Download Epidemiology of Air-borne Diseases - University of Yeditepe Faculty

Epidemiology of Airborne
Diseases
Dr. Yeşim YASİN
Fall-2013
Outline
• Basics of epidemiology
• Basics of airborne infections
• Epidemiology of “tuberculosis”
• Epidemiology of “measles”
• Epidemiology of “influenza”
Introduction
• “Epidemiology: The study of the
distribution and determinants of a healthrelated events and application of this
study to control of health problems” (John
Last, 1988).
• Epidemiology of air-borne diseases
provides an overview of airborne disease
burden and its likely future evolution.
Basics of Epidemiology
• INFECTIVITY: The ability of an agent to invade and
multiply (produce infection) in a susceptible host.
• How to measure (Infectivity); ease & spread of
infection?
Secondary Attack Rate
The proportion of exposed susceptible persons
who become infected.
Measles has high infectivity whereas leprosy has low
infectivity.
Basics of Epidemiology (cont.)
• PATHOGENICITY: It is the ability of the
organisms to produce specific clinical reaction
after infection. It refers to the proportion of
infected persons who develop clinical disease.
• How to measure pathogenicity?
• By the ratio of clinical to sub-clinical cases.
Measles has high pathogenicity whereas TB
has low pathogenicity.
Basics of Epidemiology (cont.)
• VIRAL SHEDDING
Multiplication of a virus in an infected person
with subsequent release of the virus from that
infected person, such that others who come into
contact with the person may become infected. A
state of being contagious.
• VIRULENCE
The degree of pathogenicity of an infectious agent. i.e.
the ability of the agent to invade and damage tissues of
the host causing severe manifestations or death.
Modes of transmission
Airborne transmission
Transmission medium
Airborne transmission
Airborne transmission occurs by particles that are
suspended in air.
There are two types of these particles:
- dust
- droplet nuclei
1. Dust particles:
- result from re-suspension of particles that have settled
on floor or bedding,
- infectious particles blown from the soil by the wind.
Example: Fungal spores.
Airborne transmission (cont.)
2. Droplet nuclei
• They represent the dried residue of droplets that have
been coughed or sneezed into the air.
• They are very tiny particles less than 5 µ (microns) in
size and may remain suspended in the air for long
periods.
Examples:
• Tuberculosis is transmitted more often indirectly,
through droplet nuclei, than directly, through direct
droplet spread.
• Legionnaires’ disease and histoplasmosis also spread
through airborne transmission.
Airborne infection requirements
• Pathogen must be dispersed as fine particles
(1-5 μm size)
• Respiratory tract-cough aerosol
• TB wound
• Remain suspended in air
• Reach the alveolar level (TB)
• Resistant upper respiratory tract
• Minute infectious dose (droplet nucleus)
Particle size and suspension in air
• Particle size &
deposition site
•
•
•
•
100 μ
20 μ
10 μ-upper airway
1-5 μ-alveolar
deposition
• Time to fall the
height of a room
•
•
•
•
10 sec
4 min
17 min
Suspended indefinitely
by room air currents
Droplet vs. airborne spread
• Transmission within a
meter of the source
• Relatively large numbers
of organisms in inoculum
(small inoculum may be
tolerated)
• Access to vulnerable site
(mucosal membranes of
eye, nose, mouth,
trachea, etc.)
• Hand washing may be
effective
• Transmission beyond a
meter-shared breathing
volume
• Relatively small numbers
of organisms in
inoculum-virulence
required
• Access to vulnerable site
(alveoli in the case of TB)
• Hand washing not
effective.
Mycobacterium
tuberculosis?
Model airborne infections
• Focus on TB (MDR, XDR-TB) and measles but
implications for other infections that are
partially, opportunistically, or conditionally
airborne.
• Rhinovirus, influenza, adenovirus, SARS, Bioterrorist
agents (smallpox, anthrax), environmental agents
(M. bovis, coccidiomycosis, Q-fever, Hanta – not
necessarily person to person)
MEASLES
Agent and transmission
• Agent: A virus of the paramyxovirus (RNA)
family causes measles. The measles virus
normally grows in the cells that line the back
of the throat and lungs.
