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 Prototype Viral
Hemorrhagic Fever
Pathogen
 Filovirus:enveloped,
non-segmented, negative-
stranded RNA virus
 Severe disease with high
case fatality
 Absence of specific
treatment or vaccine
 >20 previous Ebola and
Marburg virus outbreaks
 2014 West Africa Ebola
outbreak caused by
Zaire ebolavirus species
(five known Ebola virus
species)
 First appeared in Africa 1976
 “African Hemorrhagic Fever”
 acute, mostly fatal disease
 causes blood vessel “bursting”
 systemic (all organs/tissues)
 humans and nonhuman primates
 Excluding 2000 outbreak
 1,500 cases
 over 1,000 deaths
Scientific Classification:
 Order: Mononegavirales
 Family: Filoviridae
 Genus: Ebola like viruses
 Species: Ebola
Subtypes:
◦ Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast
 disease in humans
◦ Ebola-Reston
 disease in nonhuman primates
 2002- Fruit Bats
 Antibodies against
Ebola
 Ebola Gene sequences
in liver and spleen
 Fruit bats do not show
any symptoms
 Best candidate to be
the reservoir
 More research needs to
be done
 The link between human infection by the Ebola
virus and their proximity to primates is clear.
-Outbreaks occurred in countries that house 80
percent of the world’s remaining wild gorilla and
chimpanzee populations.
- The outbreaks coincided with the outbreaks in
wild animals.
- The same distinct viral strains were isolated in
animal carcasses and in the bodies of those who
handled those carcasses.
- These outbreaks were preceded by an
abnormally high death reports in wild Gorilla
populations.
Country
Reporting
Date
Total Cases
Confirmed
Cases
Total Deaths
Guinea 27 Oct 14 1,906 1,391 997
Liberia 25 Oct 14 6,535 2,515 2,413
Sierra Leone 27 Oct 14 5,235 3,700 1,500
Nigeria** 15 Oct 14 20 19 8
Spain 27 Oct 14 1 1 0
Senegal** 15 Oct 14 1 1 0
United
States
24 Oct 14 4 4 1
Mali 23 Oct 14 1 1 1
TOTAL 13,733 7,632 4,920
 Virus present in high quantity in blood, body fluids,
and excreta of symptomatic EVD-infected patients
 Opportunities for human-to-human transmission
 Direct contact (through broken skin or unprotected mucous
membranes) with an EVD-infected patient’s blood or body
fluids
 Sharps injury (with EVD-contaminated needle or other
sharp)
 Direct contact with the corpse of a person who died of EVD
 Indirect contact with an EVD-infected patient’s blood or
body fluids via a contaminated object (soiled linens or used
utensils)
 Ebola can also be transmitted via contact with blood,
fluids, or meat of an infected animal
 Infected persons are not contagious until onset of
symptoms
 Infectiousness of body fluids (e.g., viral load)
increases as patient becomes more ill
 Remains from deceased infected persons are highly
infectious
 Human-to-human transmission of Ebola virus via
inhalation (aerosols) has not been demonstrated
 Direct infection of tissues
 Immune dysregulation
 Hypovolemia and vascular
collapse
 Electrolyte abnormalities
 Multi-organ failure, septic
shock
 Disseminated intravascular
coagulation (DIC) and
coagulopathy
Other possible infectious causes of symptoms: (Differential Diagnosis)
Malaria, typhoid fever, meningococcemia, Lassa fever and other
bacterial infections like pneumonia which are all very common in Africa.
 Incubation period: 2-21 days
 Stage I (unspecific):
-Extreme asthenia (body weakness)
-diarrhea, nausea and vomiting, anorexia
abdominal pain
- headaches
- arthralgia (neuralgic pain in joints)
- myalgia (muscular pain or tenderness), back pain
- mucosal redness of the oral cavity, dysphagia (difficulty
in swallowing)
- conjunctivitis.
