EBOLA VIRUS DISEASE

NUR SUMAIYYAH LAWSON

BIOMEDICAL DIAGNOSTIC 11

(BBD 4024)

CLINICAL MICROBIOLOGY

INTRODUCTION

DISASTER• A total of 2,615 Ebola infections and 1,427 deaths• highest case fatality rates of any human virus, 88%

ETYMOLOGY• First recorded outbreak at, Yambuku in democratic republic of

congo (EBOLA RIVER)

VIRUS ( Latin virulentus)• Viruses do not contain enzymes for energy production or

protein synthesis.• small infectous agent that replicates only inside the

living cells of other organisms

STROKES YEAR REGIONS AFFECTED

DESCRIPTION

FIRST 1976 Democratic republic of congo (ZAIRE) & sudan

First outbreak of Ebola. Hemorrhagic fever

SECOND 1989 Reston ,Virginia mysterious outbreak. (initially diagnosed as Simian hemorrhagic fever virus (SHFV)) among a shipment of crab-eating macaque monkeys imported from the Philippines. named Reston ebolavirus (REBOV)

THIRD 2014 WEST AFRICA-affecting Guinea,

Sierra Leone, Liberia and Nigeria.

largest outbreak to the date

Ebola Taxonomy

• Group : Group V (-)sense RNA

• Order : Mononegavirales

• Family : Filoviridae

• Genus : Ebolavirus

Sudan(SUDV)

Bundibugyo(BDBV)

Tai forest(TAFV)

Formerly Cote d-Ivoire

Species

Zaire ebola(EBOV)

The most dangerous

Reston(RESTV)

Non-humans

Ebola Species

Virological Aspects

• Family Filoviridae in the order Mononegavirales

• Five species• Zaire, Sudan, Taï,

Reston, Bundibugyo• Enveloped, non-

segmented, negative-strand RNA virus, filamentous

• Genes arranged linearly coding for seven structural proteins - NP, VP35, VP40, GP, VP30, VP24 and L with NP

• GP, transmembrane protein and responsible for receptor binding and membrane fusion

Rizwan SA, VMCHRI

STRUCTURE

• Viral cores

–stack up in cell

–migrate to the cell surface

–Produce trans-membrane proteins

–Push through cell surface

–Become enveloped by cell

membrane

• ssRNA- Genome Mutations

–Capable of rapid mutation

–very adaptable to evade host

defenses and environmental change

Ebola Virus

Attach to walls

Leakage of blood and serum into

surrounding tissue

Wbcs’attack

Wbcs’ dissolve

Chemical released

Pro-inflammatory

cytokinesPro coagulantsAlso released

Blood vessels more

damaged

Permanent bleeding

Entire body leaks

and dissolves

Ebola Pathophysiology

Ebola Pathophysiology

Modes of Transmission

• Direct contact (through broken skin or mucousmembranes) with

– a sick person's blood or body fluids (urine, saliva,faeces, vomit, semen)

– objects (such as needles) that have beencontaminated with infected body fluids

– infected animals

• High risk groups – bush meat hunters, relatives ofpatients, funeral attendees, corpse handlers, labpersonnel

I

Transmission

CAUSES

• Ebola Virus Disease in humans is caused by 4of the 5 viruses of the genus Ebolavirus. The four are Bundibugyo virus , Sudan virus, TaïForest virus and one called Ebola virus (EBOV).

• EBOV, species Zaire ebolavirus, is the most dangerous of the viruses causing the largest number of outbreaks.

Zaire Ebolavirus

SIGNS AND SYMPTOMS (1)

Early symptoms : Influenza(fever,headache,joint & abdominal

pain)

Vomiting,diarrhoea

Loss of appetite

Chest pain,shortness of breath

Weakness

Maculopapular rash(50% cases)

Maculopapular Rash

SIGNS AND SYMPTOMS (2)

Acute symptoms :Bleeding from mucous membrane(eg.nose)

Bleeding of the skin

Subconjunctival haemorrhages

Decreased blood clotting

Multiple organ dysfunction syndrome which leads to death

Bleeding of the Skin

Subconjunctival Haemorrhagesin GI tract

COMPLICATIONS

• Recovery may begin between 7 and 14 days after first symptom.

