Comparison of Paired Immunofluorescent Antibody Serology and Real-Time Polymerase Chain Reaction Testing for the Detection of Acute Q Fever among Febrile Patients in Kilimanjaro, Tanzania, 2012–2014

Robert J. Rolfe Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, North Carolina;

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John A. Crump Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, North Carolina;
Duke University Global Health Institute, Durham, North Carolina;
Centre for International Health, University of Otago, Dunedin, New Zealand;
Kilimanjaro Christian Medical Centre, Moshi, Tanzania;

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Venance P. Maro Kilimanjaro Christian Medical Centre, Moshi, Tanzania;
Kilimanjaro Christian Medical University College, Moshi, Tanzania;

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Blandina T. Mmbaga Kilimanjaro Christian Medical Centre, Moshi, Tanzania;
Kilimanjaro Christian Medical University College, Moshi, Tanzania;
Kilimanjaro Clinical Research Institute, Moshi, Tanzania;

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Wilbrod Saganda Mawenzi Regional Referral Hospital, Moshi, Tanzania;

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Bingileki F. Lwezaula Mawenzi Regional Referral Hospital, Moshi, Tanzania;

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Marc Roger Couturier Associated Regional and University Pathologists, Inc, Salt Lake City, Utah;
Department of Pathology, University of Utah, Salt Lake City, Utah;

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Weston C. Hymas Associated Regional and University Pathologists, Inc, Salt Lake City, Utah;

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Jamie L. Perniciaro Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;

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William L. Nicholson Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;

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Gilbert J. Kersh Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;

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Matthew P. Rubach Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, North Carolina;
Duke University Global Health Institute, Durham, North Carolina;
Kilimanjaro Christian Medical Centre, Moshi, Tanzania;
Kilimanjaro Clinical Research Institute, Moshi, Tanzania;
Duke-National University of Singapore Medical School, Singapore

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ABSTRACT.

Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii (C. burnetii) phase II antigens using immunofluorescent antibody (IFA) testing, and acute serum was tested for C. burnetii with PCR. Acute Q fever was defined as a fourfold or greater rise from the acute to convalescent sample in IFA reciprocal titer or PCR detection that was confirmed through repeat testing. Test characteristics were tabulated. Among 496 participants tested using both paired IFA and PCR testing, 463 (93.3%) tested negative on both IFA and PCR, five (1.0%) tested positive for Q fever on both IFA and PCR, and 28 (5.6%) tested positive for Q fever on IFA alone. The sensitivity of PCR testing using paired IFA testing as an index was 0.15 (5/33), and the specificity was 1 (463/463). C. burnetii PCR testing provides a clinically specific method that may aid in timely diagnosis in settings in which acute Q fever is a common cause of febrile illness. However, we found a low clinical sensitivity of PCR testing on serum when compared with paired IFA serology.

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Author Notes

Financial support: This research was supported by the joint US NIH (www.nih.gov) and National Science Foundation (www.nsf.gov) Ecology of Infectious Disease program (R01TW009237), the Research Councils United Kingdom, the United Kingdom Department for International Development, and the United Kingdom Biotechnology and Biological Sciences Research Council (www.bbsrc.ac.uk; grant numbers BB/J010367/1). This research was supported in part by the Research Councils United Kingdom, the United Kingdom Department for International Development, and the Defense Science and Technology Laboratory under the Zoonoses and Emerging Livestock Systems program (BB/L018926, BB/L017679, BB/L018845). J. A. Crump, V. P. Maro, and M. P. Rubach received support from R01AI121378. M. P. Rubach also received support from R25TW009337 and K23AI116869.

Disclosures: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. The use of trade names and commercial sources is for identification only and does not imply endorsement by the US Department of Health and Human Services or the CDC. This study was approved by the Kilimanjaro Christian Medical University College Health Research Ethics Committee, the Tanzania National Institute for Medical Research National Research Ethics Coordinating Committee, and an Institutional Review Board of the Duke University Hospital System. A material transfer agreement was fully executed between KCMC and ARUP Laboratories and between the KCMC and the United States CDC. Informed consent was obtained from all participants or the participant’s parent or guardian. The United States Department of Health and Human Services human subjects research guidelines were followed.

Current contact information: Robert J. Rolfe, Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC, E-mail: robert.rolfe@duke.edu. John A. Crump, Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC, Duke University Global Health Institute, Durham, NC, Centre for International Health, University of Otago, Dunedin, New Zealand, and Kilimanjaro Christian Medical Centre, Moshi, Tanzania, E-mail: john.crump@otago.ac.nz. Venance P. Maro, Kilimanjaro Christian Medical Centre, Moshi, Tanzania, and Kilimanjaro Christian Medical University College, Moshi, Tanzania, E-mail: venmaro@ymail.com. Blandina T. Mmbaga, Kilimanjaro Christian Medical Centre, Moshi, Tanzania, Kilimanjaro Christian Medical University College, Moshi, Tanzania, and Kilimanjaro Clinical Research Institute, Moshi, Tanzania, E-mail: blaymt@gmail.com. Wilbrod Saganda and Bingileki F. Lwezaula, Mawenzi Regional Referral Hospital, Moshi, Tanzania, E-mails: wilbrod.saganda@gmail.com and lwezaula@gmail.com. Marc Roger Couturier, Associated Regional and University Pathologists, Inc., Salt Lake City, UT, and Department of Pathology, University of Utah, Salt Lake City, UT, E-mail: marc.couturier@aruplab.com. Weston C. Hymas, Associated Regional and University Pathologists, Inc., Salt Lake City, UT, E-mail: hymasw@aruplab.com. Jamie L. Perniciaro, William L. Nicholson, and Gilbert J. Kersh, Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: uvo6@cdc.gov, wan6@cdc.gov, and hws7@cdc.gov. Matthew P. Rubach, Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC, Duke University Global Health Institute, Durham, NC, Kilimanjaro Christian Medical Centre, Moshi, Tanzania, Kilimanjaro Clinical Research Institute, Moshi, Tanzania, and Duke-National University of Singapore Medical School, Singapore, E-mail: matthew.rubach@duke.edu.

Address correspondence to Matthew P. Rubach, Division of Infectious Diseases and International Health, Department of Medicine, Duke University, 315 Trent Dr., Room 256, DUMC, PO Box 102359, Durham, NC 27710. E-mail: matthew.rubach@duke.edu
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