Failure to Collide
Ebola and Modern Medicine, 2014
Paul Farmer, MD, PhD
Harvard Medical School
Brigham and Women’s Hospital
Partners In Health
Kapuscinski Development Lecture
King’s College London
April 20, 2015
Photo by Rebecca E. Rollins
Slow Plague vs. Fast Plague?
Zoonoses from equatorial Africa
• Marburg, Germany (1967)
• Yambuku, Zaire (1976)
• Nzara, Sudan (1976)
Photo by Lyle Conrad
Long DDx in Sub-Saharan Africa
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Malaria (“choleraic presentation”)
Cholera
Enteric fever due to S. typhi
Lassa fever
Dengue fever
Yellow fever
Relapsing fever
Shigellosis
Meningococcemia
Listeriosis
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Staph/strep bacteremia
Anthrax
Measles
Varicella
Chikungunya virus
Leptospirosis
Toxic shock syndrome
Fulminant viral hepatitis
Influenza
Kikwit, 1995
Pathophysiology
• Enters through mucosa, breaks in skin, parenteral introduction (e.g needlestick);
environmental testing: no viable RNA on high-touch surfaces (e.g. bed rails, BR
tiles) but easily cultured from human remains for days to weeks
• Target cells include monocytes, macrophages, dendritic cells; then on to lymph
nodes, liver, spleen
• EBOV readily isolated from most bodily fluids (and ET suctioning) during
illness (begins 5-10 days after infection; earlier with direct inoculation)
• Infection of adrenal cortical cells; impaired synthesis of steroids, Na+
• ?Mechanism of GI involvement (?translocation of gut bacteria)
• Coagulopathy
• Autopsy studies/non-human primate models unremarkable for irreversible
vascular lesions (“infection of endothelial cells by Zaire Ebola virus was
infrequent and was mainly restricted to terminal stages of disease,” Feldmann
and Geisbert 2011)
Feldmann H, Geisbert TW. Seminar: Ebola Hemorrhagic Fever. Lancet 2011; 377: 849-862.
Slow vs. Fast Responses?
• Current (“25th recorded”)
outbreak of EVD thought to
begin in 12/2013 in Guinea Rain
Forest
• Patients not dx’d until epidemic
among HCWs
• Cases in all 3 countries by 4/2014
• WHO warns against “overreaction” in 4/2014
• MSF declares EVD “out of
control” in 6/2014
• As of 4/2015, 25,556 cases
Video source: WHO Ebola Response Team. Ebola Virus Disease in West Africa—The First 9 Months of the Epidemic and Forward Projections. NEJM
2014; 371: 1481-95.
How Did Ebola Spread So Quickly?
Ebola As Caregivers’ Disease
Freetown, Sierra Leone
October 2014
Photo by Rebecca Rollins
CDS (Clinical Datapenia Syndrome) in Ebola Epidemics
• Prodrome of fatigue/F/C/malaise/myalgias
• Predominance of GI symptoms (N/V/D, abdominal pain) f/b
hypovolemic shock and MSOF
• Hemorrhagic sx (petechiae, uncontrolled bleeding at venipuncture
site, hematemesis, melena) in minority of patients (1/44 in Kenema)
• Dizziness, headache common; delirium, stupor, meningo-encephalitis
in 10-15%; arthralgias also seen
• Little lab data except PCR. When reported: lymphopenia, plt,
transaminitis (AST>ALT); elevated BUN/Cr; acidosis common;
+
+
++; ?DIC
Na , K , Ca
• Long-term sequelae (i.e. opthalmalhogic, neurologic, ?)
CFR and “No-Overlap Syndrome”
The Collision of Modern Medicine and Hemorrhagic Viruses
Marburg Virus Disease, 1967 vs. Marburg Virus Since
• High mortality in Germany, Yugoslavia
• Grotesque mortality in sub-Saharan Africa,
even in cities (e.g. Angola, 2005)
85.9%
22.6%
Central Europe, 1967 Africa, 1968-2007
(7/31)
(462/538)
70.8%
Ebola Virus Disease in West Africa vs. US Hospitals
• From Kikwit (82%) to Kenema (74%)
• All Americans have survived w/ proper care
World Health Organization. Marburg Hemorrhagic Fever Fact Sheet 2014.
West Africans, 2014
(2,839/4,010)
95% CI:
[0.0-0.0%]
0.0%
Americans, 2014
(0/10)
WHO Ebola Response Team. Ebola Virus Disease in West Africa—The First 9 Months of the Epidemic and Forward Projections. NEJM 2014; 371:
1481-95.
Clinical Course Revealed by the Collision (8/2)
Lyon GM, Mehta AK, Varkey JB, et al. Clinical Care of Two Patients with Ebola Virus Disease in the United States. NEJM 2014; 371: 2402-2409.
