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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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) 15-Apr-17 Hemorrhagic Fevers

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. 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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) 15-Apr-17 Hemorrhagic Fevers

15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers 5

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 15-Apr-17 Hemorrhagic Fevers 6

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 15-Apr-17 Hemorrhagic Fevers 7

Aedes aegypti Mosquito 15-Apr-17 Hemorrhagic Fevers 8

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,.. 15-Apr-17 Hemorrhagic Fevers 9

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) 15-Apr-17 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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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 15-Apr-17 Hemorrhagic Fevers

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

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. 15-Apr-17 Hemorrhagic Fevers

Thank You 15-Apr-17 Hemorrhagic Fevers