7/29/2018

1

Dengue UpdateAdam 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

7/29/2018

2

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

7/29/2018

3

7/29/2018

4

VectorAedes 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

eggs

Treeholes, bamboo internodes, but

can use household containers

Zika, Chikungunya, Yellow Fever,

Mayaro, Wolbachia*

Zika, Chikungunya, Yellow Fever,

Dirofilaria immitis, Usutu virus,

Wolbachia*

https://www.cdc.gov/dengue/resources/30jan2012/comparisondenguevectors.pdf

Vector

7/29/2018

5

So, let’s dive into Dengue

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

Family:▪ Bunyaviradae

▪ Flaviviridae

▪ Reoviridae

▪ Togavirus

Arbovirus

7/29/2018

6

Arbovirus (Taxonomy I)4 families: 2 subfamilies: 7 genus

Family Genus Species

Bunyaviradae

❖ Nairovirus ❖ Crimean–Congo Hemorrhagic Fever

❖ Orthobunyavirus

❖ Bunyamwera Virus

❖ California

Encephalitis

❖ Jamestown Canyon virus (JCV)

❖ La Crosse Encephalitis

❖ Phlebovirus ❖ Rift Valley Fever

❖ Toscana Virus

❖ Heartland Virus

Flaviviridae ❖ Flavivirus

GROUPS SPECIES

❖ Tick Borne Virus: ❖ Kyasanur Forest Disease Virus (KFDV)

❖ Tick-Borne Encephalitis Virus (TBEV)

❖ Mosquito Born

Virus:❖ Dengue Virus Group

❖ Japanese

❖ Encephalitis

Group:

❖ Japanese Encephalitis

❖ Murray Valley

Encephalitis

❖ St. Louis Encephalitis

❖ West Nile Virus

❖ Spondweni

Group:

❖ Spondweni Virus

❖ Zika Virus (ZIKV)

❖ Yellow Fever Virus

Group:❖ Yellow Fever Virus (YFV)

Arbovirus (Taxonomy II)

Family Subfamily Genus Species

Reoviridae SedoreovirinaeOrbivirus ❖ African Horse Sickness Virus (AHSV)

❖ Bluetongue Disease Virus (BTV)

❖ Equine Encephalitis Virus (EEV)

Seadornavirus ❖ Banna Virus

Spinareovirinae Coltivirus ❖ Colorado Tick Fever Virus

Family Genus Species

TogavirusAlphavirus

❖ Eastern Equine Encephalitis Virus (EEE)

❖ Ross River Virus (RRV)

❖ Venezuelan Equine Encephalitis Virus (VEE)

❖ Western Equine Encephalitis Virus (WEE)

❖ Chikungunya Virus (CHIKV)

7/29/2018

7

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

7/29/2018

8

Symptom Timeline

https://www.cdc.gov/dengue/epidemiology/index.html

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)

Timeline

https://www.cdc.gov/dengue/epidemiology/index.html

7/29/2018

9

Rash

7/29/2018

10

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

7/29/2018

11

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)

7/29/2018

12

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

7/29/2018

13

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

7/29/2018

14

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

7/29/2018

15

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)

7/29/2018

16

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

7/29/2018

17

Outlook

Vaccines being developed

Prevention tactics

Treatment modalities

Watch CDC website for

changing guidelines

Recognizing Dengue early