• Death is often due to low blood pressure from fluid loss. In general, bleeding often indicates a worse outcome, and blood loss may result in coma and death.

• Those who survive often have ongoing muscular and joint pain, liver inflammation, and may have continued feelings of tiredness and weakness, decreased appetite.

DIAGNOSIS (1)

• Laboratory indicators include a low platelet count; an initially decreased WBC count followed by an increased WBC count; elevated levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and abnormalities in blood clotting often consistent with disseminated intravascular coagulation

(DIVC) such as a prolonged prothrombin time,

partial thromboplastin time, and bleeding time.

TEST NORMAL VALUE

Platelet count 150000-300000mcL

WBC count 4500-10000mcL

Alanine aminotransferase(ALT) 10-40U/L (males)7-35U/L(females)

Aspartate aminotransferase(AST) 14-20U/L (males)10-36U/L (females)

Prothrombin time (PT) 10-12 sec

Partial thromboplastin time (aPTT) 25-38 sec

Bleeding time (BT) 3-7 min

DIAGNOSIS (2)

• In early phase - ELISA,PCR, Virus isolation

• In later phase - IgM and IgG antibodies

• In deceased patients – immunohistochemistry, PCR, virus isolation

• Strict precautions during transportation of samples.

PCR Test

ELISA test

TREATMENT

• No proven antiviral drug

• Providing intravenous fluids and balancing electrolytes (body salts)

• Treating other infections if they occur

• Personal Protective Equipment

• Isolation of Ebola patients from contact

• No licensed vaccine for EVD is available. Several vaccines are being tested, but none are available for clinical use.

Experimental Treatments

• ZMapp – a combo of 3 monoclonal antibodies

• TKM-Ebola – targets RNA of the virus

• MB-2003 - prevents infection when administered within one to two days

• BCX-4430 – RNA polymerase

• Whole blood and serum transfusion from recovered patients

PREVENTION (1)

• Public health measures -early detection andisolation, contact tracingand rigorous infectioncontrol measures

• Screening of travellersfrom affected countries inairports, seaports and landborders

• Quarantine andobservation of suspectedcases for 21 days fromexposure

PREVENTION (2)• All suspected or confirmed

cases, single closed patientroom

• Avoiding contact

• A log book containing detailsof persons entering

• Personalprotective equipmentfor caretakers

• Minimum use of sharps.

In this 2014 photo provided by the Samaritan's Purse aid organization, Dr. Kent Brantly, left, treats an Ebola patient at the Samaritan's Purse Ebola Case Management Center in Monrovia, Liberia. On Saturday, July 26, 2014, the North Carolina-based aid organization said Brantly tested positive for the disease and was being treated at a hospital in Monrovia.

View of an isolation center for people infected with Ebola at Donka Hospital in Conakry.

CASE STUDY (1)

• On the 5 November 1976 one investigator at the Microbiological Research Establishment accidentally pricked his thumb through a protective rubber glove while transferring homogenized liver from a guinea-pig infected with a new virus. According to standard safety protocol he immediately removed the glove and immersed his thumb in hypochlorite solution then squeezed it vigorously. There was no bleeding and careful examination with a hand lens failed to reveal a puncture wound. He was kept under surveillance, and on the sixth day became ill.

CASE STUDY

• Shortly after midnight on 11 November his temperature rose to 37 4°C. During the early morning he complained of central abdominal pain and nausea. He developed an erythematous rash. He did not vomit or have the headache or myalgia. He was transferred to the high-security infectious diseases unit . When he was admitted he felt physically exhausted and complained of anorexia, nausea, and central abdominal pain.His temperature was 38°C . He was alert and did not seem to be particularly ill.

• Apart from slight abdominal tenderness there were no other abnormal findings. Treatment was started with human interferon given by intramuscular injection in a dose of 3 million units every 12 hours for 14 days.

CASE STUDY

• The next morning his temperature was normal and he was free from symptoms, but later in the evening his temperature rose again to 39°C. Apart from loss of appetite there were no other symptoms. By this time direct electron microscopy had shown virus particles in the patient's blood. In view of this finding it was thought advisable to give the patient convalescent serum from people convalescing after the recent African outbreak. The serum was given by slow intravenous infusion over a period of four hours.

