Controversies in dengue pathogenesis

Figures & data

Figure 1. WHO 2009 suggested dengue case classification and levels of severity9

Box 1 WHO 1997 case definitions for DF, DHF and DSS55

DF	Probable
	• An acute febrile illness with two or more of the following manifestations: headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations and leucopenia
	and
	• Supportive serology (a reciprocal haemagglutination-inhibition antibody titre ⩾1280, a comparable IgG enzyme-linked immunosorbent assay (ELISA, see chapter 455) titre or a positive IgM antibody test on a late acute or convalescent-phase serum specimen)
	or
	• Occurrence at the same location and time as other DF cases
	Confirmed
	• A case confirmed by one of the following laboratory criteria:
	– Isolation of the dengue virus from serum/autopsy samples
	– At least a four-fold change in reciprocal IgG/IgM titres to one or more dengue virus antigens in paired samples
	– 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)
	Reportable
	• Any probable or confirmed case should be reported
DHF	For a diagnosis of DHF, a case must meet all four of the following criteria:
	• Fever or history of fever lasting 2–7 days, occasionally biphasic
	• A haemorrhagic tendency shown by at least one of the following: a positive tourniquet test*; petechiae, ecchymoses or purpura; bleeding from the mucosa, gastro-intestinal tract, injection sites or other locations; haematemesis or melaena
	• Thrombocytopenia [⩽100,000 cells/mm^3 (100×10^9/L)]^†
	• Evidence of plasma leakage due to increased vascular permeability shown by: an increase in the haematocrit ⩾20% above average for age, sex and population; a decrease in the haematocrit after intervention ⩾20% of baseline; signs of plasma leakage such as pleural effusion, ascites or hypoproteinaemia
DSS	For a case of DSS, all four criteria for DHF must be met, in addition to evidence of circulatory failure manifested by:
	• Rapid and weak pulse
	and
	• Narrow pulse pressure (<20 mmHg or 2·7 kPa)
	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 cm² (1 inch) 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.

^† This number represents a direct count using a phase-contrast microscope (normal is 200,000–500,000/mm³). In practice, for outpatients, an approximate count from a peripheral blood smear is acceptable. In normal persons, 4–10 platelets per oil-immersion field (100×; the average of the readings from 10 oil-immersion fields is recommended) indicates an adequate platelet count. An average of 3 platelets per oil-immersion field is considered low (i.e. 100,000/mm³).

World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: WHO, 2009.

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World Health Organization. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, 2nd edn. Geneva, Switzerland: WHO, 1997.

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