Ask the Experts: Dengue

Results (37)

Dengue is an infectious disease caused by dengue viruses (DENV) spread among people through the bite of an infected mosquito from the Aedes species (Ae. aegypti or Ae. albopictus). DENV are members of the genus Flavivirus in the family Flaviviridae.

There are four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), all of which circulate globally. The four dengue virus serotypes are closely related but can be differentiated on serologic tests. Infection with one serotype generally produces long-lived immunity to that serotype, but only provides short-lived protection against infection with other serotypes. For this reason, a person can be infected with DENV as many as four times in their lifetime.

Symptoms of dengue range from asymptomatic or very mild (75% of cases) to severe disease complicated by shock, bleeding, or severe organ impairment. Fever is the most common symptom of dengue. Other symptoms can include sudden onset of headache, pain behind the eyes, loss of appetite, abdominal pain, nausea, vomiting, muscle aches, bone and joint pain, and flushing of the face. A generalized flat, red rash is often seen within 3–4 days of fever onset. Symptoms typically last 2–7 days, with most people recovering after about a week.

About 1 in 20 patients with dengue progress to severe dengue, typically 24-48 hours after the fever resolves. Severe dengue can become life-threatening within hours, often as a result of hypovolemic shock due to plasma leakage from the vasculature. There is no specific treatment for dengue. With proper supportive care in a hospital or intensive care unit setting, fewer than one in 100 people with severe dengue may die; fatality rates have been reported as high as 13% in the absence of adequate supportive care.

A person’s risk for progression to severe dengue varies based on several factors. Age (over 60), comorbidities (including pregnancy), host genetics, and the infecting virus strain are risk factors for severe dengue. For any individual, the second infection with a different DENV serotype is the most likely to cause severe dengue compared with the first, third, or fourth infections.

CDC has a website with additional details on the clinical presentation of dengue:
www.cdc.gov/dengue/healthcare-providers/clinical-presentation.html.

Last reviewed: February 16, 2022

Dengue is common throughout tropical and subtropical regions of the world. About half of the world’s population lives in areas suitable for DENV transmission and the main vector of dengue, the Aedes aegypti mosquito, is difficult to control and continues to expand its geographic range. Each year, up to 400 million people get infected with dengue viruses. Approximately 100 million people get sick from infection, and about 40,000 die from severe dengue.

Dengue is endemic in the United States territories and freely associated states of Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. CDC classifies an area as endemic for dengue if the area has frequent or continuous dengue transmission, with evidence of more than 10 dengue cases in at least three of the previous 10 years. Dengue epidemics occur in a cyclical pattern every 3–7 years, with all four DENV serotypes reported in the Pacific Islands and the Caribbean. Limited surveillance data are available from the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau.

Dengue can cause outbreaks with high numbers of cases in some years. In 2021, only 435 cases were reported in US territories, and 63 cases were reported in U.S. states. About 90% of the population at risk for dengue in US territories live in Puerto Rico. From 2010-20, approximately 95% of locally acquired dengue cases in the US occurred in Puerto Rico (29,779 cases), with the most cases and hospitalizations in Puerto Rico occurring among adolescents age 10 through 19 years (11,000 cases leading to 4,000 hospitalizations). Small convenience studies of children ages 9 through 16 conducted during vaccine trials estimated that 50% to 56% of children in this age group showed serologic evidence of past DENV infection. Dengue is not endemic in the continental United States or Hawaii; however, outbreaks and travel-associated cases have occurred in Texas, Florida, and Hawaii in recent years.

Last reviewed: February 16, 2022

Multiple complex mechanisms likely contribute to increased disease severity during a second DENV infection. The published ACIP recommendation provides a detailed description of these mechanisms at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf. In addition, CDC has developed simple illustrations and descriptions to explain this phenomenon at www.cdc.gov/dengue/vaccine/hcp/eligibility/index.html.

