Class 4- ARIs Flashcards
Influenza Virus
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.
Where does recombination most commonly occur
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
Number of annual deaths due to influenza
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%
How is influenza classified?
Classified as epizootic which means… - Present in animal population- Specifically birds!
How many types of influenza are there?
Three virus types of influenza – A, B, & C
When was influenza first cultured and studied?
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
Spanish Flu
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
Why was the Spanish Flu the “perfect storm of influenza outbreak?
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
Influenza in tropical and subtropical regions
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
The role of viral surface glycoproteins
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
- 5 specific antigenic epitope
NA (Neuraminidase)
- Allows virus to release from host epithelial cells Influences in host spread of virus
Hemagglutininn (HA)
Antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected.
Neuraminidase
Enzymes that cleave the glycosidic linkages of neuraminic acids
Immune responses to influenza
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.
Antigenic Shift and Drift
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
What role do pigs play in reassortment?
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
What makes a shift pandemic?
- Virus retains the ability to replicate well in humans
- Efficient transmission
- Has new surface HA or NA determinants that evade existing antibody profiles
Duration and magnitude of exposure influences on disease
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
Tamaflu and other Tx
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)
Common Respiratory infections
- Bronchiolitis
- Bronchitis
- Laryngitis
- Measles
- Otitis media
- Pertusis
- Pharyngitis
- Pneumonia
- Sinusitis
Account for 18% of all deaths worldwide among children younger than 5
8.2% of all disability and premature mortality
ARI overview
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
Two major respiratory pathogens responsible for ARIs
- Streptococcus pneumoniae
- Haemophilus influenza group B (HiB)
ARI Morbidity vs. Mortality
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
- Accounting for:
75% of antibiotic prescriptions Introduction of better hygiene penicillin, sulfa drugs, and other antibiotics have helped reduce pneumonia related mortality in the US
Viral agents responsible for ARIs
- Adenoviruses
- Coronaviruses
- Enteroviruses
- Influenza
- Parainfluenza virus 1, 2, and 3
- Respiratory syncytial virus
- Rhinoviruses
Common characteristics of viral respiratory infections
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
Why is it difficult in pinpoint the cause of respiratory symptoms for viruses?
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
Acute viral Rhinitis – common cold
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
Respiratory syncytial virus (RSV) impact
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)
RSV overview
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.
Community-acquired pneumonia (CAP)
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
Bacterial respiratory infection agents
- Haemophilus influenza
- Legionella sp.
- Staphylococcus aureus
- Streptococcus pneumoniae
Pneumococcal Pneumonia
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)
Pneumonococcal vaccine
23-valent vaccine
Recommended for children under the age of 5, elderly over 65, and at risk populations
Haemophilus influenzae type B (Hib)
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
Staphylococcal Pneumonia
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
Susceptibility Factors- ARIs
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
