Download 4-Viral Hemorrhagic Fevers (Jan 2010).

VIRAL HEAMORRHAGIC FEVERS
Ahmed Mandil
Prof of Epidemiology
Dept of Family & Community Medicine
College 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, DEN4 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 flaviviruses (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 Virus
by Aedes aegypti
Mosquito refeeds /
transmits virus
Mosquito feeds /
acquires virus
Extrinsic
incubation
period
Intrinsic
incubation
period
Viremia
Viremia
5
0
Illness
Human #1
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12
16
DAYS
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24
28
Illness
Human #2
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Replication and Transmission
of Dengue Virus (I)
1
1. Virus transmitted
to human in mosquito
saliva
2. Virus replicates in
target organs
2
3. Virus infects
white
blood cells and
lymphatic tissues
4. Virus released and
circulates in blood
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Hemorrhagic Fevers
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Replication and Transmission
of Dengue Virus (II)
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5. Second mosquito
ingests virus with
blood
6. Virus replicates in
mosquito mid-gut and
other organs, infects
salivary glands
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5
7. Virus replicates in
salivary glands
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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 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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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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