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EBOLA VIRUS 
DISEASE(EVD) 
BY 
Dr Aminu Arzet 
Department of Internal 
medicine, 
N. Mandela School of Med. 
University of K/Natal, 
Durban..
CONTENTS 
INTRODUCTION 
EPEDEMIOLOGY 
CLASSIFICATION 
TRANSMISION 
PATHOPHYSIOLOGY 
CLINICAL MANIFESTATION 
DIAGNOSIS 
TREATMENT 
PROGNOSIS 
CONTROL AND PREVENTION 
25th September, 2014
INTRODUCTION 
Ebola virus disease (EVD), formerly Ebola 
hemorrhagic fever(EHF) is a Zoonotic dx, caused by 
Ebola virus. 
Ebola is single stranded monosagmented RNA virus. 
It causes severe hemorrhagic fever that resembles 
fulminant septic shock. 
Acquired upon contact with blood or body fluid of 
an infected person or animal.
Epidemiology 
1st discovered in 1976, near River Ebola in DRC. 
Outbreaks; Several outbreaks mainly in Africa (DRC, 
Sudan, Uganda, Gabon, Liberia , Sierra Leone, Nig.) 
2014 Outbreak in West Africa; 
Started from Guinea in 2013, spread to Liberia, 
Sierra Leone, Nigeria, and Senegal. 
As of Sept 2014, 4390 laboratory-confirmed 
including 2226 deaths (case-fatality rate 51%).
Epidemiology Continuation 
Johannesburg 1996; Med Doc from Gabon, 
infected a Nurse- she died. 
Few infections in Italy, USA, UK, Russia, 
Philippines; Laboratory contamination.
Epidemiology cont
Classification 
 Belongs to ORDER MONONEGAVIRALES. 
FAMILY; FILOVIRIDAE. Filum in Latin=Thread like. 
Members= Ebola + Marburg virus. 
GENUS; EBOLAVIRUS- named after River Ebola in DR 
Congo(where 1st case was recorded in 1976) 
Has 5 species; 
• Zaire Virus; Most virulent, fatality rate upto 90%.
Classification Continue 
• Sudan Virus; Fatality rate of upto 50% 
•Cote d’ivoire Virus, formerly Tai River Virus. 
• Bundibugyo Virus; Least virulent,30% fatality rate. 
Uganda. 
• Reston Virus; Not pathogenic in human, seen in 
animal reservoir, mostly in Philippines/USA. 
Classified as "hemorrhagic fever viruses" due to 
clinical presentation; Coagulation defects 
capillary leak syndrome, and shock.
Transmission 
 Bats drop partially eaten fruits, which 
Monkeys, Antelopes, Man, etc feed on and 
contact the disease. 
 Contact with Blood or body fluid of infected 
animals/person. 
 Burial ceremonies- Direct contact with the corpse 
of infected person. Embalming 
 Formites; Utensils used by infected person, can 
spread the disease.
Transmission Continue 
Sexually; Men who have recovered from the 
disease, can transmit the virus, through their semen 
for up to 8/52 after recovery from illness. 
Aerosol; Its documented in Laboratories, not in real 
life. Reston Virus. 
Accidental Laboratories infections- USA, UK, 
Russia, Italy, Philippines. 
Biological warfare; Speculation. 
Asymptomatic person in incubation period, 
likely non infectious.
TRANSMISSION
Pathogenesis 
Body entry; The Virus Enters the body through 
mucous membranes, breaks in the skin, or 
parenterally. 
Glycoprotein synthesis(GP); After infection, the 
Virus synthesize GP called Ebola virus GP, that binds 
the virus to Macrophages/ neutrophils, Dendritic 
cells, and Endothelial cells of blood vessels.
Pathogenesis Continue 
Macrophage/ Nuetrophils inactivation; EV uses EV 
GP to invade Macrophage/ Neutrophil, then inhibit 
early steps of their activation. 
This inactivation allows the virus to evade immune 
system, colonize the host cells, and begin to 
replicate in large number. 
