14-ID-10
Committee:
Title:
Infectious Disease
Revision of Case Definitions for National Notification of Dengue
I. Statement of the Problem
In 2009, CSTE made dengue a nationally reportable condition. Although national reporting of dengue
cases has proved useful in documenting trends in both travel-associated and locally-acquired dengue,
multiple jurisdictions have requested additional guidance in classification of suspect dengue cases and
interpretation of dengue diagnostic test results to improve reporting accuracy. As such, modifications to the
current CSTE case definitions are proposed to meet these requests by providing updates in clinical case
definitions and advances in dengue diagnostics, which should improve dengue case reporting in the
United States.
II. Background and Justification
Dengue is a potentially fatal acute febrile illness caused by infection with any of four dengue viruses
(DENV-1, -2, -3 and -4). Dengue is a major public health problem worldwide [1], where an estimated 400
million DENV infections and 100 million clinically apparent dengue cases occurred in 2010 [2]. Although
~75% of individuals infected with a DENV will be asymptomatic, ~5% of individuals that develop dengue
will progress to severe dengue, an illness characterized by plasma leakage leading to hypovolemic shock,
hemorrhage, and potentially death [1]. The case-fatality rate for individuals with severe dengue can be as
high as 10% if untreated, or <0.1% with appropriate clinical management [3].
DENVs are transmitted primarily through the bite of Aedes aegypti and Ae. albopictus mosquitoes.
Because these mosquitoes are endemic throughout the tropics and sub-tropics, an estimated 40% of the
world’s population is at risk for DENV infection [1]. These mosquitoes are also present in the United
States. Ae. aegypti is present throughout southern Florida, southern Louisiana, parts of New Mexico and
Arizona, southern and central Texas (most prominently around urban centers such as Houston, Dallas,
and Austin) [4], and have recently been detected in central California and southern Utah. Ae. albopictus is
widely present throughout most of the southern United States and as far north as Illinois and New York [5].
The largest burden of dengue in the United States is in the territories of Puerto Rico and the U.S. Virgin
Islands where it is endemic. As such, the majority of reported dengue cases in the U.S. come from these
two territories, where existing surveillance systems are in place to capture both the incidence and to some
degree the spectrum of disease. Other areas of the US where dengue is or has been endemic include
American Samoa, the Northern Marianas, and Guam. In addition, hundreds of travel-associated dengue
cases occur each year, primarily in the 50 United States and the District of Columbia.
Since dengue became a reportable condition in 2010, 1,507–10,674 cases per year have been reported
from US Territories. During 2008–2011, only 1,120 (20%) of at least 5,807 laboratory-positive dengue
cases were reported from the 50 United States and the District of Columbia to ArboNET, the national
arboviral surveillance system; nearly all of these cases were travel-associated (CDC, unpublished data). In
addition, local dengue outbreaks occurred in several states, presumably initiated by traveler-introduced
DENV, in areas with Ae. aegypti and/or Ae. albopictus. Such outbreaks occurred in 2009–2010 in Key
West, Florida (n = 93 confirmed cases) [6,7]; in 2011 in Oahu, Hawaii (n = 6); and in 2013 in southern
Texas (n = 23), Martin County, Florida (n = 24), and Long Island, New York (n = 1).
Since 2005, six local dengue outbreaks have occurred in non-endemic areas of the United States, of which
five were investigated through use of enhanced surveillance techniques (e.g., retrospective and
prospective hospital-based case-finding, household-based serosurveys), which enabled identification of
additional cases. Reasons why case-patients were not previously identified or reported included failure to
seek medical attention; incorrect diagnosis by a clinician; and failure to report diagnosed dengue cases to
health authorities. Other reasons for not reporting suspect dengue cases included clinicians not obtaining
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sufficient clinical information to achieve a case classification, and incorrect interpretation and/or selection
of dengue diagnostic tests based on the timing of specimen collection. In addition, among cases that were
identified but not reported were those that did not meet the existing clinical case definition in spite of
having confirmatory laboratory evidence of dengue (i.e., persons with a febrile illness, for which DENV was
detected by diagnostic testing).
Dengue diagnostic test availability, performance and interpretation have changed considerably since
adoption of the 2009 CSTE dengue statement. Two FDA-approved tests are currently available for
diagnosis of dengue using a single serum specimen obtained during the febrile (acute) phase of the
illness. One test detects viremia and the other detects the DENV-specific IgM antibody response. When
used in combination, these tests have high sensitivity and specificity in dengue diagnosis.
