Revista Romana Boli Infectioase - 2008 - Vol. XI - Nr.3

7/27/2019 Revista Romana Boli Infectioase - 2008 - Vol. XI - Nr.3

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COD CNCSIS 770

ISSN 1454-3389

Revista Romn de

BOLI INFECIOASE

Volumul XI

Nr. 3Anul 2008

Redactor efLudovic Pun

Redactor ef AdjunctMircea Chiotan

Secretar de RedacieSimin-Aysel Florescu

CONSILIUL TIINIFIC

Petre Calistru BucuretiDumitru Crstina ClujEmanoil Ceauu BucuretiAugustin Cupa CraiovaOlga Dorob BucuretiDoinia Ispas Bucureti

Vasile Luca Iai

Lucian Negruiu TimioaraRodica Pascu Tg. MureIleana Rebedea BucuretiSorin Rugin ConstanaDoina Stnescu TimioaraAdrian Streinu-Cercel Bucureti

Dumitru Suciu Sibiu

Editura Medical AMALTEA

Editori: Dr. M.C. PopescuDr. Cristian Crstoiu

Director executiv:George StancaRedactori: Oana Cristina Plcint, Alina-Nicoleta Ilie

Prepress: AMALTEA TehnoPlusTehnoredactor: Gabriela Cpitnescu

DTP: Petronella Andrei, Gabriela CpitnescuProducie: Mihaela Conea

Distribuie: Mihaela Stanca________________

CONTACT: [email protected]: [email protected]

TIPAR:

EMPIRE Print RomExpo, Pavilion T, Bucuretitel.: 021 / 316 96 40, 031 / 405 99 99

email: [email protected]

Secretariatul Redaciei:

Simin-Aysel FlorescuClinica de Boli Infecioase

i Tropicale Victor Babe,os. Mihai Bravu nr. 281, sector 3, Bucureti

Telefon/Fax: 01 - 317 27 20


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Cuprins

1. Cuvnt ctre cititori ____________________________________________________________ 123

Ludovic Pun

2. Bolile infecioase, armele biologice, bioterorismul, provocare major a societiicivile contemporane ____________________________________________________________ 125Ludovic Pun

3. Influenza Activity ______________________________________________________________ 127Department of Health and Human Services Center for Disease Control and Prevention

4. Bacterial Pneumonia and Pandemic Influenza Planning ____________________________ 133Ravindra K. Gupta, Robert George, Jonathan S. Nguyen-Van-Tam

5. Deaths from Bacterial Pneumonia during 1918-19 Influenza Pandemic _______________ 139John F. Brundage, G. Dennis Shankst

6. Environmental Contamination during Influenza A Virus (H5N1) Outbreaks,Cambodia, 2006_______________________________________________________________ 146Sirenda Vong, Sowath Ly, Sek Mardy, Davun Holl, Philippe Buchy

7. Highly Pathogenic Avian Influenza Virus (H5N1) in Experimentally InfectedAdult Mute Swans _____________________________________________________________ 149Donata Kalthoff, Angela Breithaupt, Jens P. Teifke, Anja Globig, Timm Harder,Thomas C. Mettenleiter, Martin Beer

8. Highly Pathogenic Avian Influenza Virus (H5N1) Isolated from Whooper Swans, Japan _____ 153Yuko Uchida, Masaji Mase, Kumiko Yoneda, Atsumu Kimura, Tsuyoshi Obara,Seikou Kumagai, Takehiko Saito, Yu Yamamoto, Kikuyasu Nakamura, Kenji Tsukamoto,Shigeo Yamaguchi

9. Oseltamivir Prescribing in Pharmacy-Benefits Database, United States, 2004-2005 _____ 156Justin R. Ortiz, Laurie Kamimoto, Ronald E. Aubert, Jianying Yao, David K. Shay,Joseph S. Bresee, Robert S. Epstein

10.Pandemic Influenza and Excess Intensive-Care Workload __________________________ 160Raoul E. Nap, Maarten P.H.M. Andriessen, Nico E.L. Meessen, Dinis dos Reis MirandaTjip S. van der Werf

11.Influenza Virus (H5N1) in Live Bird Markets and Food Markets, Thailand____________ 168Alongkorn Amonsin, Chuensakon Choatrakol, Jiradej Lapkuntod,Rachod Tantilertcharoen, Roongroje Thanawongnuwech, Sanipa Suradhat,Kamol Suwannakarn, Apiradee Theamboonlers, and Yong Poovorawan

12.Replacement of Sublineages of Avian Influenza (H5N1) by Reassortments,

Sub-Saharan Africa____________________________________________________________ 173Ademola A. Owoade, Nancy A. Gerloff, Mariette F. Ducatez, Jolaoso O. Taiwo,Jacques R. Kremer, and Claude P. Muller

13. Bibliografie de consultat _______________________________________________________ 178


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REVISTA ROMNDE BOLI INFECIOASE VOL. XI, NR. 3, AN 2008 123

1

Stimai cititori,

n orientarea activiti i editoriale, Consiliultiinific al Revistei Romne de Boli Infecioase aaderat la punctul actual de vedere, care consi-der specialitatea de boli infecioase o specialitateclinic, independent, implicat n Cl inica,Diagnosticul, Terapia i Profilaxia mbolnvirilorproduse de ageni etiologici cunoscui sau n cursde identificare, patogenii la toate vrstele deo-potriv i n evoluiile epidemiologice ale bolilorinfecioase acute transmisibile n comunitileumane (focare infecioase, epidemii, pandemii).

Acest mod de abordare a bolilor infecioaseacute transmisibile a determinat cu necesitate, ncondiiile Globalizrii* patologiei infecioase,elaborarea i aplicarea la nivel mondial, de ctrerile membre ale Organizaiei Mondiale a Sntii(OMS), (incluznd n program i rile care nu sunt

nc membre OMS) a Regulamentului SanitarInternaional, OMS 2005 (Revista Romn de BoliInfecioase, Regulamentul Sanitar InternaionalVol. XI, Nr. 1/2008), activitate programat s sedesfoare pe durata a 5 ani, ncepnd cu anul2005.

Dinamica bolilor infecioase acute transmisibilela sfritul secolului XX i nceputul secolului alXXI-lea, severitatea evoluiilor naturale ale acestora,determinat de diversitatea fondului etiologiccomun pe Tera i n Cosmos, att natural, ct imodificat intenionat Weaponizat** a permisaprecierea ameninrii neconvenionale laadresa securitii naionale (John C. Ganon TheGlobal Infectious Threat and Its Implications forUnites Statter NIE 99, 17 January, 2000). Ataculcu Spori de Bacillus anthracis, 11 Septembrie2001, a reprezentat doar o dovad nedorit, dar,din pcate, nu unic.

