RICKETTSIAL DISEASES: RISK FOR INDONESIA

Allen L. Richards*, Eko Rahardjo**, Djoko W. Soeatmadji***

ABSTRAK

PENYAKIT RICKETTSU: RISIKO UNTUK INDONESIA

Penyakit bersifat endemik hampir di seluruh bagian dunia, dun begitu juga di Indonesia. Termasuk dalam penyakit-penyakit rickettsia adalah tifus epidemik, tifus murine, 'kcrub ," dun 'kpotted fever." Tifus epidemik, yang ditularkan kepada manusia melalui tuma pada tubuh manusia, dun dapat menyebabkan sakit berat dun kematian. Tifus murine (tifus endemik), bersumber pada pinjal hewan, merupakan penyakit vang mirip tifus epidemik, tetapi dengan gejala-gejala yang lebih ringan dun jarang menyebabkan kentatian. "", merupakan penyakit yang dapat ringan sampai berat dun dapat nlembahayakan hidup, ditularkan kepada manusia melalui gigitan tungau yang belum dewasa yang dikenal sebagai "chigger". ": (demam yang disertai dengan bintik-bentik pada kulit), disebabkan karena terinfeksi oleh salah satu dari berbagai spesies rickettsia dari kelompok "spotted fever", dun ditularkan kepada manusia oleh pejamu (hospes) vertebrata melalui gigitan capluk () yang terinfeksi. penyakif yang disebabkan oleh organisma yang menyerupai rickettsia (rickettsia-like organism) adalah: "", yaitu penyakit yang akut atau kronis yang diduga ditularkan secara alamiah akibat terhirup oleh partikel udara yang terinfeksi Coxiella burnetti sejenis bakteri yang sangat resisten terhadap upaya menonaktifiannya secara kimiawi dun jsik. atau penyakit Carridn, ditemukan pada daerah dengan ketinggian sedang di Andes, Amerika Selatan. Penyakit ini ditularkan oleh lalat pasir (sand pies). "Trench feverf', mirip dengan tifus epidemik, ditularkan kepada nlanusia oleh tuma; penyakit ini sembuh sendiri. Penyakit garutan kucing (Cat-scratch disease), disebabkan oleh infeksi henselae di tempat gigitan atau garutan kucing rumah yang merupakan hospes. Demam sennetsu, merupakan penyakit yang dapat sembuh sendiri dun hanya diternukan di Jepang dun Malaysia. Pengobatan dengan tetrasiklin atau kloramfenikol untuk penyakit Rickettsia dav penyakit yang menyerupai Rickettsia, serta monositik dun granulositik pada manusia, menunjukkan hasil yang baik. Ehrlichiosis pada manusia merupakan penyakit baru yang tidak diketahur penyebarannya di seluruh dunia, sangat mungkin ditularkan oleh "tickf: Walaupun umumnya dapat sembuh sendiri, angka kematian ehrlichiosis dilaporkan mencapai 2-10%. Sebagian besar penyakit rickettsia dun penyakit yang rnenyerupai rickettsia tersebut di atas belurn dikaji secara intensf di Asia Tenggara. Walaupun nrasih terbatas, di Indonesia sudah dilakukan penelitian-penelitian tentang "scrub typhus" dun "." Sedangkan penyakit-penyakit yang ada hublingan denpan kutu penyebar Rickettsia seperti "tick typhusffatau "spottedfever': "': bartonellosis, "Qfever", dun ehrlichiosis masih terabaikan di Indonesia. Tinjauan ini bertujuan untuk memperkenalkan hasil-hasil penelitian tentang penyakit-penyakit rickettsia di Indonesia, dun nlemperlihatkan berberapa penyakit yang penyebarannya sekarang telah diketahui disebnbkan oleh arthroioda.

* Rickettsia1 Diseases Program, Department of Immunology, Naval Medical Research Unit No. 2, Jakarta, Indonesia ** Pusat Penelitian Penyakit Menular, Badan Litbangkes, Jakarta, Indonesia *** Fakultas Kedokteran, Universitas Brawijaya, Malang, Indonesia.