Systemic Spread; spread to LN, Liver, spleen, 
fibroblasts, and many other cell types, resulting in 
extensive tissue damage.
Pathogenesis Continue 
Systemic Inflammatory response; 
The presence of viral particles, 
extensive tissue/cell damage, and break down 
product of necrotic cells, causes the release of 
cytokines, chemokines, and other proinflammatory 
mediators, like; 
TNF-α, IL-6, IL-8, macrophage chemotactic 
protein (MCP)-1, and nitric oxide (NO) from 
infected macrophages and other cells. 
This chemicals result in fever, inflammation, 
malaise, vasodilatation, increased vascular 
permeability, hypotension, and shock.
Pathogenesis Continue 
Coagulation defects ; 
• Viral invasion of hepatocytes and vascular 
endothelial cells, results in vascular and Liver damage. 
•Infected macrophages synthesize tissue factor 
(TF), triggering the extrinsic coagulation pathway. 
•Proinflammatory cytokines also induce 
macrophages to produce Tissue Factor. These 
processes lead to coagulopathy seen in EVD
Pathogenesis Continue 
Impairment of adaptive immunity; 
•EV disable antigen-specific immune responses, by 
damaging Dendritic cells, which are responsibility for 
the initiation of adaptive immune responses. 
•Infected Dendritic cells fail to undergo maturation, 
thus unable to present antigens to lymphocytes, as 
such Ebola pt, fail to develop antibodies to the virus. 
•Failure of adaptive immunity and lymphocyte 
apoptosis, explain how EV cause severe/fatal illness.
Pathogenesis Continuation 
•Lymphocytes remain uninfected, but undergo 
reactionary apoptosis, most likely due to 
inflammatory mediators and/or the loss of support 
signals from dendritic cells. 
•Virus-specific lymphocyte proliferation still occurs, 
despite massive apoptosis, but it arrives too late to 
prevent a fatal outcome.
CLINICAL MANIFESTATION 
Incubation period = 2-21 days. Averagely 8 -10 days. 
EARLY SYMPTOMS; 
•Muscle weakness/pain 
•Headache. 
•Sore throat/ Pharyngitis /Cough 
•Ebola tongue(white furry). 
•Fever 
•Diarrhea/Nausea/vomiting 
•Skin Rashes
LATE SYMPTOM/SIGN; 
•Ecchymosis /bruising, 
•Oozing from venipuncture site. 
•Bleeding nose, ear. 
•Eye inflammation(conjunctivitis). 
•Bleeding from mouth/rectum. 
•Genital swelling(labia/scrotum). 
•Roof of mouth looks red. 
•Spontaneous miscarriages. 
•Confusion, Seizures, coma. 
•Death mostly due to Shock.
SING/SYMPTOMS CONT. 
•The disease could progress to multi organ failure and 
septic shock, with eventual death( averagely 6-10). 
•In fatal disease, patients fail to mount adequate 
immune response for unknown reasons. 
•. 
•In non-fatal cases, patients improve 6-11 days after 
the onset of symptoms. 
•The formation of antigen-antibody complexes during 
recovery may cause acute arthralgias and other 
symptoms.
DIAGONOSIS 
Clinical Diagnosis; 
• Difficult, early symptoms are none specific. 
• Its takes high index of suspicion. 
Laboratory Diagnosis; 
•(ELISA) testing; 
•Polymerase chain reaction(PCR)- DNA test. 
•Virus isolation. 
•Immunohistochemistry/ Immunoflorescence test
Diagnosis Continuation 
Laboratory findings; 
•Leucophenia; Is start with Lymphopenia, followed 
Neutrophilia (WCC 1000/microL ). 
•Thrombocytopenia; Platelet counts 50,000- 
100,000/microL). 
•Transaminitis; Elevated serum AST/ALT and Amylase 
•Decrease in total plasma protein; Hepatocytes 
damage/capillary leak syndrome.
L A B ORATORY FINDING CONTINUATION 
•Renal abnormality; Proteinuria and renal 
insufficiency. 
