Hantavirus pulmonary syndrome: Report of four Alberta cases

I MAY 1993, THE FIRST CASES OF HAN TA VI RUS PUL MO NARY SYN drome (HPS) were re ported from the Four Cor ners re gion of the south west ern United States in clud ing New Mex ico, Ari zona, Colo rado and Utah (1). As of Feb ru ary 1, 1995, 103 cases have been re ported in 21 states with an over all mor tal ity of 52% (per sonal com mu ni ca tion). The first con firmed cases in Can ada were docu mented in Brit ish Co lum bia be tween Feb ru ary and June 1994 (2). In 1994, fol low ing me dia re port ing of the Ameri can HPS cases, a pa tient who had been ad mit ted to an Ed mon ton hos pi tal in 1990 with adult res pi ra tory dis tress syn drome of un known eti ol ogy wrote to lo cal phy si cians re quest ing that his case be re viewed re gard ing a pos si ble di ag no sis of HPS. Stored se rum was posi tive for im mu no globu lin (Ig) M an ti bod ies to han ta vi rus. Within the next three months, two fur ther cases were rec og nized. Epi de mi ol ogi cal in ves ti ga tions led to the dis cov ery of a fourth case. We pres ent a de scrip tion of the clini cal courses of the four Al berta cases.

tioned at a ru ral camp site, where there had been spray ing of bio logi cal in sec ti cide.He had also driven a die sel pow ered tank in which he had been ex posed to ex haust fumes.There was no his tory of re cent for eign travel.He later ad mit ted to shar ing his tent with deer mice.
Fol low ing ad mis sion, he was found to be hy poxe mic with bi lat eral in ter sti tial in fil trates on chest x-ray.He was treated with in tra ve nous eryth ro my cin and, as he de vel oped pro gressive res pi ra tory fail ure, was in tu bated and trans ferred to an Ed mon ton ter ti ary care hos pi tal for in ten sive care.
On ex ami na tion he had a tem pera ture of 37.7°C, blood pres sure 92/50 mmHg and pulse 88 beats/min.Ex ami na tion of the chest re vealed bi ba si lar crack les.Frac tion of in spired oxy gen (FiO 2 ) of 1.0 was re quired to main tain ade quate oxygena tion.
Ad mis sion labo ra tory find ings are listed in Ta ble 1. Pe ripheral smear showed neu tro phil leu ko cy to sis with in creased band forms and a low plate let count.
A pro vi sional di ag no sis of atypi cal pneu mo nia was made, with a dif fer en tial di ag no sis of acute in sec ti cide poi son ing or hy per sen si tiv ity pneu mo ni tis.
Fol low ing trans fer to the in ten sive care unit (ICU), the patient was ven ti lated with pro gres sively higher re quire ments of in spired oxy gen and posi tive end-expiratory pres sure.He was treated em piri cally with in tra ve nous eryth ro my cin, ce furox ime and strep to my cin.Car diac moni tor ing via a Swan Ganz (Ed wards Labo ra to ries, Di vi sion of Bax ter, Cali for nia) cathe ter re vealed a pul mo nary cap il lary wedge mean pressure of 25 mmHg, mean ar te rial pres sure of 62 mmHg, cardiac in dex of 3.28 L/min/m 2 and sys temic vas cu lar re sis tance in dex of 1170 dyne/sec/cm -5 /m 2. Sev eral pneu motho ra ces were drained.Bron cho scopy re vealed no gross ab nor mali ties.
By day 5 of ad mis sion, the pa ti ent's oxy gena tion had improved.By day 7, chest x-ray also showed marked im provement and FiO 2 had de creased to 0.45.Af ter this ini tial im prove ment, oxy gena tion once again de te rio rated and he be came he mo dy nami cally un sta ble re quir ing ino tropic support.Chest x-ray showed bi lat eral air space con soli da tion and he was given in tra ve nous piper acil lin and to bra my cin as empiri cal treat ment for pre sumed no so comial pneu mo nia.
