LETTERS was our opinion that this patient quali- of the mother during pregnancy. Infection. Novel fi ed for rabies PEP. 1977;5:49–50. 3. Chutivongse S, Wilde H. Postexposure from Diseased Several studies of the safety of ra- rabies vaccination during pregnancy: bies PEP for pregnant patients demon- experience with 21 patients. . Crow, Finland strated no association between treat- 1989;7:546–8. ment and adverse outcomes (3–6). In 1 4. Chutivongse S, Wilde H, Benjavong- To the Editor: Corvids, especial- kulchai M, Chomchey P, Punthawong S. study, tissue culture-derived ly American crows (Corvus brachy- Postexposure rabies vaccination during rhynchos), are reported to be highly and human immune globulin did not pregnancy: effect on 202 women and their lead to an increased risk for congenital infants. Clin Infect Dis. 1995;20:818–20. susceptible to lineage 1 of West Nile anomalies; no effects were observed 5. Figueroa Damián R, Ortiz-Ibarra FJ, Arre- (WNV), which causes them to dondo-Garcia JL. Post-exposure antirabies on intrauterine or infant growth or show symptoms of encephalitis. They prophylaxis in pregnant women [in Span- are regarded as indicator species in the development with a follow-up period ish]. Ginecol Obstet Mex. 1994;62:13–6. of 1 year postpartum (6). Although 6. Sudarshan MK, Madhusudana SN, Ma- surveillance of WNV in the United these studies are not comprehensive hendra BJ. Post-exposure prophylaxis States (1). In parts of Europe, WNV with purifi ed vero cell rabies vaccine dur- in their assessment of all reproductive is endemic and studies are ongoing to ing pregnancy—safety and immunogenic- detect WNV in wild birds. Thus far, outcomes, they do suggest that PEP is ity. J Commun Dis. 1999;31:229–36. generally safe. 7. American College of Obstetricians and no evidence of WNV in birds has been On the basis of the exposure and Gynecologists. ACOG Committee opin- found in northern Europe. ion. Immunization during pregnancy. Ob- our literature review, we recommend- In August 2002, in southern Fin- stet Gynecol. 2003;101:207–12. land, a diseased wild hooded crow ed that the patient receive rabies PEP. 8. Centers for Disease Control and Preven- After discussing options with her hus- tion. Recommendations of the Advisory (Corvus corone cornix) was found band, the patient chose not to receive Committee on Immunization Practices fl ying abnormally with coordination (ACIP). Human rabies prevention–Unit- treatment, citing continued concern problems, abnormal postures, cramps, ed States. MMWR Recomm Rep. 1999; and paralysis. Because WNV infection about the effect of rabies PEP on the 48(RR-1):1–21. fetus. There must be a greater public 9. Rupprecht CE, Gibbons RV. Clinical prac- was suspected, virologic tests were health effort to educate clinicians and tice. Prophylaxis against rabies. N Engl J performed, which resulted in the iso- Med. 2004;351:2626–35. the public about proper response to bat lation of a novel orthoreovirus, which 10. Messenger SL, Smith JS, Rupprecht CE. was likely the causative agent of the exposures, particularly undetectable Emerging epidemiology of bat associ- bite exposures such as this case. Had ated cryptic cases of rabies in humans disease. public health authorities been contact- in the United States. Clin Infect Dis. Avian (ARVs) 2002;35:738–47. ed to collect and test the captured bat belong to the family , ge- for rabies, there would have been no nus Orthoreovirus. They infect wild Address for correspondence: Sandro Cinti, and farm-raised birds and are im- ambiguity as to the appropriate course Infectious Diseases, University of Michigan of action. portant fowl pathogens associated Hospitals/Ann Arbor VA Health Systems, 2215 with various disease conditions such Fuller Rd, Ann Arbor, MI 48105, USA; email: as gastrointestinal malabsorption This research was supported by Uni- [email protected] syndrome, tenosynovitis (arthritis), versity of Michigan Medical Scientist growth retardation, and sudden death. Training Program Grant No. GM0786. Letters They have also been isolated from Letters commenting on recent articles as asymptomatic birds. The reovirus vi- Mohamed E. Abazeed* well as letters reporting cases, outbreaks, rion is icosahedral, nonenveloped, or original research are welcome. Letters and has a double-capsid structure and Sandro Cinti† commenting on articles should contain no *University of Michigan Medical School, more than 300 words and 5 references; they that shelters the segmented double- Ann Arbor, Michigan, USA; and †University are more likely to be published if submit- stranded RNA genome (2). of Michigan Hospitals/Ann Arbor VA Medi- ted within 4 weeks of the original article’s Heart, lung, liver, kidney, and publication. Letters reporting cases, out- cal Center, Ann Arbor, Michigan, USA brain tissues of the diseased crow breaks, or original research should contain tested negative for WNV RNA. Virus no more than 800 words and 10 references. References They may have one Figure or Table and isolation from brain homogenate was should not be divided into sections. All let- carried out in BHK (baby hamster 1. Sipahioglu U, Alpaut S. Transplacen- ters should contain material not previously kidney)–21 cells. On day 2 after in- tal rabies in humans. Mikrobiyol Bul. published and include a word count. fection, a strong cytopathic effect was 1985;19:95–9. 2. Muller-Holve W, Leitritz H, Knorr E. Ear- observed, including syncytium forma- ly development of a child following rabies tion. Spherical, spiked virus particles,

