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7/29/2018 Dengue Update Adam C. Hunt, D.O., M.H.S. Covenant Emergency Care Center, Saginaw, MI Disclosures None This lecture is 99.6% free of any Russian collusion 1 7/29/2018 Goals/Objectives 1. Epidemiology of Dengue 2. Virus and Vectors 3. Transmission 4. Clinical Presentation 5. Labs 6. Treatment 7. Prevention/Vaccine Epidemiology 4 viruses (DENV-1, DENV-2, DENV-3, DENV-4) Positive sense, single stranded RNA Flaviviruses AKA “Breakbone Fever”, “Three Day Fever”, “Dandy Fever” 1/3 of the world’s population at risk ~400 million people infected annually 75% of infections are asymptomatic Epidemics in the tropics Caribbean, Latin America, Southern Asia, Africa, Pacific Islands Rarely in US, but sporadic outbreaks in Florida, Hawaii and Tex-Mex Border Most Cases in the US are imported (tourist/travelers) www.cdc.gov/dengue/index.html 2 7/29/2018 3 7/29/2018 Vector Aedes aegypti Aedes albopictus AKA “Yellow Fever Mosquito” AKA “Asian Tiger Mosquito” Urban Associated with thickets and arboreal vegetation Indoor and Outdoor Outdoor or Garden Mosquito Sneaky biter Aggressive biter Humans (almost entirely) Any vertebrate (not picky) Main vector Secondary Uses household containers to lay Treeholes, bamboo internodes, but eggs can use household containers Zika, Chikungunya, Yellow Fever, Zika, Chikungunya, Yellow Fever, Mayaro, Wolbachia* Dirofilaria immitis, Usutu virus, Wolbachia* https://www.cdc.gov/dengue/resources/30jan2012/comparisondenguevectors.pdf Vector 4 7/29/2018 So, let’s dive into Dengue Arbovirus Family: ▪ Bunyaviradae ▪ Flaviviridae ▪ Reoviridae ▪ Togavirus A group of viruses that are transmitted by Arthropod vectors. The word arbovirus is an acronym : ARthropod-BOrne virus 5 7/29/2018 Arbovirus (Taxonomy I) 4 families: 2 subfamilies: 7 genus Family Genus Species ❖ Nairovirus ❖ Crimean–Congo Hemorrhagic Fever Bunyaviradae ❖ Bunyamwera Virus ❖ Jamestown Canyon virus (JCV) ❖ Orthobunyavirus ❖ California ❖ La Crosse Encephalitis Encephalitis ❖ Phlebovirus ❖ Rift Valley Fever ❖ Heartland Virus ❖ Toscana Virus GROUPS SPECIES ❖ Tick Borne Virus: ❖ Kyasanur Forest Disease Virus (KFDV) ❖ Tick-Borne Encephalitis Virus (TBEV) ❖ Mosquito Born ❖ Dengue Virus Group Flaviviridae ❖ Flavivirus Virus: ❖ Japanese ❖ Japanese Encephalitis ❖ St. Louis Encephalitis ❖ Encephalitis ❖ Murray Valley ❖ West Nile Virus Group: Encephalitis ❖ Spondweni ❖ Spondweni Virus Group: ❖ Zika Virus (ZIKV) ❖ Yellow Fever Virus ❖ Yellow Fever Virus (YFV) Group: Arbovirus (Taxonomy II) Family Subfamily Genus Species Orbivirus ❖ African Horse Sickness Virus (AHSV) ❖ Bluetongue Disease Virus (BTV) Reoviridae Sedoreovirinae ❖ Equine Encephalitis Virus (EEV) Seadornavirus ❖ Banna Virus Spinareovirinae Coltivirus ❖ Colorado Tick Fever Virus Family Genus Species ❖ Eastern Equine Encephalitis Virus (EEE) Togavirus ❖ Ross River Virus (RRV) Alphavirus ❖ Venezuelan Equine Encephalitis Virus (VEE) ❖ Western Equine Encephalitis Virus (WEE) ❖ Chikungunya Virus (CHIKV) 6 7/29/2018 Dengue Timeline Transmission Humans are only hosts Mosquitos are vectors No congenital transmission, but transmission can occur at time of delivery Can be spread thru breastmilk Not sexually transmitted Rare, but documented cases of transmission in organ transplant and blood transfusions https://www.cdc.gov/dengue/epidemiology/index.html 7 7/29/2018 Symptom Timeline Symptoms start 4-7 days after mosquito bite High Fever (lasts 2-7 days) Headache, Retro-orbital pain, Myalgias/arthralgias (1-2 days after fever) Flushing of face, Anorexia, Abdominal Pain, RASH (3-4 days after fever) Rash on trunk, medial aspect of arms/thighs, plantar and palmar