1. Training structure EFFO Safety and good quality work
Module 1: Ebola Virus Disease
Module 2:
Epidemic control on different levels
Module 3:
Standard precautions & disinfection
Module 4:
Screening & isolation
Module 5:
Personal protective equipment
Module 6:
Waste management & cleaning
Support from the community
Support from the hospital administration
Support from the population
The structure of the training shows the logo of the project with the content. Module 1 to Module 6 are part of the training. The parameters in the base of the structure are essential for the success of the training, but these cannot be monitored by the project. The “roof” of the structure is the objective of the training.

2. Ebola virus disease Module 1 (Part 2)

3. Learning objectives module 1 (part 2)
General objectives
To know general information on Ebola virus disease
to be motivated to practice to gain more confidence and skills when dealing with suspected Ebola patients.
Specific objectives
To know the principle of diagnosis
To know the basics of pathophysiology
To recognise the bases on the treatment of Ebola virus disease
To know the special challenges when working in an isolation unit 3

4. Presentation outline Module 1
Part 1
- already dealt with-
Epidemiology
Information about the Ebola virus
Modes of transmission and incubation period
Symptomatology
Differential diagnosis
Part 2
- now -
Laboratory diagnosis: PCR, rapid tests
Pathophysiology
Care of cases
Work in the isolation area and the stress caused

5. In the hospitals, a suspected case must be detected:
by the symptoms
by the case definition

6. Diagnosis
The definitive laboratory diagnosis is carried out in a specialized laboratory
Source: RKI
blood oral urine
swabs
Source: RKI
Avoid accidents when taking samples or during packaging and transportation!

7. Ebola virus disease - Laboratory diagnosis (I)
There are different specialised laboratories, e.g.
the BSL-4 lab or
the stationary lab with a glovebox
© RKI Martin Richter b) a)
Source a), b): RKI 7

8. Ebola virus disease-Laboratory diagnosis (II)
c) the mobile lab with a small glovebox c) c)
Additional information
The European Mobile Lab was used for laboratory diagnosis of Ebola virus disease for example in Guinea, Liberia and Sierra Leone.
Literature
In an outbreak the diagnosis is mostly made in a mobile lab.
Source c): RKI c)

9. Ebola virus disease-Laboratory diagnosis (III)
In the specialized laboratory, RNA of the Ebola virus is detected in a thermocycler by real-time RT-PCR.
The laboratory takes about 3-4 hours to screen for Ebola virus.
Long transport distances can sometimes markedly delay the diagnosis!
© RKI Martin Richter
Additional information
Detection of Ebola virus nucleic acid (RNA) by real-time RT-PCR (real-time reverse transcriptase polymerase chain reaction)
Repeated testing with a new blood sample is needed for patients with symptoms for fewer than 3 days duration, if the first test was negative.
A negative RT-PCR test that is collected > 72 hours after the onset of symptoms rules out Ebola virus disease.
Literature:
e.g.:
Bray M et al. Clinical manifestations and diagnosis of Ebola virus disease. (2016) Ebola-virus-disease
PCR – Thermocycler
Source: RKI 9

10. Laboratory diagnosis using rapid tests
WHO has assessed different rapid diagnostic tests based on the detection of Ebola virus proteins.
Rapid tests are not as reliable as PCR, they can be false negative or false positive.
Recommendation by WHO: Where possible, results from rapid test should be confirmed by testing a new blood sample using an approved nucleic acid test. a)
Additional information
- Rapid tests = immunochromatographic tests, e.g.:
ReEBOV Antigen Rapid Test
SD Q Line Rapid Test Kit
OraQuick Ebola Test
DPP Ebola Antigen Assay
If the rapid test is positive  Immediate isolation of the patient!
There have to be developed rapid tests, based on emerging technologies, such as a sandwich assay based on monoclonal antibodies, biospecific monoclonal antibodies and/or IgY to detect antigen levels seen in patient body fluid samples for screening applications in hospital settings.
Literature
e.g.:
WHO Emergency Use Assessment and Listing procedure (EUAL) for Ebola Virus Disease IVDs
Broadhurst MJ et al. ReEBOV antigen rapid test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study. Lancet 2015; 386:
Singh B et al. Current and Future Diagnostic Tests for Ebola Virus Disease. J Pharm Pharm Sci 2016; 19:
© RKI Martin Richter b)
Source a), b): RKI 10

11. Pathophysiology (I)
Infection through damaged skin, mucous membranes or parenterally
The Ebola virus enters the immune cells (monocytes, macrophages, dendritic cells)
The infected cells migrate to regional lymph nodes, liver, spleen  dissemination of infection
The immune response is individual.
The symptoms and complications can differ.
Literature
e.g.:
Clinical review: Beeching NJ et al. Ebola virus disease. BMJ 2014; 349:g7348 doi: /bmj.g7348, 1-15. 11