- rash all over body except in face
** If the patients don’t recover gradually at this point, there is a high
probability that the disease will progress to the second phase,
resulting in complications which eventually lead to death (Mupapa et
al., 1999).
 Stage II (Specific):
- Hemorrhage
- neuropsychiatric abnormalities
- anuria (the absence of urine formation)
- hiccups
- tachypnea (rapid breathing).
** Patients who progressed to phase two EHF almost
always die. (Ndambi et al., 1999)
 Late Complications:
-Arthralgia
- ocular diseases (ocular pain, photophobia and
hyperlacrimation)
- hearing loss
- unilateral orchitis( inflammation of one or both of the
testes)
** These conditions are usually relieved with the treatment
of 1% atropine and steroids
 Nonspecific early symptoms progress to:
 Hypovolemic shock and multi-organ failure
 Hemorrhagic disease
 Death
 Non-fatal cases typically improve 6–11 days after
symptoms onset
 Fatal disease associated with more severe early
symptoms
 Fatality rates of 70% have been reported in rural Africa
 Intensive care, especially early intravenous and
electrolyte management, may increase the survival rate
Organ System Clinical Manifestation
General Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)
Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%)
Cardiovascular Chest pain (37%),
Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%)
Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal
pain (44%), dysphagia (33%), jaundice (10%)
Hematological Any unexplained bleeding (18%), melena/hematochezia (6%),
hematemesis (4%), vaginal bleeding (3%), gingival bleeding
(2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site
(2%), hematuria (1%), petechiae/ecchymoses (1%)
Integumentary Conjunctivitis (21%), rash (6%)
 Thrombocytopenia (50,000–100,000/mL range)
 Leukopenia followed by neutrophilia
 Transaminase elevation: elevation serum aspartate
amino-transferase (AST) > alanine transferase (ALT)
 Electrolyte abnormalities from fluid shifts
 Coagulation: PT and PTT prolonged
 Renal: proteinuria, increased creatinine
Timeline of infection Diagnostic tests available
Within a few days after onset  Antigen-capture enzyme-
linked immunosorbent assay
(ELISA) testing
 IgM ELISA
 Polymerase chain reaction
(PCR)
 Virus isolation
Later in disease course or after
recovery
 Serology: IgM and IgG
Retrospectively in deceased
patients
 Immunohistochemistry testing
 PCR
 Virus isolation
 Hypovolemia and Sepsis Physiology
 Aggressive intravenous fluid resuscitation
 Hemodynamic support and critical care management if
necessary
 Electrolyte and acid-base abnormalities
 Aggressive electrolyte repletion
 Correction of acid-base derangements
 Symptomatic management of fever and
gastrointestinal symptoms
 Avoid NSAIDS
 Multisystem organ failure can develop and may
require
 Oxygenation and mechanical ventilation in ICU settings
 Correction of severe coagulopathy
 Renal replacement therapy
 No approved Ebola-specific prophylaxis or treatment
 Ribavirin has no in-vitro or in-vivo effect on Ebola virus
 Therapeutics in development with limited human clinical trial
data
• Convalescent serum
• Therapeutic medications
o Zmapp – chimeric human-mouse monoclonal antibodies
o Tekmira – lipid nanoparticle small interfering RNA
o Brincidofovir – oral nucleotide analogue with antiviral
activity
 Vaccines – in clinical trials
• Chimpanzee-derived adenovirus with an Ebola virus gene
inserted
• Attenuated vesicular stomatitis virus with an Ebola virus
gene inserted
 Case-fatality rate 71% in the 2014 Ebola outbreak
 Case-fatality rate is likely much lower with access to intensive
care
 Patients who survive often have signs of clinical
improvement by the second week of illness
 Associated with the development of virus-specific antibodies
 Antibody with neutralizing activity against Ebola persists
greater than 12 years after infection
 Prolonged convalescence
 Includes arthralgia, myalgia, abdominal pain, extreme fatigue,
and anorexia; many symptoms resolve by 21 months
 Significant arthralgia and myalgia may persist for >21 months
 Skin sloughing and hair loss has also been reported
The world is currently facing the biggest and most complex
Ebola outbreak in history. On August 8, 2014, the Ebola
outbreak in West Africa was declared by the World Health
Organization (WHO) to be a Public Health Emergency of
International Concern (PHEIC) because it was determined to be
an "extraordinary event" with public health risks to other
countries. The possible consequences of further international
spread are particularly serious considering the following
factors:
 The virulence (ability to cause serious disease or death) of
the virus.
