ESCMID Online Lecture Library @ by Author

Ebola virus disease clinical features - what did we learn? Connaught Hospital Freetown King´s Sierra Leone partnership ESCMID Online Lecture Library @ by author

Previous outbreaks VHF

• In 1976 South-Sudan and in a bordering region in North Zaire near the river Ebola.

• More outbreaks of Ebola and Marburg: Gabon, Democratic Republic of the Congo, Republic of the Congo-Brazzaville, South-Sudan, Uganda andESCMID Angola Online Lecture Library

@ by author CHRONOLOGY EVD OUTBREAK

ESCMID Online Lecture Library @ by author EBOLA MANUALS March 2014

ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author SENSITIZATION and TRAINING

ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author Page 11 PPE TRAINING

ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author CASE DEFINITION March 2014

SUSPECTED CASE

History of acute Fever and signs of bleeding: • Bleeding of the gums • Nosebleed • Red eyes • Rash • Blood in / black stool • Vomiting blood • Other unexplained bleeding CONNAUGHT GOVERNMENT HOSPITAL AND Accident & Emergency TRIAGE GUIDANCE FOR ISOLATION ROOM All persons with a history of acute fever + 3 or more of:

All persons presenting with a history of fever and signs of bleeding: ! Headache History within the previous 1 month of: ! Bleeding of the gums ! Vomiting or nausea ! Nosebleed ! Appetite • Travel to Guinea ! Red eyes ! Diarrhoea ! Rash ! Intense fatigue

! Blood in / black stool ! Abdominal pain OR ! Vomiting blood ! Muscular / joint pain

! Other unexplained bleeding ! Difficulty swallowing • Contact with a person from or that had been ! Difficulty breathing OR ! Hiccoughs recently in Guinea who are or had been ! Contact with a clinical case of Ebola haemorrhagic fever !

AND! TAKE TO RESUSCITATION ROOM AND INFORM ! A history of fever ! sick with a febrile disease DOCTOR IMMEDIATELY ! TAKE THE PATIENT TO THE ISOLATION ROOM ESCMID Online LectureAND INFORM DOCTOR IM MEDLibraryIATELY @ by author CASE DEFINITION April 2014

History of acute fever WITH signs of bleeding: Sudden onset fever with signs of bleeding • Bleeding of the gums • Nosebleed • Red eyes • Rash • Blood in / black stool • Vomiting blood • Other unexplained bleeding OR Sudden onset fever with 3 or more of: • Headache • vomiting/nausea • anorexia/loss of appetite • diarrhea • weakness/severe fatigue • abdominal pain • generalized muscular or articular pain • difficulty in swallowing • difficulty in breathing • hiccoughs

PLUS History within the previous one month of: DEFINITION OF CONTACT: travel to Guinea or Liberia – OR ESCMID Online LectureContact is any person who comes Library into contact with a case by: – contact with someone from Guinea or Liberia 1. Sleeping in the same household within one month who has been sick with a febrile illness 2. Direct physical contact with the case (dead or alive) 3. Touching his/her linens or body fluid

@ by author

CASE DEFINITION June 2014

ESCMID Online Lecture Library @ by author No specific district affected: ALL COUNTRY A HOT SPOT! August 2014 September 2014

October 2014

ESCMID Online Lecture Library @ by author CASE DEFINITION September 2014

History of contact not ESCMID Online Lecturecompulsory!!! Library @ by author SCREENING at Connaught Hospital

OCTOBER 2014Appendix(4:(Training(Pack( (

ESCMID Online Lecture Library

( ( @ by author ( ( ( (

49 A&E Visits with an Isolation Unit

Freetown Start to 1st Case regular A&E No closure elective Shutdow 400 surgery n or SOP

350

300 Junior Screening doctors Tent Opens strike 250

200

150

Dr Cole tests 100 positive

50ESCMID Online Lecture Library

0 7/7/14 7/14/14@7/21/14 by7/28/14 8/4/14author8/11/14 8/18/14 8/25/14 9/1/14 9/8/14 9/15/14 9/22/14 9/29/14 10/6/1410/13/1410/20/1410/27/14 New Admission to the General Wards (Medical & Surgical) are improving

45 No elective Lock down, surgery or SOP 40 adherence to health care System 35

25 Medical (W10)

20 Surgical (W2)

10 ESCMID5 Online Lecture Library 0 May June July August September October @ by author ADMISIONS HOLDING UNIT CONNAUGHT HOSPITAL May – December 2014 October 2014 November 2014

