Introduction
Dengue is an arbovirus disease caused by any one of four closely related viruses that do not provide cross-protective immunity; a person can be infected as many as four times, once with each serotype. Dengue viruses are transmitted from person to person by the Aedes aegypti mosquito in the domestic environment. Periodic epidemics have occurred in the Western Hemisphere for over 200 years. In the past 20 years, however, dengue transmission and frequency of epidemics have increased greatly in most tropical countries of the American region. As this has occurred, dengue hemorrhagic fever (DHF) has emerged and produced epidemics in many countries of the region.

Clinical Diagnosis
Dengue
Classic dengue fever is characterized by acute onset of high fever, frontal headache, retro-orbital pain, myalgias, arthralgias, nausea, vomiting, and often a maculopapular rash. In addition, many patients may notice a change in taste sensation. Symptoms tend to be milder in children than in adults, and the illness may be clinically indistinguishable from influenza, measles, or rubella. The disease manifestations can range in intensity from inapparent illness to the symptoms described. The acute phase of up to 1 week is followed by a 1- to 2-week period of convalescence which is characterized by weakness, malaise, and anorexia. Treatment emphasizes relief of these symptoms.

Dengue Hemorrhagic Fever/Dengue Shock Syndrome
During the first few days of illness, dengue hemorrhagic fever (DHF), a severe and sometimes fatal form of dengue, may resemble classic dengue or other viral syndromes. Patients with DHF may have fever lasting 2 to 7 days and a variety of nonspecific signs and symptoms. At about the time the fever begins to subside, the patient may become restless or lethargic, show signs of circulatory failure, and experience hemorrhagic manifestations. The most common of these manifestations are skin hemorrhages such as petechiae, purpura, or ecchymoses, but may also include epistaxis, bleeding gums, hematemesis, and melena. DHF patients develop thrombocytopenia and hemoconcentration, the latter as a result of the leakage of plasma from the vascular compartment. The condition of these patients may rapidly evolve into dengue shock syndrome (DSS), which, if not immediately corrected, can lead to profound shock and death. Advance warning signs of DSS include severe abdominal pain, protracted vomiting, marked change in temperature (from fever to hypothermia), or change in mental status (irritability or obtundation). Early signs of DSS include restlessness, cold clammy skin, rapid weak pulse, and narrowing of pulse pressure and/or hypotension. Fatality rates among those with DSS may be as high as 44%. DHF/DSS can occur in children and adults.

Treatment
Fortunately, DHF/DSS can be effectively managed by fluid replacement therapy, and if diagnosed early, fatality rates can be kept below 1%. It is very important, that physicians and other health care providers learn to recognize this disease. Once a person acquires dengue, the key to survival is early diagnosis and appropriate treatment.

To manage the pain and fever, patients suspected of having a dengue infection should be given acetaminophen preparations rather than aspirin, because the anticoagulant effects of aspirin may aggravate the bleeding tendency associated with some dengue infections.

Laboratory Diagnosis
Unequivocal diagnosis of dengue infection requires laboratory confirmation, either by isolating the virus or detecting specific antibodies. For virus isolation, a serum specimen should be collected as soon as possible or within 5 days after onset of symptoms. For serologic diagnosis, a convalescent-phase serum specimen obtained at least 6 days after onset of symptoms is required. These specimens may be tested for anti-dengue antibodies by enzyme-linked immunosorbent assay (ELISA). Acute-phase and convalescent-phase samples should be collected and sent to the state health department with a request to forward them to CDC for testing. Acute-phase samples for virus diagnosis may be stored indefinitely on dry ice (-60°C) or, if delivery can be made within 1 week, stored unfrozen in a refrigerator (4°C). Convalescent-phase samples should be sent in a rigid container without ice, if next-day delivery is assured. Otherwise they should be shipped on ice to avoid heat exposure during transit.

Epidemiology
A dengue epidemic requires the presence of 1) the vector mosquito (Aedes aegypti), 2) the virus, and 3) a large number of susceptible human hosts. Outbreaks may be explosive or progressive, depending on the density and susceptibility of the vector, the strain of dengue virus, the immune level in the human population, and the amount of vector-human contact. Dengue should be considered as the possible etiology where influenza, rubella, or measles is suspected in a dengue-receptive area, i.e., at a time and place where vector mosquito populations are abundant and active. In most countries of the Caribbean Basin, Aedes aegypti is abundant year-round. In the United States, this species is seasonally abundant only in Gulf and southeastern states, including parts of Texas, Louisiana, Mississippi, Alabama, Georgia, Florida, North Carolina, South Carolina, Tennessee, and Arkansas.

In 1985, a mosquito from Asia, Aedes albopictus, was found in the U.S. This species is now found in most states in the eastern half of the U.S. and limited areas of Brazil, Mexico, Guatemala, El Salvador, and the Dominican Republic. This species is a peridomestic mosquito and can also transmit dengue viruses although its preference for humans and its density in urban areas are not as great as that of Aedes aegypti.

Predicting epidemics of dengue and DHF is difficult but, as noted previously, the frequency of epidemic disease has increased significantly in the past 20 years. This is likely due to increased air travel, which provides the ideal mechanism for dengue viruses to be carried around the world into areas where Aedes aegypti occurs. This rapid movement of travelers around the world is also the reason that dengue infections may be detected in virtually any part of the world.

If a dengue-like illness is observed in a person in the continental United States who has recently traveled to a tropical area, a blood specimen, associated clinical information, and a brief travel history should be sent to the state public health laboratory with a request that the specimen be tested for dengue there or at CDC. If that is not possible, contact the Centers for Disease Control and Prevention at the address below.

In Puerto Rico and the U.S. Virgin Islands, specimens and clinical information can be sent through the respective island department of health or directly to the address below.

For further Information, contact:

Dengue Branch
Centers for Disease Control and Prevention
1324 Calle Cañada
San Juan, Puerto Rico 00920-3860
Tel. (787) 706-2399; Fax (787) 706-2496