Last reviewed: February 16, 2022

Dengvaxia (Sanofi Pasteur) is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. It is designed to protect against all four DENV serotypes. It was licensed by the FDA in May 2019 for children and adolescents age 9 through 16 years with a confirmed history of previous dengue infection. The recommendation for vaccination is restricted to people with confirmed previous DENV infection because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination.

Last reviewed: February 16, 2022

Vaccine efficacy (VE) during clinical trials in multiple countries ranged from 76% to 82%. VE varied by serotype and was highest for DENV-4 (89% point estimate) and lowest for DENV-1 and DENV-2 (67% point estimate). Among study participants ages 9 through 16 years who developed protective antibodies, the vaccine reduced their risk of hospitalization with dengue by 79%, and reduced their risk of severe dengue by 84% over the 5-year follow-up period after vaccination. Studies are ongoing to determine how long protection from hospitalization or severe disease may last, but current evidence show protection lasting at least 6 years after the last dose of vaccine.

Last reviewed: February 16, 2022

No, Dengvaxia does not protect the recipient against yellow fever.

Last reviewed: February 16, 2022

In June 2021, ACIP voted to recommend Dengvaxia for routine use in children age 9 through 16 years with laboratory-confirmed previous dengue virus infection and living in areas where CDC has classified dengue as endemic. The recommendation is only for persons with confirmed previous DENV infection because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination.

The vaccine is not approved for use in U.S. travelers who are visiting but not living in an area where dengue is common.

The most current ACIP recommendations for Dengvaxia are available at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf.

CDC has developed a pre-vaccination checklist for evaluating whether a child should receive Dengvaxia: www.cdc.gov/dengue/resources/DVBD_FS_Vaccination_Checklist-508.pdf.

Last reviewed: February 16, 2022

Yes. Dengvaxia is included in the VFC program. The most current VFC resolution is available at www.cdc.gov/vaccines/programs/vfc/downloads/resolutions/2021-6-1-Dengue-508.pdf.

The cost of the pre-vaccination screening test will be covered by Medicaid for those who are eligible.

Last reviewed: February 16, 2022

Children with confirmation of previous DENV infection need three doses of Dengvaxia, given 6 months apart, for complete protection (0, 6 months, 12 months).

Recipients achieve significant protection following dose 1. Ongoing evaluation will determine whether the schedule could be simplified in the future.

Last reviewed: February 16, 2022

No, it is not. It is only recommended for children and teens ages 9 through 16 who reside in dengue endemic areas.

Last reviewed: February 16, 2022

No. Dengvaxia is FDA-licensed only for children and teens ages 9 through 16 years.

Last reviewed: February 16, 2022

CDC does not recommend Dengvaxia for non-residents of areas where dengue is endemic. If the child spends regular extended periods in Puerto Rico to point that they are considered a part-time resident, the family should consult with the child’s health care provider in Puerto Rico for assessment.

Last reviewed: February 16, 2022

Dengvaxia is a live-attenuated vaccine. Live virus vaccines are generally not recommended during pregnancy; however, people infected with DENV during pregnancy are at increased risk of severe dengue. Perinatal transmission may occur with peripartum maternal infection increasing the risk of symptomatic illness in the newborn. The ACIP recommendations classify pregnancy as a precaution to vaccination with Dengvaxia.

Pregnant people were not explicitly enrolled and studied in the Dengvaxia vaccine trials. A minimal number of pregnant women in the trial inadvertently received Dengvaxia. There was no increased frequency of adverse pregnancy outcomes (e.g., spontaneous abortion, intrauterine death, stillbirth) noted compared to the control group. However, due to the small sample size, no conclusions can be made on the possible effect of Dengvaxia on pregnancy.

Providers should consider the pregnant person’s risk of DENV infection and its complications when deciding whether or not to recommend Dengvaxia during pregnancy or to defer until after pregnancy.

