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Ebola (3)DR. GIULIANO RIZZARDINI AND DR. MARIA V IT TORIA COSSU
ASST FATEBENEFRATELL I L .SACCO HOSPITAL
GIULIANO.RIZZARDINI@ASST -FBF -SACCO. IT & MARIA .COSSU@ASST -FBF-SAC CO. IT
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INTRODUCTION
VIRUS
RESERVOIRS
TRANSMISSION
PREVIOUS OUTBREAKS
EBOLA 2013-2016 IN WEST AFRICA
SIGNS AND SYMPTOMS
DIAGNOSIS
TREATMENT
ITALIAN EXPERIENCE
PREVENTION
TtT: BACK UP SLIDES
Outline
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Pathogenesis of Ebolavirus
Destroys cells – focal necrosis in many organs
Suppresses inflammation
Causes cytokine storm
Induces clotting
Multi-organ focal necrosis and disseminated intravascular coagulation with focal haemorrhage and minimal inflammation
Liver with Ebolavirus (red)Martines et al J Pathol 2014
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EBOV Effects on Immune SystemHigh mortality rate believed to be the result of EBOV proteins capability of defeating the immune system
◦ Elimination of Innate IS with VP24 and VP35 proteins
◦ Prevention of enhancement of Adaptive response
◦ Infected macrophages induces apoptosis in lymphocytes
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Ebola virus: unravelling pathogenesis to combat a deadly disease.
Hoenen et al. Trends in Molecular Medicine. May 2006, 12(5).
EBOV Effect on Tissue
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Figure 3
The Lancet Infectious Diseases 2004 4, 487-498DOI: (10.1016/S1473-3099(04)01103-X)
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Ebola PathogenesisEnters Bloodstream
◦ skin, membranes, open wounds
Cell Level
◦ docks with cell membrane
Viral RNA
◦ released into cytoplasm
◦ production new viral proteins
New viral genomes
◦ rapidly coated in protein
◦ create cores
• 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
ebolaAttach to
walls
Leakage of blood and serum into surroundin
g tissue
Wbcs’ attack
Wbcs’ dissolv
e
Chemical released
Pro-inflammatory
cytokinesPro
coagulantsAlso released
Blood vessels more
damaged
Permanent bleeding
Entire body
leaks and dissolves
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Signs and symptomsPRODROME:
sudden onset of fever, intense weakness, muscle pain, headache and sore throat.
VIRAEMIA:
vomiting, diarrhoea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding (DIC)
Patients are infectious as long as their blood and secretions contain the virus.
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Fauci AS.N Engl J Med 2014
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Organ System Clinical Manifestation
General Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)
Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%)
Cardiovascular Chest pain (37%),
Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%)
Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%), jaundice (10%)
Hematological Any unexplained bleeding (18%), melena/hematochezia (6%), hematemesis (4%), vaginal bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hematuria (1%), petechiae/ecchymoses (1%)
Integumentary Conjunctivitis (21%), rash (6%)
WHO Ebola Response team. NEJM. 2014
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Characteristics, Symptoms, Vital Signs,
and Time Course of Clinical Progression of
37 Patients with Confirmed Ebola Virus
Disease (EVD).
Bah EI et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1411249
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Therapies Received by 37 Patients Hospitalized for EVD.
In a multivariable analysis, older had a death RR of 3.49 (1.4-8.6), as compared with younger (p = 0.007). No differences between survivors and nonsurvivors in the number of days between symptom onset and admission and viral load on admission (0.98; 0.91- 1.07; P = 0.72).
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Bleeding
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WHO Ebola responsegroup. N Engl J Med2014;371:1481-95
Bleeding
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Schieffelin JS et al, N Engl J Med 2014
Mortality associated factors
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Virus in blood
CDC. 2014 http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html
>100 million viruses per ml
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The Ebola virus disease (EVD) epidemic of 2013–16 resulted in 28616 cases and left more than 17000 survivors.
Much of what was encountered about EVD was new, mainly complexity of post-EVD sequelae:
mild or asymptomatic disease, persistent viraemia, sexual transmission, and recrudescence.
Ebola virus disease sequelae: a challenge that is not going away
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76% of patients presented with post-EVD symptoms a median of 1 year after discharge.
The most frequent symptoms were those classed as general (fatigue, fever, and anorexia; 40%), musculoskeletal pain (38%), headache (35%), depression (17%), abdominal pain (22%), and
ocular disorders (18%).
Positive Ebola virus RT-PCR was found in 5% of adult men at a maximum of 548 days after disease onset.