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INTRODUCTION as 60% without proper treatment. The intensity and duration of the maladies are sigruficantly Rickettsiae are gram-negative, obligate decreased by intervention with antibiotic intracellular bacteria which are responsible for a therapy (e.g., tetracycline or chloramphenicol). large number of arthropod transmitted diseases Untreated illness may be a source of significant in man. These diseases include: epidemic (R. morbidity and mortality". There are currently prowazekii), and murine (R. @phi) typhus; no commercial vaccines available for any of Rocky Mountain spotted fever (R. rickettsii), these diseases and indeed specific diagnosis is Mediterranean spotted fever (R. conorii), accomplished only by a few specialized Siberian tick typhus (R. sibirica), laboratories around the world because of the (R. akari), and Australian tick typhus (R. hazardous nature and fastidious growth australis); and 3) scrub typhus (R. characteristics of the organisms involved. tsutsugamushi). In addition, other related Diagnosis is generally by symptomatology and "rickettsial diseases" associated with man case history with laboratory confirmation done include: 1) trench fever (Bartonella rarely"'. Thus, the base of information on (Rochalirnaea) quinfana); 2) Q fever (Coxiella especially in Indonesia, as an burnetii); ehrlichiosis (Ehrlichia sennetsu, 6 important contributor to acute human febrile chafleensis). A list of these diseases and some disease, is limited',4. of their properties are presented in Table 1.

Rickettsial diseases and diseases due to RICKETTSIAL DISEASES rickettsial-like bacteria (accept for trench fever and sennetsu ehrlichiosis) are ever present Rickettsiosis as shown in Table 1 has been zoonoses which exhibit periodic fluctuations in divided into three groups based upon the attack rates due to environmental influences on antigenic relatedness of the bacteria causing the the vectors and hosts and variations in human diseases. The following is a detailed description (accidental host) a~tivities'.~. The resulting of these rickettsial groups as well as diseases disease is associated with the infection of the due to infection with bacteria related to host's endothelial cells or cells associated with rickettsiae. the endotheliun~,or blood cells',2. The result of rickettsial infection of the endothelium leads to an intense vasculitis in the affected organs TYPHUS GROUP (including brain, lungs, kidneys, heart, and liver), which leads to headache, fever. malaise, Within the typhus group is epidemic rnvalgia and in many cases a macular, typhus also known as louse-borne or classic maculo-papular or papular (rarely in Q t-yphus. Thc etiologic agent is Rickettsia fever)'-4. Infections involving the cells of the prowazekii which is passed among man by the blood system result in bactercmia with fever and human body louse (Pediculus hunranus hcadach~for infections with bartonellae, and huntanus), or among flying squirrels and to man sudden o~~cctoffevcr chills, headache. myalgia, by unknown squirrel ectopara~itesl.~,~.The arthralgia and anorcsca for chrlichiaez. The bacteria are passed to man via the arthropod illnesses are oftcn self-limiting (approximately vector fxes rubbcd into skin abrasions or the 15 days of fever). houcv:r, depending on !hc conj~~ncti+.e.or bj. inhalation of dried infectious agcnt involvcd the rnortnlii!, rate may bc as high feces. Ep~demic typhus has world wide

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Table 1. Rickettsial Diseases of Human Importance

DISEASE ' SPECIES VECTOR HOST Endemicto Indonesia

Typhus Group

Epidemic Typhus Rickettsia prowazekri Human body louse Human Unknown Squirrel ectoparasites Flying squirrel

Brill-Zinsser's Disease R. prowazekri Recrudescence of latent Human Unknown epidemic tyrhus

Murine Typhus R. typhi Rat Rodents Yes

Scrub Typhus Group Scrub Typhus R. fsutsugamushr Trombiculid mites Rodents Yes

Spotted Fever Group

Rocky Mountain Spotted Fever R. rrckettsir lxodid R~detlts,Dogs, Unknown Foxes

Mediterranean Spotted Fever R. conorrr lxodid ticks Dogs, Rodents U~~known

Siberian Tick Typhus R. srbrrrca Ixodid ticks Rodents Unknown

Australian Tick Typhus R. ausfrabs lxodid ticks Rodents, Unknown Marsupials

Rickettsialpox R. akarr Hematophagous mites House mouse,other Unknown commensal rodents

