Respiratory System Infections

Pharyngitis

• Group A Disease (Streptococcus pyogenes)

Strep Throat (Streptococcal Pharyngitis)

• Causative Agent: Streptococcus pyogenes (GAS) or Group A Streptococcus.
• Characteristics:
  • Gram +.
  • Streptococcus arrangement.
  • Positive for beta-hemolysis on blood agar plate.
• Primary Reservoir: Humans.
• Signs/Symptoms:
  • Pharyngitis.
  • Red patches on throat.
  • Fever.
  • Swollen lymph nodes.
  • Tonsils develop pus-filled lesions.
  • Throat pain.

Strep Throat (Streptococcal Pharyngitis)

• Pathogenesis: Virulence factors
  • C5a protease: Degrades complement.
  • Capsule: Prevents phagocytosis.
  • M-protein: Resists phagocytosis; can mimic host cell proteins & trigger autoimmunity.
  • Streptolysins O and S (hemolysins): Lyse WBCs and RBCs.

Strep Throat (Streptococcal Pharyngitis)

• Complications:
  • Scarlet fever:
    • 2 days after pharyngitis a diffuse rash appears, initially on chest).
    • Strawberry tongue.
    • Streptococcal pyrogenic exotoxins cause severe complications (toxins acquired via bacteriophage infection).
    • Toxin attacks membrane of capillary endothelial cells.

Strep Throat (Streptococcal Pharyngitis)

• Non-Toxin Mediated Complications:
  • Acute glomerulonephritis
    • Immune complexes (IgG & Ag) get deposited in Glomeruli.
  • Rheumatic fever (inflammatory disease affects joints, heart, skin- more rare)
    • M-protein mimics cardiac myosin protein (Ages: 6-15 yrs.).
  • Flesh-eating strep (due to skin infection; NOT pharyngitis)

Strep Throat (Streptococcal Pharyngitis)

• Epidemiology: Transmission via respiratory droplets or saliva.
  • Epidemics via carriers.

Tuberculosis

• Causative agent: Mycobacterium tuberculosis
• Characteristics: Acid fast rods (cultures must be kept for 8 weeks to confirm if negative!; long

Tuberculosis Epidemiology

• Major infectious disease!
• 30% of world’s population infected
• 3 million deaths per year
• HIV & TB are the 2 most common causes of death from infectious disease!
• Diabetes is most common risk factor for TB
• TB is the leading killer of those living with HIV

Tuberculosis

• Epidemiology
  • Transmission: Mucous droplets & aerosols
  • Approximately 1/3 of the world’s population infected; ≈10% develop active TB in their lifetime
  • HIV+ have an increased risk of active TB disease; is leading cause of death in HIV+
  • Most cases in U.S.:
    • Immigrant population
    • AIDS patients
    • Alcoholism is risk factor

Pathogenesis

• Resistance to digestion by phagocytes (mycolic acid) leads to systemic infection (NO TOXINS made!).
• Characterized by “tubercules” (Granulomas- small area of inflammation/nodules due to tissue injury- ‘walls off infection’ but live organism in center!) in the lung. Contain WBC’s (lots of macrophages!) & collagen. Can perforate blood vessels leads to blood in sputum.
• Majority of cases leads to granulomas form leads to Latent form of disease= “non-diseased” state
• “Active Disease”= Organisms can leave lungs & reinfect lungs and/or spread via circulatory system= Miliary Tuberculosis (lesions develop throughout the body)

Tuberculosis Stages

• Tubercle bacilli that reach the alveoli of the lung are ingested by macrophages, but some often survive. Infection is present, but no symptoms of disease.
• Tubercle bacilli multiplying in macrophages cause a chemotactic response that brings additional macrophages and other defensive cells to the area. These form a surrounding layer and, in turn, an early tubercle. Most of the surrounding macrophages are not successful in destroying bacteria but release enzymes and cytokines that cause a lung-damaging inflammation.
• After a few weeks, disease symptoms appear as many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. The aerobic tubercle bacilli do not grow well in this location. However, many remain dormant (latent TB) and serve as a basis for later reactivation of the disease. The disease may be arrested at this stage, and the lesions become calcified.
• In some individuals, disease symptoms appear as a mature tubercle is formed. The disease progresses as the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and forms an air-filled tuberculous cavity in which the aerobic bacilli multiply outside macrophages.
• Liquefaction continues until the tubercle ruptures, allowing bacilli to spill into a bronchiole and thus be disseminated throughout the lungs and then to the circulatory and lymphatic systems.

Prevention

• Bacille-Calmette- Guerin (BCG) vaccine
• Live, attenuated vaccine
• Derived from strain of Mycobacterium bovis
• Use in U.S.???

