1. VIRAL HEAMORRHAGIC FEVERS Ahmed Mandil Prof of Epidemiology Dept of Family & Community Medicine College of Medicine, King Saud University

2. 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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3. 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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4. Major global demographic changes: urbanization and population growth
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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5. Inadequate mosquito control services
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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6. 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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7. 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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9. 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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10. 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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11. Transmission of Dengue Virus by Aedes aegypti
Viremia
Extrinsic
incubation
period
DAYS 5 8 12 16 20 24 28
Human #1
Human #2
Illness
Mosquito feeds /
acquires virus
Mosquito refeeds /
transmits virus
Intrinsic
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12. Replication and Transmission of 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 tissues
4. Virus released and
circulates in blood 3 4 1 2
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13. Replication and Transmission of Dengue Virus (II)
5. Second mosquito
ingests virus with blood
6. 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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14. Aedes aegypti Mosquito
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15. 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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16. Clinical Characteristics of 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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
15-Apr-17
Hemorrhagic Fevers

24. Further Information
World Health Organization (WHO)
Centers for Disease Control & Prevention (CDC):
Halsted SB. Dengue Epidemiology. Pediatric Dengue Vaccine Initiative
Selvaraj I. Dengue and dengue hemorrhagic fever. India.
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25. Thank You
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