Perspectiva evoluiei pandemice naturale agripei A (H5N1) a impus:

a. instituirea alertei epidemiologice, n ciudanumrului redus de cazuri umane (n jur de100, localizate n marea majoritate n riledin Asia de Sud-Est);

b. abordarea actual a manifestrilor clinice,diagnosticul i terapia cazurilor individualede grip;

c. precum i reactualizarea, compararea ivalorificarea concluziilor rezultate dinstudiul actualizat al evoluiilor pandemiei degrip A (H5N1), 1918-1919 (articolele 3,4, 5 din Sumar).

Consiliul tiinific al Revistei Romne de BoliIn fec ioase a cons iderat opor tun acordareaspaiului editorial al Nr. 4/2008, pentru infor-marea Corpului medical din Romnia, a GrupuluiTehnic de specialiti (clinicieni n boli infecioase

aduli i copii) epidemiologi, microbiologi cudatele i opiniile publicate n: Emerging Infectious

Diseases, Vol. 14, Nr. 8, August, Nr. 9, Septembrie2008 i Morbidity and Mortality Weekly Report,Iunie 27/2008, Vol. 57, Nr. 25. Ambele publicaiisunt de acord cu reproducerea integral (pag. 132;pag. 159). Publicarea sumarelor articolelor i nlimba romn o considerm o facilitate pentrucititori.

n legtur cu Gripa Pandemic A (H5N1) sau

Gripa viral determinat de alt tip de virus,Consiliul tiinific consider c procednd ne-convenional la ntocmirea sumarului Nr. 4/2008al Revistei Romne de Boli Infecioase a doveditflexibilitate n abordarea marilor probleme pe carele ridic morbiditatea prin boli infecioase iinformarea specialitilor n secolul al XXI-lea.Dup ce va obine punctul de vedere al cititorilor

n legtur cu iniiativa sa, Consiliul tiinific vacontinua s acorde spaiu editorial, de preferin

CUVNT CTRE CITITORIForeword

*) Concept universal, ce dorete a surprinde evoluiile mondiale naturale social-economice i politice dup cel de-al Doilea Rzboi Mondiali al Rzboiului Rece i ncearc s codifice i s clasifice reaciile persoanelor, grupurilor de persoane, organizaii etc. care recurg inclusivla violen n lupta pentru putere (James M. Lutz i Brenda Lutz n Global Terrorism Rontledge, 2004, Causes of Terrorism, pag. 17)**) Transformat prin procedee biotehnologice genetice specifice n arme biologice.


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124 REVISTA ROMNDE BOLI INFECIOASE VOL. XI, NR. 3, AN 2008

n suplimente la numerele curente, lsnd liberspaiul editorial al revistei pentru publicarea lu-crrilor cu caracter de originalitate individual saua grupurilor de specialiti.

n acest sens, ar putea fi elaborate Sumarepentru: Infeciile cu genul Vibrio, Etiologiainfecioas a bolilor cronice, Bioterorismul nSecolul al XXI-lea.

Redactor ef,Prof. Dr. Ludovic Pun

Adres de coresponden:Prof. Dr. Ludovic Pun, Spitalul Clinic de Boli Infecioase i Tropicale Dr. Victor Babe, os. Mihai Bravu, Nr. 281, Sector 3,Bucureti


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nativilor americani precolumbieni, iar n epidemiamondial de grip (H5N1) 1918-1919 au decedatpeste 21 de milioane de oameni, n mare majoritatetineri, mai muli dect au fost omori prin armelede foc n cursul celui de-al Doilea Rzboi Mondial(3). Cu toate sucesele obinute n limitarea morbi-

ditii prin boli infecioase, n SUA mor anualaproximativ 150.000 de oameni (3). n prezent,prevenirea epidemiilor majore de boli infecioasereprezint o provocare mai mare dect anterior,din cauza globalizrii, cltoriilor i comerului,marilor concentraii ale populaiilor, convieuiriin proximitatea animalelor, ale cror boli (unele!)

pot fi transmise oamenilor (3).La ameninrile bolilor infecioase transmise

natural se adaug ameninrile bioteroriste (2)!Una dintre particularitile armelor biologice

const n faptul c acestea (armele biologice) facparte dintre organismele vii, spre deosebire de altearme cu extindere n mas (explozive, nucleare,chimice); armele biologice (forme vii de existen)sunt o prezen universal, n mediul fizic i biologic,pe Terra i n cosmos, fondul etiologic comun.

n aceste condiii (existena dualist a for-melor unicelulare i multicelulare de via), secreeaz n mod obligatoriu fie relaii echilibrate,fie dezechilibre biologice care implic sntatea

i calitatea vieii, induc evoluii epidemiologieindividuale i de grup, inclusiv bioterorismul.

Relaiiie biologice ntre cele dou existene viisunt concretizate prin manifestri clinice, epide-miologice, date i explorri de laborator, markeriai evoluiei biologice, care, consemnate i sintetizatealturi de supravegherea clinic, se constituie nbaza de date necesar managementului, dup caz,a unei epidemii naturale i/sau a unui atac bioterorist.

Un raport, declasificat recent n Statele Unite,

elaborat de National Intelligence Council pentru

Central Intelligence Agency (CIA), concluzioneazc: Bolile infecioase nu sunt numai o problemde sntate public, ci i una de securitatenaional (4), populaia Statelor Unite este vulne-rabil att la bolile infecioase emergente, ct ireemergente (4).

n anul 1993, U.S. Congresionat Office ofTechonology estima c diseminarea a 100 dekilograme, spori de Antrax, asupra aezrii umaneWashington DC, ar putea produce ntre 130.000 3 milioane de decese, i ar putea fi considerate oarm la fel de letal ca i o bomba cu hidrogen (3).

Accidentul Sewerdlowsk (URSS, 1979) cuspori de Bacillus anthracis insuficient mediatizat,i mai ales atacul bioterorist cu spori de Bacillusanthracis, SUA 2001, ca i ameninrile teroristecu recurgerea la armele biologice se constituie n

dovezi clare pentru susinerea existenei provo-crii majore actuale pe care bolile infecioase (nevoluia natural), armele biologice (evoluiepro-vocat) i bioterorismul (manifestri pshiologicede mas) le dezvolt la adresa societii civile.

Informaiile difuzate pe Internet cu privire lafabricarea armelor biologice constituie o surstehnic de sprijin pentru cei ce provoac sau sepregtesc s practice bioterorismul. Este necesarca guvernele, prin structurile de Sntate Public,

mpreun cu Structurile informative i a celor deAplicare a legii s reacioneze tehnic, prompt iinteligent n eventualitatea suspiciunii unei epi-demii, indiferent dac aceast epidemie este na-tural sau provocat, disjuncie foarte greu derealizat n primele ore de la debut, altfel hotrtoare,

n legtur cu evoluiile ulterioare ale epidemiei.Exerciiile Dark Winter (Variola) (2) i Topoff(ciuma) (3), dou exerciii efectuate n SUA, atragatenia asupra necesitii amplificrii activitii deprevenire i rspuns la atacul bioterorist asupra

societii civile n ntregul su.

