Ebola virus disease (EVD)

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Ebola Virus Disease By Harshit Jadav NIPER-Gandhinagar Harshit Jadav 1

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Ebola Virus Disease (EVD)

Ebola Virus DiseaseByHarshit JadavNIPER-GandhinagarHarshit Jadav1Ebola Virus Disease (EVD)Ebola virus disease is a severe, fatal, zoonotic filovirus infectionThe current outbreak in west Africa, (first case notified in 1976)Fatality rates are between 80% and 100%This filovirus is classified as a biological class 4 pathogenThe most severely affected countries are Guinea, Sierra Leone and LiberiaHarshit Jadav2Harshit Jadav2

Harshit Jadav3 Ebola virusLipid-enveloped, non-segmented, negatively stranded RNA virus Appears to have spikes due to Glycoprotein membraneBelongs to the viral family FiloviridaeThe natural reservoir of the virus is unknownCDC found that it is a zoonotic virus mostly found in bats

Harshit Jadav4Species of EbolavirusThe virus family Filoviridae includes 3 genera: Cuevavirus, Marburgvirus, and EbolavirusThere are five species of Ebola virusZaire ebolavirusSudan ebolavirusTa Forest ebolavirus Bundibugyo ebolavirus Reston ebolavirus

Harshit Jadav5Order: MononegaviralesFamily: FiloviridaeGenes: Ebola virusSpecies: Zaire ebolavirus

Zaire ebolavirus is responsible for the current outbreak in west Africa

Harshit Jadav6Outbreak (in small population)(eg. Ebola in West Africa, MERS in Soudi Arabia )Epidemic (in specific community or region)(eg. Cholera in India, yellow fever in Africa)Pandemic (in very large population)(eg. SARS , Influenza)Harshit Jadav7Article informationJournal: The New England Journal Of Medicine

Author: WHO Ebola Response team

Volume: 365 (16)

Date of publication: 16th October, 2014

Impact factor: 54.42Harshit Jadav8Epidemiology Since December 2013 and as of 19 October 2014, WHO has reported 9936 cases of Ebola virus disease (EVD) in West Africa including 7877 deaths42% healthcare workers were infected with EVD

Harshit Jadav9Ebola hemorrhagic fever (EHF) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates

Harshit Jadav10Transmission The virus is thought to be initially acquired by exposure to body fluids or tissue from infected animals, such as bats and non-human primatesHuman to human transmission occurs through contact with body fluids from infected patientsMost cases result from close physical contact or contact with body fluids (such as sweat, blood, faeces, vomit, saliva, genital secretions, urine, and breast milk) of infected patients.The incubation period after infection is usually 5-9 days

Harshit Jadav11Pathophysiology Most of the studies were performed in non-human primate and rodent modelsThe virus genome consists of a single 19 kb strand of negative sense RNA with seven viral genes that are transcribed by the viral RNA dependent RNA polymerase present in the virion.single strand of RNA is covered by helically arranged viral nucleoproteins NP and VP30, which are linked by matrix proteins VP24 and VP4 to the lipid bilayer that coats the virionHarshit Jadav12Pathophysiology (contd)Harshit Jadav13Who are at risk?Contacts of infected patients (including healthcare workers and household contacts) - if they were exposed to the patients body fluids without protective equipment within the past 21 days.Persons involved in Burial ceremonies of infected patientsHealth-care workersHousehold persons of infected patients

Harshit Jadav14A contactA contact is defined by WHO as someone who has slept in the same household as a patient;had direct physical contact with the patient during the illness or at the funeral; touched the patients body fluids, clothes, or bed linens during the illness; or been breast fed by the patient

Harshit Jadav15Phase of EVDThere are typically three phases of illnessA few days of non-specific fever, headache, and myalgia (5-7 days)A gastrointestinal phase in which diarrhoea and vomiting, abdominal symptoms, and dehydration are prominent. In the second week, the patient may recover or deteriorate (8-15 days)Collapse, neurological manifestations, and bleeding, shock, coma, death (16-21 days)Harshit Jadav16Typical symptoms Fever 101FFatigueNausea or vomitingDiarrhoeaHeadacheAbdominal painMyalgiaProstrationSore throatUnexplained bleeding or bruisingSpontaneous abortion or miscarriageHiccupsRashAll the symptoms are common so it mislead to flu or malariaHarshit Jadav17Clinical features The most common symptoms reported were

fever (87.1%),fatigue (76.4%), loss of appetite (64.5%), vomiting (67.6%),diarrhoea (65.6%), headache (53.4%), abdominal pain (44.3%),unexplained bleeding (18%)Harshit Jadav18Diagnostic test of EVD Antigen capture enzyme linked immunosorbent assay (ELISA) testingA useful diagnostic test with high specificityCan be used to confirm the diagnosis along with a positive reverse transcriptase-polymerase chain reaction resultFull blood countDecreasing platelet count with low haemoglobin countCoagulation studies Prolonged prothrombin time or activated partial thromboplastinHarshit Jadav19Diagnostic test of EVD Blood culturesNegative blood cultures are helpfulEbola specific IgM and IgG antibodiesIgM antibodies can appear in serum as early as day 2 after infection but results are variable up to day 9. They become negative between 30 and 168 days after symptom onsetIgG response develops between days 6 and 18 and can persist for several yearsHarshit Jadav20Management of EVDThere is no any specific vaccine or treatment for EVD.Patients just get symptomatic treatmentIsolation of patients is necessary to patients as well as other personals