ESCMID Online Lecture Library @ by author ADMISIONS EBOLA HOLDING UNIT CONNAUGHT HOSPITAL May – December 2014

• 850 patient admitted in 192 days - 464 (64.1%) confirmed diagnosis EVD • 100 (21.6%) cases and 40 (15.4%) non-cases reported a risk factor for EVD: - Travel to hot spot area - HealthESCMID care worker Online Lecture Library - Funeral attendance - Contact @with infected by family author member or friend CONFIRMED CASES Sierra Leone May 2014 – January 2015

ESCMID Online Lecture Library @ by author

Day 0-5 Day 5-10 Pseudomalarial Syndrome Gastrointestinal Syndrome

Mild fever (37.5-38.5ºC) Lower chest/epigastric pain, nausea and vomiting Body and joint pain, (responds well to antiemetics), (ocasionally back pain), hiccups, diarrhea (ocassionally with mucus), progressive weakness, loss of apetite, crumps or diffuse abdominal pain sore throat, headache. (sometimes right upper quadrant abdominal pain:

liver tenderness).

Day 10-14 Hypovolemic Syndrome-Dehydration Oligoanuria, dry mucosas, hypoglycemia, tachypnea, tachycardia, disminished consciousness or >14 day: coma. Resolution of gastrointestinal symptoms and fever, Recovery: Increased appetite. Neurological involvement-Encephalitis Convalescent weakness. Fever, confusion and disorientation, agitation (constant falling on the floor), bradipsichia (unable to OR keep atention), extreme weakness (unable to stand up and walk), Multiorganic failure, tachypnea conjuntivitis. Late complications: (Kussmaul breathing more tan respiratory), seizures, DEATH. Probably electrolitic disfuntion in patients with previous DEATH IN 24-48h* good outcome. after the Neurological abnormalities

Haemorrhagic complications Gums bleeding, melena, Haematemesis, epistaxis,ESCMID bleeding from punture and IVOnline lines sites. Lecture Library

@ by author

Classification Clinical stages, ETU Kerrytown Clinical features Ministry of Defense, UK MSF Filovirus Infection Guidelines

WHO VHF Guidelines Sierra Leone Version

Clinical management of patients in the Ebola Treatment Centres and other care centres in Sierra Leone

December 2014

KSLP Guidelines

ESCMID Online Lecture Library

@ by authorI SYMPTOMS at Connaught Hospital Ebola Holding Unit from May 2014-December 2014 450 400

350 300 250 200 150 Frequency 100 EVD +ve 50 EVD -ve 0 Fever Loss of… Vomiting Anorexia Jaundice Confusion Dyspnoea Headache Dysphagia Chest pain Conjunctivitis

Fever (82.7%) Pain behind eye Intense fatigue (68.4%) Vomiting (50.4%) Diarrhoea (40.6%) AnorexiaESCMID (36.9%) Online Lecture Library Abdominal pain( 32.6%) @ by author

SYMPTOMS High probability of a confirmed EVD diagnosis: at Connaught Hospital - Confusion Ebola Holding Unit - Conjuntivitis - Intense fatigue May 2014- - Hiccups - Diarrhea Dec 2014

A combination of 3 or more symptoms Increased the odds of EVD by 3.19% (95% CI 2.29-4.44)

Sensitivity of this approach of identification of EVD cases was 57.8% (95% CI 52.1-62.4)

28% of non cases presented with 3 or more, Specificity of 70.8% (95% CI 64.7-76.4) ESCMID Online Lecture Library

@ by author August September LOC LOC Pain behind Confusion Pain behind eye Confusion eye Hiccups Hiccups Rash Rash Sore throat Fever Fever

Jaundice Dysphagia Conjunctivitis Jaundice Cough Sore throat Conjunctivitis Dyspnoea Dysphagia Vomiting Headache Vomiting Joint pain Cough Dyspnoea Muscle pain Headache Haematemesis Chest pain Diarrhoea Diarrhoea Haematemesis Joint pain Malaena Abdominal Chest Intense fatigue Malaena pain pain Anorexia Intense fatigue Muscle Abdominal pain Anorexia pain

