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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

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  1. VIRAL HEAMORRHAGIC FEVERS Ahmed MandilProf of EpidemiologyDept of Family & Community MedicineCollege 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 Hemorrhagic Fevers

  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 Hemorrhagic Fevers

  4. 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 Aedesaegypti - borne disease (overcrowding in cities with poor sanitation) Hemorrhagic Fevers

  5. 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. Hemorrhagic Fevers

  6. Dengue Fever: Overview • While 2.5 billion people are at risk of infectionworld-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 Hemorrhagic Fevers

  7. Risk Factors for DHF Occurrence • Virus serotype: greatest forDEN-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) Hemorrhagic Fevers

  8. Hemorrhagic Fevers

  9. Hemorrhagic Fevers

  10. 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 Aedesaegypti mosquito (indirect vector-borne), no person-to-person transmission • Portal of entry: skin-piercing-blood • Susceptible host: universal Hemorrhagic Fevers

  11. 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 Hemorrhagic Fevers

  12. Mosquito refeeds / Mosquito feeds / transmits virus acquires virus Intrinsic incubation period Extrinsic incubation period Viremia Viremia 5 0 8 12 16 20 24 28 DAYS Illness Illness Human #1 Human #2 Transmission of Dengue Virusby Aedes aegypti Hemorrhagic Fevers

  13. 1 1. Virus transmitted to human in mosquito saliva 2 2. Virus replicates in target organs 4 3. Virus infects white blood cells and lymphatic tissues 3 4. Virus released and circulates in blood Replication and Transmissionof Dengue Virus (I) Hemorrhagic Fevers

  14. 6 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito mid-gut and other organs, infects salivary glands 7 5 7. Virus replicates in salivary glands Replication and Transmissionof Dengue Virus (II) Hemorrhagic Fevers

  15. Aedes aegypti Mosquito Hemorrhagic Fevers

  16. Aedes aegypti • Dengue Fever is transmitted by infected female Aedes aegyptimosquito • 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,.. Hemorrhagic Fevers

  17. 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) Hemorrhagic Fevers

  18. 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 Hemorrhagic Fevers

  19. 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 Hemorrhagic Fevers

  20. Prevention • The best preventive measure is vector control • Personal protectionagainst mosquito biting • Screening doors and windows • Protective clothing • Application of mosquito repellents on exposed skin Hemorrhagic Fevers

  21. 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 Aedesaegyptiis fully domesticated and mosquitoes may have resistance to commercial aerosol sprays Hemorrhagic Fevers

  22. Community Participation • Prevention and mosquito control through active community involvement and participation to reduce larval breeding sourcesis the key to success • Public health educationon 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 Hemorrhagic Fevers

  23. 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 Hemorrhagic Fevers

  24. 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 Hemorrhagic Fevers

  25. Further Information • World Health Organization (WHO) http://www.who.int/denguenet/ • Centers for Disease Control & Prevention (CDC): http://www.cdc.gov/ncidod/dvbid/dengue/ • Halsted SB. Dengue Epidemiology. Pediatric Dengue Vaccine Initiative • Selvaraj I. Dengue and dengue hemorrhagic fever. India. Hemorrhagic Fevers

  26. Thank You Hemorrhagic Fevers

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