•Coagulation abnormalities; Prolonged Prothrombin 
(PT) and partial thromboplastin times (PTT). Fibrin 
degradation products are elevated, consistent with 
disseminated intravascular coagulation (DIC). 
Differential Diagnosis; 
•Other Heamorrhagic fevers; Marburg/Dangue/Yellow 
•Typhoid Fever 
•Malaria
PREVENTION AND CONTROL 
•Avoid bush-meat. 
•Regular washing of hands. 
•Early detection/Contact tracing/Isolation. 
•Screening travelers from affected countries 
•Quarantine of suspected case(21/7) 
•Barrier nursing techniques 
•Use personal protective equip.(PPE) 
•Proper sterilization of equipments 
•No washing of carcass 
•Proper burials of died. 
•Public awareness.
PROGNOSIS 
•EVD is the most lethal disease known to mankind 
•Has poor prognosis, with fatality rate upto 90%. 
•Effected people die from Shock. 
•Ebola Virus Zaire is most deadly, fatality of 90%. 
•Ebola virus Bundibugyo and Sudan has the 
Fatality upto 50%.
TREATMENT 
Ebola has no cure. 
Supportive treatment only; 
• Oxygen; Help breathing 
•Antibiotics; Prevent 2’ bacterial infection. 
•Analgesic; Fever and body ache. 
•IVF; Maintain fluid and electrolyte balance. 
•Transfusion; Bleeding
EXPERIMENTAL DRUGS 
Zmapp 
•Is a combination of 3 different monoclonal 
antibodies that bind to the protein of the Ebola 
virus. Mapp Biopharmaceutical Inc, USA. 
•Has not yet been tested in humans for safety or 
effectiveness. 
Nano Silver; A Nigerian drug. Little is know 
about it.
VACCINE 
•None Available at present. 
Virus like particles: VSV-EBOV, is Canadian made 
Vaccine. At trial level 
Non-replicating vectors: alpha virus, DNA vaccines, 
recombinant adenovirus based vectors (rAD)
References; 
CDC website http://www.cdc.gov/vhf/ebola/about.html 
WHO website http://www.who.int/csr/disease/ebola/en/ 
The Lancet Ebola Resource Centre http://ebola.thelancet.com/ 
Journals - Bulletin of the WHO, NEJM and BMJ, August and 
September 2014 issues 
Wikipedia 
Daily trust newspaper 
Image courtesy – bbc.co.uk, Google images, CDC and WHO

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Ebola virus disease by Aminu Arzet

  • 1. EBOLA VIRUS DISEASE(EVD) BY Dr Aminu Arzet Department of Internal medicine, N. Mandela School of Med. University of K/Natal, Durban..
  • 2. CONTENTS INTRODUCTION EPEDEMIOLOGY CLASSIFICATION TRANSMISION PATHOPHYSIOLOGY CLINICAL MANIFESTATION DIAGNOSIS TREATMENT PROGNOSIS CONTROL AND PREVENTION 25th September, 2014
  • 3. INTRODUCTION Ebola virus disease (EVD), formerly Ebola hemorrhagic fever(EHF) is a Zoonotic dx, caused by Ebola virus. Ebola is single stranded monosagmented RNA virus. It causes severe hemorrhagic fever that resembles fulminant septic shock. Acquired upon contact with blood or body fluid of an infected person or animal.
  • 4. Epidemiology 1st discovered in 1976, near River Ebola in DRC. Outbreaks; Several outbreaks mainly in Africa (DRC, Sudan, Uganda, Gabon, Liberia , Sierra Leone, Nig.) 2014 Outbreak in West Africa; Started from Guinea in 2013, spread to Liberia, Sierra Leone, Nigeria, and Senegal. As of Sept 2014, 4390 laboratory-confirmed including 2226 deaths (case-fatality rate 51%).
  • 5. Epidemiology Continuation Johannesburg 1996; Med Doc from Gabon, infected a Nurse- she died. Few infections in Italy, USA, UK, Russia, Philippines; Laboratory contamination.
