Discuss morphology and antigenic types of dengue virus. Describe the clinical manifestations and laboratory diagnosis of dengue fever.

Morphology of Dengue Virus

Dengue virus belongs to the Flaviviridae family, genus Flavivirus. It is a single-stranded, positive-sense RNA virus with a genome approximately 10.7 kb in length. The virion is enveloped and approximately 40-60 nm in diameter.

• Envelope: Contains two major envelope proteins, E (envelope protein) and M (membrane protein), crucial for viral entry into host cells.
• Capsid: Encloses the RNA genome and is composed of the capsid (C) protein.
• Genome: The single RNA strand is associated with proteins forming the nucleocapsid.
• NS proteins: Non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) are essential for viral replication and immune evasion. NS1 is particularly important as it is released during infection and can be detected in serum.

Antigenic Types of Dengue Virus

There are four distinct serotypes of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4). These serotypes are antigenically related but sufficiently different that infection with one serotype provides lifelong immunity to that serotype, but only temporary and partial protection against others.

Serotype	Antigenic Characteristics	Geographical Distribution (as of 2023)
DENV-1	Possesses unique epitopes on its E protein.	Asia, Africa, Americas
DENV-2	Highly virulent, often associated with severe dengue outbreaks.	Asia, Latin America
DENV-3	Can cause outbreaks with atypical clinical presentations.	Southeast Asia, India, Africa
DENV-4	Generally less virulent, but can contribute to disease burden.	Southeast Asia, Pacific Islands

Sequential infection with different serotypes increases the risk of severe dengue due to antibody-dependent enhancement (ADE), where pre-existing antibodies enhance viral entry into immune cells.

Clinical Manifestations of Dengue Fever

Dengue fever typically presents with an incubation period of 4-10 days. The clinical course is often divided into three phases:

1. Febrile Phase (2-7 days)

• Sudden onset of high fever (40°C/104°F)
• Severe headache, particularly retro-orbital pain
• Myalgia (muscle pain) and arthralgia (joint pain) – hence the nickname “breakbone fever”
• Nausea, vomiting
• Maculopapular rash

2. Critical Phase (24-48 hours)

This phase occurs as the fever subsides and is characterized by increased vascular permeability, leading to plasma leakage.

• Abdominal pain
• Persistent vomiting
• Bleeding manifestations (e.g., petechiae, epistaxis, gum bleeding)
• Lethargy and restlessness
• Hypotension and shock (DSS)

3. Recovery Phase (2-3 days)

• Gradual reabsorption of extravasated fluid
• Improvement in general condition
• Bradycardia
• Rash may reappear (convalescent rash)

Laboratory Diagnosis of Dengue Fever

Diagnosis relies on a combination of clinical suspicion and laboratory confirmation.

• Complete Blood Count (CBC): Thrombocytopenia (low platelet count) is a hallmark of dengue fever. Leukopenia (low white blood cell count) is also common.
• NS1 Antigen Detection: Detects the NS1 protein in serum, highly sensitive during the early febrile phase (first 5 days).
• IgM and IgG Antibody Detection: IgM antibodies appear after 5-7 days of illness and persist for 30-60 days. IgG antibodies appear later and provide long-term immunity.
• RT-PCR: Detects viral RNA, most sensitive during the first 5 days of illness. Useful for serotyping.
• Plaque Reduction Neutralization Test (PRNT): Gold standard for serotyping, but time-consuming and requires specialized expertise.