• Modes of transmission:
• Direct: Droplet
• Indirect: Airborne
The virus spreads by the respiratory route via aerosol
droplets and respiratory secretions which can remain
infectious for several hours. The infection is acquired
through the upper respiratory tract or conjunctiva.
Reservoir
• Reservoir: Humans in the form of:
• Carriers (sub-clinical, during the incubation
period)
• Cases (through-out the course of the clinical
syndrome)
• In contrast to the influenza virus, measles does not have
an animal reservoir, which makes it candidate for
“elimination” if we manage to successfully prevent
infection among human reservoirs.
Time and portals
• Temporal pattern: Peak in late winterspring
• Portals of exit/entry
Respiratory system
• Exit: exhalation
• Entry: inhalation
Incubation and clinical features
• The incubation period: 7 to 21 days with an average of
14 days.
• After incubation period, the patient enters the
prodromal stage with fever, coryza, malaise, sneezing,
rhinitis, congestion, conjunctivitis and cough followed
by a maculopapular rash that usually appears first on
the face and then spreads distally. A case of measles is
infectious for a period of 4 days prior to the onset of
rash until 4 days after the onset of rash.
Clinical features
• Koplik's spots, which are pathognomonic for measles,
appear on the buccal and lower labial mucosa opposite
the lower molars.
• The distinctive maculo-papular rash appears about 4
days after exposure and starts behind the ears and on
the forehead. From here the rash spreads to involve the
whole body.
Complications and risk groups
• Measles can cause complications such as otitis media,
pneumonia, severe diarrhea, and encephalitis leading to
hospitalization and death in severe cases. The rates of
hospitalization due to complications can be as high as 40%
even in developed countries.
• Due to its high communicability, even a minor decrease in
immunization coverage can result in rapidly spreading
outbreaks and re-establishment of endemic transmission, as
noted in the United Kingdom in the recent past.
• Unvaccinated children and young adults are at a higher risk of
developing measles and they place vulnerable groups such as
infants and persons with contraindications to immunization at
risk.
Spread
• Airborne spread through aerosolized droplet
nuclei has been documented in closed
environments (e.g., clinics or waiting rooms)
for up to 2 hours after the infected person
has left the area.
• The R0 (expected number of secondary
cases resulting from a primary case in the
absence of community immunity) for
measles is approximately 15, more than 10
times higher than that of the swine-origin
H1N1, and three times higher than smallpox.
Treatment
• No specific antiviral treatment exists.
• Severe complications due to measles can be avoided
through supportive care that ensures good nutrition,
adequate fluid intake and treatment of dehydration.
• This solution replaces fluids and other essential
elements that are lost through diarrhea or vomiting.
Antibiotics should be prescribed to treat eye and ear
infections, and pneumonia.
• All children in developing countries diagnosed with
measles should receive two doses of vitamin A
supplements, given 24 hours apart.
Control
• Controlling the spread of such a contagious disease
that has an 8-9 day-long period of infectiousness
remains a major public health challenge.
• In addition to the isolation of all laboratory-confirmed
cases, post-exposure immunization of susceptible
contacts with a single dose of measles-containing
vaccine within 72 hours of exposure has been
demonstrated to decrease transmission and is a
standard recommendation.
• Both serologic and epidemiologic evidence suggest
that the immunity induced by the vaccine remains
effective long term and possibly for life, in most
individuals.
Control (cont.)
• In spite of the progress achieved over the past
few decades in eliminating and controlling the
disease from many parts of the world through
immunization, regions of high measles
transmission still exist.
• Global migration and international travel to and
from such regions pose a constant threat of reintroduction of virus transmission in regions that
have eliminated measles.
Distribution of Laboratory-Confirmed Measles Cases by
WHO Region, 2011.
Measles in Turkey
• 20509 cases in 2001 (9 deaths), 1119 cases in 2005 and
34 cases in 2006 whereas 349 cases in 2012
• As of September 2013: 6983 cases
• Measles case burden: Third country in the world
• Notification is mandatory
• Elimination program prevails
Prevention
• Routine measles vaccination for children,
combined with mass immunization campaigns in
countries with high case and death rates, are key
public health strategies to reduce global measles
deaths.
