reviewing mers hospital outbreaks

Reviewing

MERS Hospital Outbreaks

Macao Association of Health Policy

Dr. Tong Ka Io

2015.10

Internet photos

Internet photo

Time Place Hospitals Cases HCW% CFR

2012.03-04 Jordan, Zarqa 1~2 9 (+2) 67% 22%

2013.04-05 KSA, Al-Hasa 4 23 (+11) 9% 65%

2014.03-04 KSA, Tabuk 1 10 70% ?

2014.03-06 KSA, Jeddah 14 ~200 31% 37%

2014.04 KSA, Riyadh 1 15 ? ?

2014.04-05 UAE, Al-Ain >1 28 70% ?

2014.09-11 KSA, Taif & Riyadh >3 27 ? ?

2015.04-06 KSA, Hofuf 13 44 14% 45%

2015.05-07 ROK, Seoul & others 16 186 21% 20%

Major Hospital-Associated MERS Outbreaks Ever Reported

HCW = Health care workers CFR = Case fatality rate

Outline

2012.03-04, Zarqa, Jordan

2013.04-05, Al-Hasa, KSA

2014.03-06, Jeddah, KSA

2015.05-07, Republic of Korea

Critical lessons

Implications for prevention

2012.03-04, Zarqa, Jordan

ECDC Epidemiological Updates

Internet map

Zarqa, Jordan Internet photo

The outbreak

2012.04.19, Jordan MOH reported an outbreak of

pneumonia in the Zarqa Public Hospital’s CCU-ICU.

7 nurses, 1 doctor and 1 brother of a nurse were among

the 13 suspect cases.

2012.04.20, ICU closed after death of 1 nurse.

The outbreak






2012.09, MERS-CoV first identified in a patient from Saudi

Arabia.

The outbreak






2012.09, MERS-CoV first identified in a patient from Saudi

Arabia.

2012.11, testing of stored samples from 2 died patients of

Jordan cluster confirmed MERS-CoV infection.

2014, 7 more cases were retrospectively confirmed by

serologic tests

Hijawi B, Abdallat M, Sayaydeh A, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a

retrospective investigation. East Mediterr Health J 2013; 19 (Suppl 1):S12-S18.

303

9

3

2

1

12

11

6

4

?

Estimated by author of this presentation

Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital-associated outbreak of Middle East respiratory syndrome

coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis 2014; 59:1225-1233.

Magnitude

Confirmed cases: 9

Probable cases: 2





Case pattern

Sex: male 67% (6/9)

Age: 40y (25-60y)

Underlying illness: 44% (4/9), atrial septal defect,

hypertension, pregnancy

Manifestations: among 8 hospitalized cases,

cough 88%, fever 75%, dyspnea 63%, wheezing

25%; pneumonia 88%





Impact

ICU admission: 44% (4/9)

Mechanical ventilation: 22% (2/9)

Death: 22% (2/9)





Interpersonal characteristics

Links: animal 0%, travel 0%, HCW 67%,

patient 11%, relative 22%

Transmissibility: non-spreader [67%],

spreader [33%], super-spreader [0%]

Generations: [3~4], primary case

unknown [ ] = estimated by author of this presentation





Temporal characteristics

First – last onset: 03.21(?)-04.26(?)

Incubation period: ≦10d

Serial interval: [10-17d]

[ ] = estimated by author of this presentation





Spatial characteristics

Sites of transmission

Zarqa Hospital (public, 300 beds) CCU-ICU

“there were no physical barriers between CCU and ICU beds,

spaced approximately 3 meters. Isolation or negative-pressure

rooms were not present and infection control compliance issues

were reported during the outbreak.”

Distance of transmission

Same open unit





2013.04-05, Al-Hasa, KSA

Internet map

Al-Hasa, KSA Internet photo

The outbreak

2013.04.01-05.23, a total of 23 cases of MERS-

CoV infection were reported in the governorate

of Al-Hasa, eastern province of Saudi Arabia

Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013;

369:407-416.

Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013; 369:407-416.

