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October/November 2012
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IDSA Journal Club
October-November 2012

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

Adverse Clinical Outcomes Associated with Unrecognized Viral Respiratory Tract Infections in the NICU
Reviewed by Jason B. Weinberg, MD

Unsuspected and largely asymptomatic respiratory viral infection (RVI) is correlated with adverse clinical outcomes in premature infants, according to a recent report in the November 2012 issue of the Journal of Pediatrics.

The authors performed a one-year prospective observational study in two neonatal intensive care units (NICUs). They obtained nasopharyngeal specimens from 50 premature infants shortly after birth and then twice a week for the duration of their hospital stay. Samples were analyzed using a multiplex polymerase chain reaction assay to detect 17 different respiratory viruses.

In the absence of clinical suspicion for RVI, 52 percent of the infants tested positive for at least one virus during the study period. Importantly, infants with positive testing were more likely to need supplemental oxygen, were intubated longer (51 days, versus 13 days for virus-negative infants), and had longer hospital stays (70 days, versus 35 days for virus-negative infants). Infants in whom viruses were detected were also significantly more likely to be diagnosed with bronchopulmonary dysplasia. A statistical path model suggested that the impact of RVI on hospital stay was mediated by direct effects and indirectly, via effects on oxygenation and intubation.

This study does not prove that detection of virus represented true infection in the premature infants. However, persistent virus detection in more than one sample, which suggests viral replication, occurred frequently. The results of the study do not establish a causal link between RVI and the various clinical outcomes that were studied. However, the correlation between virus detection and both short- and long-term adverse outcomes is striking. These results raise important questions that should be addressed in larger studies in order to better define ways in which respiratory viruses are transmitted in the NICU and how this can be effectively prevented.

(Bennett et al. J Pediatr 2012; 161:814-8.)

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An Ehrlichiosis Impersonator in the Heartland?
Reviewed by George R. Thompson III, MD

A recent report in The New England Journal of Medicine identified a novel phlebovirus responsible for symptoms and lab abnormalities that may be mistaken for ehrlichiosis.

In the journal’s Aug. 30 issue, authors described two patients residing in northwestern Missouri who admitted to frequent tick exposure. Both patients shared similar clinical symptoms of fever, fatigue, anorexia, diarrhea with leukopenia, thrombocytopenia, and elevated hepatic aminotransferase levels observed on laboratory profiles. Additionally both were initially diagnosed with ehrlichiosis and received doxycycline without clinical improvement.

Blood smear and PCR for Ehrlichia and Anaplasma species were negative; however a novel member of the Bunyaviridae was identified and subsequently has been named the Heartland virus. More than two years after initial presentation, both patients remain seropositive at titers exceeding 1:6400.

The remainder of Koch’s postulates have yet to be fulfilled, so a causal relationship between the virus and disease has not yet been firmly established. However, it is speculated that the virus resides in Amblyomma americanum ticks, and the reported patients may therefore represent those with more severe disease, while most cases are unrecognized.

Epidemiologic and ecologic studies are needed to define the disease burden and natural hosts, and clinicians should consider this novel virus as a possible etiologic agent in patients with clinical syndromes consistent with tick-borne disease who are unresponsive to doxycycline.

(McMullan et al.  N Engl J Med.  2012;367(9): 834-841.)

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The Kissing Disease: Primary EBV Infection Among College Students
Reviewed by Kathryn E. Stephenson, MD, MPH

Despite the high prevalence of Epstein-Barr virus (EBV), we still know little about the incidence and risk factors associated with primary EBV infection. In The Journal of Infectious Diseases, researchers describe the results of a prospective study to address these questions among college students at the University of Minnesota.

The authors identified a cohort of 143 freshmen who were EBV naïve and tested their sera every 8 weeks for EBV VCA IgG antibodies until the students graduated from college. Students who tested positive or were symptomatic received additional testing, including EBV viral load, flow cytometry, and cytokine profiling. Students were diagnosed with infectious mononucleosis if they had at least two of the following symptoms: sore throat, cervical lymphadenopathy, fever, or fatigue.

The authors found that 66 of the 143 students experienced primary EBV infection during college. The incidence among freshmen was more than twice the mean incidence during the following 3 years (26 vs. 10 cases per 100 person-years, P=0.002). Nearly one in four students with primary EBV infection did not have infectious mononucleosis, but 89 percent of cases did have symptoms. These symptoms lasted a median of 10 days, and were most commonly a sore throat (93 percent), cervical lymphadenopathy (76 percent), fatigue (66 percent), and upper respiratory symptoms (61 percent). More severe symptoms were significantly associated with a higher EBV viral load, as well as greater CD8 lymphocytosis. Primary EBV infection was significantly associated with deep kissing (with or without coitus, P<0.01), and oral cells were positive for EBV for a median of 175 days.

These results demonstrate that transmission of EBV among college students occurred primarily during the first year, probably through exposure to EBV-infected oral secretions via kissing. These data suggest that efforts to reduce EBV viremia – through immunization or antiviral therapy – could lessen symptoms, or even reduce EBV transmission.

(Balfour et al. J Infect Dis. Advance Access published Oct. 24, 2012, doi: 10.1093/infdis/jis646)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

Nov. 15

  • Treatment of Community-Acquired Pneumonia in Hospitalized Patients: Is Doxycycline an Effective Substitute for a Macrolide?
  • Treatment of Hemolytic Uremic Syndrome: Some Surprises and Time to Rethink

Nov. 1

  • Candida Infections in Liver Transplant Recipients
  • Systemic Inflammatory Response After Endovascular Abdominal Aortic Aneurysm Repair – A Syndrome or Just Another Post-Procedure Febrile Illness?

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