Ebola virus

Ebola virus Presenter- Dr Gautam Chakma Moderator- Prof Lallan Prasad

Introduction Ebola virus causes Ebola virus disease (EVD)/Ebola hemorrhagic fever(EHF) an acute, severe, often fatal illness, with a death rate of up to 90%Illness affects humans and nonhuman primates (monkeys,gorillas,chimpanzees)Ebola viruses found in several African countriesEbola first appeared in 1976 in 2 simultaneous outbreaks, in nzara, sudan and in yambuku near the ebola river, democratic republic of Congo

Since then, outbreaks have appeared sporadically in Africa The recent ebola outbreak in west Africa 2014 is the largest,Cases and deaths surpassed all previous combinedOn August 8,2014 the WHO Director-General declared this outbreak a Public Health Emergency of International Concern

Ebola virus disease(EVD) Acute febrile illness characterized by multisystem involvementBegins with abrupt onset headache, myalgias and feverProceeds to prostration, rash,shock and often to bleeding manifestationsEpidemics usually begin with a single case acquired from an unknown reservoir in natureSpread mainly through close contact with sick persons or their body fluids

Virology Ebola bolongs to virus family Filoviridae ( 3 genera- Cuevavirus, Marburgvirus, Ebolavirus)Genus ebolavirus comprises 5 distinct species- 1)Bundibugyo ebolavirus (BDBV),2)Zaire ebolavirus (EBOV) ,3)Sudan ebolavirus (SUDV),4)Reston ebolavirus (RESTV),5)Ta forest ebolavirus (TAFV)2014 west African outbreak due to Zaire speciesReston ebolavirus has caused disease in nonhuman primates but not in humans

The viruses destroyed by heat 60C, 30 min and by acidityIt may persist for weeks in blood at room temperature Ebola virus are biosafety level 4 pathogens because of high associated mortality rate and aerosol infectivity

Molecular structureFilamentous, enveloped RNA virus ,Approx. 19 kb in length or 60-80 nm in diameterSingle-stranded, linear, non-segmented ,Negative-sense RNA (encoded in a 3 to 5 direction)Appears to have spikes due to glycoprotein on Outside membrane

Ebola outbreaks2014 west africa outbreak till Feb 2015, WHO and respective governments have reported a total of 23,406 suspected cases and 9,467 deathsWHO believes that this substantially understates the magnitude of the outbreak

YearCountryEbolavirus speciesCasesDeathsCase fatality2012Democratic Republic of CongoBundibugyo572951%2012UgandaSudan7457%2012UgandaSudan241771%2011UgandaSudan11100%2008Democratic Republic of CongoZaire321444%2007UgandaBundibugyo1493725%2007Democratic Republic of CongoZaire26418771%2005CongoZaire121083%2004SudanSudan17741%2003 (Nov-Dec)CongoZaire352983%2003 (Jan-Apr)CongoZaire14312890%2001-2002CongoZaire594475%

yearcountryspeciescasesdeathMortality rate2001-2002GabonZaire655382%2000UgandaSudan42522453%1996South Africa (ex-Gabon)Zaire11100%1996 (Jul-Dec)GabonZaire604575%1996 (Jan-Apr)GabonZaire312168%1995Democratic Republic of CongoZaire31525481%1994Cote d'IvoireTa Forest100%1994GabonZaire523160%1979SudanSudan342265%1977Democratic Republic of CongoZaire11100%1976SudanSudan28415153%1976Democratic Republic of CongoZaire31828088%

Reservior Natural hosts: In Africa, fruit bats (Pteropodidae family) three species tested positive for Ebola, but had no symptoms of the virus, are considered possible natural hosts for ebola.Hammer-headed bats (Hypsignathus monstrosus),Franquet's epauletted fruit bats (Epomops franqueti) andlittle collared fruitbats ( Myonycteris torquata )Animals monkeys, apes, or pigs may become infected when they eat fruit partially eaten by bats carrying the virus

Transmission From animals Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animalsAnimals such as chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.Undercooked meat. bushmeat

Animal to human transmission

There is no evidence that mosquitos or other insects can transmit Ebola virusHuman-to-human transmission: Direct contact through broken skin or mucous membranes (eyes, nose,mouth) with the blood, secretions, organs or other bodily fluids (including but not limited to feces, saliva, sweat, urine, vomit, breast milk, and semen) of infected people.

Contact with objects contaminated (bedding, clothing, needles, syringes etc.) with such fluids Burial ceremonies in which mourners have direct contact with the body of the deceased person. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.

Health-care workers: This has occurred when infection control precautions are not strictly practiced while treating patients with suspected or confirmed EVD

PathogenesisAcute infection associated with high levels of circulating virus and viral antigenEbola replicate well in virtually all cell typesViral replication is associated with cellular necrosisVirus interacts with the cellular cytokine system releases high proinflammatory cytokines contribute to severity of illness

The glycoprotein spike mediate attachment to cells and fusion. The glycoprotein's high sugar content may contribute to ineffective neutralizing antibodies. A smaller circulating glycoprotein may suppress the immune response to the virion surface protein or block antiviral effector mechanisms. Glycoprotein expression inhibits V integrin expression, an effect that leads to detachment and subsequent death of endothelial cells

PathogenesisGPSecreted GPFull length transmembrane GPBinds to endothelial cells, monocytes, macrophagesMultiplicationDimeric proteinInhibition of Neutrophils activationRelease of cytokinesInflammatory dysregulation, Immune suppression, Loss of vascular integrity.

