Respiratory System Infections pt2

Mycobacterium tuberculosis

  • Corded growth.
  • LM 5 μm.

Antibiotic Resistance

  • Selective advantage of antibiotic resistance.
  • Antimicrobial drug is added; sensitive organisms are killed or inhibited.
  • Resistant survivors can multiply without competition.

Influenza (The Flu)

  • Causative agent: Influenza virus.
  • Epidemiology: ~500,000 hospitalizations and ~30,000-35,000 deaths in the U.S. each year.

Influenza Pathogenesis

  • 4 types of Influenza: A, B, C, D (A & B are significant types).
    • Type A: divided into sub-types (based on 2 surface proteins) = 131 sub-types detected in nature.
    • Only one linked to Pandemics!
    • Sub-types divided up into strains
  • Virus antigens (spike proteins):
    • Hemagglutinin (H): required for attachment.
    • Neuraminidase (N):
    • Used by virus to penetrate mucous layer.
    • Required for budding.

Influenza Significance

  • Antigenic drift:
    • Small changes in H or N antigens, due to random mutation of genes.
  • Antigenic shifts:
    • Major changes in H or N antigens.
    • Due to genetic recombination: genetic info is “shuffled”.

Influenza Virus

  • N spike.
  • Capsid layer.
  • H spike.
  • Envelope.
  • 2 of 8 RNA segments in genome.
  • 25 nm.

Influenza Virus Binding

  • Influenza virus binds to respiratory tract cells.
  • Hemagglutinin (HA) surface proteins bind to sialic acid receptors on the surface of human cells like a key to a lock.
  • The influenza virus is then able to enter and infect the cell, marking the beginning of a flu infection.

Antigenic Drift and Shift

  • Antigenic drift: Mutation in H and N antigens.
  • Antigenic shift: Reassortment of genome segments.

Influenza Prevention & Treatments

  • Transmission: Mucous droplets.
  • Prevention:
    • Influenza vaccine: given yearly.
    • Flu shot: Inactivated, whole virus.
    • FluMist.
  • Treatment:
    • Block uncoating of virus: Amantadine and Rimantidine (H1N1-resistant to both).
    • Block neuraminidase (viral release): Zanamivir (Relenza) and Oseltamivir phosphate (Tamiflu).

FluMist (Nasal Spray)

  • Live, attenuated vaccine.
  • More effective in children than flu shot.

Prevention Tips

  • Cover nose and mouth when you cough or sneeze.
  • Wash your hands!!!
  • If you feel ill, stay home!!!!
  • Avoid touching your eyes, nose, or mouth.

Bacterial Pneumonia

  • Top 10 cause of death in the U.S.
  • Predisposing factors:
    • Prior viral infection - cold or influenza.
    • Exposure to pollution.
    • Smoking.
    • Poor nutrition, alcoholism, drug use.
    • Other health problems - heart, lung, etc.

Pneumococcal Pneumonia

  • Causative agent: Streptococcus pneumoniae (the most lethal cause of pneumonia).
    • 90 serotypes! (distinct variations w/in the species)
  • Epidemiology: normal microbiota in 20-40% of healthy children! (5-10% of healthy adults); Predisposing factors: Influenza, diabetes, heart or lung disease, alcoholism, drug use.
    • Children have high carriage rate! (peaks at 1-2 yrs.!) Incubation period is short!
  • Transmission: Bacteria is inhaled deep into lungs or mucous droplets from another carrier (health care workers!).

Pneumococcal Pneumonia Signs/Symptoms

  • Sudden onset!:
    • Cough, fever, sharp chest pain, “Productive” cough – pink or rust-colored sputum produced; Shaking chills; shortness of breath.
  • Pathogenesis:
    • Capsule prevents phagocytosis, inflammation in lungs, fluid accumulation & edema builds up in lung tissue (visible on chest x-ray).

Streptococcus pneumoniae

  • Cytoplasm, cell wall, cell membrane, capsule.

Pneumococcal Pneumonia Details

  • Infants/Elderly: tend to develop bronchial pneumonia vs. lobar pneumonia.
  • Complications: Invasive pneumococcal infection:
    • Endocarditis, Meningitis (leading cause of death in kids under 5 yrs.; highest mortality rate among pneumococcal infections! ~40%!), Septicemia.

Consolidation in Pneumonia

  • Consolidation: Replacement of air in lungs with fluid, pus, cells, etc.
  • Pneumonia vs. Normal Chest X-Ray.

Pneumococcal Pneumonia Prevention & Treatment

  • Prevention: Pneumococcal vaccine.
    • PCV13 or Prevnar 13 can begin as early as 2 months (4 dose series); prevents “invasive” disease & otitis media.
    • Adults 65 yrs. & older & “high risk” persons 2-64 yrs. : PPSV23 (Pneumovax).
  • Treatment: Penicillin or erythromycin.
    • Note: Antibiotic resistance has increased markedly in the last 10 years!!!
    • Antibiotic susceptibility testing needed to ID best treatment.