  • 7. Classification  Belongs to ORDER MONONEGAVIRALES. FAMILY; FILOVIRIDAE. Filum in Latin=Thread like. Members= Ebola + Marburg virus. GENUS; EBOLAVIRUS- named after River Ebola in DR Congo(where 1st case was recorded in 1976) Has 5 species; • Zaire Virus; Most virulent, fatality rate upto 90%.
  • 8. Classification Continue • Sudan Virus; Fatality rate of upto 50% •Cote d’ivoire Virus, formerly Tai River Virus. • Bundibugyo Virus; Least virulent,30% fatality rate. Uganda. • Reston Virus; Not pathogenic in human, seen in animal reservoir, mostly in Philippines/USA. Classified as "hemorrhagic fever viruses" due to clinical presentation; Coagulation defects capillary leak syndrome, and shock.
  • 9. Transmission  Bats drop partially eaten fruits, which Monkeys, Antelopes, Man, etc feed on and contact the disease.  Contact with Blood or body fluid of infected animals/person.  Burial ceremonies- Direct contact with the corpse of infected person. Embalming  Formites; Utensils used by infected person, can spread the disease.
  • 10. Transmission Continue Sexually; Men who have recovered from the disease, can transmit the virus, through their semen for up to 8/52 after recovery from illness. Aerosol; Its documented in Laboratories, not in real life. Reston Virus. Accidental Laboratories infections- USA, UK, Russia, Italy, Philippines. Biological warfare; Speculation. Asymptomatic person in incubation period, likely non infectious.
  • 12. Pathogenesis Body entry; The Virus Enters the body through mucous membranes, breaks in the skin, or parenterally. Glycoprotein synthesis(GP); After infection, the Virus synthesize GP called Ebola virus GP, that binds the virus to Macrophages/ neutrophils, Dendritic cells, and Endothelial cells of blood vessels.
  • 13. Pathogenesis Continue Macrophage/ Nuetrophils inactivation; EV uses EV GP to invade Macrophage/ Neutrophil, then inhibit early steps of their activation. This inactivation allows the virus to evade immune system, colonize the host cells, and begin to replicate in large number. Systemic Spread; spread to LN, Liver, spleen, fibroblasts, and many other cell types, resulting in extensive tissue damage.
  • 14. Pathogenesis Continue Systemic Inflammatory response; The presence of viral particles, extensive tissue/cell damage, and break down product of necrotic cells, causes the release of cytokines, chemokines, and other proinflammatory mediators, like; TNF-α, IL-6, IL-8, macrophage chemotactic protein (MCP)-1, and nitric oxide (NO) from infected macrophages and other cells. This chemicals result in fever, inflammation, malaise, vasodilatation, increased vascular permeability, hypotension, and shock.
  • 15. Pathogenesis Continue Coagulation defects ; • Viral invasion of hepatocytes and vascular endothelial cells, results in vascular and Liver damage. •Infected macrophages synthesize tissue factor (TF), triggering the extrinsic coagulation pathway. •Proinflammatory cytokines also induce macrophages to produce Tissue Factor. These processes lead to coagulopathy seen in EVD
  • 16. Pathogenesis Continue Impairment of adaptive immunity; •EV disable antigen-specific immune responses, by damaging Dendritic cells, which are responsibility for the initiation of adaptive immune responses. •Infected Dendritic cells fail to undergo maturation, thus unable to present antigens to lymphocytes, as such Ebola pt, fail to develop antibodies to the virus. •Failure of adaptive immunity and lymphocyte apoptosis, explain how EV cause severe/fatal illness.
  • 17. Pathogenesis Continuation •Lymphocytes remain uninfected, but undergo reactionary apoptosis, most likely due to inflammatory mediators and/or the loss of support signals from dendritic cells. •Virus-specific lymphocyte proliferation still occurs, despite massive apoptosis, but it arrives too late to prevent a fatal outcome.
