Dengue

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.

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.

• 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 specimens, autopsy tissue and mosquitoes. The test is highly sensitive, being its ability to detect positive cases close to 100%.
• Detection of the NS1 viral protein: It is a highly sensitive test performed by enzyme-linked immunosorbent assay (ELISA).
• Serology:  It consists of the detection of IgM antibodies against dengue virus. The recommended technique is the capture ELISA or some other variants of it.
• Viral isolation: This category includes some tests with high levels of complexity that require performance by qualified personnel. In general, these tests are performed in national and international reference laboratories.
• Immunohistochemistry: With immunohistochemical methods, it is possible to detect viral antigen in a wide variety of tissues. These methods are particularly useful for the confirmation of DENV infections in tissues from deceased patients.
• Rapid tests: Rapid (immunochromatographic) tests are not recommended as an integral part of laboratory confirmation algorithms. 

There is no specific drug to treat dengue fever. Medical evaluation through an appropriate medical history and physical examination by a health care professional is key to proper management of the disease. Recognition of the warning signs of dengue is essential to avoid progression to severe forms of dengue.

What to do if you have symptoms of dengue?

• Consult your physician.
• Watch for warning signs. If any of them appear, go immediately to the nearest health facility.
• Drink plenty of fluids to prevent dehydration, preferably oral rehydration salts.
• 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.

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.

Integrated Management Strategy for Arboviral Disease Prevention and Control is the best working model available to address dengue. 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).

Regarding the dengue vaccine developed by Takeda (TAK-003), please refer to the XI ad hoc Meeting of the PAHO Technical Advisory Group (TAG) on Vaccine-Preventable Diseases.

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.

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.

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.

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.