• The measles vaccine has been in use for over 40
years. It is safe, effective and inexpensive. It
costs less than one US dollar to immunize a child
against measles.
Prevention (cont.)
• The measles vaccine is often incorporated with
rubella and/or mumps vaccines in countries where
these illnesses are problems. It is equally effective in
the single or combined form.
• In 2011, about 84% of the world's children received
one dose of measles vaccine by their first birthday
through routine health services – up from 72% in
2000.
• Two doses of the vaccine are recommended to
ensure immunity and prevent outbreaks, as about
15% of vaccinated children fail to develop immunity
from the first dose.
Measles vaccine
• Composition
Live virus
• Efficacy
95% (range, 90%-98%) The
seroconversion rate is 95% and the immunity lasts
lifelong.
• Duration of
Immunity
Lifelong
• Schedule
2 doses
• Should be administered with
mumps and rubella as MMR
or with mumps, rubella and
varicella as MMRV.
Control
• In the majority of patients, measles is an acute selflimiting disease that will run its course without the need
for specific treatment. However, it is far more serious in
the immuno-compromised, the undernourished, and
children with chronic debilitating diseases. Such patients
can be protected by the administration of human antimeasles gamma-globulin if given within the first 3 days
after exposure. Alternatively, the exposed individual can
simply be vaccinated within 72 hours of exposure.
• Pneumonia - antibiotics may be indicated in cases of
secondary bacterial pneumonia or otitis media.
• Encephalitis - treatment of acute measles encephalitis
is only symptomatic and supportive. A wide variety of
treatment has been tried for SSPE but no convincing
effects have been demonstrated.
Global Plan
• In April 2012, the MR Initiative launched a new Global
Measles and Rubella Strategic Plan which covers the period
2012-2020.
• The Plan includes new global goals for 2015 and 2020:
• By the end of 2015
- To reduce global measles deaths by at least 95%
compared with 2000 levels.
- To achieve regional measles and rubella/congenital
rubella syndrome (CRS) elimination goals.
Global Plan (cont.)
• By the end of 2020
• To achieve measles and rubella elimination in at least five WHO
regions.
The strategy focuses on the implementation of five core components:
• achieve and maintain high vaccination coverage with two doses of
measles- and rubella-containing vaccines;
• monitor the disease using effective surveillance, and evaluate
programmatic efforts to ensure progress and the positive impact of
vaccination activities;
• develop and maintain outbreak preparedness, rapid response to
outbreaks and the effective treatment of cases;
• communicate and engage to build public confidence and demand for
immunization;
• perform the research and development needed to support costeffective action and improve vaccination and diagnostic tools.
Overview
• Measles is one of the leading causes of death among young
children even though a safe and cost-effective vaccine is
available.
• In 2011, there were 158 000 measles deaths globally
• More than 95% of measles deaths occur in low-income
countries with weak health infrastructures.
• Measles vaccination resulted in a 71% drop in measles deaths
between 2000 and 2011 worldwide.
• In 2011, about 84% of the world's children received one dose
of measles vaccine by their first birthday through routine
health services – up from 72% in 2000.
INFLUENZA
Definitions of Terms
• Seasonal influenza: Influenza that occurs every
year with gradual variations in the previous
year’s virus surface proteins (antigenic drift)
• Avian Influenza: a disease of birds that
occasionally jumps species and infects humans.
