Ebola Virus DiseaseImplications for NMCP Staff and Patients

CDR Karl C Kronmann, MD MPHInfectious Disease Staff, NMCP

ACP, 17 Oct 2014

Objectives

• State of the Ebola Outbreak in West Africa• Ebola Virus Disease

– Signs and symptoms, – Diagnosis and management (Respond)

• Infection Control – Transmission of EVD– Early Identification (Detect)– Precautions (Protect)

How Bad Is It?• By January 20, 2015 if no additional interventions or behavior changes

occur, Liberia and Sierra Leone will have approximately 550,000 Ebola Cases (1.4 million when corrected for underreporting)

- CDC published in MMWR Sep 23, 2014

• “For the medium term, at least, we must therefore face the possibility that EVD will become endemic among the human population of West Africa, a prospect that has never previously been contemplated.”

- WHO published NEJM Sep 23, 2014

Ebola – What is different this time?

Nurse visits graves from the 1976 Ebola outbreak in Zaire (DRC)

18 August 2014

MONROVIA, Liberia (AP) — Authorities in Liberia urgently searched on Monday for 17 people who fled an Ebola medical center over the weekend when it was attacked by looters who stole blood-stained sheets and mattresses and took them into an enormous slum.

Ebola 2014

18 August 2014

MONROVIA, Liberia (AP) — Authorities in Liberia urgently searched on Monday for 17 people who fled an Ebola medical center over the weekend when it was attacked by looters who stole blood-stained sheets and mattresses and took them into an enormous slum.

Ebola 2014

18 August 2014

MONROVIA, Liberia (AP) — Authorities in Liberia urgently searched on Monday for 17 people who fled an Ebola medical center over the weekend when it was attacked by looters who stole blood-stained sheets and mattresses and took them into an enormous slum.

Ebola 2014

25 new cases

38 new cases

56 new cases

12 days

12 days

12 days

Total 119 cases predicted as of today

???

18 August 2014

MONROVIA, Liberia (AP) — Authorities in Liberia urgently searched on Monday for 17 people who fled an Ebola medical center over the weekend when it was attacked by looters who stole blood-stained sheets and mattresses and took them into an enormous slum.

Ebola 2014

Ebola 2014

Numbers 2014

Briand S, et al. The international Ebola emergency. Aug 20, NEJM 2014

As of August 11

Ebola – 38 years of EVD Outbreaks Total cases prior to 2014: 2,390 (CFR=66.6%)

Total cases in West Africa in 2014: 5,927 (CFR=47%) (as of 22 Sep)

Recent Increase in Cases

Department of Defense (AFHSC): West Africa Ebola Surveillance Summary #31: Sep 18, 2014

Geographic differences

Source: CDC

Map of Guinea Showing Initial Locations of the Outbreak of Ebola Virus Disease.

Baize S et al. Emergence of Zaire Ebola Virus Disease in Guinea – Preliminary Report N Engl J Med 2014.

Country Profiles

Country

Per Capita GDP

Life Expectancy at birth

Multidimensional poverty

Official Language Religion

$ rank years rank

USA 52,800 14 79.56 42 n.a. English Christian – 77%None – 12%Muslim – 1%

Sierra Leone

1,400 208 57.39 201 72.68% English (limited)

Muslim – 60%Christian – 10%Indigenous – 30%

Haiti 1,300 209 63.18 186 50.16% French,Creole

Christian – 96%

Guinea 1,100 218 59.60 195 86.49% French Muslim – 85%Christian – 8%Indigenous – 7%

Liberia 700 223 58.21 199 81.86% English (20%) Christian – 85%Muslim – 12%

CIA World Fact Book and United Nations Development Programme

Transmission Chains in the Outbreak of Ebola Virus Disease in Guinea.

Baize S et al. Emergence of Zaire Ebola Virus Disease in Guinea – Preliminary Report N Engl J Med April 16, 2014.

Transmission Chains in the Outbreak of Ebola Virus Disease in Guinea.

March 10 – MOH notified of cluster of mysterious deaths

March 12 – MSF contacted

Baize S et al. Emergence of Zaire Ebola Virus Disease in Guinea – Preliminary Report N Engl J Med April 16, 2014.

