Wildlife and Human Implications of Emerging Viral Zoonotic Diseases in Southeast Asia

2004·0.54 MB·English

by  Dudley, Joseph P

Commentary
NAT. HIST. BULL. SIAM Soc. 52(2): 123-132，2004
WILDLIFE AND HUMAN IMPLICATIONS OF EMERGING
VIRAL ZOONOTIC DISEASES IN SOUTHEAST ASIA
Joseph P. Dudleyl
ABSTRACT
The 7000+ year history of intimate association between humans，wi ldlife，do mesticated
liv巴stockand poultry in southeastern Asia makes this area af ertile ground for the evolution and
emergence of novel viruses of humans and domesticated animals，pa rticular匂virusesthat may
infect poultry，s wine，a nd/or humans. Recent experiences with the emergence of the SARS
virus in Guangzhou and Hong Kong，a nd the proliferation of an ew and more dangerous
zoonotic strain of the H5NI avian influenza virus demonstrat theimportance of southern
巴
China and nearby ar巴asof Southeast Asia as an incubatorium for emerging viral diseases that
could have severe global public heath impacts.
The confirmed human case-rate mortality from the H5NI avian flu strain of 2003/2004
(-70%) is seven times higher than that repo口edfor the SARS virus，a nd roughly equivalent
to that associated with recent outbreaks of the Ebola virus in central Africa and Nipah virus
in Bangladesh. Demonstration of known changes in the virulence and infectivity of the H5NI
avian influenza virus and the apparent recent emergence of the SARS clearly demonstrate the
importance of increasing our knowledge of the emergence of recombinant zoonotic viruses and
the evolutionary dynamics of viral host/pathogen relationships. Recent experience with the
H5N1 a vian influenza virus and the genetics of the SARS virus has demonstrated that the host
affiniti巴sand epidemiological characteristics of these zoonotic viruses may continue to change，
and巴ith巴rone or both of these pathogens may become ev巴nmore infectious and more virulent
to both animals and humans within the forese巴ablefuture.
Current evidence indicates that H5N1 a vian influenza viruses with pandemic potential
have now become endemic in domesticated duck populations in China and southeastern Asia，
and may not easily eradicable or even controllable for the near future. Although wild ducks，
storks，a nd other migratory birds have been implicated as potential vectors and reservoirs for
the H5N1 v irus，e vidence to date suggests that wildlife are more often victims than vectors of
this potentially deadly disease of that is now known to infect birds，h umans，a nd several species
of wild and domesticated mammals.
Key words: Asia，o rigin，a vian intluenza，S ARS，v irus，z oonoses
Southeast Asia was one of the earliest centers of human agriculture，a nd the region has
had al onger history of continuous，i ntensive agriculture than any other area on earth. The
7，000 year or more history of intimate association between humans， wildlife， and
domesticated animals in southern China makes this area af ertile ground for the evolution
and emergence of novel viruses of humans and domesticated animals，pa rticularly influenza
viruses capable of infecting poultry，s wine，an d/or humans. Unlike agricultural 訂easof the
Middle East having civilizations of similar antiquity，th ese agricultural areas of China have
[S enior Analyst，I ntellibridge Corporation; Research Associate Department of Earth Sciences，U niversity of
Alaska Museum，I nstitute of Arctic Biology，U niversity of Alaska，F airbanks，A laska 99775. Email:
f町[email protected]，or [email protected]
Received 12 July 2004; accepted 20 September 2004
123
124 JOSEPI-I P.D UDLEY
・
ProvInc蝿 reportd
Countr胸囲B・側、白書簡d
量撞量
FigUl巴1.Avianin tlllenzast illationas ofJlI ne2 004
http://www.fao.org/ag/AGAかIGAJ-J/EMPRES/ll1lages/avIaI125062004_640x480.gif
ah istory of continuouso ccupation with at riad consisting of dOll1esticated ducks-the
naturalh osto f the typ巴 A(H5N1)a vian influenza-wild and dOll1esticated swin巴，and
hUll1ans. R巴cent巴xp巴nenc巴swith th巴巴m巴rgenceoft heS ARS virusi n Guangzhoua nd
HongK ong，th eN ipahv irusi n Malaysiaa nd Bangladesh，a nd th proilfrationof an ew
巴 巴，
andl l10red angerousz oonotics train of th巴H5N1a viani nflllenza virus，d ell10nstrate the
ill1portance of southeastern Asiaa s ani ncubatoriull1 for巴ll1erg川gvirald iseases thatc ould
have sev巴r巴globalpublich 巴athill1pacts.
