Dengue Virus: definition of the disease

Dengue fever occurs in most tropical countries, including Africa, Asia, and Central and South America. However, with the warming climate, dengue is spreading to new areas, including parts of southern Europe. Reports of locally transmitted cases have emerged in several southern European countries in recent years.

In the United States, dengue fever is most commonly encountered in travelers returning from tropical or subtropical regions. Locally transmitted cases have been reported in Florida, Texas, and Hawaii due to the presence of the Aedes mosquito, which spreads the virus.

With symptoms ranging from mild to severe, including dengue hemorrhagic fever and dengue shock syndrome, the quest for an effective vaccine has been both urgent and complex due to the virus’s four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).

Dengue Fever Symptoms

Dengue fever is typically mild and may include one or more of the following symptoms:

• High fever with chills and sweating
• Severe headache
• Muscle and joint pain
• Bloodshot eyes

After a few days of illness, a measles-like rash may appear. At a later stage, pinpoint skin hemorrhages can develop, especially on the tops of the feet, hands, and in the armpits. The disease usually runs its course in about a week, from onset to recovery.

A small percentage of cases progress to hemorrhagic dengue, which becomes severe after an initial improvement. This is a much more serious condition characterized by internal bleeding, including from the gastrointestinal tract, which can be life-threatening. Early symptomatic treatment is crucial for a good prognosis. It is rare for tourists who contract dengue fever abroad to develop the hemorrhagic form of the disease.

Dengue fever comes in different types, and each type causes specific symptoms. Let’s look at each type to understand what happens in your body when you get infected.

1. Classical Dengue Fever

This is the most common and usually mildest form of dengue. When someone gets classical dengue, they usually start feeling sick about 4-7 days after being bitten by an infected mosquito. The main symptoms include:

• A sudden high fever that can reach 104°F (40°C)
• Severe headache, especially behind the eyes
• Strong muscle and joint pains (this is why it’s called “breakbone fever”)
• Feeling very tired
• Loss of appetite
• Sometimes a mild rash
• Mild bleeding from gums or nose

These symptoms typically last about a week, and most people recover completely with rest and proper hydration.

2. Sever Dengue

This type is more serious than classical dengue fever. It happens when the infection starts causing more severe problems in your body. The warning signs usually appear after the fever starts going down, around day 3-7 of the illness. You’ll notice the usual dengue symptoms plus these additional warning signs:

• Severe stomach pain
• Throwing up repeatedly
• Bleeding from gums or nose that’s harder to stop
• Feeling very tired or restless
• Rapid breathing
• Cold, clammy skin
• Small spots of bleeding under the skin

If someone shows these warning signs, they need immediate medical attention because the disease might be getting worse.

3. Dengue Hemorrhagic Fever (DHF)

This is the most dangerous type of dengue fever. It used to be called dengue hemorrhagic fever. In severe dengue, the body starts having serious problems that can be life-threatening if not treated quickly. The symptoms include:

• Severe bleeding (from multiple sites)
• Severe stomach pain
• Difficulty breathing
• Confusion or changes in consciousness
• Inability to drink fluids
• No urination for 6-8 hours
• Cold, clammy skin
• Weak pulse
• Signs of shock

Dengue Shock Syndrome

This is a dangerous complication of severe dengue where your blood vessels start leaking and your blood pressure drops dangerously low. The symptoms include:

• Very low blood pressure
• Cold sweats
• Rapid heartbeat
• Confusion
• Pale and cold hands and feet
• Difficulty staying awake
• Severe stomach pain
• Deep breathing

Secondary Dengue Fever Infection

This happens when someone who has already had dengue once gets infected again with a different type of the dengue virus. Secondary infections can be more dangerous because your immune system might overreact. The symptoms might start like classical dengue but can quickly become more severe.

When to Get Medical Help?

You should go to the hospital immediately if you notice:

• Severe stomach pain
• Persistent vomiting
• Bleeding from nose or gums that won’t stop
• Extreme tiredness or restlessness
• Difficulty breathing
• Cold and clammy skin
• Any signs of shock

Disease Progression and Clinical Phases of Dengue Fever

The illness typically progresses through three distinct phases, each requiring specific attention and management approaches.

The Febrile Phase (Days 1-3):

During this initial stage, patients experience sudden onset of high fever, typically reaching 40°C (104°F). The fever pattern shows interesting characteristics – it often spikes and reduces, but never completely normalizes during this phase. Patients describe severe muscle and joint pain, lending dengue its historical name “breakbone fever.” Many also report intense headaches, particularly behind the eyes, and extreme fatigue.

Another notable feature during this phase involves taste disturbance and marked loss of appetite. The combination of fever and severe body aches often leaves patients bedridden. Some develop a transient facial flushing that makes their faces appear sunburned.

The Critical Phase (Days 4-6):

This phase requires the closest monitoring as it determines whether the infection will resolve uneventfully or progress to severe dengue. The fever typically breaks during this time, but this improvement can be deceptive.

Careful attention must focus on warning signs that might indicate deterioration.

Warning signs include severe abdominal pain, persistent vomiting, mucosal bleeding (such as nose bleeds or bleeding gums), lethargy, and restlessness. Laboratory findings often show dropping platelet counts and rising hematocrit levels, indicating plasma leakage – a dangerous complication requiring immediate medical intervention.

The Recovery Phase (Days 7-10):

If patients successfully navigate the critical phase, they enter recovery. During this time, their appetite returns, gastrointestinal symptoms improve, and hemodynamic status stabilizes. However, some patients develop a characteristic rash described as “islands of white in a sea of red.” While usually benign, this rash often causes significant itching.

