doi 10.1098/rspb.2000.1204

Fragiletransmissionc yclesof -borne encephalitisvirusmaybedisruptedbypredicted climatechange Sarah E.Randolph * and David J.Rogers Department of Zoology,University of Oxford, SouthP arks Road, Oxford OX13PS, U K Repeatedpredictions that -bornedisease prevalencewill increase withglobal warming are usually basedon univariatemodels. T oaccommodatethe fullrange of constraints, the present-daydistribution of tick-borneencephalitis (TBEv) was matched statistically tocurrent climatic variables,to provide a multivariatedescription of present-day areas of disease risk.This was then appliedto outputs ofageneral circulationmodel that predicts howclimatic variablesmay change in the future, andfuture distributions ofTBEv were predicted forthem. Theexpected summer rise intemperature anddecrease inmoisture appearsto drive the distributionof TBEv into higher-latitude and higher-altitude regions progressively throughthe 2020s,2050s and 208 0s.The ¢ naltoe-hold in the 2080smay be con¢ ned to a small partof Scandinavia,including new foci in southern Finland. The reason for this apparentcontraction of the rangeof TBEv is that its cycles dependon a particularpattern oftick seasonal dynamics, whichmay be disrupted byclimate change.The observed marked increase inincidence of tick-borne encephalitisin most parts ofEuropesince 1993may be dueto non-biological causes, such aspoliticaland sociologicalchanges. Keywords: ; tick-borneencephalitis; global warming ;climate matching;risk maps

the winterwith minimum temperatures below 712 8C. 1.INTRODUCTION Further south,in areas with medium tohigh tick densi- Tick-borneencephalitis (TBE) ,causedby two subtypes of ties, further increases intick abundance were related to a £avivirus(TBEv) transmitted bythe ticks ricinus combinationof milder winters (fewer dayswith minimum and I.persulcatus ,is the most signi¢cant vector-borne temperatures below 7 7 8C)andextended spring and disease inEurope and Eurasia. Central nervous system autumnseasons (more dayswith minimum temperatures pathologycauses acase morbidityrate of1 0^30%and a of 5^8 8C).Usingthe excellentnational registration of case mortalityrate oftypically1^2% but as highas 24% TBEcases inSweden since the 1950s,Lindgren ( 1998 b) inthe FarEast (ImmunoAg 1997).Priorto 1 992,infec- relatedthe increase inTBE incidencefrom 1 960to1995 tionincidence was typically 2^40% in areasbut inStockholm County ,ahigh-endemicregion, to higher since 1993TBE cases haveincreased two -to1 7-foldin wintertemperatures permitting aprolongedseason of tick manyparts ofEurope (Immuno Ag1 997;Su « ss & Kahl activityand hence transmission. Here the major 1997;S.Dittman andW .Jilg,unpublished data) and new increase occurredfrom 1984 onwards: 1 960^1983,mean focihave been identi¢ ed. TBE is atypicalzoonosis, with annualcases 18.6(range 6^36); 1 984^1995,mean annual enzooticcycles maintainedin natural rodent ^tick cycles cases 45.1(range33^74) . (Labuda& Randolph1 999); may be infected if Events atthe extreme limit ofan organism’ sdistribu- accidentallybitten byan infected tickor by drinking tion,however ,maynot re£ ect future events atthe coreof untreated milkfrom infected sheep orgoats (which the range.In Europe, TBEv is highlyfocal in its distribu- cannotthemselves pass the virusto ticks) (Labuda et al. tion,limited toa well-de¢ned region in central Europe, 1997).Increased risk tohumans may therefore arise in wherethe distributionis verypatchy ,anda quasi- three ways:(i) improvedconditions for natural trans- separateregion covering the Balticstates andthe south- mission cycles resulting inhigher densities ofinfected eastern rim ofScandinavia, where the distributionis ticks; (ii) changedhuman behaviour resulting ingreater more continuous(¢ gure 1 ).Thispattern hasbeen exposureto ticks; and(iii) changedagricultural practices predicted with85% accuracy from satellite-derived data resulting ina higherconsumption of rawmilk. As bothof onenvironmental conditions (Randolph 20 00)and its the ¢rst twofactors are climate dependent,TBEv is biologicalbasis is nowclearly understood. The reason includedin the list ofvector-borne anticipated TBEvoccurs inonly a narrowsubset ofsuitabletick habi- tobecome more ofa threat tohumans in a predicted tats is becauseits cycles aremaintained by transmission warmerworld (Lindgren 1998 a;Martens 1999). ofnon-systemic infectionsbetween infected nymphsand Onlyin Sweden has this predictionbeen explicitly uninfectedlarval ticks co-feedingon small rodenthosts, tested forTBEv .Lindgren et al.(2000)showed that the principallymurids (Labuda et al.1993).Theforce of northwardexpansion of the geographicalrange of transmission is su¤ciently high only when there isahigh I. ricinus (Talleklint& Jaenson1 998)between the early degreeof coincident feeding of larval and nymphal ticks 1980sand the mid-1990swas related to fewer days during (Randolph et al.1999).Thisdepends on a particular pattern ofseasonal tick-population dynamics determined *Author forcorrespondence (sarah.randolph@zoology .ox.ac.uk) byrather precise climatic conditions,speci¢ cally the