Last reviewed: February 16, 2022

CDC recommends that Dengvaxia should be used with precaution in breastfeeding individuals. There are no data in humans to evaluate the safety of Dengvaxia in infants who are breastfed. Providers and breastfeeding parents should weigh the benefits of breastfeeding and the risk of DENV infection in the mother and the infant.

Last reviewed: February 16, 2022

Dengvaxia is a live-attenuated vaccine and is contraindicated in children with severe immunodeficiency or immunosuppression due to underlying disease or therapy, including children with symptomatic HIV infection or CD4+ T-lymphocyte count below 200 per cubic milliliter.

The ACIP recommendations state that Dengvaxia may be used with precaution in people with HIV infection who do not meet the criteria for contraindication, based on an assessment of the person’s risk of vaccination against the risk of dengue and its complications.

Last reviewed: February 16, 2022

Administration of Dengvaxia to a person who has never been infected with DENV may result in an increased risk of hospitalization and severe dengue illness if they are infected with natural (wild type) DENV for the first time after vaccination. Multiple complex mechanisms likely contribute to increased disease severity during a second DENV infection. The published ACIP recommendation provides a detailed description of these mechanisms at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf. In addition, CDC has developed simple illustrations and descriptions to explain this phenomenon at www.cdc.gov/dengue/vaccine/hcp/eligibility/index.html.

In a person who has never been infected with DENV, vaccination with Dengvaxia may “stand in” (immunologically) for the first natural infection, resulting in an increased risk of severe dengue in response to the first natural infection because the immune system responds as if that infection were the “second” infection.

Last reviewed: February 16, 2022

CDC has established strict accuracy criteria for the laboratory tests considered acceptable proof of past DENV infection before vaccination of a child.

No test is perfectly accurate: wrong results lead to different types of risk. A false negative test result means a child who is at increased risk of severe dengue would not be protected by vaccination. A false positive test means a child who was not at high risk of severe dengue would be vaccinated, potentially increasing the child’s risk of severe dengue if the child experiences a subsequent DENV infection.

All dengue IgG tests for pre-vaccination screening must have a minimum specificity of at least 98% to minimize the chance of misclassifying a person who should have a true negative test result as positive. This high specificity minimizes the risk of vaccinating a person who should not be vaccinated.

Pre-vaccination screening tests must also have a sensitivity of at least 75% to accurately identify a high proportion of children and adolescents with past dengue virus infections who can benefit from vaccination.

Acceptable laboratory confirmation of previous dengue virus infection can be obtained by:

  • Evidence of prior acute dengue virus infection with
    • Positive dengue RT-PCR test result, or
    • Positive dengue NS1 antigen test result
  • OR, positive results on BOTH of the following anti-dengue virus IgG antibody tests in a two-step testing algorithm:
    • EUROIMMUN Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG) and
    • CTK BIOTECH OnSite Dengue IgG Rapid Test

Visit www.cdc.gov/dengue/vaccine/hcp/testing.html. for additional information about laboratory testing requirements for vaccination with Dengvaxia. As additional tests are evaluated and approved as acceptable, information will be updated by CDC.

Vaccinators are encouraged to use the CDC prevaccination checklist to evaluate patient eligibility: www.cdc.gov/dengue/resources/DVBD_FS_Vaccination_Checklist-508.pdf.

Last reviewed: February 16, 2022

No. IgM tests for acute DENV infection are not sufficiently accurate to be acceptable evidence for the purposes of vaccination. These tests may be falsely positive as a result of other flavivirus infections that may cause similar symptoms (such as Zika).

Acceptable evidence of acute infection with DENV is either a positive dengue RT-PCR test result, or a positive dengue NS1 antigen test result.

Visit CDC’s website on laboratory testing requirements for vaccination with Dengvaxia for additional information: www.cdc.gov/dengue/vaccine/hcp/testing.html.

Last reviewed: February 16, 2022

Patients with a negative test should be re-tested every 1 or 2 years (while remaining between the ages of 9 through 16 years) or based on the clinical judgment of the health care provider.

