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lyme disease - Lyme Disease A bacterium transmitted to...

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Unformatted text preview: Lyme Disease A bacterium transmitted to human beings lty tite ltite of a deer ticlt causes this hazard of summertime. interleukin-1, an immune-system regulator, may mediate its potentially serious arthritis-like symptoms. Gal] 5- Hahicl'lh Gregory Beck and Jorge L Benach fate. issr ticlthorne bacterial dhease that is most liltely tobecontractedduringthemonthsoillrne through Sepflmber, when youngsters and aciulls are-outdoors, walking bareleged in woods and long ass. EFLFlt is spreading rapidly and is now the most t're- quently diagnosed Edi-transmitted illness in the 1.15., it' not in the world. In 1915, 5'9 cases were recorded in Connection; in 1985 the number had climbed to 363 cases- Moreover, Lyme disease has now spread to three regions of the 1.1.5. {see Figure 3.1]: the Northeast {in oo-astal ate-as}, the northern Middle West [Minnesota and Iil'tliscot'usini and the West {parts of California, Greg-3n, Utah and hie- trade}. The disease is also found throughout Europe and has been recorded in dissuade, the Soviet Union, China. Japan and Africa. Because its symptoms can he severe, ranging from acute headache to neurological impairment and manifestations resembling rheumatoid arthritis, the disease has elicited concern in the 12 years sinceit was first described. The discovery of this disease, From its recognition as a clinical entity to the idenli- iication of its causative agent, is a triumph of mod- LymediseeseisanafiiclionofsorcunerJtisa five efforts of a great many scientists. Lynne disease was first reported in November of 1955, when the Conneclicut State Health Depart- ment reoeiyed telephone calls irom two mothers whose children had just been diagnosed as having juvenile rheumatoid arthritis. The condition is a de- I«restarting one that can lead to lifelong suffering and physical dehilitalion, and it is not surprising that these mothers were concerned. What alarmed Health Department officials, however, was the news that these cases were not isolated ones: ac— cording to the women who telephoned, a number of adulla and chllclt'En in the town of Lyme had re- cently been diagnosed as having rheumatoid arthri- t'ts. Health officials conduded that this was more than a regional anomaly and might represent some thing very sedans: either the presence of an entri- ronniental boadn or possibly the beginning at an epidemic. '1" hey contacted Allen C- Steere, who was then a postdoctoral fellow in rheumatology at the Yale Llrlitrersity School of Medicine- He had just corne pleted training with the epidemic-intelligence ser— L't'ME DISEASE ' 19 Flyue 3.] LIME DISEASE rantiauer. In spread Ihrllflgil- euflreufietthuhaen rlpdfiflhfilhlfl-Hfllltflfl are Eaund lining. the Net“: Miami-I: mart tram Manchu- I-E'Ill Ia Marti: Earathtl. ht t-Hnnerafl and thmain, in Tens-and: IIIII'LE thPatlflmeflinCallfincnh-ndflreym. vice at' the US- lIii'enters t'ar Dim Central in At- lanta. Il'i'iIiEIIEd by this bizarre authreait ai' arthritis, he agreed ta- undeflalte an epidemidlagicai inves- Hgadan Steere and his calieaguea diecmrered that the dia— easewee limitedta threetnamshipaineastem Can- necticuh I{lid Lyme, Lyme and East Haddam which are adjacent celrtrnurtities en the east bani: at the taunt-cecal: River. Juvenile thematnid ”fluid!- is numeliy a rare candidate affecting early one in Iii-Ell,iltli} children. and yet eat of a tatai pepulatian nf lmflflh‘ntheee Haeemwnefltl children. [arid 12 adults} had bean diapaeed a5 having the candilian: lilil times the narrnal accurrence. Mereeyer, distinct chatter patterns emerged within each ten-m. Mat-t fictiee: lived in heavily weadedareasandaniyafeweithemintemn eentera. in Did Lyme and East Haddam hait'et' the effected htdividuaie lived cm iuat fem made, and here the frequency in children wee mam tintea higher than nemtal: ene in It] children a: appealed te an expected tune in Iflflrflflfl. 