Download SARS

‫‪1‬‬
‫کوروناویروس ‪MERS‬‬
‫و سایر بیماری های حاد تنفس ی نوپدید‬
‫دکتر فرشید رضایی‬
‫مرکز مدیریت بیمار یهای واگیر‬
‫وزارت بهداشت درمان و آموزش پزشکی‬
The great mistake!

2
In the mid-1970s, the U.S. Surgeon
General:
 Infectious
diseases had been
“conquered” through the
development and use of
antibiotics and vaccines
it was time to shift the government’s attention and
resources to the “War on Cancer”
HIV, Lyme, Legionnaire’s disease, hantavirus, SARS,…
Helicobacter pylori: infectious nature of other “noninfectious”
diseases such as atherosclerosis, peptic ulcer and gastric cancer
Emerging infectious disease
EID
3

Since the 1980s , EIDs Emerge as a Major Public Concern
•
Australia: Hendra virus disease
•
Malaysia: Nipah virus encephalitis
•
Africa: Ebola, Marburg, Rift Valley fever , Yellow fever
and Plague
•
United States: West Nile virus fever, human monkeypox,
and Escherichia coli O157:H7 outbreaks
•
Globally:
•
HIV, SARS, avian influenza, dengue fever outbreaks …
In the past 30 years alone 37 new pathogens have
been identified as human disease threats
Importance of
Zoonotics and EIDs

868 (61%) of human
pathogens (>1400), are
zoonotic (Taylor et al., 2001)
Human Pathogens
Non zoonotic
60%
Non EID
Zoonotic
4
Non zoonotic
0%
Zoonotic
40%
Zoonotic EIDs
Human pathogens
Non EID
88%
0%
EID
12%
Zoonotic
9%
Non
zoonotic
3%
Definitive Host
(zoonotic reservoir)
Human (dead end Host)
Intermediate
Host?*
5
emerging infectious diseases 1940-2004


6
335 emerging infectious diseases identified between 1940
and 2004

60.3% were zoonoses

71.8% of these originated in wildlife
Jones, Patel, Levy, et. al. Nature, 2008 Feb. 21; 451 (7181):990-3
Main Categories of Drivers Associated
with Emergence of Human Pathogens

1. Changes in land use or agricultural practices

2. Changes in human demographics and society

3. Poor population health (e.g., HIV, malnutrition)

4. Hospitals and medical procedures

5. Pathogen evolution (e.g., antimicrobial drug
resistance, increased virulence)

6. Contamination of food sources or water supplies

7. International travel

9. International trade

8. Failure of public health programs

10. Climate change
7
Development, Health and Infectious
Diseases
Continually growing physical infrastructure:
•
Housing
•
Manufacturing
•
Energy
•
Transportation
•
Waste disposal
8
Examples of emerging infectious
disease throughout the world
9
Severe Acute Respiratory
Syndrome (SARS)

Pneumonia caused by a
coronavirus

Fatal pneumonia

Fever (>100.4 F or 38 C); Dry cough,
shortness of breath, difficulty
breathing

Tx: Supportive therapy only

Incubation period, ~6 days

Case fatality proportion, 5-15%

Much higher in persons over 60 years
10
Discovering SARS


First recognized in Viet Nam, February 2003

Businessman traveled from Guangdong

Hospital outbreak among persons exposed to him
BUT

Occurred in Guangdong Province as early as
November 2002 :

small outbreaks occurred between November 2002
and early January 2003.

A larger outbreak, triggered by nosocomial
transmissions in 2 hospitals, began during mid-January
2003 in Guangzhou city, the capital of Guangdong
Province
11
Late global alert on March 2003
12

when WHO issued a global alert on March 12, 2003,
the virus had already spread to other countries!!!

Hong Kong,

China;

Hanoi, Vietnam;

Singapore;

Toronto, Ontario, Canada
How is SARS Spread?

Droplet?


