What is dengue and severe dengue?
Dengue is a mosquito-borne viral disease that has rapidly spread in all regions in recent years.
As quoted by the World Health Organisation (WHO), dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus. These mosquitoes are also vectors of chikungunya, yellow fever and Zika viruses.
Dengue is widespread throughout the tropics, with local variations in risk influenced by rainfall, temperature, relative humidity and unplanned rapid urbanization.
Dengue causes a wide spectrum of disease. This can range from subclinical disease (people may not know they are even infected) to severe flu-like symptoms in those infected. Although less common, some people develop severe dengue, which can be any number of complications associated with severe bleeding, organ impairment and/or plasma leakage.
Severe dengue has a higher risk of death when not managed appropriately. Severe dengue was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children and adults in these regions.
Recovery from infection provides lifelong immunity against that particular serotype. However, cross-immunity to the other serotypes after recovery is only partial, and temporary. Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue.
Dengue has distinct epidemiological patters, associated with the four serotypes of the virus. These can co-circulate within a region/country and indeed many countries are hyper-endemic for all four serotypes.
Dengue has an alarming impact on both human health and the global and national economies. Dengue virus is frequently transported from one place to another by infected travelers; when susceptible vectors are present in these new areas, there is the potential for local transmission to be established.
Global burden of dengue
The incidence of dengue has grown dramatically around the world in recent decades. A vast majority of cases are asymptomatic or mild and self-managed, and hence the actual numbers of dengue cases are under-reported. Many cases are also misdiagnosed as other febrile illnesses.
Distribution and outbreaks of dengue
Before 1970, only 9 countries had experienced severe dengue epidemics. The disease is now endemic in more than 100 countries in the WHO regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific. The America, South-East Asia and Western Pacific regions are the most seriously affected, with Asia representing ~70% of the global burden of disease.
Cases across the Americas, South-East Asia and Western Pacific exceeded 1.2 million in 2008 and over 3.34 million in 2016 (based on official data submitted by Member States).
The year 2016 was characterized by large dengue outbreaks worldwide. The Region of the Americas region reported more than 2.38 million cases in 2016, where Brazil alone contributed slightly less than 1.5 million cases, approximately three times higher than in 2014. 1032 dengue deaths were also reported in the region.
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The Western Pacific Region reported more than 375,000 suspected cases of dengue in 2016, of which the Philippines reported 176 411 and Malaysia 100 028 cases, representing a similar burden to the previous year for both countries. The Solomon Islands declared an outbreak with more than 7000 suspected. In the African Region, Burkina Faso reported a localized outbreak of dengue with 1061 probable cases.
In 2017, a significant reduction was reported in the number of dengue cases in the Americas – from 2 177 171 cases in 2016 to 584 263 cases in 2017. This represents a reduction of 73%. Panama, Peru and Aruba were the only countries that registered an increase in cases during 2017.
After a drop in the number of cases in 2017-18, a sharp increase in cases is being observed in 2019. In the Western Pacific region, increase in cases have been observed in Australia, Cambodia, China, Lao PDR, Malaysia, Philippines, Singapore, Vietnam. DENV-2 was reported in New Caledonia and DENV-1 in French Polynesia. Dengue outbreaks have also been reported in Congo, Côte d’Ivoire, Tanzania in the African region; Several countries of the American region -Brazil, Colombia, Nicaragua and Honduras have also observed an increase in the number of cases. Bangladesh, Nepal, Sri Lanka, Thailand, parts of India have also recorded increase in dengue cases in South-East Asian region and Pakistan and Sudan have also reported increase in the Eastern Mediterranean region.
The virus is transmitted to humans through the bites of infected female mosquitoes, primarily the Aedes aegypti mosquito. Other species within the Aedes genus can also act as vectors, but their contribution is secondary to Aedes aegypti.
After feeding on a DENV-infected person, the virus replicates in the mosquito midgut, before it disseminates to secondary tissues, including the salivary glands.
The time it takes from ingesting the virus to actual transmission to a new host is termed the extrinsic incubation period (EIP). The EIP takes about 8-12 days when the ambient temperature is between 25-28°C .
Variations in the extrinsic incubation period are not only influenced by ambient temperature; a number of factors such as the magnitude of daily temperature fluctuations, virus genotype , and initial viral concentration  can also alter the time it takes for a mosquito to transmit virus. Once infectious, the mosquito is capable of transmitting virus for the rest of its life.
Mosquitoes can become infected from people who are viremic with DENV. This can be someone who has a symptomatic dengue infection, someone who is yet to have a symptomatic infection (they are pre-symptomatic), but also people who show no signs of illness as well (they are asymptomatic).
