Baud, David

Borel, Nicole

Goy, Genevieve

Greub, Gilbert

Osterheld, Maria-Chiara

Pospischil, Andreas

Vial, Yvan

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Waddlia chondrophila: FromBovine Abortion to HumanMiscarriageTo the Editor—Miscarriage is themost common complication of preg-nancy, affecting every fourth womanduring her life [1]. Despite thoroughinvestigations, an etiology is elucidatedin only 50% of cases. A recent serologicalstudy has suggested a role of Waddliachondrophila, a strict intracellular bac-teria belonging to the Chlamydiales or-der, in human miscarriage [2]. Thus, 96out of 438 women exhibited an anti-Waddlia immunoglobulin G (IgG) titerR1:64. This seroprevalence was signifi-cantly higher in patients with mis-carriage (32%) compared with controlwomen with an uneventful pregnancy(7%, P , .001). Anti-Waddlia anti-bodies were specific, as they did notcross-react with antibodies directedagainst other Chlamydiaceae (ie, Chla-mydia trachomatis, Chlamydia pneumo-niae, or Chlamydia psittaci) or otherintracellular bacteria such as Rickettsia,Coxiella, Wolbachia, and Anaplasma[2–4]. Moreover, the strong statisticalassociation between miscarriage and IgGreactivity against Waddlia remainedwhen adjusted for possible confoundingfactors in various multivariate logisticregression models [2]. However, directdemonstration of Waddlia in humanplacenta has not yet been reported. Wethus investigated the role of Waddlia inhuman miscarriage prospectively as partof an ongoing study. This study has beenapproved by the local ethical committee(reference number 138/06). We hereindocument the first case of Waddlia-associated miscarriage by demonstratingthe direct presence of Waddlia in thecervicovaginal secretion and in theplacenta by polymerase chain reaction(PCR) and immunohistochemistry.After a normal pregnancy and a firstearly miscarriage, a 34-year-old whitewoman presented with a second mis-carriage at week 10 of gestation. Thepatient did not report any prior medicalor surgical history. She neither had petsnor contact with animals, and she didnot live in a rural area. The patientunderwent a dilatation and curettage,during which retained products of con-ception, serum, and cervicovaginal swabwere collected. Postoperative follow-upwas uneventful.Immunofluorescence was performedas previously described [2] and showeda positive anti-Waddlia antibody sero-logy (titer 1:64). In addition, DNA ofWaddlia was amplified from the cervi-covaginal swab using a Waddlia specificreal-time PCR [5]. The patient hadneither Chlamydia trachomatis–positiveserology nor DNA in the cervicovaginalswab. Placental histology showed thepresence of numerous polymorpho-nuclear cells in the fibrin of the de-cidua, compatible with an early infection(Figure 1A). Moreover, Waddlia immu-nohistochemistry showed the presenceof Waddlia infected cells localised inthe glandular epithelium (Figures 1B, C,and D).We thus show here strong evidenceof human infection with WaddliaCORRESPONDENCE d CID 2011:52 (15 June) d 1469chondrophila. Indeed, Waddlia infectionwas documented by serology, by PCR,and by immunohistochemistry. The lat-ter test confirmed the presence ofWaddlia in the placenta, in an area ex-hibiting signs of recent infection.Animals are an important infectionsource and reservoir of emerging humanpathogens. Waddlia was first identified inbovine abortion [1, 3, 4]. Other zoonoticpathogens, such as Toxoplasma goondii,Chlamydophila abortus, and Coxiellaburnetti are well-known agents of adversehuman pregnancy outcomes. Whetherhuman infection with Waddlia occursthrough contact with animals is stillquestionable. In this case, the patient didnot have any contact with animals. Buttransmission might also occur throughingestion of contaminated milk or meat.Since Waddlia has also been recoveredin the vaginal and respiratory tract areaof humans [5], human-to-human trans-mission is also possible. The highWaddlia seroprevalence in women suffer-ing from miscarriage [2] makes furtherinvestigations urgently necessary to ex-plore the role of Waddlia in this setting.This first report of Waddlia in miscarriagemight give new insight in the preventionand investigation of miscarriage, the