EBOLA VIRUS DISEASE(EVD)

BY

Dr Aminu ArzetDepartment of Internal medicine,N. Mandela School of Med. University of K/Natal,Durban..

CONTENTSINTRODUCTIONEPEDEMIOLOGYCLASSIFICATIONTRANSMISIONPATHOPHYSIOLOGYCLINICAL MANIFESTATIONDIAGNOSISTREATMENTPROGNOSISCONTROL AND PREVENTION

25th September, 2014

INTRODUCTIONEbola 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.

Epidemiology1st 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 ContinueSexually; 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

PathogenesisBody 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 ContinueMacrophage/ 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 ContinueSystemic 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 ContinueCoagulation 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 ContinueImpairment 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.

DIAGONOSISClinical 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 ContinuationLaboratory 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.

LABORATORY 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%.

TREATMENTEbola 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 issuesWikipedia Daily trust newspaperImage courtesy – bbc.co.uk, Google images, CDC and WHO