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Home , Chikungunya, Ebola, Filoviridae

7/25/2015

49th Annual Meeting Disclosure

 I do not have a vested interest in or affiliation with any corporate organization offering financial Pause for Possible : , support or grant monies for this continuing education and Dengue activity, or any affiliation with an organization whose philosophy could potentially bias my Marianne Pop, Pharm.D., BCPS presentation Clinical Assistant Professor/ Medicine Clinical Pharmacist University of Illinois-Rockford

OWNING CHANGE: Taking Charge of Your Profession

Objectives Epidemiological Terms

 Define common epidemiological terms used to  Endemic describe the spread of  Ongoing and associated with a specific region or group of people  Ex: and  List risk factors and modes of for Ebola,  Epidemic  Confined to a small area but has affected a large number of individuals Chikungunya and Dengue  Ex: Severe Respiratory Syndrome (SARS) 2003

 Outbreak  Recognize and explain common  Disease cases in excess of what is expected associated with each of these  Ex: 2015

 Describe treatment modalities recommended in the  Affecting many across a large region or worldwide management of each of these diseases  Ex: HIV/AIDS

 Pandemic potential  Identify and describe the role of pharmacists and  Capability of spreading globally pharmacy technicians in emergency preparedness  Ex: Avian (H5N1, H7N9)

Kilbourne ED. Emerg Infect Dis 2006.

Epidemiological Terms Ebola

 Zoonotic  Transmission from animal to or animal to animal

 Carries from one to another

 Host  Provides virus means for replication

National Institute of Environmental Health Sciences. Vectorborne and Zoonotic Diseases & Climate Change 2013. http://phil.cdc.gov/phil/details.asp?pid=1833

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History History 1976-2014

(Ebola, and Cuevavirus)  Zoonotic  Fruit , , , monkeys, antelope and porcupines

 Five species of Ebola virus  Ebola (), , Reston, Tai Forest and Bundibugyo

 Identified in 1976

 In U.S. (Reston)  1980, 1990 and 1996 Feldmann H, et al. Lancet 2011. Baize S, et al. N Engl J Med 2014. World Health Organization. Ebola virus disease. 2014. http://www.who.int/mediacentre/factsheets/fs103/en/

Ebola 2014 Outbreak Suspected Case Zero (updated May 1,2015)

 Meliandou Village, Guéckédou

 2 yo male  Onset December 2, 2013  , black stool and  Died December 6, 2013

 Spread through family, nurse and village midwife

 Midwife hospitalized in Guéckédou where health care worker triggered the spread of the virus to Macenta, Nzérékoré, and Kissidougou

http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html Baize S, et al. N Engl J Med 2014.

In the “News” U.S. Timeline

 March 2014-Present outbreak Jul. 2014 • Dr. Brantly and Writebol diagnosed and received ZMapp  , , , Nigeria, and Senegal Aug. 2014  ~10,892 deaths • Dr. Brantly and Writebol flown to Emory  Suspected, probable, and confirmed cases (Updated May 1, 2015) Sep. 2014 • Dr. Sacra flown to Nebraska Medical Center; received Dr. Brantly transfusion • First U.S. diagnosis: Duncan arrived in U.S., went to Texas Presbyterian Health Hospital Oct. 2014 • Photojournalist Mukpo flown to Nebraska Medical Center • Duncan died • Nurse Vinson flew to Cleveland, diagnosed on return, flown to Emory • Anonymous lab worker boarded cruise ship, diagnosed on ship • Nurse Pham diagnosed, flown to NIH • Dr. Spencer flew to NY, diagnosed at Nov. 2014 • Dr. Salia flown to Nebraska Medical Center

World Health Organization. Ebola virus disease, West Africa. 2014. Mar. 2015 CDC. Ebola Outbreak West Africa.2014. • U.S. clinician flown to National Institutes of Health Bethesda, Maryland http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/cumulative-cases-graphs.html