CASE STUDY

• On the fourth day of illness his temperature fell to normal. About midday he had a sudden violent bout of shivering followed by a sharp rise in temperature to 40°C. This was accompanied by nausea and a single episode of vomiting. His mental state began to change and over the next 24 hours there was striking deterioration in concentration and memory. Protein was detected in his urine for the first time and persisted thereafter until the fever subsided

CASE STUDY

• Over the next 72 hours, there was severe malaise and extreme weakness. Profuse watery diarrhea developed and continued for two days accompanied by persistent vomiting.

• On the sixth day of illness, a further 330 ml of convalescent serum was infused and followed by Hartmann's solution to correct the dehydration. His general condition started to improve and he made an uneventful and slow recovery over 10 weeks.

DISCUSSION (1)

• The nature of the accident and the absence-of a visible puncture mark indicate the invasiveness of Ebola virus and the high susceptibility of man. The course and duration of the illness were similar to patients infected with Ebola with the characteristic clinical syndrome of the rash, excessive fatigue, and considerable gastrointestinal disturbance.

• The oliguria and proteinuria present at the height of the illness could have been attributed to deposition of immune complexes in the kidney

DISCUSSION (2)

• The relatively mild course of the illness and the absence of haemorrhage might have been due to early treatment with interferon and convalescent serum. At present, apart from the use of convalescent serum, there is no definitive cure for Ebola infection making this a potentially fatal disease.

CONCLUSION

• Ebola virus disease also known as Ebola hemorrhagic fever is a disease of humans and other primates caused by ebolaviruses. It has a high risk of death, with patients developing internal and external bleeding. There is no definitive cure and management is mainly supportive ensuring adequate hydration and symptomatic treatment. Prevention through isolation, barrier nursing and contact tracing is essential.

QUESTIONS

1. When is the first outbreak of Ebola occur?

2. What are the five types of species in Ebola species chart?

3. What are the name of the seven genes arranged linearly coding for structural proteins ?

4. Explain briefly about the Ebola pathophysiology

5. What are the symptoms that were developed over the next 72 hours in the case study?

ANSWERS

1. 19762. Bundibugyo species , Sudan species, Taï Forest

species , Zaire ebola species and Reston species3. NP, VP35, VP40, GP, VP30, VP24 and L with NP 4. Ebola virus attach to the walls causing leakage of blood

and serum into the surrounding tissue. WBC attack and dissolved.Chemical,proinflammatory,cytokines,procoagulants are releases causing the blood vessel to be damaged. This causes permenant bleeding and as a result,entirebody leaks and dissolves.

5. Severe malaise and extreme weakness. Profuse watery diarrhea developed

REFERENCES

• Emond R T D, Evans B., Bowen E T W , Lloyd G, A case of Ebola virus infection British Medical Journal, 1977, 2, 541-544

• Martini, G A, Postgraduate Medical Journal, 1973, 49, 542. 2

• Gear, J S S, et al, British Medical,Journal, 1975, 4, 489.

• H Nishiura, G Chowell, Early transmission dynamics of Ebola virus disease (EVD), West Africa, - Euro Surveill March to August 2014 researchgate.net

REFERENCES

• Watt A, Moukambi F ,Banadyga L , Groseth A, Callison J ,Herwig A ,Ebihara H, Feldmann H ,a Hoenen T, A Novel Life Cycle Modeling System for Ebola Virus Shows a Genome Length-Dependent Role of VP24 in Virus Infectivity Journal of Virology September 2014 Volume 88 Number 18 p. 10511–10524

REFERENCES

• Kikwit, Dowell S.F., Mukunu R, Ksiazek T.G , Khan S, Rollin P.E., and C. J. Peters Transmission of Ebola Hemorrhagic Fever: A Study of Risk Factors in Family Members, The Journal of Infectious Diseases 1999;179(Suppl1):S87–91

• Peters C.J. and LeDuc J.W. An Introduction to Ebola: The Virus and the Disease. The Journal of Infectious Diseases 1999;179(Suppl 1):ix–xvi