Upload
buidan
View
223
Download
2
Embed Size (px)
Citation preview
(Re)Vivre après Ebola : Evaluation et accompagnement des
patients déclarés guéris d'une infection par le virus Ebola en Guinée
Eric Delaporte for the PostEbogui Study Group
Coordination Nationale de lutte contre Ebola
Background
• Guinea declared Ebola-free on May 31, 2016
• 3811 cases, 2536 deaths
• 1270 survivors (33%) – Children < 15: 16%
– Female: 55%
– Health workers: 8%
66,7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0
20
40
60
80
100
120
140
160
180
200
52
-13
02
-14
04
-14
06
-14
08
-14
10
-14
12
-14
14
-14
16
-14
18
-14
20
-14
22
-14
24
-14
26
-14
28
-14
30
-14
32
-14
34
-14
36
-14
38
-14
40
-14
42
-14
44
-14
46
-14
48
-14
50
-14
52
-14
02
-15
04
-15
06
-15
08
-15
10
-15
12
-15
14
-15
16
-15
18
-15
20
-15
22
-15
24
-15
26
-15
28
-15
30
-15
32
-15
34
-15
36
-15
38
-15
40
-15
42
-15
44
-15
46
-15
48
-15
50
-15
Décès probables
Décès confirmés
Guéris
Létalité cumulée
Lé
ta
lité
cu
mu
lée
(%)In
cid
en
ce
dé
cla
ré
e
Semaine de début des signes
Source: René Migliani
Postebogui Project
- Public Health support
- Care of survivors
- Capacity building
- Training
- Research projects
- Postebogui cohort
- Contactebogui
- Reservoir
Rationale
Few data on survivors from previous outbreaks, limited cases
New questions : clinical sequels, reactivation, reservoir
• Long-term medical problems
• Psychosocial consequences
• Viral clearance in the body compartments
Which package of care to respond to the survivors’ needs?
Rationale
Few data on survivors from previous outbreaks, limited cases
New questions : clinical sequels, reactivation, reservoir
• Long-term medical problems
• Psychosocial consequences
• Viral clearance in the body compartments
Which package of care to respond to the survivors’ needs?
Objectives
Clinical, immunological, genetic and virological component
• Clinical symptoms and sequels after discharge
• Viral clearance in the different body compartments
• Immunological and genetic studies (on-going)
Psychological component
• Psychological consequences of Ebola disease (individual and family)
Social and anthropological component
• Analysis of social effects
• Subjective experience of illness and cure, impact on health workers
Design
• Ethical clearance: 16 February 2015
• Eligibility: > 12 mths old, survivor’s certificate, residency in Guinea, consent
• Recruitment sites:
– Conakry, Macenta, N’Zérékoré, Forécariah
• First inclusion: 23 March 2015,
• Expected final size: up to 800
• Follow-up schedule: D0, M1, M3, M6,…,M24
Survivors’ map, WHO. Recruitment site
Investigations
• General clinical examination and reference to specialists (ophthalmology, psychiatry, rheumatology)
• Psychological assessment using age-dependent depression scales
• Standard biological assessment
• RT-PCR in body compartments (blood, saliva, tears, maternal breast milk, urines, feces, cervicovaginal secretions, semen)
Free medical package, reimbursement of transportation:
Social emergency fund (French Embassy)
Inclusion and follow-up
0 200 400 600 800Number of visits
M12 n=201
M9 n=297
M6 n=451
M3 n=686
M1 n=752
M0 n=802
Note : 5 participants died during the follow-up
From 23 March 2016 to 2 September 2016
Number of follow-up visits - POSTEBOGUI Cohort
0
200
400
600
800
Num
ber
of in
clu
sio
ns
01apr2015 01jul2015 01oct2015 01jan2016 01apr2016 01jul2016Date
Participants were recruited from 23 March 2015 to 11 July 2016
Cumulative number of inclusions - POSTEBOGUI Cohort
Characteristics at inclusion n=802
Age : median 28.4 years [range: 1.0-79,9]
Male : 45%
Children : 20%
Median delay after discharge : 350 days (IQR: 223-491).
