An Introduction to Dengue, Zika and Chikungunya Viruses Natalie Marzec, MD, MPH Zoonoses Epidemiologist 2017 Global Health and Disasters Course
Objectives Arbovirus Overview Public Health Activities Clinical Presentations Diagnostic Testing Prevention and Control Where are we headed?
Arbovirus Overview
Go YY et al Clin Exp Vaccine Res 2013
General Transmission Cycle
The Vectors Aedes albopictus Aedes aegypti *Images from the CDC Public Health Image Library
Ae. aegypti Ae. albopictus Kraemer M, et al. elife 2015
Why is Aedes aegypti such a good vector? Prefers artificial water containers for larvae Prefers areas where humans live as adults Prefers human blood for meals Adult females often feed on multiple hosts in a gonotrophic cycle
Public Health Activities
U.S. Public Health Agencies Federal government: Centers for Disease Control and Prevention -> National Center for Emerging and Zoonotic Infectious Diseases -> Division of Vector-Borne Diseases -> Arboviral Diseases Branch & Dengue Branch State government: Colorado Department of Public Health and Environment -> Disease Control and Environmental Epidemiology Division -> Communicable Diseases Branch -> Zoonoses Program Local Public Health Agencies (county or region level)
Notifiable Conditions Every state and territory has a list of Reportable Conditions Dengue, Zika, and chikungunya (along with other arboviral infections) are reportable https://www.colorado.gov/pacific/cdphe/report-adisease
Arboviral Surveillance ArboNET: CDC s national system Human and animal data States provide the data CEDRS: CDPHE s disease reporting system Case investigations primarily by local agencies
Clinical Presentations
A 30 year old female 3 days of fever, muscle and joint aches, and headache No significant past medical history Does not take any medications (recently stopped using birth control) Vital signs: T 101.1, P 90, BP 120/65, RR 12, O2 sat 98% What additional history do you want?
Travel History 5 days ago she and her husband returned from a 2 week trip to Puerto Rico Which viruses are or have been transmitted in Puerto Rico? A. Zika B. Dengue C. Chikungunya D. All of the above
Travel History 5 days ago she and her husband returned from a 2 week trip to Puerto Rico Which viruses are or have been transmitted in Puerto Rico? A. Zika B. Dengue C. Chikungunya D. All of the above
Similar Presentations Make Diagnosis Difficult Feature Zika Dengue Chikungunya Fever ++ +++ +++ Rash +++ + ++ Conjunctivitis ++ - - Arthralgia ++ + +++ Myalgia + ++ + Headache + ++ ++ Hemorrhage - ++ - Shock - + -
Zika
Status of the Americas Outbreak Graph from PAHO
Areas with Zika Risk as of 9/14/2017 Map from CDC.gov
Non-Mosquito Transmission Sexual Vertical Lab work Potentially via transfusions www.giantmicrobes.com
Zika Symptoms Incubation period: 3-12 days Symptoms last 4-7 days but most people are probably asymptomatic Fever Rash Joint pain Conjunctivitis
Congenital Zika Syndrome Syndrome of severe birth defects associated with congenital Zika virus infection Other reported birth defects: Postnatal microcephaly Neural tube defects Possibly more Graphic from CDC.gov
Guillain-Barré Syndrome A demyelinating disease weakness and tingling -> possible paralysis First associated with Zika in the 2013-2014 French Polynesia outbreak Americas outbreak: countries reporting increases in GBS Appears to be strongly linked to Zika but uncommon Iillustration from Mosby s Medical Dictionary online
Dengue: break-bone fever
Dengue Serotypes Four serotypes: DEN-1 through DEN-4 Distinct genotypes within serotypes Recovery from one serotype leads to lifelong immunity TO THAT SEROTYPE Immunity to one serotype does not fully protect against other serotypes Subsequent infection with a different serotype increases the risk of severe dengue
Non-Mosquito Transmission Rarely through transfusions or transplants Evidence that vertical transmission via placenta or at birth can occur www.giantmicrobes.com
Dengue Symptoms Incubation period: 4-10 days Main symptoms are high fever AND: Severe headache Severe retroorbital pain Joint and/or muscle or bone pain Rash Mild bleeding Leukopenia Logo from www.breakdengue.org
Undifferentiated Fever Fever with non-specific, mild symptoms Unable to be distinguished from other acute febrile illnesses Tend to be young children, or people infected for the first time Usually recover without need for inpatient care
Dengue Fever (+/- hemorrhage) 2-7 days of high fever 2 or more of the following: Severe headache Retroorbital pain Myalgias/arthralgias Erythematous maculopapular rash Mild hemorrhagic manifestation
Dengue Hemorrhagic Fever Febrile Phase: looks like Dengue Fever Critical (Plasma Leak) Phase: Increase in hematocrit, ascites, pleural effusion, low albumin/protein Can progress to Dengue Shock Syndrome Convalescent (Reabsorption) Phase Associated with secondary infections
Severe Dengue Warning Signs 3-7 days after symptom onset: Severe abdominal pain, persistent vomiting Red spots on the skin Nose or gum bleeding Hematemesis/melena Drowsiness Irritability Pale, cold, or clammy skin Difficulty breathing
Chikungunya: that which bends up
Map from CDC.gov; Data as of 4/22/16
Non-Mosquito Transmission Rarely mother to child at birth No reports of transmission via breastmilk Possibly via blood transfusion but no reports so far www.cdc.gov
Chikungunya Symptoms Incubation: 3-7 days Most people develop symptoms Symptoms last about a week: Most common: fever & joint pain Also: headache, muscle pain, joint swelling, rash Joint pain can persist for months or relapse after recovery
Diagnostic Testing
Emergency Use Authorization Used by FDA to make tests and treatments available in public health emergencies in this case specifically in response to the Americas Zika outbreak Certain criteria must be met for testing: Pregnant with potential exposure Symptomatic with potential exposure
Nucleic Acid PCR can be used during viremic period: Dengue: up to 5 days Zika: up to 14 days (and maybe more) Chikungunya: up to 8 days Trioplex: tests for Zika, dengue and chikungunya
Serology IgM Testing Dengue: after a week; IgM may last over 90 days Zika: IgM may be present for prolonged period Chikungunya: after a week Flavivirus IgM testing is complicated by cross reactivity!
Serology PRNT Testing Plaque reduction neutralization test To determine which flavivirus is present Does not help determine timing of infection Used to confirm Zika IgM positive testing
Testing our case patient 3 days after symptom onset -> PCR What if it were 21 days after symptom onset? What if she were pregnant?
Prevention & Control
Prevention Vaccination: Vaccines are in development None licensed in U.S. Mosquito bite prevention Repellent Long sleeves and pants Screens on windows, eliminate standing water
Integrated Mosquito Management Public education and community involvement Source reduction Larval surveillance and control Adult surveillance and control AMCA www.mosquito.org
Where are we headed?
What will be the next epidemic arbovirus?
Factors that allow for emergence Genetic changes in viruses: increased virulence, higher viremic levels, better vector competence Ecologic changes: new niches, host vertebrate invasion into new environments Environmental changes: global warming -> increased vector distribution, longer transmission seasons, shorter gonotrophic cycles, shorter extrinsic incubation times
Thank you! Natalie Marzec 303.692.6314 natalie.marzec@state.co.us