Conjunctivitis Confusion Conjunctivitis Hiccups Pain behind eye Pain behind eye October Sore throat November Sore Rash Hiccups LOC Confusion throat Dysphagia LOC Jaundice Rash Jaundice Dysphagia Dyspnoea Dyspnoea Fever Cough Fever Cough Headache Headache Joint pain Vomiting Vomiting Haematemesis Muscle pain Haematemesis Joint pain Diarrhoea Malaena Muscle Malaena Chest pain Diarrhoea pain ESCMID Online Lecture LibraryIntense Abdominal pain Intense Chest pain fatigue Anorexia fatigue @ by author Abdominal pain Anorexia Pain behind eye December Hiccups Symptoms getting more common LOC Conjunctivitis Confusion Sore Rash 100 throat Jaundice Dysphagia 90 Fever Dyspnoea 80 Cough Intense fatigue Headache 70 60 Vomiting Vomiting % 50 Diarrhoea Joint pain Haematemesis 40 Anorexia Muscle pain Malaena 30 Abdominal pain Chest pain Diarrhoea 20 Abdominal Muscle pain 10 pain Headache Intense fatigue 0 Anorexia % % % % % % Jul Aug Sep Oct Nov Dec Symptoms getting less common 100 90 80 70 60 % 50 Fever 40 Conjunctivitis 30 Confusion 20 ESCMID Online Lecture10 Library 0 % % % % % % @ by author Jul Aug Sep Oct Nov Dec Survival of EVD patients EHU

Death occurred 177/464 EVD + patients (38.1%)

Incidence of death was significantly higher among EVD +ve than EVD –ve patients (16.4 vs 3.1 per 100 patients/day) incidence rate ratio 5.23 (95% CI 3.56 to 7.93).

Increased risk of death in EVD patients with: Age (40-59 HR 2.53, ≥60 HR 2.32) Loss of consciousness (HR 3.57) Confusion (HR 2.57) Jaundice (HR 13.0)

DurationESCMID of illness not associated Online with death Lecture Library @ by author FEVER is typically the most common symptom, but not universally in all EVD cases

• Schieffelin JS, Shaffer JG, Goba A, et al. Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone. N Engl J Med 2014; 371:2092-100. History of fever in 89% of confirmed EVD cases in Kenema Government Hospital, Sierra Leone, from May 25 to June 19 2014

• Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med 2015;372:40-7. Fever in 84% of EVD admissions from March 25 to AprilESCMID 26 2014 in Online Conakry, Guinea. Lecture Library

@ by author Connaught Hospital, Sierra Leone May to Dec 2014. - Fever was absent in 15% confirmed EVD case - Neither fever nor risk factor in 7.4%

ESCMID Online Lecture Library @ by author New Screening tools???? Defence Science and Technology Laboratory DSTL EVD Rapid Test

24 RDT positives: 15 EVD PCR positive ESCMID Online9 EVD PCR negative Lecture Library @ by author DSTL EVD Rapid Test

Higher CT scores were found in patients EVD + Compared to EVD -

ESCMID Online Lecture Library @ by author Relationship between EVD PCR cycle threshold and DSTL RDT CT score

EVD PCR cycle threshold value for DSTL RDT CT Score

r = -0.1*

EVD PCR Cycle Threshold Cycle PCR EVD 15 5 6 7 8 9 10 11 DSTL RDT CT score

EVD PCR CT values were available for 13 EVD PCR positive patients in DSTL RDT study: ESCMID11 patient samples processed Online at PHE Port Loko, 1 sample Lecture processed at Italian Lab Goderich Library NB: 1 PHE PL sample excluded from analysis as RDT not performed on same day as sample collection @ by author *Pearson Correlation, two-tailed analysis, 95% CI -0.6-0.5,, p=0.75 DSTL EVD Rapid Test

The specificity of the test increased with higher CT score threshold for a positive result, but the corresponding sensitivity was reduced for a CT score of 8 or above.

The positive predictive value (PPV) of the DSTL EVD RDT, for the study population EVD prevalence of 11.5%, was 79.0% (95% CI: 54.4–93.8) for a CT score of 6 and above and increased at higher CT score thresholds for a positive result. A negative predictive value of 100% was achievable if a CT score 2 and above, a CT score 4 and above, or a CT scoreESCMID 6 and above, were classified Online as a positive Lecture Library result. @ by author DSTL EVD Rapid Test

• DSTL EVD RDT is highly sensitive, specific and performs well in an operational setting. ‘RULE - OUT’ screening test - The high sensitivity of the RDT would allow RDT- negative patients to be discharged - Those with a positive RDT should be considered high-probability suspected EVD cases, prioritized for isolation and tested. - In addition, emergency surgical procedures and obstetric deliveries could be performed without ESCMIDEVD transmission Online risk, following Lecture a negative Library RDT.