Median follow-up : 176 days (IQR : 92-357)
18 10 13
232
106
48
116
6
52
33 22
192
1
73
5
18
4 14
135
51 51
135
2
60
42
21
190
2
72
5
0
50
100
150
200
250
N = 802
ANSS PostEboGui
Representativeness of the Postebogui cohort
68% of the 1270 declared free post ETC
71% of the 1128 survivors identified by the National Coordination (ANNSS)
Characteristics of Postebogui patients during the acute EBOV disease phase
All patients Adults Children P-value
Inclusion in a clinical trial:
0.8
No 685 (85) 545 (85) 140 (89)
Favipiravir trial 58 (7) 49 (8) 9 (6)
Plasmapheresis 44 (5) 37 (6) 7 (4)
Favipiravir and plasmapheresis
1 (0) 1 (0) 0 (0)
Plasmapheresis (other schemes)
14 (2) 12 (2) 2 (1)
Symptoms:
General symptoms 592 (74) 483 (75) 109 (69) 0.1
Haemorrhage 138 (17) 118 (18) 20 (13) 0.09
Abdominal symptoms 553 (69) 453 (70) 100 (63) 0.09
Myalgia 314 (39) 268 (42) 46 (29) 0.004
Dyspnoea 78 (10) 68 (11) 10 (6) 0.1
Ocular disorders 61 (8) 57 (9) 4 (3) 0.007
Hearing disorders 29 (4) 28 (4) 1 (1) 0.03
Neurological disorders 503 (63) 418 (65) 85 (54) 0.01
Behaviour troubles 6 (1) 6 (1) 0 (0) 0.2
Reported symptoms at inclusion
All patients Adults Children P-value
All symptoms ‡ 606 (76) 505 (78) 101 (64) 0.02
General symptoms 324 (40) 250 (39) 74 (47) <0.0001
Abdominal symptoms
198 (25) 163 (25) 35 (22) 0.4
Ocular symptoms/signs
142 (18) 124 (19) 18 (11) 0.2
Musculoskeletal symptoms
303 (38) 274 (43) 29 (18) <0.0001
Neurosensory disorders
289 (37) 231 (36) 67 (42) 0.1
Hearing disorders (deafness)
19 (2) 16 (2) 3 (2) 0.8
Association between clinical events at inclusion
General
symptoms
Neurological
disorders
Ocular symptom
s Deafness
Abdominal
symptoms
Musculo. symptom
s
General symptoms
1
Neurological disorders
<0.00001 1
Ocular symptoms
0.9 <0.00001 1
Deafness 0.3 0.06 0.05 1
Abdominal symptoms
<0.00001 <0.00001 0.8 0.2 1
Musculoskeletal symptoms
<0.00001 <0.00001 0.01 0.7 <0.0000
1 1
Acute Phase Post EVD
Phase P-value
General
symptoms 592 (74) 324 (40) 0.004
Fever 563 (70) 209 (26) 0.03
Fatigue 497 (62) 190 (24) <0.0001
Anorexia 314 (39) 89 (11) 0.5
Abdominal
symptoms 553 (69) 198 (25) 0.9
Abdominal
pain 360 (45) 178 (22) 0.02
Myalgia 314 (39) 111 (14) <0.0001
Ocular troubles 61 (8) 142 (18) <0.0001
Hearing
troubles 29 (4) 19 (2) <0.0001
Neurological
signs 503 (63) 298 (37) 0.1
Headache 502 (63) 278 (35) 0.07
Comparison of clinical events between acute and post-EVD phase
Clinical events according to participation in clinical trials
Inclusion in a clinical trial ?
