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| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
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| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ❑ '''''Hemorrhagic tendencies, evidenced by at least <u>one</u> of the following:''''' <BR> &nbsp;&nbsp; ❑ A positive tourniquet test <sup>†</sup><BR> &nbsp;&nbsp; ❑ Petechiae, ecchymoses, or purpura<BR> &nbsp;&nbsp; ❑ Bleeding from the mucosa, gastrointestinal tract, injection sites or other locations<BR> &nbsp;&nbsp; ❑ Hematemesis or melena
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ❑ '''''Hemorrhagic tendencies, evidenced by at least <u>one</u> of the following:''''' <BR> &nbsp;&nbsp; ❑ A positive tourniquet test<sup>†</sup><BR> &nbsp;&nbsp; ❑ Petechiae, ecchymoses, or purpura<BR> &nbsp;&nbsp; ❑ Bleeding from the mucosa, gastrointestinal tract, injection sites or other locations<BR> &nbsp;&nbsp; ❑ Hematemesis or melena
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&nbsp;&nbsp;<SMALL> <sup>†</sup> 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. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. 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.</SMALL>
&nbsp;&nbsp;<SMALL> <sup>†</sup> The tourniquet test is performed by inflating a [[Sphygmomanometer|blood pressure cuff]] on the upper arm to a point midway between the [[SBP|systolic]] and [[DBP|diastolic pressures]] for 5 minutes. A test is considered positive when 20 or more [[petechiae]] per 2.5 cm (1 inch) square are observed. 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]].</SMALL>


===2009 WHO Classification===
===2009 WHO Classification===


Newer classification published by WHO in 2009 categorizes the disease into '''probable dengue''' or '''laboratory-confirmed dengue''' (''with or without warning signs'') and '''severe dengue''' (encompassing ''severe plasma leakage'', ''severe bleeding'', and ''severe organ involvement''). However, it has been criticized as overly inclusive for several reasons:<ref name=CDC>{{cite web | title = Infectious Diseases Related To Travel | url = http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/dengue }}</ref>
A newer classification published by WHO in 2009 categorizes the disease into '''probable dengue''' or '''laboratory-confirmed dengue''' (''with or without warning signs'') and '''severe dengue''' (encompassing ''severe plasma leakage'', ''severe bleeding'', and ''severe organ involvement''). However, it has been criticized as overly inclusive for several reasons:<ref name=CDC>{{cite web | title = Infectious Diseases Related To Travel | url = http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/dengue }}</ref>


* It allows several different ways to qualify for severe dengue.
* It allows several different ways to qualify for severe dengue.
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| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ❑ '''''<u>Two</u> of the following criteria:''''' <BR> &nbsp;&nbsp; ❑ Nausea or vomiting <BR> &nbsp;&nbsp; ❑ Rash <BR> &nbsp;&nbsp; ❑ Aches and pains <BR> &nbsp;&nbsp; ❑ Tourniquet test positive <sup>†</sup><BR> &nbsp;&nbsp; ❑ Leukopenia <BR> &nbsp;&nbsp; ❑ Any warning sign
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ❑ '''''<u>Two</u> of the following criteria:''''' <BR> &nbsp;&nbsp; ❑ Nausea or vomiting <BR> &nbsp;&nbsp; ❑ Rash <BR> &nbsp;&nbsp; ❑ Aches and pains <BR> &nbsp;&nbsp; ❑ Tourniquet test positive<sup>†</sup><BR> &nbsp;&nbsp; ❑ Leukopenia <BR> &nbsp;&nbsp; ❑ Any warning sign
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| style="padding: 0 5px; font-size: 90%; background: #F5F5F5; font-weight: bold; font-style: italic;" align=center | Warning Signs
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5; font-weight: bold; font-style: italic;" align=center | Warning Signs
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| style="padding: 0 5px; font-size: 90%; background: #F5F5F5; font-weight: bold; font-style: italic;" align=center | Severe Organ Involvement
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5; font-weight: bold; font-style: italic;" align=center | Severe Organ Involvement
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ❑ '''''Severe organ involvement indicated by:'''''<BR> &nbsp;&nbsp; ❑ Liver: AST or ALT ≥1000 IU/L<BR> &nbsp;&nbsp; ❑ CNS: impaired consciousness<BR> &nbsp;&nbsp; ❑ Heart or other organs
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC; height: 81px;" align=left | ❑ '''''Severe organ involvement indicated by:'''''<BR> &nbsp;&nbsp; ❑ Liver: AST or ALT ≥1000 IU/L<BR> &nbsp;&nbsp; ❑ CNS: impaired consciousness<BR> &nbsp;&nbsp; ❑ Heart or other organs
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&nbsp;&nbsp;<SMALL> <sup>†</sup> 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. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. 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.</SMALL>
&nbsp;&nbsp;<SMALL> <sup>†</sup> The tourniquet test is performed by inflating a [[Sphygmomanometer|blood pressure cuff]] on the upper arm to a point midway between the [[SBP|systolic]] and [[DBP|diastolic pressures]] for 5 minutes. A test is considered positive when 20 or more [[petechiae]] per 2.5 cm (1 inch) square are observed. 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]].</SMALL>