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The patient A may have been exposed to
Ebola through sex intercourse with
survivor A, with PCR positive semen 199
days (September 9, 2014 to March 27,
2015) after his likely Ebola onset.
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Look to the future
• The duration of virus persistence is surprising nonetheless, and determination of its significance warrants further investigation
• Protocols for monitoring PCR in semen for 6 months as minimum follow-up
• Long lasting sequels and infectivness
• Research on how positive PCR relates to infectivity
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INTRODUCTION
VIRUS
RESERVOIRS
TRANSMISSION
PREVIOUS OUTBREAKS
EBOLA 2013-2016 IN WEST AFRICA
SIGNS AND SYMPTOMS
DIAGNOSIS
TREATMENT
ITALIAN EXPERIENCE
PREVENTION
TtT: BACK UP SLIDES
Outline
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DIFFERENTIAL DiagnosisAlways rule out
Other Viral Haemorrhagic Fevers.MalariaYellow feverDengue LeptospirosisTyphoid FeverShigellosisRickettsiosisRelapsing FeverCholeraPlagueHepatitis
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Diagnosis of Ebola
Timeline of Infection Diagnostic tests available
Within a few days after symptoms begin
•Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing•IgM ELISA•Polymerase chain reaction (PCR)•Virus isolation
Later in disease course or after recovery •IgM and IgG antibodies
Retrospectively in deceased patients•Immunohistochemistry testing•PCR•Virus isolation
• Diagnosing Ebola can be difficult at first since early symptoms, such as fever, are nonspecific to Ebola infection.
• However, if a person has the early symptoms and has had contact with Ebola they should be isolated and public health professionals notified.
• Samples from the patient can then be collected and tested to confirm infection.
Source: Centers for Disease Control and Prevention http://www.cdc.gov/vhf/ebola/diagnosis/index.html Accessed Oct. 14, 2014
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DiagnosisDefinitive diagnosis by
Antibody-capture ELISA
Antigen detection tests
Serum neutralization test- serological surveys
RT-PCR assay
Virus isolation by cell culture.
Skin biopsies in postmortem diagnosis of infection with Ebola virus
Blood samples collection and transport according to guidelines and to WHO accredited labs only
Highly sensitive and confirmatory tests
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Expected diagnostic test results over time
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Interpreting Negative Ebola RT-PCR Result
If symptoms started ≥3 days before the negative result
EVD is unlikely consider other diagnoses
Infection control precautions for EVD can be discontinued unless clinical suspicion for EVD persists
If symptoms started <3 days before the negative RT-PCR result
Interpret result with caution
Repeat the test at ≥72 hours after onset of symptoms
Keep in isolation as a suspected case until a repeat RT-PCR ≥72 hours after onset of symptoms is negative
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Laboratory findings
Thrombocytopenia, leukopenia with a pronounced lymphopenia.
Neutrophilia develops after several days
Elevations in aspartate aminotransferase and alanine aminotransferase.
Bilirubin may be normal or slightly elevated.
With onset of anuria, BUN and serum creatinine rise.
Terminally ill patients : metabolic acidosis
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Lab findings and outcome
Schieffelin JS et al, N Engl J Med 2014
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WHO situation rep 25 March 2015
Providing capacity for prompt and accurate diagnosis of cases of EVD is an integral part of the response to the EVD outbreak • 27 laboratories have the
capacity to confirm EVD
cases
• 9 operational laboratories
in Guinea
• 5 operational laboratories
in Liberia
• 13 operational
laboratories in Sierra
Leone
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Laboratories
CDC has developed interim guidance for U.S. laboratory workers and other healthcare personnel who collect or handle specimens
This guidance includes information about the appropriate steps for collecting, transporting, and testing specimens from patients who are suspected to be infected with Ebola
Specimens should NOT be shipped to CDC without consultation with CDC and local/state health departmentsInformation available at: http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-specimen-collection-submission-patients-suspected-infection-ebola.html
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Packaging & Shipping Clinical Specimens to CDC for Ebola Testing
http://www.cdc.gov/vhf/ebola/hcp/packaging-diagram.html
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Thank you for your attention
DR. GIULIANO RIZZARDINI AND DR. MARIA V IT TORIA COSSU
ASST FATEBENEFRATELL I L .SACCO HOSPITAL
GIULIANO.RIZZARDINI@ASST -FBF -SACCO. IT & MARIA .COSSU@ASST -FBF-SAC CO. IT