@ by author

ReEBOV Antigen Rapid Test

The WHO approved the first RDT for use as a screening test for EVD - Sensitivity of 91.8% (95% CI: 84.5–96.8) - Specificity of 84.6% (95% CI: 78.8–89.4).

This RDT was evaluated on 147 fresh venous blood and 146 frozen plasma samples in a laboratory setting in Sierra Leone. World Health Organization (WHO). WHO emergency use assessment and listing for Ebola virus disease IVDs. Public report. Product: ReEBOVTM Antigen Rapid Test Kit EUAL Number: EA 0011-011-00. Geneva: WHO; 2015.

Performance of this test in an operational setting has not been reported.

This would allow healthcare workers to confidently and safely treat non-EVD conditions and may allow normal healthcare services to be maintained in future epidemics

ESCMID Online Lecture Library

@ by author Healthcare worker infections (N=520):

Site n % Public hospital 149 57%* Community health center 29 11% Holding/transit center 23 9% Maternal/child health post 13 5% Private hospital 10 4% Other healthcare facility 10 4% Peripheral health unit 9 3% Community health post 6 2% Ebola treatment center 5 2% OutpatientESCMID setting Online4 Lecture2% Library DHMT office@ by author 3 1% CDC, WHO, MoHS SL Healthcare worker infections (N=520):

Case Tot % of definition* al total Confirmed 316 71% Suspect 41 9% Probable 86 19% TOTAL 442 100%

Characteristic n % Sex (N=520) Male 297 57% Female 223 43% AgeESCMID (N=463) Online Lecture Library Mean, median (range) 39.1, 38.0 (16-90) @ by author CDC, WHO, MoHS SL Healthcare worker infections by district (n=518)*

65 2 3

64 32 25

Western 37

7 33 169 4 ESCMID Online Lecture Library77

CDC, WHO, MoHS SL *2 missing district@ info. Western, by Kono author, Bombali, Tonkolili , Port Loko, Kambia infections actively detected; others passively. HCW infections as a proportion of all infections in VHF are declining % of all infections % of all infections represented HCWby represented

ESCMID Online Lecture Library @ by authorOnset month, 2014 CDC, WHO, MoHS SL WHO EBOLA SITUATION REPORT 1 APRIL 2015

ESCMID Online Lecture Library @ by author 30th March- 12nd April

• 8,547 cumulative confirmed cases • 3,491 Laboratory confirmed deaths • 3,357 survivors

• Currently, all EVD cases have only been coming from: Western Area, Port Loko and Kambia. While these districts continue to experience constant EVD transmission, 11 other districts in the countryESCMID did not report Online any Lecture Library positive cases. @ by author Where we are today on EVD # of new confirmed EVD cases by epidemiological week (May 2014 - 5 April 2015)

ESCMIDSource: Weekly Ebola Surveillance Online Report - LectureMOHS, Sierra Leone (07Library April 2015) @ by author Login Register

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Sierra Leone Ebola More Pictures Response Getting To A Resilient Zero Videos Zero Ebola Campaign – File Download: Women in Yellow on Ebola Update April 8, 2015 th Thursday 26 March Ebola Update April 7, 2015 Ebola Update April 6, 2015 Women are agents of change Ebola Update April 5, 2015 and champions in the Ebola fight. Our mothers, sisters and Ebola Update April 4, 2015 daughters have played key roles Read more in helping our families get early treatment and make the right decisions. As a symbol of the hope and energy that women bring, all women in Sierra Leone are asked to show their solidarity towards ending Ebola by wearing yellow on Thursday 26th March, the day before the Stay at Home begins. Lets end this together…

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ESCMID Online Lecture Library @ by author Safe Burials in Sierra Leone

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ESCMID Online Lecture Library @ by author ESCMID Online Lecture Library @ by author Dr. Marta Lado [email protected] Clinical Lead King´sESCMID Sierra Leone partnership Online Lecture Library @ by author