The reverse transcriptase-polymerase chain reaction (RT-PCR) test reliably detects nucleic acid from
DENV-1–4 during the 5–7 days after illness onset. This is considered confirmatory evidence of dengue. In
2012, the first molecular diagnostic test was approved by the FDA (CDC DENV-1-4 Real-Time RT-PCR
Assay, CDC Dengue Branch) [8] and is being used in a number of public health and clinical laboratories
where it has replaced laboratory developed assays for dengue diagnostics. In 2011, the FDA approved the
first test to detect IgM anti-DENV by IgM capture enzyme-linked immunosorbent assay (MAC ELISA;
DENV Detect™ IgMCAPTURE ELISA, Inbios International, Inc., Seattle, WA). This test can reliably detect
anti-DENV IgM starting 3-4 days after illness onset and through roughly 90 days after illness onset [9].
However, interpretation of a positive IgM anti-DENV result in a single specimen is more complex due to
some degree of cross-reactivity with IgM antibody to other flaviviruses. Thus, final interpretation of a
positive test result must take into account the likelihood that the patient was recently infected with or
vaccinated against another flavivirus (e.g., West Nile, Saint Louis encephalitis, yellow fever, Japanese
encephalitis).
In addition, a number of non-FDA approved dengue diagnostic tests have been rigorously evaluated for
their performance in carefully designed studies, and include ELISAs for detection of non-structural protein
1 (NS1) antigen and IgM anti-DENV [10] [CDC, unpublished data]. In addition, some laboratories use cell
culture isolation of DENV from serum; detection of DENV antigen in tissue of fatal cases by
immunofluorescence or immunohistochemistry; detection of a four-fold rise in anti-DENV IgG antibody by
ELISA in paired acute and convalescent serum specimens; anti-DENV IgM seroconversion in paired
specimens; or detection of IgG anti-DENV by the plaque reduction neutralization tests (PRNT) as
serological evidence of dengue. At present, all private diagnostic laboratories in the United States perform
anti-DENV IgM and IgG ELISA on submitted specimens, regardless of day post-illness onset that the
specimen was collected.
Unfortunately, IgG anti-DENV is of very limited diagnostic utility in the acute illness because prior DENV
infection, infection with another flavivirus (e.g., West Nile), or vaccination against another flavivirus (e.g.,
yellow fever (YFV), Japanese encephalitis (JEV)) can produce lasting cross-reactive antibodies to the
DENV antigens in these ELISAs. This is particularly a problem for individuals that have previously lived in
or traveled to dengue endemic areas where they may have been infected with a DENV. Thus, IgG ELISA
results alone cannot be used to confirm a dengue case.
The large majority of reported dengue cases in the continental United States are travel-associated, of
which most report a travel history to Latin America, or less frequently, Southeast Asia. WNV is not
currently circulating in South or Central America, and YFV outbreaks occur only rarely. Therefore, travelers
with a dengue-like illness returning from Latin America with detectable IgM anti-DENV are highly likely to
have only been infected with DENV, and while JEV is a possible cause of illness in travelers returning from
Southeast Asia, it rarely occurs. Epidemiologists should consult recent surveillance data to determine if
infection with YFV or JEV is a realistic possible exposure for a returning traveler in order to best interpret a
serologic dengue diagnostic test result. Such information can be obtained online at www.healthmap.org/.
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Position Statement Template: Standardized Surveillance for Diseases or Conditions, Revised 2014
The 2009 CSTE Dengue Position Statement employed the 1997 WHO dengue case definitions [11] which
were: 1) undifferentiated febrile illness; 2) dengue fever; 3) dengue hemorrhagic fever (DHF); and 4)
dengue shock syndrome (DSS). However, in 2008 and 2009 two new sets of case definitions were
adopted by WHO. In 2009, WHO published ―Dengue: Guidelines for Diagnosis, Treatment, Prevention and
Control‖, which classified dengue as: 1) dengue; 2) dengue with warning signs; and 3) severe dengue,
which included DHF and DSS as subsets of this latter classification [12]. In 2008, WHO published a case
definition for dengue fever for use in clinical trials to determine the efficacy of candidate dengue vaccines
[13,14]. This definition defined dengue as a febrile illness plus laboratory evidence of viremia detected by
molecular diagnostics or ELISA for NS1 antigen detection. This definition of dengue was based on, and
has been confirmed by, a growing body of data that has shown that no combination of symptoms is more
sensitive than fever plus viremia to define the syndrome of dengue [15-17]. The 2009 CSTE Position
Statement indicated that future changes in dengue case classifications would be incorporated into CSTE
and ArboNET definitions for case reporting.
Surveillance for dengue is syndromic and no combination of signs or symptoms is diagnostically specific
during the acute (febrile) phase of the illness. Plasma leakage is diagnostically specific for dengue, but is
very insensitive for the purposes of surveillance since this finding only occurs in a low percentage of
patients late in the illness. Therefore, the consensus in the dengue field is that syndromic surveillance for
dengue must include dengue presenting only as an acute febrile illness and laboratory confirmation of all
suspected cases.
