MMG065 EXAM 3

-itis

a suffix used in pathological terms that denotes inflammation of an organ/body site

upper respiratory tract (URT)

-paranasal sinuses
-nasal cavity
-pharynx (throat)
-epiglottis

lower respiratory tract (LRT)

-larynx (voice box)
-trachea (windpipe)
-bronchi
-bronchiole
-alveolar sac
-alveoli

innate defenses of the respiratory tract

-mucous membranes: goblet cells and mucus, ciliated epithelial cells, mucociliary escalator
-mucosa-associated lymphoid tissue (MALT): including adenoids/tonsils
-alveolar macrophages
-normal microbiota

nasal cavity microbiota

-similar to skin flora
-can include opportunistic pathogens in low numbers

pharynx microbiota

-similar to skin and mouth flora
-can include opportunistic pathogens in low numbers

lungs microbiota

-transient microbes only
-effectively sterile

normal microbiota

-varies from person to person
-affected by many factors including immune status, antibiotic use, and smoking

common cold causative agent

->200 different viruses
-rhinoviruses and coronaviruses (40-60%)
-HPIV, RSV, ADV

common cold transmission

-respiratory droplets
-fomites

fomites

inanimate objects

common cold diagnosis

-based on clinical symptoms
-NAAT (nasal or nasopharyngeal swab, rule out serious viral agents)

common cold treatment

supportive care

common cold vaccine

none

cold viruses that can cause more serious infections

-HPIV
-RSV
-ADV

human parainfluenza virus (HPIV)

-RNA, enveloped virus
-especially serious for

respiratory syncytial virus (RSV)

-RNA, enveloped virus
-especially serious for

adenovirus (ADV)

-DNA, naked virus
-common vector for recombinant vaccines
-many different strains causing conjunctivitis, gastroenteritis, and cystitis
-live attenuated vaccines for type 4 and 7, military only

cold vs. flu

Cold
-symptom onset: gradual
-fever: rare
-aches: slight
-headache: rare

Flu
-symptom onset: abrupt
-fever: usual
-aches: usual
-headache: common

influenza virus infections pathogenesis and virulence factors

-binds ciliates cells of URT
-hemagglutinin (H) and neuraminidase (N) glycoprotein spikes

influenza virus infections diagnosis and treatment

-nasopharyngeal swab, NAAT (RT-PCR)
-supportive care
-influenza specific antiviral drugs in serious cases
-Tamiflu and related drugs inhibit N
-Xofluza blocks viral replication

influenza virus infections causative agent

-RNA viruses with segmented genome, enveloped
-3 types of influenza virus: A, B, and C

influenza virus infections transmission and infection

-respiratory droplets and fomites
-sanitation practices and hand washing

influenza virus infections vaccine

-seasonal
-whole inactivated, recombinant, and live attenuated

influenza type A

-most common cause of human flu epidemics
-new strains can cause an influenza pandemic

influenza type B

less impactful, but still causes epidemics

influenza type C

-causes mild respiratory illness
-not associated with epidemics

subtyping influenza A viruses

-based on surface glycoprotein spikes (H and N)
-~170 influenza A strains with different H and N combinations

3 main influenza A subtypes that infect humans

-H1N1 (swine flue)
-H2N2
-H3N2

influenza virus infections seasonal outbreaks vs. worldwide pandemics

-emergence of new strains is common because virus' RNA genome mutates quickly and has the ability to genetically mix-and-match RNA segments
-antigenic drift: random mutations, minor changes to H and N spikes, allows for seasonal epidemics
-antigenic shift: major genetic change, major alterations in viral antigens, can allow for pandemics

SARS-CoV-2

-newly emerged viral pathogen
-little to 0 immunity in humans in 2019/2020
-COVID-19: COronaVirus Disease 2019
-RNA, non-segmented, enveloped virus
-complete genome sequenced January, 2020
-important virulence factor: spike protein

SARS-CoV-2 infection of human cells

-spike protein binds human ACE2 (angiotensin-converting enzyme 2)
-enters by receptor-mediated endocytosis

cells that express ACE2

-respiratory tract
-kidneys
-heart
-blood vessels
-neurons

recently emerged coronaviruses

-sever acute respiratory syndrome coronavirus: SARS-CoV (now referred to as SARS-CoV-1)
-Middle East respiratory syndrome coronavirus: MERS-CoV
-novel coronavirus 2019: nCoV-2019 (now referred to as SARS-CoV-2)

seasonal flu vs. COVID-19

seasonal flu
-CFR: ~0.1%
-immunity: partial based on prior exposures
-treatment: Tamiflu
-prevention: annual flu vaccination (live attenuated)

