The clinical manifestations of dengue infection include a wide spectrum of syndromes, from asymptomatic infection or minimally symptomatic disease to severe illness and sometimes death. There are at least four categories of disease severity: undifferentiated fever, dengue fever (the classic "breakbone fever"), DHF (which includes dengue shock syndrome [DSS]), and "unusual manifestations," including severe gastrointestinal hemorrhage, hepatic failure, cardiomyopathy, and encephalopathy or encephalitis.
Dengue fever is characterized by sudden onset of fever, frontal headache, retro-orbital pain, general malaise, generalized myalgias and arthralgias, nausea, vomiting, and rash. One characteristic feature of dengue fever is the severity of body pain, which can be incapacitating and explains why the disease is sometimes called breakbone fever. Other nonspecific symptoms may be present, such as anorexia, mild conjunctival injection, diarrhea, pruritus, and changes in taste sensation. Leukopenia and thrombocytopenia are frequent, and liver enzymes may be mildly elevated. The febrile period lasts 5-7 days, but the patient may remain symptomatic for several more days. The disappearance of fever correlates with the disappearance of viremia. Convalescence may be marked by a period of lassitude. There have been reports of severe depression after the acute period of illness (4,5).
Skin eruptions may be more common in primary infections (6). The rash may be present in different ways, including flushing of the face, neck, or chest during the febrile period; an erythematous or maculopapular rash after the third or fourth day; a confluent petechial rash with round pale areas of normal skin; or a combination of these. Less frequent than rash but not rare are mild hemorrhagic manifestations, such as petechiae, epistaxis, gingival hemorrhage, gastrointestinal hemorrhage, and microscopic hematuria. Hemorrhage is more commonly associated with a platelet count below 50,000/mm3, although hemorrhage does not necessarily occur with a low platelet count (7). The tourniquet test, a method for the assessment of capillary fragility or platelet function, may be positive in more than one-third of patients with dengue fever. To perform the tourniquet test, the blood pressure cuff is inflated to a point midway between the systolic and diastolic blood pressures and maintained for 5 minutes. After deflating the cuff and waiting for the skin to return to its normal color, the number of petechiae in a 1-in.2 area on the ventral surface of the forearm is counted. Twenty or more petechiae in the patch constitutes a positive test (8).
Clinical findings alone are not very helpful for distinguishing dengue fever from other febrile illnesses, such as influenza, measles, rubella, mild leptospirosis, typhoid, or malaria. If symptoms start more than 2 weeks after the patient has left a dengue-endemic area or if the fever lasts more than 2 weeks, dengue can probably be ruled out.
Several risk factors have been associated with severe disease, including virus strain, the presence of preexisting anti-dengue antibodies, factors related to host genetics, and age. The risk for developing DHF is higher in locations with two or more virus sero-
types circulating simultaneously, especially when the second infecting serotype is of Southeast Asian origin (9). The presence of circulating anti-dengue antibodies, acquired actively (by prior infection) or passively (by transplacental passage of maternal dengue immunoglobulin [Ig] G antibody in infants) is the most frequently reported of the multiple contributing causes of a severe response to dengue (10,11).
Several studies have demonstrated the transplacental passage of anti-dengue IgG antibodies to the fetus (12-17). Infants with maternal antibodies may be at risk of developing DHF/DSS (18).
The course of the disease provides warnings of an increased probability of DHF. The first (and easiest) information for the physician to ascertain is the time elapsed since the onset of symptoms. DHF/DSS usually develops around days 3-7 of illness, near the time of defervescence, a period when intensified observation of the patient should occur. A progressive drop in platelet count and a concurrent increase in hemat-ocrit are indicators of the onset of excessive capillary leakage and increased probability of impending shock. The less-frequent but severe complications of dengue infection (abrupt gastrointestinal hemorrhage, hepatic failure, cardiomyopathy, and encephal-opathy or encephalitis) may not follow the course of DHF/DSS and are associated with a high risk of death.
Dengue Hemorrhagic Fever/Dengue Shock Syndrome
DHF is defined by the World Health Organization as an acute febrile illness with minor or major hemorrhage, thrombocytopenia of 100,000 platelets/mm3 or less, and evidence of excessive plasma leakage documented by hemoconcentration (hematocrit increased by 20% or more or decreased by the same amount after intravenous fluid therapy), evidence of pleural or other effusions, or hypoalbuminemia or hypoproteine-mia. The severity of DHF is classified into four grades, all of which must also fulfill the above criteria:
Grade I: A hemorrhagic manifestation is provoked, that is, a positive tourniquet test. Grade II: The patient has spontaneous hemorrhage, the most common is skin hemorrhages. Grade III: The patient shows signs of circulatory failure, manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less), or hypotension, with the presence of cold, clammy skin and restlessness.
Grade IV: Profound shock with undetectable blood pressure and pulse.
DHF grades III and IV are considered DSS, the most severe presentation of dengue infection, which is characterized by rapid onset of shock, generally occurring near the time of defervescence. Prognosis depends on the anticipation and early recognition and treatment of shock, which may have a short duration but is life-threatening. In hospitals with experience in DSS management, the case fatality rate in DHF can be as low as 0.2%. Once shock has set in, the fatality rate may be over 10% (19).
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