The duration of fever in dengue (including those among cases only with an acute febrile illness) can be
variable, but in the large majority it lasts for 2–7 days and in some it may be biphasic [1]. In rare instances
patients may develop a rare complication called hemophagocytic lymphohistiocytosis [18,19] or have a
nosocomial infection during hospitalization and remain febrile >7 days. For these reasons, we propose not
rigidly limiting the febrile period to 7 days.
The 2009 CSTE Dengue Position Statement included the reporting of DENV-positive asymptomatic blood
donors identified through pilot screening projects in dengue endemic areas. However, these screening
projects have ended, no cases were reported, and we propose deleting this reporting category and limiting
reporting to persons with symptomatic DENV infection (i.e., dengue).
III. Statement of the desired action(s) to be taken
1. Utilize standard sources (e.g. reporting*) for case ascertainment for dengue. Surveillance for dengue
should use the following recommended sources of data to the extent of coverage presented in Table III.
Table III. Recommended sources of data and extent of coverage for ascertaining cases of dengue
Coverage
Source of data for case ascertainment
Population-wide
clinician reporting
X
laboratory reporting
X
reporting by other entities (e.g., hospitals)
X
death certificates
X
hospital discharge or outpatient records
X
extracts from electronic medical records
X
Sentinel sites
telephone survey
school-based survey
X
*
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other _____________________
*Only in dengue endemic areas
2. Utilize standardized criteria for case identification and classification (Sections VI and VII) for dengue
disease and continue to include dengue on the Nationally Notifiable Condition List as ―routinely notifiable.‖
3. CDC should publish data on dengue as appropriate in MMWR and other venues (see Section IX).
CSTE recommends that all jurisdictions (e.g. States or Territories) with legal authority to conduct public
health surveillance follow the recommended methods as outlined above.
Terminology:
* Reporting: process of a healthcare provider or other entity submitting a report (case information) of a condition under public health
surveillance TO local or state public health.
**Notification: process of a local or state public health authority submitting a report (case information) of a condition on the Nationally
Notifiable Condition List TO CDC.
IV. Goals of Surveillance
Enable accurate national reporting and capture of all laboratory-positive dengue cases (i.e., symptomatic
DENV infection) identified by clinicians and diagnostic laboratories and reported to local, state and
territorial health departments.
V. Methods for Surveillance: Surveillance for dengue should use the recommended sources of data
and the extent of coverage listed in Table III.
Case ascertainment will continue to be conducted through passive, syndromic surveillance. Reports of
suspected dengue cases will derive from clinician and laboratory reporting to local, state and territorial
health departments, which will conduct individual follow-up to resolve the final case status for purposes of
reporting. In dengue endemic areas, most dengue diagnostic testing takes place in public sector
laboratories, while in non-endemic areas most testing takes place in private sector reference laboratories.
These reports should be obtained by the appropriate jurisdictions for subsequent case follow-up and
reporting. State-of-the-art dengue diagnostic testing is now available in a number of public health
laboratories and in private sector reference laboratories. CDC Dengue Branch in San Juan, Puerto Rico
provides reference diagnostic testing to laboratories providing routine dengue diagnostic testing and
consultation to clinicians and health departments regarding diagnostically challenging cases.
VI. Criteria for case identification
Reporting refers to the process of healthcare providers or institutions (e.g., clinical laboratories, hospitals)
submitting basic information to governmental public health agencies about cases of illness that meet
certain reporting requirements or criteria. The purpose of this section is to provide those criteria that should
be used to determine whether a specific illness should be reported.
