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Enterovirus D68 is Making the Rounds


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Grant C. Paulsen, MD
Cincinnati Children's Hospital Medical Center
Cincinnati, OH, USA
grant.paulsen@cchmc.org



The late summer cold season has been dominated by dramatic coverage of Enterovirus species D 68 (EV-D68) by most major media outlets. Many showed footage of busy Emergency Rooms and small children receiving breathing treatments. Initially reported as the 'Mystery Respiratory Virus' by some, it was subsequently determined that a strain of enterovirus was largely responsible.

Enteroviral infections are common, often asymptomatic, and typically occur in the summer and fall. When symptoms do occur, they vary widely and in immune competent hosts may include mild upper respiratory infection, fever with rash, and neurologic illness, such as aseptic meningitis and encephalitis. Enterovirus infections in transplant patients are not frequently reported, but have been most often documented in stem cell transplant recipients [1,2]. In contrast to the other enteroviruses, EV-D68 primarily causes mild to severe respiratory illness.

EV-D68 was first isolated in California in 1962 [3], and was infrequently reported as a cause of illness until the last few years. Between 2008 and 2010, there were outbreaks of respiratory illness associated with EV-D68 worldwide, including the Philippines (2008), Japan (2010), the Netherlands (2010), and the United States (2009-2010) [4].

This year has seen a well-documented increase in patients hospitalized with severe respiratory illness due to EV-D68 in Missouri, Illinois and a number of other states [5]. From mid-August through September 22, a total of 175 patients from 27 states were confirmed by either the CDC or the state public health lab to have EV-D68 [6], with more likely to be added.

EV-D68 infection is frequently seen in children, with peak incidence in those 0-4 years of age[4]. Underlying respiratory disease, such as asthma, appears to be the most significant risk factor for severe illness, and was seen in 68-73% of recently reported cases [5]. Frequently reported symptoms include cough, wheezing, dyspnea, hypoxemia, retractions, and perihilar infiltrate on chest radiograph [4,5]. Fever is less common, seen only in 18-26%. While there is likely some component of selection bias, it is notable that 19/19 patients from Kansas City, and 10/11 patients from Chicago required admission to the intensive care unit.

There are little data available regarding EV-D68 and solid organ transplantation. An analysis from the Netherlands of 24 patients with EV-D68 in 2010 included 3 lung transplant patients; all of whom survived [7]. With respect to donor organs, it is likely not advisable to accept lungs from a donor with suspicion for EV-D68 infection. While EV-D68 dissemination to the heart is unclear, enteroviruses have been found to be cardiotropic and associated with adverse clinical events in pediatric heart transplant recipients [8], potentially placing donor hearts from EV-D68 infected patients at higher risk as well.

Diagnosis of enteroviral infection is most commonly done with PCR testing. It is often not part of the standard 'respiratory panel' offered by commercial or institutional labs, and therefore may need to be requested separately. Further complicating diagnosis is the risk that some platforms may incorrectly identify EV-D68 as a rhinovirus. If EV-D68 is suspected, communication with the testing lab is advisable. Currently, specific testing for EV-D68 is available from the CDC and some state public health labs. CDC's Picornavirus Laboratory (e-mail: wnix@cdc.gov) is available to assist with testing.

There is no specific therapy available for enterovirus infections, care is supportive. Additionally, since this strain has not been circulating widely in recent years, it is unlikely, or at least unknown, if current supplies of intravenous immune globulin (IVIG) contain therapeutic quantities of EV-D68 type-specific antibody.

The above average number of ED visits and hospital admissions reported this season can place a significant strain on institutional resources. Experience in our community from early August thru mid-September demonstrated a 10-fold increase in ED visits for respiratory illness diagnoses compared to the same time period over the last two years, as well as a 10-fold increase in pediatric intensive care unit admissions for wheezing or respiratory compromise. The specific etiology of this increase is unknown, but the spectrum of disease appears consistent with that reported from Kansas City and Chicago. The direct impact of this increased volume has been to limit bed availability, which may influence a center's decision to proceed with transplant. It's unclear if this is limited to pediatric facilities, or will be seen in adult hospitals as well.

Currently, this enteroviral season appears to be heavily influenced by a strain with a preference for the respiratory tract, placing patients with underlying lung disease at much higher risk of severe respiratory illness. The CDC requests that health care providers should consider EV-D68 as a possible cause of acute, unexplained severe respiratory illness; and suspected outbreaks should be reported to local or state health departments [5]. ■

Disclosure Statement: The author has no conflicts of interest to disclose.


References:

  1. Chakrabarti, S, et al., Enterovirus infections following T-cell depleted allogeneic transplants in adults. Bone Marrow Transplant 2004;33(4):425-30.
  2. Gonzalez, Y, et al., Pulmonary enterovirus infections in stem cell transplant recipients. Bone Marrow Transplant 1999;23(5):511-3.
  3. Schieble, JH, V.L. Fox, and E.H. Lennette, A probable new human picornavirus associated with respiratory diseases. Am J Epidemiol 1967;85(2):297-310.
  4. Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. MMWR Morb Mortal Wkly Rep 2011;60(38):1301-4.
  5. Midgley, CM, et al., Severe respiratory illness associated with enterovirus d68 - missouri and illinois, 2014. MMWR Morb Mortal Wkly Rep 2014;63(36):798-9.
  6. States with Lab-confirmed Enterovirus D68. 2014; Available from: http://www.cdc.gov/non-polio-enterovirus/about/EV-D68-states.html.
  7. Rahamat-Langendoen, J., et al., Upsurge of human enterovirus 68 infections in patients with severe respiratory tract infections. J Clin Virol 2011;52(2):103-6.
  8. Shirali, GS, et al., Association of viral genome with graft loss in children after cardiac transplantation. N Engl J Med 2001;344(20):1498-503.



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