BIBLIOGRAFIE

1. History of the development and use of weapons. CDR AylenM.Marty. Clinics in Laboratory Medicine, Vol. 21, No.3, September2001, 421-423.

2 . Ludovic Pun Boli fnfecioase, Arme Biologice, Bioterorism. Ed.Amaltea, Bucureti 2003.

3. Laurence O. Gostin et al The State Emergency Health PowerAct for and Response to Bioterorism and Naturally Occuring

(infectious Diseases JAMA, August 7, 2002, Vol. 2B8, No. 5, p.622-625

4 . John C. Cavon The Global Infectious Diseases Threat and itsImplications for the Planing Unites States NIE, 99-17D January 2000

5 . Jamis M. Hughes Center for Disease Control and PreventionAtlanta Georgia USA, The Emerging Threat Bioterrorism http;//

www.c.d.c. govf ricidod/E iDA/o l.15, no.4 hughost btm. (5)

Adres de coresponden:Prof. Dr. Ludovic Pun, Spitalul Clinic de Boli Infecioase i Tropicale Dr. Victor Babe, os. Mihai Bravu, Nr. 281, Sector 3,Bucureti


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Th e Morbidity and Mo rtal ity We ek ly Report(MMWR) Series is prepared by the Centers forDisease Control and Prevention (CDC) and isavailable free of charge in electronic format. Torecive an electronic copy each week, send an e-mail message to [email protected]. Thebody content should read SUBscribe mmurtoc.

Electronic copy also is available from CDCsInternet server at http://www.cdc.glov/mmwrorfrom CDCs file transfer protocol server at ftp://

ftp.c dc .go vp ub licat ion s/ mmw r. Paper copysubscriptions are available through theSuperimendent of Documents, U.S. GovernmentPrinting Office, Washintong, DC 20402; telephone202-512-1800.Data in the weekly MMWR are provisional, basedon weekly reports to CDC by state healthdepartments. The reporting week concludes at clos

of bussines on Friday; compiled data on a nationalbasis are officially released to the public on thefollowing Friday. Data are complied in theNational Center for Public Health Informatics,

Division of Integrated Surveillance System.Address all inquiries about the MMWR Series,including material to be considered for publication,to Editor,MMWR Series. Mailstop E-90, CDC, 1600Clifron Rd., N.E., Adanta, GA 30333 or [email protected] materia in the MMWR Series is in the public

domain and may be used and reprinted withoutpermission; citation as to source, however, isappreciated.Use of trade names and commercial sources is foridentification only and does not imply endorsementby the U.S. Department of Health and HumanServices.References to non-CDC sites on the Internet areprovided as a service to MMWR teaders and donot constitute or imply endorsement of theseorganizations or their programs by CDC or the

U.S. Department of Health and Human Services.CDC is not responsable for the content of thesesires. URI, addresse listed in MMWR were currentas of the date of publication.

REZUMATn cursul sezonului gripal 2007-2008, activitatea gripei a atins punctul culminant n Statele Unite la mijlocul luni i februarie i a fostasociat cu o mortalitate i o frecven mare a internrilor n spital a copiilor ntre 0-4 ani, n comparaie cu cele trei sezoaneanterioare. n Statele Unite, gripa A (H1N1) a predominat la nceputul sezonului; virusurile grupei A (H3N2) i-au intensificatcirculaia n luna ianuarie i au predominat peste tot, n timp ce gripa cu virusurile A (H1N1), A (H3N2) i B circulau la nivel mondial.Gripa cu virusul A (H1N1) a fost mult mai frecvent raportat n Canada, Europa i Africa, iar gripa cu virusul B a fost predominant

n rile Asiei. Acest raport sintetizeaz activitatea gripal n Statele Unite i la nivel mondial n cursul sezonului gripal 2007-2008

(30 septembrie 2007 - 17 mai 2008).


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* Articol preluat din: Emerging Infectious Disease. www.cdc.gov/eid. Vol. 14, No. 8, August 2008

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* Articol preluat din: Emerging Infectious Diseases. www.cdc.gov/eid. Vol. 14, No. 8, August 2008

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REZUMATDecesele din timpul pandemiei de grip 1918-1919 au fost atribuite unei sue hipervirulente de grip (virus). Pregtirile pentrupandemia urmtoare se concentreaz aproape n exclusivitate pe prevenirea prin vaccin ca msur preventiv i tratament

antiviral pentru noua su de virus gripal. Cu toate acestea, noi emitem ipoteza c infeciile cu su pandemic de virus provoaco boal autolimitant n general (rar fatal), boal care favorizeaz sue colonizante de bacterii, capabile s produc pandemiisevere asociate cu mortalitate ridicat. Aceast ipotez secvenial este concordant cu pandemia1917-1918, cu opinia experilorcontemporani i cunotinele curente cu privire la efectele fiziopatologice ale virusurilor gripale i interaciunile acestora cubacteriile respiratorii. Aceast ipotez sugereaz oportuniti de prevenire i tratament n cursul urmtoarei pandemii (cu vaccinuriantimicrobiene i medicamente antimicrobiene), n special dac vaccinul pandemic specific de su nu este disponibil sau esteinaccesibil pentru cei izolai, mulimi sau populaii fr sau cu puin asisten medical.


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REZUMATPentru a determina riscul potenial pentru transmiterea de la psri la om a gripei A (A5H1), n cursul epidemiei printre psrile decurte n mediul rural din Cambodgia, am colectat mostre din mediul nconjurtor. RNA-ul viral a fost detectat n 27 (35%) din 77 demostre de noroi, ap din eleteu, plante de ap i cruste din sol. Rezultatele noastre descurajeaz nevoia de dezinfecie regulat

n ari ile cu psri .


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REZUMATLebedele adulte sntoase au fost infectate experimental cu virusul gripal aviar nalt patogen A /Cygnus cygnus/Germany/R 65/2006, subtipul H5N1. Psrile naive imunologic au murit, n timp ce acelea cu anticorpi naturali virus specifici preexisteni audevenit infectate asimptomatic i purttoare de virus. Lebedele adulte sunt nalt susceptibile, execret virus i pot fi protejate clinicprin imunitatea obinut anterior.


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REZUMATn data de 21 aprilie 2008, patru lebede iptoare au fost gsite moarte pe Lacul Towada, Prefectura Akito, Japonia. A fost izolat dinspecimenele recoltate de la psrile afectate virusul gripal nalt patogen A, subtipul H5N1. Gena hemaglutininei (HA) ale izolateloraparine cladei 2.3.2., din arborele filogenetic HA.