Other Bacteria that Cause Pneumonia

  • Haemophilus influenzae
  • Klebsiella pneumoniae
  • Mycoplasma pneumoniae- "walking pneumonia"

COVID-19 (Coronavirus Disease of 2019)

  • Causative agent:
    • Family= Coronaviridae; Species= Severe acute respiratory syndrome related coronavirus
    • Subspecies: Severe acute respiratory syndrome coronavirus 2 (designates a particular strain)
  • Epidemiology:
    • Zoonotic origins: close genetic similarity to bat coronaviruses.
    • Aside from bats; it’s unclear which animals are infected- a tiger at an NY zoo got infected (1st reported).
    • Novel virus= 1st isolated in Wuhan, China.
    • Coronaviruses- 1st isolated in 1930s in chickens!
    • Vary a lot in lethality: some linked to common cold (15% of cases); where as other strains are more “severe”.
    • SARS-CoV= outbreak in 2003; ~10% mortality rate (higher in elderly).
    • MERS-CoV= novel virus; appeared in 2012; affecting Middle Eastern countries; 1st reported in Saudi Arabia; Reservoir= Camels; ~34% mortality rate!

COVID-19 Viral Structure

  • Enveloped; single stranded RNA virus.
  • Rather large in size: 50-200 nm in diameter.
  • Viral envelope contains 3 proteins: M protein; E protein; and S (spike) protein.
  • S protein= responsible for attachment & fusion of virus & gives “distinctive crown appearance”.
  • The death to case ratio (Johns Hopkins)= 6.6% as of May 2020 (other countries include “suspected” cases in statistics).

COVID-19 Transmission

  • Mucous droplets! (coughing; sneezing; singing; talking); more likely within 6 feet.
  • Droplets land on surfaces- fomites (Indirectly transferred to people); food is less likely vehicle.
  • More contagious than flu but less contagious than Measles.
  • Virus can be detected in stool= fecal/oral transmission less likely.
  • High viral load in sputum and saliva!
  • Asymptomatic persons can transmit virus.
  • Incubation time: 1-14 days (5 days).

COVID-19 Life Cycle

  • S or “spike” protein= attaches to receptor- enzyme called ACE2 (found in alveoli & GI tract- could be entry point); enzyme cleaves a hormone into a vasodilator.
  • Entry: fusion OR pinocytosis.
  • Viral RNA enters cytoplasm & immediately converted in viral proteins.
  • Virus utilizes ribosomes on rough ER.
  • Viral particles ‘bud’ off from Golgi (gather envelope there).
  • Release: Fusion (does not kill host cell).

COVID-19 Prevention

  • Wash hands with soap! Soap disrupts lipid layer!
  • Avoid crowds! Avoid ‘loud’ places!
  • Avoid touching eyes; nose; and mouth with dirty hands!
  • Stay in well ventilated areas.
  • Wear a cloth face mask= protects others if you are infected.
  • Proper use of Mask!
    • Do NOT touch mask while wearing it!
    • Avoid “gaps” between your face & the mask!
    • Make sure mask fits snugly on bridge of nose!
    • Treat the FRONT of your mask as being contaminated!
    • Do not REMOVE mask by touching the mask! Grab it from behind!

Measles or Rubeola

  • Causative agent: Morbillivirus (formerly called Measles virus).
  • Epidemiology:
    • Humans are the only reservoir.
    • “Acute” viral respiratory illness & highly contagious!
    • In 2000; measles was eliminated from the U.S. (meets standard if eliminated for 12 months or longer).
    • “risk” factors: include international travel & exposure to international airports!

Measles or Rubeola Transmission

  • Direct Contact (mucous secretions OR airborne via mucous droplets) or Aerosols (up to 2 hours!).
  • Signs/Symptoms:
    • Fever- increases to 103-105ºF.
    • 3 “C”’s= cough, coryza (runny nose), conjunctivitis (prodromal period).
    • Koplik’s Spots: clustered white lesions (cheek mucosa).
    • Maculopapular rash (5-6 days); begins around hairline/face & then spread towards limbs= flat & reddened with elevated bumps.

Measles or Rubeola Complications

  • Common Complications (30% of time):
    • Diarrhea (most common); otitis media; pneumonia (linked to most deaths).
  • Rare Complications:
    • Acute encephalitis (seizures) or SSPE (subacute pan encephalitis)- persistent infection of brain (on avg. 7 yrs. after infection)- NO CURE.
    • SSPE- Causes behavioral changes & fatal w/in 1-3 yrs. of diagnosis.

Measles or Rubeola Treatment & Prevention

  • Treatment: NONE; manage symptoms.
  • Prevention:
    • 1 measles virus vaccine in US.
    • Live; very attenuated (compared to previous formulations).
    • High protection rate even afer 1st dose in kids.
    • 2 shots (1st shot can’t be given before 1st birthday).
    • Shot is SAFE for person’s with egg allergy!