Mantoux Tuberculin Skin Test

• 0.1 mL of PPD (purified protein derivative; protein from M. tuberculosis)
• Memory T cells respond to antigen if patient was exposed (includes vaccinated patients)

Reading the Tuberculin Skin Test

• Read reaction 48-72 hours after injection
• Measure only induration
• Record reaction in millimeters

Classifying the Tuberculin Reaction

• ≥5 mm is classified as positive in
  • HIV-positive persons
  • Recent contacts of TB case
  • Persons with fibrotic changes on chest radiograph consistent with old healed TB
  • Patients with organ transplants and other immunosuppressed patients

Classifying the Tuberculin Reaction (cont.)

• ≥15 mm is classified as positive in
  • Persons with no known risk factors for TB
  • Targeted skin testing programs should only be conducted among high-risk groups

Diagnosis: Acid Fast Staining Procedure

• Differential Stain- steam is used!
• Stains for Mycobacterium genus
• Mycobacterium- appear pink!

Tuberculosis

• Treatment: 3+ antibiotics for 6 months
  • Isoniazid, ethambutol, rifampicin, & streptomycin
• Preventions: BCG vaccine (not used in U.S.), not an effective for adults
• Diagnosis: via TB skin test, chest x-rays, stain sputum

Demographics for Tuberculosis in the US

• TB case rates are 33x higher for Asian persons than White persons.
• Percentage of TB Cases by Race/Ethnicity, United States, 2020 (N=7,174)
  • Black/African American: 30%
  • Hispanic/Latino: 20%
  • White: 11%
  • American Indian/Alaska Native: 1%
  • Native Hawaiian/Other Pacific Islander: 2%
  • Multiple race: 1%
  • Asian: 36%
• Top countries of origin for TB cases among Asian persons:
  • Philippines: 12.5%
  • India: 10.4%
  • Vietnam: 8.2%
  • China: 5.1%
  • Myanmar: 1.6%

XDR-Tuberculosis in the US

• XDR TB= Extensively drug- resistant TB
• This type of TB= resistant 1st line of drugs used to treat TB (Rifampicin, Isoniazid) & some 2nd line drugs
• Why so dangerous?
  • Patients are left with less effective & more $$$ treatment options= high mortality rate

Microbial Resistance

• Microbes are constantly evolving to avoid antimicrobials made by other organisms!
  1. Intrinsic – Drug has no effect on microbe
     • Ex. Penicillin doesn’t kill Gram (-) bacteria
     • Antibiotics don’t work on viruses
  2. Acquired “developed” resistance: organism was previously “susceptible”
     • Due to mutation or new genetic element (plasmid)
     • How is resistance “acquired”? (conjugation, transformation, sharing plasmids)= also promotes “spread” of resistance
     • Lab tests help w/ monitoring Plasmids

How can microbes become resistant? (“usually” genetic changes)

1.  Inactivation of the antibiotic
    *   Ex. b-lactamase
2.  Alteration of target site (mutation in chromosome- Antibiotics don’t create this!)
    *   Ex. mutation in ribosome
3.  Decrease uptake of drug
    *   Ex. alteration in cell wall porin
4.  Increased elimination of drug
    *   Ex. efflux pumps

Influenza (The Flu)

• Causative agent: Influenza virus
• Epidemiology: ~500,000 hospitalizations; and ~30-35,000 deaths in the U.S. each year
  • The most LETHAL epidemic in history 1918 Spanish Flu (deaths primarily in young adults; NOT 65+)
• Signs / Symptoms:

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: Pathogenesis 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”
  • Account for major outbreaks of flu
  • Occur every 10-20 years
  • Rare event: 7 have occurred over last 100 years (includes: 1918 & 2009)
  • Can occur before vaccine is developed

Influenza Prevention & Treatments

• Transmission: Mucous Droplets
• Complications:
  • Reye Syndrome (esp. those under 18 yrs.; Aspirin has been implicated), pneumonia
• Prevention:

Influenza: Prevention

• FluMist (Nasal Spray)

More Prevention

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

Bacterial Pneumonia

• (top 10 cause of death in the U.S. across ALL age groups!)
• 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 leads to inflammation in lungs leads to fluid accumulation & edema builds up in lung tissue (visible on chest x-ray); pore forming toxin induces inflammation!

Pneumococcal Pneumonia

• 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

Pneumococcal Pneumonia

• 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. leads to 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 (Coronavirus Disease of 2019)

• 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 of Virus:
  • S or “spike” protein= attaches to receptor- enzyme called ACE2 (found in upper respiratory tract & GI tract- could be entry point);
  • Normal Function: enzyme cleaves a hormone into a vasodilator
  • Entry: fusion OR pinocytosis
  • Biosynthesis: viral particles replicate
  • 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); BUT it is endemic in other parts of world!
  • “risk” factors: include international travel & exposure to international airports!
  • Highly virulent strains- higher mortality rate (as high as 15%)

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 (cheeck 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: 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!