'I'I‘dti wat- Ideally I": ardlruary Farm at rheumateid arthritis, and there we few clues to guide Steer-e in his hweeligatian. Nevertheless, he made sevelal hnperiant finding- Salter-rd met. hmfll'. have the teen rep-areal! learn Arkansas. Flatt-ta. Gear-5h. Indium Kentucky. Heine. Hithifill'lr Mmt-Ill-h Nevada, I'HE'IIIII flung-hire, flhia, Tart- neflee, Utah and. h'ernam.‘1'he emetic-“ted Electrical: are Indicated l'e ruler. [the war. that the disease is net ertictflariy canta- gieue: individuals in the same andIy after; .33“. treated it In difierent years. sinether was that the majarity cl! caries. regardieee at the year, first pre- sented sympt-arna during. the warmer nmtha. lune threugh September. A third finding was that 15 percent hi the patients Steere heat-viewed ten-rem- beredhaehtgaetrangeshinraahtrammetaaeeeral weeics hefure the anaet at arthri'lisr-lilte sympterns. The desa‘iptiens at' the rashes were rentarhably stat- flantlwyhadelartedaaaredpapuiearfimali hump. and gradually expanded tn farm a hairs-eye free-I lit to 5D ce'ntimetere in diameter. The accur- rence at the rash an the cheat. ahdmnen. back at hutteclu elf meet patients suggested that meat likely a trawling, rather than a Hyh‘ig, htaect Dr art arachn nidhad Meantittedthediaease.altheughheene eeuid clearly ren'tinfnher being bitten. teere eeneluded an the battle of the-fie finding that he was. dealing with a prefiuteily Unread;— nixed riiaeaae pra'heh-iycauaedby aviraeandh'anaw Initted by an unhnm arthI-ttrpthd [the WW h: which insects. apidera and ticks he'lcrngj. He named it Lynne arthritis er Lyme disease far the town in 30 ' GAIL S. HABICHT, GREGORY BECK AND JORGE L. BENACH which it was first observed. In 1975—76 he began testing sera from Victims of Lyme disease for the presence of specific antibodies against 38 known tick-transmitted diseases and 178 other arthropod- transmitted viruses. Not a single test result was positive As he carried out research on the disease and its probable causes, howeVer, Steere came across some . interesting information. In 1909a similar phenome- non had been described in Europe. A Swedish phy- sician, Arvid‘ Afzelius, described an expanding red . skin rash in patients who had been bitten by the tick ’ ' _ Ixodes ridinus. Afzelius named the rash erythema chronicu‘m migrans (ECM), which literally means “chronic migrating red rash " ECM sounded remarkably like the bull's s—eye rash that had been observed in Lyme disease patients. Although it lacked the arthritis-like symptoms char- acteristic of Lyme disease, Steere concluded that ECM and Lyme disease might be closely related and have similar modes- of transmission... ‘ European physicians had successfully treated ECM with penicillin, indicating that the most likely agent of infection was not a virus but a bacterium. Yet when fluid was removed frOm the joints of Lyme disease patients and cultured, no microorganisms could be found. Meanwhile the number of cases of Lyme disease continued to climb. inally,’ m 1977, nine patients affected by the ECM rash that year remembered having been bitten by a tick at'the'site of th'earash. One of them had removed the tick and s'aVed it, and. was able to give it to Steere for identification. The tick, barely larger than a pinhead, was a dark brown,” hard-bodied animal that might easily be mistaken fora scab or. a piece of- dirt. It was not surprising that it had taken Steere and his group almost two years to locate it. The tick was identified by Andrew Spielman of the Harvard School of Public Health as Ixodes dam- mim' (see Figure 3. 