Ebola Virus OutbreakEbola Virus OutbreakEbola Virus Disease EVDEbola Virus Disease EVD

Dr. Khaled Mahmoud Abd ElazizDr. Khaled Mahmoud Abd Elaziz Associate Prof. of public health and preventive Associate Prof. of public health and preventive

medicine Faculty of Medicine- Ain Shams medicine Faculty of Medicine- Ain ShamsUniversityUniversity

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Ebola virusEbola virusPrototype Viral Hemorrhagic Fever Pathogen

Filovirus: enveloped, non-segmented, negative-stranded RNA virus Severe disease with high case fatalityAbsence of specific treatment or vaccine>20 previous Ebola and Marburg virus outbreaks2014 West Africa Ebola outbreak caused by Zaire ebolavirus species (five known Ebola virus species) Ebola virus (Zaire),Sudan virus, Taii forest virus, Bundibogyi virus, Reston (non human)

Where does Ebola hideWhere does Ebola hide??

2002- Fruit Bats2002- Fruit Bats Antibodies against EbolaAntibodies against Ebola Ebola Gene sequences in Ebola Gene sequences in

liver and spleenliver and spleen Fruit bats do not show any Fruit bats do not show any

symptomssymptoms Best candidate to be the Best candidate to be the

reservoirreservoir More research needs to be More research needs to be

donedone

Link between outbreak and animalsLink between outbreak and animals

The link between human infection by the Ebola virus and The link between human infection by the Ebola virus and their proximity to primates is clear.their proximity to primates is clear.

-Outbreaks occurred in countries that house 80 percent of -Outbreaks occurred in countries that house 80 percent of the world’s remaining wild gorilla and chimpanzee the world’s remaining wild gorilla and chimpanzee populations.populations.

- The outbreaks coincided with the outbreaks in wild - The outbreaks coincided with the outbreaks in wild animals. animals.

- The same distinct viral strains were isolated in animal - The same distinct viral strains were isolated in animal carcasses and in the bodies of those who handled those carcasses and in the bodies of those who handled those carcasses. carcasses.

- These outbreaks were preceded by an abnormally large - These outbreaks were preceded by an abnormally large death in wild Gorilla populations.death in wild Gorilla populations.

Ebola SubtypesEbola Subtypes Ebola-Zaire Ebola-Zaire

(ZEBOV)(ZEBOV) Ebola-Sudan (SEBOV)Ebola-Sudan (SEBOV) Ebola Ivory-Coast Ebola Ivory-Coast

(ICEBOV)(ICEBOV) Ebola-Reston Ebola-Reston

(REBOV)(REBOV)

Previous outbreaksPrevious outbreaks

Ebola Hemorrhagic Fever was first found in 1976 Ebola Hemorrhagic Fever was first found in 1976 It struck two countries within that yearIt struck two countries within that year a. Sudan – in a town called N’zaraa. Sudan – in a town called N’zara b. Zaire, now known as the Democratic Republic of b. Zaire, now known as the Democratic Republic of

CongoCongo In these two instances the mortality rate was In these two instances the mortality rate was

between between 50 –90%50 –90% Following those epidemics, Ebola hit Africa in many Following those epidemics, Ebola hit Africa in many

other instances the worst yet being in the year 2000 other instances the worst yet being in the year 2000 when it struck Uganda infecting more than 400 when it struck Uganda infecting more than 400 people. people.

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Ebola virusEbola virusZoonotic virus – bats the most likely reservoir, although species unknownSpillover event from infected wild animals (e.g., fruit bats, monkey, duiker) to humans, followed by human-human transmissionSpillover infection: Occurs when a reservoir population causes an epidemic in a novel host population. The epidemic is transmitted by the reservoir population and not the host population.