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Transmission

 Blood or secretions  Urine, , , , and others Myth No. 1:  Direct contact during of Ebola virus patients  Contaminated inanimate objects

Ebola is an airborne or  Incubation 2-21 days (8-10 days) waterborne disease  Febrile, later stages, and post-mortem  Infectious up to 7 weeks post recovery

for 10 years with infected strain

CDC. Ebola Hemorrhagic Fever Transmission. 2014. Borio L, et al. JAMA. 2002. Feldmann H, et al.. Lancet 2011. World Health Organization. Ebola virus disease, West Africa. 2014.

Risk

Myth No. 1:  unknown  Exposure currently confined to endemic areas Ebola is an airborne or  West, Central, and South Africa  Health care workers and family/friends waterborne disease  Epidemiologic risk factors  Contact with blood or body fluids within last 3 weeks (known or suspected Ebola)  Recent travel to endemic/epidemic area  Direct handling of bats, or from endemic areas CDC. Ebola Hemorrhagic Fever Risk. 2014. Borio L, et al. JAMA. 2002. Feldmann H, et al. Lancet 2011.

Signs and Symptoms Signs and Symptoms

 Fever 

 Red eyes

 Joint and muscle 

aches  Cough

 Vomiting  Dyspnea

 Stomach Pain  Hemorrhagia  Lack of appetite

Pigott DC. Crit Care Clin. 2005. Borio L, et al. JAMA. 2002. Feldmann H, et al. Lancet 2011. CDC. Signs and Symptoms. 2014. CDC. Signs and Symptoms. 2014.

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Screening Screening

 Consistent symptoms and risk factors  If yes… Fever > 100.4° F and other symptoms  Isolate patient in single room with a private bathroom and with the door to hallway closed AND  Contact and droplet precautions Epidemiologic risk factors  Notify Control Program and other staff Residence or travel to active Ebola area within 3  Evaluate for any risk exposures for Ebola weeks of symptoms  Report to the department of health (DOH) Contact with known or suspected Ebola patient  CDC hospital checklist www.cdc.gov/vhf/ebola/hcp/index.html CDC Guidelines for Evaluation of US Patients Suspected of Having Ebola. 2014. CDC Guidelines for Evaluation of US Patients Suspected of Having Ebola. 2014.

Testing Recommendation Testing Recommendation

 According to exposure risk (review with DOH)  High-risk exposure without fever  High risk exposure + fever:  Only if clinical symptoms present and blood work abnormal  Percutaneous, mucous membrane exposure or direct skin contact  Asymptomatic persons with high or low-risk exposures  Direct care or exposure without personal protective equipment (PPE)  Twice daily monitoring for fever and symptoms for 21 days  Lab processing of body fluids of suspected or confirmed Ebola cases without appropriate PPE from the last known exposure  Participation in rites or other direct exposure  No known exposures + fever + symptoms and  Low risk exposure + fever + symptoms: abnormal bloodwork within 21 days of visiting  Household member endemic country  Providing patient care or low risk casual contact  Consider testing if no other diagnosis is found

CDC Guidelines for Evaluation of US Patients Suspected of Having Ebola . 2014. CDC Guidelines for Evaluation of US Patients Suspected of Having Ebola . 2014. CDC Case Definition for Ebola Virus Disease. 2014. CDC Case Definition for Ebola Virus Disease. 2014.