2), a species closely related to I. ricinus, thetic-k responsible for European 13cm. Now that I. dammini was identified, investigators work- ing on Lymedisease ”hoped to isolate _- the actual agent of infection. First they had to be certain that the tick was indeed the vector for Lyme disease. If the distributiOn of I. dummini in the wild corre- sponded to the outbreak of Lyme disease, the cir- curristantial evidence linking the two would be strong indeed. Biologists at Yale set out animal traps on both sides of the Connecticut River 1n order to map the distribution of Idees along the river and at the same . time find out On which mammalian species it was : , feeding. The distribution of ticks was just as they hoped: the dog tick Dermacentor variabilis was equally common on both sides of the river, but I. . dammini was 12 times more abundant on the east . ,sidewnear Lyme, Old Lyme and East Haddam, where Lyme disease was by that time kndwn to be longer-mil The workers were convinced that I. dam- ' mini must be the primary vector in the transmission _ of Lyme disease. till the agent responsible for both ECM and Lyme § disease remained elusive. Repeated cell cultures ' and microscopic examinations of the tick’s internal ' organs failed to reveal the presence of a bacterium ' or any other pathogen. Then, in the fall of 1981, a j fatal case of Rocky Mountain spotted fever, a rick- ettsial disease transmitted by the dog tick, was re- 5 ported on Shelter Island, off the coast of eastern I Long Island. The New York State Department of _ Health sent a team of biologists to the island to Collect live ticks. Because the nOrmal vector, Derma- f' cantor'variabilis, is not found in the fall, adult Ixodes dammini were collected instead and were Sent to the " Rocky MOuntain Laboratories in Hamilton, Mont, -- for study. ' There Willy Burgdorfer, an international author- ity on tickborne diseases, squashed the digestive ”p- tract of the Ixodes-tick and examined-it by dark-field 5, ' microscopy. To his surprise hefound the gut teem- : ing not with the rickettsiae that cause RockyMoun- tain spotted fever but with long, irregularly shaped spirochete, bacteria. Burgdorfer knew that I. dam- _- mini had been implicated as the probable vector for Lyme disease, and” he also knew that the spirochetes 2" were not the infectious agent of Rocky Mountain «- spotted fever. He wondered whether these bacteria. c0uld be the cause of Lyme disease. Fortunately f Alan G. Barbour, then at the Rocky Mountain Labo- . ratories, was able to grow the spirochetes in pure 1, culture and obtain them' in sufficient quantities for) experimentation. - .7, Because patients exposed to an infectious agent; have antibodies in their serum that react to the; agent, an antibody test can be a good indicator of}: infection.- Serum samples from New York patients: infected with Lyme disease were sent to Burgdorfer, who tested them for the presence of antibodies;- against the spirochetes. Unlike the earlier series of}? .tests conducted by. Steere, the results this timewerei: positive: the sera showed a pronounced antibody}; L‘i'h'lF. DISEASE . .31 Flgure 3.1 SCANNING ELECTflflM HICRDEIAFHE ofa female I. dammisi show the animal. enlarged twill-meters. in dorsal view lief" and a clone-up at the head, enlarged us diameters. In ventral slew {righti— The legs have claws and adhesive peas sHhelr lips Ihat help the Iiel: dingto its host while feeding. The head consists of a mall cranium and a large probes-as, called the hyjpostome. snrroondesthy response- to the bacteria, inclicaling that the patients had in fact been iniected by the sph'ocheie. A more direct tat of the pathogenicin ot' the spirochete 1was carried out on rabbits- Ephcchete- infected ticlcs were placed on the shaved skin of albino lab-hits, where they could be observed feed- ing on the blood of their hosts. After several weeks lesions similar to use sma rash appeared. and micro- scopic examination of the skin at the site of ticit attachment revealed the presence of li‘ll'li‘ api- rod1etes- rom this point investigations proceeded rapidly. By the summer of 1932 spirochetes had been isolated from the blood, slain and cuebrospinal fluid of Lyme disease victims by inyeatigators at the New York State Department of Health and at Yale. Rus- sell C- {oi-Laser: and his colleagues at the University of Minnesota Medical School studied the Lyme dis— ease spirochete and determined. on the bests of its DNA. that it was. a new speci- in the genus lion-c- l'irt- In 