An open lung bi opsy on day 12 showed chronic dif fuse alveo lar in jury and hya line mem branes con sis tent with adult res pi ra tory dis tress syn drome of prob able vi ral eti ol ogy.
In tra ve nous meth yl predni so lone was com menced on day 13 at 1 g in tra ve nously daily for three days.By day 14, he had again im proved with FiO 2 re duced to 0.6.Chest x-ray still showed bi lat eral air space con soli da tion.
On day 17, a tra cheostomy was per formed.On day 22, increas ing pu ru lent se cre tions and an ele vated tem pera ture with new al veo lar con soli da tion on chest x-ray prompted a sec ond di ag no sis of no so comial pneu mo nia.He was treated for Escheri chia coli iso lated from spu tum.His ICU stay was further com pli cated by the de vel op ment of a large pul mo nary em bo lus, which re quired throm boly sis.
He was weaned from the ven ti la tor on day 73, when his main prob lems in cluded gen er al ized weak ness due to loss of mus cle mass and mild pe riph eral neu ro pa thy of un de termined eti ol ogy.Pul mo nary func tion tests be fore dis charge on day 81 re vealed a re stric tive de fect with re duced dif fus ing capac ity.
Bron cho scopy speci mens from early ad mis sion were nega tive on di rect mi cro scopic ex ami na tion and cul ture for acid-fast ba cilli, fungi and bac te ria in clud ing le gionella.Sil ver stain for Pneu mo cys tis car inii was nega tive.Se rol ogy for in - A ret ro spec tive di ag no sis of HPS was made in 1994 by testing for han ta vi rus an ti bod ies.Both IgM an ti bod ies from stored se rum and IgG an ti bod ies from fresh se rum were posi tive for Sin Nom bre vi rus at ti tres greater than 1:1600 by en zyme immu no as say (EIA).Lung tis sue from the origi nal open lung biopsy was also posi tive by im mu no his to chemi cal stain ing for han ta vi rus (per sonal com mu ni ca tion).

CASE TWO
A 55-year-old male was trans ferred to an Ed mon ton hos pital from a ru ral hos pi tal on Oc to ber 4, 1994.One week be fore trans fer, he had de vel oped fe ver, nau sea, vom it ing, di ar rhea and a non pro duc tive cough.On Oc to ber 2, he was seen at the emer gency de part ment of his lo cal hos pi tal where he was treated with in tra ve nous flu ids for a pre sumed gas tro en teri tis and dis charged home.
The fol low ing day he was ad mit ted to the same hos pi tal after pre sent ing with wors en ing res pi ra tory symp toms.Chest x-ray showed patchy left lower lobe con soli da tion, and he was started on in tra ve nous peni cil lin and eryth ro my cin.He had a pulse rate of 104 beats/min, tem pera ture of 38.1°C and res pira tory rate of 56 breaths/min.Labo ra tory find ings in cluded hemo glo bin of 156 g/L, leu ko cyte count of 15.2 x 10 9 /L with a left shift and plate let count of 50x10 9 /L.Se rum so dium was 130 mmol/L and glu cose was 15.2 mmol/L.
The pa tient de vel oped pro gres sive res pi ra tory dis tress requir ing in tu ba tion and trans fer to a city hos pi tal ICU the fol lowing morn ing.Be fore trans fer, he re ceived in tra ve nous meth yl predni so lone and in haled bron cho di la tors.
Fur ther his tory ob tained from the pa ti ent's wife in di cated that two weeks ear lier, he had trapped a mouse in a kitchen cup board on their acre age.He had dis posed of the mouse by throw ing it be yond their back yard and had vac uumed the drop pings from the back of the cup board.The only his tory of travel was to Brit ish Co lum bia in June of that year.
Past medi cal his tory was re mark able for re mote al co hol abuse and pep tic ul cer dis ease.He was a forty pack-year smoker.