CDC recommends that children and adolescents who are acutely ill with dengue virus infection should wait at least 6 months after the date dengue virus infection is confirmed to begin the vaccine series. www.cdc.gov/dengue/vaccine/hcp/schedule-dosing.html.

Last reviewed: February 16, 2022

ACIP recommends a 3-dose Dengvaxia vaccine schedule, with doses administered at 0, 6 months, and 12 months.

Last reviewed: February 16, 2022

The recommended interval is 6 calendar months between each dose, and the minimum interval is 5 calendar months between each dose. In accordance with CDC’s general best practice guidelines, a dose administered up to 4 days before the minimum interval may be counted as valid. If a dose is given too early, the recommendation is to repeat the dose at the minimum interval of 5 months.

Last reviewed: February 16, 2022

Dengvaxia is administered as a 3-dose series, spaced 6 months apart (0, 6, and 12 months). Each dose is 0.5 mL in volume, administered subcutaneously. The vaccine comes in powder form (lyophilized) in single dose vials. Each lyophilized vaccine vial should be mixed with the supplied diluent, a vial of saline diluent (0.4% NaCl). To reconstitute Dengvaxia, withdraw 0.6 ml from the diluent vial and inject it into the lyophilized vaccine vial. Swirl the vial gently. After reconstitution, the suspension is colorless and may develop trace amounts of white to translucent particles.

After reconstitution, 0.5 mL of Dengvaxia should be withdrawn and immediately administered subcutaneously. If not used immediately, the reconstituted vaccine should be refrigerated at 36°F–46°F (2°C–8°C) and used within 30 minutes. Do not use the vaccine more than 30 minutes after reconstitution.

Dengvaxia is for subcutaneous use only. Dengvaxia should not be administered by intramuscular injection; however, if administered intramuscularly in error, the dose does not need to be repeated.

CDC has a web page dedicated to the storage and reconstitution of Dengvaxia: www.cdc.gov/dengue/vaccine/hcp/storage-handling.html.

Last reviewed: February 16, 2022

No, the dose should not be repeated. In accordance with CDC’s “General Best Practice Guidelines for Immunization”, the immune response to vaccines recommended to be administered by the subcutaneous route is unlikely to be affected if the vaccines are inadvertently administered by the intramuscular route. For this reason, repeating doses of vaccine administered by the intramuscular route when recommended by the subcutaneous route is not necessary (www.cdc.gov/vaccines/hcp/acip-recs/general-recs/administration.html).

Last reviewed: February 16, 2022

Yes, Dengvaxia may be given at the same visit with any live or non-live vaccines that are also indicated for the patient.

If Dengvaxia is not administered on the same day as another live vaccine, the two vaccines should be separated by at least 4 weeks to minimize the potential risk of interference.

Last reviewed: February 16, 2022

You should continue where the patient left off and complete the series. You never have to restart the series.

Last reviewed: February 16, 2022

Yes. You must initiate the series while the recipient is age 16 years, but you may complete the series even if the recipient turns 17 before the series is completed.

Last reviewed: February 16, 2022

The parent/caregiver should be notified immediately, warned of the possible increased risk for hospitalization and severe dengue if the person develops a subsequent natural dengue infection, and the need to seek immediate medical attention if warning signs of severe dengue develop.

Clinic staff should review the incident and ensure that staff members responsible for vaccination have had sufficient training and protocols are in place to prevent such errors.

The use of tools, such as the CDC prevaccination checklist, helps prevent such errors: (www.cdc.gov/dengue/resources/DVBD_FS_Vaccination_Checklist-508.pdf).

Last reviewed: February 16, 2022

Children and adolescents who have been diagnosed with acute dengue should wait at least 6 months after the date the dengue illness is confirmed to begin the vaccine series.

Last reviewed: February 16, 2022

Dengvaxia is contraindicated for people with a history of immediate hypersensitivity to any vaccine component or a previous dose of this vaccine. A complete list of vaccine components is available in the package insert at www.fda.gov/media/124379/download.