A. Narrative: A description of suggested criteria for case ascertainment of a specific condition.
Report any illness to public health authorities that meets any of the following criteria:
1. A person with a history of fever and one or more of the following laboratory findings:
 Detection of DENV nucleic acid in serum, plasma, blood, cerebrospinal fluid (CSF), other body
fluid or tissue by validated reverse transcriptase-polymerase chain reaction (PCR), or
 Detection of DENV antigens in tissue a fatal case by a validated immunofluorescence or
immunohistochemistry assay, or
 Detection in serum or plasma of DENV NS1 antigen by a validated immunoassay; or
 Cell culture isolation of DENV from a serum, plasma, or CSF specimen; or
 Detection of IgM anti-DENV by validated immunoassay in a serum specimen or CSF in a
person living in a dengue endemic or non-endemic area of the United States irrespective of
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whether there is other flavivirus transmission occurring (e.g., WNV, SLEV), or whether the
person has had recent vaccination against a flavivirus (e.g., YFV, JEV); or
 Detection of IgM anti-DENV in a serum specimen or CSF by validated immunoassay in a
traveler returning from a dengue endemic area without ongoing transmission of another
flavivirus (e.g., WNV, JEV, YFV), clinical evidence of co-infection with one of these
flaviviruses, or recent vaccination against a flavivirus (e.g., YFV, JEV); or
 IgM anti-DENV seroconversion by validated immunoassay in acute (i.e., collected <5 days of
illness onset) and convalescent (i.e., collected >5 days after illness onset) serum specimens;
or
 The absence of IgM anti-DENV by validated immunoassay in a serum or CSF specimen
collected <5 days after illness onset and in which molecular diagnostic testing was not
performed in a patient with an epidemiologic linkage; or
 IgG anti-DENV seroconversion or ≥4-fold rise in titer by a validated immunoassay in serum
specimens collected >2 weeks apart, and confirmed by a neutralization test (e.g., plaque
reduction neutralization test [12]) with a >4-fold higher end point titer as compared to other
flaviviruses tested.
2. A person with a history of fever and one or more of the following epidemiological findings:
 During the two weeks prior to onset of fever, travel to a dengue endemic country or presence
in a location experiencing an ongoing dengue outbreak, OR
 During the two weeks prior to onset of fever, association in time and place with a confirmed or
probable dengue case.
Table VI-B. Table of criteria to determine whether a case should be reported to public health
authorities
Reporting
Criterion
1
2
N
N
Clinical Evidence
Fever as reported by the patient or healthcare provider
Laboratory Evidence
For any patient with history of fever, the detection in serum, plasma, CSF or tissue of DENVspecific genome sequences by RT-PCR or another molecular diagnostic test; OR
O
Detection in serum or plasma of DENV NS1 antigen by immunoassay; OR
O
Cell culture isolation of DENV from serum, plasma, CSF or other clinical specimens; OR
O
Detection of DENV antigen in tissue from a fatal case by immunofluorescence or
immunohistochemistry; OR
O
¶
Detection of IgM anti-DENV by validated immunoassay in a serum specimen or CSF in a
person living in a dengue endemic or non-endemic area of the United States irrespective of
whether there is other flavivirus transmission (e.g., WNV, SLEV) occurring or whether the
person has had recent vaccination against a flavivirus (e.g., YFV, JEV); OR
O
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¶
Detection of IgM anti-DENV in a serum specimen or CSF by validated immunoassay in a
traveler returning from a dengue endemic area without ongoing transmission of another
flavivirus (e.g., WNV, JEV, YFV), clinical evidence of co-infection with one of these
flaviviruses, or recent vaccination against a flavivirus (e.g., YFV, JEV); OR
O
¶
IgM anti-DENV seroconversion by validated immunoassay in acute (i.e., collected <5 days of
illness onset) and convalescent (i.e., collected >5 days after illness onset) serum specimens;
OR
O
¶
The absence of IgM anti-DENV by validated immunoassay in a serum or CSF specimen
collected <5 days after illness onset and in which molecular diagnostic testing was not
performed, in a patient with an epidemiologic linkage, and without recent vaccination against
a flavivirus (e.g., YFV, JEV.
O
¶
IgG anti-DENV seroconversion or ≥4-fold rise in titer by a validated immunoassay in serum
specimens collected >2 weeks apart, and confirmed by a neutralization test (e.g., plaque
reduction neutralization test [12]) with a >4-fold higher end point titer as compared to other
flaviviruses tested.
O
Epidemiological Evidence
During the two weeks prior to onset of fever, travel to a dengue endemic country or presence
in a location experiencing an ongoing dengue outbreak, OR
O
During the two weeks prior to onset of fever, association in time and place with a confirmed or
probable dengue case.
O
Notes:
S = This criterion alone is Sufficient to report a case.
N = All ―N‖ criteria in the same column are Necessary to report a case.
O = At least one of these ―O‖ (Optional) criteria in each category (e.g., clinical evidence and laboratory
evidence) in the same column—in conjunction with all ―N‖ criteria in the same column—is required to
report a case.
* A requisition or order for any of the ―S‖ laboratory tests is sufficient to meet the reporting criteria.
¶
Validated diagnostic tests are defined as FDA-approved or laboratory-developed assays if supported by
evaluation studies.
C. Disease-specific data elements
The following information is needed to identify instances of autochthonous transmission (i.e., locally
acquired cases) versus dengue cases resulting from importation from another country (i.e., travelassociated dengue cases).