Cotten, M et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a

descriptive genomic study. The Lancet , 2013 Volume 382, Issue 9909 , 1993 – 2002.

Magnitude

Confirmed cases: 23

Probable cases: 11


369:407-416.

Case pattern

Sex: male 74% (17/23)

Age: 56y (24-94y)

Underlying illness: Diabetes Mellitus 74%, end-

stage renal disease 52%, lung disease 43%,

cardiac disease 39%, obesity 24%

Manifestations: cough 87%, fever 87%, dyspnea

48%, gastrointestinal symptoms 35%;

pneumonia 70%


369:407-416.

Impact

ICU admission: 78% (18/23)

Mechanical ventilation: 78% (18/23)

Death: 65% (15/23)


369:407-416.


Links: animal ?%, travel ?%, HCW 9%,


Transmissibility: non-spreader [61%],

spreader [39%], super-spreader [0%]

Generations: [4~5], more than one

primary cases unknown



369:407-416.


First – last onset: 04.08-05.12

Incubation period: 5.2d (1.9-14.7d)

Serial interval: 7.6d (2.5-23.1d)


369:407-416.



Hospital A (general, 150 beds) dialysis unit (open unit

with 16 beds spaced 1.3-1.5m apart), ICU (two open 6-

bed bays), Ward

Hospital B (general) ward; Hospital C (general) dialysis;

Hospital D (regional referral) ICU, ward


Same ward, up to 3 rooms separated


369:407-416.

2014.03-06, Jeddah, KSA

WHO Disease Outbreak News

Situation in the Middle East

2014 spring, an exponential increase of MERS

cases occurred in Kingdom of Saudi Arabia –

concentrated in health care facilities of Riyadh

and Jeddah – and United Arab Emirates.

Jeddah, KSA: ~200 cases, 14 hospitals, one

phylogenetic clade

Riyadh, KSA: ~200 cases, multiple hospital outbreaks,

at least 6 different clades

Tabuk, KSA: 10 cases, one hospital

Al Ain, UAE: 28 cases, one hospital

Drosten C, Muth D, Corman VM, et al. An observational, laboratory-based study of outbreaks of Middle East respiratory

syndrome corona virus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014. Clin Infect Dis 2015; 60:369-377.


Internet map

Riyadh, KSA Internet photo

Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome

coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis 2014; 29:301-306.

(Riyadh)

Tabuk, KSA Internet photo

Al Ain, UAE Internet photo

Jeddah, KSA Internet photo

Magnitude

Confirmed cases (2014.01-06)

Jeddah, KSA: ~200, one phylogenetic clade




Case pattern

Sex: male 68%

Age: 45y (interquartile 30-59y)

Underlying illness: ?

Manifestations: asymptomatic or mild 25%

Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERS-CoV outbreak in Jeddah: a link to healthcare facilities. N Engl J

Med 2015; 372:846-854.

Impact

ICU admission: 37%

Mechanical ventilation: ?

Death: 37%


Med 2015; 372:846-854.


Links: animal ?%, travel ?%, HCW 31%,

exposure to a health care facility 88%

Transmissibility: non-spreader ?%,

spreader ?%, super-spreader >0%

Generations: ?


Med 2015; 372:846-854.


First – last onset: Mar-Jun

Incubation period: ?

Serial interval: ?


Med 2015; 372:846-854.



King Fahd Hospital: largest communal hospital; “bad

management, crowding and lax hygiene”

Other 13 Hospitals

Sites of super-spreading

Hospitals ?


?



Al-Tawfiq JA, Perl TM. Middle East respiratory syndrome coronavirus in healthcare settings. Curr Opin Infect Dis. 2015

Aug;28(4):392-6.

2015.05-07, Republic of Korea

Situation in the Middle East

2015.01.01-07.21, KSA reported 222 MERS cases

Riyadh, KSA: 88 cases

Hofuf, KSA: 46 cases, mainly from an outbreak

involving 13 hospitals



Internet photo Hofuf, KSA

Seoul, ROK Internet photo

The outbreak

2015.05.20, ROK reported the first imported case

of MERS of the country. The case further led to

the largest transmission cluster of the disease

worldwide.

