Dengue fever has been on the rise all over the world, with more cases than usual in many countries, including the United States. 2024 was a “banner year” for dengue, with up to 400 million cases worldwide and up to a 2000% increase in cases in different regions compared to the year beforehand. While most cases are mild, severe cases of dengue fever can lead to death. It’s important for front-line clinicians who see sick patients in ambulatory settings to be familiar with how dengue fever presents, to manage it, and to predict if a patient may develop severe disease and, therefore, need a higher level of care.
What is Dengue fever?
Dengue fever is a mosquito-borne viral illness and the leading cause of arthropod-borne viral illness worldwide. It has two illuminating nicknames: “Break bone fever,” which gives a helpful clue about what symptoms to expect, and “7-day fever,” which provides insight into the duration of symptoms. Not surprisingly, we see dengue fever the most in areas mosquitoes love: warm, humid, damp settings and crowded urban areas.
The Dengue virus
The dengue virus is a single-stranded RNA virus in the Flavivirus genus, including Zika and West Nile viruses. There are four serotypes of the dengue virus. If a person becomes infected with one serotype, they will have lifelong immunity to that specific serotype but not the other three serotypes. A repeat infection with a different serotype is a risk factor for developing severe disease. The typical incubation period is around four to seven days, and the duration of symptoms is around three to ten days - hence the “7-day fever” nickname. The virus can be transmitted vertically from a pregnant patient to a fetus.
A wide range of symptoms
The presentation of dengue fever can range from no symptoms in up to 75% of people to severe disease, including hemorrhage and shock. It’s important (and reassuring) for us to know that the vast majority of cases are mild and self-limiting. Fewer than 5% of cases evolve into severe dengue. Fatality estimates vary, but up to 20% of patients with severe dengue may die if not identified and treated early, especially younger children.
Mild dengue
When dengue fever is mild, it has many symptoms associated with a typical viral infection: fever, malaise, and myalgias. Some defining features include higher patient temperatures, such as 40 degrees Celsius or 104 degrees Fahrenheit, and severe muscle spasms and joint pain leading to its “breakbone fever” nickname. There are three phases of illness with dengue fever:
- The febrile phase: Up to seven days of high fever, myalgias, malaise, and perhaps some nausea and vomiting
- The critical phase: Lasts around one to two days. The fever breaks, and now there is increased capillary permeability. If left untreated, mild dengue can become severe dengue.
- The recovery phase: A gradual return to normal.
What about severe dengue?
Patients who become sick in the second, critical phase of the illness develop increased microvascular permeability, leading to several potentially catastrophic sequellae: hemorrhage, large fluid shifts leading to pleural effusions and ascites, shock, altered mental status, and end-organ damage. These are known as “warning signs” in the dengue literature, along with hepatomegaly on exam and a new decrease in platelet count on labs. A patient demonstrating any of these signs or symptoms must be sent to the nearest emergency department immediately.
Risk factors for severe disease
People at greater risk for more severe disease are children, adults over the age of 40, pregnant patients (especially in the third trimester), and patients with comorbid asthma, diabetes mellitus, or sickle cell disease. Some literature points to infection with a second serotype of the dengue virus, after a patient has already recovered from a first infection with a different serotype, as a risk factor for severe illness.
Making the diagnosis
As with so many illnesses, our history, physical exam, and lab data will help us make the diagnosis. A specific question to ask our patients is if they have traveled to or live in a dengue-endemic area, such as the Caribbean, Central or South America, Southeast Asia, or the Pacific Islands.
Per the CDC’s case definition for dengue fever, the patient must have a fever plus two of the following symptoms:
- Myalgias
- Arthralgias
- Nausea
- Vomiting
- Rash
- Leukopenia
- Tourniquet test positive
- Any of the aforementioned warning signs for severe disease, such as fluid shifts, bleeding, low platelet count
An interesting feature to test for is the “Tourniquet Test Sign,” which is included within both the WHO and CDC case definitions for dengue fever. This test can be performed in virtually any setting, including resource-limited ones. To perform this test:
- Inflate a BP cuff on the upper arm to a number of millimeters of mercury about halfway between the patient’s systolic and diastolic pressures
- Hold this pressure steady for 5 minutes
The test is considered positive if there are >10-20 petechiae per square inch on the skin of the forearm.
When it comes to laboratory data, every patient should have a CMP and CBC drawn to look for liver function test abnormalities, elevated hemoglobin and hematocrit, and leukopenia.
Serologies
More specific testing for dengue does exist, though it may not be available in every practice setting. The preferred test is a Nucleic Acid Amplification Test, which detects viral RNA in the serum. If this test is positive, the diagnosis is confirmed. If it’s negative, dengue has not been ruled out, and we need to test for IgM antibodies as well. The WHO 2022 guidelines have a thorough algorithm for which serologies to order based on the duration of symptoms and travel location.
Treatment
The treatment of dengue fever is largely supportive. If the disease is mild, we can encourage the patient to drink lots of fluids, take acetaminophen, and be on the lookout for any worsening of symptoms so that they know when to seek a higher level of care. In a dream world, they are following up with us every day so we can ensure their symptoms are getting better and not worse.
Importantly, we should discourage patients from using aspirin or NSAIDs, given the concern for potential bleeding. If our patient needs hospitalization, the mainstay of treatment is supportive in this setting as well, including IV fluids, packed red blood cell transfusions with careful attention to the patient’s volume status, and treating end-organ damage and shock.
An ounce of prevention…
…is indeed worth a pound of cure when it comes to dengue fever. In endemic areas, some incredibly helpful measures to prevent the spread of dengue include:
- Netting around beds
- Applying insecticide to curtains
- Using mosquito repellents on body and clothing
- Wearing long-sleeved shirts and pants
- Covering sources of standing water when possible
Interestingly, if a person is infected, we should encourage them to protect against further mosquito bites so that these new mosquitoes don’t transmit dengue to other people!
Is there a vaccine?
Yes and no. CYD-TDV (Dengvaxia ®) is the first licensed live tetravalent dengue vaccine, approved for use in 20 endemic countries and the only vaccine approved in the U.S. However, the manufacturer, Sanofi-Pasteur, announced in May 2024 that it would stop manufacturing this vaccine due to inadequate demand globally. Other vaccines are in the pipeline, but none are approved for use in the U.S. yet.
Do we need to tell anyone if a patient has dengue?
Dengue fever is a nationally notifiable disease per the CDC, so we should report positive cases to our local or state health departments.
Dengue fever has been on the rise throughout 2024, and it is reasonable to expect this trend to continue. With climate change leading to higher temperatures and longer rainy seasons worldwide, along with urbanization leading to more crowded living conditions and global travel bringing us all into one big community, front-line clinicians should be prepared to think about dengue fever in a patient with fever and myalgias, ask about recent travel and risk factors, and be able to diagnose and treat this increasingly common mosquito-borne viral illness.
For more, check out our Primary Care RAP episode, “DangIt, Dengue! Dengue Fever On the Rise.”