●
●
●
●
●
●
●
●
●
Name, age, sex, race, ethnicity
Current state of residence and foreign travel destination(s)
Date of symptom onset
Travel history in last 2 weeks on a country-by-country basis
History of vaccination against yellow fever or Japanese encephalitis
History of prior infection with dengue virus, West Nile virus, Japanese encephalitis virus
Clinical signs and symptoms. See description below.
Initial results of diagnostic testing
Hospitalizations, need for intensive care, death
VII. Case Definition for Case Classification
A. Narrative: Description of criteria to determine how a case should be classified.
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Clinical presentation criteria
Dengue-like illness is defined by fever as reported by the patient or healthcare provider.
Dengue is defined by fever as reported by the patient or healthcare provider and the presence of one or
more of the following signs and symptoms:
●
Nausea/vomiting
●
Rash
●
Aches and pains (e.g., headache, retro-orbital pain, joint pain, myalgia, arthralgia)
●
Tourniquet test positive
●
Leukopenia (a total white blood cell count of <5,000/mm ), or
●
Any warning sign for severe dengue:
3
o
Abdominal pain or tenderness
o
Persistent vomiting
o
Extravascular fluid accumulation (e.g., pleural or pericardial effusion, ascites)
o
Mucosal bleeding at any site
o
Liver enlargement >2 centimeters
o
Increasing hematocrit concurrent with rapid decrease in platelet count
Severe dengue is defined as dengue with any one or more of the following scenarios:
●
Severe plasma leakage evidenced by hypovolemic shock and/or extravascular fluid accumulation
(e.g., pleural or pericardial effusion, ascites) with respiratory distress. A high hematocrit value for
patient age and sex offers further evidence of plasma leakage.
●
Severe bleeding from the gastrointestinal tract (e.g., hematemesis, melena) or vagina
(menorrhagia) as defined by requirement for medical intervention including intravenous fluid
resuscitation or blood transfusion.
●
Severe organ involvement, including any of the following:
o Elevated liver transaminases: aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) >1,000 units per liter (U/L)
o Impaired level of consciousness and/or diagnosis of encephalitis, encephalopathy, or
meningitis
o
Heart or other organ involvement including myocarditis, cholecystitis, and pancreatitis
Laboratory criteria
Diagnostic testing should be requested for patients in whom there is a high index of suspicion for
dengue, based either on signs and symptoms, or epidemiological linkage to a confirmed or probably
dengue case.
Confirmatory:
 Detection of DENV nucleic acid in serum, plasma, blood, cerebrospinal fluid (CSF), other body
fluid or tissue by validated reverse transcriptase-polymerase chain reaction (PCR), or
 Detection of DENV antigens in tissue a fatal case by a validated immunofluorescence or
immunohistochemistry assay, or
 Detection in serum or plasma of DENV NS1 antigen by a validated immunoassay; or
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




Probable


Cell culture isolation of DENV from a serum, plasma, or CSF specimen; or
Detection of IgM anti-DENV by validated immunoassay in a serum specimen or CSF in a
person living in a dengue endemic or non-endemic area of the United States without evidence
of other flavivirus transmission (e.g., WNV, SLEV, or recent vaccination against a flavivirus
(e.g., YFV, JEV); or
Detection of IgM anti-DENV in a serum specimen or CSF by validated immunoassay in a
traveler returning from a dengue endemic area without ongoing transmission of another
flavivirus (e.g., WNV, JEV, YFV), clinical evidence of co-infection with one of these
flaviviruses, or recent vaccination against a flavivirus (e.g., YFV, JEV); or
IgM anti-DENV seroconversion by validated immunoassay in acute (i.e., collected <5 days of
illness onset) and convalescent (i.e., collected >5 days after illness onset) serum specimens;
or
IgG anti-DENV seroconversion or ≥4-fold rise in titer by a validated immunoassay in serum
specimens collected >2 weeks apart, and confirmed by a neutralization test (e.g., plaque
reduction neutralization test [12]) with a >4-fold higher end point titer as compared to other
flaviviruses tested.
Detection of IgM anti-DENV by validated immunoassay in a serum specimen or CSF in a
person living in a dengue endemic or non-endemic area of the United States with evidence of
other flavivirus transmission (e.g., WNV, SLEV), or recent vaccination against a flavivirus
(e.g., YFV, JEV).
Detection of IgM anti-DENV in a serum specimen or CSF by validated immunoassay in a
traveler returning from a dengue endemic area with ongoing transmission of another flavivirus
(e.g., WNV, JEV, YFV), clinical evidence of co-infection with one of these flaviviruses, or
recent vaccination against a flavivirus (e.g., YFV, JEV).
Suspected
 The absence of IgM anti-DENV by validated immunoassay in a serum or CSF specimen
collected <5 days after illness onset and in which molecular diagnostic testing was not
performed in a patient with an epidemiologic linkage.
