Dengue Virus: Infectious substances pathogen safety data sheet

For more information on Dengue Virus, see the following:

• Dengue fever - Travel.gc.ca
• Dengue fever - Canada.ca

Section I – Infectious agent

Name

Dengue Virus

Agent type

Virus

Taxonomy

Family

Flaviridae

Genus

Orthoflavivirus

Species

denguei

Subspecies/strain/clonal isolate

Subspecies include DENV-1, DENV-2, DENV-3, and DENV-4^{Footnote 1}.

Synonym or cross-reference

Dengue virus is also known as breakbone fever or dandy fever^{Footnote 2}. Causative agent of the Dengue viral fever (DVF).

Characteristics

Brief description

Dengue virus (DENV) particles are spherical with a diameter of approximately 50 nm and have an 11kb linear, single-stranded, positive sense RNA genome^{Footnote 3}. Upon entering the host cell and being released from the capsid, the positive single stranded RNA genome is translated to a polyprotein of 3400 amino acids in length, which is then subsequently cleaved by viral and host encoded proteases to yield 10 proteins: three structural proteins (C, E, prM) and seven non-structural proteins labeled as NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5^{Footnote 3}. Multiple copies of the capsid (C) protein encapsulates the RNA genome, creating the nucleocapsid, which forms the core of the DENV particle. The core is covered by a lipid bilayer, where two transmembrane proteins are positioned, forming an outer glycoprotein protective casing. This protective layer is composed of 180 copies of envelope (E) and membrane (prM/M) proteins, with varying configuration depending on the stage of maturity.

Properties

Dengue infections are caused by four closely related viruses: DENV-1, DENV-2, DENV-3, DENV-4 which share approximately 60%-70% amino acid sequence homology^{Footnote 3Footnote 4}. During DENV infection the structural proteins are vital for virion assembly, release, maturation, and infectivity; while the non-structural proteins play a major role in viral replication and in eluding the host immune response^{Footnote 3}. The E protein enables virus entry into susceptible cells by binding cellular receptors.

DENV exhibits two distinct morphological forms, the intracellular immature virion and mature virion^{Footnote 5}. The immature virion has asymmetric spikes on the surface but undergoes extensive rearrangement of these intracellular virus-encoded surface proteins upon acidification during maturation in the infected cells^{Footnote 5Footnote 6Footnote 7}. The mature virion is distinguished by the virus-encoded membrane-associated E and M proteins, forming a relatively smooth surface. The intracellular immature virion has E protein and a precursor membrane (prM) protein which will be cleaved proteolytically into the M protein during maturation.

Section II – Hazard identification

Pathogenicity and toxicity

Infection with any of the four DENV serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes^{Footnote 8}. Dengue viral illness can be divided into asymptomatic, uncomplicated DVF and severe DVF^{Footnote 7}. Fever is typically the first symptom for both, presenting a biphasic pattern in which the fever subsides and reoccurs 2 days later^{Footnote 9}. Fever can last from 2 to 7 days and maybe associated with cranial, musculoskeletal, and gastrointestinal manifestations. Cranial manifestations include severe headaches and retro-orbital eye pain. Musculoskeletal manifestations include arthralgia and myalgia, and are the key symptoms associated with dengue viral illness. Gastrointestinal manifestations vary from intermittent nausea and vomiting to anorexia. A characteristic rash is typically the secondary symptom to fever. A primary rash occurs 3-6 days after fever onset^{Footnote 9}. In severe dengue fever, haemorrhage manifested by petechiae, epistaxis, positive tourniquet test or thrombocytopenia, and plasma leakage, pleural effusion, and ascites are typical^{Footnote 7}. Hospitalizations for severe DVF occur mainly among children, with the case fatality rate exceeding 5% in some areas^{Footnote 10}. Untreated severe DVF has a fatality rate of 10-20%^{Footnote 2}.