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All material published in Emerging Infectious Diseases is in the public domain and may be usedreprinted without special permission; proper citation, however, is required.

REZUMATNoi am revzut informaiile din baza de date ale managerilor beneficiari ntre 2004 i 2005, perioad cu activitate gripal mic. Amcalculat rata de prescripii ale Oseltamivirului pentru cei nscrii. Rata prescrierilor a crescut semnificativ de la 27,3%/100.000 n2004, la 134/100.000 n 2005 (p


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* Articol preluat din: Emerging Infectious Diseases. www.cdc.gov/eid. Vol. 14, No. 10, October 2008

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REZUMATn rile de jos, Olanda, majoritatea pregtirilor planificate pentru o epidemie sau pandemie constau n meninerea serviciilor publiceeseniale, de exemplu poliia, departamentul pompierilor, personal organizat din cadrul armatei i muncitorii sanitari. Noi asigurmestimrile pentru vrful cererii pentru muncitorii sanitari, apreciem absenteismul printre muncitorii din sntate i folosim estimriledin modelele epidemiologice publicate n relaie cu impactul pe vrful valului capacitii facilitilor de ngrijiri de sntate i unitile

de terapie intensiv (ICUS). Folosind scenarii variate publicate, noi estimm eforturile lor n creterea disponibilitii ngrijitorilor desntate pentru sarcinile unei pandemii. Noi artm c n vrful epidemiei tuturor pacienilor care necesit internri n spital i nunitile de terapie intensiv li se poate asigura internarea, inclusiv a acelora care sufer de alte maladii dect gripa sau complicai ileacesteia. Pentru aceast difereniere riguroas sunt eseniale: ierarhizarea clar a managementului, comunicarea/informareaneechivoc i disciplinarea; noi recomandm informarea i instruirea muncitorilor din sntate, alii dect cei care lucreaz ndepartamentele de terapie intensiv despre sarcinile din unitile de terapie intensiv.


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In Thailand, from 2004 through 2008, 6 majoroutbreaks of avian influenza occurred (JanuaryMarch 2004, JulyOctober 2004, OctoberDecember 2005, JanuaryMarch 2006,NovemberMarch 2007, and January 2008). Wereport on a 14-month avian influenza surveillanceprogram and its finding of influenza virus (H5N1)

in live bird and food markets in Thailand.The Study

From July 2006 through August 2007, aninfluenza (H5N1) surveillance program wasconducted in live bird and food markets in 10provinces of central Thailand (Figure 1). Cloacalswabs (n = 381) were sampled from live chickens,ducks, pigeons, and house sparrows. Visceralorgans and bird meats (n = 549) were collectedfrom carcasses of chickens, ducks, quails, water

cocks, water hens, swamp hens, crakes, parakeets,and moor hens at local food markets (Tables 1,2). An average of 4 markets (range 16) werevisited each month, and 18 samples werecollected from each market. All samples were frombackyard animals or local meat birds. None werefrom birds from standard farming systems withhigh biosecurity.

The viruses were propagated by embryonatedegg inoculation (1). Allantoic fluids were tested

for influenza subtype H5N1 by hemagglutination(HA). Multiplex reverse transcriptionPCR (RT-PCR) was performed to amplify H5, neuraminidase(N) 1, and matrix (M) genes from HA-positivesamples (2).

Influenza virus (H5N1) was identified in 12 of930 samples tested. In November 2006, a total of

5 samples with influenza virus (H5N1) wereisolated from 1 healthy chicken and 4 visceralorgans obtained from 1 live bird market (chicken)and 3 different food markets (moor hen, watercock, and quail). In December 2006, a total of 5samples with influenza virus (H5N1) were isolatedfrom 5 visceral organs (quail, water cock) from 1food market. In January 2007, a total of 2 sampleswith influenza virus (H5N1) were isolated from 2healthy ducks obtained from 1 live bird market.In the study, 7 isolates were sequenced for whole

genome analysis, and the remaining 5 sampleswere sequenced for H5 and N1 genes. Therespective viruses were designated as A/moorhen/Thailand/CU-317/2006 (GenBank accession nos.EU616825EU616826), A/moorhen/Thailand/CU-318/2006 (EU616827EU616828), A/watercock/Thailand/CU-319/2006 (EU616829EU616830), A/quail/Thailand/CU-320/2006(EU616831EU616832), A/chicken/Thailand/CU-321/2006 (EU616833EU616834), A/quail/

11INFLUENZA VIRUS (H5N1) IN LIVE BIRDMARKETS AND FOOD MARKETS,

THAILANDAlongkorn Amonsin, Chuensakon Choatrakol, Jiradej Lapkuntod, RachodTantilertcharoen, Roongroje Thanawongnuwech, Sanipa Suradhat,Kamol Suwannakarn, Apiradee Theamboonlers, and Yong Poovorawan

ABSTRACTA surveillance program for influenza A viruses (H5N1) was conducted in live bird and food markets in central Thailand during July2006August 2007. Twelve subtype H5N1 viruses were isolated. The subtype H5N1 viruses circulating in the markets were

genetically related to those that circulated in Thailand during 20042005.

Author affiliation: Chulalongkorn University, Pathumwan, Bangkok, Thailand

*

* Articol preluat din: Emerging Infectious Diseases. www.cdc.gov/eid. Vol. 14, No. 11, November 2008


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Thailand/CU-330/2006 (EU616851EU616858),A/quail/Thailand/CU-331/2006 (EU616859EU616866), A/quail/Thailand/CU-332/2006(EU616867EU616874), A/quail/Thailand/CU-

333/2006 (EU616875EU616882), A/watercock/Thailand/CU-334/2006 (EU61683EU616890),A/duck/Thailand/CU-328/2007 (EU616835EU616842), and A/duck/Thailand/CU-329/2007(EU616843EU616850).

To analyze the isolates, nucleotide sequences

were compared with those of influenza subtypeH5N1 viruses in Thailand, Peoples Republic ofChina, Vietnam, Indonesia, Lao, Myanmar, andCambodia. The sequences were aligned by usingthe DNASTAR program (3) to elucidate andcompare the genetic changes. Phylogeneticanalysis was conducted by applying the PAUPprogram (4) with the neighbor-joining algorithmand using branch swapping and bootstrap analysiswith 1,000 replicates.

