Zoonotic Filariasis Caused by Novel Brugia Sp. Nematode, United States

LETTERS

Fabrice Compain, Enterobacteriaceae in Europe. Clin Micro- that primarily parasitize nonhuman Dominique Decré, biol Infect. 2012;18:413–31. http://dx.doi. vertebrates, rarely humans (1–3). In org/10.1111/j.1469-0691.2012.03821.x Isabelle Frazier, 6. Lepelletier D, Andremont A, Grandbastien contrast to classical lymphatic filaria- Astrid Ramahefasolo, B; National Working Group. Risk of sis caused by B. malayi and B. timori, Marie Lavollay, highly resistant bacteria importation from which are found in Asia, most zoonotic Etienne Carbonnelle, repatriates and travelers hospitalized in Brugia infections have been reported foreign countries: about the French recom- Hidayeth Rostane, Arzu Tackin, mendations to limit their spread. J Travel from the northeastern United States Anne Berger-Carbonne, Med. 2011;18:344–51. http://dx.doi.org/ (2,3) or South America (3). We report a and Isabelle Podglajen 10.1111/j.1708-8305.2011.00547.x case of symptomatic brugian infection 7. Haut Conseil de la Santé Publique. Author affiliations: Hôpital Européen in a New York City resident who had Prévention de la transmission croisée des Georges Pompidou, AP-HP, Paris, France Bactéries Hautement Résistantes aux anti- not traveled to the Eastern Hemisphere. (F. Compain, I. Frazier, A. Ramahefasolo, biotiques émergentes (BHRe) [cited 2013 In 2011, a 53-year-old White man M. Lavollay, E. Carbonnelle, H. Rostane, A. Jul 10]. http://www.hcsp.fr/Explore.cgi/ first noted tenderness and swelling be- Telecharger?NomFichier=hcspr20130710_ Tackin, A. Berger-Carbonne, I. Podglajen); hind his penis and in his right groin recoprevtransxbhre.pdf. Université Pierre et Marie Curie, Paris (D. 8. Vardakas KZ, Rafailidis PI, Konstantelias after having fallen 3 months earlier. Decré); Université Paris Descartes, Paris AA, Falagas ME. Predictors of mortality The tenderness was relieved by non- (M. Lavollay, E. Carbonnelle, I. Podglajen); in patients with infections due to multi- steroidal antiinflammatory drugs, but drug resistant Gram negative bacteria: Collège de France Centre de Recherche the swelling continued; an oral antimi- the study, the patient, the bug or the drug? Interdisciplinaire en Biologie, Paris (I. Podg- J Infect. 2013;66:401–14. http://dx.doi. crobial drug, prescribed for presumed lajen); and Institut National de la Santé et org/10.1016/j.jinf.2012.10.028 cellulitis, produced no improvement. de la Recherche Médicale, Paris (M. Lavol- 9. Dortet L, Poirel L, Nordmann P. Rapid At the time of examination, the patient identification of carbapenemase types in lay, E. Carbonnelle, I. Podglajen) had no fever or other signs or symp- Enterobacteriaceae and Pseudomonas toms. Only a 3.0-cm × 3.0-cm firm, DOI: http://dx.doi.org/10.3201/eid2007.131638 spp. by using a biochemical test. Antimi- crob Agents Chemother. 2012;56:6437–40. nonfixed right inguinal nodule without References http://dx.doi.org/10.1128/AAC.01395-12 warmth or tenderness was noted. Labo- 10. Dortet L, Cuzon G, Nordmann P. ratory findings were remarkable for 1. Savard P, Perl TM. A call for action: Dissemination of carbapenemase-pro- 9 ducing Enterobacteriaceae in France. total leukocytes of 6.4 × 10 , eosino- managing the emergence of multidrug- 3 resistant Enterobacteriaceae in the acute J Antimicrob Chemother. 2014;69:623–7. philia (12%, 600 cells/mm ), decreased care settings. Curr Opin Infect Dis. http://dx.doi.org/10.1093/jac/dkt433 hemoglobin level (10.0 g/dL), and low 2012;25:371–7. http://dx.doi.org/10.1097/ hematocrit of 31.2%. An excisional QCO.0b013e3283558c17 Address for correspondence: Isabelle Podglajen, biopsy sample revealed intralymphatic 2. Glasner C, Albiger B, Buist G, Service de Microbiologie, Assistance Publique- Tambić Andrasević A, Canton R, adult nematodes with viable-appearing Hôpitaux de Paris, Hôpital Européen Georges Carmeli Y, et al.; European Survey on microfilaria (online Technical Ap- Carbapenemase-Producing Enterobacte- Pompidou, 20 rue Leblanc, 75015, Paris, pendix Figure, wwwnc.cdc.gov/EID/ riaceae Working Group. Carbapenemase- France; email: [email protected] article/20/7/13-1654-Techapp1.pdf). producing Enterobacteriaceae in Europe: a survey among national experts from 39 The patient had been born and countries, February 2013. Euro Surveill. raised in Champlain, Illinois, and had 2013;18:20525. resided in the Bronx, New York, since 3. Centers for Disease Control and Preven- 1979; he had no history of travel to tion, National Center for Emerging and Zoonotic Infectious Diseases. Guidance filariasis-endemic regions. Character- for control of infections with carbapenem- istics of the adult worms and microfi- resistant or carbapenemase-producing laria were most consistent with those Enterobacteriaceae in acute care facilities of Brugia spp., which was surprising [cited 2013 Mar 5]. http://www.cdc.gov/ hai/pdfs/cre/CRE-guidance-508.pdf Zoonotic Filariasis because classical brugian lymphatic 4. Vaux S, Carbonne A, Thiolet JM, Caused by filariasis seems to be limited to Asia Jarlier V, Coignard B; RAISIN and Ex- (B. malayi) and Indonesia (B. timori) pert Laboratories Groups. Emergence of Novel Brugia sp. (4,5). However, the adult filariae were carbapenemase-producing Enterobac- teriaceae in France, 2004 to 2011. Euro Nematode, smaller than expected for B. malayi Surveill. 2011;16:19880. United States, 2011 or B. timori nematodes, prompting 5. Cantón R, Akóva M, Carmeli Y, consideration of zoonotic filariasis Giske CG, Glupczynski Y, Gniad- To the Editor: Zoonotic brugian (1,6). The adult worms and microfi- kowski M, et al.; European Network on filariasis is an incidental infection of Carbapenemases. Rapid evolution laria seemed to be viable, although and spread of carbapenemases among humans with Brugia spp. nematodes zoonotic Brugia spp. in histologic