Treatment Pipeline Agents

 Supportive  Treatments  Fluids and electrolytes  ZMapp  MOA: that provide  Oxygen status and blood pressure   Treat complicating  MOA: pro-drug of cidofovir, stops  Blood transfusion  and BCX-4430  Whole blood and convalescent blood  MOA: inhibition of viral RNA polymerase

 TKM-Ebola and AVI-7537  Previously tested in eight patients in the 1995 Kikwit Ebola outbreak  MOA: interferes with the expression of specific  Non-FDA approved treatments and

WHO. Ebola virus disease, West Africa. 2014. Feldmann H, et al. Lancet 2011. Mupapa K, et al. J Infect Dis. 1999. Borio L, et al. JAMA. 2002. ClinicalTrials.gov

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Pipeline Agents Ethics

 Vaccines  FDA compassionate use  cAd3-ZEBOV  MOA: Chimp adenovirus vector  Limited supply  rVSV-ZEBOV  Efficacy  MOA: Attenuated vesicular stomatitis virus  Ad5-EBOV  Funding  MOA: Adenovirus vector  Trials

ClinicalTrials.gov

Infection Prevention and Control PPE

 Patient placement and visitors

 Personal protective equipment (PPE)

 Patient care equipment

 Limit blood exposure procedures

 Avoid aerosol generating procedures

 Hand

 Environmental infection control

 Monitor exposed personnel/visitors

 Burials  Strong protective clothing and gloves (trained professionals)  Buried immediately

Pigott DC. Crit Care Clin. 2005. WHO. Ebola virus disease, West Africa. 2014. CDC Infection Prevention and Control Recommendations for Hospitalized Patients with Known or Suspected Ebola Hemorrhagic Fever in U.S. Hospitals. 2014. http://www.scmp.com/comment/insight-opinion/article/1572317/hong-kong-unprepared-ebola-crisis

Chikungunya Virus

Myth No. 2: The is free of -borne diseases

http://www.cdc.gov/media/DPK/2014/dpk-chikungunya.html

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History In the “News”

 1952 identified in  July 2014  2005-2006 Reunion and Mauritus Island outbreak:  First acquired case in Florida 272,000 infected  August 2014  2006 India: 1.5 million infected  Chikungunya carrying mosquito identified in Texas

 2007 Italy: 197 infected  January 2015  2006-2013: 200 imported cases in U.S.  Nationally notifiable condition

 2013 Islands: 436,586 cases  February 2015

 2014 U.S. territories: 4,513 cases  U.S. cases: 2,492 for 2014  11 were Florida local transmissions

CDC. Chikungunya virus in the United States. 2014. CDC. Chikungunya virus in the United States. 2014. CDC. Chikungunya virus.2014. Pialoux G, et al. Lancet Infect Dis 2007. Morens DM, et al. N Engl J Med. 2014. Staples JE, et al. N Engl J Med. 2014. Fischer M, et al. MMWR Morb Mortal Wkly Rep 2014. Bridget M. JAMA. 2014.

2014 U.S. Chikungunya Reported Cases (as of February 2015) Myth No. 2: The United States is free of mosquito-borne diseases

http://www.cdc.gov/chikungunya/geo/united-states-2014.html

Transmission Increased Risk

 Vector: aegypti and  Newborns (intrapartum exposure)  Bites viremic host (5 days) incubation 10 days  ≥ 65 years  Host:   Bitten by infected mosquito incubation: 3-7 days (1-12 days) Medical conditions

 Blood-borne transmission possible  Hypertension  Laboratory personnel and health care workers  Diabetes nd  Rare in utero transmission (2 trimester)  Cardiovascular disease  Intrapartum transmission (mothers viremic at delivery)

 Transmission from host to mosquito is highest during first week of illness

Pialoux G, et al. Lancet Infect Dis 2007. Pan American Health Organization (PAHO) and CDC. Preparedness and response for chikungunya virus introduction in the . 2011. CDC Mosquito Fact Sheet. 2012.

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Signs and Symptoms Chikungunya

 Onset: 3-7 days after bite (1-12 days) , fever and polyarthralgia  >102° F

 Headache, muscle pain, , /vomiting, joint swelling, and maculopapular rash

 Lab results  Lymphopenia, , elevated SCr, erythrocyte sedimentaton rate, C-reactive , and hepatic transminases

Pialoux G, et al. Lancet Infect Dis 2007. http://wwwnc.cdc.gov/eid/article/18/3/11-0838-f1 WHO Chikungunya. 2014. Bandyopadhyay D , et al. J Dermatol. 2010 .