Oriental Spotted Fever R. japonica Ticks? Rodents? Unknown

Others

Q Fever Coxrella burnebr Ticks? Rodents, Sheep, Yes Cattle, Goats

BartoneUa Group

Bartonellosis Disease Barfonella banllfonnrs Sandfly Rodents Unknown

Trench Fever B. (Rochahmaea)qulnfana Lice Human Unknown

Cat Scratch Disease B. henselae Ticksitleas? Cats Unknown

Ehrlichia Group

Sennetsu Ehrlichiosis Ehrlrchia sennetsu Unknown Human Unknown

Human Monocytic Ehrlichiosis E. chaffeensrs Amblyomma sp.? Deer? Unknown Dermacentor sp.? Dog?

Human Granulocytic Ehrl~chiosls Unknown Ixodes sp.? Deer? Ilnknown Dermacentor sp.? Dog?

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distribution and has been involved in throughout the world9.10. The disease is due to determining man's destiny especially during an infection with R. @phi (R. mooseri). This times of war'. The symptoms follow an agent is passed to man by the rat flea incubat~onperiod of 1-2 weeks. They include (Xenopsylla cheopis) or possibly other an abrupt onset of fever, chills, headache and arthropod vectors. The infection is started when myalgia. Macular rash of upper trunk and either the flea feces is rubbed into bite or other axillary folds occurs around day five. The wound, or the host inhales dried fece~'.~.~,'~. maculopapular rash spreads over the entire body Symptoms are similar to , but except for the face, palms and soles. Death may milder. There is a gradual onset of disease with occur in the third week, with stupor, peripheral non-productive cough, fever, headache, vascular collapse and renal failure. Diagnosis is myalgia, nausea, vomiting and in about 50% of the cases a macular or maculopapular rash4. usually based on clinical suspicion plus reaction The illness maybe debilitating, especially with to the antigens' OX19 + OX2 v neurologic or nephrotic changes, fatalities are and no reaction to the P. rnirabilis Kingsbury rare". For diagnosis the nonspecific Weil-Felix strain OXK antigen in the nonspecific Weil- reaction generally gives the following results: Felix serological te~t~.~.There are also some OX19 + OX2 v OXK -2,4. If a reference rickettsial antigen specific noncommercial laboratory is available serologies, in which a enzyme immuno- assays (EIA) that are used in four fold rise in titer is diagnostic, and PCR a few reference laboratories. In even fewer with specific primers, can be performed'.'.".''. laboratories there are the capabilities to culture Clinical specimens can be cultured for R. typhi, clinical specimens (blood) for rickettsial but this is difficult and hazardous to laboratory isolation4. Recently, the polymerase chain personnel. Treatment as with other rickettsial reaction has allowed the identification of diseases incorporates use of one of the bacteria in blood of acute ill patientss. This tetracyclines or chl~ramphenicol'~~~'' . procedure is very sensitive, but is also technically difficult. The treatment for In Indonesia, endemicity of epidemic epidemic typhus is tetracycline (doxycycline) or typhus and Brill-Zinsser diseases is unknown4, chl~ramphenicol'~~~~. whereas, it is known that murine typhus is endemic throughout the archipelago 4,13-'7. Brill-Zinsser disease has been determined Nevertheless, murine typhus is rarely diagnosed to be a recrudescence of epidemic typhus. The or is misdiagnosed during acute illness, due to reemerging agent, R. prowazekii, produces a its mild, nonspecific clinical manifestations9-". similar but much milder illness then during the Therefore, little is known of the actual primary disease','. Diagnosis is usually based prevalence of this disease, but only of the upon a history of epidemic typhus. The prevalence of antibodies to R. @phi4"-I7. In Weil-Felix reaction and EIA results are usually Java, R. @phi has been isolated from rodent unreliable. Culture of R. prowazekii is possible hosts and arthropod vectors" and the presence and PCR has been proven successful with specific primerse. Treatment involves use of of rickettsial nucleic acid in X. cheopis has either tetracycline or chloramphenicol. been detected by PCR (Rusidy AF, Richards Brill-Zinsser diseabe is also distributed AL, Soeatmadji DW, Church, et al unpublished world-wide','. observ?tion) utilizing a procedure describe previcu;lyi2. Enteric fever, is also endemic to Murine typhus, also known as endemic, Indonesia .and often presents with clinical flea-borne, shop, or urban typhus, 1s endemic manifestations similar to those of rickettsiosis,