 The widespread transmission in communities and healthcare
facilities in the currently affected countries and
 The strained health systems in the currently affected and
most at-risk countries.
PHIEC
•Widespread on multiple fronts
•Affected large cities
•Weak and fragile infrastructure
•Lack of knowledge of the disease
•Distrust of government and foreigners
•Not seeking voluntary health care
•Social rituals / burial rituals
•Delayed response; more resources needed
Context for outbreak
Impact on social determinants of health
 Trading, industry, agriculture, tourism
 Worsening poverty
 Hunger
 Orphans
 Stigma
 School closures
 Other diseases not being treated
 Lack of preventive care: prenatal care, vaccination
 Bio-geographical Ethics is defined as
motivation based on ideas of right and wrong
when dealing with the geographical distribution
of animals and plants.
 This concept of can be used to explain the
world’s shockingly small response to the Ebola
Virus.
 As there was little travel to that region by
people of more developed countries, there was
not much economic drive for a vaccine,
treatment and aid in prevention.
 The Ebola Virus is now however on the “A” list
for hopeful vaccination development.
 Experiments have even been formed to show
how Ebola can be used as a bioterror agent.
RISK LEVEL PUBLIC HEALTH ACTION
Monitoring Restricted
Public Activities
Restricted
Travel
HIGH risk
Direct Active
Monitoring
Yes Yes
SOME risk
Direct Active
Monitoring
Case-by-
case
assessment
Case-by-
case
assessment
LOW risk
Active Monitoring
for some;
Direct Active
Monitoring
for others
No No
NO risk No No No
What if?

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Ebola Seminar

  • 1.
  • 2.  Prototype Viral Hemorrhagic Fever Pathogen  Filovirus:enveloped, non-segmented, negative- stranded RNA virus  Severe disease with high case fatality  Absence of specific treatment or vaccine  >20 previous Ebola and Marburg virus outbreaks  2014 West Africa Ebola outbreak caused by Zaire ebolavirus species (five known Ebola virus species)
  • 3.  First appeared in Africa 1976  “African Hemorrhagic Fever”  acute, mostly fatal disease  causes blood vessel “bursting”  systemic (all organs/tissues)  humans and nonhuman primates  Excluding 2000 outbreak  1,500 cases  over 1,000 deaths
  • 4. Scientific Classification:  Order: Mononegavirales  Family: Filoviridae  Genus: Ebola like viruses  Species: Ebola Subtypes: ◦ Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast  disease in humans ◦ Ebola-Reston  disease in nonhuman primates
  • 5.
  • 6.  2002- Fruit Bats  Antibodies against Ebola  Ebola Gene sequences in liver and spleen  Fruit bats do not show any symptoms  Best candidate to be the reservoir  More research needs to be done
  • 7.  The link between human infection by the Ebola virus and their proximity to primates is clear. -Outbreaks occurred in countries that house 80 percent of the world’s remaining wild gorilla and chimpanzee populations. - The outbreaks coincided with the outbreaks in wild animals. - The same distinct viral strains were isolated in animal carcasses and in the bodies of those who handled those carcasses. - These outbreaks were preceded by an abnormally high death reports in wild Gorilla populations.
  • 8.