Criteria for epidemiologic linkage
 Travel to a dengue endemic country or presence at location with ongoing outbreak within
previous two weeks of onset of an acute febrile illness or dengue, or
 Association in time and place (e.g., household member, family member, classmate, or
neighbor) with a confirmed or probable dengue case.
Case classification
Confirmed
A clinically compatible case of dengue-like illness, dengue, or severe dengue with confirmatory laboratory
results, as listed above.
Probable
A clinically compatible case of dengue-like illness, dengue, or severe dengue with laboratory results
indicative of probable infection, as listed above.
Suspect
A clinically compatible case of dengue-like illness, dengue, or severe dengue with an epidemiologic
linkage, as listed above.
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Criteria to distinguish a new case of this disease or condition from reports or notifications which
should not be enumerated as a new case for surveillance
DENV infection results in long-lasting immunity to symptomatic infection (dengue) with that DENV-type.
However, cross-protective (heterotypic) immunity against dengue is short-lived with estimated durations of
1–3 years [21]. In dengue endemic areas where infection pressure is high, individuals have been shown to
infrequently have sequential episodes of dengue with two different infecting serotypes.
Based on these data, a person with two clinical episodes of dengue occurring at least two weeks apart and
shown to be due to different infecting serotypes confirmed by molecular diagnostic testing would be
classified as two different cases.
However, for two clinical episodes of dengue in the same person diagnosed only by IgM anti-DENV on the
second episode; for these to be considered separate cases, they would have to occur >90 days apart due
to the persistence of detectable IgM anti-DENV for ~90 days.
Table VII-B. Classification Tables. Criteria for defining a case of dengue
Criterion
Reporting of Dengue
Confirmed
Probable
Suspected
N
N
S
Fever as reported by the patient or healthcare provider
N
N
N
Nausea/vomiting
O
O
O
Rash
O
O
O
Aches and pains (e.g. headache, retro-orbital pain, joint pain,
myalgia)
O
O
O
O
O
O
O
O
O
O
O
O
Dengue, as defined above
N
N
N
Severe plasma leakage leading to hypovolemic shock or fluid
accumulation (e.g., pleural effusions, ascites, pericardial effusion)
with respiratory distress
O
O
O
Severe bleeding from gastrointestinal tract or vagina
O
O
O
Severe organ involvement
O
O
O
Clinical Evidence
Dengue-like illness
Fever as reported by the patient or healthcare provider
Dengue
Tourniquet test positive
**
3
Leukopenia ( total white blood cell count <5,000/mm )
Any severe dengue warning sign
***
Severe Dengue
Laboratory evidence
For any patient with signs or symptoms of suspect dengue, the
detection in serum, plasma, CSF or tissue of DENV-specific
genome sequences by RT-PCR or another molecular diagnostic
test; OR
S
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Detection in serum or plasma of DENV NS1 antigen by
immunoassay; OR
S
Cell culture isolation of DENV from serum, plasma, CSF or other
clinical specimens; OR
S
Detection of DENV antigens in tissue from a fatal case by
immunofluorescence or immunohistochemistry, OR
S
¶
Detection of IgM anti-DENV by validated immunoassay in a
serum specimen or CSF in a person living in a dengue endemic or
non-endemic area of the United States without evidence of other
flavivirus transmission (e.g., WNV, SLEV), or recent vaccination
against a flavivirus (e.g., YFV, JEV); OR
S
Detection of IgM anti-DENV by validated¶ immunoassay in a
serum specimen or CSF in a person living in a dengue endemic or
non-endemic area of the United States with evidence of other
flavivirus transmission (e.g., WNV, SLEV), or recent vaccination
against a flavivirus (e.g., YFV, JEV).
S
Detection of IgM anti-DENV in a serum specimen or CSF by
validated immunoassay in a traveler returning from a dengue
endemic area with ongoing transmission of another flavivirus
(e.g., WNV, JEV, YFV), clinical evidence of co-infection with one
of these flaviviruses, or recent vaccination against a flavivirus
(e.g., YFV, JEV);
S
Detection of IgM anti-DENV in a serum specimen or CSF by
¶
validated immunoassay in a traveler returning from a dengue
endemic area without ongoing transmission of another flavivirus
(e.g., WNV, JEV, YFV), clinical evidence of co-infection with one
of these flaviviruses, or recent vaccination against a flavivirus
(e.g., YFV, JEV); OR
S
¶
IgM anti-DENV seroconversion by validated immunoassay in
acute (i.e., collected <5 days of illness onset) and convalescent
(i.e., collected >5 days after illness onset) serum specimens; OR
IgG anti-DENV seroconversion or ≥4-fold rise in titer by a
¶
validated immunoassay in serum specimens collected >2 weeks
apart, and confirmed by a neutralization test (e.g., plaque
reduction neutralization test [12]) with a >4-fold higher end point
titer as compared to other flaviviruses tested.