Days between “first” symptomatic case and MOH notification = 98

Days between death of grandmother and MOH notification = 68

Outbreak dynamicsDisease R0 Generation time/

serial timeTransmission Route CFR

Measles 12-18 11-12 days Airborne 2%

Influenza 1.4-4.0 3-4 days Droplet (Airborne) 0.1%

Ebola 2014 1.4-2.02 9-15 days Contact, Droplet ~70%

Polio 2-20 10 days Fecal-Oral 5-10%

Smallpox 5-7 14-16 days Airborne 30%

SARS 2-5 4-12 days Airborne 11%

Epidemic Curve

WHO: Ebola Response Roadmap Situation Report: 18 September 2014 http://apps.who.int/iris/bitstream/10665/133833/1/roadmapsitrep4_eng.pdf?ua=1

24 June: MSF says outbreak is “out of control” and requests help

8 Aug: WHO declares PHEIC

10 March: Outbreak recognized

Video

http://nyti.ms/1qnLOQB

CDC Checklist for Health Care Facility Preparedness

□ Review facility infection control policies □ Review environmental cleaning procedures and provide education/refresher training for cleaning staff □ Begin education and refresher training for HCP on

– EVD signs and symptoms, – diagnosis, – how to obtain specimens for testing,– appropriate PPE use (including putting on and taking off PPE),– triage procedures (including patient placement), – HCP sick leave policies, – how and to whom EVD cases should be reported, – procedures to take following unprotected exposures

□ Review triage procedures and ensure relevant questions (e.g., exposure to case, travel within 21 days from affected country) are asked during the triage process for patients arriving with compatible illnesses

Pathogenesis

Feldman H, Geisbert TW. Ebola Hemorrhagic Fever. Lancet 2011

Signs and SymptomsBleeding/Hemorrhage

Year Location Bleeding/Hemorrhage

2014 Guinea 27% (4/15)

1995 DRC 41% (42/103)

1976 Zaire (DRC) 78% (174/223) Fatal cases18% (6/34) Survivors

1976 Sudan 71% (130/183)

Most common manifestation MELENA

Ebola Virus Disease vs.Ebola Hemorrhagic fever

Signs and SymptomsDiarrhea

Year Location Diarrhea

2014 Guinea, Liberia, Sierra Leone

78% (11/15)66% (721/1099)

1995 DRC 85% (87/103)

1976 Zaire (DRC) 79% (180/228) Fatal cases44% (15/34) Survivors

1976 Sudan 81% (130/183)

Signs and SymptomsSudden Onset

Fever (> 101.5 F) Severe headache

Symptom Timing

WHO Ebola in Sudan 1976. Bull WHO 1978

infection symptom onset

day 7 day 14 day 21 day 28+

Infectious Risk

survivors fatalities

DeathDay 8 (2-14)

Incubation 2-21 days

Burial or cremation

Semen and? breast milk

CDC Definition:Person Under Investigation (PUI)

• Clinical Criteria: (at least one)– Temp > 101.5 F– Severe headache– Diarrhea– Muscle pain, vomiting, abdominal pain, or unexplained bleeding

AND

• Epidemiologic risk within past 21 days: (any one)– Contact with blood, other body fluid or human remains of a suspected EVD

case– Travel to (or residence in) an area where EVD transmission is active– Direct handling of bats or non-human primates from disease endemic areas.

Initial Management

• INFECTION CONTROL! (Discussed separately)• Consider empiric therapy

– antimalarials and– broad spectrum antibiotics

• Supportive– Tylenol (avoid antiplatelet drugs)– HYDRATION (Oral Rehydration Solution or IV)– Antiemetics

• Management of sepsis and shock if needed

Estimated 2014 deaths to date Liberia, Guinea, Sierra LeoneEVD 2,759

Malaria 23,105

Diagnosis1. INFECTION CONTROL!

2. Contact ID/VDH/CDC

3. 4 ml in plastic EDTA tube

4. RT-PCR or Serology done at CDC

5. Rule out malaria.

6. Consider other diagnoses

Differential Diagnosis

• Malaria• Typhoid• Lassa fever• Shigellosis (Dysentery)• Meningococcal septicemia• Bacterial sepsis• Plague, leptospirosis, anthrax, relapsing fever, typhus, murine

typhus, yellow fever, Chikungunya fever, and fulminant viral hepatitis, ?enterovirus, HIV-1.

1. Gire SK, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 20142. Feldman H, Geisbert TW. Ebola Hemorrhagic Fever. Lancet 2011

Experimental Treatments“Secret Serums”

• Antibodies– Transfusion from convalescent patients– Three monoclonal antibody combo (ZMAPP)

• Antisense oligonucleotides– Small interfering RNAs (Tekmira TKM-Ebola)

• Inflammatory modulators– Type 1 interferons, ?statins

• Coagulation inhibitors– Heparin sulfate, APC

• Vaccines (Two are starting phase 1 trials soon)– Post exposure – Pre-exposure

Feldman H, Geisbert TW. Ebola Hemorrhagic Fever. Lancet 2011

Expert Opinion

“. . .the chance that the [Ebola] virus will establish a foothold in the United States or another high-resource country remains extremely small.”