Proc. R.Soc.Lond. B (2000) 267, 1741^1744 1741 © 2000The RoyalSociety Received 2 March 2000 Accepted 25 May 2000 1742S. E. Randolphand D .J. Rogers TBE virus transmission disrupted by climate change

pointswithin themapped limits of TBEv (Immuno Ag 1 997) and60 0pointsoutside, but within 8 8 oflongitudeor latitude of, thelimits. Data for each point were derived from 30-year (1960^1990)average monthly climate surfaces at 0.5 8 longitude andlatitude resolution (New et al.1999)for the mean ( TM), maximum (TX)andminimum ( TN)temperature,rainfall ( R) andsaturation vapour pressure (SVP) variables. These surfaces werepre-processed by temporal F ourieranalysis (Rogers et al. probability 1996)of themonthly data (essentially smoothing the data) ,from 0.65–1.0 which themean, maximum and minimum of each variable were 0.55–0.649 extractedfor each training-set location. Data were ¢ rstclustered 0.50–0.549 0.45–0.499 using the `k-meanscluster’ option of SPSS (SPSS,Inc., IL, USA) , 0.35–0.449 producingthree clusters each for presence (p) and absence (a) 00–0.349 observed sites.Stepwise discriminant analysis (Rogers et al.1996)of the resultingsix clusters, using the criterion of maximizing the Figure1. The present-daydistribution of tick-borne Mahalanobisdistance between all pairs of dissimilar(i.e. p toa encephalitisvirus in Europe(yellow hatched polygons) and anda top) clusters, chose the minimum TN, minimum TX, distributionpredicted using maximum-like lihoodmethods mean TX, maximum TM andmaximum SVP as the ¢ vemost basedon 1960^1990average monthly climate surfaces (red importantdiscriminating variables for describing the current togreenposterior probability scale in key).Training-set western-typeTBEv situation (¢ gure 1 ).Onlythese, which areall predictions( 4 0.5probability) 86% correct, 12% false consistentwith theresults of the predictive mapping based on positivesand 2% falsenegatives. satellite-deriveddata ( Randolph200 0),wereused to make the predictivemaps of posteriorprobabilities ( Rogers et al. 1996) on seasonalland-surface temperature pro¢le (Randolph ascaleof 0.0(red in ¢gure1 )to1.0 (green) . 2000;Randolph et al.2000).Itmust behotenough in the The resultsof the above exercise were applied to GCM summer toallow rapid tick development, especially of the scenarios( Johns et al.1997)to produce predictions for the eggs,but cool down rapidly in the autumnto send the future,i.e. the covariance matrices from the present-day emergent larvaeinto behavioural diapause over the climate-matchingexercise were used to identify places where winter.Inthis way,larvaeand nymphs become active in conditionsfor TBEv presence or absence will occurin the synchronyin the springand e¤ cient virustransmission is future.The futureclimate scenarios have been constructed for achieved.At the same time, moisture availabilityto ticks low, medium^low, medium^highand high degrees of change onthe ground,as measured bya remotelysensed vegeta- projectedto the 2020s, 2050s and 2080s, at an original spatial tionindex, must besu¤cient toensure goodtick survival. resolutionof 3.75 8 longitudeand 2.5 8 latitude,but then spatially Likemany vector-borne pathogen cycles that depend interpolatedusing cubic splines to give the same resolution as onthe interactionof so many biotic agents with each thelong-term past climate data sets. GCM predictionsare given otherand with their abioticenvironment, enzootic cycles asthechange from the modelled present to the modelled future ofTBEv have an inherent fragility.Theircontinuing climateand, following standard practice, these values are added survivalor expansion cannot be predicted fromsimple tothe present observed climate averages to the future. univariatecorrelations. Ideally ,robust biologicalmodels Forexample, the 2050s `high’ scenario from the HadCM2 areneeded to capture the complexityof such systems. The experiment(http:/ /www.met-o¤ce.gov .uk/sec5/sec5pgl.html)pre- quantitativebiological information needed to give an dictsmean global land surface changes of + 3.45, + 3.63 and accuratedescription of eventhe current situationis notyet + 3.29 8Cin mean,minimum and maximum temperatures, available,however ,sothis approachcannot yet be used to + 1.87hpa for SVP and + 0.127 mm day71 forprecipitation by givereliable predictions about the future. Instead,we here 2050.These ¢ gurestake account of the greater rise in tempera- adopta two-step statistical approachto matching TBEv tureover the land than over the sea, but not the di¡ erential distributions topresent andfuture climatic conditions. seasonalchanges :temperaturesrise by more than the average in thesummer, while rainfalllevels drop.

