EBOLA in Lessons learnt Dr Marta Lado Infectious Diseases coordinator Kings Sierra Leone partnership, KSLP. Kings Global Health partners. Kings College London CONNAUGHT HOSPITAL Freetown, Sierra Leona

UNIVERSITY OF SIERRA LEONE TEACHING HOSPITALS COMPLEX

King´s Sierra Leone Partnership (KSLP) CONNAUGHT COLLEGE OF MEDICINE & MINISTRY OF HEALTH GOVERNMENT HOSPITAL ALLIED HEALTH SCIENCES AND SANITATION

SIERRA LEONE GOVERNMENT Connaught is the main COMAHS is Sierra Leone’s only KSLP works closely with MOHS to government referral and teaching medical and pharmacy school and ensure that all activities are MINISTRY OF HEALTH AND SANITATION hospital, providing general adult main institution for basic and aligned with government priorities and paediatric surgical care. specialist nursing. and plans, and support work on policy.

EBOLA NATIONAL TASKFORCE at MoHS CASE MANAGEMENT PILLAR

CREATION GUIDELINES AND SOP NATIONAL MEETINGS

EBOLA PREPAREDNESS ASSESMENT EBOLA OUTBREAK AWARENESS MANUALS EBOLA March 2014 TRAINING EVD for Health Care Workers COMMAND CENTER WESTERN AREA

BED CAPACITY AMBULANCE SERVICE BURIAL TEAM CONNAUGHT HOSPITAL ISOLATION UNIT SCREENING CONNAUGHT HOSPITAL

SAFE MEDICAL BURIALS

LABORATORY DIAGNOSIS IN EBOLA

1. RT-PCR: rapid, more sensitive than antigen detection ELISA, and provides specific identification of genetic fragments of the

2. ELISA: allows the detection of the viral antigen or on inactivated specimens, such as blood, serum, or tissue suspensions

3. Virus isolation: requires a Biosafety Level- 4 laboratory and can take several days

4. Immuno-histochemical staining and histopathology: On collected tissue or dead animals; localizes viral antigen MANAGEMENT OF LABORATORY SAMPLES

LAB CLOSE BY

Decontamination at the collection point

SPRAY 0.5% Chlorine

1. Labeled 4. (several samples) sample

LABORATORY IN SITE 2. 50 ml- sample 3. ziplock 4. (several samples) Map: Google Maps

RAPID TEST EBOLA Defence Science and Technology Laboratory (DSTL)

24 RDT positives: 15 EVD PCR positive 9 EVD PCR negative

Ebola treatment facility, Ebola treatment facility, Goderich, Sierra Leone— Royal Free Hospital, London, February 2015 UK—September 2014

- 27 patients with EVD treated Emory University Hospital special isolation unit. Outside West Africa (Aug 2014- May 2015) – 5 deaths 11 US 3 SPAIN 3 UK 3 GERMANY 2 FRANCE 1 NORWAY 2 ITALY 1 SWITZERLAND 1 NETHERLANDS

14/27 got infected in Sierra Leone

NEW THERAPIES

• : Guinea *Sierra Leona: prophylaxis POST EXPOSURE (KSLP)- 14 dias.

INITIAL: 6,000 mg (2,400 mg 0h y 8h) LATER 1,200 mg (16h). MANTEINANCE: 1,200mg/12h

• : Liberia (MSF) • AMIODARONE 79 patients Sierra Leona – CRF: 42% vs 52% • ZMAPP Monoclonal: Western Area y Lunsar. • FX06: 2 expatriated • Zmab: 4 expatriated • EVD SURVIVOR CONVALENCENT PLASMA Brincidofovir – Chimerix TKM-Ebola – Tekmira

CMX001 a broad-spectrum antiviral for the TKM-Ebola, an experimental prevention and treatment of clinically for EVD, is a combination of small interfering significant caused by DNA . RNAs targeting three of the seven proteins in Brincidofovir is an oral nucleotide analogue Ebola virus: Zaire Ebola L polymerase, Zaire that has shown in vitro antiviral activity Ebola membrane-associated protein (VP24), against all five families of DNA viruses that and Zaire Ebola polymerase complex protein affect humans, including (VP35). The drug was effective in rhesus (CMV), adenovirus (AdV), BK virus and monkeys infected with Ebola. herpes simplex viruses. Favipiravir – Toyama ZMapp™ – Mapp Bio

