Dengue

Dengue is transmitted by the bite of an infected mosquito. It is an illness that affects infants, young children, and adults, with symptoms ranging from mild fever to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. The illness can evolve to severe dengue, characterized by shock, respiratory distress, severe bleeding, and/or serious organ impairment. The disease has a seasonal pattern: most cases in the southern hemisphere occur in the first half of the year, and most cases in the northern hemisphere in the second half. This pattern corresponds to the warmer, rainy months.

In the Americas, Aedes aegypti is the mosquito vector that is the main source of dengue transmission.

Campaign against mosquitoes-children also collaborate — Photo: PAHO/WHO. Campaign against mosquitoes: Children also collaborate.

Key facts

Approximately 500 million people in the Americas are today at risk of dengue.
Dengue incidence has increased in the Americas over the past four decades, from 1.5 million cumulative cases in the 1980s to 16,2 million in the decade 2010-2019.
2013 was an epidemic year in the Americas, with 2 million cases and an incidence of 430,8 per 100,000 inhabitants. There were 37,692 severe cases and 1,280 deaths in the hemisphere. In 2019, more than 3,1 million cases were registered, 28,000 severe and, 1,534 deaths
The four dengue serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) circulate throughout the Americas, and in some countries simultaneously.
Following infection with one serotype, subsequent infection with a different serotype increases a person's risk of severe dengue and death.
Ae. aegypti is the vector mosquito for dengue and is widely distributed in the Americas. Only Canada and continental Chile are free from dengue and its vector. Uruguay has no dengue cases, but it does have Ae. aegypti.

Fact sheet

About Dengue...

It is transmitted by the bite of a mosquito infected with one of the four serotypes of dengue virus.
It is a febrile illness that affects infants, children and adults. The infection may be asymptomatic, or it may present with symptoms ranging from a moderate fever to a disabling high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rashes.The disease can evolve into severe dengue, characterized by shock, shortness of breath, severe bleeding and / or complications in the organs.
There is no a specific medicine to treat dengue.
The disease has a pattern according to the seasons: the majority of cases in the southern hemisphere occur in the first part of the year, and the majority of cases in the northern hemisphere occur in the second half.
Dengue prevention and control must be intersectoral and involve the family and the community.

About Aedes aegypti...

Habitat

Aedes aegypti is the vector that presents the greatest risk of arbovirus transmission in the Americas and is present in almost all countries of the hemisphere (except Canada and continental Chile). It is a domestic mosquito (that lives in and near houses) that reproduces in any artificial or natural container that contains water.

Life cicle

The mosquito can complete its life cycle, from the egg to the adult, in 7-10 days; adult mosquitoes usually live 4 to 6 weeks. The female Aedes aegypti is responsible for the transmission of diseases because she needs human blood for the development of her eggs and for her metabolism. The male does not feed on blood.

Activity

The mosquito is most active early in the morning and at dusk, so these are the periods of greatest risk of bites. However, females, who need to continue feeding, will seek a source of blood at other times. The female Aedes aegypti feeds every 3-4 days; however, if they cannot draw enough blood, they continue feeding each moment they can.

How to eliminate them?

Aedes aegypti prefers to lay its eggs in artificial containers that contain water (drums, barrels and tires, mainly) in and around homes, schools and workplaces. Aedes aegypti eggs can withstand dry environmental conditions for more than a year: in fact, this is one of the most important strategies that the species uses to survive and spread.

To eliminate mosquitoes, the following actions are recommended: avoid collecting water in open-air containers (pots, bottles or other containers that can collect water) so that they do not become breeding sites for mosquitoes; adequately cover water tanks and reservoirs to keep mosquitoes away; avoid accumulating garbage, throwing garbage in closed plastic bags.