Ultimately is the source of new influenza A
viruses in humans that can lead to pandemics
• Pandemic influenza: a worldwide surge in
human influenza cases caused by the introduction
of a new type A virus surface protein (antigenic
shift)
42
Influenza Viruses
• Classified into types A, B, and C
• Types A and B cause significant disease
worldwide
• Types B and C limited to humans
• Type A viruses
• More virulent
• Wild waterfowl reservoir
• Affect many species
43
Influenza A Viruses
Categorized by subtype
• Classified according to two
surface proteins
• Hemagglutinin (HA) – 17 known
subtypes
• Site of attachment to host cells
• Antibody to HA is protective
• Neuraminidase (NA) – 10 known
subtypes
• Helps release virions from cells
• Antibody to NA can help modify
disease severity
44
Influenza A HA and NA Subtypes
H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11
H12
H13
H14
H15
H16
N1
N2
Other Animals
Other Animals
Other Animals
Other Animals
N3
N4
N5
N6
N7
N8
N9
Other Animals
Other Animals
45
Importance of Influenza
• Global burden largely unknown
• Data from temperate climates
• 3-5 million severe cases/year
• 300,000 - 500,000 deaths/year
46
Transmission
• Influenza is an acute respiratory disease
(causative agent is influenza virus from
Orthomyxoviridae family)
• Signs and symptoms reflect respiratory
route
• Fever, cough, headache, muscle aches
• Sometimes lower respiratory
• Transmission of influenza viruses
• Person-to-person through droplets from coughing or
sneezing
• Transmission from objects (fomites) possible
• Infectious 1 day before and up to 5 days after
becoming sick
47
Communicability
• Viral shedding can begin 1
day before symptom onset
• Peak shedding first 3 days
of illness
• Subsides usually by 5-7th
day in adults
• Infants, children and the
immunosuppressed may
shed virus longer
48
Seasonality
Incubation period
• Time from exposure to onset of symptoms
• Average 2 days (range = 1-4 days)
• Peak shedding first 3 days of illness
Seasonality
• In temperate zones, increases in winter months
• Driven by mutations and viral preference for cold, dry weather
conditions
• In tropical zones, circulates year-round
• Fall-winter and rainy season increase has been observed
• More international data are needed
49
Clinical Disease, Human Influenza
• Clinical symptoms non-specific
• Couple with laboratory data to verify
diagnosis.
• Abrupt onset
• Fever, chills, body aches, sore throat, nonproductive cough, runny nose, headache.
• GI symptoms and muscle inflammation
more common in young children
50
Human Influenza Complications
• Sinus and ear infections
• Viral and bacterial pneumonia
• Myocarditis and Pericarditis
• Myositis
• Encephalopathy and encephalitis
• Febrile seizures
• Worsening of underlying chronic
conditions
• Sepsis-like syndrome in infants
51
Individuals at Increased Risk for
Hospitalizations and Death
• Adults>65 years
• Adults and children with chronic medical
conditions
 Neuromuscular dysfunction
 Heart disease
 Asthma
 Chronic lung disease
 Liver disease
 Diabetes
 Immune compromised
• Pregnant women
• Nursing home residents
• Children on long-term aspirin therapy
52
Influenza Vaccination
• Best way to prevent influenza
• Developed from 3 circulating strains
(2 Type A and 1 Type B strain)
• Seasonal “flu shot” only works for
3 influenza subtypes and will not
work on pandemic strains
• Inactivated, intramuscular vaccine
injection for persons 6 months and
older
• Live, intranasal spray vaccine for
healthy non-pregnant persons (2 – 49
years old)
53
Influenza Antiviral Medications
• Can be used for both prevention and for
treatment:
• Adamantanes
Rimantadine and Amantadine
Only for Type A viruses
Currently not recommended for use due to resistance among
circulating influenza A viruses
• Neuraminidase inhibitors
Oseltamivir (Tamiflu®) and Zanamivir (Relenza®)
Type A and B viruses
Emergence of global resistance to Oseltamivir in influenza
A (H1N1) viruses in 2007-08
54
Infection Control Measures for Seasonal,
Avian, and Pandemic Influenza
• Mostly in healthcare settings and nursing homes
• Standard precautions
For example, gloves, hand washing and cough etiquette
• Transmission-based precautions
For example, contact, droplet and sometimes droplet nuclei
precautions
• Annual influenza vaccination of all healthcare workers
55
Non-Pharmaceutical
Interventions (NPIs)
• Social distancing
• Personal protective