An Effective Ebola Response Requires
Integration of Prevention and Care
“[We] felt a certain unease about treating a highly transmissible illness for which there is no
vaccine, no specific therapy, and a high mortality rate. Yet we also appreciated that most viral
illnesses, and certainly most critical illnesses, have no specific therapy. After spending much
of the past 5 months treating patients with Ebola virus disease, we are convinced that it’s
possible to save many more patients. Our optimism is fueled by the observation that
supportive care is also specific care for EVD—and in all likelihood reduces mortality.
Unfortunately, many patients in West Africa continue to die for lack of the opportunity to
receive such basic care” (Lamontagne et al, NEJM, 9/25/14)
“The handling of diarrhea and vomitus, which can contain infectious EBOV, poses a threat
of infection to HCWs and cleaners, and precautions should be emphasized in preventive
training. However, it is incumbent on HCWs to ensure that EVD facilities are focused on
improving the survival of patients, rather than merely on providing a setting for quarantine”
(Schieffelin et al, NEJM, 10/29/14)
Lamontagne F, Clément C, Fletcher T, et al. Doing Today’s Work Superbly Well—Treating Ebola with Current Tools. NEJM 2014; 371: 1565-1566.
Schieffelin JS, Shaffer JG, Goba SA, et al. Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone. NEJM 2014; 371: 2092-2100.
Preliminary Conclusion
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An effective Ebola response relies on
understanding epidemiology, pathophysiology,
and clinical course
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And needs staff, stuff, space, and systems for
safe supportive care
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Caregivers at greatest risk; survivors essential
part of response
Responding to Ebola: The Four “Ss”
ETUs
“Grey Zone”
Community Health Workers
Staff: Two Tasks, One Team
Photo by Rebecca Rollins
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RNs, MDs (esp. critical care)
Nurses’ aides
Psychosocial team
Community health workers
Logisticians
Administrators/managers
Researchers/epidemiologists
Cleaners/sprayers
Cooks
Gardeners
Plumbers
Projectionists
Priests
Photo by Rebecca Rollins
Stuff: Personal Protective Equipment
Ebola Virus: For Want of
Rubber Gloves, Doctors Die
By Drew Hinshaw
August 16, 2014
1928 ad feat.
Margibi County,
Liberia
Stuff: Planes, Trains, and Automobiles
Photo by Partners In Health
Stuff: Preventives, Diagnostics, Therapeutics
Space: “One Way In, Two Ways Out”
Photo by Jon Lascher
Photo by Daniel Berehulak
Systems: Respond to Ebola, Build/Rebuild Health Systems
Systems: Respond to Ebola, Build/Rebuild Health Systems
Visits for short-term
family planning methods,
Marie Stopes International Sierra Leone
Children aged 12-23 months given
measles conjugate vaccine in Liberia
100%
37,381
80%
60%
40%
20%
1,724
0%
1999
2002
2005
2008
2011
2014
May-14
May
2014
August-14
August
2014
WHO. Vaccine-Preventable Diseases Monitoring System: 2014 Update.
Hamilton J. “Ebola Is Preventing Kids from Getting Vaccinated in Liberia.” NPR: October 23, 2014.
UNFPA Sierra Leone Country Office. Impact of Ebola Outbreak on Reproductive Health and Proposed Mitigation Strategy. October 2014.
Systems: Respond to Ebola, Build/Rebuild Health Systems
2,500
Sierra Leone
Liberia
Guinea
2,000
1,500
Maternal deaths per
100,000 live births
1,000
500
0
1990
1995
2000
2005
WHO, UNICEF, UNFPA, and The World Bank. Trends in Maternal Mortality: 1990 to 2013. Geneva: WHO, 2014.
Hayden EC. Maternal Health: Ebola’s Lasting Legacy. Nature 2015; 519: 24-26.
2010
2015
Systems: Respond to Ebola, Build/Rebuild Health Systems
2,500
Sierra Leone
Liberia
Guinea
2,000
1,500
Maternal deaths per
100,000 live births
1,000
500
0
1990
1995
2000
2005
WHO, UNICEF, UNFPA, and The World Bank. Trends in Maternal Mortality: 1990 to 2013. Geneva: WHO, 2014.
Hayden EC. Maternal Health: Ebola’s Lasting Legacy. Nature 2015; 519: 24-26.
2010
2015
What Never Happens with Emergency Responses?
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Health systems strengthening
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Training/capacity building
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Research
$5.4B?
Photo by Clinton Foundation
What Would This Look Like?
Photo by Rebecca Rollins
Ebola isolation center in Zwedru, Liberia
Photo by Partners In Health
University Hospital, Mirebalais, Haiti
Thank
You
Glenna Gordon, The Wall Street Journal
Monrovia, Liberia: September 29, 2014