Th巴stillon-goingp and巴ll1icof H5NJa viani nfluenza in Asiai sa bsolutelyu niqu巴and
unprecedentedI n itsv irul巴nce，rate of proilf巴lraiton，geographics cope，a nd duration.J.2 As
of巴arlyAugust2 004， new outbreaks of th巴H5Nlwel巴beingreportedf roll1 Thaliand，
Malaysia，a nd Vietnam. Thaliandh as reported 16 laboratoryc onfirm巴dcaseso f human
H5N 1i nfectionsd uringt hep eriod btweenIJ anuarya nd 5O ctob 2004，fo ur of which
巴 巴l'
occurredd uringt he1 l10nth ofS eptember2 004. As of 5O ctober2 004，r eported hllman
cas巴ーrat巴mortalityfrom theH 5N Iv irusin Vietnam and Thaliand has b巴巴napproxill1ately
72 % (31o f 43c onfirmedc ases).3 Confirll1巴dcase-ratem ortalityf or hllmani nfectionsb y
theH 5Nl aviani nflu巴nzavirusin Vietnam and Thaliand ar巴ashigh0 1' higherth ant hos巴
I巴cordedforh llmanc ases of theE bolav irusin centralA frica orN ipahv irusi n Malaysia
andB angladesh.T h巴confirll1巴dhumanc as巴-rat巴mortalityfrom H5N1 a vianf lu duringt he
2003/2004o utbreak hasb eena pproximatelyt wo times higherth anth athi storicaIIya ssociat巴d
EMERGING VIRALZ OONOTIC DISEASES 125
Y/IV\v.hpa.org.uk
Fig山巴2.Porton Down Illap 0 "1reported recentA vianl nflu巴nzaoutbreaksI n Thaliand
11ft/):
126 JOSEPH P. DUDLEY
SARS:C umulatlve Number of Reported Probable_Cases
Total number of cases:5 462 as of 29 Apr li2003.1 7:00 GMT+ 2
、
)
Cumulative number ofRe ported Cases
(・From 1N ov回embe・r・. ・02 to 29 Aprll 03) Type oftr ansmlss ion
21・1 0 士 101・∞1田0 仁コ 耐問1悶0副問rann悶sm凶ls
働 、h • 11・1 >10 - 拍刷ra悶nsm倒 o叩n
∞"lh"cIhp噛erp守創e1、e・s出ret←r.tOα‘"ell:'i憎開指。輸定一.I防ーm.t富市凶ll CH1，岡1"'ð一山1.相. 川命ニ0・・胆，m-唱・、国"。岡'由副I国首制b'舗.l切嗣ril'岡erl，市gst"c憎.-~同bod闘u'I咽唱:;I制e.蜘t.us附ol2e・nye岨市刷ess、民iOn畑0i1otIr nyf，句ci拙tyo~ra.r.e凶e sO醐fo咽llls mDMC.oaaめlmp9“mSP地ru0 ・onUfd・iuI'cI田atcOrbipole WwnO::OIaPliidusob enl.aHisFeec'a(lsHtfleh 喝(沼aC 訓OD凶"r匂gaMmazppailniognTe 3m
Figl1re 3. Worldwide dislribl1lion of SARS巴pidemicin 2003
Irl/p://www.wlro.Il1t/cSJゾs'ars/map-2003_04_ 29.gif
with smallpox Vario/a major，4 sevent imes high巴1・thanthec onfirmedd eath rat巴forth巴
SARS coronavirus，5a nd comparabl巴toconfirmed human case-rat巴mortalityrecorded from
outbreaks of Nipah Virus in Bangladsh(60-74 percent) and Ebolav irusin cntralAfrica
巴 6 巴
(50-90p er cent).7
The unusuallyl arge numbero f domesitcatedd ucks dyingf rom bird flu in southern
Chinai ndicates the H5Nl virusc irculatinσin 2003-2004 isa m utated strain that isa lso
D
morev irulent in birdsa nd mammalst hanH 5N 1s trains ncountredin prviousyars
巴 巴 巴 巴
(L.L.M.P OON，pe rsonal communication).8T h巴H5N1s train circulatingi n 2003/2004 isn ot
onlym ore highly virulent in mammalst hat strainsc oll巴ctedin pr巴viousyears，9 but has
reportedly callsed fatal infectionsin am uch broaderra nge of mammalsp ecies than dllring
previous outbraks .gdomesticated catsitgrcloudedle opard)U.S.and Britishs cintlsts
巴 (巴 ， ， 巴， 巴
目
recentlyd 巴tenmn巴dthat the1 918“Spanish"i nflu巴nzaviruse stima t巴dto have killed as
manya s 50 millionp eople worldwidew as actuallya na viani nfluenza-typev irus，a nd not
as Wlne 111日uenzavirusa sr eported by previouss tudies.'o Th巴 19]8f lu virusd iffers
significantly in itsg enitcstructuref rom theH 5N1 a vian flu virusc urrntlycirculatingi n
巴 巴
Vietnam and Thailandhowverand th currntH5N Is train dosnot appearto possess
， 巴 ， 巴 巴 巴
th human-to-humancontagiona nd transmissionc apability exhibitdby th so-called
巴 巴 巴
“Spanish"i nfluenza virus( a misnom巴'1，as epid巴ll1iologicalevid巴ncesugg巴ststh巴vixus
originallye merged in the United Stat巴S).IO
Current evidence indicates that H5N 1a viani nflunzavirusswith pande icp otential
巴 巴 ll1
have now becom巴巴nd巴ll1icin dom巴st1cat巴dduck populationsi n Chinaa nd south巴astern
EMERGING VIRAL ZOONOTIC DISEASES 127
