Dengue

What is Dengue Fever?

Dengue fever is a disease caused by mosquitoes infected by the dengue virus and is prevalent in the tropical regions of the world. It is a painful, disabling disease, with the severity of pain similar to that of bones breaking - hence it is also known as 'Breakbone' fever.

Dengue fever affects close to 400 million people worldwide each year, with about 40% of the world's population being at risk of exposure and infection. Since dengue fever is caused by a virus, it cannot be cured by antibiotics.(1^✔)

What are the Symptoms of Dengue Fever?

The major symptoms of dengue fever include sudden high fever (as high as 40 �C or 104 �F), chills, severe headache (usually behind the eyes), muscle ache and joint pain, nausea, vomiting, flushed skin and in some cases, a skin rash similar to measles. Dengue fever symptoms may be mild initially and mistaken for a flu, cold or a viral infection. In rare cases, dengue fever may develop into a more life threatening form known as dengue hemorrhagic fever, which results in bleeding, decreased blood platelet count or thrombocytopenia, blood plasma leakage or the more fatal dengue shock syndrome, which causes dangerously low blood pressure.(2^✔)

How is Dengue Fever Caused and Spread?

Dengue fever and dengue hemorrhagic fever spread from human-to-mosquito-to-human by the bite of mosquitoes carrying the dengue virus. The dengue virus belongs to a group known as Flavivirus and can be typically divided into four viral serotypes, DEN-1, DEN-2, DEN-3, and DEN-4, which are closely related but differ in their antigens. Many species of mosquitoes under the genus Aedes transmit dengue; in particular, the Aedes aegypti species is most commonly associated with it and the major cause of dengue transmission. This species of mosquito breeds in stagnant waters and usually bites during daylight hours. The virus circulates in the blood for 2-7 days after a person is infected, during which time a mosquito biting the person would acquire it and in turn bites and infects another person.

The symptoms typically develop anywhere between 3 to 14 days, but usually start within 4 to 7 days of infection, and may last from 7 or 10 days. The dengue virus doesn't have any detrimental effect on the mosquito that carries it, and the mosquito remains infected for life. Dengue disease is spread when a mosquito bites an infected person and becomes a carrier of the dengue virus. The mosquito then bites another healthy person and thus spreads the disease causing a possible epidemic breakout. A person infected with a single type of dengue virus serotype out of the four, develops resistance to only that particular virus. However, they become much more susceptible to infection by the other three serotypes.(3^✔)

What are the Complications of Dengue Fever?

Dengue fever may sometimes develop into more dangerous forms such as dengue hemorrhagic fever or dengue shock syndrome, which may lead to the development of life-threatening symptoms. Some of the complications caused by the disease include:

• Severe dehydration
• Continuous bleeding
• Low platelets, due to which clotting of blood doesn't occur
• Blood pressure may go dangerously low
• Bradycardia (heart beating less than 60 counts per minute)
• Damage to the brain due to bleeding, seizures or encephalitis
• Damage to the immune system
• Enlargement of liver and liver damage

How Do You Diagnose Dengue Fever?

Diagnosis of dengue is considered when sudden high fever is accompanied by severe body, muscle or joint pain. It is important to be evaluated when a person develops fever within two weeks of being in the tropics or sub-tropics. Dengue often causes symptoms that are similar to other diseases such as flu, measles, and typhoid fever etc. Hence investigations are always performed to exclude other disease conditions. Usually, the blood of the patient is tested for the presence of antibodies and virus. Diagnosis of dengue infection can be done by the following methods:

• Isolating the virus by collecting serum sample from patients within 5 days of appearance of symptoms.
• Detection of specific antibodies can be done by collecting serum within 6 days after onset of symptoms. The serum is tested for specific anti-dengue antibodies by Enzyme-linked Immunosorbent Assay (ELISA). Titres of IgM and IgG antibodies increase four-fold in serum sample.
• Using Polymerase Chain Reaction (PCR) for detecting viral genomic sequence from Serum or Cerebro Spinal Fluid (CSF) samples collected from the patient, which is more expensive and complicated.

In the case of more serious complications such as dengue hemorrhagic fever, the following diagnosis must be performed:

• A tourniquet test is to be conducted, where a tourniquet is tied to the arm and if blood blotches tend to appear beyond the tourniquet, the patient may be suffering from increased bleeding, which may indicate dengue hemorrhagic fever
• A decrease in platelet count, also known as thrombocytopenia occurs when platelet count falls below 100,000. Normal platelet counts are between 150,000 to 400,000. A decreased platelet count may be due to dengue fever.
• An increase in hematocrit i.e., the volume percentage of red blood cells (RBCs), by 20% could be another indicator as it occurs due to a rise in the vascular permeability of the plasma. Signs of plasma leakage appear as increased fluid accumulation in the chest and abdominal cavity known as pleural effusion or ascites respectively.(4^✔)

How Do You Treat Dengue Fever?

