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{{Dengue fever}}
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==Overview==


==Overview==
The earliest abnormality in the [[complete blood count]] is decreased [[white cell]] count ([[leukopenia]]), which usually occurs during the febrile phase and should alert the physician to a high probability of dengue.  The [[platelet]] count usually begins to drop when the temperature is returning to normal and is followed by findings indicative of plasma leakage such as elevated [[hematocrit]] level and [[hypoproteinemia]]. However, the extent of [[hemoconcentration]] may be affected by dilutional effect from excessive fluid administration or significant [[hemorrhage]] from the [[gastrointestinal tract]] and the [[white cell]] count may increase as a result of [[stress response]]. [[Serology]] and [[virology]] tests are used to confirm the diagnosis of dengue virus infection.


==Laboratory Findings==
==Laboratory Findings==


===Electrolyte and Biomarker Studies===
{| style="float: right; width: 350px;"
| [[File:The course of dengue illness.png|400px|thumb|none|Adapted from ''Dengue: guidelines for diagnosis, treatment, prevention and control''. © World Health Organization 2009<ref name=WHO2009>{{cite web | title = Dengue: guidelines for diagnosis, treatment, prevention and control | url = http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf?ua=1 }}</ref>]]
|}
 
===Complete Blood Count===
 
* Progressive [[leukopenia]] (≤5000 cells/mm<sup>3</sup>) is the earliest laboratory abnormality in dengue virus infeciton. It is usually followed by an abrupt decline in the [[platelet]] count to about 100,000 cells/mm<sup>3</sup> before the emergence of signs of plasma leakage.
 
* Rising hematocrit concentrations may suggest impending hemorrhage. Plasma leakage is heralded by a rising [[hematocrit]] above the baseline value, and the extent of [[hemoconcentration]] reflects the severity of plasma leakage. However, this may be obscured by excessive [[intravenous therapy|intravenous fluid]] administration or significant [[hemorrhage]] from the [[gastrointestinal tract]]. Frequent [[hematocrit]] determinations are essential for guiding [[intravenous therapy|intravenous fluid therapy]].
 
* The [[hematocrit]] level normalizes or may be lower than the baseline due to the dilutional effect.  The [[white cell]] count usually starts to rise soon after defervescence, while the recovery of the [[platelet]] count is typically delayed.
 
===Metabolic Panel===
 
* [[Hypoproteinemia]], accompanied by fluid accumulation such as [[pleural effusions]] or [[ascites]], may be evident.
 
* [[Metabolic acidosis]], [[electrolyte]] disturbances, and abnormalities suggestive of organ dysfunction (including elevated [[aspartate transaminase]], [[alanine transaminase]], [[blood urea nitrogen]], and [[creatinine]]) may occur as a result of [[hypoperfusion|tissue hypoperfusion]] associated with prolonged [[shock]].
 
==Laboratory Diagnostics==
 
===Virology and Serology Tests===
 
* Although the diagnosis is generally clinical in endemic areas, a diagnosis of '''confirmed dengue infection''' is ''definitively'' 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>
 
{| style="border: 0px; font-size: 85%; margin: 3px;" align=center
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Definition}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Method<sup>†</sup>}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Interpretation<sup>†</sup>}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Sample Characteristics}}
|-
! style="padding: 5px 5px; background: #DCDCDC;" rowspan=6 | Confirmed Dengue Infection
! style="padding: 5px 5px; background: #DCDCDC;" | Viral isolation
| style="padding: 5px 5px; background: #DCDCDC;" | Virus isolated
| style="padding: 5px 5px; background: #DCDCDC;" rowspan=3 | Serum (collected at 1–5 days of fever) or necropsy tissues
|-
! style="padding: 5px 5px; background: #DCDCDC;" | Genome detection
| style="padding: 5px 5px; background: #DCDCDC;" | Positive RT-PCR or positive real-time RT-PCR
|-
! style="padding: 5px 5px; background: #DCDCDC;" rowspan=2 | Antigen detection
| style="padding: 5px 5px; background: #DCDCDC;" | Positive NS1 Ag
|-
| style="padding: 5px 5px; background: #DCDCDC;" | Positive immunohistochemical
| style="padding: 5px 5px; background: #DCDCDC;" | Necropsy tissues
|-
! style="padding: 5px 5px; background: #DCDCDC;" | IgM seroconversion
| style="padding: 5px 5px; background: #DCDCDC;" | From negative IgM to positive IgM in paired sera
| style="padding: 5px 5px; background: #DCDCDC;" rowspan=2 | Acute serum (days 1–5) and convalescent serum (15–21 days after first serum)
|-
! 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: #F5F5F5;" rowspan=2 | Probable Dengue Infection
! style="padding: 5px 5px; background: #F5F5F5;" | Positive IgM
| style="padding: 5px 5px; background: #F5F5F5;" | Positive IgM
| style="padding: 5px 5px; background: #F5F5F5;" rowspan=2 | Single serum collected after day 5
|-
! style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels
| style="padding: 5px 5px; background: #F5F5F5;" | High IgG levels by ELISA or hemagglutination inhibition assay (≥1280)
|}
 
&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>


[[Serology]] and [[PCR]] (polymerase chain reaction) studies are available to confirm the diagnosis of dengue if clinically indicated.
==Referemces==


==References==
{{reflist|2}}
{{Reflist|2}}


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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

The earliest abnormality in the complete blood count is decreased white cell count (leukopenia), which usually occurs during the febrile phase and should alert the physician to a high probability of dengue. The platelet count usually begins to drop when the temperature is returning to normal and is followed by findings indicative of plasma leakage such as elevated hematocrit level and hypoproteinemia. However, the extent of hemoconcentration may be affected by dilutional effect from excessive fluid administration or significant hemorrhage from the gastrointestinal tract and the white cell count may increase as a result of stress response. Serology and virology tests are used to confirm the diagnosis of dengue virus infection.

Laboratory Findings

Adapted from Dengue: guidelines for diagnosis, treatment, prevention and control. © World Health Organization 2009[1]

Complete Blood Count

  • Progressive leukopenia (≤5000 cells/mm3) is the earliest laboratory abnormality in dengue virus infeciton. It is usually followed by an abrupt decline in the platelet count to about 100,000 cells/mm3 before the emergence of signs of plasma leakage.
  • The hematocrit level normalizes or may be lower than the baseline due to the dilutional effect. The white cell count usually starts to rise soon after defervescence, while the recovery of the platelet count is typically delayed.

Metabolic Panel

Laboratory Diagnostics

Virology and Serology Tests

  • Although the diagnosis is generally clinical in endemic areas, a diagnosis of confirmed dengue infection is definitively 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 sera.
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: guidelines for diagnosis, treatment, prevention and control" (PDF).
  2. "Handbook for Clinical Management of dengue" (PDF).