Epidemiology

There are approximately 400 million cases and 22,000 deaths due to dengue worldwide each year^{Footnote 11}. The incidence of dengue has increased 30-fold over the last 50 years with 3 billion people now living in the over 100 endemic countries in tropical and subtropical regions^{Footnote 12}. Symptomatic dengue is primarily a disease experienced by older children and young adults (5-14 years old) in hyper-endemic regions^{Footnote 13Footnote 14}. There is a heightened risk for severe disease among infants^{Footnote 14Footnote 15Footnote 16}. A large epidemiological study from Brazil showed that symptomatic dengue during pregnancy is associated with an increased risk of preterm birth and fetal death^{Footnote 14Footnote 17}. Dengue in pregnancy adversely affects maternal and fetal outcomes with prematurity and postpartum haemorrhage possible and a high maternal mortality rate of 15.9%^{Footnote 18}. A study in Thailand also showed that the 0-4 year-old age group had the highest death rate^{Footnote 13Footnote 14}. The elderly are also at an increased risk of severe dengue infection due to frequent age-related co-morbidities that can complicate dengue infection, among these, cardiovascular disease, diabetes, respiratory disease, and renal disease are the most common^{Footnote 14Footnote 19}. In 2023, several countries, including Bangladesh, Brazil, Burkina Faso, Fiji, Pakistan, the Philippines, and Viet Nam, reported a notable surge in dengue cases compared to previous years^{Footnote 20}. In 2024, over 14 million dengue cases and over 10 000 dengue-related deaths have been reported globally^{Footnote 21}. Most cases globally have been reported from the WHO region of the Pan American Health Organization (PAHO) region. This region reported over 12.5 million cases, 53% of which were laboratory confirmed, and over 7 000 deaths. Brazil has reported the most cases (over 10 million) followed by Argentina, Mexico, Colombia and Paraguay.

There are approximately 200-300 imported cases of dengue identified and diagnosed every year in Canada^{Footnote 22}. All of these cases have been among travellers returning from countries where the DENV is present. Most Canadian travellers infected with the virus will show no, or only mild symptoms. Therefore the actual number of imported dengue cases in Canada is likely much higher.

Host range

Natural host(s)

Humans, non-human primates, and mosquitoes are primary hosts. DENV is transmitted to humans by horizontal transmission, which occurs through the bite of infected females from mosquito host species Aedes aegypti or Aedes albopictus^{Footnote 23}. Sylvatic cycles of DENV have been demonstrated in Asia, where serologic and virus isolation data suggest an association between Macaca and Presbytis monkeys and zoonotic DENV-1,-2, and -4, with Aedes niveus mosquitos as the primary vectors^{Footnote 24Footnote 25}.

A recent study reported DENV positivity in a range of animals and birds, including pigs (34.1%), marsupials (13%), birds (11%), bats (10.1%), horses (5.1%), bovids (4.1%), rodents (3.5%), dogs (1.6%), and other small animals (7.3%)^{Footnote 26}.

Other host(s)

Experimentally infected animals include mice, non-human primates, pigs, and shrews^{Footnote 27}.

Infectious dose

Fewer than 10 plaque forming units (PFU) led to infection in 50% of volunteers treated with an attenuated DENV vaccine candidate^{Footnote 28}.

Incubation period

The typical incubation period for the disease is 4 to 7 days, but can range from 3 to 10 days. Symptoms more than two weeks after exposure are unlikely to be due to DENV^{Footnote 2}.

Communicability

Two primary transmission cycles maintain the dengue virus: 1) mosquitos carry the virus from a non-human primate to a non-human primate, and 2) mosquitos carry the virus from human to human^{Footnote 2Footnote 7Footnote 29}. The urban transmission cycle to humans occurs in domestic/peri-domestic habitats by female mosquitoes mainly of the species Ae. aegypti and, to a lesser extent, Ae. albopticus^{Footnote 2Footnote 30Footnote 31}. Transmission in tropical and subtropical regions of the world includes a sylvatic, enzootic cycle between non-human primates and arboreal mosquitoes of the genus Aedes^{Footnote 32}. Although spill over from the sylvatic cycle to humans is believed to be possible there is no evidence of sylvatic amplification of human outbreaks. Transmission perinatally, through blood transfusions, breast milk, and organ transplantation have been reported^{Footnote 33}.

Section III – Dissemination

Reservoir

Humans and non-human primates^{Footnote 2Footnote 7Footnote 32}.

Zoonosis

None.

Vectors

Mosquitoes are vectors for DENV; Aedes aegypti and Aedes albopictus transmit the virus in humans, and Aedes niveus transmits the virus in non-human primates^{Footnote 23Footnote 31}.

Section IV – Stability and viability

Drug susceptibility/resistance

None.

Susceptibility to disinfectants

DENV is susceptible to a 1:10 bleach dilution and 70% ethanol^{Footnote 28}. Viruses are sensitive to 1% sodium hypochlorite, 2% glutaraldehyde, 2% peracetic acid, iodophors, phenolic compounds, and 3-6% hydrogen peroxide^{Footnote 34}.