surfaces Petechial, macular, papular, maculopapular, purpura Rash does not itch Hemorrhagic (Nose bleeds, bleeding gums, internal bleeding, shock) https://www.cdc.gov/dengue/epidemiology/index.html Timeline https://www.cdc.gov/dengue/epidemiology/index.html 8 7/29/2018 Rash 9 7/29/2018 Rash Diagnosis WHO Classification Dengue: Febrile with travel/living in area of risk AND ≥2: Nausea, vomiting, rash, aches/pains, +tourniquet test, leukopenia Warning signs that this may progress to Severe Dengue: Abd Pain/tenderness, persistent vomiting, clinical fluid collection, mucosal bleeding, lethargy, restlessness, hepatomegaly Severe Dengue: Dengue + Severe plasma leakage leading to shock or fluid overaccumulation with respiratory distress, severe bleeding or organ impairment Ex: Tranaminases ≥1000, impaired consciousness or heart impairment https://www.cdc.gov/dengue/clinicallab/casedef.html 10 7/29/2018 Tourniquet Test Diagnosis Vitals History & PE Standard Labs CBC, CMP, Sed rate, CRP Diagnostic Labs RT-PCR ≤ 5 days from symptom onset NS1 (Nonstructural Protein 1 antigen immunoassay): ≤ 5 days from fever onset and may be positive for up to 9 days IgM ELISA ≥ 4 days after fever onset and can test up to 90 days post fever onset High Cross reactivity with other Flaviviruses (YF, West Nile, JE, Zika) 11 7/29/2018 Diagnosis Lab findings: CBC: Leukopenia and thrombocytopenia CMP: elevated AST/ALT, Hyponatremia Normal Sed rate Rapid NS1 takes 15 mins… if your hospital carries it RT-PCR takes days and only certain labs use it IgM ELISA test kit can be done in the same day… if you have it Treatment (Easy Answer) Treat the symptoms Supportive Care 12 7/29/2018 Treatment (Difficult Answer) Supportive care Early recognition and prompt supportive care can lower rates of medical complications and death No antivirals available for Dengue Avoid ASA and NSAIDS, use tylenol Do not transfuse platelets, shown to do more harm than good No corticosteroids. No shown benefit, possible harm. Unless, Immune Thrombocytopenic purpura (ITP) Severe Dengue Bad to worse Capillaries leak Third space Pressure dump 13 7/29/2018 Travel Advisories You saw the map… check the CDC website for specific travel details Vaccine Dengue Vaccine Initiative www.denguevaccine.org GDAC- Global Dengue & Aedes-transmitted Diseases Consortium www.preventdengue.org Major roadblock… who gets severe dengue? Not well understood, but thought to be immune modulated. Possible Antibody-dependant enhancement Possible Cytokine storm Possible cross reactive T-cells 14 7/29/2018 Vaccine Dengvaxia by Sanofi Pasteur (France) Live attenuated, recombinant, tetravalent 3 dose (0, 6, 12 months) Registered for use in endemic areas Globally 65% effective, but 81.9% effective on seropositive and 52.5% effective in seronegative at baseline Current use in Mexico, Brazil, Thailand, Phillipines www.who.int/immunization/research/development/dengue_vaccines/en/ Vaccine Phase III trials Butantan-DV (Brazil) Tetravalent, live attenuated Ongoing Trial (Brazil) Takeda’s-TDV (Japan) Tetravalent, live attenuated TIDES trial (Latin America & Asia) 15 7/29/2018 Vaccine Discussion Why is the dengue vaccine not available in the US? Because there is a higher incidence of severe dengue in seronegatives that get the vaccine (most of the US population). You can test IgG antibodies (ELISA), but this gets expensive. Prevention Avoiding mosquitos Barrier control/repellants Travel Planning Water containers/breeding ground control 16 7/29/2018 Outlook Vaccines being developed Prevention tactics Treatment modalities Watch CDC website for changing guidelines Recognizing Dengue early 17.
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