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Focus On: Dengue Fever

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ACEP News
June 2008

By José G. Cabañas, MD, and Jorge Falcón-Chevere, MD

Learning Objectives

After reading this article, the physician should be able to:

  • Discuss the current epidemiological trends in dengue transmission.
  • Identify the signs and symptoms of dengue fever.
  • Review current treatment modalities for patients with dengue fever and dengue hemorrhagic fever (DHF).
  • Discuss the clinical predictors for dengue shock syndrome and DHF.

Dengue fever is a common, worldwide, acute viral illness. The infection typically presents as a severe flu-like illness and may affect children and adults.

It is usually a nonfatal disease, but it may progress to a severe form know as dengue hemorrhagic fever (DHF). It is well known that the disease is transmitted through the bite of infected mosquitoes of the genus Aedes. Dengue is common in, but not exclusive to, tropical areas. The disease may be seen in subtropical territories as well.

The World Health Organization (WHO) considers dengue a major international health threat. The ongoing impact is staggering. It is estimated that there are more than 100 million cases of dengue worldwide every year.1

In recent decades, dengue has become a growing world pandemic. Currently, 2.5 billion people around the world live in areas at risk of the disease.2 There have been several reported epidemics of dengue fever in the Caribbean, Asia, and North and South America.

Because the disease is present all over the world, it is possible that travelers may come to the United States from places where there is a dengue epidemic. Emergency physicians must be able to recognize dengue and understand the clinical strategies to treat it.

What is Dengue?

Dengue fever is an arboviral illness. The disease, also known as "break-bone" fever, is transmitted by infected mosquitoes and characterized by several major clinical manifestations: high fever, rash, retro-orbital headache, joint pain, and back pain. Dengue is among the most important globally re-emerging infectious diseases.3

The disease is caused by four virus serotypes (DEN-1, DEN-2, DEN-3, or DEN-4). Aedes aegypti is the traditional vector. However, other Aedes species, such Aedes albopictus, may be involved in disease transmission, especially in the Western Hemisphere. This mosquito is present in 36 states in the United States.4

Usually, people get infected after being bitten by a contaminated mosquito. It is important to note that once a person is infected with a specific virus serotype, that person will develop lifelong immunity. However, people may develop a second dengue infection through another virus serotype. This second exposure is considered high risk for developing the severe form of dengue, DHF.

Traditionally, physicians have known dengue as a disease exclusively of tropical areas such as the Caribbean. Many people in the United States do not understand the importance of such a disease.

In 2001, a dengue epidemic was reported in Hawaii. This was the first outbreak in Hawaii in more than 50 years. In September 2001, 1,644 patients with dengue-like illness were evaluated and 122 tested positive for the disease. No DHF or shock syndrome was reported.5 Furthermore, in 2005 a case of DHF without travel history was reported in Brownsville, Texas. An investigation led to retrospective discovery of 24 cases of dengue, two of them without travel.6

In a JAMA report, a Centers for Disease Control and Prevention editorial states that all dengue serotypes have been present along the Mexican border and south Texas. These reports, and the fact that mosquito vectors responsible for transmission of the disease are present in a number of states and territories, including Puerto Rico,7 clearly affirm that there is a presence of dengue in the United States.

Dengue transmission is present all year long in Puerto Rico, with a higher incidence from July to January.8 It has had an impact of approximately $250 million in health care costs during the last 10 years.

The number of cases that are not reported may be significant. Some patients may not feel sick enough to seek care. If patients don't request care and the illness subsides, the case doesn't get reported. It is important for emergency physicians to understand the disease, because most ill patients will seek care in a nearby emergency department.

Dengue fever can be prevented. The most essential public health intervention is the implementation of vector control. Ideally, all stagnant water should be eliminated. Proper methods for disposal of solid waste are crucial. The goal is to prevent mosquito breeding. The use of spray insecticides is recommended, but be aware of their safety profile. No vaccine is currently available, but clinical research continues in this area.

How to Diagnose Dengue Fever

The diagnosis of dengue fever relies on good clinical skills and judgment. Patients may arrive in the emergency department with nonspecific complaints. Most times, the diagnosis will be suspected during the gathering of the history. It is imperative to ask about recent travel, rash, bleeding, and constitutional symptoms. The key is to obtain a good history and suspect the diagnosis early.