Similar Illnesses

The symptoms of dengue fever resemble those of other mosquito-borne arboviruses, such as chikungunya or Zika virus infections.

Transmission and Incubation

The incubation period is 5–10 days from the time of infection. Dengue fever is caused by a virus transmitted to humans through the bite of infected mosquitoes, primarily the Aedes aegypti and Aedes albopictus species.

Dengue Fever Treatment

Since there’s no specific antiviral medication for dengue fever, treatment focuses on managing symptoms and preventing complications. Let’s explore how dengue is treated, from mild cases that can be managed at home to severe cases requiring hospitalization.

Home Treatment for Mild Dengue

For mild cases of dengue fever, doctors typically recommend home care with careful monitoring. The main focus is on:

• Maintaining proper hydration. Drinking plenty of fluids is crucial – water, oral rehydration solutions, and clear broths help replace fluids lost through fever and sweating. The key is to drink even when you don’t feel thirsty, as dengue can mask the feeling of thirst.
• Managing fever and pain. Doctors recommend taking acetaminophen (Tylenol) to reduce fever and ease pain. It’s very important to avoid aspirin and NSAIDs like ibuprofen because they can increase bleeding risks due to their effects on blood platelets.
• Getting plenty of rest. Your body needs extra energy to fight the infection, so adequate rest is essential for recovery. Most people need to stay in bed for several days during the acute phase of the illness.

Hospital Treatment for Severe Cases

When dengue becomes severe or shows warning signs, hospital treatment becomes necessary. In the hospital, treatment includes:

• Intravenous fluid therapy. This is the cornerstone of hospital treatment. Doctors carefully calculate and monitor fluid administration to prevent both dehydration and fluid overload. The amount and type of fluids given depend on the patient’s age, weight, and severity of symptoms.
• Blood and platelet transfusions. If severe bleeding occurs or platelet counts become dangerously low, patients may need blood products. However, platelet transfusions are only given when there’s significant bleeding or an extremely low platelet count.
• Oxygen therapy. For patients having difficulty breathing or showing signs of shock, supplemental oxygen helps ensure adequate oxygen delivery to vital organs.

Is There a Vaccine Against Dengue Fever?

1. Dengvaxia (CYD-TDV):

Developed by Sanofi Pasteur, Dengvaxia was the first dengue vaccine to be licensed. It is recommended for individuals aged 9 to 45 years who have previously been infected with dengue, as evidenced by seropositivity testing. Here’s what you need to know:

• Administration: Three doses are administered over a 12-month period (0, 6, and 12 months).
• Efficacy: It has shown variable efficacy across the serotypes, with about 60% effectiveness in preventing hospitalization due to dengue. However, there’s a significant caveat; it increases the risk of severe dengue in individuals who have never been infected if they are later exposed to the virus. This has led to a more cautious approach in its use.
• Controversies: Due to concerns about increased risk of severe dengue in seronegative individuals, its use has been limited, especially after a 2017 controversy where it was administered without prior serology testing in the Philippines, leading to public health debates and policy changes.

2. Qdenga (TAK-003):

Takeda’s Qdenga, another tetravalent dengue vaccine, has been approved in several countries, including those in Asia and Latin America, focusing on children aged 6 to 16 years:

• Administration: Given in two doses, three months apart.
• Efficacy: Clinical trials have indicated an efficacy of around 80.2% in preventing symptomatic dengue cases within 12 months post-vaccination, with higher protection against severe disease (90.4% effectiveness in reducing hospitalization).
• Target Population: Recommended for areas with high dengue transmission intensity, particularly for those who have not been previously infected, differing from Dengvaxia’s seropositive-only recommendation.

Challenges and Considerations

1. Serotype Coverage: Vaccines must protect against all four serotypes to be truly effective, as infection with one serotype can predispose individuals to more severe disease upon subsequent infection with another serotype, a phenomenon known as antibody-dependent enhancement (ADE).
2. Pre-vaccination Screening: The necessity for pre-vaccination screening for Dengvaxia complicates its widespread use. Qdenga does not require this, broadening its applicability but still with considerations for optimal use based on transmission intensity and age groups.
3. Geographic Variation: The effectiveness and safety of these vaccines can vary by region due to differing serotype distributions and disease burden, requiring tailored public health strategies.

Medical Responsibilities

Healthcare providers have the following responsibilities:

1. Medical Care
   • Inform the patient of the diagnosis.
   • Provide symptomatic treatment, as there is no specific antiviral medication for dengue.
   • Educate the patient that dengue fever is not contagious between humans.
2. Travel History and Surveillance
   • While dengue fever is not a mandatory reportable disease for contact tracing in the U.S., it is crucial to document the country, region, and specific locations where the patient traveled. This information aids in understanding the epidemiology of dengue and tracking emerging risk areas.
3. Vaccination Advice
   • Advise patients planning future travel to high-risk areas to consider vaccination. Vaccination can reduce the risk of severe dengue if exposed to a different strain of the virus.

Laboratory Findings and Monitoring

For healthcare providers, several laboratory parameters require careful monitoring:

• Complete blood count showing progressive decrease in white blood cells and platelets
• Hematocrit levels indicating plasma leakage
• Liver function tests often showing elevated transaminases
• Coagulation studies in severe cases

The tourniquet test, while not always reliable, can help assess capillary fragility and platelet function, particularly in resource-limited settings.

Prevention and Public Health Implications

When treating suspected dengue cases, always remember that early recognition of warning signs and prompt intervention make the difference between good outcomes and potentially life-threatening complications. Both patients and healthcare providers must maintain vigilance throughout the illness course, particularly during the critical phase.