mostfrequent complication of human preg-nancy.AcknowledgmentsWe thank all midwives and doctors who par-ticipated in the sampling for this study. Their in-volvement was essential to the whole process, andthey enthusiastically gave their time to provideinformation and samples. We thank SebastienAeby for technical help, and Francoise Damnonand Andre Baud for computer assistance.Financial support. This work was supportedby the University of Lausanne (interdisciplinarygrant); the Swiss National Science Foundation(FN3200B0-116445 and FN310030-130466); theInstitute of Microbiology; the Department ofObstetrics and Gynecology; the Socie´te´ Aca-de´mique Vaudoise (‘‘Paul Blanc’’ grant to D. B.);the SICPA Foundation (D. B.); and the LeenardsFoundation (Bourse Leenards pour la rele`veacade´mique en me´decine clinique a` Lausanne[career award] to G. G.).Potential conflicts of interest. All authors:No reported conflicts.All authors have submitted the ICMJE Formfor Disclosure of Potential Conflicts of Interest.Conflicts that the editors consider relevant to thecontent of the manuscript have been disclosed inthe Acknowledgements section.David Baud,1,2 Genevieve Goy,1 Maria-ChiaraOsterheld,3 Nicole Borel,4 Yvan Vial,2 AndreasPospischil,4 and Gilbert Greub1,51Department of Laboratory, Institute of Microbiology,University Hospital Centre and University ofLausanne, 2Department of Obstetrics andGynaecology, Maternity, University Hospital Centre,and, 3Vetsuisse Faculty, Institute of Pathology,University Hospital Centre, Lausanne, Switzerland;4Department of Laboratory Medicine, Institute ofVeterinary Pathology, University of Zu¨rich, Zu¨rich,Switzerland; and 5Infectious Disease Service,Department of Internal Medicine, University HospitalCentre, Lausanne, SwitzerlandReferences1. Baud D, Regan L, Greub G. Emerging role ofChlamydia and Chlamydia-like organisms inadverse pregnancy outcomes. Curr Opin In-fect Dis 2008; 21:70–6.2. Baud D, Thomas V, Arafa A, Regan L, GreubG. Waddlia chondrophila, a potential agent ofhuman fetal death. Emerg Infect Dis 2007;13:1239–43.3. Rurangirwa FR, Dilbeck PM, Crawford TB,McGuire TC, McElwain TF. Analysis ofthe 16S rRNA gene of micro-organism WSU86-1044 from an aborted bovine foetus re-veals that it is a member of the order Chla-Figure 1. Histological Pictures and Immunohistochemistry to Detect Waddlia chondrophila. (A),Hematoxylineosin–stained histological sections of the placenta (magnification 3200). (B, C, andD) Immunohistochemistry (magnification 3200 for B, 3400 for C and D) using a specific rabbitpolyclonal antibody (dilution of 1:12,000) to investigate for the presence of Waddlia in theplacenta. Detection was performed with the Dako ChemMate Detection Kit according to themanufacturer's instructions. The histological picture (A) shows infiltration of the placenta withnumerous polymorphonuclear cells compatible with early infection. Immunohistochemistry (B, C,and D) demonstrated the presence of Waddlia in epithelial cells of the endometrial glands.1470 d CID 2011:52 (15 June) d CORRESPONDENCEmydiales: Proposal of Waddliaceae fam. nov.,Waddlia chondrophila gen. nov., sp. nov. Int JSyst Bacteriol 1999; 49(Pt 2);577–81.4. Henning K, Schares G, Granzow H, et al.Neospora caninum and Waddlia chondrophilastrain 2032/99 in a septic stillborn calf. VetMicrobiol 2002; 85:285–92.5. Goy G, Croxatto A, Posfay-Barbe KM,Gervaix A, Greub G. Development of a real-time PCR for the specific detection ofWaddlia chondrophila in clinical samples.Eur J Clin Microbiol Infect Dis 2009;28:1483–6.Correspondence: Gilbert Greub, MD, PhD, Center forResearch on Intracellular Bacteria (CRIB), Institute ofMicrobiology, University Hospital Center and University ofLausanne, Bugnon 48, 1011 Lausanne, Switzerland (gilbert.-greub@chuv.ch).Clinical Infectious Diseases 2011;52(12):1469–1471 The Author 2011. Published by Oxford University Press onbehalf of the Infectious Diseases Society of America.All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.1058-4838/2011/5212-0013$14.00DOI: 10.1093/cid/cir205CORRESPONDENCE d CID 2011:52 (15 June) d 1471

Waddlia chondrophila: From Bovine Abortion to Human Miscarriage

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