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i.e., fever, headache, malaise and in 30-50% of up to 50% of patients died because of lack of a cases of , rose sp~ts'~. known treatment at that timez2. Today, the Unfortunately, many enteric fevers, like treatment of choice for scrub typhus is rickettsial fevers, are difficult to diagnose by tetracycline or chloramphenicol which generally laboratory methods available in Ind~nesia'~. produces a rapid clinical improvement in the The commonly used Weil-Felix and Widal patient with defervescence of clinical syniptoms serological tests are nonspecific tests for usually seen within two day~l.~,~~.However, rickettsial diseases and typhoid fcbcr. there have been recent reports of drug resistant respectively, and require assessing both acute scrub tvphrls described both in Thailand and and convalescent serum samples far 1~di~26,RuphanathD personal commmcabon In addition, the isolation and culture of the causative agents are often difficult Scrub typhus is considered a rural, tropical and require specialized equipment which are disease niost commonly found afflicting not routinely found in the clinical laboratories individuals traversing through or working in of Indonesia19. Thus, illresses characterized by terrain encompassing secondary vegetation fever and headache in Indonesia are often resulting from previously cleared forest or clinically diagnosed as "tifus," which may abandoned agricultural a:casl.22-24. However. include many enteric fevers as well as other there have been reports of individuals acquiring infectious diseases including rickettsial fevers. scrub typhus in urban settirigs of Hong Kong, "Tifus" is one of the leading reported causes of Ja~an'~.~'and while gardening in suburban and hospital admission in Jakarta2'. urban areas of South Korea2". Scrub tqphus cases havc been reported from the southern section of Jakarta by Gispen ct al.". R. SCRUB TYPHUS GROUP tsut.vugamushi has been isolated from Scrub typhus is a zoonosis that causes trombiculid mites and three different species of human disease comrnonly seen in rats collected in North J;akarta'4. Recently. a ~~i~~,z,d,5.~5.16.22-24. The etiologic agent, R. case of scrub typhus in an individual residing in (Orientia) tsutsugamushi, the only species in the central Jakarta has been identified3'. SCRUB TYPHUS GROUP, is acquired following the feeding of an infected chigger, the The species, H. tsutsugattiu.~h:hi,is made up six legged larval stage of trombiculid mites, on of many distinct strains that vary in virulence32 skin tissue fluids of a human host. The and antibiotic rc~istance~~.Immunity to subsequent rickettsial infection is characterized hornologous strains of scn~btyphus rickettsiae by first a local then a systemic vasculitis. A may continue for years. however. immunity to cutaneous lesion or eschar begins at the site of the many heterologous strains of R. the chigger bite, and the vascular inflammation ts~tsugamushi may onlv persist for a few spreads throughout the blood vessels of the body months3'. Conseaoently, individuals can involving various orga~is'~~~.Though scrub become infected more than once with H. typhus has been known since the late 1800's its tstrtsugatn~shi"~'~.This lack of cross immunity notoriety did not emerge until World War 11, and the previously successful treatment with where in the Pacific theater, it was feared by antibiotics dinlinishcd the drive for and the military personnel more than malaria22.2'. This successful completion of the development of an was due in part to the high nlortality rate, where effective vaccine for scrub typlit~s'~.

