Dengue Management

Evaluation

Criteria for Home Management

Patients may be sent home if they tolerate adequate oral fluids, with urine output every 6 hours, and there are no warning signs (ie abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy, restlessness, >2 cm increase in liver size, increasing hematocrit concomitant with decreasing platelet count), especially during defervescence.  

Criteria for Hospitalization

General Condition  

Hospital admission is recommended if there is a continuous fever for ≥3 days, lethargy, restlessness, irritability, excessive tiredness, drowsiness, generalized flushing, shortness of breath, and if there is no improvement or there is worsening of the condition.  

Dehydration  

Hospital admission is recommended in patients who are unable to tolerate oral fluid intake or have vomiting or diarrhea.  

Abdominal Discomfort  

In patients suffering from epigastric pain or tender hepatomegaly, hospital admission is recommended.  

Hemorrhagic Manifestations            

Patients with a positive tourniquet test, petechiae, ecchymoses or purpura, spontaneous mucosal bleeding, epistaxis, gastrointestinal bleeding, excessive menstrual bleeding, hematuria, or thrombocytopenia (platelet count of ≤100,000/mm³) should be admitted in a hospital. Patients with active bleeding regardless of platelet count and patients without bleeding tendency but with platelet count on a rapid downward trend should also be admitted.  

Plasma Leakage            

Patients with rapidly rising hematocrit, hematocrit of ≥20% of baseline, serositis (eg pleural effusion, ascites), or suspected plasma leakage (males with hematocrit of >47% or females with hematocrit >40%) should be admitted in the hospital.  

Circulatory Failure or Shock  

Patients with a rapid and weak pulse, narrowing of the pulse pressure to <20 mmHg, hypotension, cool, mottled, or pale skin, cold extremities with circumoral cyanosis, changes in mental status, restlessness, lethargy, oliguria, tachypnea due to metabolic acidosis, or acute renal failure should be admitted in a hospital.  

Criteria for Emergency Treatment

Emergency treatment should be given if there is a presence of severe plasma leakage that may lead to shock and/or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment (ie hepatic damage, renal impairment, cardiomyopathy, encephalopathy, encephalitis).  

Clinical Predictors for Bleeding

The following are the clinical predictors for bleeding:

• Hypotension
• Narrowing of pulse pressure to <20 mmHg
• Hepatosplenomegaly or hepatomegaly
• Severe thrombocytopenia (platelet count <50,000/mm³)
• Leukopenia
• Elevated serum ALT (>3x compared to normal value)
• Presence of vomiting, abdominal pain, restlessness, serosal effusion, or rashes

Pharmacological therapy

Symptomatic Therapy

Antipyretics and Analgesics

Example drugs: Paracetamol (Acetaminophen), Metamizole (Dipyrone, Noramidopyrine)  

These drugs help keep the body temperature below 40°C and relieve body pain. They are indicated for patients with hyperpyrexia particularly those with a history of febrile convulsions. It is important to advise patients to avoid Aspirin and other salicylates which may cause gastritis, bleeding, and acidosis. Advise patients to avoid NSAIDs as well since aside from possibly causing gastritis, gastrointestinal tract bleeding, and acidosis, NSAIDs also have an antiplatelet effect.  

Sedatives  

Give mild sedatives to patients with severe pain. It is necessary to calm agitated patients, especially children. 

Nonpharmacological

Supportive Therapy

Bed rest is advisable during the acute febrile phase of dengue. Tepid sponging may be done to keep the body temperature below 40°C.            

Advise patients to ensure an adequate diet and to drink plenty of oral fluids to prevent dehydration. Fruit juice or electrolyte replacement solution is preferable over plain water.  

Emphasize the need to monitor for dehydration and the presence of warning signs (eg severe abdominal pain, persistent vomiting, skin rash, bleeding from nose or gums, vomiting blood, dark stools, drowsiness or irritability, pale or cool skin, dyspnea) and instruct the patient to go to the nearest hospital promptly once detected.  

Advise patients to look for mosquito breeding places in their homes and eliminate them.            

Oxygen should be provided for all patients in shock. 

Fluid Replacement Therapy

Intravenous (IV) Fluids  

Judicious volume replacement therapy is mandatory in patients with intravascular volume loss or with at least one warning sign, and to prevent or reverse hypovolemic shock.  

Isotonic crystalloid solutions should be given during the critical period. Hyperoncotic colloid solutions (eg 10% Dextran 40 in normal saline, starch solution) may be given to patients unresponsive to crystalloids or those with immense plasma leakage. The volume and rate of intravenous fluid therapy should be adjusted according to the volume and rate of plasma loss. For isotonic dehydration, 5% glucose diluted 1:1 or 1:2 in NSS should be used.  