Conclusions

In the course of the 14-month surveillanceprogram, we isolated influenza virus (H5N1) from12 samples from live birds and from bird meatsobtained from the markets. Bird meats were thesource of 9 virus-containing samples (5 quail, 2moor hens, and 2 water cocks), which indicates arisk for influenza virus (H5N1) contamination inbird meats, especially quail. In addition, 3 highlypathogenic avian influenza viruses were isolated

from healthy live poultry (1 chicken and 2 ducks).However, the samples that contained influenzavirus subtype H5N1 were detected only duringthe 3-month winter season (NovemberJanuary).A possible explanation for virus contamination inlive bird and food markets may be animalmovement from outbreak areas to the markets as

Figure 1

A) Poultry at live bird market; B) house sparrows at livebird market; C) chicken meat at food market;D) moor hen meat at food market.

Table 1Test results for samples

collected duringinfluenza virus (H5N1)surveillance program inlive bird and foodmarkets, by collectiondate, central Thailand


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well as an attempt to sell infected (dead or dying)birds, especially quail, as bird meat. In addition,most animals or meats in the markets came frombackyard farms, where they were in unavoidablyclose contact with wild birds.

Phylogenetic analysis of the virus HA and NAgenes indicated that all 12 subtype H5N1 isolateswere part of the Vietnam and Thailand lineage(clade 1). The viruses were closely related to thoseinvestigated in Thailand (20042005) as well as

to other subtype H5N1 isolates in clade 1. Incontrast, they differed from influenza subtypeH5N1 viruses of the south China and Indonesialineages (clade 2) (Figure 2). In this study, we didnot discern any Thailand isolates closely relatedto the south China lineage, as previouslyestablished in Lao and Cambodia (5). Phylogeneticanalysis of 6 remaining genes showed them to bealso closely related to the Vietnam and Thailandisolates.

Table 2Test results for samples collected during the influenza virus (H5N1) surveillance programin live bird and food markets, by bird species, central Thailand

Figure 2Phylogenetic analysis ofthe hemagglutinin (A) andneuraminidase genes (B)of influenza virus (H5N1)isolates. Phylogenetictrees were generated byusing the PAUP computerprogram (4) and applyingthe neighbor-joining

algorithm with branchswapping and bootstrapanalysis with 1,000replicates. The trees wererooted to A/goose/China/Guangdong/1/96 (H5N1).


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Analysis of the deduced amino acid sequencesof the HA and NA proteins indicated that theviruses had characteristics of highly pathogenicavian influenza. The HA cleavage site consists ofmultiple basic amino acids RERRRKKR (in 1isolate, CU-329, REKRRKKR). All influenza

subtype viruses harbor Glu-222 and Gly-224 atthe receptor binding site, indicating preferentialbinding to the avian receptor SA--2, 3-Gal. Inaddition, the virus sequences contain 7glycosylation sites as previously identified in mostisolates from Thailand (6). A glycosylation siteadjacent to receptor binding sites may help increasevirus infectivity in host cells (7). In some isolates,polymorphisms of amino acids related to antigenicproperties of the viruses at position V86A, L138Q,and K140N were observed. All 12 subtype H5N1

viruses had a 20-aa deletion in the NA protein,typical for the NA stalk region of recent subtypeH5N1 isolates (20032007) (8,9). None of thesubtype H5N1 isolates had any amino acidsindicating oseltamivir resistance at the crucialpositions 119 (E), 275 (H), 293 (R), and 295 (N)of the NA protein. In summary, the 12 virusesisolated from this study were similar to the virusesfrom other sources in Thailand, which indicatesthat the viruses are endemic to Thailand, arecirculating in the country, and can be found inany exposed species.

The route of influenza virus (H5N1)introduction into the markets remains to beestablished. We suspect that this contaminationmight have occurred as a consequence of animalmovement from outbreak areas or from virus-contaminated cages, trucks, and equipment.

Unfortunately, the original sources of animals inthe markets could not be identified because birdsfrom different sources were housed in 1 or severalcages. Fortunately, no human infection was foundduring 20072008 in those provinces where theviruses were isolated.

It has been known that live bird and wetmarkets play a major role in facilitating emergenceor reemergence of influenza and some otherrespiratory diseases (1012). Monitoring of livebird and food markets as an early warning systemshould be implemented in Asian countries wheresuch markets are still commonplace, and routinesurveillance of these markets should be conductedyear-round. In addition, raw bird meats should behandled with caution, and consumption of rawbird meats should be avoided. Increased public

awareness about the risks for influenza virus(H5N1) in association with live bird and foodmarkets will help prevent and control subtypeH5N1 infection in humans.

Acknowledgment

We thank Petra Hirsch for reviewing themanuscript.

This study was supported by grants from theNational Research Council of Thailand and

Chulalongkorn University, RachadaphisetShomphod Endowment Fund (ChulalongkornUniversity) for fiscal year 2006, and the ThailandResearch Fund, Senior Research Scholar.

Dr Amonsin is an associate professor inVeterinary Public Health at ChulalongkornUniversity, Bangkok. His research interests includemolecular epidemiology of emerging diseases.

REFERENCES

1. World Organisation for Animal Health Manual of standards fordiagnostic tests and vaccines, 4th ed. Paris: The Organisation; 2000.

2. Payungporn S, Phakdeewirot P, Chutinimitkul S,Theamboonlers A, Keawcharoen J, Oraveerakul K, et al Single-step multiplex reverse transcription-polymerase chain reaction(RT-PCR) for influenza A virus subtype H5N1 detection. ViralImmunol. 2004;17:58893. PubMed DOI

3. Burland TG DNASTARs Lasergene sequence analysis software.Methods Mol Biol. 2000;132:7191.

4. Swofford DL. PAUP Phylogenetic analysis using parsimony

(*and other methods), version 4. Sunderland (MA): SinauerAssociates; 2002.

5. Boltz DA, Douangngeun B, Sinthasak S, Phommachanh P,Rolston S, Chen H, et al H5N1 influenza viruses in LaoPeoples Democratic Republic. Emerg Infect Dis. 2006;12:15935.

6. Amonsin A, Chutinimitkul S, Pariyothorn N, Songserm T,Damrongwantanapokin S, Puranaveja S, et al Genetic

characterization of influenza A viruses (H5N1) isolated from 3rd waveof Thailand AI outbreaks. Virus Res. 2006;122:1949. PubMed DOI

7. Matrosovich M, Zhou N, Kawaoka Y, Webster R The surfaceglycoproteins of H5 influenza viruses isolated from humans,chickens, and wild aquatic birds have distinguishable properties. JVirol. 1999;73:114655.