On ex ami na tion af ter trans fer, the pa tient was mark edly dia pho retic with dif fuse skin mot tling.Pulse rate was 130 beats/min, blood pres sure was 90/60 mmHg and body tempera ture was 38.5°C.He had pin point pu pils, scleral edema and a pal pa ble left sub man dibu lar lymph node.Chest ex amina tion re vealed coarse, dif fuse crack les.
Labo ra tory find ings are shown in Ta ble 1. Pe riph eral smear showed leu ko cy to sis with atypi cal lym pho cytes.Chest x-ray re vealed ex ten sive air space con soli da tion.HPS was included in the dif fer en tial di ag no sis of atypi cal pneu mo nia.
Fol low ing ad mis sion, the pa tient was started on ceftazidime, eryth ro my cin and pres sor agents.Bron cho scopy re vealed a dif fusely in flamed and bron cho spas tic air way with no en do bron chial le sions.Af ter ini tially ap pear ing to sta bi lize, his con di tion de te rio rated rap idly with hy poten sion un re spon -sive to in tra ve nous flu ids and pen tas tarch.He re ceived a to tal of 24 L of fluid dur ing ad mis sion.
He de vel oped se vere meta bolic aci do sis (se rum lac tate ris ing to 20.4 mmol/L) un re spon sive to so dium bi car bon ate, co agu lo pa thy with prothrom bin time in ter na tional nor mal ized ra tio ris ing to greater than 7, par tial throm bo plas tin time to 129 s and re nal dys func tion with se rum cre ati nine ris ing to 312 µmol/L.He died 30 h fol low ing ad mis sion.
Post mor tem ex ami na tion was lim ited to a liver bi opsy due to con cerns re gard ing biosafety.His tol ogy showed mild steato sis and promi nent he patic con ges tion with mild re ac tive changes in the he pa to cytes.
Bac te rial cul tures from bron cho scopy speci mens grew mixed oro pha ryn geal flora and small amounts of yeast as well as Haf nei alvei.Di rect fluo res cent an ti body test ing and cultures for Chla my dia pneu mo niae, Le gionella pneu mo phila, ad eno vi rus, parain flu enza vi rus and cy tomega lovi rus were nega tive.Cy tol ogy was nega tive for ma lig nant cells and P car inii.Cul tures for Myco plasma pneu mo niae and acid-fast ba cilli were also nega tive.Se rol ogy for M pneu mo niae, C pneu mo niae and L pneu mo phila were also nega tive.
The di ag no sis of HPS was sub se quently con firmed with posi tive IgM an ti bod ies to Sin Nom bre vi rus by EIA.

CASE THREE
On Oc to ber 19, 1994, a 32-year-old farmer was ad mit ted to a lo cal hos pi tal.Since the spring of that year, he had been in ter mit tently un well, with sev eral epi sodes of fe ver and influenza-like ill ness.Three days be fore ad mis sion, he de veloped a fe ver to 39.9°C, chills, rig ors and neck stiff ness.He was ad mit ted with a di ag no sis of feb rile ill ness of un known etiol ogy and treated with aceta mino phen and cephalexin.Admis sion chest x-ray was nor mal.
Due to per sis tently ele vated tem pera ture and lack of clinical re sponse to em piri cal an ti bi otic ther apy, he was transferred to an Ed mon ton hos pi tal on Oc to ber 21.Chest x-ray be fore trans fer showed in creased lin ear mark ings in the perihi lar re gions and fluid in the fis sures.When seen in the emergency de part ment, he com plained of a bi fron tal head ache, non pro duc tive cough and dy suria.Past his tory was non contribu tory.
On ini tial ex ami na tion af ter trans fer, he was dia pho retic.Tem pera ture was 39.9°C, pulse rate was 118 beats/min, blood pres sure was 140/50 mmHg and res pi ra tory rate was 28 breaths/min.Chest ex ami na tion re vealed crepi ta tions at the right lung base.