Virions are abundant in fibroblasts, interstitium lesser extent the appendages of the subcutaneous tissues. Viruse escape through small breaks in the skin or possibly through sweat glands may occurRecovery is apparently mediated by the cellular immune response Convalescent-phase plasma has little in vitro virus-neutralizing capacity and is not protective

Clinical featuresIncubation period: 2-21 days. A person infected with Ebola virus is not contagious until symptoms appear. Early Stage (non-specific) : Fever,generalised body weakness headaches,arthralgia,myalgia,back pain,mucosal redness of the oral cavity,dysphagia,conjunctivitis,rash all over body except in faceIf the patients dont recover gradually at this point, there is a high probability that the disease will progress to the second phase, resulting in complications which eventually lead to death (Mupapa et al., 1999).

Advanced Stage (specific) : Vominting, diarrhoea, impaired renal function, anuria, impaired liver function, tachypnea, internal and external bleeding, neuropsychiatric manifestationsPatients who progressed to phase two almost always die. (Ndambi et al., 1999)

Additional findings include edema of the face, neck, and/or scrotum; hepatomegaly; flushing; conjunctival injection; and pharyngitisLate hepatitis, uveitis, and orchitis have been reported, with isolation of virus from semen or detection of PCR products in vaginal secretions for several weeks

Around 1012 days after the onset of disease, the sustained fever may break, with improvement and eventual recovery of the patient.Recrudescence of fever may be associated with secondary bacterial infections or possibly with localized virus persistence. Some people who have recovered from Ebola have developed long-term complications, such as joint and muscle pain and vision problems

Lab findingsInitially Leukopenia later neutrophilia.Platelet counts fall below 50,000/L. Laboratory evidence of DIC Elevated liver enzymes. The serum amylase elevation may be associated with abdominal pain, suggesting pancreatitis. Proteinuria is usual; Decreased kidney function is proportional to shock.

Diagnosis Clinical diagnosis: Difficult because early symptoms are nonspecific to virus. Laboratory tests used in diagnosis include:- 1.Within a few days after symptoms begin: Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, Polymerase chain reaction (PCR),Virus isolation 2.Later in disease course or after recovery: IgM and IgG antibodies 3.Retrospectively in deceased patients: Immuno- histochemistry testing, PCR, Virus isolation

Differential diagnosis More common febrile diseases Malaria, Typhoid fever, Shigellosis, Cholera, leptospirosis, Plague, Rickettsiosis Relapsing fever, Meningitis, Hepatitis and other viral haemorrhagic fever

Treatment No specific antiviral therapy (e.g., antiviral drug) or vaccine is available for EbolaSymptoms of Ebola and complications are treated as they appear The following basic interventions, when used early, can significantly improve the chances of survival- 1) Providing intravenous fluids and balancing electrolytes (body salts), 2) Maintaining oxygen status and blood pressure, 3) Treating other infections if they occur

Extensive viral involvement in fatal casessupportive treatment may not be as useful as was once hoped. Vigorous treatment of shock should take into account the likelihood of vascular leak in the pulmonary and systemic circulation and of myocardial functional compromise Experimental: drugfavipiravir(Avigan)& vaccinescAd3-EBOZandVSV-ZEBOV

Prevention and control Reducing the risk of wildlife-to-human transmission: Avoid Contact with infected fruit bats or monkeys/apesAnimals should be handled with gloves and other appropriate protective clothingAvoid consumption of their raw meat Animal products (blood and meat) should be thoroughly cooked before consumption

Reducing the risk of human-to-human transmission:Avoid Direct/close contact with infected patients & their bodily fluids Not handle items (e.g. clothes, bedding, needles, and medical equipment) that may have come in contact with an infected persons blood or body fluidsAvoid funeral or burial rituals that require handling the body of someone who has died from EbolaGloves and appropriate personal protective equipment should be worn when taking care of ill patients at home.Regular hand washing with soap and water or an alcohol-based hand sanitizer is required after visiting patients in hospital, as well as after taking care of patients at home.

Controlling infection in health-care settingApply standard precautions consistently with all patients regardless of their diagnosis in all work practices at all timesBasic hand hygiene, respiratory hygiene, the use of personal protective equipment (according to the risk of splashes or other contact with infected materials), safe injection practices and safe burial practicesSamples taken from humans and animals for investigation of Ebola infection should be handled by trained staff and processed in suitably equipped laboratories

While caring for patients with suspected or confirmed ebola virus :In addition to standard precautions,Avoid any exposure to the patients blood and body fluids Avoid Direct unprotected contact with the possibly contaminated environment When in close contact (within 1 metre) Of patients with EBV:Wear face protection (a face shield or a medical mask and goggles) A clean, non-sterile long-sleeved gownGloves (sterile gloves for some procedures)

Good outbreak control relies on applying a package of interventions,Case management Surveillance and contact tracing, a good laboratory serviceSafe burials and social mobilisation

Community engagement is key to successfully controlling outbreaks

Educating the communities affected: Raising awareness of risk factors for Ebola infection and protective measures that individuals can take is an effective way to reduce human transmission About the nature of the disease About outbreak containment measures Prompt and safe burial of the dead

Outbreak containment measuresincluding- Prompt and safe burial of the deadIdentifying people who may have been in contact with someone infected with Ebola Monitoring the health of contacts for 21 daysThe importance of separating the healthy from the sick to prevent further spread The importance of good hygiene and maintaining a clean environment

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