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 health-related 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?

More than 1m!

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: AirborneThe 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 winter-spring

• 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 re-introduction 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 ofImmunity 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 self-limiting

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 anti-measles 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 cost-effective 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

H1H2H3H4H5H6H7H8H9H10H11H12H13H14H15H16

N1 N2N3N4N5N6N7N8N9

45

Influenza A HA and NA Subtypes

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

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, non-

productive cough, runny nose, headache.• GI symptoms and muscle inflammation

more common in young children50

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

conditionsNeuromuscular dysfunctionHeart diseaseAsthmaChronic lung diseaseLiver diseaseDiabetes 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 AmantadineOnly for Type A virusesCurrently not recommended for use due to resistance among

circulating influenza A viruses• Neuraminidase inhibitors

Oseltamivir (Tamiflu®) and Zanamivir (Relenza®)Type A and B virusesEmergence of global resistance to Oseltamivir in influenza A

(H1N1) viruses in 2007-0854

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 countriesExpanded from Asia to the Middle

East, Europe, and Africa• Largest epizootic of avian influenza

ever describedOver 200 million birds died or

destroyed58

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) virusesMost common influenza virus infection in birdsCauses mild clinical and

unapparent infectionsMay be any subtype (H1 to H16)

• Highly pathogenic AI (HPAI) virusesSome H5 or H7 virus strains to dateCauses severe illness in poultry and often deathLPAI H5 or H7 virus subtypes can mutate

into HPAI H5 or H7 virus subtypesUsually no symptoms or mild symptoms in wild birds

• Determined by molecular and pathogenicity criteria61

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-to-

human 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 AnimalsH5N1 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

65

Wild Water Fowl

Domestic Birds

Transmission Across Species

Influenza A subtypescirculate in wild birds which can then infect

domestic birds.

Wild birds arereservoir for Influenza A strains and are the source for viruses

infecting other species.

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 HumansYear 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

• Direct and close contact with sick or dead poultry• Slaughtering or cleaning poultry• Visiting a live poultry market

• No evidence of sustained person-to-person spread

• Limited probable person-to-person spread1

72

Human H5N1 Epidemiology

1 World Health Organization. NEJM 2008; 358:261-73.

Possible Mechanisms of International Spread • Legal poultry business• Illegal bird trade • Migrating birds • Humans (contaminated objects)• Untreated fertilizer

73

.

74

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 personCauses severe disease

• Essentially no pre-existing immunity; everybody at risk

Characterized by ability to change:• Continually (antigenic drift) → yearly

epidemics• Drastically (antigenic shift) → rare pandemics

75

Influenza Viruses

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-to-person spread)

77

Drift and Shift, Illustrated

78

79

Human virus

Reassortantvirus

Non-humanvirus

Re-assortment and Direct Transmission

DIRECT

Requirements for an Influenza Pandemic Virus• A new influenza A subtype virus emerges that

can infect humans AND

• Causes serious illnessAND

• Spreads easily from human-to-human in a sustained manner

80

Pandemic Influenza

81

• Timing unpredictable

• High sickness rates across age groups

• Increased mortalityHigher proportion of deaths in younger persons

Estimated Mortality from Previous Influenza Pandemics

82

• 1918-19 (H1N1)20 -50 million deaths

worldwide

• 1957-58 (H2N2)1 million deaths

worldwide

• 1968-69 (H3N2)1 million deaths

worldwide

Human Influenza • A public health problem

each year

• Usually some immunity built up from previous exposures to the same subtype

• Infants and elderly most at risk

• Result of Antigenic Drift

Influenza Pandemics• Appear in the human

population rarely and unpredictably

• Human population lacks immunity to a new influenza A virus subtype

• All age groups, including healthy young adults, may be at increased risk for serious complications

• Result of Antigenic Shift 83

Seasonal Epidemics vs. Pandemics

84

Timeline of New Influenza A Subtype Virus Infections in Humans

H1

H3H2

1918Spanish

Influenza H1N1

1957Asian

InfluenzaH2N2

1968Hong KongInfluenza

H3N2

1915 1925 1935 1945 1955 1965 1975 1985 1995 2005 2009

H7H5

Avian Influenza

H9

H1

1977Emergence

of H1N1

2003Emergence

of H5N1

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

• Seasonal Flu

• Avian Flu

• Pandemic Flu

• Occurred 3 times in the 20th century

• Outbreaks result from antigenic drift

• Usually does not infect people

86

Match each term to the statement that it best fits

Potential Strategies to Decrease the Impact of a Pandemic• Prevent or delay introduction, slow spread• Decrease morbidity and death

Vaccine when availableAntiviral treatment and isolation for people with illnessNon-pharmaceutical interventions

87

Weeks

Impact

Prepared

Unprepared

WHO Phases of a Pandemic

88http://www.who.int/csr/disease/avian_influenza/phase/en/index.html

WHO Phases of a PandemicInter-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-to- human spread

Phase 4: Small, localized clusters of human-to-human spread

Phase 5: Larger clusters, still localized; virus adapting to humans

Pandemic PeriodPhase 6: Increased and sustained transmission in the general population.

Post Pandemic PeriodRecovery phase

89

THANK YOU!