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SPOTTED FEVER GROUP response develops, causing vasculitis, and the triad of fever, head ache and rash (rash may The spotted fever group is composed of only occur in 50% of the patients and is more more than 20 antigenically related rickettsia1 difficult to see in darker pigmented people). species'. Described here are several human The disease often affects multiple organs with diseases associated with the spotted fever group manifestations involving the skin, skeletal rickettsiae. Rocky Mountain spotted fever (R. muscles, central nervous system, myocardium, rickettsii) is found only in the Western lungs, liver and kidneys'". Diagnosis often Hemisphere. The vectors are the ixodid ticks depends on the history and clinical presentation. and the normal hosts include rodents, dogs and The Weil-Felix agglutination reaction is foxes. Mediterranean Spotted Fever also known variable for both the OX19 and OX2 antigens as , Kenya tick typhus, Indian and negative for the OXK. A four fold or tick typhus and South African tick typhus (R. greater rise in titer for EIA or IFA followed by conorii) is also vectored by ixodid ticks. Hosts ;onfirmatory Western blot analysis will provide include dogs and rodents. Mediterranean laboratory diagnosis for spotted fever Spotted Fever distribution includes the di~ease".'~. However, for species identification Mediterranean, Black and Caspian Sea areas, the method of choice is culture of the agent in and in the Middle East, India and Africa. laboratory animals or tissue culture. In Siberian tick typhus or addition, PCR has been shown to detect (R. sibirica) is found in Siberia, Armenia, rickettsial nucleic acid from blot clots of Mongolia, Central Asia & Europe. Ixodid ticks individuals with acute cases of Rocky Mountain are the vectors and rodents are the usual hosts. spotted fever)9, and species identification can be Australian or (R. ascertained utilizing PCR and restriction australis) was discovered in Queensland, fragment length polymorphisms (RFLP) Australia, but has now been reported in other analy~is~~.~'.Spotted fever disease may be fatal, areas of A~stralia'~. The vectors are ixodid but when identified and treated early with ticks and the hosts are rodents and marsupials. tetracycline or chloramphenicol mortality can Rickettsialpox (R. akari) has been located be reduced ~ignificantly'.'.~~. mainly in urban areas of North America and Russia, but has also been found in Southern Members of the spotted fever group of Africa and Korea'.'. The vector is the rickettsiae have not been reported in Indonesia hematophagous mite (A/lodermanyssus though they are endemic in other Asia countries sanguineus). Hosts include the house mouse and Australial.2,4,5,?2.36. There has been a lack of and other commensal rodents. seroreactivity found in Indonesian populations that were surveyed utilizing an EIA with R. Infection with spotted fever group conorii antigen preparation". rickettsiae usually involves the bacteria entering the human body through openings or abrasions io the skin due to the tick or mite bite, or by the DISEASES DUE TO RICKETTSIA-LIm infection of the conjunctiva by fingers ORGANISMS contaminated after crushing the arthropod vectors. The organisms multiply locally at the Q fever (C. burnetii) is found worldwide site of invasion and spread to the endothelial and is associated with domestic animals and cells of blood vessels. An inflammatory rodents. Though C. burnetii has been found in Rickettsia1 diseases: Risk for ...... Allen L. Richards et al

