Tuesday, May 7, 2013

Dengue Classification: WHO 1997, WHO 2009, WHO 2012

World Health Organization 1997 classification:

According to WHO Dengue guidelines 1997, Dengue virus infections can be asymptomatic or symptomatic that could be classified into undifferentiated fever, dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).

Dengue fever:

The symptoms of DF frequently depend on the age of the patient.  Undifferentiated febrile disease, often with maculopapular rash is often seen in infants and young children.  Mild febrile syndrome or classic features of DF such as abrupt onset of high fever, severe headache, retro-orbital pain, muscle, bones or joint pain, nausea and vomiting and rash is more common observed in older children and adults. Lab abnormalities such as leucopenia and thrombocytopenia can be observed. Petechiae is not uncommon and bleeding complications such as epistaxis, gingival bleeding, gastrointestinal bleeding, hematuria, and menorrhagia can also be observed in DF is some epidemics.

In order to differentiate DF with unusual bleeding and DHF , we need to rely on lab abnormality which is hemoconcentration.

The case definition for DF:

Given the variability in the clinical illness associated with dengue infection, it is not appropriate to adopt a detailed clinical definition of dengue fever. Rather, the need for laboratory confirmation is emphasised.
The following classifications are proposed:

• Probable – an acute febrile illness with two or more of the following manifestations:

·      Headache
·      Retro-orbital pain
·      Myalgia
·      Arthralgia
·      Rash
·      Hemorrhagic manifestation
·      Leucopenia 
·      Supportive serology (a reciprocal haemagglutination-inhibition antibody titre 1280, a comparable IgG enzyme-linked immunosorbent assay (ELISA) titre or a positive IgM antibody test on a late acute or convalescent-phase serum specimen)
·      Occurrence at the same location and time as other confirmed cases of dengue fever
Confirmed – a case confirmed by laboratory criteria (see below).
Reportable – any probable or confirmed case should be reported.

Laboratory criteria for confirmation of dengue fever are: 
·      Isolation of the dengue virus from serum or autopsy samples:or
·    Demonstration of a fourfold or greater change in reciprocal IgG or IgM antibody titres to one or more dengue virus antigens in paired serum samples; or

· Demonstration of dengue virus antigen in autopsy tissue, serum or cerebrospinal fluid samples by immunohistochemistry, immunofluorescence or ELISA;
· Detection of dengue virus genomic sequences in autopsy tissue serum or cerebrospinal fluid samples by polymerase chain reaction (PCR).

Dengue hemorrhagic fever (DHF):

 There are four major clinical manifestations in typical case of DHF: high fever, hemorrhagic phenomena, and often hepatomegaly and circulatory failure. In term of lab findings, we could see moderate to marked thrombocytopenia with concurrent hemoconcentration. Plasma leakage is the key to differentiate between DF and DHF that is manifested by hemoconcentration, a serous effusion and hypoproteinemia.

            Manifestations in children could be somehow different. They may present with sudden rise in temperature accompanied by facial flush and other symptoms such as anorexia, vomiting, headache, muscle or bone and joint pain. Other symptoms and signs that might be observed include sore throat, injected pharynx, mild conjunctival injection, epigastric discomfort, right costal margin tenderness and generalized abdominal and febrile convulsion.

Case definition for dengue hemorrhagic fever:

.    Fever, or history of acute fever, lasting 2–7 days, occasionally biphasic.
.    Haemorrhagic 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.
·      haematemesis or melaena
.    Thrombocytopenia (100,000 cells per mm3 or less).
.    Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following:
·      a rise in the HCT equal to or greater than 20% above average for age, sex and population;
·      a drop in the HCT following volume-replacement treatment equal to or greater than 20% or baseline;
·      signs of plasma leakage such as pleural effusion, ascites and hypoproteinaemia

Dengue shock syndrome:   
Case definition for dengue shock syndrome:
All of the above four criteria for DHR must be present plus, evidence of circulatory failure manifested by:

·          Rapid and weak pulse, and
·          Narrow pulse pressure (<20 kpa="" mmhg="" o:p="">

Or manifested by:

·          Hypotension for age, and
·           Cold, clammy skin and restlessness

Grade I: Fever accompanied by non-specific constitutional manifestation. The only hemorrhagic manifestation is positive tourniquet test and or easy bruising.

Grade II: Spontaneous bleeding, in addition to the manifestation of Grade I patients, usually in the form skin or other hemorrhages.

Grade III:  Circulatory failure manifested by a rapid, weak pulse and narrowing of pulse pressure or hypotension with the presence of cold, clammy skin and restlessness.

Grade IV: Profound shock with undetectable blood pressure or pulse.

Limitation in WHO 1997:
It has been observed that the existing WHO classification scheme has several limitations as the disease has spread to new regions and infected older age groups. For example:
.    Dengue with shock without fulfilling all the 4 criteria for DHF
. There have been many case reports of patients with severe dengue with shock who do not fulfill all the 4 criteria for DHF. These patients would have been classified as dengue fever if the WHO criteria are to be strictly applied.
.    Severe organ impairment
: Patients with severe organ impairment such as liver, respiratory, cardiac and brain dysfunction are not captured as having severe disease based on the existing classification.
.    Plasma leakage in DHF. 
The requirement of 20% increase in HCT as one of the evidence of plasma leakage is difficult to fulfill due to several issues: Baseline HCT is not available in most patients and therefore, the interpretation of plasma leak can only be made retrospectively, early fluid administration may affect the level of HCT, bleeding will affect the HCT level.
.    The existing classification scheme is often not useful for disease management because the correct disease classification can only be made towards the end of the illness.

World Health Organization 2009 classification:

This suggested classification is based on severity level. It has a high potential for being of practical use in clinicians’ decision in term of where and how intensively the patients should be observed and treated, more consistent reporting in the national and international surveillance system, and as end-point measure in dengue vaccine and drug trials. This model has been suggested by an expert group (Geneva, Switzerland, 2008) and was tested in 18 countries by comparing its performance in practical settings to the WHO  1997 case classification.
In this classification, dengue is divided into dengue with or without warning signs and severe dengue.

World Health Organization 2012 classification:

.     Basically, this classification is similar with WHO 2009. Since many countries have started to use this new suggested model, so the new WHO 2012 Dengue guideline has adopted this system

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