Emerging Infectious Diseases 2016:

Menace of the Mosquito

Infectious Diseases & Emergency Medicine Washington University School of Medicine No disclosures

October 13, 2016

Define what is an emerging infectious disease, how they come about, and why they matter in prehospital care. Update providers on current clinical knowledge & approach to Chikungunya and Zika virus infection.

Zoonoses

SARS coronavirus (civet, bat)

Nipah virus (bat)

Avian influenza (poultry)

2009 H1N1 influenza (pig)

MERS coronavirus (camel)

Ebola virus (bat, monkey)

Vector-borne diseases West Nile virus (mosquito)

Chikungunya virus (mosquito)

Zika virus (mosquito)

(Can also be zoonoses)

• War • Famine • Poverty & social inequality • Lack of political will

• Climate & weather • Economic development

Intent to harm

Changing ecosystem

Cohen. Nature 2000;406:762.

2015: U.S. & foreign air carriers transported 196.3 million passengers between the U.S. & the rest of the world

Europe: 56.3 million

C. America: 33.7 million

Asia: 28.8 million

www.transportation.gov

U.S.

Arbovirus Alphavirus

Single-stranded RNA Vector-borne Swahili/Makonde: “to walk bent over”

Incapacitating arthralgias Can look like dengue

Traditionally a tropical disease

http://phil.cdc.gov/

Excluding countries/territories w/ only imported cases

As of April 22, 2016 http://www.cdc.gov/chikungunya

• Endemic to parts of W. Africa • 2005-6: Réunion Island • 2007: Italy • 2013: Caribbean (St. Martin)

2013 – present

http://www.paho.org/chikungunya

Local transmission: • Late 2013:

Caribbean • Early 2014:

Florida, Puerto Rico, U.S. Virgin Islands

• Since 2014: 45 countries/ territories

• >1.7 million suspected cases reported

2006-2013: 28 cases/yr 2014: 2,799 cases

http://www.cdc.gov/chikungunya

Florida (2014): 11 locally-transmitted cases

2014

http://www.cdc.gov/chikungunya

2016

93 cases (CONUS), 137 (P.R.) As of October 11, 2016

• Asian tiger mosquito • Mostly outdoors (garden) • Aggressive biter

• Yellow fever mosquito • Indoors & outdoors • Sneaky biter

http://www.cdc.gov/chikungunya

Life cycle Infected pts spread virus via travel

Europe: Indian Ocean islands, India, Malaysia N. America: Caribbean, S. America

Competent vectors + seasonal synchrony = local transmission Nosocomial transmission: blood, corneal grafts Vertical transmission (mother-fetus):

Reunion Island epidemic (48.7%)

Curr Opin Virol 2011;1(4):310-7.

Monkeys, rodents, birds, other vertebrates Human (epidemics)

Incubation period: 2-4 d (range 1-14) Fever Polyarthralgias (2-5 d after onset of fever)

Intense, disabling Often ≥ 10 joint groups Often symmetrical Distal > proximal

Polyarthralgia (96%) %

Ankle 66.2

Knee 60.9

Metacarpophalangeal joints 49.6

Metatarsal joints 41.0

Shoulder 36.4

Elbow 31.7

Wrist 29.1

Sternoclavicular joints 15.0

Hip 7.2

157 pts, Réunion Island (2005-6) Clin Infect Dis 2007;44:1401-7

Maculopapular rash (50%; ≥3d after onset of fever)

Pruritus, bullous dermatitis (children)

Headache, conjunctivitis, myalgias, N/V Swollen joints (ankle, MTP, wrist, MCP)

Lymphopenia, thrombocytopenia, elevated liver enzymes Symptoms typically resolve within 7-10 d Rarely life-threatening (<0.1%)

Meningoencephalitis Cardiovascular, respiratory, renal failure

J Am Acad Dermatol 2008;58:308-16.

Lancet Infect Dis 2007;7:319-27.