- Dr Anthony Fauci, NEJM Sept 18

“We do not view Ebola as a significant public health threat to the United States.”

- Dr Beth Bell, CDC testimony to Congress, Sept 17

“And we have no doubt that we will stop [Ebola] in its tracks in Texas.”- Dr Tom Frieden, CDC Director Oct 5

Nursing barrier precautions

Khan AS, et al. The Reemergence of Ebola Hemorrhagic Fever, DRC 1995 JID 1999

TRANSMISSION:Kikwit Risk Factors

1. Direct physical contactOR = undefined, p<0.01

2. Contact with Body fluidsOR = 3.8, 95%CI (1.9-6.8)

Dowell SF, et al. Transmission of Ebola Hemorrhagic Fever, DRC. JID 1999

No contact = no disease

Transmission of VHF in European healthcare settings

Ftika and Maltezou. Viral Hemorrhagic Fevers in Healthcare Settings. J Hosp Inf 2013

Unsuspected Ebola in a Modern Hospital in South Africa

Patient Number of hospital days

Procedures performed

Outcome Infection Control

Number of secondary cases

40 year old male physician returning from Gabon

14 EGDColonoscopyCentral lineThigh muscle bx

Survived Standard 1

46 year old female anesthetist assistant caring for source patient

13 (4 as sick staff,9 as patient)

LPBone marrow bxDialysisLaparotomy

Transferred Standard 0

9 Swan-Ganz IntubationLaparotomy

Died High level barrier plus airborne

0

300 contacts followed with no secondary cases

Richards GA, et al. Unexepected Ebola virus in a tertiary setting: Clinical and epidemiologic aspects. Crit Care Med 2000

Why the Confidence?LOCATION PUBLIC HEALTH INFRASTRUCTURE HOSPITAL INFECTION CONTROLGUINEA, SIERRA LEONE,LIBERIA

• Public distrust• Minimal presence of permanent

staff outside capital cities• Access to rural locations difficult

• Unreliable electricity• Running water not always available• PPE (e.g. gloves) rarely available• Minimal or no routine Infection

Control and cleaning• Limited diagnostic and treatment

capacity -> Lack of confidence in hospitals

• Barrier nursing techniques not used

USAEUROPE

• High public trust• Staff available for contact tracing

and monitoring• Public acceptance of quarantine,

etc.• No access issues

• Routine IC procedures• Basic PPE plentiful• Routine cleaning procedures• Familiarity with barrier nursing

techniques

Why the Confidence?LOCATION PUBLIC HEALTH INFRASTRUCTURE HOSPITAL INFECTION CONTROLGUINEA, SIERRA LEONE,LIBERIA

• Public distrust• Minimal presence of permanent

staff outside capital cities• Access to rural locations difficult

• Unreliable electricity• Running water not always available• PPE (e.g. gloves) rarely available• Minimal or no routine Infection

Control and cleaning• Limited diagnostic and treatment

capacity -> Lack of confidence in hospitals

• Barrier nursing techniques not used

USAEUROPE

• High public trust• Staff available for contact tracing

and monitoring• Public acceptance of quarantine,

etc.• No access issues

• Routine IC procedures• Basic PPE plentiful• Routine cleaning procedures• Familiarity with barrier nursing

techniques

• Contact identification and monitoring limited

• Quarantine disrupted and disobeyed

• No problem with contact identification and monitoring

• Quarantine accepted

• Insufficient hospital bed capacity

• Unfamiliarity with barrier nursing techniques

• Plenty of hospital bed capacity

• Familiarity with routine Infection Control

Preventing or ending an Ebola outbreak

• Early Identification of cases– Isolate symptomatic patients – barrier nursing– Trace and monitor contacts – isolate if symptoms– Decontaminate environment and prevent contact

with cadavers (funeral preparation)

• Good hospital infection control and hygiene

MSF Staff Members Lead a Young Patient with Suspected Ebola into the Case-Management Center.

Wolz A. N Engl J Med 2014. DOI: 10.1056/NEJMp1410179

Early Identification of PUI at NMCP

Signs at patient entry points

1. Send patient to ER2. ER eyeball triage 3. Send to Special Precautions Unit4. ID confirmation of PUI5. Further management in SPU (3

days to to rule out

CDC Case Definition

Probable Case – PUI with risk exposure1. High Risk

a) Needlestick or mucous membrane exposure from EVD caseb) Exposure without PPE

I. Direct skin exposure to blood or body fluid of EVD caseII. Processing blood or body fluid of EVD caseIII. Contact with dead body in area where EVD is occurring

2. Low Riska) Household contact of EVD caseb) Exposure without PPE

i. Close contact (< 3 feet) for a prolonged period with EVD caseii. Brief direct contact with EVD case

Interim Guidance for Monitoring and Movement of Persons with Ebola Virus Disease

Infection Control Plan at NMCP

1. Early identification and isolation2. Standard plus ENHANCED Contact plus

Airborne precautions3. Limit staff4. Limit visitors5. Limit labs and procedures6. Appropriate environmental cleaning

Enhanced Contact Precautions

• Enhanced PPE– Fluid impervious gowns or coveralls– Extras for sicker patients (boots, aprons, hoods, etc.)