Close contact appears important

Household contacts

Healthcare workers (HCW)
But… many unanswered questions

Aerosol pattern in some cases
 “Super-spreaders”

Still unsure about…

Fomite transmission

Asymptomatic transmission
13

Spreading SARS From Hong Kong (March 2003):
Then visitors traveled to Canada, Singapore, Taiwan, and Vietnam
14
Amoy Gardens, Hong Kong
Aerosolized virus from improperly ventilated
U-traps spread up outside ventilation shaft in
an apartment building
SARS Cases Reported to WHO as of June 13, 2003
8,445 cases; 790 deaths
18
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Margaret Chan, WHO

19
SARS was a 21st century disease in its mode and
speed of spread.
But it was eventually defeated using 19th century
tools

She effectively managed outbreaks of
avian influenza and of severe acute
respiratory syndrome (SARS).
IHR 2005

20
for the 1st time they defined a series of core capacities
that each country is required to establish to
detect, report, and control public health emergencies of
international concern
The Influenza A Virus

Typically spherical
 50-120
nm diameter
Single-stranded RNA
virus
 Genome in 8 segments

 Encode
key surface
glycoproteins
 Haemagglutinin (HA)
 Neuraminidase
(NA)
H and N

18 different H antigens (H1 to H18) and

11 different N antigens (N1 to N11).

H17 was isolated from fruit bats in 2012.

H18N11 was discovered in a Peruvian bat in 2013.
23
What Was So Striking…

Characteristic symptoms & outcomes

High global death tolls


24
Large numbers of deaths among healthy adults
So completely ignored for so long
Characteristic Symptoms and outcomes
25

“…dusky heliotrope cyanosis of the face, lips, and ears…
[and] purulent bronchitis with bronchopneumonia”

Case fatality proportion 25-50%
The Death Toll

Global estimates

1920’s: ~21.5 million dead



India alone: 18 million
1998 conference: 50-100 million !!!
Varied greatly by country & region

Africa: 20-445 deaths/1,000
people

Asia/Pacific: 3-220 deaths/1,000

Europe & N. America: 3-20
people
deaths/1,000
26
27
Oct-Nov 1918
(second wave)
Deaths Among
Healthy Adults

Rates during 1918
 Infants
& over 40
~2-10-fold higher
 10-20
yrs old:
20-100-fold higher
 20-30
yrs old
20-180-fold higher
Shift vs. Drift

Usually “antigenic drift”

“Normal” mutations

Changes in surface glycoprotiens

can cross-react with existing immunity

Sometimes “antigenic shift”

Segments can rearrange when co-infecting
same cell

Re-assortments by very different strains can
profoundly change ability to recognize
29
Pandemic in
th
20
century
30
Human flu

H1N1:

1918 flu pandemic ("Spanish flu")

seasonal human flu

2009 flu pandemic ("swine flu")

H1N2, pig and human

H2N2, "Asian flu"

H3N2,


"Hong Kong flu"

seasonal human flu
H5N1, ("bird flu")
31





H5N6 (2014)
H6N1(2013)
H7N2, infected two people
H7N3, infected two people
H7N7, killed one person
 H7N9
 H9N2, infected three people
 H10N7, which has infected
two people
 H10N8 (2014)
Avian Influenza H5N1

32
1997Hong Kong,

18 people hospitalized; 6 die

Young adults affected

directly from chickens

No easily person-to-person transmission:

predominately limited to family clusters

2003:

report of 2 human cases in Hong Kong (one fatal) both with
history of travel to Fujian Province, China
H5N1

incubation period is about 3-4 days

average time from onset to
hospitalization : 4-5 days.

The majority of cases: young adults
(20-39 years),

followed by children (0-19 years)

equal sex distribution
33
Avian Flu in 2003-4

December 2003 H5N1 avian flu identified in Vietnam

By March 10th, 2004

33 cases with 22 deaths in Vietnam and Thailand

Infected birds in 8 Asian countries

Cambodia, China, Indonesia, Japan, Laos, South Korea,
Thailand, and Vietnam
34
H5N1…
35

Since 2003, the WHO reports 648 cases from 15 countries.