Typically, the disease has a high fever with duration of 2-7 days. Emergency physicians must be able to recognize and intervene early with the patient who may be at risk of developing shock or hemorrhagic complications. Usually, the disease will be characterized by fever, retro-orbital headache, arthralgias, myalgias, and sometimes vomiting.9

Patients also present with a variety of rashes, including a maculopapular type. Patients may also have petechiae and conjunctival and pharyngeal infection. Clinically, patients may be dehydrated and febrile. During initial evaluation, a complete blood count should be performed, with special attention given to platelets, hematocrit, and white blood cells. A hematocrit level elevated more than 20% above normal suggests hemoconcentration, especially after treatment with intravenous fluids. This finding precedes shock.

In addition, thrombocytopenia and leukopenia are common in dengue patients. The WHO states a platelet count less than 100,000 indicates a risk for DHF, although a decreased platelet count does not necessarily mean the case will evolve to the hemorrhagic disease. In the electrolyte panel, hyponatremia is the most common abnormality in dengue fever.

During the initial examination, a chest x-ray should be obtained, because pleural effusions may be present, especially on the right side. The use of bedside ultrasound may be an option for lung exam. Other laboratory tests or imaging studies should be ordered as needed.

The definitive diagnosis of dengue is through laboratory testing, which is not readily available in the emergency department. Dengue testing is utilized for epidemiological purposes only, and it will not change current treatment strategies, especially in the emergency department.

In addition, emergency physicians should be familiar with the tourniquet test. The tourniquet test (also known as the Rumpel-Leede test) is used as an additional tool to diagnose DHF. Inflate a blood pressure cuff at a point between the systolic and diastolic pressure for 4-5 minutes. If the patient develops more than 20 petechiae per square inch, the tourniquet test is considered positive. For practical purposes, the emergency physician may draw a 2.5 cm circle on the arm and count the petechiae. A count of more than five petechiae is abnormal.

How to Treat Dengue

There is no specific medication for the treatment of this disease. Dengue fever, like many other viral illnesses, is a self-limited infectious condition, and most of the time it requires only supportive care.

Recommendations include rest, oral hydration, analgesics, and antipyretics. Treat the patient with acetaminophen for fever, and avoid the use of nonsteroidal anti-inflammatory drugs and aspirin because of the increased risk of bleeding in the presence of thrombocytopenia.

Hematocrit and platelets must be monitored if dengue fever is suspected. Monitoring should start after the third day of illness and continue until the second day after resolution of fever. If improvement is documented and no complications are evident, monitoring can be done in an outpatient setting.

When moderate to severe dehydration and hemoconcentration (defined as hematocrit increase greater than 20%) are evident, the intravascular volume deficit must be corrected using isotonic fluids. Normal saline solution (20 mL/kg boluses) can be administered every 15 minutes as needed. If improvement does not result despite aggressive hydration, or if hemoconcentration is present, consider internal bleeding that may require a blood transfusion. If the patient is coagulopathic, treat with fresh frozen plasma.

Intravenous fluids can be stopped once the patient is hemodynamically stable, intravascular volume is restored, and hematocrit reaches 40%, to avoid fluid overload.

The patient can be discharged from the hospital once he or she is afebrile, tolerating oral ingestion, and experiencing no respiratory difficulty, and has a platelet count above 50,000 per microliter, hematocrit returned to baseline, and normal renal function.

Dengue Hemorrhagic Fever/Shock Syndrome

Dengue hemorrhagic fever was first recognized and described in the Philippines in 1953. The incidence of DHF has increased in Latin America and the Caribbean and throughout the Western Hemisphere during the past 2 decades.10 DHF is the most severe manifestation of dengue fever. The WHO states that the incidence of DHF is around 500,000 cases, with 22,000 deaths every year, especially children. Prior to 1970, only nine countries had reported cases of DHF. Today, that number has multiplied four times and is expected to continue to rise.

The WHO has specific clinical criteria for the diagnosis of DHF (see sidebar). Dengue hemorrhagic fever is caused by the same virus as dengue. It should be suspected in patients with hemorrhagic signs, such as mucosal or gastrointestinal bleeding, petechiae, ecchymoses, or purpura, and thrombocytopenia.

Dengue shock syndrome is characterized by the presence of dengue hemorrhagic criteria, as well as hypotension, tachycardia, cold clammy skin, and altered mental status. Currently, mortality is less than 1%.

Summary

Dengue fever is a global epidemic that is currently increasing its presence in the United States. The disease is characterized by high fever, 2- to 7-day evolution, rash, retro-orbital headache, joint pain, and back pain. Emergency physicians should recognize key clinical findings that may predict hemorrhagic complications and shock. Hemoconcentration, a positive tourniquet test, and signs of hemodynamic instability are some findings that may portend an adverse outcome such as DHF and/or dengue shock syndrome.