EVD Cases and Deaths*EVD Cases and Deaths*

Reporting Reporting DateDate Total CasesTotal Cases Confirmed Confirmed

CasesCases Total DeathsTotal Deaths

GuineaGuinea 3 Nov 143 Nov 14 1,7601,760 1,4791,479 1,0541,054

LiberiaLiberia 4 Nov 144 Nov 14 6,6196,619 2,5142,514 2,7662,766

Sierra LeoneSierra Leone 4 Nov 144 Nov 14 4,8624,862 4,1494,149 1,1301,130

Nigeria**Nigeria** 15 Oct 1415 Oct 14 2020 1919 88

SpainSpain 27 Oct 1427 Oct 14 11 11 00

Senegal**Senegal** 15 Oct 1415 Oct 14 11 11 00

United StatesUnited States 24 Oct 1424 Oct 14 44 44 11

MaliMali 23 Oct 1423 Oct 14 11 11 11

TOTALTOTAL 13,26813,268 8,1688,168 4,9604,960

Updated case counts available at Updated case counts available at http://http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.htmlwww.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html. . *Reported by WHO using data from Ministries of Health *Reported by WHO using data from Ministries of Health **The outbreaks of EVD in Senegal and Nigeria were declared over on October 17 and 19, respectively. **The outbreaks of EVD in Senegal and Nigeria were declared over on October 17 and 19, respectively.

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Ebola Virus TransmissionEbola Virus Transmission Virus present in high quantity in blood, body Virus present in high quantity in blood, body

fluids, and excreta of fluids, and excreta of symptomaticsymptomatic EVD-infected EVD-infected patientspatients

Opportunities for human-to-human transmissionOpportunities for human-to-human transmission Direct contact (through broken skin orDirect contact (through broken skin or unprotected mucous membranes) with an unprotected mucous membranes) with an

EVD-infected patient’s blood or body fluidsEVD-infected patient’s blood or body fluids Sharps injury (with EVD-contaminated needle Sharps injury (with EVD-contaminated needle

or other sharp)or other sharp) Direct contact with the corpse of a person who Direct contact with the corpse of a person who

died of EVDdied of EVD Indirect contact with an EVD-infected patient’s Indirect contact with an EVD-infected patient’s

blood or body fluids via a contaminated object blood or body fluids via a contaminated object (soiled linens or used utensils)(soiled linens or used utensils)

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Ebola Virus TransmissionEbola Virus Transmission Ebola can also be transmitted via contact with Ebola can also be transmitted via contact with

blood, fluids, or meat of an infected animalblood, fluids, or meat of an infected animal Limited evidence that dogs become infected Limited evidence that dogs become infected

with Ebola virus with Ebola virus No reports of dogs or cats becoming sick with No reports of dogs or cats becoming sick with

or transmitting Ebolaor transmitting Ebola

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Detection of Ebola Virus in Different Detection of Ebola Virus in Different Human Body Fluids over TimeHuman Body Fluids over Time

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Human-to-Human TransmissionHuman-to-Human Transmission

Infected persons are not contagious until onset of Infected persons are not contagious until onset of symptomssymptoms

Infectiousness of body fluids (e.g., viral load) increases as Infectiousness of body fluids (e.g., viral load) increases as patient becomes more illpatient becomes more ill

Remains from deceased infected persons are highly infectious Remains from deceased infected persons are highly infectious

Human-to-human transmission of Ebola virus via inhalation Human-to-human transmission of Ebola virus via inhalation (aerosols) has not been demonstrated(aerosols) has not been demonstrated

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EVD Risk AssessmentEVD Risk Assessment

**CDC Website to check current affected areas: **CDC Website to check current affected areas: www.cdc.gov/vhf/ebolawww.cdc.gov/vhf/ebola

Ebola Virus PathogenesisEbola Virus Pathogenesis Direct infection of tissuesDirect infection of tissues

Immune dysregulationImmune dysregulation

Hypovolemia and vascular collapseHypovolemia and vascular collapse

Electrolyte abnormalitiesElectrolyte abnormalities

Multi-organ failure, septic shockMulti-organ failure, septic shock

Disseminated intravascular coagulation (DIC) and Disseminated intravascular coagulation (DIC) and coagulopathycoagulopathy

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Early Clinical PresentationEarly Clinical Presentation Acute onset; typically 8–10 days after exposure Acute onset; typically 8–10 days after exposure

(range 2–21 days)(range 2–21 days)

