Medical Science Publication No. 4, Volume II
RICKETTSIAL DISEASES AND THE KOREAN CONFLICT*
HENRY S. FULLER, M.D., AND JOSEPH E. SMADEL,M. D.
This report reviews certain important contributions to our knowledgeof rickettsial diseases which have been made since the close of World WarII. Attention is centered upon aspects which are of particular importanceto military medicine. The discussion is concerned mainly with louse-bornetyphus and with scrub typhus, the other rickettsial diseases being consideredbriefly. The period covered is January 1946 through December 1953.
Basic information on rickettsial diseases, available at the close ofWorld War II, has been presented in detail (1). This informationhas been translated into effective control measures (2). For authoritativeaccounts of rickettsial diseases, chapters by various authors (3)should be consulted.
Louse-borne Epidemic Typhus
At the close of World War II, the more obvious problems of epidemictyphus were: (a) the need for specific therapeutic agents otherthan para-aminobenzoic acid; and (b) further clarification of theinterepidemic reservoir of the disease. When the possibility that the vectormight prove resistant to DDT became an actuality in Korea, the need foreffective insecticides was immediate. These problems merit further consideration.
Specific Therapeutic Agents. Three antibiotics are establishedas effective in the treatment of persons suffering from each of the rickettsialinfections: chloramphenicol, aureomycin and terramycin. They are rickettsiostatic,not rickettsiocidal, in action; recognition of this fact is essential toan understanding of their proper clinical use. Although the recommendeddoses (4) are non-toxic, nausea, vomiting, or diarrhea may accompanytheir administration. In evaluating reports of the rare occurrence of blooddyscrasias, attributed to chloramphenicol, the very low risk of the occurrenceof such complications should be contrasted with the much higher case fatalityrate in the rickettsial diseases of military importance. In no known instance
*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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have any of the three effective antibiotics failed to prevent a fataloutcome, when given a reasonable therapeutic trial in a human case of rickettsialinfection. Thus the available rickettsiostatic agents are eminently satisfactory.If further search for antibiotics is made, one would aim at finding a compoundwhich is rickettsiocidal and which is non-toxic to man (4).
Interepidemic Reservoir. The studies of Murray et al (5-7),sponsored by the Armed Forces Epidemiological Board, have verified thehypothesis that Brill's disease represents a recrudescence of louse-bornetyphus. It is postulated that viable rickettsiae persist during the latentinterval somewhere in the tissues of some individuals. The factors whichdisturb the immunologic balance in such persons, permitting the sequesteredrickettsiae to emerge and again produce disease, are poorly understood.
It has been demonstrated that lice become infected by feeding on patientswho have Brill's disease, hence the epidemiologic significance of suchpersons is obvious. When cases of Brill's disease occur in a louse-infestedcommunity, they may serve as foci from which an epidemic of louse-bornetyphus can spread to susceptible members of the population. Similarly,they may serve to introduce typhus into an area where it has not been knownfor some time. Thus, the potential hazard of such persons emphasizes theneed for louse control as an integral part of measures designed to preventoutbreaks of typhus in louse-infested populations.
Control of Lice and Lousiness. The principle of vector controlas an important weapon in the control of an arthropod-borne disease iswell illustrated by experience with louse-borne typhus. The effectivenessof delousing in controlling the spread of epidemic typhus was demonstratedduring World War I. Delousing methods in use at that time employed heatto kill the insects and their eggs in clothing and other effects, togetherwith the concurrent cleansing of individuals. Subsequent studies of variouschemical insecticides culminated in the use of DDT during World War II,and in the development of effective methods for its application to largenumbers of persons (1). A noteworthy property of DDT is its residualeffect, whereby reinfestation with susceptible insects is reduced to nilduring a period of several weeks following proper application. An insecticidewhich has these features of effectiveness, ease of application, relativenon-toxicity to man, and residual effect, is admirably suited to the controlof human body lice.