8. Obenauer JC, Denson J, Mehta PK, Su X, Mukatira S,Finkelstein DB, et al Large-scale sequence analysis of avianinfluenza isolates. Science. 2006;311:157680. PubMed DOI

9. Viseshakul N, Thanawongnuwech R, Amonsin A, Suradhat

S, Payungporn S, Keawchareon J, et al The genomesequence analysis of H5N1 avian influenza A virus isolated from theoutbreak among poultry populations in Thailand. Virology.2004;328:16976. PubMed DOI

10. Liu M, He S, Walker D, Zhou N, Perez DR, Mo B, et al Theinfluenza virus gene pool in a poultry market in south central China.Virology. 2003;305:26775. PubMed DOI


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11. Wang M, Di B, Zhou DH, Zheng BJ, Jing H, Lin YP, et al Food markets with live birds as source of avian influenza. EmergInfect Dis. 2006;12:17735.

Address for correspondence: Yong Poovorawan, Center of Excellence inViral Hepatitis Research, Department of Pediatrics, Faculty of Medicine,Chulalongkorn University, Bangkok 10330, Thailand; email:[email protected]

12. Webster RG Wet marketsa continuing source of severe acuterespiratory syndrome and influenza? Lancet. 2004;363:2346.PubMed DOI

REZUMAT

Un program de Supraveghere pentru Virusul Gripal A (H5N1) a fost efectuat la psrile vii i pieele alimentare din centrul Tailandein intervalul iulie 2006 - august 2007. Au fost izolate 12 subtipuri de virusuri H5N1. Subtipul de virus H5N1 care circula n piee eranrudit genetic cu cel care a circulat n Tai landa n cursul anilor 2004-2005.


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Highly pathogenic avian influenza (HPAI) virussubtype H5N1 in Africa was first reported fromnorthern Nigeria in February 2006. Phylogeneticanalysis of the complete genome showed that theseviruses were clearly distinct from the 2 lineages

that were found during the same period insouthwestern Nigeria (1,2 ). The 3 sublineages(referred to as A, B, and C), 2 of which emergedfrom a common node, had evolved from subtypeH5N1 strains that were originally found aroundQinghai Lake in 2005. These strains clustered withviruses isolated from 2006 from southern Russia,Europe, and the Middle East (clade 2.2,www.who.int/csr/disease/influenza/tree_large.pdf)but not with the strains prevalent in southeast Asia(3). The timeline, the observed influenza A

(H5N1) substitution rates in Africa, and thephylogenetic relationship suggested that thesublineages were independently introduced intothe country (1,2 ). These sublineages were laterfound throughout Africa with a distinct geographicdistribution (2,4). Sublineage A was also found inNiger and Togo (hemagglutinin [HA] sequence);sublineage B was detected in Egypt and in a human

patient in Djibouti (partial HA sequence), andsublineage C was found in Burkina Faso, Sudan,Cte dIvoire, Ghana (HA and neuraminidase [NA]sequences) (5) and Cameroon (NA sequence) (6).Sublineage A strains were also referred to as EMA

2, and both sublineages B and C belong to EMA 1(3). In 2006, one strain with reassorted genes wasreported among 35 full-length sequences of theEuropeanMiddle EasternAfrican lineage (14).We describe new HPAI (H5N1) strains collected insouthwestern Nigeria during the second half of2007, most of which were different reassortants ofsublineages A and C.

Materials and Methods

Cloacal swabs were obtained from 8 chicken

farms in Lagos (1), Ogun (5), Oyo (1) and Ekiti(1) States from June through November 2007.RNA extraction from cloacal swabs, reversetranscriptionPCR amplification, and genesequencing were conducted as described (1). Formost viruses, complete sequences were obtainedfor all gene segments. Kimura distances werecalculated on the basis of complete or partial gene

12REPLACEMENT OF SUBLINEAGES OF

AVIAN INFLUENZA (H5N1) BY

REASSORTMENTS, SUB-SAHARAN AFRICAAdemola A. Owoade,1 Nancy A. Gerloff,1 Mariette F. Ducatez,2 Jolaoso O.

Taiwo, Jacques R. Kremer, and Claude P. Muller

ABSTRACTEight new full-length sequences from highly pathogenic avian influenza viruses (H5N1) from 4 states in southwest Nigeria wereanalyzed. All gene sequences were more closely related to the first strains found in Nigeria in 2006 than to any strain found outsidethe country. Six viruses had evolved by at least 3 reassortment events (ACHA/NS, ACNS) from previously identified sublineages A

(EMA 2) and C (EMA 1). Our results suggest that highly pathogenic avian influenza viruses (H5N1) initially imported into Nigeriain 2006 have been gradually replaced by various reassortments. In all reassortants, nonstructural genes were derived fromsublineage C with 2 characteristic amino acids (compared with sublineage A). If the high prevalence of reassortants was typicalfor West Africa in 2007, the absence of such reassortants anywhere else suggests that reintroductions of influenza A (H5N1) fromAfrica into Eurasia must be rare.

Author affiliations: University of Ibadan, Ibadan, Nigeria (A.A. Owoade); National Public Health Laboratory, Luxembourg (N.A.Gerloff, M.F. Ducatez, J.R. Kremer, C.P. Muller); and Ogun State Ministry of Agriculture, Abeokuta, Nigeria (J.O. Taiwo)

1These authors contributed equally to this article.2Current affiliation: St. Jude Childrens Research Hospital, Memphis, Tennessee, USA.

* Articol preluat din: Emerging Infectious Diseases. www.cdc.gov/eid. Vol. 14, No. 11, November 2008

*


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sequences by including the maximum sequencelength available from all strains included in thecomparison. Phylogenetic trees were calculated byusing PAUP version 4.0 beta 10 (7) with themaximum-likelihood method. The best model wasdetermined by using MODELTEST (8). The

sequences have been submitted to GenBank withthe accession nos. FM160635FM160642 andFM164800FM164855.

Results

Reassortants

All genes of A/chicken/NIE/EKI15/2007 andA/chicken/NIE/OYO14/2007 clustered phyloge-netically with sublineage A strains (Figures 1, 2).

Figure 1Phylogeny of hemagglutinin (A) and neuraminidase (B)genes from 8 HPAI (H5N1) viruses collected in Nigeriaduring the second half of 2007 (p), in comparison withpreviously identified sublineage A (EMA 2), sublineageB and C (EMA 1), and (EMA 3) strains (1,3). The tree

Figure 2Schematic presentation of sublineage Aderived highlypathogenic avian influenza viruses (H5N1) andreassortants of sublineage A and sublineage Cderived viruses identified in Nigeria in 2007. The

reassortant reported from Salzberg and others in 2007(3) is also shown. Sublineage Aderived genesegments are shown in blue; sublineage Cderivedgene segments are shown in red. Gene segments arerepresented in the following order (from top): PB2, PB1,PA, HA, NP, NA, M, NS.

was calculated by using the maximum likelihoodmethod implemented in PAUP 4.0 (7). The substitutionmodel was obtained by using MODELTEST (8).Bootstrap values (%) were calculated with themaximum-likelihood method with 1,000 replicationsand are indicated on key nodes. Scale bars represent1% of nucleotide changes between close relatives. A/duck/Anyang/AVL-1/2001 was used as an outgroup.