T-705 selected as a clinical candidate based ZMapp™ is composed of three “humanized” on its remarkable therapeutic efficacy monoclonal manufactured in demonstrated in mice infected with plants, specifically Nicotiana. Antibody genes virus. T-705 possesses potent and are infiltrated into tobacco plants to broad spectrum antiviral activity against transiently manufacture the ZMapp™ multiple strains of influenza virus in antibodies. It is an optimized cocktail vitro and in vivo. Directly inhibits RNA combining the best components of MB‐003 dependent RNA polymerase. (Mapp) and ZMAb (Defyrus/PHAC). Refs: www.chimerix.com/discovery-clinical-trials/brincidofovir/ mappbio.com/zmapp-faq/ www.toyama-chemical.co.jp/en/rd/area/infection.html en.wikipedia.org/wiki/TKM-Ebola Haque A, Hober D, Blondiax J. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks. Antimicrob. Agents Chemother 2015:59(10):5892-5902 Trial Design M Patients Enrolment Endpoint Outcome C reached Brincindofovir Single-arm 1 4 01/01/15- No – trial All 4 died phase 2 trial 31/01/15 terminated

Favipiravir - JIKI Single-arm 4 126 (540 historic 17/12/14- No – reported Nuanced conclusions – phase 1 trial controls) 08/04/15 differently limited tolerability

Favipiravir – Jui Single-arm 1 39 (85 historic 01/11/14- N/A Survival rate (56% [22/39] phase 2 trial controls) 10/11/14 vs 35% [30/85]; p= 0.027).

TKM-Ebola Single-arm 1 14 (3 cohort, 11/03/15- No No survival benefit phase 2 trial observational) 15/06/15

ZMapp RCT (non- 11 36 (35 controls), 01/03/15- No – stopped Mortality rate (37% [13/35] blinded) Guineans had FVP, 01/11/15 early, low EVD vs 22% unclear if matched numbers [8/36]; 91.2% posterior probability). Plasma Non-random 1 99 (507 controls) 17/02/15- No – ? if any Mortality rate (31% {26/84] comparative 03/08/15 neutralizing vs 38% [158/418]); p=0.92 study antibody after age/CT adjustment

Refs: Dunning J et al. Experimental Treatment of EVD with Brincidofovir. PLoS One 2016;11(9):e0162199. Sissoko D et al. Experimental Treatment with Favipiravir for EVD (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of- Concept Trial in Guinea. PLoS Med 2016:13(3):e1001967. Bai C et al. Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)—Sierra Leone, 2014. Clin Infect Dis 2016;pii:ciw571. Dunning J et al. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single Arm Phase 2 . PLoS Med 2016; 13(4):e1001997. van Griensven J et al. Evaluation of Convalescent Plasma for EVD in Guinea. NEJM 2016; 374:33-42. OTHER THERAPIES

AVI-7537 Amiodarone BCX4430 Chloroquine JK-05 FGI-106 Imipramine U18666A Statins Clomiphene Artemisinin Toremiphene FTY720

Refs: www.chimerix.com/discovery-clinical-trials/brincidofovir/ mappbio.com/zmapp-faq/ www.toyama-chemical.co.jp/en/rd/area/infection.html en.wikipedia.org/wiki/TKM-Ebola Haque A, Hober D, Blondiax J. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks. Antimicrob. Agents Chemother 2015:59(10):5892-5902 VACCINE VSV EVD Lancet 2015;386:857-866.

Vaccinated Immediate 21 days Infected (48 - 4123) (42 -3528)

Non Vaccinated

0 16 infections infections

vaccine efficacy of 100% (95% CI 74·7–100·0; p=0·0036) cluster vaccine efficacy of 75% (95% CI -7.1–95.1; p=0·1791)

Lancet December 22, 2016 http://dx.doi.org/10.1016/ S0140-6736(16)32621-6

Dr. Salia Dr. Rogers Dr. Kahn

Sister Hajara Abdulai Dr. Cole