Asia，a nd may not easily eradicable or even controllable for the near future.8T he new
deadly and highly persistent strain of H5Nl avian influenza virus circulating in Thai1and
could pose continuing threats to public health，w i1dlife heath，v eterinary health，t rade
and tourism in southeastern Asia-and potentially around the entire globe-unless effective
control measures for this dangerous zoonotic pathogen can be successfully developed
and implemented in Thailand，C hina，V ietnam，Ma laysia，L aos，M y mar，and Indonesia.
阻
Although wild ducks，st orks，a nd other migratory birds have been implicated as potential
vectors and reservoirs for the H5Nl virus，ev idence to date suggests that wildlife 'emore
釘
often victims血anvectors of this disease.
Severe acute respiratory syndrome (SARS) is ad eadly form of pneumonia caused by
an apparently newly emerged mutated coronavirus，w hich the available evidence suggests
is derived from an endemic Asian virus associated with one or more species of wild
mammals，p ticularlymustelids，n ative to southern and eastern Asia. Coronaviruses
ぽ
(Coronaviridae) eav iral farnily known to causes infections in aw ide variety of animals，
紅
including (among others) humans，pi gs，c ows，mi ce，ca ts，an d birds. The SARS virus itself
has been identified as ar ecent1y-mutated strain that originated through a2 9nucleotide
・
deletion mutation of ac losely-related coronovirus which has been isolated from several
species of wild animals taken from live-animal s悦 etmarkets in mainland China (i.e，pa lm
civet Paguma larvata，r accoon dog Nyctereutes procyonoides，f erret badgers Melogale
sppふ11Domestic cats and domestic ferrets have been experimentally inf~cted with the
SARS virus，12 and subsequent studies have reportedly discovered the SARS virus in foxes，
voles，ra ts，a nd domestic cats.13
Chinese health officials reported new studies in April 2004 showing血attesting of
humans and wild animals has confirmed earlier suspicions血atanimals other由加vive町ids
(civits) may be responsible for spreading SARS in humans. Indeed，t he earliest known
SARS victim was linked to possible infection from ad omestic cat or as nake，ra ther血an
any wild marnmal species.13 Researchers who traced the virus白紙 causesSARS to the
palm civet Paguma larvata identified antibodies to SARS in traders of live wild animals
in southern China markets who had not developed symptoms of the disease.14 Tests on
workers at wild animal markets in 16 cities in Guangdong Province found antibodies to the
SARS virus in nearly 100 of the 994 animal traders exhibited，wh ile SARS antibodies were
found in only 4o f the 123 workers involved in the captive husbandry of the palm civet
Paguma larvata，th e species originally identified as血esuspected source or reservoir for
血eSARS virus in China.14，15，16 Throat and anal swabs from animals at wildlife markets in
Guangzhou subsequently confirmed SARS in raccoon dogs Nyctereutes procyonides (15 of
15 snplespositive)，fo xes (species uncertain: 3o f 5p ositive)，vo les (Rodentia: Microtinidae，
創
1o f 6p ositive)，a nd cats (Felis cattus，4 o f 20 positive).13 The reported identification of
SARS virus in“foxes" [Vulpes spp ?] and voles (Rodentia: Cricetinae gen.lsp. incertae，
identified as“hedge-shrews" in English language sources) appe tobe entirely new host
紅
records for canids and microtine rodents. The finding of SARS in cats and voles is not
unexpected，ho wever，as laboratory studies performed in 2003 showed由atdomestic catsl2
'esusceptible to the SARS virus，a nd the SARS virus was reportedly confirmed from
紅
several rats trapped in the aptmentof aS ARS victim in Guangzhou，C hina.17
訂
Two recently published genetic studies provide evidence白紙 theSARS virus is a
recombinant virus白紙incorporatesgenetic material from both avian and marnmal viruses.18.19
