Dengue Fever - Symptoms, Causes, Diagnosis and Treatment

Sometimes, dengue fever symptoms are mild and can be mistaken for those of the flu or another viral infection. Younger children and people who have never had the infection before tend to have milder cases than older children and adults.

However, serious problems can develop. These include dengue hemorrhagic fever, a rare complication characterized by high fever, damage to lymph and blood vessels, bleeding from the nose and gums, enlargement of the liver, and failure of the circulatory system. The symptoms may progress to massive bleeding, shock, and death. This is called dengue shock syndrome (DSS).

People with weakened immune systems as well as those with a second or subsequent dengue infection are believed to be at greater risk for developing dengue haemorrhagic fever.

Dengue fever is caused by one of four dengue viruses (DENV). Transmission of these viruses to humans happens through the bites of an infected mosquito. The most common types of mosquitoes responsible for spreading dengue fever are Aedes aegypti and Aedes albopictus mosquitoes.

These mosquitoes are widely found in tropical and subtropical regions, including Southeast Asia, the western Pacific islands, Latin America, and Africa. When an infected mosquito bites a person, the virus initially enters the bloodstream, targets the liver, and then propagates to other organs. It replicates there and impairs the liver's functioning, accumulating toxins in the blood, resulting in fever, muscle pain, headache, and rash. If not managed, its severity may cause liver failure.

Dengue haemorrhagic fever is a severe and fatal condition of patent suffering from dengue fever. The patient may develop dengue hemorrhagic fever symptoms that include pain in the abdomen, persistent vomiting, change in body temperature from fever to hypothermia, irritability, confusion, and haemorrhagic manifestations. The patient might show early signs of shock, including weak pulse, restlessness, and cold clammy skin.

Abnormal haemostasis and plasma leakage are the pathological cause of the occurrence of haemorrhagic dengue fever. The plasma leakage is due to the cytokine-mediated increased vascular permeability.

Vascular permeability is defined as the ability of blood vessels to regulate the bidirectional flow of molecules and immune cells up to a particular size and to prevent the extravasation of larger molecules. In normal circumstances, molecules lesser than 40 kDa can pass through, whereas molecules such as albumin (66 kDa) and transferrin (80 kDa) retain. In case of disease conditions, such as inflammation or allergy, molecules of 2,000 kDa may extravasate, resulting in plasma leakage.

Dengue haemorrhagic fever is mainly observed in children and infants. Epidemiological studies reported, dengue haemorrhagic fever occurs, especially in children with a secondary infection with a dengue virus or infected with different serotypes from their primary (initial) dengue infection. In infants, they acquire dengue antibodies from the mother and experience dengue infection.

As per World Health Organization (WHO) criteria, the following are the criteria defined for dengue hemorrhagic fever. 

• Presence of any haemorrhagic manifestation
• Thrombocytopenia (decrease in platelet count; <100,000 cells/mm3)
• Increased body temperature or recent history of fever (lasting for 2–7 days)
• Evidence of increased vascular permeability
  

Dengue hemorrhagic fever is a serious complication of dengue fever and is more likely to be seen in pregnant women than non-pregnant. This might be due to changes in immunologic, physiologic, endocrinologic and metabolic changes during pregnancy that increase the risk of having infections.

Most pregnant women are more likely to infect in the third trimester. Placental injury and possible vertical transmission of the virus occur as a result of increased vascular permeability and endothelial leakage in dengue hemorrhagic fever. During the first trimesters, spontaneous abortion and in the third trimester, premature birth and severe and prolonged bleeding after surgical births are serious complications. 

Dengue Shock Syndrome

Diagnosis of Dengue Fever

Doctors can diagnose dengue infection with a blood test to check for the virus or antibodies to it. If you become sick after travelling or living near to people those already having dengue infection, let your doctor know. This will allow your doctor to evaluate the possibility that your symptoms were caused by a dengue infection.

Doctors may suggest a combination of blood tests and imaging tests to diagnose dengue fever infection, because the body’s immune response to the virus is complex and dynamic. The dengue infection is difficult to diagnose without laboratory and radiology tests because initially symptoms may be the same as other diseases, such as malaria. Tests may include:

• Complete blood count (CBC or CBP) - to check the platelet count typical of the later stages of the illness and to detect the decrease in hematocrit, hemoglobin, and red blood cell (RBC) count (evidence of anemia) that would occur with blood loss associated with severe dengue fever.
• Dengue Serology Test (Dengue IgG & IgM) - to detect antibodies produced by the immune system when a person has been exposed to the virus; these tests are most effective when performed at least 4 days after exposure in both primary and secondary infections.
• Dengue Virus Antigen Detection (NS1) - to confirm Dengue viral infection. This test is useful to diagnose early dengue infection and can be conducted within 1-2 days following Dengue infection.