H5N1 and 384 deaths (case fatality of 58% among recognized
cases)

The most cases to date globally have occurred in


indonesia (195 cases/163 deaths) and

egypt (173/63), reporting the most cases since 2009.
In 2013 there were 38 human cases and 24 deaths (case
fatality of 63%).

reported in egypt (4/3), china (2/2), vietnam (2/1) and bangladesh

the most recent cases have been from cambodia (26 cases/14
deaths in total in 2013) and indonesia (3/3).
New H7N7

New H7N7 bird flu strain discovered that could
pose threat to humans (August 2013)

H7N7 virus, found in chickens at markets in China,
can kill ferrets
36
Melaka Virus:
Respiratory reovirus

Substantial proportion of respiratory infections are
caused by unknown etiological agents.

"Melaka virus" isolated from a 39-year-old male
patient in Melaka, Malaysia, who was suffering
from high fever and acute respiratory disease at
the time of virus isolation.

Two of his family members developed similar
symptoms approximately 1 week later and had
serological evidence of infection with the same
virus.

The family was exposed to a bat in the house
approximately 1 week before the onset of the
father's clinical symptoms.

Reoviruses (respiratory enteric orphan viruses)
were first isolated from humans in the early 1950s

37
Influenza A H7N9
•
First reported internationally in April 2013
•
Most have been exposed to infected poultry or
contaminated environments before illness

Control measures (closing live bird markets)

Natural seasonal pattern of avian flu viruses
38
Genetic evolution of H7N9
2013
39
40
41
Criteria for an Influenza
Pandemic
42
• Criteria for a pandemic:
 Novel strain that is not recognized by the human
immune system
 Causes increased sickness and death
XSustained person-to-person transmission
East and Southeast Asia:
as a hot spot of EID