1934, to honor :ils dist:classifier.I Burgdnrfen they named it Estrella burgdoirferi. B. heiydoifcrt' is a typical spirochete: it is a unicel- my palpa. The hyp-nllosre drllll through the skin oil host uni-ll it reaches a capillary and linen draw] blood out of the hull and Into lire risk. The serrations on the hypoa- totne's luriace its-Jpn In anehor il in place once ll: ha- pierced n blood yesseL [Photos by 5. F. [-Lsyel. W. Enrgdorlier and M- D. Ear-win at the Rocky Mountain Laboratoriem lular, loosely coiled. left—handed helix {that is, it coils in a counterclockwise direction}. lta length varies but averages 30 mirrometers tthousandtha of a millimeter}. with seven turns of the coil. Like most spirachetec it is small and airlines to detect: the diameter of the cell ranges from -13 to .15 n'iiccome- tar, allowing it to pass through many filters de— signed to retain bacteI-la Dnce B. hurgderfcn' had been conclusively identi- fied as the agent of Lyme disease it was possible to track its distribution in nature. Edward lei. Bosler of the New "r'orlt State Department of Health found the spirochete in the tissues of several mammals. including field IllitE, soles and deer. as well as in all stages of i. dometfrti {see Figure 3.3}. Detection of the spirochele in mammalian tissue is difficult. Not only is the spirochete extremely small but also it is normally pnesent in W1]? low numbers- The preferred method of detection there- fore depends on fluormcein-laheled antibodies spe- cific for ll. hurydorferi. 'l'l-Lese bind to the spirochetes and floors-ace on illumination with ultraviolet light. making it possible to detect the presence of even a few spirochetes. Such studios halite-ale that Hamlin .11 1' EML 5. i-LtflCI-IT. GREWR'I’ BECK. AND iflltflE L EEHMI-I F] 3.! WHEN DIEEAEEEAERTING Heirs in the ii an the dag tieh: [Irma-center eartaia‘fl's in]. which inhibits the bacterium that taeaea Emig- Muumfln Elm' tesl fever. and fie cieer 'Ilrl ladies flifltfltfli till. tsl'l'tiflt humitltheLymediseaaeaplraeltete.fln-thtlchspetifi ieedenlheblnedcimafluhflhinclfldinghum travels widely ence it enters the bleedsti'eatn: it has been detected in the eyes. kidneys. spleen. liver. testes and brain at nenheman neme‘talian heslat and also in several species at passerhie birds. [The gee-graphic dishihttflen et' Lyme disease suggests that Bar-relic spreads when Heirs infested 1with the bacterium attach themselves in migrates-y birds} Barrett's burgdetfiri can he detected in the get at l'. densest by dark-field Iriicrescepy er by remeving the cements at the til-Jr's gut and greeting the spine- cheteti in culture. Surveys alcrng the North Atlantic ceastline indicate that in highly endemic areas tram Si] it: Hi} element at trades ticics have 3. bargderferi in their gastruintestinal systems. in ennttast. only .3 percent at all trades fated en the West Ceastharher the apirechete. a finding that cenflates well with the much lower hiddence ct' Lyme disease there. he life cycle at l. demrrtirri eternally spans twc years {see Figure 14). Eggs are depestted in the spring and hatch trite free-living lmae a Inc-nth later- timing the lir'stsummer the larva t'eeda lance [fare perindefttvedayflenthebiee-d atahcsttanci then enters a stage ceincident with the unset at celd Weather in the tall. The fella-Hing spring the larva melts. enters a strand immature stage called the nymphai stage and again attaches itself In an animal hast. this lime in leed fer three at icur days- beings. and may triple in Illa tallest-in; a ueaL The bet- ter: ultralight» the actual site nil-each tick ages-cinema] (umpire ti that have net ted serenity ll'tfl't with titli- fltflarengergedhyameailrigitLTheinp-fiatr leniargedfiaurtimesilhnw greater minimiflitllli'iLmF Mthaugh the larvae and nymphs attach a variety cf vertebrates. the maimity at the ticles in these age ceherts are inland en the whitenicreted amuse. Fern— nryscus lea-capes. it is at this BE? that ticics are meat likely he attach ves e smarts. mm'artsewmm int-:1 the adult stage. They an he heard