2. METHODS 3. RESULTS This analysisis con¢ned to Europe where western-type TBEv istransmitted by I. ricinus.First,the present-day distribution of Theextent, althoughnot the focalization,of the TBEv( ImmunoAg 1997) is matched statistically to current present distributioncan be predicted verywell (86% climaticvariables, to provide a multivariatedescription of accuracy)from the above¢ veclimatic variables(¢ gure 1 ). present-dayareas of disease risk. This understandingis then Themajor inaccuracy is the falseprediction of TBEv appliedto outputs of a generalcirculation model (GCM) that presence throughsouthern Poland and in south-western predictshow climatic variables may change in thefuture ( Johns Sweden. et al.1997),andfuture TBEv distributions are predicted for Therise intemperature anddecrease inmoisture in them.The approach,therefore, is essentially a `pattern- the summer predicted underthe `medium ^high’scenario matching’exercise, from which conclusionsmay also be drawn appearsto drive the distributionof TBEv into higher- aboutthe likely climatic sensitivity of vectorsand/ ordiseases. latitudeand higher-altitude regions progressively through Obtaininga good¢ tofthe present-day distributions to the 2020s,2050s and 2080s (¢ gure 2 a^c). The Alps, present-dayclimates is a necessary¢ rststep in thismodelling however,arealways too high to become a regionof risk. exercise.The analysisrandomly selected a trainingset of 20 0 Inthe 2020s,F rance,Switzerland, Slovenia, Hungary

Proc. R.Soc.Lond. B (2000) TBE virus transmission disrupted by climate change S.E. Randolphand D .J.Rogers 1743

highdegrees ofchange, TBEv is pushedfurther north- (a) east ofits present range,only moving westwards in southernScandinavia. Only under the `low’and `medium^low’scenarios does TBEv remain in central and eastern Europeto any extent bythe 2050s.