Criteria for Dengue Hemorrhagic Fever

The following must all be present:

arrow redFever, or history of acute fever, lasting 2-7 days, occasionally biphasic.

arrow redHemorrhagic 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.
  • Melena or hematemesis.

arrow redThrombocytopenia < 100,000/mm3)

arrow redEvidence of plasma leakage because of increased vascular permeability, manifested by at least one of the following:

  • An increase in the hematocrit > 20% above average for age, sex, and population.
  • A decrease in the hematocrit following volume replacement treatment > 20% of baseline.
  • Signs of plasma leakage such as pleural effusion, ascites, and hypoproteinemia.

Source: World Health Organization

References

  1. Centers for Disease Control and Prevention. Dengue Fact Sheet, 2005, p. 1-3.
  2. World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment, prevention and control. 2nd ed. Geneva, Switzerland: World Health Organization, 1997. Available at www.who.int/csr/resources/publications/dengue/Denguepublication/en/.
  3. Morens D.M., Sather G.E., Gubler D.J., Rammohan M., Woodall J.P. Dengue shock syndrome in an American traveler. Am. J. Trop. Med. Hyg. 1987;36:424-6.
  4. Benedict M.Q., Levine R.S., Hawley W.A., Lounibos L.P. Spread of the tiger: global risk of invasion by the mosquito Aedes albopictus. Vector Borne Zoonotic Dis. 2007;7:76-85.
  5. Effler P., Pang L., Kitsutani P., et al. Dengue fever, Hawaii, 2001-2002. Emerg. Infect. Dis. [serial on the Internet]. 2005 May. Available at www.cdc.gov/ncidod/EID/vol11no05/04-1063.htm.
  6. Centers for Disease Control and Prevention. Dengue Hemorrhagic Fever--U.S.-Mexico Border, 2005. MMWR 2007;56:785-9.
  7. Rigau-Perez J.G., Laufer M.K. Dengue-related deaths in Puerto Rico, 1992-1996: diagnosis and clinical alarm signals. Clin. Infect. Dis. 2006;42:1241-6.
  8. Centers for Disease Control and Prevention. Dengue outbreak associated with multiple serotypes--Puerto Rico, MMWR 1998;47:952-6.
  9. Kalayanarooj S., Vaughn D.W., Nimmannitya S., et al. Early clinical and laboratory indicators of acute dengue illness. J. Infect. Dis. 1997;176:313-21.
  10. Gubler D.J. Dengue and dengue hemorrhagic fever. In: Guerrant R., Walker D., Weller P., eds. Tropical infectious diseases. 2nd ed. Philadelphia: Elsevier;2006:813-22.
  11. Centers for Disease Control and Prevention. Underdiagnosis of dengue--Laredo, Texas, 1999. MMWR 2001;50:57-9.
  12. Price D., Dengue Fever. Emedicine Web MD. Emergency Medicine/Infectious Diseases. January 2008. www.emedicine.com/emerg/topic124.htm.

Contributors

Dr. Cabañas is academic chief resident in the Emergency Medicine Program at the University of Puerto Rico. Dr. Falcón-Chevere is associate program dictor of the Emergency Medicine Program at the University of Puerto Rico. Medical Editor Dr. Robert C. Solomon is an attending emergency physician at Trinity Health System in Steubenville, Ohio, and clinical assistant professor of emergency medicine at the West Virginia School of Osteopathic Medicine.

Disclosures

In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards and American College of Emergency Physicians policy, contributors and editors must disclose to the program audience the existence of significant financial interests in or relationships with manufacturers of commercial products that might have a direct interest in the subject matter.

Dr. Cabañas, Dr. Falcón-Chevere, and Dr. Solomon have disclosed that they have no significant relationships with or financial interests in any commercial companies that pertain to this educational activity.

"Focus On: Dengue Fever" has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME).

ACEP is accredited by the ACCME to provide continuing medical education for physicians. ACEP designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he or she actually spent in the educational activity.

"Focus On: Dengue Fever" is approved by ACEP for one ACEP Category 1 credit.

Disclaimer

ACEP makes every effort to ensure that contributors to College-sponsored programs are knowledgeable authorities in their fields. Participants are nevertheless advised that the statements and opinions expressed in this article are provided as guidelines and should not be construed as College policy.

The material contained herein is not intended to establish policy, procedure, or a standard of care. The views expressed in this article are those of the contributors and not necessarily the opinion or recommendation of ACEP. The College disclaims any liability or responsibility for the consequences of any actions taken in reliance on those statements or opinions.

Dengue Fever CME

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