1248 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 20, No. 7, July 2014 LETTERS sections often appear degenerated The products were fractionated on clinical signs and subsequent persis- (1,2,6). The diameters of the adult 2% agarose gel and stained with tent adenopathy were reminiscent of worms were similar to those reported ethidium bromide. The internal tran- unilateral lymphadenitis, lymphangi- from South America (females 90–100 scribed spacer (ITS) 1 PCR prod- tis, and induration that are typical of µm, males 50 µm) (7,8) rather than uct (182 bp) was automatically B. malayi or B. timori filariasis, and those from North America (females sequenced by using the same prim- the microfilariae in the original biopsy 35–75 µm, males 32–52 µm) (1). Pe- ers used for PCR. Lasergene software sample appeared to be viable, we em- ripheral blood was repeatedly nega- (DNASTAR, Madison, WI, USA) was piricially prescribed a standard dosage tive for microfilaria. Serum sent to the used to align the sequences obtained of oral doxycycline for 6 weeks, fol- Centers for Disease Control and Pre- with Brugia spp. sequences deposited lowed by single doses of ivermectin vention (Atlanta, GA, USA) for ELI- in GenBank; detailed sequence com- at 400 µg/kg and 800 mg albendazole. SA testing for B. malayi anti-filarial parison identified the isolate as a novel The patient has been well, without fur- IgG 4 showed optical density of 0.13, Brugia (Nematoda: Onchocercidae) ther adenopathy or eosinophilia, for below the ELISA cutoff for filariasis. species closely related to B. pahangi >2 years. Because adult filariae can Because micromorphologic in- and B. malayi (Figure). The ITS-1 se- live for >10 years, the place of acqui- formation was not adequate for spe- quence was submitted to the EMBL sition cannot be stated with certainty. cies identification, paraffin-embedded Nucleotide Sequence Database (ac- The prevalence of zoonotic in- biopsy specimens were submitted for cession no. HE856316). fection with Brugia spp. nematodes molecular testing. Genomic DNA ex- Removal of an affected lymph is unknown. Many reported cases are tracted from paraffin-embedded tissue node without additional treatment is asymptomatic or diagnosed inciden- with the QIAamp DNA–formalin- often considered sufficient treatment tally during evaluation for persistent fixed, paraffin-embedded tissue pro- for zoonotic filariases. However, for adenopathy (1–3). Conversely, dif- cedure was amplified by using the the patient reported here, persistence ferentiation of zoonotic from classi- primer sets DiBu-F(5′ GCTAGATAT- of inguinal swelling prompted a repeat cal filariasis is unlikely in disease- GCTACCAACAAAA-3′)/ITS1 R(5′- biopsy 4 months later; the specimen endemic areas; most cases published CTCAATGCGTCTGCAATTCGC-3′) again demonstrated reactive follicu- since the initial 1962 case report (1) and BuF2-(5-CATTTATGCTAG- lar hyperplasia, although no parasites occurred in the United States. Most ATATGCTACCAAC-3′)/ITS1-R. were seen. Because the patient’s initial case-patients were from the Northeast,