PAHO Response

PAHO/WHO provides advice and technical support for dengue prevention and control based on a regional strategy adopted by PAHO / WHO member States in 2016, called the "Strategy for arboviral disease prevention and control" (CD55.R6).
In 2008, PAHO / WHO Member States established a Network of Dengue Laboratories of the Americas (RELDA), to strengthen technical capacities for diagnosing dengue. RELDA has now been expanded to include chikungunya and Zika fever and now comprises 32 laboratories in 26 countries of the Region.
PAHO/WHO is supporting the development of an integrated dengue surveillance system model in the context of the circulation of other arboviruses to generate standardized information for all the Americas.
In 2010, PAHO / WHO adapted the 2009 WHO clinical guidelines on the management of dengue patients for use in the Americas. After its implementation, the lethality rate in dengue cases decreased in 2019 from 0,07% to 0,05%, which means a 30% reduction. A second edition of the PAHO / WHO clinical guidelines was published in 2015, incorporating new elements, including dengue during pregnancy, dengue in newborns, dengue in the elderly and preparation and response to dengue outbreaks.
A tool for the diagnosis and care of patients with suspected arbovirosis (dengue, chikungunya and Zika) was published in 2016. Currently, the first clinical guide for arbovirosis is being developed following the GRADE methodology. This guide will be published in 2020.

Detailed Information

Disease phases

Feverish phase

Patients develop a sudden, high fever. This acute febrile phase lasts from 2 to 7 days and is usually accompanied by facial flushing, erythema, generalized body pain, myalgia, arthralgia, headache, and retro-ocular pain. Minor hemorrhagic manifestations such as petechiae and skin ecchymoses may occur. Patients who improve after the fever subsides are considered dengue cases without warning signs.

Problems that can occur in the febrile phase: dehydration; high fever can be associated with neurological disorders, and seizures in young children.

Critical phase

Near the disappearance of the fever, when the temperature drops to 37.5 degrees Celsius or less and stays below this level, usually in the first 3 to 7 days of the disease, capillary permeability can increase in parallel with hematocrit levels. This marks the beginning of the critical phase. Patients who worsen with the drop in fever and show alarm signs are cases of dengue with warning signs.

Problems that can occur in the critical phase: shock due to plasma leakage; severe bleeding, serious organ involvement.

Recovery phase

When the patient survives the critical phase (which does not exceed 48 to 72 hours), they move on to the recovery phase. There is an improvement in the general state, appetite recovers, gastrointestinal symptoms improve, the hemodynamic state stabilizes, and diuresis increases.

Problems that may occur in the recovery phase: hypervolemia (if intravenous fluid therapy has been excessive or has been extended in this period).

Revised Dengue Classification

The classification recommended by the World Health Organization in 2009 is the so-called revised classification, which emerged from the DENCO results, which included almost 2,000 confirmed cases of dengue from eight countries and two continents and establishes two forms of the Dengue disease and severe dengue.

Dengue revised classification diagram. The so-called dengue with alarm signs is part of the dengue form but, it is described separately because its knowledge is extremely important to decide therapeutic behaviors and prevent - if possible - severe dengue.

Dengue without warning signs: The disease can manifest as a "nonspecific fever syndrome." The presence of other confirmed cases in the environment to which the patient belongs is decisive to suspect the clinical diagnosis of dengue.
Dengue with warning signs: The patient may present intense and continuous abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, altered consciousness, hepatomegaly and progressive increase in hematocrit.
Severe dengue: Severe forms of dengue are defined by one or more of the following: (i) shock from plasma leakage, fluid accumulation with respiratory distress, or both; (ii) profuse bleeding that is considered clinically important by treating physicians, or (iii) severe organ involvement. liver: AST or ALT ≥ 1000; CNS: alteration of consciousness, and that includes the heart and other organs.

Diagnostic

Differential diagnosis

When making the diagnosis, it should be kept in mind that some symptoms can be confused with those of other diseases such as malaria, rubella, measles, typhoid fever, meningitis and influenza. In dengue fever there is no rhinorrhea (discharge of mucus from the nose) or nasal congestion.

Laboratory diagnosis

The definitive diagnosis of dengue infection is made in the laboratory and depends on the detection of specific antibodies in the patient's serum, detection of viral antigen or viral RNA in serum or tissue, or viral isolation. A blood sample in the acute phase should be taken as soon as possible after the onset of febrile illness. A blood sample in the convalescent phase should ideally be taken 2-3 weeks later.