The Kimura distances between the genes of theseviruses were 0.4%1.4%. Among all subtypeH5N1 virus sequences published in the InfluenzaSequence Database (5), NIE/EKI15/2007 andNIE/OYO14/2007 gene sequences were mostclosely related to those found throughout 2006and 2007 in Nigeria. Thus, these viruses have mostprobably evolved from a sublineage A virusinitially imported into the country in 2006. Thisfinding is also corroborated by published sub-

stitution rates from Africa (2).Five viruses had HA and nonstructural (NS)

genes grouping with sublineage C virus genes,whereas the other gene segments were mostclosely related to sublineage A viruses (e.g., A/chicken/NIE/OG2/2007 and OG5/2007, Figures1, 2). These viruses evolved by reassortment fromsublineages A and C viruses (ACHA/NS reassor-tment, Figure 2).

Another virus (A/chicken/NIE/LAG6/2007)also showed evidence of reassortment between


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sublineage A and sublineage C. However, in thisvirus only the NS gene belonged to sublineage C(Figures 1, 2). The other 7 gene segments of A/chicken/NIE/LAG6/2007 were derived fromsublineage A (ACNS reassortant).

Reassortments between ReassortantsFour of the ACHA/NS reassortants (A/chicken/

NIE/OG2/2007, A/chicken/NIE/OG4/2007, A/chicken/NIE/OG10/2007, and A/chicken/NIE/OG11/2007), all of which were from Ogun State,had similar sequences in all genes (Kimuradistances 0%0.7 %). The ACNS reassortant A/chicken/NIE/LAG6/2007, obtained from a chickenfarm in Lagos State, diverged by 0.9 % in thecomplete NS gene (derived from C lineage) andby 0.7% to 1.4 % in sublineage Arelated genesegments from the latter 4 ACHA/NS reassortants.Some gene segments of the ACHA/NS reassortantA/chicken/NIE/OG5/2007 were most closelyrelated to the other 4 ACHA/NS reassortants,whereas, other gene segments were closer to theACNS reassortant A/chicken/NIE/LAG6/2007.Matrix protein, HA, NS, NA, and nucleocapsidprotein (NP) genes of NIE/OG5/2007 showed amaximal Kimura distance of only


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the asymmetry in gene divergence of A/chicken/NIE/OG5/2007 compared with the other ACHA/NSand ACNS reassortants suggests that additionalreassortment events have taken place.

In 2006, only 1 reassorted strain was foundamong 35 EuropeanMiddle Eastern African

strains, including 19 viruses reported from Nigeria,belonging to 3 parent sublineages (14). In thebeginning of 2007, 10 of 12 from northern,southern, and central states all belonged to the sameACHA/NS reassortants (15), distinct from the ACPB1/HA/NP/NS reassortant detected in 2006 (3). Similarreassortants were also found in other regions of sub-Saharan Africa (unpub. data). During the secondhalf of 2007, we found 6 reassortants including 3distinct reassortants among 8 strains collected from8 farms located in 4 contiguous Federal States ofNigeria (Figure 2). These results suggest thatreassortants have largely replaced the initialsublineages from which they were derived and thatreassortments are pervasive. This finding confirmsthat reassortments between subtype H5N1 virusesoccur frequently when different strains cocirculatein the same region (16) and is of particular concernif the increasing prevalence is the result ofadaptation to the African environment.

Although segments of the replication complex

(PB1, PB2, PA, and NP) may reassort individuallywithout affecting viral fitness (16), there seems tobe a coordinated evolution of the HA and NAgenes (17). In all but 1 of the Nigerian reassortants,HA and NA genes originated from differentsublineages (C and A), suggesting compatibilitybetween phenotypes of both sublineages. Allreassortants from Nigeria included sublineage Cderived NS genes, which may suggest a higherfitness of these viruses. Sublineage Cderived NS1and NS2 sequences from all Nigerian reassortantsand 11 unpublished sequences from ACHA/NSreassortants identified in other sub-Saharanregions showed 2 amino acids (NS1 V194 andNS2 R34), which were never identified insublineage A viruses. It has been shown thatmodifications in the NS proteins, including aminoacids adjacent to V194, may modulate thevirulence of HPAI (H5N1) (18,19). Alternatively,the observation that all reassortants in West Africahave sublineage Cderived NS genes may suggest

a better adaptation to the African environment ofviruses that came from the cold temperatures ofcentral Asia. Thus, the influence of differences inecology between Africa and Eurasia on viralselection and dynamics deserves further attention.

Although no reassortments have been reportedamong clade 2.2 viruses (www.who.int/csr/disease/influenza/tree_large.pdf) in Central Asia,Europe, and the Middle East since their emergencefrom Qinghai Lake region in 2005, reassortmentsof these viruses seem to be rampant in sub-Saharan

Africa, where they have become the criticaldeterminant of genetic diversity of HPAI (H5N1).Because of low prevalence, mainly in wild birds,clade 2.2 viruses have few opportunities to reassortin Eurasia. In contrast, opportunities to reassortseem to be frequent in sub-Saharan Africa becauseof great difficulties in setting up a sensitivesurveillance system in a complex socioeconomicenvironment, where backyard farms and largecommercial farms with variable biosafety levelscoexist, and where culling may threaten thelivelihood and survival of the farm.

If the high prevalence of reassortants wastypical for West Africa in 2007, the absence ofsuch reassortants anywhere else suggests thatreintroductions of subtype H5N1 from WesternAfrica into Eurasia must be rare. Moreover, allHPAI (H5N1) strains from Nigeria in 2007 weremore similar to those found in Nigeria in 2006than to even the closest relative from Europe in2007 (Hungary). Although subtype H5N1 has

been found in wild birds from Africa, such asvultures (4), HPAI (H5N1) has so far not beenreported in long-distance migrating birds in WestAfrica. Thus, the exchange of subtype H5N1between Eurasia and Africa seems to be a rareevent, which in 2006 may have been triggered byunusual bird migration as a result of the centralAsian cold spell.

The biological significance of reassortmentsbetween genetically similar viruses may bearguable, but the frequency of reassortment eventsis an important marker of virus endemicity in aregion. Moreover, endemicity of HPAI (H5N1)and a high propensity of reassorting in a regionwhere seasonal influenza is unchecked areessential ingredients of the anticipated pandemic.

Acknowledgments

We thank the Department of VeterinaryPathology of the University of Ibadan for accessto samples from Ekiti and Oyo States, and Emilie

Charpentier, Aurlie Sausy, and Sbastian deLandtsheer for their technical help.

