Distinguishing Dengue from Other Infections

Five clinical and laboratory findings were independently associated with dengue infection in patients with febrile
illnesses.

Early diagnosis of dengue fever can improve patient outcomes and help prevent further spread of the virus.
Investigators recently analyzed data for 2007 and 2008 from an enhanced dengue surveillance system in Puerto Rico,
where the illness is endemic, to identify early clinical features that were independently associated with dengue fever.
They included all laboratory-positive and laboratory-negative cases of suspected dengue fever and excluded cases
with dengue-indeterminate laboratory results and those in children aged <1 year. Laboratory confirmation was
defined as anti-dengue IgM seroconversion, anti-dengue IgM positivity on a specimen, or virus identification through
serotype-specific reverse-transcriptase polymerase chain reaction (PCR).

Of the 1955 cases of suspected dengue that were analyzed, 108 were dengue laboratory positive, and 1847 were
laboratory negative. Patients with laboratory-positive dengue were older than those with laboratory-negative infection
(median, 18.8 years vs. 11.5 years). All four dengue serotypes were represented in the 60 cases with positive PCR
results. Among the 51 patients for whom primary or secondary infection status could be determined, 17 had primary
and 34 had secondary infections.

In a logistic regression model, five variables were independently associated with confirmed dengue infection: retro-
orbital pain, rash, platelet count <240,000 cells/mm3, absence of sore throat, and absence of cough. Predictive findings
varied by age, and leukopenia was predictive only in patients aged 20 years. An all-ages model constructed from the
authors' data distinguished dengue from other acute febrile illnesses significantly more accurately than models
generated from the WHO's current or proposed case definitions.

— Mary E. Wilson, MD
— Published in Journal Watch Infectious Diseases May 12, 2010

Comment: In areas where laboratory resources are limited or unavailable, these findings can help clinicians diagnose
dengue early so that they can remain alert to findings that signal development of severe disease. The authors discuss
retro-orbital pain and note many recent papers that report ocular manifestations of dengue, including macular and
retinal hemorrhage.
 Hypothermia plus Hemicraniectomy vs. Hemicraniectomy Alone for Massive Infarcts

The combination may be better, but is the benefit clinically important?

The best approach to patients with massive hemispheric strokes ("malignant MCA territory infarcts") remains unclear.
In selected patients, decompressive craniectomy allows the brain to herniate outward instead of inward, potentially
resulting in dramatic resolution of midline shift and reduced mortality. Although this approach is increasingly
accepted, randomized evidence is generally lacking, and long-term clinical outcomes are unknown. Hypothermia may
also be beneficial in ischemic stroke, but translating the benefits seen in animal studies into clinical practice has been
difficult.

These researchers randomized 25 consecutive patients with malignant MCA territory infarcts to undergo either
decompressive craniectomy followed by hypothermia (35ºC) maintained for 48 hours, or craniectomy alone. Inclusion
criteria were age <65, severe stroke (NIHSS score >20 for left-sided infarcts and >15 for right-sided ones), and infarct
involving more than two thirds of the MCA territory with no diffusion–perfusion mismatch.

Immediate postsurgical mortality did not differ between the two groups; nor did length of stay or duration of
mechanical ventilation. At 6 months, the combination-therapy group had a trend toward better outcomes compared
with the surgery-only group (mean Barthel index, 81 vs. 70). The combination-therapy group required higher mean
doses of norepinephrine to maintain blood pressure during hypothermia (1.3 mg/hour vs. 0.9 mg/hour; P=0.05). The
authors concluded that, given the trend toward improved outcome with combination therapy, this approach should be
considered as "an additional treatment option" for these patients.

— Michael De Georgia, MD
— Dr. De Georgia is Head of the Neurological Intensive Care Section at the Cleveland Clinic Foundation,
Cleveland. Published in Journal Watch Neurology March 9, 2010

Comment: Although hemicraniectomy plus hypothermia is promising and certainly warrants further study,
recommending it as a standard of care for ischemic stroke would be premature. First, most of the mortality and
morbidity associated with massive hemispheric infarcts results from brain tissue shift and subsequent brainstem and
diencephalic damage. Reducing infarct volume to prevent shift is a rational strategy. However, in this study, given the
lack of salvageable tissue evident on MRI, the large infarct size, and the time of hypothermia onset (well beyond 2
hours after ischemia onset), it is unlikely that hypothermia effectively reduced infarct volume. Hypothermia induced
so late may attenuate brain edema, but given that craniectomy alone is so effective in reducing midline shift, any
added benefit that hypothermia contributes to the long-term clinical outcome through reduced edema may be
marginal. Second, cooled patients required higher doses of vasopressor agents. From an intensivist’s perspective, this
may seem insignificant, but these factors can help cancel out positive therapeutic effects or even tip the balance
toward a worse outcome (N Eng J Med 2001; 344:556). Larger randomized controlled trials are needed to sort out the
risks and benefits of decompressive surgery alone, hypothermia alone, and the two combined.
 A New Diagnostic Test for Acute Appendicitis
A screening test with high negative predictive value could improve diagnostic accuracy for acute appendicitis and
reduce the number of patients needing imaging studies and consultation. In a prospective pilot study, researchers
evaluated whether S100A8/A9, a calcium-binding protein that is secreted in inflammatory conditions, is a useful
biomarker for acute appendicitis. The study was conducted by the manufacturer of the biomarker assay.

Plasma levels of S100A8/A9 and total white blood cell (WBC) counts were measured in 181 adults and children who
presented to three emergency departments with right-sided or infraumbilical acute abdominal pain of less than 2
weeks' duration and no dysuria or recent trauma. The prevalence of acute appendicitis was 23%. For predicting acute
appendicitis, S199A8/A9 (at a cutoff of 20 units) had a sensitivity of 93%, specificity of 54%, negative predictive
value of 96%, and positive predictive value of 37%. Corresponding values for total WBC count (at a cutoff of 10 to
the third power) were 62%, 67%, 86%, and 36%.

— Diane M. Birnbaumer, MD, FACEP

Published in Journal Watch Emergency Medicine March 26, 2010

Comment: These preliminary data show promise for the S100A8/A9 test in patients with possible acute appendicitis,
but the findings of this pilot study must be validated in a prospective trial. This study also shows, yet again, the
futility of the outdated and discredited — but surprisingly persistent — practice of using WBC count to diagnose
appendicitis.