Serological diagnosis: Can be made by: immunoglobulin M enzyme immunocapture assay (MAC-ELISA) and indirect immunoglobulin G (ELISA), inhibition-hemagglutination (IH), complement fixation (CF), neutralization (NT) and dengue non-structural protein antigen detection (NS1 ELISA).
Viral isolation: CFour viral isolation systems have been used for dengue virus, intracerebral inoculation of 1-3 day old mice, mammalian cell culture (LLC-MK2), intrathoracic inoculation of adult mosquitoes and the use of mosquito cell culture.
Viral Identification: The method of choice for dengue virus reporting is IFA; serospecific monoclonal antibodies, produced in tissue culture or mouse ascitic fluid and fluorescein-isothiocyanate conjugated IgG.
RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction): It is a rapid, sensitive, simple and reproducible method with adequate controls. It is used to detect viral RNA in human clinical samples, autopsy tissue and mosquitoes. It has a similar sensitivity to viral isolation with the advantage that problems in handling, storage and the presence of antibodies do not influence its result. However, it should be emphasized that PCR is not a substitute for viral isolation.
Immunohistochemistry: With immunohistochemical methods, it is possible to detect viral antigen in a wide variety of tissues. These methods involve enzyme conjugation with phosphatases and peroxidases in conjunction with mono- and polyclonal antibodies.
Rapid tests: The clinical features of dengue are often nonspecific and therefore require laboratory confirmation.

Accurate but sophisticated methods such as virus isolation or polymerase chain reaction (RT-PCR) require advanced equipment and infrastructure. Serological assays are widely available and can provide an alternative to support diagnosis. Primary (new) DENV infections typically have a stronger and more specific IgM response; subsequent (secondary) infections demonstrate a weaker IgM response but a strong IgG response.

These patterns of differentiation of IgM response to infection underscore the need to evaluate the sensitivity and specificity of commercially available tests, especially for the diagnosis of secondary DENV infections. WHO/TDR and the Pediatric Dengue Vaccine Initiative (PDVI) collaborated to evaluate commercially available IgM anti-DENV diagnostic tests. A network of seven laboratories in Asia and Latin America was established to perform the work.

The report, Evaluation of Commercially Available Anti-Dengue virus Immunoglobulin M Tests, WHO 2009 describes the results of an evaluation of nine commercially available anti-DENV IgM tests using a panel of well-characterized specimens, with sera from patients with confirmed DENV infections and from patients with other infections and potentially confounding conditions.

NS1 is a recently introduced rapid test on the market that has a high specificity for the diagnosis of dengue (90 to 100%), but a low sensitivity (52 - 62%), indicating that a negative result from this test does not rule out dengue infection and making a complementary test necessary for confirmation of dengue.
Complementary tests:
1. Complete blood count with leukocyte and platelet counts.
2. Examination of cerebrospinal fluid provided there is no risk of bleeding.
3. In cases of shock, arterial blood gases, electrolytes, liver and kidney function tests should be determined.
4. Laboratory tests such as ultrasound, chest x-ray and computed axial tomography.

Treatment

Good primary care not only reduces the number of unnecessary hospitalizations, but also saves the lives of dengue patients. Early notification of dengue cases seen in primary and secondary care is crucial for identifying outbreaks and initiating timely response.

What to do if you have symptoms of dengue?

Consult your physician.
Watch for warning signs.
Do not self-medicate, do not use aspirin, because its effect can cause bleeding.
Do not use antibiotics because dengue is caused by a virus and antibiotics only attack bacteria.

Progress of the dengue vaccine

Regarding the commercially available dengue vaccine (Dengvaxia CYD-TDV) and considering the conditions for the use of this vaccine and the lack of evidence on some aspects of safety and effectiveness, PAHO's Technical Advisory Group on Immunizations (TAG) reiterates its recommendation (made in July 2015) that the introduction of dengue vaccine into national immunization programs at the country level is not yet recommended.

Countries in the Americas should continue surveillance strengthening activities to improve knowledge about the burden of dengue disease. Strengthened surveillance activities are highly important in the context of outbreaks of other vector-borne diseases, including Zika and Chikungunya.

For more information, please refer to the 23rd GTA Final Report (2015) y and 01 GTA Ad-hoc Final Report (2016).