This study was supported by University ofIbadan Senate Research Grant (SRG/FVM/2006/10A) and Bourse Formation Recherche fellowship


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of the Ministry of Research and Higher Education,Luxembourg.

The official designation of sublineages A, B,and C can be found in the WHO HPAI (H5N1)clade nomenclature update, to be published soon(www.who.int).

REFERENCES

1. Ducatez MF, Olinger CM, Owoade AA, De Landtsheer S,Ammerlaan W, Niesters HG, et al Avian flu: multipleintroductions of H5N1 in Nigeria. Nature. 2006;442:37. PubMed DOI

2. Ducatez MF, Olinger CM, Owoade AA, Tarnagda Z, Tahita MC,Sow A, et al Molecular and antigenic evolution and geographicalspread of H5N1 highly pathogenic avian influenza viruses in westernAfrica. J Gen Virol. 2007;88:2297306. PubMed DOI

3. Salzberg SL, Kingsford C, Cattoli G, Spiro DJ, Janies DA,Aly MM, et al Genome analysis linking recent European andAfrican influenza (H5N1) viruses. Emerg Infect Dis. 2007;13:7138.

4. Ducatez MF, Tarnagda Z, Tahita MC, Sow A, de Landtsheer S,Londt BZ, et al Genetic characterization of HPAI (H5N1) virusesfrom poultry and wild vultures, Burkina Faso. Emerg Infect Dis.2007;13:6113.

5. Macken C, Lu H, Goodman J, Boykin L The value of adatabase in surveillance and vaccine selection. In: Osterhaus AD,Cox, N, Hampson, AW, editors. Options for the control of influenzaIV. Amsterdam: Elsevier Science; 2001. p. 1036.

6. Njouom R, Aubin JT, Bella AL, Demsa BM, Rouquet P, GakeB, et al Highly pathogenic avian influenza virus subtype H5N1 inducks in the Northern part of Cameroon. Vet Microbiol.2008;130:3804.

7. Wilgenbusch JC, Swofford D Inferring evolutionary trees withPAUP*. In: Curr Protoc Bioinformatics. Hoboken (NJ): John Wiley &Sons, Inc; 2003.

8. Posada D, Crandal l KA MODELTEST: testing the model ofDNA substitution. Bioinformatics. 1998;14:8178. PubMed DOI

9. Ha Y, Stevens DJ, Skehel JJ, Wiley DC X-ray structures of H5avian and H9 swine influenza virus hemagglutinins bound to avianand human receptor analogs. Proc Natl Acad Sci U S A.2001;98:111816. PubMed DOI

10. Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y PB2amino acid at position 627 affects replicative efficiency, but not cell

Dr Owoade is a senior lecturer, poultry diseasespecialist, and consultant to the VeterinaryTeaching Hospital of the University of Ibadan,Nigeria. His main field of research is the molecularepidemiology of avian viruses in sub-SaharanAfrica.

tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology.2004;320:25866. PubMed DOI

11. Chen H, Li Y, Li Z, Shi J, Shinya K, Deng G, et al Propertiesand dissemination of H5N1 viruses isolated during an influenzaoutbreak in migratory waterfowl in western China. J Virol.2006;80:597683. PubMed DOI

12. Subbarao EK, London W, Murphy BR A single amino acid inthe PB2 gene of influenza A virus is a determinant of host range. JVirol. 1993;67:17614.

13. Scholtissek C, Quack G, Klenk HD, Webster RG How toovercome resistance of influenza A viruses against adamantanederivatives. Antiviral Res. 1998;37:8395. PubMed DOI

14. de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, NguyenVC, et al Oseltamivir resistance during treatment of influenza A(H5N1) infection. N Engl J Med. 2005;353:266772. PubMed DOI

15. Monne I, Joannis TM, Fusaro A, De Benedictis P, LombinLH, Ularamu H, et al Reassortant avian influenza virus (H5N1)in poultry, Nigeria, 2007. Emerg Infect Dis. 2008;14:63740.

16. Macken CA, Webby RJ, Bruno WJ Genotype turnover byreassortment of replication complex genes from avian influenza Avirus. J Gen Virol. 2006;87:280315. PubMed DOI

17. Wagner R, Matrosovich M, Klenk, HD Functional balancebetween haemagglutinin and neuraminidase in influenza virusinfections. Rev Med Virol. 2002;12:15966. PubMed DOI

18. Twu KY, Noah DL, Rao P, Kuo RL, Krug RM The CPSF30binding site on the NS1A protein of influenza A virus is a potentialantiviral target. J Virol. 2006;80:395765. PubMed DOI

19. Zhu Q, Yang H, Chen W, Cao W, Zhong G, Jiao P, et al Anaturally occurring deletion in its NS gene contributes to theattenuation of an H5N1 swine influenza virus in chickens. J Virol.2008;82:2208. PubMed DOI

Address for correspondence: Claude P. Muller, Laboratoire National deSant, 20A, rue Auguste Lumire, L-1950 Luxembourg; email:[email protected]

REZUMATAu fost analizate nou secvene de mrime natural de la virusul gripar aviar nalt patogen (H5N1) din patru state din sud-vestulNigeriei. n toate secvenele genice au fost mult mai strns legate, surs gsit n Nigeria n 2006, dect de orice alt surs dinafara rii. ase virusuri au evoluat la cel puin trei evenimente reassortment (reaezri) (ACHANSIACNS) de la identificareaanterioar a sublineajului A(EMA2) i C(EMA1). Rezultatele noastre sugereaz c virusul aviar nalt patogen (H5N1) importat nNigeria, n 2006, a fost treptat nlocuit prin variate reaezri. n toate reaezrile genele nestructurale au derivat din sublineajul Ccu doi aminoacizi caracteristici (n comparaie cu sublineajul A). Dac prevalena nalt a reasorbanilor a fost tipic pentru Africa

de Vest, n 2007, absena acestor reabsorbani oriunde n alt fel sugereaz c reintroducerea gripei A (H5N1) din Africa n Europatrebuie s fie rar.


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1 rezident, specialist, primar2 preparator, asistent, ef de lucrri, confereniar, profesor3 doctor n boli infecioase sau specialitate asociat4 se marcheaz cu x n csua aleas

Scrisoarea de nscriere se trimite la adresa Societii Naionale Romne de Boli Infecioase: Str. IonelPerlea, Nr. 10, Cod 70754, Bucureti, sector 1.

Cotizaiile se trimit prin mandat potal n contul IBAN RO57RNCB0082044163730001, BCR,Sucursala Unirea, Bucureti sau la banc prin foaie de vrsmnt. Cod fiscal 13742044.

Revista Romana Boli Infectioase - 2008 - Vol. XI - Nr.3

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Transcript of Revista Romana Boli Infectioase - 2008 - Vol. XI - Nr.3