=====Laboratory Method, Interpretation, and Sample Characteristics for Confirmed and Probable Dengue=====
====Laboratory Tests for Confirmed and Probable Dengue Infection====


A diagnosis of dengue infection is confirmed by the detection of the virus, the viral genome or NS1 antigen, or seroconversion of IgM or IgG (from negative to positive IgM/IgG or four-fold increase in the specific antibody titer) in paired sera.<ref name=WHO2012>{{cite web | title = Handbook for Clinical Management of dengue | url = http://apps.who.int/iris/bitstream/10665/76887/1/9789241504713_eng.pdf?ua=1 }}</ref>
* A diagnosis of '''confirmed dengue infection''' is established by isolation of the [[virus]], detection of viral [[genome]] or NS1 [[antigen]], or [[seroconversion]] of [[IgM]] or [[IgG]] (from negative to positive [[IgM]]/[[IgG]] or fourfold increase in the specific [[antibody]] titer) in paired [[serum|sera]].
 
* A positive [[IgM]] [[serology]] or a [[hemagglutination inhibition assay|hemagglutination inhibition assay (HIA)]] [[antibody]] titer of 1280 or higher (or comparable figures by [[ELISA]] in a single specimen), are diagnostic of a '''probable dengue infection'''. Both probable and confirmed dengue cases should be notified to health authorities.<ref name=WHO2012>{{cite web | title = Handbook for Clinical Management of dengue | url = http://apps.who.int/iris/bitstream/10665/76887/1/9789241504713_eng.pdf?ua=1 }}</ref>


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! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Definition}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Definition}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Method}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Method<sup>†</sup>}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Interpretation}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Interpretation<sup>†</sup>}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Sample Characteristics}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Sample Characteristics}}
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! style="padding: 5px 5px; background: #DCDCDC;" | IgG seroconversion
! style="padding: 5px 5px; background: #DCDCDC;" | IgG seroconversion
| style="padding: 5px 5px; background: #DCDCDC;" | From negative IgG to positive IgG in paired sera or 4-fold increase IgG levels among paired sera
| style="padding: 5px 5px; background: #DCDCDC;" | From negative IgG to positive IgG in paired sera or 4-fold increase IgG levels among paired sera
|-
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! style="padding: 5px 5px; background: #F5F5F5;" rowspan=2 | Probable Dengue Infection
! style="padding: 5px 5px; background: #F5F5F5;" rowspan=2 | Probable Dengue Infection
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! style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels
! style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels
| style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels by ELISA or HI (≥1280)
| style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels by ELISA or hemagglutination inhibition assay (≥1280)
|}
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&nbsp;&nbsp;<SMALL> <sup>†</sup> ELISA = enzyme-linked immunosorbent assay; IgG = immunoglobulin G; IgM = immunoglobulin M; NS1 Ag = non-structural protein 1 antigen; RT-PCR = reverse transcriptase polymerase chain reaction</SMALL>


==Referemces==
==Referemces==
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[[Category:Flaviviruses]]
[[Category:Flaviviruses]]
[[Category:Hemorrhagic fevers]]
[[Category:Hemorrhagic fevers]]
[[Category:Infectious disease]]
[[Category:Insect-borne diseases]]
[[Category:Insect-borne diseases]]
[[Category:Neglected diseases]]
[[Category:Neglected diseases]]
[[Category:Tropical disease]]
[[Category:Tropical disease]]
[[Category:Viral diseases]]
[[Category:Viral diseases]]
[[Category:Emergency medicine]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Hematology]]
[[Category:Cardiology]]
[[Category:Gastroenterology]]

Latest revision as of 21:16, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Overview

Current WHO guideline classifies dengue into non-severe and severe disease depending on whether there is severe plasma leakage, severe bleeding, or severe organ impairment. For practical purposes, non-severe cases can be further divided into two subgroups: those with warning signs and those without them. Patients with suspected dengue should be triaged and managed accordingly.

Classification

1997 WHO Classification

Historically, symptomatic dengue virus infections were classified as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. The case definitions were found too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis.

The tables below describe the 1997 WHO dengue case classification:[1]