Since there are no known antiviral drugs or injections available for the cure of the disease, dengue fever treatment or management mainly involves plenty of supportive care that would eventually help save the patient's life. Dengue is characterized by fever and intense body ache. Dengue treatment comprises of reducing the fever with antipyretic drugs such as paracetamol and the body ache with analgesics that help relieve the pain. Drugs such as aspirin and ibuprofen should be avoided as they may increase the risk of hemorrhage. The patient can also be treated with natural home remedies such as papaya leaves, kiwi and other food items that have been proven to help in the increase of platelet count, which becomes lower during dengue. In the case of more severe forms of dengue, such as dengue hemorrhagic disease or dengue shock syndrome, the patient must be admitted to a hospital immediately and given proper care. The mortality rate of a dengue patient without hospitalization is higher by about 50 percent. Treatments such as intravenous fluid replacement should be administered to these patients to prevent shock. Patients should drink plenty of fluids, as dehydration is common among those affected with Dengue.(5^✔)

Dengue Vaccine

The world's first dengue vaccine, Dengvaxia or CYD-TDV) developed by Sanofi Pasteur was approved for use in Mexico, Philippines and Brazil in December 2015 for the prevention of the deadly mosquito borne disease in people living in dengue endemic areas.

According to "Dengue Vaccine: WHO position paper - July 2016", WHO says that countries should consider introducing the CYD-TDV in areas where there is epidemiological data suggesting a high incidence of dengue.

The discovery of CYD-TDV marks a major advance in the field of medicine. CYD-TDV is a prophylactic viral vaccine approved for use in people between the ages of 9 - 45 years. It is a triple-dose vaccine administered on a 0/6/12 month schedule via the subcutaneous route. It contains all 4 serotypes (1, 2, 3 and 4) of the dengue viruses.

CYD-TDV demonstrated protection against severe dengue cases in its phase 3 trials conducted in Asia and Latin America. However, there were limitations in its overall efficacy which was affected by factor like serotype, serostatus at vaccination (whether the person has had a prior infection or not), region or country and age.

New dengue vaccines TV003/TV005 have been developed by the National Institute of Allergy and Infectious Diseases. They produce antibodies to all 4 dengue virus serotypes. In earlier trials, a single dose of either of the vaccines was able to elicit a robust antibody and cellular immune response.

A Phase 3 trial of TV003 has begun in January 2016 in Sao Paulo to test how effective the vaccine is in preventing dengue and to test its safety. Early indications of its efficacy may be seen in less than two years.

Another vaccine developed by Takeda called the Tetravalent Dengue Vaccine (TDV) has also entered its Phase 3 trials early in 2016 in Latin America and Asia. Data from its Phase 1 and Phase 2 trials indicate that it is safe, well tolerated and immunogenic. The Phase 3 trial will check if the vaccine protects individuals at risk for symptomatic dengue across geography, irrespective of their serostatus.(6^✔, 7^✔)

How Do You Prevent Dengue Fever?

Following certain basic steps is really the most effective way to prevent and fight dengue. Since the only way to get dengue is from a mosquito bite, the best way to prevent it is to avoid mosquitoes and prevent from mosquito bites. This is particularly important if a dengue epidemic is underway in your city or town. Some ways to prevent dengue are described below:

• Mosquito breeds in stagnant water. Hence it is advisable to avoid stagnant water and pools on the ground, in flowerpots, buckets, barrels etc., in and around the neighborhood and the house. Water should always be stored in closed containers. Stagnant pools of water on the floor should be mopped up.
• Bleaching powder may be used in water sources that are not meant for drinking, as it will prevent the development of mosquito eggs.
• Avoid being bitten by the mosquitoes in the first place. Mosquitoes bite us as they require the protein present in human blood to produce eggs. To prevent being bitten, keep mosquitoes away by using mosquito repellents, mosquito repellent plants whether indoors or outdoors.
• To avoid mosquitoes, it is best to live inside a well screened or air conditioned house. If this is not possible, mosquito nets should be attached to all windows.

• Another way to prevent mosquito bites is to wear long-sleeved shirts, pants, socks, and shoes or boots when spending time outdoors.
• Mosquitoes are more active at dawn, dusk or early evening. It is therefore advisable to avoid being outdoors during these times to decrease the chances of being bitten by a dengue carrying mosquito.
• Mosquitoes are attracted to dark colored clothing, therefore it is better to wear bright and light colored clothes.
• Avoid strong perfumes or scented body lotions, as mosquitoes are drawn to strong odors.(8^✔)

References:

1. Dengue - (https://www.cdc.gov/Dengue/)
2. Dengue Fever - (https://www.nhp.gov.in/disease/musculo-skeletal-bone-joints-/dengue-fever)
3. Dengue Fever: A Wikipedia Clinical Review - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242787/)
4. Dengue Fever Test - (https://medlineplus.gov/lab-tests/dengue-fever-test/)
5. RNAi: Antiviral Therapy against Dengue Virus - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631757/)
6. Dengue Vaccine: Global Development Update - (http://apjai-journal.org/wp-content/uploads/2019/02/AP-100518-0309.pdf)
7. Dengue Vaccine Enters Phase 3 Trial in Brazil - (https://www.niaid.nih.gov/news-events/dengue-vaccine-enters-phase-3-trial-brazil)
8. Epidemic Dengue and Dengue Hemorrhagic Fever - (https://wonder.cdc.gov/wonder/prevguid/p0000010/p0000010.asp#head001002000000000)