Intravenous fluids are adjusted throughout the 24- to 48-hour period of leakage by serial hematocrit determinations and frequent assessment of vital signs and urine output to ensure adequate volume replacement and to avoid overhydration. The volume of fluid replacement should be the minimum that is sufficient to maintain effective circulation during the period of plasma leakage that occurs in the convalescent stage.  

Excessive fluid replacement and continuation after leakage stops will cause massive pleural effusion, ascites, and pulmonary congestion or edema with respiratory distress when reabsorption of the extravasated plasma occurs in the convalescent stage. An intravenous therapy duration of <60-72 hours for patients who do not have shock and <24-48 hours for those who have shock should be implemented.  

The fluid administered to correct dehydration from high fever, anorexia, and vomiting is calculated according to the degree of dehydration and electrolyte loss and should have the following composition: 5% glucose in ½ or ⅓ physiological saline solution.  

Intravenous fluids can also be administered in outpatient rehydration units in mild or moderate cases when vomiting produces or threatens to produce dehydration or acidosis or when hemoconcentration is present.  

Plasma or plasma expanders may be considered in patients with persistent shock after initial fluid resuscitation.  

Oral Rehydration Solutions (ORS)  

An example of oral rehydration solution is the WHO ORS (90 mmol of Na/L) wherein 1L solution contains 3.5 g sodium chloride (NaCl), 2.9 g Trisodium citrate dihydrate, 1.5 g potassium chloride (KCl), and 20 g Glucose; administered in a ratio of 2:1 of WHO ORS to water or fruit juice.  

Generous amounts of fluids should be given orally since high fever, anorexia, and vomiting lead to thirst and dehydration.  

The recommended amount for intense hydration with oral rehydration solution is based on the following:

• Adults: Up to 3000 mL/day
• Children: Holliday-Segar formula plus 5% (4 mL/kg/hr for the first 10 kg of body weight; 2 mL/kg/hr for the next 10 kg of body weight; 1 mL/kg/hr for each kilogram of additional body weight)

Prevention

Preventing or reducing the transmission of dengue virus is dependent on controlling mosquito vectors or disturbing human-vector contact. Infection provides long-term protection against the same type of reinfection.  

The first dengue vaccine, CYD-TDV, developed in 2019, may now be considered in individuals with a history of previous laboratory-confirmed dengue infection. Other vaccines are currently being developed. 

Methods of Vector Control

Methods to control transmission should target habitats of immature and adult stages of Aedes aegypti, one of the most efficient vectors for arboviruses, in the household and places where human-vector contact occurs. These mosquitoes mostly stay within 100 meters from where they emerged, and feed mainly during daylight hours.  

Environmental Management  

Controlling mosquito vectors is achieved mainly by eradicating container habitats that are favorable oviposition sites and developing aquatic stages through prevention of access to containers or emptying and cleaning them regularly, and by using insecticides or biological control agents to kill developing stages of adult vectors. Mosquito screens on windows or doors, mosquito nets, and clothing that covers the arms and legs may be used while sleeping during the daytime to decrease human-vector contact.  

Chemical Control  

Larvicides should be done as complementary to environmental management. Adulticides are used to target adult vectors which are applied either as surface treatments or as space treatments.     

Individual and household protection are advised to minimize exposure of skin and be protected from bites of dengue vectors during their active hours. Repellents that contain DEET (N, N-diethyl-3-methylbenzamide), IR3535 (3-[N-acetyl-N-butyl]-aminopropionic acid ethyl ester), or Icaridin (1-piperidinecarboxylic acid-2-(2-hydroxyethyl)-1-methylpropylester) may be applied to the skin or to clothes. Citronella-based repellents may also be considered. Mosquito nets that are insecticide-treated, insecticide aerosol products, or mosquito coils may also help.  

Vaccination  

In May 2019, CYD-TDV, a recombinant, live, attenuated, tetravalent dengue vaccine, was approved by the United States (US) Food and Drug Administration (FDA), then was recommended by the US Advisory Committee on Immunization Practices (ACIP) in June 2021, to prevent dengue in children aged 9 to 16 years, with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic.  

This vaccine may be used in individuals aged 9 to 45 years residing in endemic areas with at least one episode of previous dengue virus infection. As of June 2019, the dengue vaccine has been approved in 20 countries (ie Mexico, Brazil, Philippines), including the US and Europe for the prevention of dengue.  

Data from the two pivotal phase III clinical studies showed that CYD-TDV given on a 3-dose series on a 0/6/12 month schedule has a good safety profile with secondary analysis demonstrating efficacy against the four dengue serotypes and protection from severe disease and hospitalization.  

Pre-vaccination screening is recommended for countries considering the inclusion of dengue control in their vaccination program.  

Other vaccines under clinical trial evaluation include subunit, DNA and purified inactivated as well as other live-attenuated vaccines (eg TAK-003). Additional vaccines under preclinical study evaluation are the virus-vectored and VLP-based vaccines.