Signs and symptomsSigns and symptoms

Initial: Fever, chills, myalgias, malaise, anorexiaInitial: Fever, chills, myalgias, malaise, anorexia After 5 days: GI symptoms, such as nausea, vomiting, watery After 5 days: GI symptoms, such as nausea, vomiting, watery

diarrhea, abdominal paindiarrhea, abdominal pain Other: Headache, conjunctivitis, hiccups, rash, chest pain, Other: Headache, conjunctivitis, hiccups, rash, chest pain,

shortness of breath, confusion, seizuresshortness of breath, confusion, seizures Hemorrhagic symptoms in 18% of casesHemorrhagic symptoms in 18% of cases

Other possible infectious causes of symptomsOther possible infectious causes of symptoms

Malaria, typhoid fever, meningococcemia, Lassa fever and other Malaria, typhoid fever, meningococcemia, Lassa fever and other bacterial infections (e.g., pneumonia) – all very common in Africabacterial infections (e.g., pneumonia) – all very common in Africa

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Clinical FeaturesClinical Features

Nonspecific early symptoms progress to:Nonspecific early symptoms progress to:

Hypovolemic shock and multi-organ failureHypovolemic shock and multi-organ failure

Hemorrhagic diseaseHemorrhagic disease

DeathDeath

Non-fatal cases typically improve 6–11 days after Non-fatal cases typically improve 6–11 days after symptoms onsetsymptoms onset

Fatal disease associated with more severe early Fatal disease associated with more severe early symptomssymptoms

Fatality rates of 70% have been reported in rural AfricaFatality rates of 70% have been reported in rural Africa

Intensive care, especially early intravenous and electrolyte Intensive care, especially early intravenous and electrolyte management, may increase the survival ratemanagement, may increase the survival rate

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Clinical Manifestations by Organ SystemClinical Manifestations by Organ Systemin West African Ebola Outbreakin West African Ebola Outbreak

Organ SystemOrgan System Clinical ManifestationClinical Manifestation

GeneralGeneral Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)

NeurologicalNeurological Headache (53%), confusion (13%), eye pain (8%), coma (6%)Headache (53%), confusion (13%), eye pain (8%), coma (6%)

CardiovascularCardiovascular Chest pain (37%), Chest pain (37%),

PulmonaryPulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%) Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%)

GastrointestinalGastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%), jaundice (10%) (44%), dysphagia (33%), jaundice (10%)

HematologicalHematological Any unexplained bleeding (18%), melena/hematochezia (6%), Any unexplained bleeding (18%), melena/hematochezia (6%), hematemesis (4%), vaginal bleeding (3%), gingival bleeding hematemesis (4%), vaginal bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hematuria (1%), petechiae/ecchymoses (1%)(2%), hematuria (1%), petechiae/ecchymoses (1%)

IntegumentaryIntegumentary Conjunctivitis (21%), rash (6%)Conjunctivitis (21%), rash (6%)

WHO Ebola Response team. WHO Ebola Response team. NEJMNEJM. 2014. 2014

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Examples of Hemorrhagic SignsExamples of Hemorrhagic Signs

Bleeding at IV Site

Hematemesis

Gingival bleeding

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Laboratory FindingsLaboratory Findings

Thrombocytopenia (50,000–100,000/mL range)Thrombocytopenia (50,000–100,000/mL range)

Leukopenia followed by neutrophiliaLeukopenia followed by neutrophilia

Transaminase elevation: elevation serum aspartate amino-Transaminase elevation: elevation serum aspartate amino-transferase (AST) > alanine transferase (ALT)transferase (AST) > alanine transferase (ALT)

Electrolyte abnormalities from fluid shiftsElectrolyte abnormalities from fluid shifts

Coagulation: PT and PTT prolongedCoagulation: PT and PTT prolonged

Renal: proteinuria, increased creatinineRenal: proteinuria, increased creatinine

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Ebola Virus DiagnosisEbola Virus Diagnosis

Real Time PCR (RT-PCR) Real Time PCR (RT-PCR) Used to diagnose acute infection Used to diagnose acute infection

