Professional Documents
Culture Documents
Principles of Infectious Disease Epidemiology / EPI 220 UCLA School of Public Health / Department of Epidemiology Instructor: Layne / Fall 2008
Principles of Infectious Disease Epidemiology / EPI 220 UCLA School of Public Health / Department of Epidemiology Instructor: Layne / Fall 2008
GENERAL
Acute respiratory infections kill 4,000,000 annually worldwide.
SUMMARY TABLE
__________________________________________________________
Type Anatomic Etiology Peak age Mortality
Diagnosis (months)
__________________________________________________________
Upper Pharyngitis Viral No
Respiratory
Otitis media Bacterial 6-7 No
–1–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
United States
Respiratory disease accounts for 75 - 80% of acute morbidity.
80% of respiratory diseases are viral.
On average, there are 3 - 4 respiratory illnesses per year per person.
Seasonality of respiratory illnesses.
Lowest in summer and highest in winter.
–2–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
INFLUENZA
GENERAL
Influenza A — epidemics vs pandemics
In "epidemic" years, 10% - 20% of world’s population gets influenza.
Associated with 500,000 to 1,000,000 deaths worldwide.
Caused by genetic “drifts”
Point mutations in gene segments: H1 ---> H1
Nomenclature
A / Swine / Iowa / 15 / 30 (H1 N1)
type / host / location / strain number / year (H and N subtypes)
–3–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
CLINICAL FEATURES
Acute influenza A syndrome
Incubation period is brief, ~2 days.
Onset of symptoms is abrupt, develops over a few hours.
Illness reaches maximum severity fast, within 6 - 12 hours
Bacterial superinfections
Most common complication of influenza infection
Occurs during the acute or convalescent phase
Associated with worsening of patient’s condition
Most common bacteria include
Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
–4–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
Reye’s syndrome
Develops 2 - 12 days after viral infection.
Severe fatty infiltration of liver.
Cerebral edema
Associated with aspirin use
2. Superinfections
Bacterial pneumonia
Disseminated bacterial infections
EPIDEMIOLOGY
Influenza A circulates in three major pools of animals.
In humans, infection spread by respiratory-droplet route.
In wild birds, infection spread by fecal-oral route.
In farm animals, infection spread by both routes
Swine (respiratory-droplet)
Chickens and ducks (fecal-oral)
Seasonality
Higher rates of infection in winter months.
Reason for seasonal cycles is unclear.
Seasons in Southern and Northern Hemispheres are 6 months apart.
–5–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
Epidemics
Involve 10% - 20% of world’s population.
Kill 500,000 to 1,000,000 people yearly.
Predictable, yearly.
Driven by “drift” mutations.
Changes confined to hemagglutinin (H) and neuraminidase (N).
Pandemics
Involve more than 25% of world’s population.
Number of deaths varies.
Unpredictable, sporadic.
Driven by “shift” mutations.
Adaptation of animal-like to human-like strains.
Adaptation involves all 8 gene segments (polygenic selection).
Pandemics
__________________________________________________________
Year Subtypes Name Excess Mortality
1890 ? — —
1900 ? — —
1918 H1 N1 Spanish flu 40,000,000
1957 H2 N2 Asian flu 70,000
1968 H3 N2 Hong Kong flu 31,000
1977 H3 N2 and H1 N1 — 32,000
*pandemic potential
–6–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
PATHOGEN’S FEATURES
Orthomyxoviruses
Influenza A and B
Enveloped and Pleomorphic
8 gene segments code for 10 proteins
Single-stranded RNA viruses (13.6 kB)
RNA exhibits high mutation rates
–7–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
Pathogenesis (Humans)
Influenza invades respiratory epithelium.
Viral particles are directly toxic.
Impairs mechanical and cellular host responses.
Elicits acute inflammatory response
Leads to ciliary abnormalities.
Desquamation of ciliated and mucus-producing cells.
Loss of mechanical clearance of respiratory tract (no escalator).
Normal respiratory epithelium restored 2 - 10 weeks after infection.
–8–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
Humoral immunity
Anti-hemagglutinin antibody is most protective.
Anti-neuraminidase antibody is second most protective.
Anti-channel antibody is third most protective.
Laboratory Characterization
Typing
Influenza A
Influenza B
Subtyping (Influenza A only)
H1 - H16
N1 - N9
Immunologic relatedness
Hemagglutinin (binding) inhibition assays
Neuraminidase (enzyme) inhibition assays
PREVENTION
Vaccines are the only way to manage influenza’s impact worldwide.
Current inactivated vaccines are trivalent (two A types viruses and one B type).
300 million doses of inactivated trivalent vaccine manufactured yearly.
Vaccinate high-risk populations
People over 55 years of age
People with respiratory / cardiovascular illnesses
Growing evidence that children may benefit from influenza vaccination.
Live attenuated (intra-nasal) vaccine also licensed in United States.
Antiviral drugs have a limited role for small populations.
Inactivated vaccines
Single annual dose prior to each influenza season.
Guillain-Barré syndrome develops in 1 per 100,000 doses
Vaccine efficacy in elderly people (≥ 65 years)
22% (15 – 28) respiratory disease
27% (21 – 33) preventing hospitalization
24% (18 – 30) cardiac disease
47% (39 – 51) all-cause mortality
–9–
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
Antiviral agents
AMANTADINE
RIMANTADINE
Both oral agents
M2 protein antagonist
Must be given within 48 hours of onset of symptoms
Short-term (weeks) prophylaxis against influenza A
Exposure ---> give AMANTADINE plus VACCINE
Antiviral drug protects until vaccine induces immune response
Effectiveness against pandemic strains ?
Resistance increasing (>90% North America)
ZANAMAVIR*
OSELTAMIVIR**
Inhalation* and oral** agents
Neuraminidase competitive inhibitor
Must be given within 24 – 48 hours upon onset of symptoms
More expensive than AMANTADINE
Effectiveness against pandemic strains ?
Resistant strains after treatment
Treatment
Symptomatic care
Rest
Adequate fluid intake
Analgesics
Antitussives
Start AMANTADINE within first 12 - 24 hours of illness
Bacterial superinfections
Antibiotic prophylaxis is of little benefit
Does not reduce the likelihood of complications
– 10 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
– 11 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
– 12 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
BOTTOM LINES
Faster surveillance is needed.
READING
• Tubenberger JK, Morens DM. 1918 Influenza: the Mother of All Pandemics.
Emerging Infectious Diseases 2006; 12: 15 – 22.
– 13 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 1
– 14 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 2
– 15 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 3
– 16 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 4
– 17 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 5
– 18 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 6
– 19 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 7
– 20 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 8
– 21 –
Principles of Infectious Disease Epidemiology / EPI 220
UCLA School of Public Health / Department of Epidemiology
Instructor: Layne / Fall 2008
FIGURE 9
– 22 –