4.DISCUSSION Climatematching is wellable to capture the rather subtle interactionsbetween predictor variables(many of whichcovary) that areoften important in shaping distri- butions.The drawback of the pattern-matchingapproach is that it is essentiallya statistical inference method, basedon the past,and may not be a reliableguide to distributions ina climaticallychanged world where covar- (b) iationbetween climate variablesmay be di¡ erent. Itis alsopossible that the variableselection methodwill iden- tifybiologically spurious variables, so it is importantto select the variablessubmitted tothe analysison the basis ofprior biological understanding. In the case ofTBEv , this understanding,both qualitative and quantitative, exists (Randolph20 00;Randolph et al.1999,200 0):the rate ofautumnal cooling, which would be captured reasonablywell by relative annual minimum and maximumtemperatures, andmoisture conditionson the ground,monitored as SVP,arekey factors in determining the current focaldistribution of TBEv.Thefocalization of the present distribution,however ,is notpredicted aswell bythe standardGCM variablesas it isbyusing surrogates ofawiderrange of climatic variablesderived from satellite (c) imagery( Randolph20 00),resulting inthe largearea of false-positivepredictions in southern Poland and south- west Sweden.This climate-matching approach cannot take intoaccount the possibilityof genetic change permitting the virusto use subtlydi¡ erent transmission routes. Theprediction that the distributionof TBEv may expandnorth and west ofStockholm is consistent with the conclusionthat increased temperatures havealready allowedthe limit of I. ricinus tobe extended both north- wardsand westwards in Sweden (T alleklint& Jaenson 1998;Lindgren et al.2000).Elsewhere, however,fears forincreased extent ofrisk fromTBEv caused by global climate changeappear to be unfounded. Rather ,the precise conditionsrequired forenzootic cycles ofTBEv arepredicted tobe disrupted. Itis impossible to Figure2. Predicted future distribution of tick-borne distinguishbetween the e¡ects ofa changedseasonal encephalitisvirus based on climatesurfaces derived from temperature pro¢le, with its impacton tick development theHadCM2 experiment for `medium ^high’scenarios in rates andtherefore seasonalactivity patterns, and (a) 2020s, (b) 2050s and (c)2080s.The yellowoverlay and reducedsummer rainfall,with its negativeimpact on theprobability scale are the same as in ¢gure1. Greystipple: ticksurvival rates, butthe combinationappears to be nopredictionspossible. lethalfor TBEv . Althoughthe predictionscan only be as good as the andmuch ofAustria are cleared of TBEv ,andthe range climate scenariosupon which they are based, this analysis ofthis virus(though not necessarily its vector)has givesthe lieto the commonperception that awarmer contractedto inland regions of the Balticstates. Bythe worldwill necessarily be a worldunder greater threat 2050s,TBEv has moved into areas at present free ofinfec- fromvector-borne diseases. Itis true that,given the sensi- tion,notably the mountainson the Slovak ^Polishborder tivityof transmission cycles ofvector-borne pathogens to andfurther north-west inScandinavia, but central environmentalvariables, these, rather thandirectly trans- Europeis virtuallycleared of TBEv.The¢ naltoe-hold in mitted pathogens,are likely to be a¡ ected byclimatic the 2080sis con¢ned to a small partof Scandinavia, change(Rogers &Packer1 993)but inthe case ofTBEv includingnew foci in southern Finland. that changeappears to be to our advantage, while for Averysimilar progressivepattern emerges underthe malariathere maybe very little alterationto the current increasinglyextreme scenarios(not shown): from low to situation(R ogers& Randolph20 00).

Proc. R.Soc.Lond. B (2000) 1744S. E. Randolphand D .J.Rogers TBE virus transmission disrupted by climate change

