VIRAL HEAMORRHAGIC FEVERS

Ahmed MandilProf of Epidemiology

Dept of Family & Community MedicineCollege of Medicine, King Saud University

HEADLINES

• Examples

• Emerging & Re-emerging infections

• Dengue Fever (DF) versus Dengue Hemorrhagic Fever (DHF)

• Cycle of Disease Transmission of DF

• DF Agent & Vector

• DF / DHF Prevention and Control

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Common Viral Haemorrhagic Fevers

Rift valley fever, Dengue fever, Lassa fever

Ebola and Marburg viral disease

Bolivian / Argentinean haemorrhagic fever Haemorrhagic fever with renal syndromes

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Factors contributing to the emergence and re-emergence of arthropod-borne diseases (I)

• Major global demographic changes: urbanization and

population growth

• Sub-standard environmental sanitation that facilitates

transmission of Aedes aegypti - borne disease

(overcrowding in cities with poor sanitation)

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Factors contributing to the emergence and re-emergence of arthropod-borne diseases (II)

• Increased travel by airplane resulting in frequent

exchange of dengue viruses and other pathogens

• Inadequate mosquito control services

• The emergence of resistance to insecticides linked

to their increased misuse.

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Dengue Fever: Overview

• While 2.5 billion people are at risk of infection world-wide, an estimated 50 to 100 million cases of dengue fever (DF) and several hundred thousand cases of dengue hemorrhagic fever (DHF) occur per year

• DHF comprises 2-5% of secondary infections, with average case fatality rate of DHF is about 5 %

• In the last 20 years, dengue transmission and the frequency of dengue epidemics has increased greatly in most tropical countries, including Southwestern KSA, hence DF / DHF is considered a resurgent disease worldwide, especially in the tropics

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Risk Factors for DHF Occurrence

• Virus serotype: greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1

• Pre-existing anti-dengue antibody

– previous infection

– maternal antibodies in infants

• Host genetics

• Age (fatal cases are among children and young adults).

• Higher risk in secondary infections

• Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission)

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Cycle of Transmission• Agent: Dengue flaviviruses• Reservoir: human/mosquito cycle (urban tropical

areas); monkeys / mosquito cycle (western African / southeast Asian forests)

• Portal of exit: from reservoir-blood• Mode of transmission: bite of infective Aedes

aegypti mosquito (indirect vector-borne), no person-to-person transmission

• Portal of entry: skin-piercing-blood• Susceptible host: universal

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Agent: Dengue Viruses

• Four closely related single-stranded RNA Dengue flavi-

viruses (DEN-1, DEN-2, DEN-3 and DEN-4)

• Each serotype provides specific lifetime immunity, and

short-term cross-immunity

(A person can be infected as many as four times, once

with each serotype)

• All serotypes can cause severe and fatal disease

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Transmission of Dengue Virusby Aedes aegypti

Viremia Viremia

Extrinsic incubation

period

DAYS0 5 8 12 16 20 24 28

Human #1 Human #2

Illness

Mosquito feeds /acquires virus

Mosquito refeeds /transmits virus

Intrinsicincubation

period

Illness

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Replication and Transmissionof Dengue Virus (I)

1. Virus transmitted to human in mosquito saliva

2. Virus replicates in target organs

3. Virus infects white blood cells and lymphatic tissues4. Virus released and circulates in blood

3

4

1

2

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Replication and Transmissionof Dengue Virus (II)

5. Second mosquitoingests virus with blood6. Virus replicates in mosquito mid-gut and other organs, infects salivary glands

7. Virus replicates in salivary glands

6

7

5

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Aedes aegypti Mosquito

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Aedes aegypti

• Dengue Fever is transmitted by infected female Aedes

aegypti mosquito

• Primarily, it is a daytime feeder, highly domesticated

tropical mosquito, lives around human habitation

• Lays eggs and produces larvae preferentially in artificial

water containers inside and around the houses for example;

plastic containers, flower vases, buckets, used automobile

tires,..

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Clinical Characteristicsof Dengue Fever

• Incubation period 3-14 days (commonly 4-7 days)

• Fever and rash (erythema, maculo-papular)

• Pain: headache (intensive), muscles (myalgia), joints

(arthralgia), retro-orbital, etc

• Nausea / vomiting

• Hemorrhagic manifestations: DF (minor: petechiae, epistaxis,

gum-bleeding, gastro-intestinal); DHF (major: increased

vascular permeability, specific organs)

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Differential Diagnosis

• Other vector-borne diseases

• Other common maculo - papular rashes: measles (rubeola), German measles (rubella), etc

• Other systemic febrile illnesses

• Influenza, leptospirosis, typhoid fever, scrub typhus, etc

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Lab Diagnosis• Antigen detection: virus detection during acute

phase in blood / serum within 5 days of infection• Antibody detection: • IgM capture ELISA,

– RT-PCR; – Culture in mosquito cell-lines, – Immuno-flourescence, – PCR with nucleotide sequencing to detect

strains / genotypes

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Prevention

• The best preventive measure is vector control

• Personal protection against mosquito biting

– Screening doors and windows

– Protective clothing

– Application of mosquito repellents on exposed skin

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Vector Control Methods

• Biological control: largely experimental, e.g. place certain fish in

containers to feed on larvae

• Environmental control: elimination of larval habitats; covering

water holding containers, discarding artificial containers,…

– It is the most likely method to be effective in the long term.

• Chemical Control: larvicides may be used to kill immature aquatic

stages, but ultra-low volume fumigation is ineffective against adult

mosquitoes as Aedes aegypti is fully domesticated and mosquitoes

may have resistance to commercial aerosol sprays

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Community Participation

• Prevention and mosquito control through active

community involvement and participation to reduce

larval breeding sources is the key to success

• Public health education on the basics of dengue, e.g.:

– Locations for mosquito-laying of eggs

– Link between larvae and adult mosquitoes

– Dengue transmission, clinical picture, management,

vector control methods

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Dengue Vaccine?

• No licensed vaccine at present

• Effective vaccine must be tetravalent (against the 4

sero-types), where field testing of an attenuated

tetravalent vaccine currently underway

• May immunize population against yellow fever, if

dengue occurs near jungle foci, as the urban vector

for both diseases is the same

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HEADLINES

• Examples

• Emerging & Re-emerging infections

• Dengue Fever (DF) versus Dengue Hemorrhagic Fever (DHF)

• Cycle of Disease Transmission of DF

• DF Agent & Vector

• DF / DHF Prevention and Control

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Further Information

1. World Health Organization (WHO) http://www.who.int/denguenet/

2. Centers for Disease Control & Prevention (CDC): http://www.cdc.gov/ncidod/dvbid/dengue/

3. Halsted SB. Dengue Epidemiology. Pediatric Dengue Vaccine Initiative

4. Selvaraj I. Dengue and dengue hemorrhagic fever. India.

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Thank You

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