During the Korean conflict, it became apparent that not all strainsof human body lice are killed by DDT. During the winter and spring of 1951,routine applications of DDT powder to Communist prisoners of war failedto control their louse infestations. Field and laboratory
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studies showed that the lice themselves were resistant to DDT (8).DDT-resistant lice were also detected in Japan (9, 10). Tests ofother insecticides were conducted (11, 12). Six formulations ofpowder, each containing pyrethrum and allethrin as active principles, werefound to be effective if applied four times at 5-day intervals. A singletreatment of clothing with powder composed of 1 percent lindane (the gammaisomer of hex-chloro-cyclohexane) in pyrophyllite killed all lice for aslong as 9 days after application. Laboratory tests indicated, however,that more than one treatment would be required to eradicate a person'sinfestation under natural conditions (12), since the initial applicationwould have lost its effectiveness by the end of the 10-day period of incubationof louse eggs. Lindane was subsequently used effectively for control oflice in Korea.
Although currently effective insecticides are available, the possiblefuture occurrence of resistant lice must be borne in mind. In other words,although the immediate problem of DDT resistance has been solved, the potentialproblem of insecticide-resistant lice remains.
Effectiveness of Typhus Control Measures. During the Korean conflictthe hazard of infection of troops with epidemic typhus was very real. Thewidespread occurrence of famine, poverty, disruption of populations, overcrowdingand lousiness, during the latter part of 1950, provides environmental factorsknown to be conducive to the spread of louse-borne typhus (13, 14).The persons at risk included approximately 20 million South Korean nationals,numerous louse-infested Communist prisoners of war, and the personnel ofthe United Nations.
Appropriate preventive measures were applied to these three populationgroups. During the period 1 January to 30 September 1951, more than 15million (75 percent) South Koreans were treated with DDT powder (13,15), and the newer insecticides were used when they became available.More than 14.5 million South Koreans received Cox-type typhus vaccine (13).Similar measures were applied to prisoners of war (16), and standardpreventive measures were employed by military personnel of the United Statesand other United Nations.
Were these measures effective? It is estimated (14) that thetyphus incidence among South Korean civilians rose during early 1951 toan average of 3,228 cases and 473 deaths per month; while estimated monthlyaverages for the first 6 months of 1952 were 125 cases and 16 deaths.
The experience of United States military personnel is likewise relevantto an evaluation of the typhus control programs. The exposure of our personnelto lice is suggested by the fact that they became infected with relapsingfever in Korea, where the vector is presumably
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the louse. During 1951, 69 cases of relapsing fever were reported inUnited Nations troops in Korea, and 107 cases were diagnosed among prisonersof war (17). The number of cases of louse-borne typhus in UnitedStates personnel was, however, essentially nil, there being but one caseon record in a heavily exposed member of the Medical Department.
In view of these considerations, it is concluded that the effectivenessof typhus preventive measures was demonstrated by the experience in Korea.
Scrub Typhus
Recent advances in our knowledge of scrub typhus are the outcome ofstudies made mainly by members of the United States Armed Forces workingin Malaya, Japan and Korea. These include the clinical evaluation and developmentof antibiotics in the chemoprophylaxis and therapy of scrub typhus in Malaya,and important contributions to the epidemiology of the disease in Japanand Korea. Since the studies of antibiotics have been mentioned above,particular attention will be given to the advances made in Japan and Korea.
Japan. Since the close of World War II, our Armed Forces in Japanhave experienced two outbreaks of scrub typhus. Between 6 October and 13November 1948, 27 cases were diagnosed in American soldiers; of these cases,26 men had been engaged in field exercises near the town of Gotemba and1 came from a camp on the slopes of Mount Fuji (18). The generallocale became known as the Fuji-Susono area. Field studies (19, 20)revealed the presence of several species of chiggers, but Trombiculaakamushi was not found. Further surveys (21-23) of this focusresulted in the recovery of Rickettsia tsutsugamushi from pooledtissues of field mice, and in the demonstration of the presence of fourspecies of Trombicula: T. palpalis, T. intermedia, T. japonica andT. fuji.
During the period 20 to 31 October 1953, 57 mild cases of scrub typhuswere diagnosed in personnel of the Third Marine Division who were stationedin the vicinity of Mount Fuji (24). In view of the well-documentedexperience of 1948 together with the availability of effective preventivemeasures, this occurrence is regarded as an example of lessons not learned.
