Unfortunately, increased clinical diagnostic sensitivity comes at the expense of clinical diagnostic specificity. In addition, tests with high analytical sensitivity are susceptible to laboratory contamination. Thus, it is clear that diagnostically and analytically sensitive tests are subject to false-positive results. In this case, concern about the circumstances surrounding an apparently repeatably (but weakly) positive PCR result for dengue 2 RNA led to extensive and appropriate further studies that strongly support the final conclusion that the initial results were indeed due to contamination. A second and third extract from the original sample were tested multiple times and found nonreactive, and evaluation of subsequent samples for evidence of seroconversion provided supportive evidence that the donor (and the neonate recipient of her blood donation) were not infected with dengue virus. The laboratory cannot be faulted for these careful determinations, but would they have taken place in a less critical environment? Herein lies the lesson. However, a broader question that might be asked is why the testing was done in the first place and how were the analytes chosen? Given the recent finding of a dengue transfusion transmission in Singapore, and the involvement of some of the same authors in the case, it is understandable that dengue and even chikungunya viruses were of interest, but was there any helpful clinical information to provide a basis for the testing? What is the likelihood of accurately identifying the etiologic agent of a flu-like febrile illness by this approach? Could it not have been a bacterial or even parasitic infection, either of which would have had very different implications for the blood recipient? The case further illustrates that, in the absence of appropriate caution, the properties and potential failure modes of sensitive tests could lead an apparent finding of that which is expected, rather than what is really there.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: None declared.
Stock Ownership: R. Y. Dodd, Abbott Laboratories (immediate family member).
Honoraria: R. Y. Dodd, Novartis Vaccines and Diagnostics.
Research Funding: None declared.
Expert Testimony: None declared.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2010 The American Association for Clinical Chemistry