More sensitive than antigen detection ELISAMore sensitive than antigen detection ELISA Identification of specific viral genetic fragmentsIdentification of specific viral genetic fragments Performed in select CLIA-certified laboratoriesPerformed in select CLIA-certified laboratories

RT-PCR sample collectionRT-PCR sample collection

Volume: minimum volume of 4mL whole bloodVolume: minimum volume of 4mL whole blood

Plastic collection tubes (not glass or heparinized tubes)Plastic collection tubes (not glass or heparinized tubes)

Whole blood preserved with EDTA is preferred Whole blood preserved with EDTA is preferred Whole blood preserved with sodium polyanethol sulfonate (SPS), Whole blood preserved with sodium polyanethol sulfonate (SPS),

citrate, or with clot activator is acceptablecitrate, or with clot activator is acceptable

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Categories to classify Ebola CasesCategories to classify Ebola Cases

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Classification

Criteria

Suspected

Any person, alive or dead, who has (or had) sudden onset of high fever and had contact with a suspected, probable or confirmed EVD case, or a dead or sick animal OR any person with sudden onset of high fever and at least three of the following symptoms: headache, vomiting, anorexia/ loss of appetite, diarrhoea, lethargy, stomach pain, aching muscles or joints, difficulty swallowing, breathing difficulties, or hiccup; or any person with unexplained bleeding OR any sudden, unexplained death.

Probable

Any suspected case evaluated by a clinician OR any person who died from ‘suspected’ EVD and had an epidemiological link to a confirmed case but was not tested and did not have laboratory confirmation of the disease.

ConfirmedA probable or suspected case is classified as confirmed when a sample from that person tests positive for EVD in the laboratory.

 

Breakdown of the EVD cases in epidemic Breakdown of the EVD cases in epidemic countriescountries

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CountryCase 

definitionCumulative cases Cumulative deaths

Guinea

Confirmed 1745 998

Probable 216 216

Suspected 86 0

Total 2047 1214

Liberia

Confirmed 2669 *

Probable 1750 *

Suspected 2663 *

Total 7082 2963

Sierra Leone

Confirmed 5152 1058

Probable 79 174

Suspected 959 35

Total 6190 1267

Total   15 319 5444

Clinical Management of EVD: Clinical Management of EVD: Supportive, but AggressiveSupportive, but Aggressive

Hypovolemia and sepsis physiologyHypovolemia and sepsis physiology Aggressive intravenous fluid resuscitation Aggressive intravenous fluid resuscitation Hemodynamic support and critical care management if Hemodynamic support and critical care management if

necessarynecessary

Electrolyte and acid-base abnormalities Electrolyte and acid-base abnormalities Aggressive electrolyte repletionAggressive electrolyte repletion Correction of acid-base derangementsCorrection of acid-base derangements

Symptomatic management of fever and gastrointestinal Symptomatic management of fever and gastrointestinal symptomssymptoms Avoid NSAIDSAvoid NSAIDS

Multisystem organ failure can develop and may require Multisystem organ failure can develop and may require Oxygenation and mechanical ventilationOxygenation and mechanical ventilation Correction of severe coagulopathyCorrection of severe coagulopathy Renal replacement therapyRenal replacement therapy

Reference: Fowler RA et al. Reference: Fowler RA et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2014 . 2014

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Investigational Therapies for EVD PatientsInvestigational Therapies for EVD Patients No approved Ebola-specific prophylaxis or treatmentNo approved Ebola-specific prophylaxis or treatment

Ribavirin has no in-vitro or in-vivo effect on Ebola virusRibavirin has no in-vitro or in-vivo effect on Ebola virus

Therapeutics in development with limited human clinical trial Therapeutics in development with limited human clinical trial data data Convalescent serumConvalescent serum

Therapeutic medicationsTherapeutic medicationso Zmapp – chimeric human-mouse monoclonal antibodies Zmapp – chimeric human-mouse monoclonal antibodies o Tekmira – lipid nanoparticle small interfering RNATekmira – lipid nanoparticle small interfering RNAo Brincidofovir – oral nucleotide analogue with antiviral activityBrincidofovir – oral nucleotide analogue with antiviral activity