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 12, December 2007 1967 LETTERS LETTERS consistent with those of members of compared with previously described not studied, whether they were infect- the family Reoviridae, were observed orthoreovirus strains. Additionally, ed remains unclear. In Finland, a bird- by electron microscopy. The diameter a partial M3 segment was sequenced pathogenic orthoreovirus was isolated of the particles was slightly smaller (GenBank accession no. EU053426) in the same geographic region 6 years (≈70 nm) than that reported for ARV that also showed low (<40%) amino earlier from the bursa of Fabricius from (85 nm) (3). Members of the genus acid homology and genetic relation to common eider (Somateria mollissima) Orthoreovirus differ in their host res- other orthoreoviruses, which supports carcasses and was suspected to be the ervoir and capability of syncytium the result obtained from the σC gene. cause of their death (10). The eider formation; most avian orthoreoviruses To our knowledge, no sequences reovirus induced syncytium forma- are fusogenic and fail to agglutinate of ARV isolates have been previously tion, lacked hemagglutination activ- erythrocytes, unlike the mammalian available from northern Europe. The ity, and had an RNA genome segment reoviruses (4). The isolate, designated TVAV isolate described differs clearly migration pattern similar to that of as Tvärminne avian virus (TVAV), from other known ARV strains and TVAV. However, instead of showing failed to hemagglutinate chicken, could be considered a candidate for a symptoms that appeared to affect the goose, or human O erythrocytes. new species in the genus Orthoreovi- central nervous system, experimental- Members of the genus Orthoreo- rus. ARVs are not generally associated ly infected mallards (Anas platyrhyn- virus have a genome consisting of 10 with encephalitic disease, in contrast chos) showed hemorrhages in liver, dsRNA segments in 3 size classes, to reoviruses that infect mice, baboons, spleen, and bursa of Fabricius tissues. large (L1–3), medium (M1–3), and and snakes (8,9). Systemic infection Unfortunately, no sequence data are small (S1–4). The RNA was extracted with ARV could cause viremia also in available from the eider virus isolate from TVAV-infected BHK-21 cells the brain, but since other tissues were that can be compared with TVAV. Be- with TriPure isolation reagent (Roche Diagnostics, GmbH, Mannheim, Ger- many). Ten double-stranded RNA genome segments were separated by electrophoresis, showing a pattern typical of ARV with the S1 segment migrating between S- and M-segment classes (5). The S1 segment encodes the orthoreovirus type-specifi c anti- gen, σC protein, which is the minor outer-capsid protein, a spiked struc- ture mediating cell attachment. For phylogenetic analyses, the partial σC gene was amplifi ed by re- verse transcription–PCR with avian reovirus–specifi c primers (6). The ob- tained sequence (GenBank accession no. DQ470139) was aligned with 25 published orthoreovirus sequences. The phylogenetic tree was construct- ed by using the maximum likelihood method, with general-time reversible model of substitution determined by Modeltest using PAUP* (7). The anal- yses showed that TVAV did not group Figure. Maximum parsimony tree based on a 916-bp nucleotide sequence of the σC with avian or mammalian orthoreovi- gene. The scale bar indicates a branch length corresponding to 100 character-state ruses but formed a separate clade (Fig- changes. Bootstrap support values <50 are not shown. The tentative species is shown ure). In further analysis, no evidence together with the closest relatives within the Orthoreovirus genus; avian orthoreovirus for recombination events was found. (ARV), mammalian orthoreovirus (MRV). GenBank accession nos.: AF204946, AF204945, The nucleotide sequence homology AF204950, AF204947, AF18358, L39002, AF004857, AF218359, AF297217, AF297213, AF354224, AF354220, AF354225, AF297214, AF354226, AF354227, AF354219, of the σC gene was <50%, and ami- AF297215, AF297216, AF354229, AF354221, AF354223, DQ470139, M10260, AY785910, no acid homology was <40%, when AF368035.

