PMB: Infectious disease

Question 1

What do the following terms mean?

1. Pathogen
2. Primary Pathogen
3. Oppotuinisitic pathogen

Answer 1

1. Pathogen: Microorganism causing disease
2. Primary pathogen: Only associate with body to cause disease
3. Opportunist pathogen:
   
   • Often present as part of the body’s normal flora
   • Only cause disease when defence system weakened
   • e.g. S. aureus in suffers from cystic fibrosis

Question 2

What are 4 groups of microbial diseases base on transmission and examples

Answer 2

4 groups to be considered based on mode of transmission

• Respiratory conditions e.g. measles
• Sexually transmitted e.g. herpes
• Food and waterborne e.g. cholera
• Animal transmitted e.g. Yersinia pestis

Question 3

Which category is the majority of infectious diseases?

Give examples

Answer 3

• Respiratory infections are the largest group of infectious diseases
• Aerosols mean no need for direct person-to-person contact
• Globally influenza is the biggest cause of microbial death each year – more next lecture
• However both tuberculosis (rest of this lecture) and pneumonia are major causes of death as well

Question 4

1. What organisms causes tuberculosis?
2. What are the steps in tuberculosis infection?

Answer 4

1. Causes by the bacteria mycobacterium tuberculosis
2. The process of TB infection involves 2 phases

• Primary
• Secondary

Question 5

What happens in phase 1?

Answer 5

• Phase 1 is the infectious process
• The mycobacterium tuberculosis needs to be inhaled from an areosol. It then moves to the aveoli in the lungs and grows.
• Infection of the aveoli stimulates the hosts macrophages which form aggregates (tubercles) and engulf the mycobacteria.
• Some mycobacteria survive in the machrophages after phagocytosis. They do not succumb to the normal lysomal destruction process

Question 6

Why does some mycobacteria survive with the macrophages?

Answer 6

• Mycobacterial cell walls are rich in mycolic acid – a glycolipid. Not really Gram +ve or -ve.
• Mycolic acids are hydrophobic. The outside of cell is hydrophobic
• Due to this exterior surface normal phagocytosis does not occur
• It also limits the entry of antimicrobial compounds

Question 7

Describe the consquence of infection with primary tuberculosis

Answer 7

• Primary infection is normally not obvious in host
• Very rarely will acute pulmonary disease occur
• Leads to destruction of lung tissue and death
• Normally this acute form of TB only occurs in unhealthy or already sick individuals
• Following infection most people become hypersensitised to the bacterium
• This is due to cell-mediated immune response
• In most people this gives natural immunity (life long) against secondary TB

Question 8

Describe the development of secondary tuberculosis

Answer 8

Ocassionally a person with primary TB can develop seondary TB

2 Possible routes

• Reactivation of dormant bacteria in the lung macrophage
• Or Reinfection from an external source

Question 9

1. What can secondary tuberculosis lead too?
2. What is onset linked too?

Answer 9

1. Lung destruction
2. Linked too poor health
   
   • Age
   • Malnutritition
   • Poverty/ poor living conditions

Question 10

What is the danger of secondary infections?

Answer 10

• When secondary infection occurs the patient will have infective mycobacteria
• These can be released via aerosols
• Patient is highly contagious

Question 11

Describe the Heaf Test

Answer 11

• Developed by Frederick Roland George Heaf (1894–1973)
• Until 1916 known as Fritz Rudolf Georg Hief
• Spring-loaded instrument with 6 needles in a circular pattern
• Used in Scotland on children around 11-12
• Positive reaction – screened for TB with X-rays
• Negative reaction – BCG (Bacillus Calmette–Guérin) vaccination

Question 12

What is used to control TB?

Answer 12

• BCG no longer routinely used - only used in at risk group
• Antimictobials used:
  
  • Mainly Isonazid
  • Isonazid also used with rifampicin and ethambutol or pyrazinamide

Question 13

How do the following drugs work

Isonazid

Ethambutol

Rifampicin

Pyramizinamide

Answer 13

1. Isonazid is a prodrug
   
   • Activated by bacterial catalase
   • Inhibits fatty acid synthase
2. Ethambutol disrupts arabinogalactan synthesis
   
   • Inhibits the enzyme arabinosyl transferase
3. Rifampicin targets RNA polymerase
   
   • Broadly used – TB, Legionnaire’s disease, Leprosy
4. Pyrazinamide is a prodrug which the bacterial enzyme pyrazinamidase converts to pyrazinoic acid (the active form)
   
   • Highly specific and only used for treatment of Mycobacterium tuberculosis

Question 14

1. What is the generation time of TB
2. Problem?

Answer 14

1. Mycobacterium tuberculosis has a very long generation time Typically around 15 – 20 hours
2. The long generation time means that treatment is lengthy (6 months). Potential problem of compliance with treatment

Question 15

What is used in extreme TB cases

Answer 15

• Bedaquiline (Brand name = Sirturo)
• 2014 became available for use against MDR (multi-drug-resistant) TB
• Targets ATP synthase in cytoplasmic membrane
• Generally used with >3 other medications for TB