Complications Treatment

and retinitis  Hemorrhage  NO anti-viral treatment

 Myocarditis   Supportive care to minimize symptoms

 Myelitis  Rest

 Nephritis  Guillain-Barré  Fluids to prevent  Electrolyte replacement  Bullous skin lesions syndrome  Anti-pyretics and non-steroidal anti-inflammatory  Cranial nerve palsies  Polyarthralgia relapse  or physiotherapy for persistent

Pialoux G, et al. Lancet Infect Dis 2007. Pialoux G, et al. Lancet Infect Dis 2007. WHO Chikungunya. 2014.

Prevention

 NO FDA approved  Pipeline: VRC 311

 Key is vector prevention  Eliminating mosquito larvae (standing water) and spraying

 Bite prevention  Insect repellant  N,N-Diethyl-meta-toluamide (DEET), picaridin, IR3535, oil of lemon eucalyptus and para-menthane-diol  Long sleeves and pants  Stay indoors  Use window, door screens and netting

 Infected host should be protected from further mosquito exposure

 Recovery will confer life-long immunity

Pialoux G, et al. Lancet Infect Dis 2007. WHO Chikungunya. 2014. CDC. Repellant. 2014. Chang LJ , et al. Lancet 2014. http://vaccinenewsdaily.com/news/262021-scientists-use-bacteria-to-stop-dengue-virus-spread/

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History In the “News”

 100-800 years ago  September 2009  Originated in monkeys in Africa or Southeast Asia  Key West outbreak: 13 cases

 1950’s Dengue hemorrhagic fever (DHF) in  August 2013 Philippines and Thailand  Martin County outbreak: 21 cases

 1981 DHF in Caribbean and Latin America  August 2014  2001 Hawaii  Florida Health Department confirms case of imported dengue  2005 South Texas

 2007 and 2010 Puerto Rico

CDC Dengue. 2014. WHO and the Special Programme (SP) for Research and Training in Tropical Diseases. Dengue guidelines for diagnosis, treatment, prevention and control. 2009. Florida Health. Dengue. 2014. Staples JE, et al. N Engl J Med. 2014. CDC. Dengue Outbreak in Key West, Florida, USA, 2009 . 2012.

Dengue Classification

 Serotypes 1-4 Myth No. 3:  Lifelong protection of infecting serotype If you had dengue before you  Exposure to one does not confer immunity to other are forever immune to dengue  (DF)  Dengue Hemorrhagic Fever (DHF)

 Dengue Shock Syndrome (DSS)

CDC Dengue. 2014. WHO and SP. Dengue guidelines for diagnosis, treatment, prevention and control; 2009.

Dengue Classification Assessment Question #2

Dengue Virus Infection Which of the following disease states is/are associated with the possible development of Asymptomatic Symptomatic hemorrhagic fever? A. Ebola Undifferentiated B. Chikungunya DF DHF fever C. Dengue D. A and C

DSS

WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011.

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2012 U.S. reported cases: Dengue/Dengue Hemorrhagic Fever Myth No. 3: If you had dengue before you are forever immune to dengue

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6153a1.htm

Risk Transmission

 Endemic to 100 countries  Vector: and Aedes albopictus  Bites viremic host (5 days) incubation 8-12 days  Asia, Americas, Africa, and Caribbean  Host: Humans  Sub-tropical and tropical areas  Bitten by infected mosquito incubation: 1-4 days  Worldwide 100 million cases per year  Blood-borne transmission possible  transplant or blood transfusion  Laboratory personnel and health care workers

 Rare in utero transmission

 Intrapartum transmission (mothers viremic at delivery)

 Transmission from host to mosquito is highest during 5th day of infection

WHO and SP. Dengue guidelines for diagnosis, treatment, prevention and control;.2009. WHO and SP. Dengue guidelines for diagnosis, treatment, prevention and control. 2009. WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011. WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011.