in brush ale-nut lane meter abuve the greund. where they can eafly at; taeh therrrseives 11) larger mammals. Like the imma- ture ticits. the adulm feed en a variety ni manta-ta- lian heats. but In the nerflieastem LLB. they are fennel predelninately en. the whiIEvtaiied deer. Elde- csileus er'rginienas. The adult Ih'Jcs mate an the heat seen alter the female attaches herself in it. «Only the females ever-.vinter: the males diesecm alternating. ltisnetlmcrwnwher‘e theeggsareclepceited. but they hatch in the spring—1nd the entire qrcie is repeated. any-ens whcl lives in at visits an area where Lyme disease is endemic is susceptible tn the condition Warning signs have been pasted in areas where the miesndan is particularly high {see figure 3.5}. Lyme disease is indiscdardnate: it affects hath sexes and. all age glen-ups. Alti'tnugh itisprepclrtiunate numbers at children have been affected. this may simply reflect the fact that children spend mere time playing in wens-sled areas than adults de. in additien. peeple when have nettle-er animals are inlet-v11 to he figure it LIFE C't'ELH at J'. humid IIIII tar tare jun. Efll Ire dupe-liter! In the little; and the lane! [with]! have III-fly- Id]: legal energe- seceni week later. The;r teed meeduringthe Hummer. unaltyanthe blmdat'mlfl unhauebumlmlmaemnltflreiafla spring teed ltllll I] WWI] mm the Hummer—an Purim larger Illa-mull at greater rial. fer centracting Lyme disease. but it it! not clear whether this reflects a mare autdclcrr life— stylecefltefsctflistfltehununasrebitbenbyticlra attached in the far at their dumesfic maintain. Lyme disease is else rapidly becamirlg a veterinary prob—em: and hence: in mdemlc arear. have decei- aped debiliteung fclmt preblema that Veterinarians, believe are caused by Barrett's burgdmfm'. liniclllf Lyme disease can bedhricied intn three stage-st The and mat ab atsge is character-teed by the erythema chm migrant rash{aceFigu.re3Ei} wlfichdetr pafcam ataE-IJ day: after an individual has been bitten- The rash is den a: Jim-ll. bchtaswbefare mailing am a full. Adult: attach thenuelm la a hit. use. all! the white-hfllll IIII'I', where they mile. The pie-s Ille- shacflf lbleeaIfl-r. but the females teatime ta teed tn ab- Ial: the crate-tn necessary for egg flevtlapment. Funnel: II]! their :35: and 11h. such an adult: in t'reulq_1.lettti}r accan'Epanied by pmfatmtl tailgate?J fear-er; chills. headache and backache. In acme paflmm hpwe'u'er, thee-e Bjttfip-tflfl'tfi. including ecu, fail in appear. In hem 15 In Sflpcccentafcaeesseeenclsqr leeiacla appear at val-lune altea an the badge. Eccause that: lack distinct recl papillae at their center, they probably reflect the spreading airy-trachea by we}! at the bleed rather than additienal lick bitea. The crane] tag-e [aha net always uprated]: is mm]: by neumlaglvcal complications and mism— Hal-1..r muecuinakeletal pain. Apprmcimatety 5 percent of palienta decal-up cardiac difficulties lasting far from three days tu- eh: war-ins- These patimtr experi- ence palpiteflana. dizfirteaa ctr ahartneas at breath 34 ' GAIL 5. HABIEl-IT. GREGDH‘L’ BECK AND Mil-GE L BENAE'H a} TICK INFESTED AREfl run FURTHER IhFflflMiTlflH .- .. cantata; iii-3.743 'r _ lia‘__,_.—-"" Figure 3.5 HEALTH WERNING polled near the- filial-II: will in Halli I. HT... ll one of many such notice: diltflhnted throughout tickle-foam areas on Long Island. Lyme disease is rapidly inn-easing in wooded area: where associated with irregular electrical impulses to the heart [atrioyentrieular block}; and some may require tempera carriakers- Theghirdistage typically involves the onset of arlhn' .o tprohlemscharacterialicofrheumatotd arthritis occur to about till percent of Lyme disease patients who have not been treated. generally wifltin several months but not more than hut} years after the onset of EM. Attacks of arthritis usually last from. a few days to a few weeks at a time and primarily affect the knew [which can lead to diffi— cult}r in wail-ting} and other large...
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