S
S
¶
The absence of IgM anti-DENV by validated immunoassay in a
serum or CSF specimen collected <5 days after illness onset and
in which molecular diagnostic testing was not performed, in a
patient with an epidemiologic linkage.
Epidemiological evidence
S
Confirmed
During the previous two weeks prior to onset of fever, travel to a
dengue endemic country or presence in a location experiencing
Probable
Suspected
S
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Position Statement Template: Standardized Surveillance for Diseases or Conditions, Revised 2014
an ongoing dengue outbreak, OR
During the previous two weeks prior to onset of fever, association
in time and place with a confirmed or probable dengue case.
S
Notes:
S = This criterion alone is Sufficient to classify a case.
N = All ―N‖ criteria in the same column are Necessary to classify a case. A number following an ―N‖
indicates that this criterion is only required for a specific disease/condition subtype (see below).
A = This criterion must be absent (i.e., NOT present) for the case to meet the classification criteria.
O = At least one of these ―O‖ (Optional) criteria in each category (e.g., clinical evidence and laboratory
evidence) in the same column—in conjunction with all ―N‖ criteria in the same column—is required to
classify a case. (These optional criteria are alternatives, which means that a single column will have either
no O criteria or multiple O criteria; no column should have only one O.) A number following an ―O‖
indicates that this criterion is only required for a specific disease/condition subtype.*The tourniquet test is
performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and
diastolic pressures for 5 minutes.
2
2
**A test is considered positive when 10 or more petechiae per 2.5 cm (1 in ) are observed after the cuff
pressure has been released for 2 minutes. The test may be negative or mildly positive during the phase of
profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after
recovery from shock.
*** Warning signs: Abdominal pain or tenderness, persistent vomiting, extravascular fluid accumulation
(e.g., pleural or pericardial effusion, ascites), mucosal bleeding at any site, liver enlargement >2
centimeters, increasing hematocrit concurrent with rapid decrease in platelet count
Validated diagnostic tests are defined as FDA-approved or laboratory-developed assays if supported by
evaluation studies.
Rarely, a person will present with two consecutive episodes of acute febrile illness or dengue. If they occur
at least two weeks apart and are shown to be due to different infecting DENV serotypes by molecular
diagnostic testing, they should be reported as two different cases. However, if diagnosed only by IgM antiDENV in the second episode, they would be considered as separate cases only if they occur >90 days
apart due to the persistence of detectable IgM anti-DENV for up to ~90 days.
VIII. Period of Surveillance
Surveillance should be on-going.
IX. Data sharing/release and print criteria
● CDC requests standard notification of suspected, probable, and confirmed cases.
● Data flow will proceed from state and local health departments to CDC and WHO. Only fully deidentified case data will be released to the general public. Suspected case data will not be
included in final case counts. Case report data will not be used or released until verification
procedures are complete and all states have finalized their case counts.
● Data will be used to determine the burden of illness due to dengue, identify areas of risk and risk
factors to US travelers, target prevention efforts, and inform vaccination recommendations when
vaccines become available. Electronic reports of dengue will be summarized in the MMWR.
● All data will preferably be entered by arboviral coordinators into ArboNET in real-time as cases are
detected and subsequently revised as additional case information (e.g., diagnostic test results) are
made available.
● All city, county and state health departments will have access to data submitted to ArboNET to
assess available data on the trends in dengue incidence locally and throughout the country.
● State-specific compiled data will be posted on the EpiX Forum on a monthly basis. Content of this
report to the states and territories will be dependent on the current epidemiologic situation and
identified needs of stakeholders. Additional methods of data dissemination including CDC website
posting, email notices, and maps highlighting where infection contracted will be investigated.
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Council of State and Territorial Epidemiologists
Position Statement Template: Standardized Surveillance for Diseases or Conditions, Revised 2014
●
State-specific compiled data will be published in MMWR reports. All cases will be verified by the
states before publication.
X. References
1. World Health Organization (2009) Dengue: Guidelines for Diagnosis, Treatment, Prevention and
Control.
2. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, et al. (2013) The global distribution
and burden of dengue. Nature 496: 504-507.
3. Lam PK, Tam DT, Diet TV, Tam CT, Tien NT, et al. (2013) Clinical characteristics of dengue
shock syndrome in Vietnamese children: a 10-year prospective study in a single hospital. Clin
Infect Dis 57: 1577-1586.
4. Eisen L, Moore CG (2013) Aedes (Stegomyia) aegypti in the continental United States: a vector
at the cool margin of its geographic range. J Med Entomol 50: 467-478.