Labo ra tory find ings on ad mis sion are sum ma rized in Ta ble 1. Pe riph eral smear showed mod er ate throm bo cy topenia with a shift to the left in poly morphs and a few re ac tive lympho cytes.Chest x-ray showed wors en ing bi lat eral in ter sti tial in fil trates.
Fur ther in quiry de ter mined that in the two months be fore be com ing un well, the pa tient had had re peated ex po sure to mice and their nests and drop pings dur ing his farm work.HPS was sus pected.
He re ceived in tra ve nous eryth ro my cin and ce fu r ox ime and oxy gen by mask.Dur ing the course of the even ing, he be -came pro gres sively more dysp neic and de vel oped he moptysis.Ar te rial blood gases on 10 L of oxy gen by mask showed PaO 2 of 48 mmHg, PaCO 2 of 31 mmHg and oxy gen satu ration of 86%.He was trans ferred to the ICU and in tu bated.In the early hours of the fol low ing day, he de vel oped ten sion pneu motho rax, re quir ing chest tube place ment.Bron choscopy did not show any gross ab nor mali ties.By the fol low ing morn ing, he re quired an FiO 2 of 1.0 and ino tropic sup port.
His oxy gen satu ra tion de te rio rated to 84% on an FiO 2 of 1.0 and he de vel oped wors en ing pul mo nary in fil trates.He received in tra ve nous meth yl predni so lone 1 g at 14:30 h.Six hours later, he had im proved with an oxy gen satu ra tion of 91% on an FiO 2 of 1.0.He de vel oped lac tic aci do sis with serum lac tate peak ing at 3.3 mmol/L, which was treated with intra ve nous bi car bon ate.In tra ve nous ri bavi rin was started.
The pa tient im proved pro gres sively over the next few days, with FiO 2 de creased to 0.5 by day 4; he was off all inotropes by day 5. White blood cell count peaked at 9.7x10 9 /L with a marked left shift and se rum cre ati nine at 145 µmol/L.An ti bi ot ics were dis con tin ued af ter nega tive cul ture re sults were ob tained.He re ceived three doses of meth yl predni solone 1 g in tra ve nously daily and a five-day ta per ing course of in tra ve nous ri bavi rin.
On day 7, the pa tient was suc cess fully ex tu bated with chest x-ray show ing al most com plete reso lu tion of in filtrates.He was dis charged from hos pi tal seven days later.
Bron cho scopy re sults from ad mis sion showed nega tive direct fluo res cent an ti body test ing for le gionella, chla my dia, parain flu enza and ad eno vi rus.Di rect ex ami na tion and cultures for bac te ria, fungi and my co bac te ria were nega tive as was sil ver stain for P car inii.Two sets of blood cul tures, se rology for hu man im muno deficiency vi rus and myco plasma IgM an ti bod ies were nega tive as was cy tol ogy for ma lig nant cells.
When seen at follow-up six weeks later, the pa tient was diag nosed with hy per ten sion and was started on an ti hy per tensive agents.He was noted to have a strongly posi tive fam ily his tory for hy per ten sion.Pul mo nary func tion tests were normal and com plete blood count and se rum cre ati nine had normal ized.
A di ag no sis of HPS was con firmed two weeks later by positive se rum IgM an ti bod ies to Sin Nom bre vi rus with a ti tre greater than 1:1600 by EIA.

CASE FOUR
A 42-year-old farmer with a past his tory of hy per tension was ad mit ted to a com mu nity hos pi tal on Oc to ber 21, 1994 with head ache and stiff neck.He had been well un til three weeks be fore ad mis sion when he de vel oped in creas ing short ness of breath, or tho pnea and pro duc tive cough.He denied fe vers or chills.His symp toms set tled af ter a week and he re mained well un til two days be fore ad mis sion when he de vel oped sud den on set of chills with left chest heavi ness and nau sea.
