Lower Respiratory Tract Infections

Influenza Virus — Orthomyxovirus

• Genome is a RNA complement to the mRNA so must “transcribe” RNA genome into mRNA to make more virus

• Problem — cells cannot make RNA from RNA

• Solution — viruses bring own enzyme which is packaged within capsid

Influenza Classification System

• Strain A ( humans, birds, mammals )

• Strain B & C ( humans only )

• Classification includes:

  • Place of original isolation

  • Date of original isolation

  • N & H antigen types ( strain A only)

  • Animal host ( if needed )

• HA — Hemagglutinin, viral attachment protein, fusion protein, target of neutralizing antibody

• NA — Neuraminidase ( cleaves sialic acid and promotes virus release after budding )

  • To date, 16HA ( H1-16 ) & 9NA subtypes ( N1-9 ) have been found in IAVs isolated from aquatic birds

Influenza Virus Binding

• Transmission by respiratory droplet or contact

  • Virus can survive for 24 hours on surfaces

• IAVs initiate the infection process by using the HA molecules on the viral envelope to attach to surface glycoprotein / glycolipids that contain terminal sialic acid ( SA ) residues

• IAVs scan the cell surface for the proper “receptor” by using NA to remove local SAs and liberate nonproductive associations

  • Currently, the primary receptor is unknown

• HAs from avian IAVs have higher specificity for receptors with α-2,3-linked SAs, whereas HAs from human IAVs prefer an α-2,6 linkage

  • Mutations in the HAs of some IAVs permit binding to both equally well

Antigenic Shift & Antigen Drift

• Antigenic shift: reassortment of segments during coinfection with different strains

  • Responsible for major epidemics

  • Found in migratory ducks

• Antigen drift: nucleotide mutations in N and H genes resulting from error prone replication using RNA polymerase

Typical Course of Infection for Uncomplicated Influenza

• Incubation period — 1-5 days, depending on dose, immune status of host

• Abrupt onset — headache, chills, dry cough, high fever, myalgias, malaise, anorexia

• Fever peaks within 24 hr, 38-40 C

• Fever declines day 2-3, gone by day 6

• As fever declines, respiratory signs intensify

• Cough changes from dry to productive

• Cough, weakness can persist 1-2 weeks

Influenza Vaccine

• Flu shot — inactivated ( killed ) whole virus of the 3 or 4 most common strains ( 2 most common type A & 1 type B)

  • Currently, only the H1N1 & H3N2 subtypes, as well as the two antigenically distinct IBV lineages (Victoria & Yamagata), are endemic in the human population, which is why many IAV vaccines include two representative IAV & IBV strains

• Flu mist — live attenuated virus containing three different H & N proteins. Capable of stimulating mucosal secretory Ab

• Why get vaccinated?

  • Antigen shift / drift

  • Flu vaccine is used to produce high levels of circulating antibody during flu season

    • Because influenza has an extremely short incubation period

    • People may shed virus to others before knowing they are ill

Tuberculosis

• Often referred to as consumption

• Symptoms:

  • Coughing

  • Pallor (paleness)

  • Lungs fill fluid & blood

  • Spitting / coughing of blood

• 2 billion people infected world-wide, 8 million active cases per year, 3 million deaths per year

• Increase in TB today:

  • Deterioration of public health facilities

  • Increase in homeless or group housing

  • Increase in immigrants from endemic areas

  • Mostly HIV / AIDS

Mycobacterium tuberculosis

• Most of the virulence factors are associated with the survival of the bacteria in the host

  • Particularly survival within phagocytic cell by blocking maturation of the endosome

    • Lysosomal fusion, acidification, etc

• A small infectious dose can be cleared without complication; a larger dose survives phagocytosis and replicates within macrophages

  • Tubercles result from a cell-mediated immune response causing granuloma formation followed by fibrin coating and calcification

• Socioeconomic status, malnutrition, immune status, & number of mycobacteria all play a role in how the infection progresses

• Mantoux test

  • Tuberculosis protein injected into forearm

  • If negative, small red bump

  • If positive, large red swollen bump

BCG Vaccine

• Uses a weakened Bovine Strain

• Efficacy uncertain — depends on vaccine variation and geography

• Can cause skin test conversion eliminating screening method so not used in US, but recommended in countries were TB is endemic

• Several newer vaccines are currently in trials to use alone or in conjunction with BCG

Typical Pneumonia

• Cough, chest pain, fever

Streptococcus pneumonia

• Common cause of community-acquired pneumonia

  • Morphology: lancet shaped diplococci

  • Habitat: nasopharynx

  • Transmission by respiratory droplets

• Key virulence factors

  • Polysaccharide capsule blocks phagocytosis

  • Pneumolysin is a pore-forming toxin that lyses white blood cells

  • IgA protease cleaves the secretory antibody

Pneumococcal (streptococcus pneumoniae) pneumonia

• First colonize mouth / throat

• Entry into lung by aspiration of fluid from mouth

  • Requires breakdown of host defenses

  • Smoking, alcoholism, binge drinking, other infections (pertussis)

• Quickly multiply, cannot be phagocytized

• Inflammation and outpouring of fluid, fibrin, PMN

• Decreased area for gas exchange

Other Causes of Typical Pneumonia

• Staphylococcus aureus (G+ cocci) is associated with hospital acquired pneumonia

• Klebsiella pneumoniae (G- rod) causes pneumonia primarily in alcoholics and those with impaired pulmonary systems

Atypical Pneumonia

• Insidious onset, cough, headache, myalgia (influenza-like symptoms)

  • Legionnaires disease (legionella)

  • Walking pneumonia (mycoplasma)

  • Q fever (coxiella)

Legionella pneumophila

• Normally found in protozoa in water habitats

• Changes in technology have aerosolized the bacteria which can be breathed into the lungs

• Named after initial outbreak; American legion convention 1976

  • Many of the mechanisms used by bacteria to survive in protozoa are used for the bacteria to live inside the phagocytes that should protect our lungs

Coxiella-Q Fever

• A flu-like sickness caused by the germ Coxiella burmetii

• Carried by animals

  • Complications can occur in those with heart / vascular conditions or immuno-compromised

  • Endocarditis / myocarditis