In case of severe symptoms Doctors may suggest other blood test and radiology imaging test to know the spread of dengue infection to other organs, these may include:

• Liver function tests (LFT) - to detect mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin caused by Aedes mosquito's virus hepatotoxic effects that can aslo lead to acute liver failure, with fatal outcomes.
• Renal Function Test (RFT) - to check the elevation of the serum creatinine level that may cause variety of renal diseases such as Acute renal failure, acute tubular necrosis, hemolytic uremic syndrome, hypotension, rhabdomyolysis, proteinuria, glomerulopathy, nephrotic syndrome or hemolysis.
• ECG - to check the heart electrical disturbances. In many patients ECG abnormalities observed mainly sinus bradyarrhythmias, ventricular asystole, sinus tachyarrhythmias, supraventricular tachycardia (SVT) and ST- and T-wave changes due to electrolyte abnormalities of potassium, calcium, magnesium caused by dengue infection.
• Ultrasound abdomen (USG) – to check the conditions like serositis, fluid in abdomen, edema of the gallbladder, pericholecystic fluid, ascites (buildup of fluid in spaces within your abdomen) mainly caused by dengue fever infection.
• Chest X-ray - to check the pleural effusion (the build-up of excess fluid between the layers of the pleura (the tissues that line the lungs and the chest)), pericardial effusion (the buildup of the fluid in the saclike double-layered structure around the heart called as pericardium) caused by dengue fever infection.
• D-dimer – to check D-dimer value in the blood, D-dimer is a protein fragment made when a blood clot dissolves in your body. Dengue fever infection can increase the D-dimer levels in the blood and that can result pain in body, sharp chest pain, high fever, trouble breathing and changes in skin color of your arm or leg.
• 2D echocardiography (2D Echo) - to check the damage to heart muscles. Severe dengue fever affects the heart structurally and functionally. Cardiac complications secondary to dengue virus infection vary from self-limiting arrhythmias to severe myocardial infarction, leading to hypotension, pulmonary edema, and cardiogenic shock.
• A fibrinogen test - to check fibrinogen levels, Fibrinogen is a blood protein made in liver and helps blood clotting. Low fibrinogen may make it difficult for blood to clot. In case of complicated dengue hemorrhagic fever patients have tendency of excessive bleeding, doctor may go for this test to check your fibrinogen levels.
• Fibrin degradation products blood test - to check the FDP levels, Fibrin degradation products (FDPs) are the substances left behind when clots dissolve in the blood. Increased FDPs may be a sign of primary or secondary fibrinolysis (clot-dissolving activity) due to dengue hemorrhagic fever.
  

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How Dengue Impact the production of White Blood Cell (WBC) & Platelets?

Dengue infection is mainly spread through the bite of a virus-infected Aedes Aegypti mosquito. The virus enters the body when the mosquito bites and begins to spread. The drop in platelets is caused by a condition called "thrombocytopenia", through direct suppression of the bone marrow or an autoimmune reaction and antibodies pushed into place. Although the dengue virus does not destroy platelets, it can trigger complications that impair platelet count and function.

Platelet loss can be recorded in many underlying conditions. A healthy person is estimated to have 1,50,000 - 4,50,000 platelets / μL. When infected with the dengue virus, platelet counts can reach minimal levels, may be less than 40,000 platelets / μL. In some cases, you can witness the decline within a day. This usually occurs at the peak of infection, during a fever of 3-4 days. Comorbidities, immunity, and age can also exacerbate platelet loss.

If necessary, regular blood transfusions can increase the platelet count. In addition to these remedies, one of the best ways to improve your platelet count is to include foods that help with recovery in your diet. Including papaya leaf extract, green leafy vegetables, fruits, iron-rich foods, foods rich in vitamin C and vitamin K, and supplements can increase and stabilize healthy platelet counts during infection.

The best way to prevent the disease is to prevent bites by infected mosquitoes. To protect yourself:

• Use mosquito repellents, even indoors.
• When outdoors, wear long-sleeved shirts and long pants tucked into socks.
• When indoors, use air conditioning if available.
• Make sure window and door screens are secure and free of holes. If sleeping areas are not screened or air-conditioned, use mosquito nets.
• If you have symptoms of dengue, speak to your doctor.
• To reduce the mosquito population, get rid of places where mosquitoes can breed. Regularly change the water in outdoor bird baths and pets' water dishes, emptying stagnant water from buckets.

If someone in your home gets dengue fever, be especially vigilant about efforts to protect yourself and other family members from mosquitoes. Mosquitoes that bite the infected family member could spread the infection to others in your home.

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