ANOTHER DIMENSIONalso why previous generations of physicians and scientists,supported by a public desperate for medical advances tosave their children, worked so long and so well to developand deploy the very vaccines that some people now avoidand decry. As we debate today how best to deal with yetanother measles epidemic in the United States, we shouldlook closely at the lessons Cotton Mather and his contemporarieslearned 3 centuries ago. Emerging infectious diseaseslike measles keep reminding us that “the past is neverdead. It isn’t even past” (12).AcknowledgmentsI thank Stephen Greenberg and the staff of the History ofMedicine Division, National Library of Medicine, NationalInstitutes of Health, for help in obtaining historical manuscripts.Dr. Morens is an epidemiologist with a long-standing interestin emerging infectious diseases, virology, tropical medicine,and medical history. Since 1998, he has worked at the NationalInstitute of Allergy and Infectious Diseases.References1. Caulfield E. Early measles epidemics in America. Yale J Biol Med.1943;15:531–56.2. Hostetter MK. What we don’t see. N Engl J Med. 2012;366:1328–34. http://dx.doi.org/10.1056/NEJMra11114213. Beall OT. Cotton Mather. Baltimore: Johns Hopkins UniversityPress; 1954.4. Hiner NR. Cotton Mather and his female children: notes on therelationship between private experience and public thought.J Psychohist. 1985;13:33–49.5. Mather C. 1713. The LIst YEAR. In: Mather C. Diary of CottonMather, 1709–1724. Massachusetts Historical Society Collections.Seventh Series. Volume VII. Boston: Massachusetts Hist Soc.;1912. p. 178–333.6. Mather C. A Letter, About a Good Management under theDistemper of the Measles, at this time Spreading in the Country.Here Published for the Benefit of the Poor, and Such as may wantthe help of Able Physicians. Boston: Cotton Mather; 1713.7. Fauci AS, Morens DM. The perpetual challenge of infectiousdiseases. N Engl J Med. 2012;366:454–61. http://dx.doi.org/10.1056/NEJMra11082968. Mather C. Right Thoughts in Sad Hours, Representing theComforts and Duties of Good Men Under All their Afflictions; andParticularly, That One, the Untimely Death of Children:in a Sermon Delivered at Charls-Town, New England; Under aFresh Experience of That Calamity. London: James Astwood; 1689.9. Morens DM. Measles in Fiji, 1875: thoughts on the history ofemerging infectious diseases. Pac Health Dialog. 1998;5:119–28.10. Morens DM, Taubenberger JK. A forgotten epidemic that changedmedicine: measles in the US Army, 1917–18. Lancet Infect Dis.In press 2015.11. Home F. On the measles as they appeared 1758 at Edinburgh, andof their inoculation. In: Home F. Medical facts and experiments.Part III. Section IV. London: A. Millar; 1759. p. 253–88.12. Faulkner W. Requiem for a nun. New York: Random House; 1950.Address for correspondence: David M. Morens, National Instituteof Allergy and Infectious Diseases, Building 7A-03, 31 Center Dr,Bethesda, MD, USA; 20892; email: dm270q@nih.govSign up for Twitter and find the latestinformation about emerging infectious diseasesfrom the EID journal.@CDC_EIDjournal1260 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015
LETTERSInfluenza A(H5N6)Virus Reassortant,Southern China, 2014Hanqin Shen, 1 Boliang Wu, 1 Yimin Chen,Yingzuo Bi, Qingmei XieAuthor affiliations: South China Agricultural University,Guangzhou, China (H. Shen, B. Wu, Y. Chen, Y. Bi, Q. Xie);Key Laboratory of Animal Health Aquaculture and EnvironmentalControl, Guangzhou (H. Shen, Q. Xie); Ministry of Agriculture,Guangzhou (B. Wu, Q. Xie); South China Collaborative InnovationCenter for Poultry Disease Control and Product Safety,Guangzhou (Q. Xie)DOI: http://dx.doi.org/10.3201/eid2107.140838To the Editor: Avian influenza A viruses generallydo not cause disease in aquatic birds, the natural reservoirof these viruses (1). Influenza A(H5N6) was first isolatedfrom mallards by García et al. in 1975 (2). Influenza virusescontinue to evolve and reassort to generate novel,highly pathogenic viruses. Novel H5 highly pathogenicavian influenza virus subtypes, such as H5N2, H5N5,and H5N8, have been reported (3,4). Highly pathogenicinfluenza A viruses are endemic to many countries(http://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza/2015/),cause tremendous economiclosses to the poultry industry, and represent a seriousthreat to public health.In March 2014, an influenza A(H5N6) outbreakcaused the death of 457 birds in Laos (http://www.oie.int/wahis_2/public%5C..