Dengue Fever
Probable Dengue Fever
An acute febrile illness
PLUS
Two or more of the following manifestations:
   ❑ Headache
   ❑ Retro-orbital pain
   ❑ Myalgia
   ❑ Arthralgia
   ❑ Rash
   ❑ Hemorrhagic manifestations
   ❑ Leukopenia
PLUS
Supportive serology
   ❑ A reciprocal hemagglutination-inhibition antibody titre ≥1280
   ❑ A comparable IgG enzyme-linked immunosorbent assay (ELISA) titer
   ❑ A positive IgM test on a late acute or convalescent-phase serum specimen
Confirmed Dengue Fever
A case confirmed by laboratory criteria
   ❑ Isolation of the dengue virus from serum or autopsy samples
   ❑ Demonstration of a fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens in paired serum samples
   ❑ Demonstration of dengue virus antigen in autopsy tissue, serum or cerebrospinal fluid (CSF) samples by immunohistochemistry, immunofluorescence or ELISA
   ❑ Detection of dengue virus genomic sequences in autopsy tissue serum or CSF samples by polymerase chain reaction (PCR)
Reportable Dengue Fever
Any probable or confirmed case should be reported
Dengue Hemorrhagic Fever & Dengue Shock Syndrome
Dengue Hemorrhagic Fever (DHF)
Fever, or history of acute fever, lasting 2–7 days, occasionally biphasic
PLUS
Hemorrhagic tendencies, evidenced by at least one of the following:
   ❑ A positive tourniquet test
   ❑ Petechiae, ecchymoses, or purpura
   ❑ Bleeding from the mucosa, gastrointestinal tract, injection sites or other locations
   ❑ Hematemesis or melena
PLUS
Thrombocytopenia (100,000 cells per mm3 or less)
PLUS
Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following:
   ❑ A rise in the hematocrit equal to or greater than 20% above average for age, sex and population
   ❑ A drop in the hematocrit following volume-replacement treatment equal to or greater than 20% of baseline
   ❑ Signs of plasma leakage such as pleural effusion, ascites and hypoproteinemia
Dengue Shock Syndrome (DSS)
All of the above four criteria for DHF must be present
PLUS
Evidence of circulatory failure manifested by:
   ❑ Rapid and weak pulse AND narrow pulse pressure
OR manifested by:
   ❑ Hypotension for age AND cold, clammy skin and restlessness

   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. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. 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.

2009 WHO Classification

A newer classification published by WHO in 2009 categorizes the disease into probable dengue or laboratory-confirmed dengue (with or without warning signs) and severe dengue (encompassing severe plasma leakage, severe bleeding, and severe organ involvement). However, it has been criticized as overly inclusive for several reasons:[2]

  • It allows several different ways to qualify for severe dengue.
  • Nonspecific warning signs are used as diagnostic criteria.
  • Severity determination is dependent on individual judgment due to the lack of explicit clinical criteria for establishing severe dengue.

The tables below describe the 2009 WHO dengue case classification:[3][4]

Dengue ± Warning Signs
Probable Dengue (live in or travel to dengue endemic area)
Fever
PLUS
Two of the following criteria:
   ❑ Nausea or vomiting
   ❑ Rash
   ❑ Aches and pains
   ❑ Tourniquet test positive
   ❑ Leukopenia
   ❑ Any warning sign
Warning Signs
Warning signs requiring strict observation and medical intervention:
   ❑ Abdominal pain or tenderness
   ❑ Persistent vomiting
   ❑ Clinical fluid accumulation
   ❑ Mucosal bleed
   ❑ Lethargy, restlessness
   ❑ Liver enlargment >2 cm
   ❑ Increase in hematocrit with rapid decrease in platelet count
Severe Dengue
Severe Plasma Leakage
Severe plasma leakage leading to:
   ❑ Shock (dengue shock syndrome)
   ❑ Fluid accumulation with respiratory disrtess
Severe Bleeding
Severe bleeding as evaluated by clinician:
   ❑ Persistent and/or severe overt bleeding in the presence of unstable hemodynamic status, regardless of the hematocrit level
   ❑ A decrease in hematocrit after fluid resuscitation together with unstable hemodynamic status
   ❑ Refractory shock unresposive to fluid resuscitation of 40–60 ml/kg
   ❑ Hypotensive shock with low/normal hematocrit before fluid resuscitation
   ❑ Persistent or worsening metabolic acidosis ± a well-maintained systolic blood pressure, especially in those with severe abdominal tenderness and distension
Severe Organ Involvement
Severe organ involvement indicated by:
   ❑ Liver: AST or ALT ≥1000 IU/L
   ❑ CNS: impaired consciousness
   ❑ Heart or other organs

   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. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. 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.

Laboratory Tests for Confirmed and Probable Dengue Infection

Definition Method Interpretation Sample Characteristics
Confirmed Dengue Infection Viral isolation Virus isolated Serum (collected at 1–5 days of fever) or necropsy tissues
Genome detection Positive RT-PCR or positive real-time RT-PCR
Antigen detection Positive NS1 Ag
Positive immunohistochemical Necropsy tissues
IgM seroconversion From negative IgM to positive IgM in paired sera Acute serum (days 1–5) and convalescent serum (15–21 days after first serum)
IgG seroconversion From negative IgG to positive IgG in paired sera or 4-fold increase IgG levels among paired sera
Probable Dengue Infection Positive IgM Positive IgM Single serum collected after day 5
High IgG levels High IgG levels by ELISA or hemagglutination inhibition assay (≥1280)

   ELISA = enzyme-linked immunosorbent assay; IgG = immunoglobulin G; IgM = immunoglobulin M; NS1 Ag = non-structural protein 1 antigen; RT-PCR = reverse transcriptase polymerase chain reaction

Referemces

  1. "Dengue haemorrhagic fever: diagnosis, treatment, prevention and control" (PDF).
  2. "Infectious Diseases Related To Travel".
  3. 3.0 3.1 "Handbook for Clinical Management of dengue" (PDF).
  4. "Dengue: guidelines for diagnosis, treatment, prevention and control" (PDF).