COVID-19
-estimated 15-20% of cases may suffer severe symptoms
-CFR:? ~2-4%
-immunity: none
-treatment: Remdesivir, inhibits viral RNA replication
-prevention: vaccines (RNA and recombinant vector)

Pfizer-BioNTech

-UK approved
-RNA
-2 doses
--70C
-US approved

Moderna

-UK approved
-RNA
-2 doses
--20C
-US approved

Johnson and Johnson

-pending UK approval
-viral vector
-1 dose
-regular fridge temperature
-US approved

viral strains and variants

-RNA viruses tend to mutate more frequently than DNA viruses
-emerging SARS-CoV-2 variants are categorized by risk: variants of interest, variants of concern (VOC), variants of high consequence

viral varient

has at least 1 genetic mutation compared to the original virus strain

new viral strain

if mutations cause viral functions to be altered, the variant is a new viral strain

COVID-19 causative agent

-SARS-CoV-2
-coronavirus, RNA, enveloped virus

COVID-19 transmission

-respiratory droplets
-fomites

COVID-19 diagnosis

NAAT (RT-PCR)

COVID-19 treatment

-supportive care
-Remdesivir inhibits viral replication
-immunotherapy (passive immunity)

COVID-19 vaccines

-RNA vaccines
-recombinant vector vaccines

otitis media

-inflammation of the middle ear
-common bacterial complication of ARI/common cold and allergies
-more common in children
-ear pain, eardrum inflammation, fever

otitis media pathogenesis

-viral URTI cause inflammation of Eustachian tubes
-inflammation causes mucus to accumulate
-lack of drainage allows for bacterial infection of the middle ear (usually bacteria belonging to normal microbiota)

otitis media diagnosis

-lab testing usually unnecessary
-diagnosis by clinical presentation

otitis media treatment

-pain relievers only
-antibiotics not recommended

otitis media prevention

-for infants: breast-feeding until at least 6 months
-tympanostomy tubes

otitis media vaccines

-bacterial causes greatly decrease with routine childhood vaccines
-Pneumococcal vaccine (conjugate vaccine): protects against some strains of Streptococcus Pneumoniae, capsule antigens of SXPN
-Hib vaccine (conjugate vaccine): protects against Haemophilus influenza type B strains only, type B capsule antigens of HAIN

otitis media causative agents

-many virus strains
-Streptococcus pneumoniae (GPC)
-nontypable Haemophilus influenza (GNCB)
-Moraxella catarrhalis (GNC)

otitis media tansmission/precautions

-noncommunicable
-no transmission precautions

GPC

gram positive cocci

GPB

gram positive bacillus

GNC

gram negative cocci

GNB

gram negative bacillus

GNBC

gram negative coccobacillus

pharyngitis

-inflammation of the pharynx
-caused by bacteria, viruses, or allergens
-most cases are viral
-bacterial pharyngitis: Streptococcus pyogenes, Group A Streptococcus (GAS)
-resistant GAS is on the CDC's list of concerning threats

why Group A Streptococcus

-classification system developed by Rebecca Lancefield (1895-1981)
-agglutination reaction with different antibodies
-14 different groups (A thru O)
-react with group "A" antibody = Group A (Streptococcus pyogenes)
-react with group "B" antibody = Group B (Streptococcus agalactiae )
-no reaction with any antibodies tested = streptococcus pneumoniae

bacterial pharyngitis pathogenesis

-many virulence factors
-capsule
-

bacterial pharyngitis lab diagnosis

-ICA (usually done as a POCT)
-if ICA is negative: culture that identifies S. pyogenes

bacterial pharyngitis treatment

-always treat with antibiotics
-typically penicillin (macrolides if pen-allergic)
-GAS are considered universally susceptible to penicillin

bacterial pharyngitis risks

-infection with GAS can lead to many sequelae
-ex. scarlet fever, rheumatic fever/rheumatic heart disease, acute glomerulonephritis (AGN)

sequelae

a condition which is the consequence of a previous disease or injury

sequelae of GAS infection: scarlet fever signs and symptoms

-red sandpaper-like rash
-"strawberry tongue"
-skin sloughs off after the rash resolves

sequelae of GAS infection: scarlet fever pathogenesis

-

superantigen

-bacterial virulence factor
-acts as toxin
-target T helper cells: causes nonspecific activation, overstimulation of the immune system, massive inflammation that is harmful to the host, usually pyrogenic
-erythrogenic toxin: superantigen, inflammation and dilation of capillaries → skin rash

sequelae of GAS infection: autoimmune reactions pathogenesis

-M protein, a surface protein
-antibodies may cross react with human tissues
-mediated by type III hypersensitivity

sequelae of GAS infection: autoimmune reactions

Rheumatic fever
-Ig cross reacts with joints, nervous system, heart, and skin
-complications: rheumatic heart disease (15 million cases worldwide)

