Dengue: Introduction, Serotypes, Symptoms, Severity, Lab Diagnosis, Treatment, Prevention, and Keynotes

Introduction

Dengue is a mosquito (Aedes aegypti)-borne viral disease. It is a major health threat in the tropical and sub-tropical territories of the world, particularly in urban and semi-urban areas. Approximately 50-100 million individuals have been infected with this fever annually (WHO data) and more than 100 countries are at risk of transmission. The following activities are responsible for contributing to fertile breeding areas for the mosquito (vector)-fast unplanned urbanization and migration of population from rural to urban sectors, climatic changes, no vector control, and poor sanitation services.

Virus Serotypes

There are four serotypes of the this virus. They are Dengue serotype-1 (DENV 1), DENV 2, DENV 3, and DENV 4. DENV-2 and DENV-4 are comparatively highly severe than DENV-1 and DENV-3.

Symptoms

• High fever (up to 104°F or 40°C)- Common
• With any of the other signs and symptoms-

1. Headache
2. Muscle, bone, or joint pain
3. Nausea
4. Vomiting
5. Swollen glands
6. Pain behind the eyes
7. Rash

Severity

Types according to severity are as follows-

Dengue without Warning Sign	Dengue with Warning Sign	Severe Dengue
Probable Dengue	Warning Signs	Severe plasma leakage
Live or travel to this disease endemic area having fever and two of the following features-	Abdominal pain or tenderness Persistent vomiting Clinical fluid accumulation Mucosal bleed Lethargy, restlessness Liver enlargement>2 cm Laboratory Findings-High HCT concurrent with a rapid decrease in platelet count	-Causing Dengue shock syndrome (DSS) -Fluid accumulation with respiratory distress
Nausea and vomiting Rash Aches and pain Tourniquet test positive Leukopenia Any warning sign	Note: Requiring strict observation and medical intervention	Severe bleeding
Laboratory confirmed dengue Important when no sign of plasma leakage		Severe organ involvement Liver-AST or ALT>=1000 CNS: Impaired consciousness

Lab Diagnosis

Viral Specific Assays-

1. NS1 Antigen Test: NS1 ( non-structural protein) antigenemia is detectable within 24 hours of infection and up to 9 days following symptom onset. The dengue virus NS1 antigen can be detected by requesting Dengue Virus NS1 Antigen. Blood is used as a separating serum for the testing.
2. Dengue IgM Test: It is used for the detection of immunoglobulin M (IgM) of present infection.
3. Dengue IgG Test: It is used for the detection of immunoglobulin G(IgG) of past infection that is not occurring now.
4. RT-PCR: The dengue serotype can be confirmed by ribonucleic acid (RNA) amplification by RT-PCR using either QunatStudio5 (applied biosystems by the Thermo Fisher Scientific) or BIO-RAD CFX96 Real-Time System (C1000 Touch Thermal Cycler) and other Kit preferred thermocyclers.
5. Vira Culture: It is a cumbersome and lengthy process. RT-PCR is preferred as a gold standard due to the rapid detection and confirmation of Dengue.

Viral non-specific assays

Viral non-specific assays-In this panel, other than viral tests are performed.

1. CBC (Complete blood count): A count of the total number of red blood cells (RBCs), white blood cells(WBCs), and platelets present in the blood.
2. Urine R/E:
3. LFT: LFT stands for liver function test and it includes SGOT, SGPT, Alkaline phosphate (ALP), Total Protein, and Albumin: Its functions clear from the title, and thus it helps to screen for liver infections, disease prognosis, alcoholic hepatitis, liver cirrhosis, and monitor possible effects of medications.
4. RFT: It is a renal (kidney) function test. It contains-Sodium, Potassium, Urea, and Creatinine: Healthy kidneys help remove waste from the body and RFT function tests check how well kidneys are working.
5. Chest X-ray: It is used to detect infection or air collecting in the space around a lung and also cancer. It is also beneficial in chronic lung conditions. e.g. emphysema and cystic fibrosis.
6. ECG: Electrocardiography (ECG) is normally used alongside other assays to help diagnose and monitor conditions affecting the heart.

Treatment

Specific antiviral drugs are lacking to treat this infection. Acetaminophen or paracetamol is preferred to control muscle aches, pains, and fever. Non-steroidal anti-inflammatory drugs(NSAIDs) like ibuprofen and aspirin are avoided due to their anticoagulant properties. Supportive care and staying well hydrated are two main conditions for patient management. A complete vaccine for all is still missing. The currently available vaccine is limited to people aged 9-45 years old and even also who have had at least one previous episode of this virus infection.  An untimely managed case may increase the risk of people developing severe condition that will be later potentially fatal.

Prevention

Saving from mosquito bites and vaccines are the most common ways of prevention but currently, the vaccine is not in full phase for everyone due to limitations. So, mosquito bites prevention is the only solution that can be practiced by following methods-

• Living in well-screened housing or air-conditioned
• Wearing protective clothing
• Using mosquito repellent. and
• Decreasing mosquito habitat

Keynotes

• Three warning signs of severe dengue are severe plasma leakage, severe hemorrhage, and severe organ impairment.
• Dengue is transmitted through mosquito bites.
• Aedes albopictus is also responsible for to transfer of dengue to a lesser extent.
• Dengue fever is also used to be called “breakbone fever due to the severe bone and muscle pain it sometimes can cause.
• Risk factors of dengue are living or traveling in tropical areas and having dengue fever in the past.

• Rapid NS1 antigen (positive), platelet count (reduction), and patient clinical features (high fever, muscle, bone, or joint pain are strong evidence of dengue.
• The addition of clinical lab tests and doctors consultations may vary according to the severity of dengue fever.
• The incubation period of dengue is 5-7 days.
• The clinical course completes into 3 phases i.e. febrile (2-7 days), critical (1-2 days), and convalescent.
• A. aegypti and A. albopictus are also vectors of chikungunya, yellow fever, and Zika viruses.

Further Reading

1. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
2. https://www.mayoclinic.org/diseases-conditions/dengue-fever/symptoms-causes/syc-20353078
3. https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0444-8
4. https://dndi.org/diseases/dengue/facts/?gclid