1968 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 12, December 2007 LETTERS cause many ARVs are poultry patho- 4. Duncan R. Extensive sequence divergence of human infection with highly patho- gens of economic importance, more and phylogenetic relationships between genic avian infl uenza A (H5N1) the fusogenic and nonfusogenic orthoreo- studies are needed to determine the viruses: a species proposal. Virology. have occurred after direct contact with taxonomic classifi cation of the TVAV 1999;260:316–28. diseased or dead poultry (2,3). Limited, isolate and its pathogenicity for avian 5. Gouvea VS, Schnitzer TJ. Polymorphism nonsustained human-to-human trans- hosts. In addition, the recognition of of the migration of double-stranded RNA mission of avian infl uenza (H5N1) genome segments of avian reoviruses. J potential avian pathogens in wild birds Virol. 1982;43:465–71. viruses is believed to have occurred is important due to the possible threat 6. Kant A, Balk F, Born L, van Roozelaar D, in some clusters (4). Every human in- for farm-raised birds and also for the Heijmans J, Gielkens A, et al. Classifi ca- fection with a novel infl uenza A virus surveillance of zoonotic viruses trans- tion of Dutch and German avian reovirus- should be investigated, and suspected es by sequencing the sigma C protein. Vet missible to humans. Res. 2003;34:203–12. clusters should be investigated imme- 7. Swofford DL. Phylogenetic analysis using diately to assess exposures and trans- Acknowledgments parsimony (*and other methods), version mission patterns. 4. Sunderland (MA): Sinauer Associates; Yang et al. applied a statistical We thank Henrikki Brummer-Ko- 2000. model to evaluate publicly available rvenkontio for assistance, Christine Ek- 8. Vieler E, Baumgartner W, Herbst W, Kohler G. Characterization of a reovirus data from 2 case clusters of human in- Kommonen for providing reagents for the isolate from a rattle snake, Crotalus viri- fection with avian infl uenza A (H5N1) hemagglutination test, and Irja Luoto for dis, with neurological dysfunction. Arch viruses (1). These clusters were investi- excellent technical assistance in electron Virol. 1994;138:341–4. gated in detail during 2006 by fi eld epi- microscopy. 9. Leland MM, Hubbard GB, Sentmore HT III, Soike KF, Hilliard JK. Outbreak demiologic investigation teams. Yang The study was supported by grants of orthoreovirus-induced meningoen- et al. suggest that statistical methods from Hospital District of Helsinki and cephalomyelitis in baboons. Comp Med. can prove or confi rm human-to-human 2000;50:199–205. Uusimaa (TYH4211, 6215) and The Finn- 10. Hollmén T, Franson JC, Kilpi M, Do- transmission, but this suggestion is ish Agency for Technology and Innovation. cherty DE, Hansen WR, Hario M, et al. misleading. Modeling approaches can Isolation and characterization of a reovirus suggest transmission modalities to ac- from common eiders (Somateria mollis- count for case patterns, but determina- Eili Huhtamo,* Nathalie Y. sima) from Finland. Avian Dis. 2002;46: Uzcátegui,* Tytti Manni,* 478–84. tion of human-to-human transmission Riggert Munsterhjelm,† requires detailed fi eld epidemiologic Markus Brummer- Address for correspondence: Eili Huhtamo, investigations in which human, animal, Korvenkontio,* † Antti Vaheri,*‡ Haartman Institute, Department of Virology, and environmental exposures as well and Olli Vapalahti*‡§ P.O. Box 21 (Haartmaninkatu 3), FIN-00014, as clinical and laboratory data are as- *Haartman Institute–University of Helsinki, University of Helsinki, Helsinki, Finland; email: sessed and interpreted. Helsinki, Finland; †Tvärminne Zoological eili.huhtamo@helsinki.fi Indication that a novel infl uenza A Station–University of Helsinki, Hanko, Fin- virus has acquired the ability to spread land; ‡HUSLAB Hospital District of Helsinki among humans could be refl ected by and Uusimaa, Helsinki, Finland; §Faculty of a change in the epidemiology of clus- Veterinary Medicine–University of Helsinki, ters, such as increases in 1) size and Helsinki, Finland frequency of clusters, 2) cases among nonrelated persons, and 3) clinically References mild cases. This ability could also be Detecting refl ected in accompanying changes in 1. Brault AC, Langevin SA, Bowen RA, Human-to-Human viruses isolated from case-patients. Panella NA, Biggerstaff BJ, Miller BR, When facing emerging infectious dis- et al. Differential virulence of West Nile Transmission of strains for American crows. Emerg Infect ease threats such as those posed by Dis. 2004;10:2161–8. Avian Infl uenza A highly pathogenic avian infl uenza A 2. McNulty MS. Reoviridae. In: Horzinek (H5N1) (H5N1) viruses, surveillance should M, editor. Virus infections of vertebrates. rapidly detect human cases and case Vol. 4. Amsterdam: Elsevier Science Pub- To the Editor: This letter is in re- lishers; 1993. p. 177–91. clusters and facilitate accurate identi- 3. Zhang X, Tang J, Walker SB, O’Hara D, sponse to a recently published article fi cation of the agent. Field epidemio- Nibert ML, Duncan R, et al. Structure of about statistical modeling to assess hu- logic investigations, initiation of evi- avian orthoreovirus virion by electron cry- man-to-human transmission of avian dence-based clinical management of omicroscopy and image reconstruction. infl uenza A (H5N1) viruses in 2 case Virology. 2005;343:25–35. case-patients, and epidemiologic dis- clusters (1). Sporadic cases and clusters ease-control methods (including ap-

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 12, December 2007 1969