  • 18. CLINICAL MANIFESTATION Incubation period = 2-21 days. Averagely 8 -10 days. EARLY SYMPTOMS; •Muscle weakness/pain •Headache. •Sore throat/ Pharyngitis /Cough •Ebola tongue(white furry). •Fever •Diarrhea/Nausea/vomiting •Skin Rashes
  • 19. LATE SYMPTOM/SIGN; •Ecchymosis /bruising, •Oozing from venipuncture site. •Bleeding nose, ear. •Eye inflammation(conjunctivitis). •Bleeding from mouth/rectum. •Genital swelling(labia/scrotum). •Roof of mouth looks red. •Spontaneous miscarriages. •Confusion, Seizures, coma. •Death mostly due to Shock.
  • 20. SING/SYMPTOMS CONT. •The disease could progress to multi organ failure and septic shock, with eventual death( averagely 6-10). •In fatal disease, patients fail to mount adequate immune response for unknown reasons. •. •In non-fatal cases, patients improve 6-11 days after the onset of symptoms. •The formation of antigen-antibody complexes during recovery may cause acute arthralgias and other symptoms.
  • 21. DIAGONOSIS Clinical Diagnosis; • Difficult, early symptoms are none specific. • Its takes high index of suspicion. Laboratory Diagnosis; •(ELISA) testing; •Polymerase chain reaction(PCR)- DNA test. •Virus isolation. •Immunohistochemistry/ Immunoflorescence test
  • 22. Diagnosis Continuation Laboratory findings; •Leucophenia; Is start with Lymphopenia, followed Neutrophilia (WCC 1000/microL ). •Thrombocytopenia; Platelet counts 50,000- 100,000/microL). •Transaminitis; Elevated serum AST/ALT and Amylase •Decrease in total plasma protein; Hepatocytes damage/capillary leak syndrome.
  • 23. L A B ORATORY FINDING CONTINUATION •Renal abnormality; Proteinuria and renal insufficiency. •Coagulation abnormalities; Prolonged Prothrombin (PT) and partial thromboplastin times (PTT). Fibrin degradation products are elevated, consistent with disseminated intravascular coagulation (DIC). Differential Diagnosis; •Other Heamorrhagic fevers; Marburg/Dangue/Yellow •Typhoid Fever •Malaria
  • 24. PREVENTION AND CONTROL •Avoid bush-meat. •Regular washing of hands. •Early detection/Contact tracing/Isolation. •Screening travelers from affected countries •Quarantine of suspected case(21/7) •Barrier nursing techniques •Use personal protective equip.(PPE) •Proper sterilization of equipments •No washing of carcass •Proper burials of died. •Public awareness.
  • 25. PROGNOSIS •EVD is the most lethal disease known to mankind •Has poor prognosis, with fatality rate upto 90%. •Effected people die from Shock. •Ebola Virus Zaire is most deadly, fatality of 90%. •Ebola virus Bundibugyo and Sudan has the Fatality upto 50%.
  • 26. TREATMENT Ebola has no cure. Supportive treatment only; • Oxygen; Help breathing •Antibiotics; Prevent 2’ bacterial infection. •Analgesic; Fever and body ache. •IVF; Maintain fluid and electrolyte balance. •Transfusion; Bleeding
  • 27. EXPERIMENTAL DRUGS Zmapp •Is a combination of 3 different monoclonal antibodies that bind to the protein of the Ebola virus. Mapp Biopharmaceutical Inc, USA. •Has not yet been tested in humans for safety or effectiveness. Nano Silver; A Nigerian drug. Little is know about it.
  • 28. VACCINE •None Available at present. Virus like particles: VSV-EBOV, is Canadian made Vaccine. At trial level Non-replicating vectors: alpha virus, DNA vaccines, recombinant adenovirus based vectors (rAD)
  • 29. References; CDC website http://www.cdc.gov/vhf/ebola/about.html WHO website http://www.who.int/csr/disease/ebola/en/ The Lancet Ebola Resource Centre http://ebola.thelancet.com/ Journals - Bulletin of the WHO, NEJM and BMJ, August and September 2014 issues Wikipedia Daily trust newspaper Image courtesy – bbc.co.uk, Google images, CDC and WHO