Internet image

Closure of ER of Samsung Medical Center Internet photo

Magnitude

Confirmed cases: 185+1 ex to China

Probable cases: ?


Case pattern

Sex: male 60%

Age: 55y (16-87y)

Underlying illness: asthma, COPD, TB,

cardiovascular disease, diabetes mellitus, renal

disease, pregnancy, ……

Manifestations: ?

Cowling BJ, Park M, Fang VJ, Wu P, Leung GM, Wu JT. Preliminary epidemiological assessment of MERS-CoV outbreak in

South Korea, May to June 2015. Euro Surveill. 2015;20(25):pii=21163.


Impact

ICU admission: ?%

Mechanical ventilation: ?%

Death: 20%



Links: animal 0%, travel 0.5%, HCW 21%,


Transmissibility: of the first 166 cases non-

spreader [87%], spreader [11%], super-

spreader 2%

Generations: [4~5]




WHO and ROK-MOH

Inpatients 44%

Relatives 35%

Nurses 8%

Doctors 4%

Caregivers 4%

Radiographers 1%

Ambulance workers 1%

Security guards 1% Transfer staff 1% Computing personnel 1%

HCWs 21%

Interpersonal distribution of 186 MERS cases of ROK

WHO and ROK-MOH

Taiwan DOH-CDC

Cowling BJ, Park M, Fang VJ,

Wu P, Leung GM, Wu JT.

Preliminary epidemiological

assessment of MERS-CoV

outbreak in South Korea, May

to June 2015. Euro Surveill.

2015;20(25):pii=21163.

Super-spreader

Case 1

M, 68y

Underlying illness: ???

Travel to Bahrain, UAE, KSA, Qatar

Onset: 05.11

Diagnosis: 05.20

Outcome: recovered

Secondary cases: ≧30

8 of them caused further transmission

Cowling BJ, Park M, Fang VJ, Wu P, Leung GM, Wu JT.

Preliminary epidemiological assessment of MERS-CoV

outbreak in South Korea, May to June 2015. Euro Surveill.

2015;20(25):pii=21163.

Super-spreader

Case 14

M, 35y

Underlying illness: TB

Same ward with case 1

Onset: 05.20

Diagnosis: 05.30

Outcome: recovered






2015;20(25):pii=21163.

Super-spreader

Case 16

M, 40y

Underlying illness: ???

Same ward with case 1

Onset: 05.20

Diagnosis: 05.31

Outcome: recovered






2015;20(25):pii=21163.


First – last onset: 05.11-07.02

Incubation period: 6.3d

Serial interval: 12.6d





16 Hospitals – ER, inpatient and outpatient

departments

Sites of super-spreading

4 Hospitals – ER, inpatient and outpatient


Same room, same ward, different floors of the same

hospital

WHO and ROK-MOH

City Hospital Units No of Cases

Seoul Samsung Medical Center 90

Gyeonggi Pyeongtaek St. Mary’s Hospital 37

Daejeon Daechung Hospital Inpatient 14

Daejeon Konyang University Hospital Inpatient, Staff cafeteria 11

Gyeonggi Hallym University Medical Center 6

Seoul Kyung Hee University Healthcare System ER 5

Seoul Konkuk University Hospital ER, Inpatient 4

Gyeonggi Pyeongtaek Goodmorning Hospital 4

Seoul Asan Medical Center ER 1

Seoul Yeouido St. Mary’s Hospital ER 1

Seoul 365 Yeol Lin Hospital Outpatient 1

Seoul Song Tae-eui Internal Medicine Clinic Outpatient 1

Busan Good Gang-An Hospital Inpatient 1

Gyeonggi Yangji Seoul Samsung Clinic Outpatient 1

Chungnam Seoul Clinic Outpatient 1

Chungnam Asan Chungmu Hospital Inpatient 1

WHO and ROK-MOH

Samsung Medical Center Internet photo

Pyeongtaek St. Mary’s Hospital Internet photo

Daechung Hospital Internet photo

Konyang University Hospital Internet photo

Factors leading to the outbreak

MERS-CoV was unexpected

and unfamiliar to most

physicians in ROK;

Sub-optimal prevention and

control measures in some

hospitals, related in part to

overcrowding;

The custom of “doctor-

shopping”, as well as visits

to hospitalized patients by

many friends and family

members.