Human-to-mosquito transmission can occur up to 2 days before someone shows symptoms of the illness [5, 11], up to 2 days after the fever has resolved.
Disease characteristics (signs and symptoms)
Dengue is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. Symptoms usually last for 2–7 days, after an incubation period of 4–10 days after the bite from an infected mosquito. The World Health Organization classifies dengue into 2 major categories: dengue (with / without warning signs) and severe dengue. The sub-classification of dengue with or without warning signs is designed to help heatlh practitioners triage patients for hospital admission, ensuring close observation, and to minimise the risk of developing the more severe dengue (see below).
Dengue should be suspected when a high fever (40°C/104°F) is accompanied by 2 of the following symptoms during the febrile phase:
- severe headache
- pain behind the eyes
- muscle and joint pains
- swollen glands
A patient enters what is called the critical phase normally about 3-7 days after illness onset. It is at this time, when the fever is dropping (below 38°C/100°F) in the patient, that warning signs associated with severe dengue can manifest. Severe dengue is a potentially fatal complication, due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.
Warning signs that doctors should look for include:
- severe abdominal pain
- persistent vomiting
- rapid breathing
- bleeding gums
- blood in vomit.
If patients manifest these symptoms during the cirtical phase, close observation for the next 24–48 hours is essential so that proper medical care can be provided, to avoid complications and risk of death.
Several methods can be used for diagnosis of DENV infection. These include virological tests (that directly detect elements of the virus) and serological tests, which detect human-derived immune components that are produced in response to the virus). Depending on the time of patient presentation, the application of different diagnostic methods are more or less appropriate. Patient samples collected during the first week of illness should be tested by both serological and virological methods (RT-PCR).
The virus may be isolated from the blood during the first few days of infection. Various reverse transcriptase–polymerase chain reaction (RT–PCR) methods are available. In general, RT–PCR assays are sensitive, but they require specialised equipment and technical training for staff implementing the test, therefore they are not always available in all medical facilities. RT–PCR products from clinical samples may also be used for genotyping of the virus, allowing comparisons with virus samples from various geographical sources.
The virus may also be detected by testing for a virus-produced protein, called NS1. There are commercially-produced rapid diagnostic tests available for this, because it takes only ~20 mins to determine the result, and the test does not require specialsied laboratory techniques or equipment.
There is no specific treatment for dengue fever.
Fever reducers and pain killers can be taken to control the symptoms of muscle aches and pains, and fever.
- The best options to treat these symptoms are acetaminophen or paracetamol.
- NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen and aspirin should be avoided. These anti-inflammatory drugs act by thinning the blood, and in a disease with risk of hemorrhage, blood thinners may exacerbate the prognosis.
For severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20% to less than 1%. Maintenance of the patient’s body fluid volume is critical to severe dengue care. Patients with dengue should seek medical advice upon the appearance of warning signs.
Vaccination against dengue
The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 and has now been approved by regulatory authorities in ~20 countries. In November 2017, the results of an additional analysis to retrospectively determine serostatus at the time of vaccination were released.
The analysis showed that the subset of trial participants who were inferred to be seronegative at time of first vaccination had a higher risk of more severe dengue and hospitalizations from dengue compared to unvaccinated participants. As such, use of the vaccine is targetted for persons living in endemic areas, ranging from 9-45 years of age, who have had at least 1 documented dengue virus infection previously.
Prevention and control
The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for dengue as well as for other diseases that these species transmit. At present, the main method to control or prevent the transmission of dengue virus is to combat the mosquito vectors. This is achieved through:
- Prevention of mosquito breeding in and around houses and places of work, schools and health facilities:
- Preventing mosquitoes from accessing egg-laying habitats by environmental management and modification; Disposing of solid waste properly and removing artificial man-made habitats. Covering, emptying and cleaning of domestic water storage containers on a weekly basis; Applying appropriate insecticides to water storage outdoor containers;
- Using of personal household protection measures, such as window screens, repellents, insecticide treated materials, coils and vaporizers (these measures must be observed during the day both inside and outside of the home (eg: at work/school) because the primary mosquito vectors bites throughout the day)
- Wearing clothing that minimises skin exposure to mosquitoes is advised; Personal protection from mosquito bites; Community engagement:
- Educating the community on the risks of mosquito-borne diseases;
- Engaging with the community to improve participation and mobilization for sustained vector control;
- Emergency vector control measures such as applying insecticides as space spraying during outbreaks may be used by health authorities;Reactive vector control:
- Active mosquito and virus surveillance:
- Active monitoring and surveillance of vector abundance and species composition should be carried out to determine effectiveness of control interventions; Prospectively monitor the prevalence of virus in the mosquito population, with active screening of sentinel mosquito collections .