several tick species and other arthropod vectors, the limited distribution of the sandfly vector it is thought to be maintained in nature (Lutzomyia verrucurum). primarily by aerosol transmission. Humans are believed to be infected by inhalation of the Trench fever, discovered among the troops airborne organisms. C. burnetii, unlike the fighting in the trenches during World War I, rickettsiae, are very resistant to inactivation by was originally named Rickettsia quintana. chemical and physical treatments. C. burnetii is However, when it was found to be able to grow known to survive on wool and other fomites for on blood agar plates and therefore determined up to one year2. Symptoms of acute Q fever are not to be an obligate intracellular parasite (it nonspecific and characterized by fever, attaches to the outer membrane of eukaryotic headache, chills, myalgia, and malaise. cells44) as are the other rickettsiae, it was Pneumonitis may occur, however, rash rarely separated into its own genus R~chalimaea'.~. does. Q fever is usually self limiting, though Bartonella (Rochalimaea) quintana is the only chronic Q fever with hepatitis or endocarditis is agent described in this review that does not not un~ommon'.~. Diagnosis by reference have a host other than humans. The vector, the laboratory usually involves performance of a human body louse (Pediculus humanus noncommercial enzyme-linked immunoassay. humanus), transmits the disease from man to Recently, PCR with species specific primers man. Humans have been known to be infectious have become available. Culture of C. burnetii, for more. than ten years2. Distribution is is risky and so is only performed in a few associated with humans, generally living in laboratories world wide. Treatment usually is poor social economic conditions, worldwide. with one of the tetracyclines, though there maybe resistance2, or chloramphenicol. Identification of the agent associated with cat scratch disease had eluded scientists for Q fever is most likely endemic in some time. It is believed now to be B. Indonesia as it is believed to have world wide (Rochalimaea) hen~elae~~.~~.The natural vector distrib~tion'.~. In addition, a serosurvey for B. henselae is unknown, but may be ticks conducted by Van Peenen, et a]., reported that andlor fleas. This agent is found worldwide and 25% of human serum tested from throughout its major host is the domestic cat4'. the archipelago had evidence of Phase I1 antibodies against C. burnetii4). The prevalence Infections for bartonellae are usually via of hospital admitted cases of Q fever in openings or abrasions in the skin of the human Indonesia is currently unknown. body due to the bite of sandfly, louse, tick or flea, by infection of the conjunctiva by fingers Very recently, the Rochalirnaea genus has contaminated after crushing vectors or as in cat been combined with that of Bartonella because scratch disease the bite or scratch of the natural of sinlilarity in 16s rRNA, and DNA host-cat. The organislris multiply locally and relatedness. The genus name Bartonella was spread through the blood vessels (bacteremia). retained because of its nomenclature priority2. The im~tiediateresponse to bacteremia includes B. hacillfornlis was identified in 1909 as the fever and headache. In Carrion's bartonellosis erythrocyte-adherent agent of bartonellosis or there are also anemia, adenopathy, thrombo- Carrion's disease. Bartonellosis is found only in cytopenia, severe myalgias and arthralgias, and the intermediate altitudes of the South possible mental status changes. Without American Andes. This is believed to be due to antibiotic treatment, fatality rates for

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bartonellosis maybe high2. Vermga pemna oxytetracycline, doxycycline and chloramphe- may be a common late-stage manifestation of nicol have been reported2. Carri6n's disease. Bacteremia due to B. quintana and B. henselae are rarely fatal though Human ehrlichiosis is a recently described the illness maybe more severe in the disease whose importance as an arthropod immunocompromised host, e.g., AIDS borne-illness continues to gr~d~~.~~"~.Recently patient$'. Cat scratch disease is commonly this disease has been divided into two similar associated with a cutaneous papule or pustule at illnesses that have different causative agents. the site of the bite or scratch and regional The original human ehrlichiosis is now known . Fever may also accompany as human monocytic ehrlichiosis (E. this self-limiting disease. Diagnosis of chaffeensis). The second, is known as human Bartonella species by culture of clinical granulocytic ehrlichiosis, the etiological agent is specimens is difficult and thus the laboratory unknown but is very closely related to E. must be instructed about the presumptive ,~hagocytophilaand E. egui5'. The tick vectors diagnosis before submitting the specimen. for the two diseases are believed to be Warthin-Stany silver technique is used for Ambylyomma and Dermacentor species for staining of tissue samples. Fourfold or greater human monocytic ehrlichiosis and Ixodes and rise in titer for EIA- and FA-IgG or the Dermacentor species for human granulocytic presence of species specific IgM is diagnostic. ehrlichiosis. The natural hosts may be deer, PCR is the most sensitive method for Bartonella dogs or other mammalss2. Distribution in the species identification. Treatment with United States is wide spread. Other locations tetracyclines, erythromycin or chloramphenicol throughout the world have not been extensively is effective'. studied5. Though different agents are involved in human monocytic and granulocytic EHRLICHIA GROUP is made up of ehrlichiosis, symptoms are similar and include a related bacteria species in the genus Ehrlichia sudden onset of fever, chills, headache, myalgia, and the tribe Ehrlichieae in the family of arthralgia, anorexia, nausea, vomiting, Rickettsiaceae4'. Several species have been and rarely rashsz. The diseases are related to animal disease and two to human self-limiting. However, fatality rates of 2-10% diseases. Sennetsu ehrlichiosis, also known as have been reported2.". Laboratory diagnosis is sennetsu fever, sennetsu rickettsiosis (E. by polymerase chain reaction to identi@ the sennetsu) was described in Southwest Japan in agent during the acute phase and by serological the late 1800's. However, the agent was not assays (EIAIIFAI Western blots) during identified until 1953. The vector is currently convale~cence~~~~~~~~.Attempts of isolation from unknown as is the natural host. The disease has blood are usually unsuc~essful~~.Recommended only been identified in Japan and Malaysiaz. treatment is with the tetracyclines The symptoms include a sudden onset of fever, (doxycycline). Chloramphe- nicol may not be chills, headache and myalgia, insomnia, effective5'. diaphoresis, sore throat, and anorexia. General lymphadenopathy is common, hepatomegaly Ehrlichiae are responsible for many animal and splenomegaly occur in approximately a and human disease^^,^^. They can be divided third of the cases. The disease is self-limiting, into two groups based upon whether they infect and no serious complications or fatalities have monocytes or granulocytes. E. sennetsu; E. been reported2. Successful treatment with chafleensis; E. canis canine ehrlichiosis,