Harshit Jadav21Symptomatic treatmentFever and painFever and pain should be treated with paracetamol first. Opioid analgesics (such as morphine) are preferable for more severe painNausea and vomitingOral or intravenous antiemetics (such as ondansetron and metoclopramide) are recommendedHeartburn, dysphagia, and upper abdominal painproton pump inhibitor (such as omeprazole) may be beneficialHarshit Jadav22Seizures - Although uncommon, seizures can be seen in advanced disease, A benzodiazepine can be used to abort the seizure and can be given intramuscularlyAgitation - haloperidol or a benzodiazepineSepsis and septic shock broad spectrum antibiotics (such as ceftriaxone, piperacillin-tazobactam, or meropenem) in the first hourMalaria should be tested for and treated with appropriate antimalarial therapySymptomatic treatment (contd)Harshit Jadav23Infection control measures for healthcare workers Wear protective clothingPractise proper infection control and sterilisation measuresIsolate suspected patients from each otherAvoid direct contact with bodies of people who have died from Ebola, or suspected Ebola

Harshit Jadav24Emerging treatments Convalescent whole blood or plasma: transfusion of blood from convalescent patients showed beneficial effect in acute phase of infection.

Harshit Jadav25Zmapp:The best known emerging treatment so far, ZMapp, is a combination of three humanised monoclonal antibodies targeted at three Ebola virus glycoprotein epitopes and is engineered for expression in tobacco plantsZMapp had proved protective when given to non-human primates 24-48 hours after infection.It has not yet been tested in humans for safety or efficacyThe whole study is supported by US govt.

Harshit Jadav26TKM-EbolaTKM-Ebola consists of a combination of small interfering RNAs that target Ebola virus RNA polymerase L, formulated with lipid nanoparticle technology.It has been shown to be protective in non-human primates (guinea pigs and monkeys)The US Food and Drug Administration has granted expanded access to this drug under an Investigational New Drug application (INDA)Under emergency protocols, it had given to a small number of patients in Zaire.Harshit Jadav27BrincidofovirFormerly known as CMX-001, brincidofovir is currently undergoing phase III trials for the treatment of cytomegalovirus and adenovirus.It also shows activity against Ebola virus in vitro.The drug has been used in patients with Ebola virus infection in the US under Emergency Investigational New Drug applications approved by the FDA.Harshit Jadav28FavipiravirFormerly known as T-705, favipiravir selectively inhibits viral RNA dependent RNA polymeraseIt is active against influenza viruses, West Nile virus, yellow fever virus, foot and mouth disease virus, as well as other flaviviruses arenaviruses, bunyavirusesIt is effective against Ebola virus in mouse modelsHuman trials are started in west AfricaHarshit Jadav29BCX-4430BCX-4430 is an adenosine analogue that is active against Ebola virus in rodentsIt is thought to act through the inhibition of viral RNA dependent RNA polymerase

Harshit Jadav30AVI-7537AVI-7537 consists of antisense phosphorodiamidate morpholino oligomers (PMOs) that target the Ebola virus VP24 geneIt confers a survival benefit to Ebola virus infected non-human primatesAV-7537 undergone phase I clinical studies.Harshit Jadav31Other agentsSome drugs approved for other indications, which have known safety profiles at clinically used doses, including chloroquine and imatinib, have shown activity against EV in vitro and, in some cases, in rodent models.They are also used in the treatment of EHF in west Africa by some hospitals

Harshit Jadav32Vaccine cAd3-ZEBOV(also known asthe NIAID/GSK Ebola vaccineorcAd3-EBO Z) is an experimentalvaccinefor twoebolaviruses, Ebola virusandSudan virus, developed by scientists atGlaxoSmithKline(GSK) and tested byNational Institute of Allergy and Infectious Disease(NIAID). The vaccine is derived from Chimpanzee adenovirus, chimp adenovirus type 3(chAd3) genetically engineered express glycoprotein from the Zaire Harshit Jadav33Vaccine (contd)rVSV-EBOVis an experimentalvaccinefor theEbolafilovirus, developed by scientists at theCanadianNational Microbiology LaboratoryrVSV-ZEBOV is an attenuated vesicular stomatitis virus with one of its genes replaced by an Ebola virus gene. Human trials have started in the USHarshit Jadav3434Harshit Jadav