Figure. Pile-up of partial ribosomal DNA sequences from Brugia NY strain (HE856316) and from other related Brugia spp. strains and clones, B. malayi BM28 (JQ327146), B. malayi C27Cat5 (EU373624), B. pahangi C61CAT5 (EU419348), B. pahangi C14Cat6 (EU373632), B. pahangi C7Cat6 (EU373630), B. pahangi Bp-1 (AY621469), B. pahangi C46CAT5 (EU419351), and B. pahangi C27Cat7 (EU373647). Boxes indicate the Brugia NY strain (HE856316); asterisks (*) indicate conserved residues; periods (.) indicate nucleotide changes; colons (:) indicate nucleotide changes just in the Brugia NY isolate; hyphens (-) are included in the sequences to maximize the comparisons among the 9 DNA molecules. Italicized numbers in parentheses indicate the percentage of similarity with the Brugia NY isolate.

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 20, No. 7, July 2014 1249 LETTERS including New York (8 cases), Mas- Instituto de Biomedicina/Instituto Venezo- Candida auris– sachusetts, Pennsylvania, Connecti- lano de los Seguros Sociales, Caracas, cut, and Rhode Island (3 cases each) Venezuela (A. Paniz Mondolfi); Instituto de Associated (1,2); single cases have been identi- Salud Carlos III, Madrid, Spain (T. Gárate, Candidemia, fied in Michigan, Ohio, North Caro- L.M. González); and Centers for Disease South Africa lina, Oklahoma, New Jersey, Loui- Control and Prevention, Atlanta, Georgia, siana, Florida, and California (1,2). USA (M. Eberhard) To the Editor: We noted the re-