5. Benedict MQ, Levine RS, Hawley WA, Lounibos LP (2007) Spread of the tiger: global risk of
invasion by the mosquito Aedes albopictus. Vector Borne Zoonotic Dis 7: 76-85.
6. Radke EG, Gregory CJ, Kintziger KW, Sauber-Schatz EK, Hunsperger EA, et al. (2012) Dengue
outbreak in Key West, Florida, USA, 2009. Emerg Infect Dis 18: 135-137.
7. Centers for Disease Control and Prevention (2010) Locally acquired Dengue--Key West,
Florida, 2009-2010. Morb Mortal Wkly Rep 59: 577-581.
8. Santiago GA, Vergne E, Quiles Y, Cosme J, Vazquez J, et al. (2013) Analytical and clinical
performance of the CDC real time RT-PCR assay for detection and typing of dengue virus. PLoS
Negl Trop Dis 7: e2311.
9. Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Araujo ES, et al. (1999)
Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis. J Clin Virol 14:
183-189.
10. Namekar M, Ellis EM, O'Connell M, Elm J, Gurary A, et al. (2013) Evaluation of a new
commercially available immunoglobulin M capture enzyme-linked immunosorbent assay for
diagnosis of dengue virus infection. J Clin Microbiol 51: 3102-3106.
11. World Health Organization (WHO) (1997) Dengue Haemorrhagic Fever: Diagnosis, Treatment,
and Control. Geneva: WHO.
12. World Health Organization (2009) Dengue: Guidelines for Diagnosis, Treatment, Prevention
and Control. First ed. Geneva.
13. Edelman R, Hombach J (2008) "Guidelines for the clinical evaluation of dengue vaccines in
endemic areas": summary of a World Health Organization Technical Consultation. Vaccine 26:
4113-4119.
14. Research WHOIfV (2008) Guidelines for the clinical evaluation of dengue vaccines in endemic
areas.
15. Sabchareon A, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, et al.
(2012) Dengue infection in children in Ratchaburi, Thailand: a cohort study. I. Epidemiology of
symptomatic acute dengue infection in children, 2006-2009. PLoSNegl Trop Dis 6: e1732.
16. Yoon IK, Srikiatkhachorn A, Hermann L, Buddhari D, Scott TW, et al. (2013) Characteristics of
mild dengue virus infection in Thai children. Am J Trop Med Hyg 89: 1081-1087.
17. Biswas HH, Ortega O, Gordon A, Standish K, Balmaseda A, et al. (2012) Early clinical features
of dengue virus infection in Nicaraguan children: a longitudinal analysis. PLoS Negl Trop Dis 6:
e1562.
18. Sharp TM, Gaul L, Muehlenbachs A, Hunsperger E, Bhatnagar J, et al. (2014) Fatal
hemophagocytic lymphohistiocytosis associated with locally acquired dengue virus infection - New
Mexico and Texas, 2012. Morb Mortal Wkly Rep 63: 49-54.
19. Tan LH, Lum LC, Omar SF, Kan FK (2012) Hemophagocytosis in dengue: comprehensive
report of six cases. J Clin Virol 55: 79-82.
20. Bhatnagar J, Blau DM, Shieh WJ, Paddock CD, Drew C, et al. (2012) Molecular detection and
typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing:
diagnostic and epidemiologic implications. Am J Trop Med Hyg 86: 335-340.
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Council of State and Territorial Epidemiologists
Position Statement Template: Standardized Surveillance for Diseases or Conditions, Revised 2014
XI. Coordination
Agencies for Response
(1) Centers for Disease Control and Prevention
Dr. Thomas Frieden
Director
1600 Clifton Road, NE
Atlanta GA 30333
(404) 639-7000
txf2@cdc.gov
XII. Submitting Author:
(1) Linda Gaul, Ph.D.
State Epidemiologist
Texas Department of State Health Services
1100 W. 49th St.
Austin, TX 78756
(512) 776-7198
Linda.Gaul@dshs.state.tx.us
Co-Author:
(1)
Carina Blackmore, DVM
State Epidemiologist
Florida Department of Health
4052 Bald Cypress Way
Tallahassee, FL 32399-1712
850-245-4117
Carina.Blackmore@flhealth.gov
(2)
Brenda Rivera Garcia, DVM
Territorial Epidemiologist
Puerto Rico Department of Health
Epidemiology and Research Office
Medical Center Area
San Juan, PR 00926
787-765-2929 x3551
brendarivera@salud.gov.pr
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Council of State and Territorial Epidemiologists
Position Statement Template: Standardized Surveillance for Diseases or Conditions, Revised 2014