  • 9. Country Reporting Date Total Cases Confirmed Cases Total Deaths Guinea 27 Oct 14 1,906 1,391 997 Liberia 25 Oct 14 6,535 2,515 2,413 Sierra Leone 27 Oct 14 5,235 3,700 1,500 Nigeria** 15 Oct 14 20 19 8 Spain 27 Oct 14 1 1 0 Senegal** 15 Oct 14 1 1 0 United States 24 Oct 14 4 4 1 Mali 23 Oct 14 1 1 1 TOTAL 13,733 7,632 4,920
  • 10.  Virus present in high quantity in blood, body fluids, and excreta of symptomatic EVD-infected patients  Opportunities for human-to-human transmission  Direct contact (through broken skin or unprotected mucous membranes) with an EVD-infected patient’s blood or body fluids  Sharps injury (with EVD-contaminated needle or other sharp)  Direct contact with the corpse of a person who died of EVD  Indirect contact with an EVD-infected patient’s blood or body fluids via a contaminated object (soiled linens or used utensils)  Ebola can also be transmitted via contact with blood, fluids, or meat of an infected animal
  • 11.  Infected persons are not contagious until onset of symptoms  Infectiousness of body fluids (e.g., viral load) increases as patient becomes more ill  Remains from deceased infected persons are highly infectious  Human-to-human transmission of Ebola virus via inhalation (aerosols) has not been demonstrated
  • 12.  Direct infection of tissues  Immune dysregulation  Hypovolemia and vascular collapse  Electrolyte abnormalities  Multi-organ failure, septic shock  Disseminated intravascular coagulation (DIC) and coagulopathy
  • 13. Other possible infectious causes of symptoms: (Differential Diagnosis) Malaria, typhoid fever, meningococcemia, Lassa fever and other bacterial infections like pneumonia which are all very common in Africa.
  • 14.
  • 15.  Incubation period: 2-21 days  Stage I (unspecific): -Extreme asthenia (body weakness) -diarrhea, nausea and vomiting, anorexia abdominal pain - headaches - arthralgia (neuralgic pain in joints) - myalgia (muscular pain or tenderness), back pain - mucosal redness of the oral cavity, dysphagia (difficulty in swallowing) - conjunctivitis. - rash all over body except in face ** If the patients don’t recover gradually at this point, there is a high probability that the disease will progress to the second phase, resulting in complications which eventually lead to death (Mupapa et al., 1999).
  • 16.  Stage II (Specific): - Hemorrhage - neuropsychiatric abnormalities - anuria (the absence of urine formation) - hiccups - tachypnea (rapid breathing). ** Patients who progressed to phase two EHF almost always die. (Ndambi et al., 1999)  Late Complications: -Arthralgia - ocular diseases (ocular pain, photophobia and hyperlacrimation) - hearing loss - unilateral orchitis( inflammation of one or both of the testes) ** These conditions are usually relieved with the treatment of 1% atropine and steroids
  • 17.  Nonspecific early symptoms progress to:  Hypovolemic shock and multi-organ failure  Hemorrhagic disease  Death  Non-fatal cases typically improve 6–11 days after symptoms onset  Fatal disease associated with more severe early symptoms  Fatality rates of 70% have been reported in rural Africa  Intensive care, especially early intravenous and electrolyte management, may increase the survival rate
  • 18. Organ System Clinical Manifestation General Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%) Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%) Cardiovascular Chest pain (37%), Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%) Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%), jaundice (10%) Hematological Any unexplained bleeding (18%), melena/hematochezia (6%), hematemesis (4%), vaginal bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hematuria (1%), petechiae/ecchymoses (1%) Integumentary Conjunctivitis (21%), rash (6%)
  • 19.  Thrombocytopenia (50,000–100,000/mL range)  Leukopenia followed by neutrophilia  Transaminase elevation: elevation serum aspartate amino-transferase (AST) > alanine transferase (ALT)  Electrolyte abnormalities from fluid shifts  Coagulation: PT and PTT prolonged  Renal: proteinuria, increased creatinine
  • 20. Timeline of infection Diagnostic tests available Within a few days after onset  Antigen-capture enzyme- linked immunosorbent assay (ELISA) testing  IgM ELISA  Polymerase chain reaction (PCR)  Virus isolation Later in disease course or after recovery  Serology: IgM and IgG Retrospectively in deceased patients  Immunohistochemistry testing  PCR  Virus isolation
  • 21.