Lancet Infect Dis 2007;7:319-27.

Chronic sequelae Polyarthralgias (previously affected joints) Polyarthritis Tenosynovitis

Wrist, hand, ankle Carpal tunnel syndrome

New-onset Raynaud phenomena

Chikungunya: “that which bends up”

Polyarthritis of hands & tenosynovitis of wrists Indian J Dermatol 2010;55(1):54-63.

Clinical features Chikungunya Dengue Fever (>38.9°C) +++ ++ Myalgias + ++ Arthralgias +++ +/– Headache ++ ++ Rash ++ + Bleeding dyscrasias +/– ++ Shock – +/– Leukopenia ++ +++ Neutropenia + +++ Lymphopenia +++ ++ Thrombocytopenia + +++

Dengue

Clin Infect Dis 2009;49:942-8

Retro-orbital

Malaria Typhoid fever Rickettsial infection Leptospirosis Other Alphaviruses (e.g., Ross River, O’nyong nyong)

Measles, Rubella, EBV Meningococcemia Seronegative rheumatoid arthritis

Viral DNA in blood RT-PCR (first 5-8 days)

Antibodies to CHIKV in blood IgM ELISA (D5 → D90) IgG ELISA (D14 → years)

Isolation of virus in culture Testing via local/state health dept, CDC

Supportive care Rest, fluids, antipyretics NSAIDs, other analgesics

No effective antivirals Ribavirin & interferon-α (in vitro activity against replication)

Infection → long-standing protective immunity

Fevers, polyarthralgias (distal joints), rash Rarely life-threatening

Unlike dengue! Arthralgias can persist A. aegypticus & albopictus mosquito

CHIKV

Flavivirus Dengue virus Yellow fever virus West Nile virus

Enveloped Single-stranded, positive-sense RNA Vector-borne

Arthropod (arbovirus) Aedes mosquito

Isolated in 1947 Rhesus monkey Zika Forest (Uganda)

Confined to Africa & Asia for 60 years

Sporadic cases (14 reported) Seroprevalence

First documented outbreak (2007)

Yap State (Micronesia)

(2007) Rash, fever, conjunctivitis, arthralgia 185 cases

49 confirmed (RNA, neutralizing antibody response)

59 probable (IgM by ELISA)

No admissions or deaths

Overall attack rate: 14.6 per 1,000 residents

Duffy et al. N Engl J Med 2009;360:2536.

Population (2000): 7,391

(2007-14)

Yap (2007) Est. 5,400 cases (73% population; >900 illnesses)

French Polynesia (2013-14) Est. 28,000 cases

(11% population)

New Caledonia (2014) 114 cases Easter Island (2014)

>50 confirmed cases

Imported cases: • Asia • Australia • Europe • U.S.

Brazil May 2015: 1st local case September 2015: microcephaly (northeast areas) Early est. 440,000 – 1,300,000 suspected cases

(2015 – present)

Mid July 2015

Late October 2015

February 2016

February 1, 2016: WHO: Public Health Emergency of International Concern (PHEIC)

February 3, 2016: CDC: Emergency Operations Center – Level 1

www.cdc.gov/zika

Travel-associated: 3,712 Locally-acquired: 105

As of 10/5/2016

U.S. territories: Travel-associated: 83 Locally-acquired: 24,118

Local transmission since mid-July 2016

Vector: Aedes spp. A. aegypti A. albopictus A. africanus A. hensilli & others

Non-vector: (blood, urine, semen, saliva, CSF, amniotic fluid, breast milk)

Sexual transmission Vertical transmission (intrauterine/intrapartum) Blood transfusion Not yet tied to breastfeeding

Yap (2007) Macular/papular rash 90% Fever (usually low-grade) 65% Arthritis/arthralgia (hands/feet) 65% Non-purulent conjunctivitis 55% Myalgia 48% Headache 45% Retro-orbital pain 39% Edema 19% Vomiting 10%

Incubation period: 2-14 days after bite Up to 80% cases are asymptomatic Mild, self-limited illness (2-7 days)

Pregnancy not associated w/ ↑risk or severity

Severe disease uncommon

Low case fatality

Duffy et al. N Engl J Med 2009;360:2536.