What, therefore, mayhave caused the widespread Korenberg,E. I.1 994Comparative ecology and epidemiology increase inTBE cases since 1993?This was a time ofgreat ofL ymedisease and tick-borne encephalitis in theformer politicalchange in Eastern Europe.The collapse of SovietUnion. Parasitol.Today 10, 157^160. communism resulted inde-collectivization of agriculture, Labuda,M. &Randolph,S. E.1999Survival of tick-borne withactive governmental encouragement of individuals encephalitisvirus: cellular basis and environmental determi- nants. Zentr.Bakteriol. 289, 513^524. tokeep £ ocksof sheep andgoats, often grazed on road- Labuda,M., Nuttall,P .A., Kozuch,O., Eleckova ¨,E.,Williams, side vergesharbouring ticks, andto use their milk T.,Zu¡ova, E. &Sabo ¨ ,A.1993Non-viraemic transmission of products.Clusters ofTBEcases havebeen recorded in the tick-borneencephalitis virus :amechanismfor Czechand Slovak R epublicswithin families orvillages survivalin . Experientia 49, 802^805. wellknown for their cheese making(M. Danieland M. Labuda,M., Kozuch,O. & Lysy,J.1997Tick-borne encepha- Labuda,personal communication) .Atthe same time, litisvirus natural foci in Slovakia:ticks, rodents, and goats. increasedpoverty arising from the collapseof centralized In FourthInternational P otsdamSym posiumon tick- bornediseases: welfarehas forced many poor people to supplement their tick-borneencephalitis and L ymeborreliosis (ed. J. Su« ss & O. diet withfruits gatheredfrom tick-infested forests. Other Kahl),pp. 34^46.Lengerich, Germany :PabstScience wealthierpeople increasingly visit such sites forleisure. Publishers. Thiswould not account for the approximatelyeightfold Lindgren,E. 1998 a Climatechange, tick-borne encephalitis and vaccinationneeds in Sweden öapredictionmodel. Ecol. rise incases inthe Baden-Wu « rttemberg regionof south- Model. 110, 55^63. west Germany( Roggendorf et al.1997).Here, however, Lindgren,E. 1998 bClimateand tickborne ence phalitis .Availableat systematic registering ofTBE cases wasintroduced in http://www/consecol.org/journal/vol2/iss1/art5/. 1994(Kaiser 1997),whilevaccination was targeted more Lindgren,E., T alleklint,L. &Polfeldt,T .2000Impact of inBavaria, south-east Germany,whereno increase in climaticchange on the northern latitude limit and population cases hasoccurred (Roggendorf et al.1997).Itis clearthat densityof the disease-transmitting European tick, Ixodes there area varietyof location-speci¢ c non-biological ricinus. Environ.Hlth P erspect . 108, 119^123. potentialcauses forthe observedchanges in TBE epide- Martens,P .1999Climate change impacts on vector-borne miologyover the past decade.I tis alsopossible that the diseasetransmission in Europe.In Climatechange and health (ed.A. Haines& A.J.McMichael),pp.45^54. modest globalwarming to date may have increased tick ^ London:The RoyalSociety . humancontact, through both changes in human beha- New,M., Hulme,M. &Jones,P .D.1999Representing viourand prolonged seasons oftick activity ,withoutyet twentieth-centuryspace ^timeclimate variability .I.Develop- disruptingthe particularpattern oftick seasonal mentof a 1961^90mean monthly terrestrial climatology . J. dynamicsnecessary forenzootic transmission cycles. Climate 12, 829^856. Ultimately,whenwe have a complete process-based Randolph,S. E.2000 Ticks and tick-borne disease systems in modelfor this complexvector-borne disease system, the spaceand from space. Adv.Parasitol .(Inthe press. ) non-biologicalvariables can beincorporatedto predict rates Randolph,S. E.,Miklisova ¨,D.,L ysy,J.,Rogers,D .J.& ofincidenceof .U ntil then, the climate-matching Labuda,M. 1999Incidence from coincidence: patterns of tick approachpresented here is the best, most inclusive,way infestationson rodents facilitate transmission of tick-borne ofidentifying the likelyimpact of multivariate climatic encephalitisvirus. 118, 177^186. Randolph,S. E.,Green,R. M., Peacey,M. F.&Rogers,D .J. conditionson the potentialgeographical range of TBEv. 2000Seasonal synchrony: the key to tick-borne encephalitis fociidenti¢ ed by satellite data. Parasitology. (Inthe press. ) This workwas supported by a WellcomeT rustSenior Research Rogers,D .J.&Packer,M. J.1 993V ector-bornediseases, Fellowship(to S.E.R. )andthe Department for International models,and global change. Lancet 342,1282^1284. Development(D.J.R. ).This studywas facilitated by Dr R. L. Rogers,D. J. & Randolph,S. 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Proc. R.Soc.Lond. B (2000)