Physical inactivation

DENV can be effectively inactivated by moist heat (121°C for at least 15 minutes), dry heat (160-170°C for at least 1 hour)^{Footnote 28}. The virus requires ultraviolet light exposure 45 minutes or longer at 75 cm distance from the source to be completely inactivated^{Footnote 35}. The virus is also inactivated at a pH of 3^{Footnote 28}.

Survival outside host

Dengue RNA was detectable in dried blood for up to 9 weeks at room temperature^{Footnote 36}. Viable DENV was recovered from platelets after 7 days at 22°C and from red blood cell concentrates after 42 days at 1-6°C^{Footnote 37}.

Section V – First aid/medical

Surveillance

Laboratory diagnosis methods for confirming DENV infection may involve detection of the virus, viral nucleic acid, antigens, or antibodies, or a combination of these techniques^{Footnote 38}. After the onset of illness, the virus can be detected in serum, plasma, circulating blood cells, and other tissues for 4-5 days. During the early stages of the disease, virus isolation, nucleic acid, or antigen detection can be used to diagnose the infection. At the end of the acute phase of infection, serology is the method of choice for diagnosis. IgM antibodies are the first immunoglobulin isotype to appear. These antibodies are detectable in 50% of patients by days 3-5 after onset of illness, increasing to 80% by day 5, and 99% by day 10. Before day 5 of illness, during the febrile period, dengue infections may be diagnosed by virus isolation in cell culture, by detection of viral RNA by reverse transcription quantitative real-time PCR (RT-qPCR) amplification or by conventional PCR, using appropriate oligonucleotide primers, or by detection of viral antigens by enzyme-linked immunosorbent assays (ELISA) or rapid tests^{Footnote 11Footnote 38}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

Treatment for uncomplicated dengue is focussed on symptomatic relief. Most cases of DVF can be treated at home with acetaminophen and oral fluids. For people with severe DVF, hospitalization is often needed^{Footnote 12}. Those with presenting with severe disease can be initiated on intravenous crystalloids^{Footnote 38}. Colloids can be started for patients in shock and are also preferred if the patient has already received previous boluses of crystalloid and has not responded. Blood transfusion is warranted in cases of severe bleeding or suspected bleeding when the patient remains unstable. Platelet transfusion is considered when platelet count drops to <20,000 cells/microliter, and there is a high risk of bleeding^{Footnote 2}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

Dengvaxia vaccine has recently been approved in the United States for children 9 through 16 years old, but only when they have been previously infected with DENV and living in areas where DENV is common^{Footnote 39}. Vaccine providers give three doses administered subcutaneously and each dose is given 6 months apart (at 0, 6, and 12 months) for full protection. Dengvaxia protects children from DVF illness, hospitalizations, and severe DVF 8 out of 10 times (80%) in children who had dengue before vaccination. Protection lasts for at least 6 years^{Footnote 38}. Dengue vaccination is not currently available in Canada, and is currently not approved for Canadian travellers to other countries^{Footnote 40}. Dengvaxia has now been registered in 20 DENV endemic countries, although immunization implementation has been limited to subnational public health programs in only two countries, Brazil and the Philippines^{Footnote 41}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

There is currently no prophylaxis for dengue disease^{Footnote 42}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

Fourteen cases were reported up to 1988. In 2014, a 30-year-old female laboratory worker from South Korea was infected with DENV by needlestick injury while conducting virus filtering and suffered symptoms such as fever, nausea, myalgia, and a maculopapular rash^{Footnote 43}. In the United States in 2018, improper doffing of gloves with an open finger wound likely resulted in cutaneous symptomatic infection^{Footnote 44}. Another laboratory acquired infection case, in Australia, involving a scientist conducting mosquito infection and transmission experiments was reported. The patient had worn proper personal protective equipment but reported a bite from an escaped non-bloodfed mosquito during that day but denied needlestick injury or mucocutaneous contact with the blood/virus mixture^{Footnote 45Footnote 46}. Upon testing, the antibody response was to the same virus serotype as was used during the laboratory experiment.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Infected human blood, human liver, lung, and kidney tissue. Non-human primate kidney cell lines, cerebrospinal fluid (CSF), spleen, and lymph nodes^{Footnote 47Footnote 48Footnote 49}.

Primary hazard

Parenteral inoculation or bites from experimentally infected mosquito^{Footnote 49}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

DENV is a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 50}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures are required.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, post mortem rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes are to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escape and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 51Footnote 52}.

For diagnostic laboratories handling primary specimens that may contain DENV, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials are to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with DENV require a Pathogen and Toxin licence issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• Domestic substances list

Last file update

January 2025

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright ^© Public Health Agency of Canada, 2025, Canada