hot spot of socioeconomic and environmental change
43
44
‫‪45‬‬
‫نگاه اجمالي به ويروس ‪MERS‬‬
‫تا كنون تنها ‪ 6‬عدد از خانواده بزرگ كوروناويروس ها با توانايي بيماريزايي در‬
‫انسان شناخته شده اند‪ .‬مابقي در حيوانات شناخته شده اند‪.‬‬
‫‪ SARS‬در سال ‪ 2003‬و ‪ MERS‬در سال ‪: 2012‬‬
‫بيماريزايي شديد و مرگ انسان‬
‫مرگ و مير ‪ MERS‬حدود ‪%40‬‬
‫آنچه درباره ‪ MERS‬مي دانيم هنوز بسياراندك‬
‫است و اين نگران كننده است‬
KSA;
The center of disease
46
47
median age: 47 years (range: <1-94 years)
64% are male
‫‪48‬‬
‫منبع و مخزن بيماري كجاست؟‬
‫مطالعات دقيق ژنتيكي ارتباط بسيار‬
‫نزديك ويروس جداشده از خفاش و‬
‫شترها را با ويروس ‪MERS‬انسان‬
‫نشان داده است‬
‫منبع و مخزن دقيق بيماري هنوز مشخص نيست‬
‫‪49‬‬
‫صنعت گوشت شتر‬
‫‪‬‬
‫‪ 5‬كشور اول پرورش دهنده و صادركننده شتر در دنيا كشورهاي آفريقايي هستند‪.‬‬
‫‪‬‬
‫دو كشور اول توليد كننده و صادركننده گوشت شتر نیز عربستان سعودي و امارات متحده‬
‫عربي هستند‬
‫‪‬‬
‫بيشتر شترهاي وارده به عربستان و امارات نیز از كشور عمان (بواسطه ازآفريقا) وارد مي شود به اهميت‬
‫مطالعه فوق الذكر مي افزايد‪.‬‬
‫ردپاي انتقال از حيوان به انسان‬
‫‪50‬‬
‫‪‬‬
‫‪ SARS‬و ‪ MERS‬شواهد انتقال از حيوان به انسان دارند‬
‫مطالعه ژنتيكي كوروناويروس شترهاي مصري‪:‬‬
‫‪ MERS .1‬در شترها شايع است‬
‫‪ .2‬شباهت ژنتيكي با ويروس انساني‬
‫‪51‬‬
‫ردپاي ويروس ‪ MERS‬در مخازن جانوري‬
‫‪ ‬مطالعات سرولوژيك گستردگي جغرافيايي وسيعي را از نظر الودگي شترها‬
‫به ويروس ‪ MERS‬نشان مي دهد كه شامل مناطقي از شمال قاره آفريقا‬
‫تا كشورهاي شبه جزيره عربستان مي گردد‬
‫‪ ‬از‪ 30‬سال قبل در شترهای سومالی و سودان وجود داشته است‬
‫‪ ‬اسیدنوکلئیک مرس در شترهای عربستان‪ ،‬امارات‪ ،‬عمان‪ ،‬مصر‪ ،‬قطرو‬
‫کویت شناسایی شده است‬
‫‪ ‬مطالعات ويروس شناختي نیز ردپاي اجداد نزديك ‪ MERS‬را تا خفاشهاي‬
‫آفريقاي جنوبي دنبال نموده اند‪.‬‬
‫‪52‬‬
‫نماي باليني‬
‫‪ ‬بيماري ‪ MERS‬نیز مانند ‪ SARS‬بيشتربه شكل‬
‫تنفس ي تظاهر مي يابد هرچند در برخي بيماران ممكن‬
‫است اشكال غیرمعمول مانند اسهال نیز ديده شود‪.‬‬
‫‪MERS‬برخالف ‪SARS‬مي تواند به بخشهاي ديگربدن‬
‫هم سرايت نموده و نارسايي چند ارگان را ايجاد كند و مرگ‬
‫و میر بيشتري دارد‬
‫‪53‬‬
‫ابتال موارد متعدد در بيمارستان شرق عربستان‬
‫‪54‬‬
‫اردن‬
‫عربستان‬
‫قطر‬
‫امارات‬
‫عمان‬
‫كويت‬
‫كشورهاي عربي گرفتار بيماري در ‪2013‬‬
Up to Dec 2013
55
Country
Cases
Deaths
Saudi Arabia
132
55
Qatar
8
5
United Arab Emirates (UAE)
10
4
United Kingdom
3
2
Kuwait
2
0
Tunisia
3
1
Jordan
2
2
France
2
1
Italy
1
0
Oman
1
1
Spain
1
0
TOTAL
165
71
56
Seventy-one of the 165 cases have died (crude mortality rate
43%).
‫‪57‬‬
‫گسترش بيماري با پروازهاي‬
‫بین املللي‬
‫هندوستان‬
‫اندونزي‬
‫تركيه‬
‫‪...‬؟‬
‫‪58‬‬
‫كشورهايي كه بيشترين زائر را دارند‬
‫‪59‬‬
‫روزبه روزوضعيت پيچيده ترمي شود‬
‫‪‬‬
‫هرچند وضعيت فعلي مشمول تعريف ‪ PHEIC‬نمي شود اما روزبه روز وضعيت جدي تر‬
‫و نگران كننده تر مي شود و نياز به رصد و مراقبت دقيق اوضاع دارد‬
‫‪PHEIC: public health emergencies of international concern‬‬
‫‪60‬‬
‫بيماري ‪ MERS‬در حال گسترش است‬
‫‪1‬‬
‫‪2‬‬
‫‪3‬‬
‫‪4‬‬
‫‪5‬‬
‫‪6‬‬
‫‪7‬‬
‫‪8‬‬
‫‪9‬‬
‫‪10‬‬
‫‪11‬‬
‫‪12‬‬
‫‪13‬‬
‫‪14‬‬
‫‪15‬‬
‫‪16‬‬
‫‪17‬‬
‫‪18‬‬
‫‪19‬‬
‫‪20‬‬
‫‪21‬‬
‫نام کشور‬
‫عربستان‬
‫امارات متحده عربی‬
‫قطر‬
‫اردن‬
‫عمان‬
‫کویت‬
‫مصر‬
‫یمن‬
‫لبنان‬
‫ایران‬
‫انگلستان‬
‫فرانسه‬
‫ایتالیا‬
‫یونان‬
‫هلند‬
‫تونس‬
‫الجزائر‬
‫مالزی‬
‫فیلیپین‬
‫ایاالت متحده آمریکا‬
‫ترکیه‬
‫مجموع‬
‫تعداد بیماران‬
‫‪770‬‬
‫‪74‬‬
‫‪10‬‬
‫‪7( 11‬مورد سرولوژیک هم محاسبه نشده است)‬
‫‪2‬‬
‫‪3‬‬
‫‪1‬‬
‫‪1‬‬
‫‪1‬‬
‫‪5‬‬
‫‪3‬‬
‫‪2‬‬
‫‪1‬‬
‫‪1‬‬
‫‪2‬‬
‫‪3‬‬
‫‪2‬‬
‫‪1‬‬
‫‪1‬‬
‫‪2‬‬
‫‪1‬‬
‫‪7( 895‬سرولوژی مثبت اردن هم محاسبه نشده است)‬
‫تعداد فوت شدگان‬
‫‪328‬‬
‫‪10‬‬
‫‪5‬‬
‫‪5‬‬
‫‪2‬‬
‫‪1‬‬
‫‪0‬‬
‫‪1‬‬
‫‪0‬‬
‫‪2‬‬
‫‪2‬‬
‫‪1‬‬
‫‪0‬‬
‫‪1‬‬
‫‪0‬‬
‫‪1‬‬
‫‪1‬‬
‫‪1‬‬
‫‪0‬‬
‫‪0‬‬
‫‪0‬‬
‫‪361‬‬
MERS-CoV case activity
17 June 2014; 830 cases