measures (e.g. masks)
• Travel screening and
restriction
• Public health
communication
campaigns
56
Avian Influenza
57
H5N1 Epizootic – 2003-2008
• Since December 2003
>60 countries have reported
H5N1 among domestic poultry
or wild birds
Current outbreaks in many
countries
Expanded from Asia to the
Middle East, Europe, and Africa
• Largest epizootic of avian
influenza ever described
Over 200 million birds died or
destroyed
58
Cause for Concern
• Avian influenza can have a large impact on
poultry
• Can cause morbidity/mortality in poultry
• Significant economic impact
• Rarely, avian influenza A virus infection can
cause illness in humans
• Highly pathogenic avian influenza A viruses
could be a source of the next pandemic
influenza virus strain
59
Avian Influenza Viruses
• Type A influenza
• Endemic in birds
• May be low pathogenic or high
pathogenic
• H5, H7 subtypes can be highly
pathogenic and cause serious
disease or death in wild birds;
often cause death in poultry
• Virus in saliva and feces of wild
birds and poultry can be directly
transmitted to humans and other
animals
60
Avian Influenza Virus Pathogenicity
• Low pathogenic AI (LPAI) viruses
Most common influenza virus infection in birds
Causes mild clinical and
unapparent infections
May be any subtype (H1 to H16)
• Highly pathogenic AI (HPAI) viruses
Some H5 or H7 virus strains to date
Causes severe illness in poultry and often death
LPAI H5 or H7 virus subtypes can mutate
into HPAI H5 or H7 virus subtypes
Usually no symptoms or mild symptoms in wild birds
• Determined by molecular and pathogenicity criteria
61
Highly Pathogenic Avian Influenza
A (H5N1) Virus (HPAIV)
• Currently spreading through Asia, Africa, Europe,
Middle East
• Can be highly lethal to domestic poultry and other
animal species
• Occasional human cases but no sustained human-tohuman transmission
• Virus of greatest concern for pandemic potential, but
other influenza viruses in animals also of concern
62
*As of September 2008
Influenza A (H5N1) viruses in
Other Animals
H5N1 viruses can infect
other animals:
• Pigs (China, Vietnam)
• Dogs
• Domestic cats; has
infected civet cats
• Tigers, leopards
(Thailand, China)
• Tiger-to-tiger
transmission (Thailand)
63
Avian Influenza Virus Infections
• Usually do not jump species
Wild bird strains do not usually infect domestic poultry
• Usually do not infect people
• Humans can become infected with avian
influenza viruses
Usually through close exposure to infected domestic poultry
64
Transmission Across Species
Wild Water
Fowl
Influenza A subtypes
circulate in wild birds
which can then infect
domestic birds.
Domestic
Birds
Wild birds are
reservoir for Influenza A strains
and are the source for viruses
infecting other species.
65
Human Infection with
H5N1 Virus
66
H5N1 in Humans: Clinical
Features
• Case fatality proportion: 63%
• Median age: 18 years
• Previously healthy children, young adults
• Incubation period: 2-7 days
• Fever, cough, shortness of breath, diarrhea
• Pneumonia, acute respiratory disease syndrome,
multi-organ failure
67
World Health Organization. New England J Medicine 2008;358:261-73.
*WHO WER;26:249-260
H5N1 Clinical Disease
• Very severe with high mortality
• Has primarily affected children and young
adults
• Severe pneumonia is common
• Incubation period may be longer than for
seasonal influenza
• Duration of infectious period likely longer
than seasonal influenza, particularly among
adults
• Multi-organ dysfunction is common
68
Avian Influenza in Humans
Year
Subtype
Location
Cases
Deaths
1996
H7N7
United Kingdom
1
0
1997
H5N1
Hong Kong
18
6
1998
H9N2
China
6
0
1999
H9N2
Hong Kong
2
0
2002
H7N2
United States
1
0
2003
H7N2
United States
1
0
2003
H9N2
Hong Kong
1
0
2003
H5N1
Hong Kong
2
1
2003
H7N7
The Netherlands
89
1
2006
H5N1
Turkey
12
4
2007
H7N2
United Kingdom
4
0
2003-13
H5N1
Worldwide
637
378
69
Worldwide H5N1 Outbreak in Birds
70
Source: WHO
Worldwide H5N1 Outbreak in Humans
71
Source: WHO
Human H5N1 Epidemiology
• Direct and close contact with sick or
dead poultry
• Slaughtering or cleaning poultry
• Visiting a live poultry market
• No evidence of sustained person-toperson spread
• Limited probable person-to-person
spread1
1 World
Health Organization. NEJM 2008; 358:261-73.
72
Possible Mechanisms of
International Spread
• Legal poultry business
• Illegal bird trade
• Migrating birds
• Humans (contaminated objects)
• Untreated fertilizer
.