Vaccines – in clinical trialsVaccines – in clinical trials Chimpanzee-derived adenovirus with an Ebola virus gene insertedChimpanzee-derived adenovirus with an Ebola virus gene inserted

Attenuated vesicular stomatitis virus with an Ebola virus gene Attenuated vesicular stomatitis virus with an Ebola virus gene insertedinserted

ReferencesReferences: : 11Huggins, JW et al. Huggins, JW et al. Rev Infect Dis Rev Infect Dis 1989; 1989; 22Ignatyev, G et al. Ignatyev, G et al. J BiotechnolJ Biotechnol 2000; 2000; 33Jarhling, P et al. Jarhling, P et al. JIJID 2007 D 2007 S400; S400; 44Mupapa, K et al. Mupapa, K et al. JIDJID 1999 S18; 1999 S18; 55Olinger, GG et al. Olinger, GG et al. PNASPNAS 2012; 2012; 66Dye, JM et al. Dye, JM et al. PNAPNAS 2012; S 2012; 77Qiu, X et al. Qiu, X et al. Sci Transl Sci Transl Med Med 2013; 2013; 88Qiu, X et al. Qiu, X et al. NatureNature 2014; 2014; 99Geisbert, TW et al. Geisbert, TW et al. JIDJID 2007; 10Geisbert, TW et al. 2007; 10Geisbert, TW et al. LancetLancet 2010; 2010; 1111Kobinger, GP et Kobinger, GP et al. al. VirologyVirology 2006; 2006; 1212Wang, D Wang, D JVJV 2006; 2006; 1313Geisbert, TW et al. Geisbert, TW et al. JIDJID 2011; and 2011; and 1414Gunther et al. Gunther et al. JIDJID 2011. 2011.

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Patient RecoveryPatient Recovery Case-fatality rate 71% in the 2014 Ebola outbreak Case-fatality rate 71% in the 2014 Ebola outbreak

Case-fatality rate is likely much lower with access to intensive Case-fatality rate is likely much lower with access to intensive carecare

Patients who survive often have signs of clinical Patients who survive often have signs of clinical improvement by the second week of illness improvement by the second week of illness Associated with the development of virus-specific antibodiesAssociated with the development of virus-specific antibodies Antibody with neutralizing activity against Ebola persists greater Antibody with neutralizing activity against Ebola persists greater

than 12 years after infectionthan 12 years after infection

Prolonged convalescenceProlonged convalescence Includes arthralgia, myalgia, abdominal pain, extreme fatigue, Includes arthralgia, myalgia, abdominal pain, extreme fatigue,

and anorexia; many symptoms resolve by 21 monthsand anorexia; many symptoms resolve by 21 months Significant arthralgia and myalgia may persist for >21 months Significant arthralgia and myalgia may persist for >21 months Skin sloughing and hair loss has also been reportedSkin sloughing and hair loss has also been reported

ReferencesReferences: : 11WHO Ebola Response Team. WHO Ebola Response Team. NEJMNEJM 2014; 2014; 22Feldman H & Geisbert TW. Feldman H & Geisbert TW. LancetLancet 2011; 2011; 33Ksiazek TG et al. Ksiazek TG et al. JIDJID 1999; 1999; 44Sanchez A et al. Sanchez A et al. J Virol J Virol 2004; 2004; 55Sobarzo A et al. Sobarzo A et al. NEJMNEJM 2013; and 2013; and 66Rowe AK et al. Rowe AK et al. JIDJID 1999. 1999.

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Controlling the spread of EbolaControlling the spread of Ebola a. a. Hospitals must follow precautionary methods, such as: Hospitals must follow precautionary methods, such as: 1. wearing gloves1. wearing gloves 2. isolating infected individuals2. isolating infected individuals 3. practicing nurse barrier techniques3. practicing nurse barrier techniques 4. proper sterilization and disposal of all equipment4. proper sterilization and disposal of all equipment b. Burials must be done correctlyb. Burials must be done correctly 1. no washing or touching carcass1. no washing or touching carcass 2. put into body bags and bury outside city2. put into body bags and bury outside city c. Report any questionable illness to officialsc. Report any questionable illness to officials

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