Four other cases have been report- DOI: http://dx.doi.org/10.3201/eid2007.131654 port by Chowdhary et al. (1) and re- ed: 3 in South America (Colombia, port Candida auris as a causative Brazil, Peru) (3,7,8) and 1 in Africa agent of candidemia in South Africa, References (Ethiopia) (9). Only a few Brugia with an estimated prevalence of 0.3% species have been identified, includ- 1. Orihel TC, Eberhard ML. Zoonotic filaria- (N.P. Govender et al., unpub. data). ing B. leporis, found in rabbits in the sis. Clin Microbiol Rev. 1998;11:366–81. First isolated in 2009, C. auris is an 2. Eberhard ML, DeMeester LJ, Martin BW, northeastern United States (1,10); B. Lammie PJ. Zoonotic Brugia infec- emerging species associated with beaveri, found in raccoons and bob- tion in western Michigan. Am J Surg clinical disease (2–6). We analyzed cats in the southern United States; Pathol. 1993;17:1058–61. http://dx.doi. 4 isolates submitted to the National and B. guyanensis, found in coati- org/10.1097/00000478-199310000-00012 Institute for Communicable Diseases 3. Orihel TC, Beaver PC. Zoonotic Brugia mundi and other vertebrates in South infections in North and South America. (Johannesburg, South Africa) from America (8). Definitive identifica- Am J Trop Med Hyg. 1989;40:638–47. 4 patients with candidemia who had tion with molecular techniques will 4. Taylor MJ, Hoerauf A, Bockarie M. been admitted to different public- and better identify causative species and Lymphatic filariasis and onchocerciasis. private-sector hospitals from October Lancet. 2010;376:1175–85. http://dx.doi. help clarify many of the ecologic and org/10.1016/S0140-6736(10)60586-7 2012 through October 2013. epidemiologic questions surrounding 5. Schneider MC, Aguilera XP, Barbosa Identification of the isolates was zoonotic filarial infections. da Silva Junior J, Ault SK, Najera P, undertaken by using ChromAgar Martinez J, et al. Elimination of neglected Candida medium (Mast Diagnos- diseases in Latin America and the Carib- This work was supported by the In- bean: a mapping of selected diseases. tics, Merseyside, UK), Vitek-2 YST stituto de Salud Carlos III, Fondo de In- PLoS Negl Trop Dis. 2011;5:e964. http:// (bioMérieux, Marcy ľEtoile, France), vestigaciónes Sanitarias, through the sixth dx.doi.org/10.1371/journal.pntd.0000964 API 20C AUX (bioMérieux), and national plan of research plus development 6. Gutierrez Y. Diagnostic features of sequencing of internal transcribed zoonotic filariae in tissue sections. plus innovation (2008–2011), Instituto de Hum Pathol. 1984;15:514–25. http://dx.doi. spacer (ITS) and D1/D2 domains Salud Carlos III -General Sub-Direction of org/10.1016/S0046-8177(84)80004-0 of the ribosomal RNA gene (7), fol- Networks and Centers for Collaborative 7. Kozek WJ, Reyes MA, Ehrman J, lowed by microbroth dilution suscep- Research (Red Temática de Investigación Garrido F, Nieto M. Enzootic Brugia tibility testing (8). All isolates were Cooperativa–Red de Investigación Coop- infection in a two-year old Colombian girl. Am J Trop Med Hyg. 1984;33:65–9. misidentified as C. haemulonii and erativa en Enfermedades Tropicales, grant 8. Baird JK, Neafie RC. South American Rhodotorula glutinis by Vitek-2 YST no. RD12/0018/003). brugian filariasis: report of a human in- and API 20C AUX assays, respec- fection acquired in Peru. Am J Trop Med tively (Table). Alberto Enrique Paniz-Mondolfi, Hyg. 1988;39:185–8. 9. Menéndez MC, Bouza M. Brugia species Similar to the findings of Chow- Teresa Gárate, in a man from western Ethiopia. Am J dhary et al., all isolates assimilated Christine Stavropoulos, Trop Med Hyg. 1988;39:189–90. N-acetyl-glucosamine (1). With the Wen Fan, 10. Beaver PC, Orihel TC. Human infection use of the CBS-KNAW database, Luis Miguel González, with filariae of animals in the United States. Am J Trop Med Hyg. 1965;14:1010–29. pairwise sequence alignment of ITS Mark Eberhard, region showed 99% sequence homol- Fred Kimmelstiel, Address for correspondence: Alberto E. ogy to Kuwait isolates, and alignment and Emilia Mia Sordillo Paniz-Mondolfi, Yale–New Haven Hospital, of D1/D2 domain showed 98% ho- Author affiliations: Yale University School Microbiology Laboratory (PS656), 55 Park mology to the Kuwait/India isolates of Medicine, New Haven, Connecticut, USA St, New Haven, CT 06511, USA; email: (9). In a neighbor-joining phyloge- (A.E. Paniz- Mondolfi); St. Luke’s-Roos- [email protected] netic tree based on ITS sequences, evelt Hospital Center of Columbia Univer- South Africa isolates formed a cluster sity College of Physicians and Surgeons, with India and Kuwait isolates (online New York, New York, USA (A.E. Paniz- Search past issues of EID at Technical Appendix Figure, http:// Mondolfi, C. Stavropoulos, W. Fan, F. Kim- wwwnc.cdc.gov/EID/article/20/7/13- melstiel, E.M. Sordillo); Servicio Autonomo wwwnc.cdc.gov/eid 1765-Techapp1.pdf).

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Article DOI: http://dx.doi.org/10.3201/eid2007.131654 Zoonotic Filariasis Caused by Novel Brugia sp. Nematode, United States

Technical Appendix

Figure. Histocytologic appearance of Brugia nematodes in 53-year-old White man from New York, USA. A) Male and female nematodes within the lymph node with reactive follicular hyperplasia and a lymphohistiocytic granulomatous infiltrate permeated by few scattered eosinophils. Hematoxylin and eosin stain, magnification ×5. B) Male (arrows) and female worms in varying longitudinal and transverse plains. Note that males are smaller than females and have a pseudocoelomic cavity containing a single reproductive tube and intestine. Females are larger and contain paired uterine tubes. Scale bar = 50 µm, hematoxylin and eosin stain, magnification ×20. C) Gravid female. The pseudocoelom is mostly occupied by 2 uterine tubes filled with developing eggs and microfilariae, and the small simple intestine. Note the thin cuticle, which becomes thickened and more prominent over the lateral cords; the low musculature consists of few muscle cells. Hematoxylin and eosin stain, magnification ×40. D) Mature microfilariae in the uterus. The arrows point out the 3 posterior nuclei. Note that the width of the microfilariae ranged from 4.5 µm to 5.5 µm. Hematoxylin and eosin stain, magnification ×100.

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