• Individualized training– Donning and doffing PPE

• Viricidal agent available• Monitor stationed outside room

Limited Staff

• Attending Physicians only (Critical Care and ID)

• Limited nursing – one RN per shift

• Monitor – Corpsman– Limit access– Assist with PPE. Verify before entry– Log all visitors

Will DoD Efforts Help West Africa?

“If by late December 2014, approximately 70% of patients were placed either in Ebola Treatment Units (ETU) or home or in a community setting such that there is a reduced risk for disease transmission (including safe burial when needed), then the epidemic would almost be ended by January 20, 2015.”

- CDC published in MMWR Sep 23, 2014

Questions

Passive Immunization with convalescent human blood or serum

Year LocationNumber of patients

Number transfusions per patient Result

1976 DRC 1 3 Died

1976 UK 1 2 Survived

1995 DRC 8 1 7 survived1 died

DRC 5 ? 4 died1 survived

2014 Liberia, USA 2? ? 2 survived

Mupapa, et al. Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients. JID 1999

Early Recognition in Africa

In African settings, what is the best way to recognize the presence of Ebola?

• Febrile disease with prominent bleeding• Clusters of severe, febrile disease in families• Spread of a severe febrile disease to HCWs• Failure to respond to treatment [for malaria]• Characteristic signs and symptoms• Characteristic laboratory findings• History of exposure to “bush meat”• High index of suspicion

Early Recognition in Africa

In African settings, what is the best way to recognize the presence of Ebola?

• Febrile disease with prominent bleeding• Clusters of severe, febrile disease in families• Spread of a severe febrile disease to HCWs• Failure to respond to treatment [for malaria]• Characteristic signs and symptoms• Characteristic laboratory findings• History of exposure to “bush meat”• High index of suspicion

Develop Health Infrastructure

Epidemiologic Curve

Department of Defense (AFHSC): West Africa Ebola Surveillance Summary #31: Sep 18, 2014

Ebola – 38 years of EVD Outbreaks Total cases prior to 2014: 2,390 (CFR=66.6%)

Total cases in West Africa in 2014: 2,722 (CFR=53%) (as of 25 Aug)Year Country Ebolavirus species Cases Deaths Case fatality

2012 Democratic Republic of Congo Bundibugyo 57 29 51%

2012 Uganda Sudan 7 4 57%2012 Uganda Sudan 24 17 71%2011 Uganda Sudan 1 1 100%

2008 Democratic Republic of Congo Zaire 32 14 44%

2007 Uganda Bundibugyo 149 37 25%

2007 Democratic Republic of Congo Zaire 264 187 71%

2005 Congo Zaire 12 10 83%2004 Sudan Sudan 17 7 41%

2003 (Nov-Dec) Congo Zaire 35 29 83%

2003 (Jan-Apr) Congo Zaire 143 128 90%

2001-2002 Congo Zaire 59 44 75%2001-2002 Gabon Zaire 65 53 82%2000 Uganda Sudan 425 224 53%

1996 South Africa (ex-Gabon) Zaire 1 1 100%

1996 (Jul-Dec) Gabon Zaire 60 45 75%

1996 (Jan-Apr) Gabon Zaire 31 21 68%

1995 Democratic Republic of Congo Zaire 315 254 81%

1994 Cote d'Ivoire Taï Forest 1 0 0%1994 Gabon Zaire 52 31 60%1979 Sudan Sudan 34 22 65%

1977 Democratic Republic of Congo Zaire 1 1 100%

1976 Sudan Sudan 284 151 53%

1976 Democratic Republic of Congo Zaire 318 280 88%

Infection Control - TransmissionDate Location Exposure Attack Rate

1976 Zaire Family, living in contiguous structure, shared eating facility

5.6%

1976 Sudan Family, sleeping in room without touching patient

0%

Sleeping in room and touching patient 23%

Sleeping in room and nursing patient 81%

1995 DRC Household members who did not share nursing duties (but may have slept in room)

0%

Transmission occurred through direct contact, unsterilized syringes (Zaire), and sexual