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Report from CDC’s Unexplained Respiratory
Disease Outbreak (URDO) Working Group

By Amesh A. Adalja MD, FACP, July 13, 2012

Novel influenza, SARS, the hantaviruses, and other emerging infectious diseases of interest present as a constellation of similar or overlapping respiratory symptoms. Most often, the clinical presentation is not accompanied by a specific confirmed diagnosis, the lack of which may be due to a patient’s prior use of antimicrobial therapy, inadequate specimens, or inadequate diagnostic testing equipment. Although most of these undiagnosed respiratory illnesses are of little public health consequence, some could be caused by pathogens of interest, in which case nascent outbreaks of serious diseases may not be recognized. In 2004, to facilitate expert consultation and address this problem, the Centers for Disease Control and Prevention (CDC) formed the Unexplained Respiratory Disease Outbreak (URDO) working group. The July 6, 2012, MMWR [1] summarizes the group’s activities for a 4.5 year period.

Fifty-seven URDO Investigations

CDC reports that from March 2007 through September 2011, 57 URDO consultations occurred. Important features of those investigations include the following:

  • CDC laboratory testing: 42
  • Field investigations: 8
  • Domestic investigations: 41
  • International investigations: 16 (in 13 nations)
  • Median case count per investigation: 14
  • Median hospitalizations: 3

Consultation was not always timely. An investigation was only launched once URDO was notified; in some cases notification occurred within 4 days of illness onset, but in some, it did not occur until 200 days after onset. The median time to notification was 33 days.

Common Pathogens Are Common

Using all forms of diagnostic technology (PCR, serology, culture, histopathology, immunohistochemistry, antigen testing) an etiology was discovered in 51% of cases. A multianalyte PCR assay (TaqMan Array) that simultaneously tests for 20 pathogens was also employed in 13 instances. In the 49% of cases for which etiology was identified, pathogens identified included the following:

  • Non-influenza respiratory viruses (RSV, parainfluenza, adenovirus, metapneumovirus, parechovirus, enterovirus, rhinovirus): 41%
  • Influenza viruses : 17%
  • Mycoplasma pneumoniae: 14%
  • Bordetella pertussis: 14%
  • Streptococcus pneumoniae: 7%
  • Other (Chlamydophila pneumoniae, HSV-2, Legionella, Bordetella parapertussis, Rickettsia rickettsii, poliovirus): 7%

Multiple pathogens were identified in 9% of investigations. Of the 13 investigations in which the TaqMan Array was used, an etiology was determined for 6, and multiple pathogens were identified in 5 of the remaining 7 cases.

A Valuable Demonstration

The report of the URDO working group is an important contribution to the field of emerging infectious diseases and outbreak investigation for several reasons. First, it documents the long delay that may occur in notifying the CDC of an outbreak of undiagnosed respiratory disease. With delay, specimens may be unavailable, patients may have died, antimicrobial therapy may have sterilized body fluids, and the efficacy of public health interventions (infection control, vaccination, post-exposure prophylaxis, etc.) may be compromised.

A second important facet of the CDC’s report is that no novel pathogens were seen. This finding underscores the fact that a large amount of surveillance is needed to detect novel diseases. However, given that 49% of investigations did not yield an etiology, current diagnostic capabilities are clearly limited.

Finally, the use of the multianalyte TaqMan Array demonstrated the value of concomitant testing of one specimen for multiple pathogens. This approach can decrease the time to identification substantially over the normal procedure of working through an algorithm of serial tests.

Overall, the URDO working group is an excellent example of how expert guidance can assist a treating clinician, with the caveat that timely notification is essential.

Is There a Role for Telemedicine Consultation?

The findings of this report suggest a novel approach that may foster more appropriate and timely diagnostic testing, promote the use of multianalyte technology, and improve notification times. The establishment of real-time telemedicine channels could provide infectious disease consultation to remote domestic facilities and international locations identified disease “hot spots.” Through such a ready presence (albeit virtual), more appropriate and timely diagnostic work-ups could be initiated, optimal therapies implemented, and early notifications made to public health officials when needed. 

Reference

  1. CDC. Unexplained respiratory disease outbreak working group activities—worldwide, March 2007-September 2011. MMWR 2012; 61:480-483. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6126a2.htm. Accessed July 12, 2012.