He in di cated that a neigh bour had re cently been ad mit ted to an Ed mon ton hos pi tal with HPS (case 3).The pa tient had also been re peat edly ex posed to mice dur ing farm ing ac tivities.This in cluded the clean ing of a hot wa ter tank that had be come in fested with mice and the feed ing of cat tle in barns where the pres ence of nu mer ous mice was noted.
On ad mis sion, the pa tient had a tem pera ture of 39.6°C and blood pres sure of 230/130 mmHg.He had dis con tin ued an ti hy per ten sive medi ca tion for eight months for fi nan cial reasons.Ini tial labo ra tory find ings are listed in Ta ble 1. Chest xray on Oc to ber 21 was re ported as nor mal.Re peat chest xray on Oc to ber 24 showed right mid dle lobe atelec ta sis.He re quired oxy gen by mask and was treated with oral cipro floxacin and cap to pril.
He was trans ferred to an Ed mon ton hos pi tal on Oc to ber 29 for fur ther as sess ment of re nal dys func tion and 'pne um on itis'.He was ad mit ted with di ag no ses of ac cel er ated hy per ten sion and atypi cal pneu mo nia.
Past his tory was non con tribu tory.He had not smoked for 20 years.
On ad mis sion, tem pera ture was 37.0°C, pulse 92 beats/min, blood pres sure 138/102 mmHg.Ex ami na tion of the chest re vealed a few dif fuse crack les.His liver edge was pal pa ble and he had mild bi lat eral pedal edema.
Labo ra tory find ings in cluded an ab so lute leu ko cyte count of 11.1x10 9 /L with 55% neu tro phils and 2% bands, he mo globin 169 g/L and plate let count 193,000/mm 3 .Se rum cre atinine was 113 µmol/L.PaO 2 was 51 mmHg with PaCO 2 26 mmHg.As par tate ami no trans fe rase was 124 µmol/L and lactate de hy dro ge nase 657 µmol/L.Uri naly sis showed no red blood cells, zero to two white blood cells and trace pro tein.Chest x-ray on Oc to ber 29 showed patchy bron cho pneumonia in the right lower lobe and a small right pleu ral ef fu sion.Spu tum for rou tine bac te rial cul ture showed no growth.Af ter trans fer, he re mained afeb rile through out hos pi tali za tion.
He was treated with an ti hy per ten sive agents and discharged five days later fol low ing reso lu tion of his res pi ra tory symp toms and con trol of his blood pres sure.Be fore discharge, oxy gen satu ra tion on room air was 94%.
Based on the pa ti ent's clini cal con di tion fol low ing trans fer, HPS was not sus pected and was di ag nosed ret ro spec tively after epi de mi ol ogi cal in ves ti ga tions.Stored se rum was re ac tive for IgM an ti bod ies to Sin Nom bre vi rus by EIA.

DIS CUS SION
Be fore the ini tial re ports of HPS in the United States, all known han ta vi rus in fec tions were col lec tively called hem orrhagic fe ver with re nal syn drome (3); this term in cludes the syn dromes re ferred to as neph ro pathica epi demica in Scan dina via and epi demic hem or rhagic fe ver in Asia.These syndromes con sist of pre domi nantly re nal and hem or rhagic com pli ca tions, but a few cases have been de scribed with coex ist ing or pri mar ily pul mo nary pa thol ogy (4).Since the recog ni tion of HPS, a few ret ro spec tive cases of hem or rhagic fe ver with re nal syn drome have been iden ti fied in the mainland United States (5).HPS has been char ac ter ized by a predomi nance of res pi ra tory symp toms (6).The typi cal pic ture is one of rap idly de vel op ing non car dio genic pul mo nary edema.Re cent re views and case re ports have sum ma rized the clinical and epi de mi ol ogi cal find ings (7)(8)(9).