12. Pathophysiology (II) Complications:
Intestinal damage leading to diarrhoea and dehydration
Secondary infections (lymphocytopenia)
Haemorrhages
Encephalopathy
Renal failure
Hepatic failure
Pancreatitis (severe abdominal pain)
Shock / DIC
Literature
e.g.:
Clinical review: Beeching NJ et al. Ebola virus disease. BMJ 2014; 349:g7348 doi: /bmj.g7348, 1-15. 12

13. Pathophysiology (III)
Ebola virus disease is associated with a high prevalence of
haematological and biochemical abnormalities!
(even in mild disease and in the absence of gastrointestinal symptoms)
These include:
Acute kidney injury
Abnormal serum potassium
Severe hepatitis
Raised C-reactive protein
Raised haematocrit
Thrombocytopenia
Granulocytosis
Literature
e.g.:
Hunt L et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. Lancet Infect Dis 2015; 15:
Severe acute kidney injury, high viral load, and severe
hepatitis were independently associated with mortality! 13

14. Care of Ebola virus disease at MSF - overview
Doctors without borders (MSF) has a lot of experience with Ebola virus disease
Treatment has changed over the years:
until 1995: symptomatic treatment
from 1995: antibiotic treatment, anti-malarial treatment, palliative care
from 2007: invasive treatment, biochemical diagnosis
from 2014: Experimental therapy (e.g. convalescent plasma, ZMapp, Favipiravir, vaccine rVSV-ZEBOV)
Additional information
The target group during the EFFO-training must be capable of implementing basic treatment (point 1 and 2) to Ebola virus disease patients.
Invasive treatment is an additional risk to the health care worker, it should only be carried out by specialists!
Literature
MSF-Congress on Ebola in Germany ( ) 14

15. Care of suspected cases
Treatment primarily consists of supportive and symptomatic treatment.
At the medical level
At the psychosocial level
Always protect yourself!
By using PPE
In physical and psychosocial terms (note: working in PPE is difficult)
Any invasive procedure represents a risk to the health care worker who performs it!
 Only perform invasive procedures when absolutely necessary!

16. Non-invasive care of Ebola virus disease
Important: fluid replacement!
Fever and/or pain  paracetamol (avoid NSAR because of effect
on platelets)
Diarrhoea, vomiting  food on demand
Hypoglycaemia  sugary drinks
Treatment of other problems/secondary infections  broad spectrum antibiotics, anti-malarial treatment
Additional information
It seems that fluid replacement may significantly reduce mortality.
Literature
e.g.:
Editorial. Guidelines for treatment of patients with Ebola virus diseases are urgently needed. Int J Infect Dis 2015; 30:e85-e86.

17. Invasive procedures in Ebola virus disease
Diarrhoea, vomiting, signs of dehydration  intravenous rehydration
Signs of hypoglycaemia: glucose solution intravenously (if it is not possible to give the patient sugary drinks)
Seizures: Diazepam intravenously or intrarectally
… (Transfusion of whole blood or platelets, dialysis, experimental therapies…)

18. Experimental therapies of Ebola virus disease (I)
Examples of drugs
Non-specific
Immunostimulants
Anti-haemorrhagic (FX06)
Anti-coagulant (rNAPc2)
Specific
Convalescent whole blood or plasma
Monoclonal antibodies (ZMapp)
Antiviral substances (Favipiravir)
Several studies with potential drugs were carried out during the West African Ebola epidemic.
But some studies were stopped without an evidence of benefit for the patients.
Additional information
Studies were stopped or suspended for: Whole blood, Brincidofovir, TKM-Ebola (antiviral drug based on RNA (siRNA)
Literature
DOI: /science.aae0164
Hayden FG et al. Experimental Therapies for Ebola Virus Disease: What Have We Learned? The Journal of infectious diseases 2017; 215: 18

19. Experimental therapies of Ebola virus disease (II)
Testing continues:
Favipiravir
Inhibits viral RNA-polymerase
Given orally it was well tolerated
Putative signal of efficacy in patients
with moderate and high viral load
Additional studies are required
ZMapp
Contains 3 monoclonal antibodies, tar-
geted at 3 Ebola virus glycoprotein epitopes
May prove promising
Further studies are needed
Source: Feldmann, N Engl J Med 2014
Literature
e.g.:
DOI: /science.aae0164
Sissoko D et al. Experimental treatment with favipiravir for Ebola virus disease (the JIKI trial): A historically controlled, single-arm proof-of-concept trial in Guinea. PLOS Medicine 2016, DOI: /journal.pmed
Hayden FG et al. Experimental Therapies for Ebola Virus Disease: What Have We Learned? The Journal of infectious diseases 2017; 215: 19

