Dengue fever classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.

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 haematocrit 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

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:

• 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:

Dengue ± Warning Signs Dengue (live in/traveled 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 haematocrit 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