The etio logi cal agent of HPS in the south west United States CAN J INFECT DIS VOL 6 NO 4 JULY/AUGUST 1995 is a mem ber of the ge nus han ta vi rus, which is a group of tri partite RNA vi ruses in the Bun yaviri dae fam ily (10).The agent im plicated in the ma jor ity of cases was iso lated from the lung tis sue of a deer mouse and was ini tially called Muerto Can yon vi rus af ter the area in New Mex ico where the first cases were iden ti fied (11).This has sub se quently been re named Sin Nom bre vi rus (12).At least two other dis tinct vi ruses have been im pli cated -Black Creek Ca nal vi rus and Bayou vi rus (13,14).
Han ta vi ruses are known to in fect ro dents in which they pro duce as ymp to matic chronic in fec tion with vi ral shed ding in urine, fe ces and sa liva (15).Ro dent to hu man trans mis sion oc curs pri mar ily by in ha la tion of in fected ro dent ex cre tions.Per son to per son trans mis sion has not been docu mented.Labo ra tory trans mis sion of han ta vi ruses has been de scribed with in fected ani mals and cell cul ture (16).Biosafety level 2 labo ra to ries are rec om mended to han dle po ten tially in fected se rum and tis sue and level 3 labo ra to ries for vi rus propa gation (16,17).
The pri mary res er voir host of Sin Nom bre vi rus is the deer mouse, Pero myscus manicu la tus (18).The se ro preva lence of an ti bod ies to han ta vi rus in a sam ple popu la tion of this species in the Four Cor ners area was 20%.This spe cies in hab its most of the United States and Can ada ex cept the south east and At lan tic sea board of the United States and the ex treme north of Can ada (2,14).The oc cur rence of cases out side the range of pero myscus has been at trib uted to the pres ence of re lated but ge neti cally dis tinct vi ruses in other ro dent spe cies.For ex am ple, in Flor ida, the Black Creek Ca nal Vi rus has been iso lated from the ro dent spe cies, Sig mo don his pidus (14).Al though mice have not been tested in the area where our cases oc curred, the se ro posi tiv ity for han ta vi rus an ti bodies in P manicu la tus tested in Al berta ranged from 1.2 to 19.6% in four ar eas where mice were trapped (per sonal commu ni ca tion).All four Al berta cases origi nated from the same re gion of east cen tral Al berta.Cli matic changes re sult ing in increases in the deer mouse popu la tion have been im pli cated in the clus ter ing of cases in the Four Cor ners area (19).The spe cific eco logi cal fac tors con trib ut ing to the Al berta cases have not been elu ci dated but an ec do tal re ports sug gest an increase in the mouse popu la tion in the fall of 1994.
Our four cases il lus trate a spec trum of ill ness rang ing from mild symp toms to death.They dem on strate the char ac ter is tic pro dro mal find ings of fe ver, cough, dysp nea, gas tro in tes ti nal symp toms and head ache.Com mon physi cal find ings in clude tachy car dia, tachyp nea and hy poten sion.Char ac ter is tic labora tory find ings may give the first clue to the di ag no sis and include leu ko cy to sis with a left shift, he mo con cen tra tion, throm bo cy topenia, pro longed prothrom bin and par tial thrombo plas tin times, ele vated lac tate de hy dro ge nase, de creased se rum pro tein and pro te in uria (8).Mild ele va tions in se rum cre ati nine are com monly seen as dem on strated by our cases.A case con trol study car ried out by the Cen ters For Dis ease Con trol and Pre ven tion ([CDC] At lanta, Geor gia) sug gested that the com bi na tion of four symp toms (my al gias, diz zi ness, cough, nau sea/vom it ing) and three labo ra tory find ings (hema to crit, plate let count and bi car bon ate level) ap plied to patients with fe ver, tachyp nea and non lo bar ra dio graphic in fil trates ac cu rately dif fer en ti ated pa tients with HPS from control sub jects (20).These find ings re quire fur ther vali da tion.No rapid di ag nos tic test is avail able.