Gene-sequence analyses indicate that the SARS virus genome is derived from a
128 JOSEPH P. DUDLEY
recombination event between mamma1ian-like and avian-like p entviruses. Demonstration
紅
of past recombination events in出eSARS coronavirus lineage indicates ah igh potentia1
for rapid unpredictable mutationa1 changes that could produce viruses capable of infeting
氾
both anima1sa nd humans，a p otentia11y important challenge for public health management
and合ugand vaccine developmen.t18 Thel ocation of the evident anima1-avian recombination
site in proximity to ar egion implicated as the human receptor site may have b ndirectly
田
responsible for the ability of the SARS coronavirus to shift from animals to humans.19
In January 2004，C hina ordered the closing of wildlife markets and the culling of an
estimated 10，000 palm civets held in wildlife markets after genetic tests linked av irus
isolated from civets to an ew confirmed case of SARS case in Guangzhou，ca pita1 city of
South China's Guangdong Province.20 The Guangdong provincial govemment announced
the ban on the breeding and sa1eo f palm civets to prevent any possible spread of血e
apparent SARS precursor virus. Producers from centra1 China who supply captive-bred
civets to Guangdong markets are protesting血eloss of markets and income caused by the
new regulations. Civets and hundreds of other species of wild anima1s 'esold in large
紅
numbers for use in food and medicinal products in Thailand，C hina，a nd other countries in
southeastem Asia. Although China had banned the trade in civets and 53 other wild
animals during April 2003，th e ban was lifted in August 2003 after scientists were unable
to confirm which anima1 species was the apparent source or reservoir of the new human
SARS viruS.21
Urban rats may prove have been the source of infection for the SARS case reported
from Guangzhou，C hina in December 2003. China Daily reported that laboratory te山
determined rats caught in the SARS victim's ap訂出lentwere carrying出eSARS v註us，17
da1出oughthe report was not confirmed by govemment health authorities，a n ew campaign
佃
to ex抑制ratswas制 ouncedby the officia1 news media at出esame time出sreport was
circulated by the local press. Local media in Guangzhou reported that the patient had been
trapping rats that had invaded his ap訂出lentbefore he showed any SARS symptoms; the
patient said that he had no known contact with the civet species identified publicly by the
Chinese govemment as the probable source or reservoir for the disease.15 Rats have been
hypothesized as ap ossible source for an outbreak in Hong Kong during March 2003.22
Should SARS become established in urban rat and cat populations，th is disease could prove
difficult or impossible to control or eradicate from Guangzhou，H ong Kong，or other large
cities or metropolitan areas in southem China.
Although SARS virus evidently did not originate in rats，th e current evidence seems
to indicate出atwhat we are witnessing and tracking at出ismoment is as ignificant
evolutionary event involving the tentative early stages of the process whereby an ewly-
mutated vira1 pathogen，th e SARS virus，es tablishes ah ost-pathogen symbiosis with an ew
reservoir host species (such as rats，ca ts，h umans，et c). If we are fortunate，th e SARS virus
in it' sc urrent form may not be able to establish itself as as elf-sustaining zoonotic pathogen
within urban rat populations，a nd the disease will occ inurban rats only as at ransient
町
and dead-end secondary host. In this case the closing of wildlife street markets to the sa1e
of potentia1 wildlife reservoir hosts (raccoon dogs，p a1m civets，et c.)23 by the govemment
of China could successfully prevent subsequent outbreaks.
