kaneko, R., and Ito, H.: The Etiology, Mode of Infection, and Specific Therapy of Weil's Disease. J. Exp. Med. Hyg. 23 : 377, 1916.

11. Unlenhuth, P., and Fromme, W.: Experimentelle untersuchungen uber die sogenannte Weilsche Krankheit (Ansteckende Gelbsucht). Med. Kl. 11 : 1202-1203, 1915.


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12. Stokes, A., and Ryle, J. A.: A Note on Weil's Disease (Spirochaetosis icterohemorrhagica) as it Occurred in the Army in Flanders. Br. Med. J. 2 : 413-417, 1916.

13. Stokes, A., Ryle, J. A., and Tyler, W. H.: Weil's Disease (Spirochaetosis icterohemorrhagica) in the British Army in Flanders. Lancet 1 : 142-155, 1917.

14. Bulmer, E.: Weil's Disease in Normandy. Its Treatment with Penicillin. Brit. Med. J. 1 : 113-114, 1945.

15. Gochenour, W. S., Jr., Smadel, J. E., Jackson, E. B., Evans, L. B., and Yager, R. H.: Leptospiral Etiology of Fort Bragg Fever. Pub. Health Reports 67 : 811-813, No. 8, Aug. 1952.

16. Data from the Medical Statistics Division, Office of The Surgeon General.

17. Gauld, R. L., Crouch, W. L., Kaminsky, A. L., Hullinghorst, R. L., Gochenour, W. S., Jr., and Yager, R. H.: Leptospiral Meningitis. Report of Outbreak among American Troops on Okinawa. J. A. M. A. 149 : 228-231, May 1952.

18. Ley, H. L., Jr., Gochenour, W. S., Jr., Wisseman, C. M., Pirrie, J. M., Patterson, P. Y., Smadel, J. E., and Hoag, W. G.: Leptospirosis in Malaya I. Human Disease Contracted in Jungle Areas. In preparation.

19. Gochenour, W. S., Jr., and Yager, R. H.: Classification of North American Leptospiras. Proc. Am. Vet. Med. Assoc. 178-183, June 1952.

20. Gochenour, W. S., Jr., Yager, R. H., Wetmore, P. W., and Hightower, J. A.: Laboratory Diagnosis of Leptospirosis. Am. J. Pub. Health 43 : 405-410, 1953.

21. Kitaoka, M.: Classification of Leptospirosis. Japanese Med. J. 4 : 181-214, 1951.

22. Monthly Technical Report: 406th Medical General Laboratory, Tokyo, September 1951.