Dengvaxia is a live-attenuated vaccine and also is contraindicated in children with severe immunodeficiency or immunosuppression due to underlying disease or therapy, including children with symptomatic HIV infection or CD4+ T-lymphocyte count of less than 200 per cubic milliliter.

Lack of laboratory evidence of previous dengue infection is also a contraindication to Dengvaxia. www.cdc.gov/vaccines/vpd/dengue/hcp/recommendations.html.

Last reviewed: February 16, 2022

A precaution to Dengvaxia is a moderate or severe acute illness with or without fever. Vaccination should be deferred until the condition improves.

ACIP recommends that Dengvaxia may be used with precaution in certain special populations for whom the risks and benefits of vaccination to prevent DENV infection must be evaluated but for whom limited safety data are available. These groups include pregnant people, breastfeeding people, and people with HIV that is controlled and does not meet the criteria for a contraindication.

Last reviewed: February 16, 2022

Administration of Dengvaxia to a person who has never been infected with DENV may result in an increased risk of hospitalization and severe dengue illness if they are infected with natural (wild type) DENV for the first time after vaccination.

Multiple complex mechanisms likely contribute to increased disease severity during a second DENV infection. The published ACIP recommendation provides a detailed description of these mechanisms at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf. In addition, CDC has developed simple illustrations and descriptions to explain this phenomenon at www.cdc.gov/dengue/vaccine/hcp/eligibility/index.html.

In a person who has never been infected with DENV, vaccination with Dengvaxia may “stand in” (immunologically) for the first natural infection, resulting in an increased risk of severe dengue in response to the first natural infection because the immune system responds as if that infection were the “second” infection.

Last reviewed: February 16, 2022

The most frequently reported side effects among vaccine recipients in the clinical trials were headache (40%), injection site pain (32%), malaise (25%), fatigue (25%), and muscle aches (29%).

As with any vaccine, healthcare providers should report any clinically significant adverse event to the Vaccine Adverse Events Reporting System (VAERS) at www.vaers.hhs.gov. even if a causal relation to vaccination is unknown or not certain.

Last reviewed: February 16, 2022

Syncope (fainting) can occur before or after vaccination because of a vasovagal response to needles. Children should be seated or lying down during vaccination. Consider observing patients (with the patient seated or lying) for 15 minutes after vaccination to decrease the risk for injury should the patient faint. If syncope develops, the patient should be observed until the symptoms resolve.

Last reviewed: February 16, 2022

Yes. The current VIS for Dengvaxia is available in both English and Spanish at www.immunize.org/vis/vis_dengue.asp.

Last reviewed: February 16, 2022

No, Dengvaxia is not included in the VICP at this time.

For additional information, visit www.hrsa.gov/vaccine-compensation/faq.

Last reviewed: February 16, 2022

No. You should only use the (0.4% NaCl) diluent provided with the Dengvaxia vaccine vial. Contact your immunization program or the manufacturer for additional guidance.

Last reviewed: February 16, 2022

Store both the vaccine antigen and the diluent in a refrigerator at 36°F–46°F (2°C–8°C). Do not freeze. Protect from light. After reconstitution, administer Dengvaxia immediately or store refrigerated at 36°F–46°F (2°C–8°C) and use within 30 minutes.

Do not use the vaccine if it has been reconstituted for over 30 minutes. Contact your public health immunization program or the manufacturer for advice if vaccination occurs using vaccine that has been reconstituted more than 30 minutes, or in the event of other storage or handling errors.

The manufacturer package insert contains additional information and can be found at www.fda.gov/media/124379/download.

For complete information on vaccine storage and handling best practices and recommendations, please refer to CDC’s Vaccine Storage and Handling Toolkit at www.cdc.gov/vaccines/hcp/admin/storage/toolkit/storage-handling-toolkit.pdf.

Last reviewed: February 16, 2022

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