Fatal Dengue Diagnosis and Alarm Signals • CID 2006:42 (1 May) • 1241
M A J O R A R T I C L E
Dengue-Related Deaths in Puerto Rico, 1992–1996:
Diagnosis and Clinical Alarm Signals
Jose ´ G. Rigau-Pe ´rez1and Miriam K. Laufer2
1Dengue Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control
and Prevention, San Juan, Puerto Rico; and
University of Maryland School of Medicine, Baltimore
2Center for Vaccine Development, Division of Infectious Diseases and Tropical Pediatrics,
decedents with laboratory results positive for dengue. Because confirmatory results are usually not availableduring
hospitalization, we examined the utility of 2 instruments for diagnosis on the basis of clinicalfindings:thedefinition
of dengue hemorrhagic fever (DHF) and the publicized (but unevaluated) clinical alarm signals for impending
We studied data from all patients with laboratory test results positive for dengue who died (23
patients) and from the 8 patients whose death certificates listed dengue as a cause of death but whose laboratory
test results were negative for dengue in Puerto Rico from 1992 through 1996. We examined hospital records to
determine whether the clinical criteria for DHF were fulfilled and evaluated the incidence and timing of clinical
alarm signals (intense, sustained abdominal pain; persistent vomiting; sudden change from fever to hypothermia;
and marked restlessness or lethargy) and the hematocrit/hemoglobin ratio as an indicator of hemoconcentration.
A similar proportion of patients with laboratory test results positive for dengue (18 [78%] of 23) and
negative for dengue (6 [75%] of 8) fulfilled the criteria for DHF. Clinical alarm signals were found only among
patients with laboratory test results positive for dengue and were usually noted on the day that the patient’s
condition deteriorated. The hematocrit/hemoglobin ratio identified 1 (6%) of 16 patients with dengue who had
significant hemoconcentration. Important comorbidities were present in 16 (70%) of the patients with laboratory
test results positive for dengue and in 4 (50%) of the patients with dengue-related deaths with laboratory test
results negative for dengue.
Dengue-related deaths in Puerto Rico often occur in patients with comorbidities. Among such
patients, the DHF definition and the hematocrit/hemoglobin ratio were not useful in identifying patients with
laboratory test results positive for dengue. In contrast, the clinical alarm signals for shock supported the dengue
diagnosis and should alert clinicians to the severity of the disease.
Dengue, although endemic in Puerto Rico, is often not mentioned in the death certificates of
Dengue, a mosquito-transmitted viral disease, has
markedly increased in incidence in Puerto Rico in the
past 3 decades . The typical episode is self-limited
and involves fever, headache, myalgia, arthralgia, and
rash. Severe forms, includingdenguehemorrhagicfever
(DHF) and dengue shock syndrome (DSS), although
less common than milder forms of infection, can be
life-threatening . Since 1987, the Dengue Branch of
the Centers for Disease Control and Prevention (CDC)
and the Puerto Rico Department of Health have per-
Received 19 September 2005; accepted 16 December 2005; electronically
published 21 March 2006.
Reprints or correspondence: Dr. Jose ´ G. Rigau, CDC Dengue Branch, 1324 Calle
Can ˜ada, San Juan, PR 00920-3860 (email@example.com).
Clinical Infectious Diseases 2006;42:1241–6
? 2006 by the Infectious Diseases Society of America. All rights reserved.
formed surveillance for deaths due to dengue using 3
overlapping sources of information: (1) the forms that
accompany blood samples submitted for diagnosis, (2)
reports from hospital infection-control nurses, and (3)
death certificates that mention dengue.
In the evaluation of fatalities that occurred during
the large 1994–1995 dengue epidemic (incidence, 7 re-
ported cases per 1000 population), discrepancies were
noted between laboratory data and some death certif-
icates . Surveillance revealed patients who had lab-
oratory evidence of dengue infection but whose death
certificates did not mention dengue, and some death
certificates that listed dengue as a cause of death were
associated with negative laboratory test results or were
for patients from whom diagnostic samples were not
received. Confirmatory laboratory results for dengue
are usually not available during hospitalization. To un-
by guest on November 20, 2015
1246 • CID 2006:42 (1 May) • Rigau-Pe ´rez and Laufer
The prominence of clinical alarm signals detected in this
small study of only the most-severe cases of dengue suggests
late in the course of the disease, but through this retrospective
review, we were unable to determine whether the timing of the
identification of these alarm signals could affect the outcome
of severe dengue disease. A prospective study is required to
evaluate the sensitivity, specificity, and utility of these signals,
not only among patients with fatal cases (rare in any hospital
or country in the Americas), but also among patients with
positive and with negative laboratory test results for dengue
who have cases of varying severity.
Our evaluation found that dengue-related deaths in Puerto
Rico may have a complex clinical history with associated co-
morbidities, a pattern that may also apply to other countries
in the Americas that have a broad age distribution among pa-
tients with dengue. Clinicians must be alert to the possibility
of concurrent illnesses, especially when patients are elderly or
when antibiotic therapy may be beneficial [19, 27]. Although
only fatal cases were included in this study, our findingssuggest
that, among patients with suspectedcasesofdengue,theclinical
alarm signals support a dengue diagnosis and should alert
health care providers of the severity of the disease and the
potential for fatal outcome.
Potential conflicts of interest.
J.G.R.-P. and M.K.L.: no conflicts.
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