Acute Glomerulonephritis (AGN)
-Ig cross reacts with kidneys → kidney damage
-causes edema, increased BP, and heart failure
-can clear up spontaneously or lead to kidney failure and death

macrolide antibiotics

-target protein synthesis (erythromycin, azithromycin/Z-pack...)
-often used to treat GAS in penicillin allergic patients

erythromycin-resistant GAS

resistant to macrolide antibiotics

GAS strains acquiring erythromycin-resistance

horizontal gene transfer
-acquisition of new genes by transformation, transduction, or conjugation

new gene, mefA
-mefA = macrolide efflux pump
-encodes an efflux pump
-specifically pumps out macrolide drugs (erythromycin, azithromycin, clarithromycin)

bacterial pharyngitis causative agent

-Streptococcus pyogenes (GAS)
-gram positive cocci in chains

bacterial pharyngitis transmission/precautions

-respiratory droplets
-droplet precautions

diphtheria

-serious childhood URT infection characterized by pseudomembrane
-low incidence due to effective combination vaccine
-DTaP vaccine (diphtheria toxoid, tetanus toxoid and acellular pertussis)

diphtheria pathogenesis

-diphtheria toxin inhibits protein synthesis of host cells, cells die
-pseudomembrane caused by death of mucosal epithelial cells

diphtheria lab diagnosis

-bacterial culture
-may take 7-10 days

diphtheria treatment

-start treatment before definitive diagnosis
-antibiotics AND diphtheria antitoxin (DAT): antibody injection that neutralized diphtheria toxin

diphtheria vaccine

toxoid vaccine against diphtheria toxin found in DTaP

diphtheria antitoxin (DAT)

antibody made in horses that will neutralize diphtheria toxin in humans

diphtheria causative agent

Corynebacterium diphtheriae (GPB)

diphtheria transmission/precautions

-respiratory droplets
-droplet precautions

pertussis catarrhal stage

-cold-like symptoms
-1-2 weeks

pertussis paroxysmal stage

-severe cough (paroxysms)
-2-6 weeks
-vomiting, fractured ribs, bleeding behind eyes and in brain

pertussis convalescent stage

-less frequent coughing
-~4 weeks

pertussis pathogenesis and virulence

-tracheal cytotoxin damages ciliated epithelial cells of URT, mucus accumulates
-pertussis toxin damages URT cells, causes inflammation

pertussis lab diagnosis

NAAT

pertussis treatment

antibiotics

pertussis vaccine

-DTaP vaccine
-acellular components of B. pertussis (subunit vaccine)

pertussis causative agent

-Bordetella pertussis (GNB)
-challenging to grow in lab

pertussis transmission/precautions

-respiratory droplets and direct contact
-droplet precautions

URT infections

-otitis media
-bacterial pharyngitis
-diphtheria
-pertussis

viral URTI

-common cold
-RSV
-HPIV
-Adenovirus
-influenza
-COVID-19

acid fast bacteria (AFB)

-thick peptidoglycan layer plus mycolic acid layer
-gram stain will not penetrate
-acid fast stain: AFB appear red/pink
-nutrients, gasses, drugs do not readily cross mycolic acid layer
-bacteria are slow growing
-antibiotic therapies require months
-mycobacterium tuberculosis

acid fast staining

-primary stain
-strong (acidic) wash/decolorizer
-secondary stain
-acid fast bacteria retain the primary stain following treatment with acid

expectorated sputum

-easy, non-invasive, most common
-commonly contaminated with mouth microbiota
-more challenging to interpret results

bronchoalveolar lavage (BAL)

-invasive, less frequently used
-bypasses oropharyngeal cavity, no microbiota from mouth
-less challenging to interpret results

lower respiratory tract infections

-tuberculosis
-typical pneumonia
-atypical pneumonia
-fungal infections