Class 4- ARIs

Question 1

Influenza Virus

Answer 1

Reservoir: primarily humans, other animals play a role as recombinant hosts

• Birds carry avian strains, which can jump to humans via recombination

Route: airborne person to person, direct contact (kissing) indirect contact (fomites contaminated with respiratory mucosa)

• Virus may persist on solid services for hours, particularly in lower temperatures and lower humidity (Hence the seasonal aspect of transmission)

Incubation: 2 days after infection

Signs and symptoms: fever, cough (usually dry), headache, myalgia, sore throat, rinnorrhea (runny nose), and gastrointestinal symptoms in children.

Communicability: greatest in the first 3-5 days of illness More commonly – secondary bacterial pneumonia may occur up to 2 weeks after acute viral infection.

Question 2

Where does recombination most commonly occur

Answer 2

In pigs. They can be infected with both Human and Avian strains. DNA is able to self-detect and delete mutations.

RNA infections are much more dangerous because it can’t correct mutations and therefore can change much more frequently

Question 3

Number of annual deaths due to influenza

Answer 3

Global total of 250,000 – 500,000 deaths per year

• In developed countries more than 50% of excess hospitalizations and more than 80% of influenza related deaths occur in people over the age of 65 30-
• 50x greater mortality than younger adults and adolescents Attack rates of 10%-30%

Question 4

How is influenza classified?

Answer 4

Classified as epizootic which means… - Present in animal population- Specifically birds!

Question 5

How many types of influenza are there?

Answer 5

Three virus types of influenza – A, B, & C

Question 6

When was influenza first cultured and studied?

Answer 6

First virus to be cultured and studied 1933

Uses nasal or throat secretions

• Must be done within 3 days of onset. That is when you have the highest viral count

Question 7

Spanish Flu

Answer 7

Attack rate of 20%- 30% in adults and 30-45% in children

• Noted for the high case fatality rate in adults (15%-50%)

Estimated 20-50 million persons died in a single year from pandemic

• Most likely a major underestimate
  
  • Africa and Asia fatalities were reported by colonial authorities

Question 8

Why was the Spanish Flu the “perfect storm of influenza outbreak?

Answer 8

Occurred at the end of World War I

• increased travel
• crowding
• unsanitary conditions

Particularly virulent strain of influenza that year

• Little to no prior immunity
• Influenza vaccines didn’t start until 1943

Question 9

Influenza in tropical and subtropical regions

Answer 9

Historically under-reported

• Lack of laboratories to confirm cases
• Reporting bias that artificially reduce estimates
• Presumptive diagnosis with tropical disease
• Studies suggest rates are 5 times higher in tropical/subtropical regions than the US

Limited vaccine usage

• Multiple strains (have exposure to North and South hemisphere strains) lead to year round transmission! Implications
• Hemisphere specific vaccines may not be suitable in subtropics regions

Question 10

The role of viral surface glycoproteins

Answer 10

HA (Hemagglutinin)

• Viral attachment to cell membranes
• Major antigentic and virulence determinant
  
  • 5 specific antigenic epitope
    
    • Antibodies to one of the 5 epitopes provides protection degree of protection against different variations of Influenza

NA (Neuraminidase)

• Allows virus to release from host epithelial cells Influences in host spread of virus

Question 11

Hemagglutininn (HA)

Answer 11

Antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected.

Question 12

Neuraminidase

Answer 12

Enzymes that cleave the glycosidic linkages of neuraminic acids

Question 13

Immune responses to influenza

Answer 13

IgM short term antibodies

IgG long lasting antibodies

If exposed to a disease a second time, less IgM antibodies are acutely created compared to the first exposure because the long lasting IgG antibodies are already in your body at a high level

A change from negative to positive antibody status is known as seroconversion and indicates infection. A four-fold rise in antibody titre between acute and convalescent samples can also indicate infection by the specific pathogen.

Question 14

Antigenic Shift and Drift

Answer 14

Antigenic Drift

• minor antigen changes through mutations, hence changes in annual flu vaccine
• Think of a ramp. Slight changes over time
  
  • Easier to track and vaccinate against

Antigenic Shift

• Comprises major change in HA, NA, or both, through reassortment
• Think of steps. Dramatic changes in short periods of time
  
  • More difficult to track and vaccinate against
  • The fewer RNA bps the more susceptible viruses are to pathogenic mutations.
    