No Plasmapheresis Total
p
Myalgia 91/699 (12%) 19/44 (43%) 110
<10-3
Occular symptoms /
signs 127/699 (17%) 15/44 (34%)
142
0.007
Focus on ophthalmology
• 341 patients examined: slit lamp, dilated fundoscopy
• uveitis: 46 (13,5%) 48% ant, 76% unilat
• episcleritis : 6 (1,8%) • interstitial keratitis: 3 (0,9%)
• 2 blindness due to cataract among two children surgery
Overall abnormal examination due to eye inflammation = 16.1%
Source: Esther Hereth
Focus on musculoskeletal symptoms
• 44 patients with arthalgia/myalgia examined by a rheumatologist
• No symmetric synovitis observed • Strong correlation with depression
Signs, Symptoms, and Diagnoses
n (%)
Mechanical pain 20 (45%) Inflammatory pain 4 (9%) Mechanical and inflammatory pain
20 (45%)
Morning stiffness 33 (75%) Myalgia 27 (61%) Muscle weakness 18 (42%) Joint pain 43 (98%)
Biological parameters at inclusion
Item All patients Adults Children
Hb (g/dL) 12.1 (10.9-
13.8) 12.5 (11.0-
14.0) 11.4 (10.3-
12.5) Anemia (< 11)
186 (23) 132 (21) 54 (34)
Creat. (µmol/L)
> 100 60 (10) 60 (13) 0 (0)
> 150 2 (0) 2 (0) 0 (0)
ASAT > 40 UI/L
52 (12) 33 (10) 19 (22)
CRP (mg/L)
> 10 43 (8) 35 (8) 8 (8)
> 40 9 (2) 7 (2) 2 (2)
Probability for EVD survivors’ semen to test positive with RT-PCR according to time from symptom onset
Psychological disorders
20 40 87 504 0%
5%
10%
15%
20%
25%
30%
3-6 years (PSYCa ) 7-12 years (CES-DC) 13-20 years (ADRS) Adultes>20 years (CES-D)
Age
Score above threshold
Sociological survey
• 81% with other EBV in their household – median number n=4
– median number of death n=1 (max 12!)
– median number of death in depressed survivors n=2
• Patients evaluated their own health status as bad/very bad:28%
• Stigmatization was felt in 204 (26%) patients
Limitations of our study
• No control group
-caution to formaly relate some symptoms to post-EBV
• Non inclusion of all the survivors
- but 74% of the identified survivors from various regions
• Robustess of the data
- difficulty to colllect data in a (post-)emergency context
• Recent reports on survivors and Postebogui contibute to the characterisation of the Postebola syndrome
– Frequent and persistent clinical symptoms long after discharge
– differences between adults and children
– rare serious complications (deaffness 2%, blindness , renal failure)
– Frequent ocular complications , which treatment??
– Frequent psychological disorders
– Long-term RNA positivity in semen (up to 18 months) w/ marked decreasing trend
• Provide care to survivors is necessary on the long term – Organize systematic follow-up visit : ophthalmology, psychological evaluation, etc
• Maintain surveillance
• Support Guinea to response to new epidemics
Discussion
Capacity building: Molecular biology laboratory in the Guinean Public Health Institute, INSP Conakry
This work is supported and funded by the « Research unit » of the
French Ebola Task Force
Sponsor: INSERM
Coordination nationale de lutte
contre la maladie à virus Ebola
French Ebola Task Force: Jean-François Delfraissy, Yazdan Yazdanpanah, Yves Lévy
Institut de Recherche pour le Développement UMI 233-INSERM U1175, Montpellier Eric Delaporte, Abdoulaye Touré, Jean-François Etard, Philippe Msellati, Sandrine Leroy, Esther Hereth, Yves-Marie Pers, Bernard Taverne, Alice Desclaux, Martine Peeters, Alpha Keita, Ahidjo Ayouba, Suzanne Izard, Bruno Granouillac, Laura March Pasteur Institute/Unit of Biology of Emerging Viral Infections, Lyon Sylvain Baize INSERM/P4, Lyon Hervé Raoul ALIMA Vincent Mendiboure, Augustin Augier INSERM U955/VRI, Paris Yves Lévy, Christine Lacabaratz
INSERM/Lab génétique humaine des maladies infectieuses, Paris Laurent Abel
INSERM/Clinical Research Dep Claire Lévy-Marchal, Cécile Etienne, Christelle Delmas
Acknowledgments
CHU Donka, Conakry Moumié Barry, Mamadou Saliou Sow, Djenaba Kassé, Saliou Bella Diallo N’Fally Magassouba, Mohamed Cissé INSP lab, Conakry Lamine Koivogui Prefectoral Hospital of Macenta Ibrahima Savané Ebola National coordination response Sakoba Keita Survivors and survivors’ associations APEGUAEG, APGEM