The definitive host reservoir for the SARS pa由ogenis still unknown at the present
time. It cannot be ruled out whether virus aerosols derived仕ommechanica1 transmission
or urine/fecal contarnination by rats (Rattus rattus andlor R. norvegicus，rather than
24
EMERGING VIRAL ZOONOTIC DISEASES 129
aerosolized virus from ac ontaminated toilet ventilation system，25 may have been the driving
mechanism for proliferation of the March 2003 SARS outbreak in the Amoy Gardens，
Hong Kong. It seems possible that if the intensive rat eradication efforts undertaken at the
sites in Guangzhou or Hong Kong where SARS outbreaks occurred were successful (or
nearly so)，it may still be possible that latent SARS infections are circulating in such av ery
sma11n umber of individua1 rats 白紙thedisease may not be evident even if it is in fact still
present in urban rat populations at these sites. It is extremely important that we investigate
and evaluate any and a11p otentia1 reservoirs and transmission mechanisms for the SARS
Vln服、26
Recent events have shown biosecurity precautions and access for laboratory cultures
of the avian influenza，th e SARS virus，an d other potentia11y lethal pathogens must be both
increased and rigorously enforced. Laboratory expos havebeen blamed for aS ARS
町田
case in Singapore血atoccurred in September 2003，a S ARS case in ar esearcher from
Taiwan during December 2003，a nd an April/May 2004 outbreak of SARS in China that
resulted in at least four confirmed human SARS cases出atprecipitated the resignation of
the chief of China's Center for Disease Con住01where the incident occurred. Nonetheless，
the confirmation of ac 出eof apparent laboratory-acquired SARS in as e凶orscientist in血e
Institute of Preventive Medicine，Na tiona1 Defense University in Taipei who recently回 veled
to am edical conference in Singapore sparked an ew wave of SARS surveillance activity
in mainland China，Ta iwan，an d Singapore，27 and may have contributed to the early detection
by Chinese officials of an ew SARS case in Guangzhou on 26 December 2003.28百lere
were also two similar incidents involving the Ebola virus during the first five months of
2004，o ne of which resulted in the death of aR ussian researcher at the Vector-State
Research Center of Virology and Biotechnology.29.3o
Thai government officia1sh ave suggested白紙migratorybirds were白ecause of avian
flu outbreaks in Thailand，a nd Cambodian agricultural authorities announced an outbreak
of H5Nl avian influenza in Cambodia discovered in September 2004 might have been
caused by wild ducks f詑quentingap ond ne紅白efarm where the outbreak was discovered.
Similar claims were made recently by South Korean officia1sw ho said白紙resultsof a9 ・
month study on the origin of widespread avian influenza indicated白紙domesticatedducks
出atwere曲esource of aw idespread outbreak in South Korea in December 2003 may have
been infected by migratory wild birds. A report issued by血egovernment of Japan in June
2004 also implicated-but could not unequivocally identify-migratory birds as白esource
of the H5Nl bird flu outbreak in Japan during January and February 2004，si nce genetic
analyses showed that the virus in Japan was identica1 to that found in South Korea.
Information collected by the au白oron血ereported incidence of avian flu in southeastern
Asia during the period from October 2003血roughOctob巴r2004 indicates that the observed
pattern of H5Nl avian influenza outbreaks during血epast ye紅 followsas outh-to-north
trajectory through the fa11a nd win飽rmonths that appears to be incompatible with a
migratory bird vector hypo血esis.The available data now show白atthe earliest known
outbreaks of the cuπ'ent H5Nl avian influenza pandemic began in Indonesia，Th ailand，an d
Vietnam during October-November 2003，f ollowed by subsequent reported outbreaks in
Korea (December 2003)，J apan (January 2004)，C ambodia (January 2004)，a nd China
(Januy2004). The available evidence does not show any evidence of correspondence
紅
between the geographic and temporal distribution of reported outbreaks in poultry and the
known migratory patterns of wild bird populations in the eastern Asia. Migratory birds
130 JOSEPH P. DUDLEY
cannot be linked to outbreaks in multiple sites located along or ne紅 majormigratory routes
for any given species or class of migratory birds (e.g.，w aterfowl，r aptors，p asserines，o r
shorebirds)，a nd the observed outbreaks in pou加ydo not appear to correspond either
spatially or tempora1ly with rnigration paUems typical of wild birds in eastem Asian
landscapes.
The public health effects and econornic impacts of the cuηent avian influenza
epidemic necessitate a thorough and exhaustive investigation of the relative roles of
domesticated poultry and wild birds in th巴transrnissionand persistence of avian influenza
in Thailand. In order to be effective，ho wever，th ese efforts will require increased cooperation
and coordination between and among scientists and govemment officials in Thailand and
other countries in Southeast Asia，a nd between intemational veterinary health officials and
public heath officia1sa nd their Thai counte叩紅ts.
ACKOWLEDGMENTS
The author thanks Warren Brockelman，S ompoad Srikosamatara，an d an anonymous
reviewer for helpful comments on the original manuscript. This work was suppo此.edby
funding from Intellibridge Corporation.
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