    • 2^8 (genome sequences) variants of Influenza or 256 variants

Question 15

What role do pigs play in reassortment?

Answer 15

Reassortment occurs in pigs because they can be infected with both avian and human strains of influenza. Most new variants do not have a survival advantage and die out

Question 16

What makes a shift pandemic?

Answer 16

1. Virus retains the ability to replicate well in humans
2. Efficient transmission
3. Has new surface HA or NA determinants that evade existing antibody profiles

Question 17

Duration and magnitude of exposure influences on disease

Answer 17

The duration of exposure greatly influences disease outcomes.

• Longer exposure = increased likelihood of infection/development of chronic disease

Same concept applies for magnitude/dose.

• Higher dose= higher risk of adverse events/increased likelihood of infection
• Consider infectious diseases, the longer you are in a room with someone household secondary infections of influenza vs chance encounter. The more time you are around infectious individuals the higher risk you have of becoming infected. Can be influenced by pathogen and host characteristics, environmental factors, and behaviors

Question 18

Tamaflu and other Tx

Answer 18

Tamaflu is a Nuraminadase (NA) inhibitor

• Can reduce duration of symptoms and communicability by 1 day.
• If taken prophylacticly – 70 to 90% effective in preventing illness during influenza A epidemics.

NA facilitates in-host spread of virus (virema)

Question 19

Common Respiratory infections

Answer 19

1. Bronchiolitis
2. Bronchitis
3. Laryngitis
4. Measles
5. Otitis media
6. Pertusis
7. Pharyngitis
8. Pneumonia
9. Sinusitis

Account for 18% of all deaths worldwide among children younger than 5

8.2% of all disability and premature mortality

Question 20

ARI overview

Answer 20

Major cause of morbidity and mortality among infants and children. ARI’s account for an estimated 2 million deaths per year (2009)

• Developing countries where infant mortality exceeds 25 per 1,000 have:
• 98% of the worlds deaths from ARI
• 99% of those deaths in children aged 1-4

Question 21

Two major respiratory pathogens responsible for ARIs

Answer 21

1. Streptococcus pneumoniae
2. Haemophilus influenza group B (HiB)

Question 22

ARI Morbidity vs. Mortality

Answer 22

Developed vs developing countries:

• Unlike mortality, share similar morbidity of ARIs
• Worlds apart when it comes to mortality.
  
  • 98-99% of child ARI deaths occur in developing countries
  • In developed countries ARIs are the leading cause of morbidity
    
    • Accounting for:
      
      • 20% of medical consultations
      • 30% of absences from work

75% of antibiotic prescriptions Introduction of better hygiene penicillin, sulfa drugs, and other antibiotics have helped reduce pneumonia related mortality in the US

Question 23

Viral agents responsible for ARIs

Answer 23

1. Adenoviruses
2. Coronaviruses
3. Enteroviruses
4. Influenza
5. Parainfluenza virus 1, 2, and 3
6. Respiratory syncytial virus
7. Rhinoviruses

Question 24

Common characteristics of viral respiratory infections

Answer 24

Viral diseases of the respiratory tract may be characterized by fever, cough, increased respiratory rate, chills, headache, general aching, malaise, anorexia, occasional GI disturbances

Symptoms usually subside within 2-5 days In adults viral causes of pneumonia are generally less important than nonviral causes

Concerns of complications from secondary bacterial infections

Question 25

Why is it difficult in pinpoint the cause of respiratory symptoms for viruses?

Answer 25

Often can be nonspecific

Vary from person to person

Attack rates can be influenced heavily by strain characteristics

Limited by lab techniques to isolate pathogen

• Viral isolation only occurs from 20-25% of specimens in several well conducted studies!
• The causes of about half of common colds has not been identified

Question 26

Acute viral Rhinitis – common cold

Answer 26

Reservoir- humans

Route- direct contact or inhalation of airborne droplets

Incubation – 12 hours to 5 days

Symptoms – coryza (inflamation of mucosal membranes in the nose), sneezing, chilliness, malaise (fever is uncommon in children over 3), for 2-7 days

• No fatalities associated with virus

Communicability- up to 24 hours before symptoms, and 5 days after onset

Over 100 recognized serotypes of Rhinoviruses

Question 27

Respiratory syncytial virus (RSV) impact

Answer 27

Pronounced: syn·cy·ti·al

Can cause upper respiratory infections (such as colds) and lower respiratory ract infections (Bronchiolitis and pneumonia).