Signs and Symptoms Treatment

DF DHF DF DHF nd th nd th  High fever on 2 -7 day of illness  High fever on 2 -7 day of illness   Fluids  Severe headache  Vomiting  Anti-pyretics  Electrolyte  Rear eye pain  Severe abdominal pain  Joint pain  Dyspnea  Rest replacement  Muscle and bone pain  Leaky capillaries  Fluids  Rash  Ascites  Mild  Pleural effusions  Electrolyte  Shock replacement  Thrombocytopenia

 Bleeding

WHO and SP. Dengue guidelines for diagnosis, treatment, prevention and control; 2009. WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011. WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011. Teixeira MG, Barreto ML. BMJ 2009.

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Prevention Florida DOH Current Testing Protocol

 NO FDA approved vaccine   Pipeline vaccines Ebola  CYD-TDV, TetraVAX, DENVax, and Vaxfectin  Report to DOH to authorize testing, CDC makes decision  MOA: live-attenuated tetravalent agents  850-245-4401 (DOH Bureau of )  Key is vector prevention  Eliminating mosquito larvae (standing water) and spraying  Bite prevention  Chikungunya and Dengue  Insect repellant  Private labs at request of provider  N,N-Diethyl-meta-toluamide (DEET), picaridin, IR3535, oil of lemon eucalyptus and para-menthane-diol  DOH can provide guidance  Long sleeves and pants  Stay indoors  Use window, door screens and netting

 Infected host should be protected from further mosquito exposure

ClinicalTrials.gov Capeding MR, et al. Lancet 2014. Florida Department of Health Hales S, van Panhuis W. Lancet 2005. CDC. Repellant..2014. CDC. Infectious Diseases Laboratories. 2014

Emergency Preparedness

 CDC Infection and Prevention Control

 Development of Infection Prevention Control at institution  Plan Emergency Preparedness  PPE enhancement  Implementation of emergency measures  Training of staff  Management of infectious patients

 Local county and state coalitions

CDC. Ebola Infection Prevention Control Recommendations. 2014. CDC Guidelines for Evaluation of US Patients Suspected of Having Ebola. 2014.

Joint Commission Role of Pharmacy

 Exercises and drills  Training  Simulation techniques  Federal Emergency Management Agency (FEMA)

 Pandemic and  Disaster Medical Assistance Team (DMAT)  Hospital decontamination assessment tool  Smart Emergency Response System (SERS)

 General references  Participate  Hospital incident command system  Writing plans (local, regional or state level)

 Codes and alerts  Disaster exercises  Points of distribution training

Colleen M , Newton S. J Am Pharm Assoc 2008. Joint Commission. Emergency Management. 2014. Pincock L, et al. Am J Health Syst Pharm. 2011.

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Role of Pharmacy Summary

 Assembling disaster kits  Ebola, Chikungunya and Dengue are bloodborne  Mass dispensing of prophylactic medications diseases necessitating key prevention techniques  Mass administration of vaccines  All three diseases present with non-specific  certification symptoms requiring the rule-out of other diseases

 Media training  Supportive care is the mainstay of therapy  Control speculation and panic  Pharmacists and pharmacy technicians have

 Advocate pharmacy associations essential roles in emergency preparedness  Roles in emergency preparedness and committees

Colleen M , Newton S. J Am Pharm Assoc 2008. Pincock L, et al. Am J Health Syst Pharm. 2011.

49th Annual Meeting

Pause for Possible Pandemics: Ebola, Chikungunya and Dengue Marianne Pop, Pharm.D., BCPS Clinical Assistant Professor/Clinical Pharmacist University of Illinois-Rockford [email protected]

OWNING CHANGE: Taking Charge of Your Profession

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