Nor mal or ele vated sys temic vas cu lar re sis tance and normal or re duced car diac out put have been re ported as typi fied by case 1.These find ings are in con trast to the changes seen with bac te rial sep sis.Chest x-ray find ings in clude sig nifi cant in ter sti tial edema with pro gres sion to air space dis ease within 48 h in the ma jor ity of pa tients (21).Pleu ral ef fu sions are also com monly seen.
Sub clini cal and mild dis ease is said to be un com mon (9).In more than 500 resi dents of the Four Cor ners area who were as ymp to matic or had mild ill ness, spe cific han ta vi rus an ti body preva lence was 1% (22).Case 4 ex pe ri enced a milder form of dis ease and his pres en ta tion was com pli cated by co ex ist ing ac cel er ated hy per ten sion.With the non spe ci ficity of ini tial symp toms and physi cal signs, the di ag no sis may be dif fi cult with only a his tory of ex po sure to deer mice or mouse drop pings to hint at the di ag no sis.
Once HPS is rec og nized, op ti mal man age ment con sists of prompt con trol of hy poxia, which can de te rio rate rap idly, the early use of ino tropic agents and avoid ance of ex ces sive fluid ad mini stra tion (6,8).Ri bavi rin is an an tivi ral drug that in hib its the rep li ca tion of sev eral han ta vi ruses.Pro spec tive doubleblind clini cal tri als of ri bavi rin in China in pa tients with hem orrhagic fe ver with re nal syn drome dem on strated a sev en fold re duc tion in mor tal ity among treated pa tients (23).The CDC car ried out an open la bel trial of in tra ve nous ri bavi rin in patients with sus pected HPS.A re view of the re sults did not demon strate a clear bene fit and the trial was ter mi nated (14).The CDC is no longer ad vo cat ing its use but ran dom ized con trolled tri als have yet to be per formed.
Al though hy per ten sion has been as so ci ated with other han ta vi ruses (24), it has not been re ported as a com pli ca tion of HPS.The de vel op ment of hy per ten sion in case 3 may have been as so ci ated with this dis ease but his fam ily his tory of hyper ten sion makes es sen tial hy per ten sion more likely.
Vari ous ac tivi ties have re sulted in HPS in fec tion, in clud ing plant ing or har vest ing field crop, oc cu py ing pre vi ously va cant barns or out build ings, clean ing barns or other out build ings, dis turb ing rodent-infested ar eas while hik ing or camp ing, inhab it ing dwell ings with in door ro dent popu la tions and re sid ing in or vis it ing ar eas with in creased ro dent den sity (25,26).All our cases had docu mented ex po sure to deer mice.
Fi nally, given the sig nifi cant pres ence of the res er voir host for HPS in Can ada, it is likely that more cases will be iden ti fied.As eradi ca tion of the pri mary host is nei ther fea si ble nor advis able (25), it is im por tant to re duce hu man con tact with poten tially in fected ro dents.In terim guide lines to re duce the risk of in fec tion have been pub lished by the CDC (25) and adapted by Ca na dian authori ties (16).

AC
KNOW LEDGE MENTS: We thank all those who con trib uted to the man age ment of the Al berta cases, in clud ing Drs D Cal laghan and W Dick out, Mis eri cor dia Hos pi tal; Drs WDN Chin and M Joffe, Uni ver sity of Al berta Hos pi tal; Dr I Fer gu son, Royal Al ex an dra Hos pi tal; Dr J Waters, Pro vin cial Epi de mi olo gist, Al berta Health; Dr H Art sob, Na tional Labo ra tory for Spe cial Patho gens, LCDC; Dr J Preik saitis and Mr E Prasad, Pro vin cial Labo ra tory, Al berta Health; Dr W Mou lai son, Depart ment of Na tional De fence; Dr Sa vard, Stony Plain Hos pi tal; Dr H Mur ray, Wain wright Health Care Com plex; Dr E York, We taski win Hos pi tal; Dr S Zaki, Cen ters for Dis ease Con trol and Pre ven tion, Atlanta.