Lecture 7

Dengue Overview

  • Professor Lance Turtle

    • PhD FRCP DTMH

    • Chair in Immunity and Infectious Diseases, University of Liverpool

    • Consultant in Infectious Diseases, Liverpool University Hospitals

  • Date: 21st October 2025

  • Institution: Department of Clinical Infection, Microbiology, and Immunology

Arboviruses Nomenclature

Types of Arboviruses

  • Diseases Caused:

    • Yellow fever virus

    • Chikungunya (meaning "that which bends up" in Tanzanian Makonde dialect)

    • O’nyong nyong virus (meaning "joint weakening" in Ugandan dialect)

    • Geography:

    • Japanese encephalitis virus

    • West Nile virus

  • Vector Biology:

    • Tick-borne encephalitis virus

    • Sandfly fever virus

Arboviruses Classification

Viral Genomes and Families

  • RNA Types:

    • Single stranded RNA (positive sense, ssRNA (+))

    • Family: Flaviviridae (Flavivirus):

      • Dengue

      • Zika

      • Yellow fever

      • West Nile

      • Japanese encephalitis

    • Family: Togaviridae (Alphavirus):

      • Chikungunya

      • Western/Eastern equine encephalitis

    • Single stranded RNA (negative sense, ssRNA (–))

    • Family: Bunyaviridae:

      • Severe fever with thrombocytopaenia syndrome virus

      • Sandfly fever

      • Rift Valley fever

    • Family: Nairoviridae:

      • Crimea Congo Haemorrhagic fever (CCHF)

    • Double stranded RNA (dsRNA)

    • Family: Reoviridae:

      • Colorado tick fever (Coltivirus)

      • Orbivirus

Human Disease Manifestations

  • Symptoms:

    • Fever

    • Arthralgia (joint pain)

    • Rash

    • Shock

    • Haemorrhage

    • Hepatitis/Jaundice

    • Central Nervous System (CNS) disease

    • Haemorrhagic fevers

Zoonotic Transmission

Modes of Transmission

  • Types of Zoonosis:

    • Person to person (e.g., dengue)

    • Zoonosis without human spread (e.g., West Nile, Rift Valley fever)

    • Zoonosis with onward human-to-human spread (e.g., Zika, yellow fever)

    • Zoonosis with amplifying cycle: "Spillover" (e.g., Japanese encephalitis)

  • Direct Contact Spread:

    • Nosocomial (hospital-acquired) (CCHF)

    • Sexual contact (Zika)

Diagnosis of Dengue Virus Infection

Diagnostic Tests

  • Sytematic Approach:

    • IgM detection

    • IgG testing

    • Viremia testing

    • Culture and PCR tests

    • Serological tests

Dengue Virus Structure

  • Characteristics of Dengue Virus:

    • Single stranded RNA virus

    • Family: Flavivirus (related to Yellow Fever, Japanese Encephalitis, West Nile Virus)

    • Has four serotypes: DENV1, DENV2, DENV3, DENV4

Structural Proteins

  • Major structural proteins include:

    • Capsid protein

    • Membrane protein (M)

    • Envelope protein (E)

    • Precursor membrane protein (prM)

  • Non-structural Proteins:

    • Seven non-structural proteins critical for viral life cycle

Pathogenesis of Dengue Virus

Infection Cycle

  • Transmission Cycle:

    1. Aedes aegypti or Aedes albopictus (tropical regions) bites infected person

    2. Mosquito ingests blood containing dengue virus

    3. Virus incubates in mosquito for 8-10 days

    4. Infected mosquito then bites another person, transmitting the virus

  • Human Cycle:

    • No intermediate host is required as the virus is well-adapted to humans and primates

Sylvatic Cycle

  • Involves Mosquitoes:

    • Aedes species such as Aedes luteocephalus and Aedes furcifer

  • Animal Hosts:

    • Documented transmission can occur between mosquitoes and various monkey species (e.g., Chlorocebus sabaeus, Papio papio)

Epidemiology of Dengue

Global Distribution and Cases

  • Recent data (November 2022 - October 2023) from the European Centre for Disease Prevention and Control (ECDC) indicate notification rates of dengue cases across various regions.

  • Rates include 0.001-0.009, 0.01-0.99, and higher, categorized per 100,000 persons in various territories

Clinical Manifestations of Dengue

Dengue Illness Types

  • Classification of Dengue Illness:

    • Asymptomatic

    • Classic dengue fever

    • Dengue hemorrhagic fever

    • Dengue shock syndrome

  • Severe dengue is more common in older infants during primary infections or secondary infections with a different serotype

  • Annual Statistics:

    • 400 million infections

    • 100 million cases

    • 500,000 severe cases

    • Approximately 20,000 deaths annually

Warning Signs of Severe Dengue

  • Criteria for severe dengue:

    • Severe plasma leakage leading to shock (DSS)

    • Severe hemorrhage

    • Severe organ impairment

  • Testing Criteria Include:

    • Positive tourniquet test

    • Fever and at least two of the following: nausea, vomiting, rash, aches and pains, leukopenia (low white blood cell count)

Criteria for Dengue with Warning Signs

Laboratory Findings

  • Increases in Hematocrit (HCT) with a concurrent quick decrease in platelet count

  • Clinical warning signs such as:

    • Abdominal pain or tenderness

    • Persistent vomiting

    • Clinical fluid accumulation

    • Mucosal bleeding

    • Lethargy or restlessness

Immune Response and Antibody Development

Antibody Dependent Enhancement

  • Mechanism:

    • Secondary infections can lead to severe dengue due to non-neutralizing, enhancing antibodies which poorly neutralize new viral particles

  • B Cell Activation:

    • Certain B cell lines are targeted during enhancement leading to pathology

Summary of Dengue Immunology

  • Types of Antibodies:

    1. Neutralising anti-envelope antibodies = beneficial

    2. Non-neutralising anti-envelope antibodies = harmful

    3. Anti-prM antibodies = likely harmful

    4. Anti-NS1 antibodies = likely beneficial

    5. Anti-NS3 or NS5 T cell responses = probably beneficial

Dengue Vaccines

  • Current Vaccination Strategies:

    • Dengue vaccines require careful consideration of prior serostatus for optimal safety and efficacy

    • Studies have indicated significant differences in vaccine performance based on baseline seropositivity status

  • Example Data:

    • The Butantan dengue vaccine (TV003) shows a cumulative incidence decrease and a reported efficacy of 79.6%

Conclusion

  • Future Implications:

    • Rising global temperatures are projected to increase the incidence of dengue, with models suggesting a potential upsurge in cases as early as 2030.

  • Continued Research:

    • Ongoing studies are essential for understanding and managing dengue outbreaks effectively.

Contact Information

  • Professor Lance Turtle:

    • Email: lance.turtle@liverpool.ac.uk

    • Social Media: @lanceturtle / @lanceturtle.bsky.social