Zanluca et al. Mem Inst Oswaldo Cruz 2015;110(4):569.

http://exanthem.dermnetnz.org/viral/zika.html

Guillain-Barre syndrome (French Polynesia, S. America)

Progressive, mostly symmetric muscle weakness Absent/depressed deep tendon reflexes Mild to complete paralysis (extremity, face, respiratory, bulbar); death (rare)

San Salvador, El Salvador

Head circumference ≥2 S.D. below mean

Sex, gest. age at birth Highest risk if infected during 1st trimester

Bahia, Brazil: 0.88-13.2% Associated findings:

Brain calcifications Ventricular enlargement Macular & optic nerve lesions

Johansson et al. N Engl J Med 2016;375:1.

Dengue Chikungunya Malaria Leptospirosis Rickettsia Group A Strep Measles Parvovirus Rubella Other viruses

Clinical feature DENV CHIKV ZIKV Fever ++++ +++ +++

Myalgia/arthralgia +++ ++++ ++

Edema of extremities 0 0 ++

Maculopapular rash ++ ++ +++

Retro-orbital pain ++ + ++

Conjunctivitis + +++

Lymphadenopathy ++ ++ +

Hepatomegaly +++ 0

Leukopenia/ thrombocytopenia

+++ +++ 0

Hemorrhage + 0 0 Ioos et al. Med Mal Infect 2014;44:302.

ZIKV

Viral DNA in serum/urine RT-PCR (first 3-7 days)

Antibodies to ZIKV IgM Neutralizing antibody titers (≥4-fold higher than DENV titers) Detectable ≥4 days of symptoms

Cross-reactivity w/ other flaviviruses (e.g., DENV, CHIKV, YFV, WNV)

Testing via local/state health dept, CDC https://health.mo.gov/living/healthcondiseases/communicable/zika.php

Supportive care Rest Fluids Fever/pain control (acetaminophen)

Avoid ASA/NSAIDs until DENV ruled out due to bleeding risk

No antivirals No vaccine After infection → immunity

Primarily mosquitoes Incubation: 2-14 days Fever, rash, arthralgias

Self-limited Assoc w/ microcephaly Symptoms & travel history should guide testing Guidelines still evolving!

Approach & Prevention

Identify: Testing for Chikungunya:

Acute infection Test for Zika:

Acute infection (≥1 symptom) + exposure (travel, sex) within 14 days of symptom onset Asymptomatic pregnant woman + exposure within the past 12 weeks

Isolate?: Not necessary!! Inform: Notify local/state health dept PPE: Standard precautions only

Avoid travel to areas w/ active transmission Minimize mosquito exposure

Insect repellants (DEET, picardin, ELO/PMD, IR3535)

Sunscreen, then repellent DEET can ↓SPF by 30%

Long sleeves & pants Permethrin-treated

Bed nets Screens, AC – stay indoors

Protect infected pts from mosquitoes (1-3 wks!) to ↓ local transmission Vector control

Eliminate breeding sites Containers are ideal larval habitats Empty standing water

Larvicides The future

Vaccine???

www.paho.org

Reduce risk for sexual transmission If exposed, avoid unprotected sex & unintended pregnancy:

Men: minimum 6 months Women: minimum 8 weeks

Pregnant women w/ male partners who have or are at risk for ZIKV infection

Condoms or abstinence for the duration of the pregnancy

Tale of 2 emerging mosquito-borne illnesses: Chikungunya & Zika Virus

Understand & mitigate exposure: Geography matters – get a brief travel history!

CDC, WHO, ProMED mail Know when & how the disease is transmitted

Hosts, vectors Refer for testing when indicated

Prevention is key!

syliang@wustl.edu