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tropical canine pancytopenia; and E. risticii REFERENCES equine monocytic ehrlichiosis, Potomac horse fever; cause monocytic ehrlichiosis. E. 1. Dasch GA, Weiss E. (1992). The Genera phagocytophila tick-borne fever of sheep, goat, Rickettsia, Rochalimaea, Ehrlichia, Cowdria, cows, bison and deer; E. equi equine and i\'eorickettsia. In: Balows A, ed. The prokaryotes. A handbook on the biology of ehrlichiosis; and E. ewingii canine granulocytic bacteria. Vol III. New York: Springer Vcrlag. ehrlichiosis are granulocytic ehrlichiosis. p:2407-2470. Currently little is known of the presence of any of these agents in Indonesia. 2. Ferraro MJ, Gilligan PH. (1995). , Rickettsia, and Related Bacteria, in Manual of Clirzical ~i4icrobiology, 6th edit. Murray PK, SUMMARY STATEMENT Baron EJ, Pfaller MA, Tenover FC, Yolken RH, eds. ASM Press, Washington DC Rickettsia1 diseases and diseases due to Ch.VI:663-695. rickettsial-like bacteria are endemic throughout 3. Walker DH. (1995). Rocky Mountain spotted the world. This includes Indonesia as well. fever: A seasonal alert. Clin Inf Dis, Scrub typhus and murine typhus have been 20:1 11 1-1 117. investigated in Indonesia, however, diseases 4. Cross JH. (1984). Rickettsia] infections in such as those related to the spotted fever group Southeast Asia. Medical Progress, 1 I : 19-26. of rickettsiae, trench fever, bartonellosis, Q fever and ehrlichiosis have been almost 5. World Health Organization Memoranda/ completely overlooked. Thus the aim of this Memorandums. (1 993). Global surveillance of rickettsia1 diseases: Memorandum from a WHO review was to promote awareness of diseases meeting. Bull WHO, 71:293-296. associated with rickettsiae and related organisms, and to stimulate rickettsia1 disease 6. Regnery RL, Fu ZY, Spruill CL. (1986). Flying research in Indonesia. squirrel-associated (epidemic typhus rickettsiae) characterized by a specific DNA fragment produced by restriction endonuclease digestion. J Clin Mcrobiol, DISCLOSURE 23: 189-1 91.

The opinions and assertions contained 7. Arnano K-I, Mizushiri S, Fuji S, Fukushi K, herein are the private ones of the authors and Suto T. (1 990). Immunological characterization of lipplysaccharides from Proteus strains used are not to be construed as ofiicial or as in Weil-Felix test and reactivity with patient reflecting the views of the U.S. Navy or the sera of tsutsugamushi diseases. Microbial Department of Defense, or Departemen Imrnunol, 34:135-145. Kesehatan RI. 8. Carl M, Tibbs CW, Dobson ME, Paparello S, Dasch GA. (1990). Diagnosis of acute typhus infection using the polymerase chain reaction. J ACKNOWLEDGMENTS Inf Dis, 16 b:791-793.

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