Studies by Japanese scientists (25) have revealed the presenceof scrub typhus on several islands located off the southern coast of Honshu.The name "Winter Scrub Typhus" emphasizes the seasonal occurrenceof human cases on these islands. The evidence summarized by the Japanese(25) suggests that T. scutellaris is the local vector.
From these various observations in Japan, the following points emerge:(a) previously unrecognized foci of the disease have been
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discovered; (b) human cases of scrub typhus can occur during the autumnand winter months; and (c) it is very likely that Trombicula akamushiis not the only Japanese chigger which carries scrub typhus to man.These points are pertinent to our consideration of the findings in Korea.
Korea. During June 1951, two cases of scrub typhus were diagnosedin troops of the British Commonwealth forces (26). The patientsexhibited eschar and local lymphadenitis, their sera agglutinated ProteusOXK, and they responded to chloramphenicol. During November 1951, a casewas diagnosed in a U. S. Marine Corps sergeant who was presumably exposednear Masan, Korea (17). Strains of Rickettsia tsutsugamushi wererecovered from two patients with scrub typhus whose acute illnesses occurredduring late October and early November 1953 (27).
The causative rickettsiae have been recovered from the common Koreanwild mouse, Apodemus agrarius, on repeated occasions (27).This rodent is known to be a suitable host for the larvae of several speciesof chiggers; however, species of chiggers proved to be vectors elsewherehave not been found in Korea, despite intensive collecting. These factssuggest that one or more of the local Korean chiggers may be functioningas vectors among rodents. The search for a vector to man, otherthan T. akamushi, is indicated in the light of the epidemiologicand ecologic patterns of scrub typhus in Japan and Korea.
Other Rickettsial Diseases
Murine typhus has not been a problem of importance in the Far East Command.Tick-borne rickettsial diseases have not been recognized among our personneloperating in Korea. The recovery of Rickettsia akari from a Koreanrodent (27) extends our knowledge of the geographic distributionof the causative agent of rickettsial pox but the ecologic interpretationof this finding requires additional data. The infection has not been identifiedin human beings in Korea. During the latter part of World War II, Q feverwas an important disease in American troops in Italy (3). Althoughthe causative agent is now known to have a worldwide distribution and abroad host range, Q fever has not been diagnosed among United Nations troopsoperating in Korea.
Summary
Since the close of World War II, much has been learned about rickettsialdiseases. The following points are of direct concern to military medicine:
1. Chloramphenicol, aureomycin and terramycin have proved their effectivenessin the specific therapy of these diseases.
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2. Persons with Brill's disease (recrudescent louse-borne typhus) mayserve to initiate typhus epidemics in a louse-infested community.
3. The occurrence of DDT-resistant body lice in Korea posed a problemin typhus control which has been solved, for the present, by theuse of lindane. The possibility of recurrence of insecticide-resistantlice should be borne in mind.
4. The effectiveness of current methods of typhus prevention and controlwas demonstrated by experiences of the Korean conflict.
5. The known geographical distribution of scrub typhus has been extendedto include Korea, where a non-classical occurrence of human cases duringautumn months has been noted. The causative rickettsiae have been foundin a common and widespread species of wild Korean mouse. One or more speciesof chigger, not previously recognized as a vector, is probably responsiblefor the transmission of scrub typhus in Korea.
6. These important contributions to our knowledge of rickettsial diseaseswere made since World War II by personnel of the Military Service or byinvestigators who were sponsored by the Armed Forces Epidemiological Board.
References
1. American Association for the Advancement of Science:The Rickettsial Diseases of Man, pp. 1-247. Am. Assn. Advancement of Science,Washington, 1948.
2. American Public Health Association: The Control ofCommunicable Diseases, Ed. 7. Am. Pub. Hlth. Assn., New York, 1950.
3. Snyder, J. C., Cox, H. R., and Smadel, J. E.: Chaptersof Viral and Rickettsial Infections of Man, pp. 578-664. Rivers, T. M.,Ed. J. B. Lippincott Co., Philadelphia, 1952.
4. Ley, H. L., and Smadel, J. E.: Antibiotic Therapy ofRickettsial Diseases. Antibiotics and Chemotherapy. (In press.)
5. Murray, E. S., Baehr, G., Schwartzman, G., Mandelbaum,R. A. Rosenthal, N., Doane, J. C., Weiss, L. B., Cohen, S., and Snyder,J. C.: Brill's Disease. I. Clinical and Laboratory Diagnosis. J. A. M.A. 142 : 1059-1063, 1950.