travel-associated cases linked to
1.
exposure in health care settings within the Arabian Peninsula:

2.
Greece, Philippines, United States.
religious pilgrimage to Saudi Arabia :

Netherlands, Jordan, Malaysia, Algeria, Iran
62
MERS in Middle east
63
‫‪64‬‬
‫وضعيت فعلي جهان‬
‫‪ ‬انتقال فرد به فرد بيماري محدود است و احتمال طغيانهاي گسترده در سطح‬
‫جامعه كم مي باشد‬
‫بيشترين خطرمربوط است به تجمع در فضاهاي كوچك مانند تماس هاي‬
‫خانگي و مهمتر ازآن دربيمارستان ها مي باشد كه افراد ناتوان بستري هستند‬
65
‫‪66‬‬
‫آغاز بهار‪1393‬‬
‫تعداد كادردرماني مبتال شده درجهان‪ 119 :‬مورد‬
‫‪67‬‬
‫مقايسه وضعيت ‪ 2‬ماه ابتداي سال ‪ 1393‬با سال‬
‫گذشته‬
‫‪ ‬تعداد مبتاليان شناسايي شده در ماه آوريل (بيش از‪ 200‬نفر)‪ ،‬به‬
‫تنهايي ازآنچه در‪ 2‬سال قبل (ازابتدا تا كنون) شناسايي شده بيشتر بوده‬
‫است‪.‬‬
‫بيمارستان هاي شهرجده تا سرحد تعطيلي و بحران جدي پيش رفتند‬
‫‪‬‬
Recent cases: 2014

Majority are secondary cases:

human-to-human transmission (predominately in
health care settings)

25% present with mild/asymptomatic illness (more
likely in secondary cases)

Case fatality: 35-40%)

Health care workers (~25% of recent cases)

The role of asymptomatic cases in transmission
remains unknown at this time.
68
‫‪MERS-CoV‬کادر بیمارستان مبتال در طی طغیان های‬
‫نگرانی های حج ‪1393‬‬
‫بعد ازیک دوره نسبتا کوتاه آرام‪ ،‬از‪ 6‬هفته قبل موارد درعربستان‬
‫افزایش داشته که برای حج نگران کننده است‪.‬‬
‫‪‬‬
‫‪ 34‬نفراضافه شد‪ 26 :‬مورد اخيربعالوه ‪ 18‬مورد ازقدیم‬
‫‪‬‬
‫‪ 13‬مورد درطائف‪ 5 :‬مورد درسپتامبرو ‪ 8‬مورد دراکتبر‬
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‫(‪ 1‬مورد فوت‪ ،‬بجز یکی همگی مذکر‪ 3 ،‬نفرکادربیمارستانی)‬
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‫مدینه‪ 1 :‬مورد در‪ 30‬سپتامبر‬
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‫چرخه اقدامات وزارت بهداشت‬