(WHO)

Internet image

Typical conditions within hospitals in ROK Internet photo

Factors related to super-spreading events

Case 1

Least knowledge of doctors

about MERS, incomplete

information from patient about

his travel

Patient had pneumonia, kept

coughing and wheezing

Patient was admitted to a

restructured room which had

no exhaust system

Hospitals were overcrowded

with patients, family members,

caregivers and visitors

Case 14

Doctors diagnosed patient as

pneumonia and failed to detect

his connection with case 1

Patient had TB, persistently

coughing and wheezing, did

not put on a mask

ER was overcrowded (200

seats in 800 square feet)

Patient waited in ER for 48

hours and sometimes loitered

outside

Critical lessons

Critical lessons

1. Animal sources

2. Primary cases

3. Interhuman transmission

4. Health care settings

5. Super-spreading events

Outbreak 1 Outbreak 2 Outbreak 3 Outbreak 4

Time Mar-Apr, 2012 Apr-May, 2013 Mar-Jun, 2014 May-Jul, 2015

Space Zarqa, Jordan Al-Hasa, KSA Jeddah, KSA

ROK,

imported from

Middle East

Animal contact none unknown unknown none

Animal sources

1. Animal sources undoubtedly exist, but the species, route

of transmission and transmissibility largely remain

unknown.

2. All outbreaks occurred in / linked to the Middle East

(natural epidemic focus), but the precise geographical

limits remain uncertain.

3. Animal-to-human transmissions occurred frequently and

dispersed in vast areas of the Middle East.

4. Apparent seasonality (March to June) was noted. This may

be coincident with calving of camels in the Middle East.

5. No effect of zoonotic risk management evidenced since

2012.

http://virologydownunder.blogspo

t.com/2015_01_01_archive.html




ROK,

imported from

Middle East


Primary case unknown unknown unknown 68y male

Onset to diagnosis unknown unknown unknown 9 days

Primary cases

1. All outbreaks were caused by delay in recognition of

one or more primary cases.

2. Primary cases linked to animal sources or the natural

epidemic focus.

3. Primary cases are more likely to be male with older

age, underlying medical conditions, severe clinical

manifestations and fatal outcome.

4. Primary cases may remain unknown after all.

5. Unknown if there are more identifiable

characteristics of primary cases.

The WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERSCoV) in

humans. PLoS Curr 2013 Nov 12;5.




ROK,

imported from

Middle East




Size of outbreak 9+2 23+11 ~200 186

Generations 3~4 4~5 ? 4~5

Non-spreaders 67% 61% ?% 87%

Super-spreaders 0, 0% 0, 0% ?, ?% 3, 2%

Interhuman transmission

1. All MERS human outbreaks were not self-sustained,

suggesting a Basic Reproduction Number (R0 ) < 1.

2. Human-to-human transmissions occurred only in

households and health care settings.

3. Great difference in transmissibility – majority of

patients were “non-spreaders”, while a few turned

out to be “super-spreaders”.

4. Normalized infection control practices are well

sufficient to promptly stop further transmission.

Cauchemez S, Van Kerkhove MD, Riley S, Donnelly CA, Fraser C, Ferguson NM. Transmission scenarios for Middle East Respiratory

Syndrome Coronavirus (MERSCoV) and how to tell them apart . Euro Surveill. 2013;18(24):pii=20503.




ROK,

imported from

Middle East







Super-spreaders 0, 0% 0, 0% ?, ?% 3, 2%

Hospitals 1~2 4 14 16

Units CCU-ICU Dialysis unit,

ICU, wards ?

ER, inpatient,

outpatient

HCW 67% 9% 31% 21%

Health care settings

1. All major MERS outbreaks were amplified in health

care settings.