6. Murray, E. S., and Snyder, J. C.: Brill's Disease.II. Etiology. Amer. J. Hyg. 53 : 22-32, 1951.
7. Murray, E. S., Psorn, T., Djakovic, P., Sielski, S.,Broz, V., Ljupsa, F., Gaon, J., Pavlevic, R., and Snyder, J. C.: Brill'sDisease. IV. Study of 26 Cases in Yugoslavia. Amer. J. Pub. Health 4l: 1359-1369, 1951.
8. Hurlbut, H. S., Altman, R. M., and Nibley, C., Jr.:DDT Resistance in Korean Body Lice. Science 115 : 11-12, 1952.
9. Barnett, H. C., and Knoblock, E. C.: Chemical and BiologicStudies on DDT Resistance of Lice. U.S. Armed Forces Med. J. 3 :297-304, 1952.
10. Kitaoka, M.: DDT-resistant Louse in Tokyo. Jap. J.Med. Sci. Biol. 5 : 75-88, 1952.
11. Eddy, G. W.: A Report on the Effectiveness of CertainInsecticides against DDT-resistant Body Lice in Korea. Confidential Report,Office of The Surgeon General, U. S. Army, 1951.
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12. Eddy, G. W.: Effectiveness of Certain Insecticidesagainst DDT-resistant Body Lice in Korea. J. Econ. Ent. 45 : 1043-1051,1952.
13. Van Bommel, L. B.: Epidemische vlektyphus on haarbestrijding in Zuid-Korea. Nederl. Tijdschr. v. Geneesk. 96 : 2562-2565,1952.
14. Office of The Surgeon General, U. S. Army: Korea:A Summary of Medical Experience, July 1950-December 1952. Reprinted fromHealth of the Army, 1953.
15. Maclaren, J. P.: Insect and Rodent Control Activitiesof UNCACK. Military Prev. Med. Assoc. Korea, 8 April 1953. MimeographedProceedings: 28-29, 1953.
16. Dews, S. C.: Mass Delousing of Personnel. MilitaryPrev. Med. Assoc. Korea, 8 April 1953. Mimeographed Proceedings: 8-10,1953.
17. 406 Medical General Laboratory: Annual HistoricalReport for 1951.
18. Thompson, A. H.: A New Endemic Area of Scrub Typhusin Japan. Bull. U. S. Army Med. Dept. 9 : 871-879, 1949.
19. 406 Medical General Laboratory: Annual HistoricalReport for 1948.
20. Kuwata, T., Berge, T. O., and Philip, C. B.: A NewSpecies of Japanese Larval Mite from a New Focus of Tsutsugamushi Diseasein Southeastern Honshu, Japan. J. Parasitol. 36 : 80-83, 1950.
21. 406 Medical General Laboratory: Annual HistoricalReport for 1950.
22. Fukuzumi, S., Obata, Y., and Kagiwada, R.: On theTrombiculid Mites and Rickettsiae Discovered in Mt. Fuji Foot Plain. KitasatoArch. Exper. Med. 23 (4) : 11-22, 1951.
23. Hayashi, H.: On the Causative Agent of TsutsugamushiDisease Isolated from Field Voles, Apodemus speciosus speciosus,Inhabiting the Foot Area of Mt. Fuji in Japan. Kitasato Arch. Exper. Med.23 : 13-19, 1951.
24. Outbreak of Scrub Typhus: Medical News Letter, UnitedStates Navy 23 (5) : 33-35, 5 March 1954.
25. Yosano, H., and co-workers: Studies on Shichito Fever.Winter Scrub Typhus of Izu Shiohito Islands, Japan, 125 pages (pp. 91-125in English), Tokyo, 1953.
26. Munro-Faure, A. D., Andrew, R., Missen, G. A. K.,and Mackay-Dick, J.: Scrub Typhus in Korea. J. Roy. Army Med. Corps 97: 227-229, 1951.
27. Army Medical Service Graduate School, Division ofCommunicable Diseases: Quarterly Reports, 1953.
