Multi-Drug Resistant TB and Influenza Virus

Multi-Drug Resistant TB (MDR-TB)

• MDR-TB occurs when a Mycobacterium tuberculosis strain is resistant to isoniazid and rifampin, two of the most powerful first-line TB drugs.
• To treat MDR-TB, a combination of second-line drugs is used.

Influenza Virus

• The genome is segmented, negative-sense, single-stranded RNA.
• The virus causes significant disease in humans.
• Antigenic drift occurs when viral polymerase makes mistakes when replicating, leading to small changes in viral epitopes that accumulate over time.
• Antigenic shift occurs when a virus arises with gene segments derived from multiple different types of influenza virus (e.g., combining human, bird, swine strains).
• Hemagglutinin (HA) binds to epithelial cells of the upper tract via sialylated glycans.
• PB1-F2 induces host cell apoptosis and impairs type 1 IFN production.
• Neuraminidase inhibitors are structural mimics of sialic acid that are effective against IAV and IBV if used within 48 hours of the appearance of symptoms.
• Live attenuated influenza virus vaccine is delivered by nasal spray.
• Inactivated influenza vaccine is composed of two IAV and two IBV strains and is delivered by intramuscular injection.

Norovirus

• It lacks durable immunity, with strain-specific immunity lasting only a few weeks after infection.
• It has a short incubation period (24-48 hours).
• It is persistent, with fecal shedding lasting up to 60 days.
• Capsids bind to histo-blood group antigens (HBGA) on the surface of mucosal epithelial cells.
• The virus can infect macrophages, dendritic cells, B lymphocytes, and the lamina propria of the small intestine.
• Viral NTPase inhibits the production of IFN-beta during infection.
• Antigen variation facilitates immune escape and reinfection.

Rotavirus

• Viroporin NSP4 (viral enterotoxin) acts on chloride channels to induce water loss.
• NSP4 also regulates calcium homeostasis to favor viral replication.
• NSP4 acts on enteric neurons to increase intestinal motility.
• Infection occurs in the enterocytes of the small intestine.
• The infection is non-inflammatory.

Poliovirus

• 2B protein (viroporin) alters membrane permeability of infected cells to increase release of new virions.
• Live-attenuated Sabin vaccine contains a mutation in the 5’ non-coding section of the RNA genome.
• The virus attaches and enters host cells by interacting with host cell CD155 receptor (also known as poliovirus receptor or PVR).
• Poliovirus replication utilizes host cell ribosomes to translate the positive-sense RNA genome into proteins.
• The virus must encode its own RNA-dependent RNA polymerase (RdRp) in order to replicate its genome.

Enterotoxigenic Escherichia coli (ETEC)

• Fimbriae attach to the intestinal epithelial cell wall.
• Fimbriae act as adhesins, binding to specific molecules on the epithelial cell surface.
• Fimbriae help ETEC avoid being washed away by the rapid flow of food.
• ETEC produce labile toxins.
  • The toxin can be produced in food and ingested or after host colonization.
  • The toxin is similar in structure and effect to cholera toxin.
  • It attaches to the surface of the small intestinal epithelial cell.
  • It disrupts ion and water flow across the membrane.
  • It causes massive secretion of water and salts into the lumen of the intestine.
  • In acute cases, salt and fluid loss leads to dehydration and death.
• Rehydration therapy (isotonic salt solutions) is very effective.

Staphylococcus Aureus Infections

• Can be a polymicrobial infection, involving multiple microbes
• Infections are superficial and do not scar
• There is no significant immune response
• Infections resolve spontaneously or with antibiotic treatment

Epidermis

• Staphylococcus Scalded Skin Syndrome (Ritter's Disease) is caused by the toxin exfoliatin, produced by certain Staphylococcus strains
• Occurs mainly in young children
• Spontaneous recovery usually happens within 7-10 days without scarring
• Secondary bacterial infections can lead to more serious complications

Dermis

• Erysipelas is usually caused by Streptococcus pyogenes
• Most common in young children and elderly individuals, as their immune systems are developing or declining
• Characterized by bright red lesions due to an immune reaction
• Treatment involves antibiotics effective against Streptococcus

Dermis Appendages

• Acne Vulgaris is prevalent in adolescence when the endocrine system is highly active

• Hormonal activity stimulates overproduction of sebum by oil glands, promoting Propionibacterium acnes growth

• Inflammation leads to the formation of comedones (plugs of sebum and keratin in oil gland ducts), causing pimples and blackheads

• Treatment includes antibacterials, antibiotics, and retinol to reduce oil gland function

• Folliculitis involves infection and inflammation of the hair follicle

• Staphylococcus aureus is the most common cause

• When occurring on the eyelid, it is called a stye

Dermis and Appendages

• Furuncles (boils) are extensions of folliculitis.
• Carbuncles result from the coalescence of multiple furuncles
• Chills and fever associated with carbuncles indicate systemic spread of Staphylococcus

Deep Dermis and Subcutaneous Fat

• Cellulitis originates from superficial skin lesions or trauma
• Characterized by hot, red lesions, chills and fever
• Strep pyogenes is the most common cause, followed by Staph aureus
• Vibrio vulnificans, a marine microorganism, can cause cellulitis after a wound injury in saltwater
• Rapid diagnosis and treatment are crucial due to the fast progression of this infection

Superficial Fascia

• Necrotizing Fasciitis affects the superficial fascia and subcutaneous fat
• Undermining of surrounding tissue leads to patchy anesthesia or gangrene
• There are two main causes, only one is described in the text:
  • One cause involves a rapid spread of infection, primarily due to Streptococcus pyogenes
  • This cause involves a more delayed spread, commonly caused by Staphylococcus aureus
  • This form causes a destructive spreading infection involving the deeper tissues and is sometimes referred to as "flesh-eating bacteria"

Explore the complexities of Multi-Drug Resistant Tuberculosis (MDR-TB) and the Influenza virus. This quiz covers key concepts such as the resistance mechanisms of MDR-TB, antigenic drift and shift in influenza, and the structural aspects of viral proteins. Test your understanding of these critical topics in infectious diseases.