2. Outbreaks occurred in wards and outpatient

departments of large hospitals, among which ER,

ICU, and dialysis unit seemed more protruding.

3. Common characteristics of the outbreak settings

included overcrowding, substandard ventilation, lax

infection control practices, and accumulation of

vulnerable individuals.

4. Normalized infection control practices are well

sufficient to promptly stop further transmission.

http://virologydownunder.blogspot.com/2014/05/pressure-testing.html




ROK,

imported from

Middle East







Super-spreaders 0, 0% 0, 0% ?, ?% 3, 2%

Hospitals 1~2 4 14 16

Units CCU-ICU Dialysis unit,

ICU, wards ?

ER, inpatient,

outpatient

HCW 67% 9% 31% 21%

http://endtimeheadlines.org/2015/06/mers-starts-to-spread-more-widely-in-korea/

Super-spreading events

1. Super-spreading events multiplied the size, temporal

and spatial extension, threat and impact of MERS

outbreaks.

2. The prerequisite of super-spreading event is a high

risk patient who sheds virus extensively (super-

spreader).

3. High risk environment (overcrowding and/or sub-

standard ventilation) and high risk activities (aerosol

generating procedures and/or lax infection control

practices) are conditioning factors for super-

spreading events.

Factors for super-spreading events

High risk activities

High risk environment

High risk patients

Implications for prevention

Core strategy

Control of sources of infection

1. Control of animal sources

2. Risk management of health care settings

3. Risk management of high risk activities

4. Early identification of primary / index cases

5. Prevention of super-spreading events

Control of animal sources

1. Further scientific studies to verify the species,

route of transmission, transmissibility, and

geographic limits of natural epidemic focus

2. Zoonotic biosecurity practices

3. Animal vaccination

4. Environment modifications

Risk management of health care

settings

1. Risk assessment of health care units and

identification of high risk settings (ER, ICU,

dialysis unit, etc.)

2. Secure optimal ventilation for high risk settings

3. Install sufficient airborne infection isolation (AII)

rooms according to the need of health care

facilities

4. Eliminate overcrowding of high risk settings

5. Stringent control regime for patients with

respiratory infection to enter high risk settings

Internet photo

Emergency Room, CSJ Central Hospital, Macao

Internet photo Hemodialysis Centre, Kiang Wu Hospital, Macao

Risk management of high risk

activities

1. Aerosol generating procedures: stringent

selection of subjects, airborne precautions,

airborne infection isolation facilities

2. Infection control practices: clear policy, training

and renewing, guidance and reminders, mutual

and hierarchical supervision, audits

3. Patient behaviors: education and supervision

4. Visit and company: defined based on risk

Early identification of primary / index

cases

1. Critical knowledge for front-line health care

professionals

Existence of natural epidemic focus

The index case may not have contact with animal or human

patient, or travel history

Even in lack of known epidemiological links, unusual /

unexplained clinical picture, clustering and/or involvement

of health care workers are hints for testing

Sensitivity of test is low for upper respiratory samples, thus

negative results do not exclude the diagnosis

2. Relevant information and education, on the disease

and the situation, for the general public

Prevention of super-spreading events

In addition to the 4 basic aforementioned strategies,

some specific efforts may target the “potential

super-spreaders”

Further scientific studies to verify the identifiable

characteristics of super-spreaders: age, underlying

conditions, immunodeficiency, symptoms, etc.

Identify patient groups and minimize their nosocomial

exposure to acute respiratory infection patients by

stringent control of entry and separation in health care

settings

Routine and close monitoring of these patients for signs of

nosocomial respiratory infection, and prompt control

Conclusion

Control of sources of infection

1. Control of animal sources

2. Risk management of health care settings

3. Risk management of high risk activities

4. Early identification of primary / index cases

5. Prevention of super-spreading events

中東呼吸綜合徵（MERS）醫院暴發綜述

澳門衛生政策學會

湯家耀醫生

2015.10

reviewing mers hospital outbreaks

Health & Medicine