73
What is Pandemic Influenza?
• Pandemic: epidemic spreading around the
world affecting hundreds of thousands of
people, across many countries
• Influenza pandemic: global epidemic of new
influenza A virus subtype that:
Passes easily from person to person
Causes severe disease
• Essentially no pre-existing immunity;
everybody at risk
74
Influenza Viruses
Characterized by ability to change:
• Continually (antigenic drift) → yearly
epidemics
• Drastically (antigenic shift) → rare pandemics
75
Antigenic “Drift”
Minor antigenic changes to the hemagglutinin protein
•
•
•
•
Point mutation in viral RNA
Continuous process during viral replication
Cause of seasonal epidemics
Immunity may be limited to a specific
strain
• Vaccine strains must be updated each year
76
Antigenic “Shift”
Major antigenic changes leading to emergence of a new human
influenza A virus subtype through:
• Genetic reassortment (human and animal
viruses)
• Direct animal (poultry) to human transmission
A pandemic can occur if:
• Efficient and sustained virus transmission
occurs among humans (sustained person-toperson spread)
77
Drift and Shift, Illustrated
78
Re-assortment and
Direct Transmission
Non-human
virus
Human
virus
Reassortant
virus
79
Requirements for an Influenza
Pandemic Virus
• A new influenza A subtype virus emerges that
can infect humans
AND
• Causes serious illness
AND
• Spreads easily from human-to-human in a
sustained manner
80
Pandemic Influenza
• Timing unpredictable
• High sickness rates across age groups
• Increased mortality
 Higher proportion of deaths in younger persons
81
Estimated Mortality from
Previous Influenza Pandemics
• 1918-19 (H1N1)
20 -50 million deaths
worldwide
• 1957-58 (H2N2)
1 million deaths
worldwide
• 1968-69 (H3N2)
1 million deaths
worldwide
82
Seasonal Epidemics vs. Pandemics
Human Influenza
Influenza Pandemics
• A public health problem
each year
• Appear in the human
population rarely and
unpredictably
• Usually some immunity
built up from previous
exposures to the same
subtype
• Human population lacks
immunity to a new influenza
A virus subtype
• Infants and elderly most at
risk
• All age groups, including
healthy young adults, may be
at increased risk for serious
complications
• Result of Antigenic Drift
• Result of Antigenic Shift
83
Timeline of New Influenza A
Subtype Virus Infections in Humans
Avian
Influenza
H9
H7
H5
H3
H2
H1
H1
1915 1925 1935 1945
1955 1965 1975 1985 1995
2005 2009
1918
1957
1968
1977
2003
Spanish
Influenza
H1N1
Asian
Influenza
H2N2
Hong Kong
Influenza
H3N2
Emergence
of H1N1
Emergence
of H5N1
84
Concerns about Pandemic
Influenza
• Rapid global spread (morbidity and mortality)
• Shortages and delays – vaccines and antiviral
medications
• Increased burden on hospitals and outpatient
care systems
• Disruption of national and community
infrastructures
85
Review Question
Match each term to the statement that it best fits
• Seasonal Flu
• Avian Flu
• Pandemic Flu
• Occurred 3 times in the
20th century
• Outbreaks result from
antigenic drift
• Usually does not infect
people
86
Potential Strategies to Decrease
the Impact of a Pandemic
• Prevent or delay introduction, slow spread
• Decrease morbidity and death
Vaccine when available
Antiviral treatment and isolation for people with illness
Non-pharmaceutical interventions
Unprepared
Impact
87
Prepared
Weeks
WHO Phases of a Pandemic
http://www.who.int/csr/disease/avian_influenza/phase/en/index.html
88
WHO Phases of a Pandemic
Inter-pandemic Period
Phase 1: No new Influenza virus subtypes in humans
Phase 2: No new virus subtypes in humans; animal subtype poses a risk
of human disease
Pandemic Alert Period
Phase 3: Human infection with novel virus; no or very limited human-tohuman spread
Phase 4: Small, localized clusters of human-to-human spread
Phase 5: Larger clusters, still localized; virus adapting to humans
Pandemic Period
Phase 6: Increased and sustained transmission in the general population.
89
Post Pandemic Period
Recovery phase
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