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

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Goals/Objectives

 1. Epidemiology of Dengue  2. and Vectors  3. Transmission  4. Clinical Presentation  5. Labs  6. Treatment  7. Prevention/Vaccine

Epidemiology

 4 (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

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Vector Aedes aegypti Aedes albopictus AKA “ 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, , Yellow Fever, Zika, Chikungunya, Yellow Fever, Mayaro, Wolbachia* Dirofilaria immitis, , Wolbachia* https://www.cdc.gov/dengue/resources/30jan2012/comparisondenguevectors.pdf

Vector

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So, let’s dive into Dengue

Arbovirus Family: ▪ Bunyaviradae ▪ ▪ ▪ Togavirus

A group of viruses that are transmitted by Arthropod vectors. The word is an acronym : ARthropod-BOrne virus

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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 ❖ Phlebovirus ❖ ❖ Heartland Virus ❖ Toscana Virus GROUPS SPECIES ❖ Tick Borne Virus: ❖ Virus (KFDV) ❖ Tick-Borne Encephalitis Virus (TBEV) ❖ Mosquito Born ❖ Dengue Virus Group Flaviviridae ❖ Flavivirus Virus: ❖ Japanese ❖ ❖ St. Louis Encephalitis ❖ Encephalitis ❖ Murray Valley ❖ Group: Encephalitis ❖ Spondweni ❖ Spondweni Virus Group: ❖ (ZIKV) ❖ Yellow Fever Virus ❖ Yellow Fever Virus (YFV) Group:

Arbovirus (Taxonomy II)

Family Subfamily Genus Species ❖ Virus (AHSV) ❖ Virus (BTV) Reoviridae ❖ Equine Encephalitis Virus (EEV) ❖ Spinareovirinae Coltivirus ❖ Colorado Tick Fever Virus

Family Genus Species

❖ Eastern Equine Encephalitis Virus (EEE) Togavirus ❖ (RRV) Alphavirus ❖ Venezuelan Equine Encephalitis Virus (VEE) ❖ Western Equine Encephalitis Virus (WEE) ❖ Chikungunya Virus (CHIKV)

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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

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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

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Rash

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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

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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)

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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

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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

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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

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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)

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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

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Outlook

 Vaccines being developed  Prevention tactics  Treatment modalities  Watch CDC website for changing guidelines  Recognizing Dengue early

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