2.1 million children under age 5 seek medical attention each year in US

• RSV is the most common cause of bronchiolitis and pneumonia is children < 1
  
  • Almost all children will have had RSV by their second birthday
  • After first exposure 25-40 of 100 will have signs or symptoms of a lower respiratory infection
  • 5-20 out of 1,000 will require hospitalization (most are under 6 months)

Question 28

RSV overview

Answer 28

Reservoir- Humans

Transmission- airborne, from direct (like kissing) and indirect (hand-door-nose/eyes) contact with nasal or oral secretions from infected people

• Can survive on hard surfaces like crib rails and tables for many hours

Incubation- 4-6 days

Symptoms- runny nose and decrease in appetite, coughing, sneezing, and fever

Communicability – 3 to 8 days after infection (as long as 4 weeks)

• Generally occur during November to April with peak occurring Jan- Feb Visits to healthcare providers for RSV are common.
• There is no specific treatment for RSV infections.

Question 29

Community-acquired pneumonia (CAP)

Answer 29

Pneumonia is a bacterial respiratory infection

• Community-acquired pneumonia (CAP) is one of the most common infectious diseases and is an important cause of mortality and morbidity worldwide.

Typical bacterial pathogens that cause the condition: -

• Streptococcus pneumoniae (penicillin-sensitive and -resistant strains)
• Haemophilus influenza (ampicillin-sensitive and -resistant strains)
• Moraxella catarrhalis (all strains penicillin-resistant).

Pathogen responsible is identified in less than 10% of cases

• A shift from identify and treat to broad-spectrum antibiotics may result in unnecessary antibiotic use

Question 30

Bacterial respiratory infection agents

Answer 30

1. Haemophilus influenza
2. Legionella sp.
3. Staphylococcus aureus
4. Streptococcus pneumoniae

Question 31

Pneumococcal Pneumonia

Answer 31

Causative agent- Streptococcus pneumoniae

Reservoir- Humans, often found in upper respiratory tract of healthy humans

Route – Droplet spread

Incubation – Not well determined, expected 1-3 days

Symptoms – sudden onset, high fever, rigors, pleuritic chest pain, dyspnea, cough productive of “rusty” sputum. Onset may be abrupt especially in elderly.

Communicability – until symptoms resolve or within 24 hours after effective antibiotic therapy

Case fatalities varies widely from 5%-35% depending on the setting (community vs. hospital) and population (HIV, smoking status, age)

Question 32

Pneumonococcal vaccine

Answer 32

23-valent vaccine

Recommended for children under the age of 5, elderly over 65, and at risk populations

Question 33

Haemophilus influenzae type B (Hib)

Answer 33

Reservoir- Human

Route – airborne through respiratory droplets

Incubation – unknown

Symptoms- Fever, neck stiffness, not as alert as usual, inflammation of the throat, joint infection, pneumonia

Communicability- varies, unless treated, its transmissible as long as organism is present in the nose and throat (even after symptoms have disappeared)

• If untreated 1 in 20 children with Hib will die.
• Vaccine preventable

Question 34

Staphylococcal Pneumonia

Answer 34

Staphylococcus aureus

Reservoir – Humans

Route- hands are the most important instrument for transmission, airborne transmission is rare Incubation period- variable/indefinite

Symptoms- pneumonia, lung abscess, osteomyelitis, sepsis

Communicability – as long as infected… Resistant to penicillin and other antibiotics

Question 35

Susceptibility Factors- ARIs

Answer 35

Age - The very young and old are most vulnerable

Gender - Mothers experience more upper respiratory illnesses than husbands, but not more lower respiratory illness

• Mothers are around the kinds more often

Environment

• Air pollution, Smoking, Crowding

Nutrition

SES

Meteorological factors

• Epidemics of ARIs are linked with low temperature, humidity and perciptation

Pneumocystis pneumonia (PCP)

• most common opportunistic infection in HIV.
• 85% of HIV infected people will develop PCP Antibiotic resistance