%5Ctemp%5Creports/en_imm_0000015052_20140507_182757.<strong>pdf</strong>). During thesame month, a flock of ducks in Guangdong Province insouthern China exhibited typical respiratory signs of influenzaA virus infection. This flock also had 70% decreasedegg production and a slightly increased mortality rate.Throat swab specimens were taken from the symptomaticand dead ducks, and the samples were used to inoculatechicken embryos for virus isolation. Hemagglutination(HA) and neuraminidase (NA) inhibition assays were performedto identify the subtype of the isolated virus, whichwas designated A/duck/Guangdong/GD01/2014 (H5N6)(GD01/2014). The complete RNA genome was amplifiedby reverse transcription PCR and cloned into the pMD-19Tvector for sequencing (5). The complete genome sequenceof the GD01/2014 virus was submitted to GenBank (accessionnos. KJ754142–KJ754149).Multiple-sequence alignments showed that the HAgene of GD01/2014 shared 97.5% nt identity with A/wild duck/Shandong/628/2011 (H5N1) and NA genes1These authors contributed equally to this article.shared 96.6% and 98.3% nt identity with A/swine/Guangdong/K6/2010(H6N6) and A/duck/Shantou/1984/2007(H6N6), respectively. All internal genes shared high levelsof nucleotide identity (97.6%–98.5%) with A/wild duck/Fujian/2/2011(H5N1). The whole genes of GD01/2014and the H5N6 viruses in Laos (LAO/2014) shared98.2%–99.7% nt identity, indicating the same genotype.Phylogenetic analysis of the HA gene revealed that theisolated virus belonged to clade 2.3.4.6 (online TechnicalAppendix Figure, panel A, http://wwwnc.cdc.gov/EID/article/21/7/14-0838-Techapp.<strong>pdf</strong>) (6). The NA gene ofGD01/2014 was clustered with some H6N6 viruses circulatingin China (online Technical Appendix Figure, panelB). The 6 internal genes of GD01/2014 were closely relatedwith A/wild duck/Fujian/2/2011(H5N1) and A/wildduck/Fujian/1/2011(H5N1) (online Technical AppendixFigure, panels C–H). Phylogenetic analysis showed thatall 8 genes of GD01/2014 and LAO/2014 were closelyrelated although genetically distant from the earlier isolatedH5N6 viruses (online Technical Appendix Figure).These findings suggest that GD01/2014 and LAO/2014are reassortants of wild duck H5N1 and H6N6 viruses,both of which have pathogenic and potential pandemic capacityin southern China. A previous report that H5N1 andH6N6 co-infected a duck suggests that GD01/2014 mightbe generated from the co-infection of H5N1 and H6N6 inthe same host (7).The intravenous pathogenicity index of GD01/2014was 3.0, which indicates that the isolate is highly pathogenicfor chickens. GD01/2014 had multiple basic aminoacids (LRERRRKR/GLF) at the cleavage site betweenHA1 and HA2; this characteristic is typical of highly virulentinfluenza viruses (8). The HA protein contained E190,R220, G225, Q226, and G228 (H3 numbering) residuesat the receptor-binding pockets, indicating that the viruspreferentially binds to the sialic acid-2,3-NeuAcGal ofthe avian-like receptor (9). The HA protein has 7 potentialN-glycosylation sites (PGSs); the HA1 protein has 5PGSs; the HA2 protein has 2 PGSs. The NA protein ofGD01/2014 and LAO/2014 had a deletion of 11 aa residuesat positions 59–69 (N6 numbering) in the NA stalk region.Moreover, a deletion of 5 aa residues from positions 80–84in the nonstructural 1 protein was found in GD01/2014 andLAO/2014. The position 627 and 701 of the polymerasebasic 2 protein were E and D, respectively, characteristicsof the avian influenza virus (10)In summary, in 2014, outbreaks of H5N6 virus occurredin China, Laos, and Vietnam and caused thedeaths of infected humans in Sichuan province, China(http://www.oie.int/en/animal-health-in-the-world/updateon-avian-influenza/2014/;http://www.wpro.who.int/china/mediacentre/releases/2014/20140507/en/). We characterizedthe novel reassortant H5N6 virus in China and found that itEmerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 1261
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