20. Prophylaxis of Ebola virus disease ?
Several candidate vaccines are under evaluation, most advanced
in clinical trials are:
 rVSV-ZEBOV
 promising!
In clinical trials it proved to
be safe and highly efficacious
(100% protection)
Approval by the American
administration FDA is
expected in 2017
 ChAd3-EBO-Z
Safe and well tolerated
Phase 1/2a completed
Proceed with phase 3 efficacy
trials in Africa
 Ad5-EBOV
Safe and highly immunogenic
Phase 2 completed
Additional information
Vaccine rVSV-ZEBOVVaccine rVSV-ZEBOV: attenuated, recombinant vesicular stomatitis virus (VSV)-based vaccine expressing an Ebola virus glycoprotein
rVSV-ZEBOV: Phase I study completed in 4 locations in Africa, Europe: save vaccine, which induces a long-lasting antibody response
The vaccine was already used in phase 3 studies in Guinea and Sierra Leone called „ring vaccination trial“, in which a „ring“ of people (contacts and contact of contacts) around a newly discovered Ebola patient is vaccinated: highly efficacious and safe
rVSV-ZEBOV: Final results of the „ring vaccination“ (ring vaccination trial) in Guinea: 100% efficacy, low adverse effects, no safety risks in adults and chidren
Approval by the Food and Drug Administration (FDA) is expected in 2017
Vaccine ChAd3-EBO-Z
Chimpanzee derived adenovirus vector (ChAd3-EBO-Z) with Ebola virus genes inserted
Safe and immunogenic, requires boost vaccination, Phase 1/2 abgeschlossen, phase 3 is ungoing
Vaccine Ad5-EBOV
Ebola vaccine based on human adenovirus 5 vector (Ad5-EBOV) proved to be highly immunogenic and safe in phase 1 trial in China, requires boost vaccination for longer protection
Ebola vaccine based on human adenovirus 5 vector (Ad5-EBOV) proved to be also highly immunogenic and safe in a phase 2 trial in Sierra Leone.
Literature
e.g.:
Agnandji ST et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med 2016; 374:
Henao-Restrepo AM et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet 2015; 386:
Henao-Restrepo AM et al. On a path to accelerate access to Ebola vaccines: The WHO‘s research and development efforts during the Ebola epidemic in West Africa. Current Opinion in Virology 2016; 17:
De Santis O et al. Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study. Lancet Infect Dis 2016; 16:
Good overview: Review: Martins KA et al. Ebola virus disease candidate vaccines under evaluation in clinical trials. Expert Review of Vaccines 2016; 15:
Li JX et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. The Lancet Global health 2017, 5: e324-e334.
Zhu FC et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2017, 389:
Henao-Restrepo AM et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ca Suffit!). Lancet 2017; 389: 20

21. The patient’s diet
Assess patients‘ nutritional status (dehydration, appetite) according to the guideline of WHO/UNICEF/WFP („decision tree“).
Meals are served in appropriate and individualized dishes.
Plates are washed and decontaminated.
Ensure a sufficient supply of vitamins.
Families can also deliver food to their relatives but the food needs to be handed over to the patient by a health care worker in PPE.
Additional information
Respect individual food intolerance (lactose, gluten)!
Literature
Interim guideline: Nutritional care of children and adults wth Ebola virus disease: with ebolavirus/en/ 21

22. Important in treating Ebola virus disease patients
Best-practice-protocols for the treatment can change!
Medication
Diet
Experimental treatments (studies are still ongoing)
Vaccines (studies are still ongoing)
Discuss the case with colleagues and the responsible authorities
to create an individual treatment plan!
Supportive and symptomatic treatment
are the base for the care of Ebola virus disease patients! 22

23. Stress caused by Ebola Physical fatigue
Physical isolation (not allowed to touch others)
Constant awareness and vigilance
Risk to become contaminated or to contaminate others
Fear of dying
Tension between protection of public health and the needs of the patient
Stigmatization
Consequences in communities and families
 Challenges for health care workers and patients
 Good communication with the patient, explain every procedure and
gesture

24. Approach of a suspected case
A patient with typical symptoms of Ebola virus disease and with a risk of infection (contact) comes to your health facility…
The patient doesn´t scare me!
Triage  suspected case identified
Patient is isolated immediately (distance of > 2 meters!)
The suspected case is communicated to the responsible persons
Contacts are documented (epidemiology)
The isolation unit is enabled
The team in PPE can take care of the patient

25. Working in the isolation unit
Always in pairs (1 “clean” and 1 “dirty” person)
Know/discuss what to do before putting on PPE (communication is more
difficult and you should not stay in the PPE for more than 1 hour))
Prepare medicines, food, waste bag, and further materials
If you forget something, you can’t turn around easily (one way flow in the
isolation unit!)
Don’t forget documentation (attention, the document stays in the red zone)
In the green zone doffing instructors need to be ready for advising decontamination and doffing of PPE

26. Thank you for your attention!
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