  • 22.  Hypovolemia and Sepsis Physiology  Aggressive intravenous fluid resuscitation  Hemodynamic support and critical care management if necessary  Electrolyte and acid-base abnormalities  Aggressive electrolyte repletion  Correction of acid-base derangements  Symptomatic management of fever and gastrointestinal symptoms  Avoid NSAIDS  Multisystem organ failure can develop and may require  Oxygenation and mechanical ventilation in ICU settings  Correction of severe coagulopathy  Renal replacement therapy
  • 23.  No approved Ebola-specific prophylaxis or treatment  Ribavirin has no in-vitro or in-vivo effect on Ebola virus  Therapeutics in development with limited human clinical trial data • Convalescent serum • Therapeutic medications o Zmapp – chimeric human-mouse monoclonal antibodies o Tekmira – lipid nanoparticle small interfering RNA o Brincidofovir – oral nucleotide analogue with antiviral activity  Vaccines – in clinical trials • Chimpanzee-derived adenovirus with an Ebola virus gene inserted • Attenuated vesicular stomatitis virus with an Ebola virus gene inserted
  • 24.  Case-fatality rate 71% in the 2014 Ebola outbreak  Case-fatality rate is likely much lower with access to intensive care  Patients who survive often have signs of clinical improvement by the second week of illness  Associated with the development of virus-specific antibodies  Antibody with neutralizing activity against Ebola persists greater than 12 years after infection  Prolonged convalescence  Includes arthralgia, myalgia, abdominal pain, extreme fatigue, and anorexia; many symptoms resolve by 21 months  Significant arthralgia and myalgia may persist for >21 months  Skin sloughing and hair loss has also been reported
  • 25. The world is currently facing the biggest and most complex Ebola outbreak in history. On August 8, 2014, the Ebola outbreak in West Africa was declared by the World Health Organization (WHO) to be a Public Health Emergency of International Concern (PHEIC) because it was determined to be an "extraordinary event" with public health risks to other countries. The possible consequences of further international spread are particularly serious considering the following factors:  The virulence (ability to cause serious disease or death) of the virus.  The widespread transmission in communities and healthcare facilities in the currently affected countries and  The strained health systems in the currently affected and most at-risk countries. PHIEC
  • 26. •Widespread on multiple fronts •Affected large cities •Weak and fragile infrastructure •Lack of knowledge of the disease •Distrust of government and foreigners •Not seeking voluntary health care •Social rituals / burial rituals •Delayed response; more resources needed Context for outbreak
  • 27. Impact on social determinants of health  Trading, industry, agriculture, tourism  Worsening poverty  Hunger  Orphans  Stigma  School closures  Other diseases not being treated  Lack of preventive care: prenatal care, vaccination
  • 28.  Bio-geographical Ethics is defined as motivation based on ideas of right and wrong when dealing with the geographical distribution of animals and plants.  This concept of can be used to explain the world’s shockingly small response to the Ebola Virus.  As there was little travel to that region by people of more developed countries, there was not much economic drive for a vaccine, treatment and aid in prevention.  The Ebola Virus is now however on the “A” list for hopeful vaccination development.  Experiments have even been formed to show how Ebola can be used as a bioterror agent.
  • 29.
  • 30. RISK LEVEL PUBLIC HEALTH ACTION Monitoring Restricted Public Activities Restricted Travel HIGH risk Direct Active Monitoring Yes Yes SOME risk Direct Active Monitoring Case-by- case assessment Case-by- case assessment LOW risk Active Monitoring for some; Direct Active Monitoring for others No No NO risk No No No
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