MInimod 1 - Medical Microbiology Flashcards
(91 cards)
1
Q
What are the 3 key factors that contribute to the infectious process?
A
- microorganisms (spectrum of pathogens)
- environment (spectrum, natural or hospital associated eg nosocomial)
- hosts (spectrum of hosts)
2
Q
What are the main principles that underpin epidemiology?
A
Diagnose
- culture identification and clinical symptoms
Treat
- antibiotics, immune therapy, oral rehydration
Prevent
- vaccination. Health and welfare, education, associated risks, infection control
3
Q
What is the definition of epidemiology?
A
Epidemiology
* derives from Greek ‘epi’ = ‘of’ and ‘demos’ = the people
* study of the nature, distribution, causation, transfer, prevention and control of disease (infectious/microbial in this case)
Also thought of as:
* natural history of disease
* the human face of ecology
4
Q
What is the key epidermiological marker?
A
Death (mortality) as a key epidemiological marker
(morbidity = disease features and pathology)
5
Q
What vaccination schemes have been majorly effective in the last century?
A
- Measles
- HIV/AIDs (emergence)
- Hepatitis
- influenza pandemics
- respiratory viruses
- small pox (eradicated)
6
Q
What are vaccination schemes that are undergoing research now and in the future?
A
Now and the future?
* HIV/AIDS
* influenza
* SARS and Ebola virus
* corona-virus 19
7
Q
What factors may cause skyrocketing in projected global death in disease?
A
- antimicrobial resistance
- corona virus
- another pandemic
8
Q
What is the current infection mortality rate? What are the 2 key global bacterial diseases involved in this number?
A
Infection mortality - approximately 1.7 billion people in the 20th century
Major global bacterial diseases - key examples:
* respiratory: Myobacterium tuberculosis
* diarrheal: Vibrio cholera
9
Q
What do infections involve?
A
- host, microorganism and enviromental interactions
- epidemiology - the nature of (human) infection
10
Q
What are the threat of bacterial infection?
A
- antibiotic resistance - reduced vaccination rates and poverty
11
Q
What are the 4 types of pathogens?
A
- opportunistic
- obligate
- facultative
- commensal
12
Q
What is a pathogen?
A
A microbe capable of causing host damage and disease
13
Q
What is an opportunistic pathogen?
A
- capable of causing damage and infection in a compromised host
14
Q
What is an obligate pathogen?
A
- causes damage and infection as part of growth and replication
15
Q
What is a facultative pathogen?
A
Causes disease as one part of its lifecycle or when in a different host
16
Q
What is a commensal pathogen?
A
-induces either no damage or clinically inappropriate damage to the host but may elicit an immune response
- can evolve through evolutionary processes or adaptive processes
17
Q
What is mycobacterium tuberculosis?
A
- causes human tuberculosis (M bovid = cattle)
- obligate pathogen
- taxonomically gram positive
- aerobe
- phylum: actinobacteria
18
Q
What is vibrio cholerae?
A
- causes cholera (a diarrhoeal disease)
- gram negative
- facultative anaerobe
- phylum: proteobacteria
- class: gammaproteobacteria
19
Q
What is pseudomonas aeruginosa?
A
- opportunistic pathogen
- causes wound, burn, blood, lung, urinary tract, eye and multiple other infections
- gram negative
- phylum: proteobacteria
- class: gammaproteobacteria
20
Q
What is staphylococcus aureus?
A
- opportunistic pathogen
- cause skin, wound and blood infections, and endocarditis (heart)
- gram positive
- phylum: firmicutes
- class: bacilli
21
Q
What is lactobacillus acidophilus?
A
- epithelial or gut bacteria
- promote health and part of normal microbiota
- gram positive
- phylum: firmicutes
- class: bacilli
22
Q
What is pneumonia?
A
- pneumonia: is swelling (inflammation) of the tissue in one or both lungs
23
Q
What is bronchitis?
A
- bronchitis: infection of the main airways of the lungs (bronchi), causing them to become irritated and inflamed
24
Q
What are the statistics for lower respiratory infections?
A
LRI leading causes of death (4.4%) due to infectious disease in the world
Associated death (2019):
* 2.5 million deaths
* 672,000 children under 5 years
* 1.23 million adults older than 70 years
25
What is streptococcus pneumoniae?
* gram positive
* cocci
* opportunistic pathogens
* extracellular bacteria
* 2021: WHO included S.pneumoniae as one
of 12 priority pathogens
Colonisation (bacterial carriage)
* obligate human host
26
What is meant by ‘bacterial carriage’?
The harbouring of a potentially disease-causing organism by a person or animal that does not contract the disease.
27
How is streptococcus pneumoniae spread?
Contamination: contact with secretions (saliva and mucus)
Invasive bacteria: In US: 5% of patients with pneumococcal pneumonia die from the disease
28
What are the treatments and prevention for streptococcus pnuemoniae?
Treatment: Oral - b-lactams, IV - ceftriaxone, cefotaxime, or amoxicillin-clavulanic acid
Vaccine :
* Pneumococcal conjugate vaccines: PCV7 and PCV13 (babies)
* Pnuemococcal polysaccharide vaccine: PPSV23 (adult>65)
29
Describe natural competence in pneumococcus?
The ability of the bacteria to take up naked DNAf from its environment and integrate it into its genome.
This a form of HGT, it is not a constant trait but rather a regulated state that pneumococcus cells enter under specific conditions.
S.pnuemoniae remodel its genome through the uptake and incorparation of exogenous DNA (natural competence) from other pneumococci or closely related oral streptococci
30
What is haemophilus influenzae?
* gram-negative
* coccobacillus with a variable shape (pleomorphic)
* opportunistic pathogen
* extracellular
* divided into typeable (six stereotypes: a to f) and non-typeable strains (NTHi) on the presence or absence of a polysaccharide capsule
Colonisation (dynamic process)
* 20% of infants
* 50% of children
* 75% of adults
31
How is haemophilus influenzae spread and what is NTHi?
Contamination
* airborne droplets
* contact with secretions
NTHi
* bronchitis in children (internal otitis)
* pneumonia in adults (underlying lung disease)
- Non-Typeable Haemopholus influenzae is the most common bacterial cause of infection of lower airways in adults with chronic obstructive disease (COPD)
32
What is the treatment for NTHi?
* beta-lactams but resistance
* cephalosporins, amoxicillin-clavlanic acid, trimethoprim-sulfamethoxade, tetracyclines, quinolones, and macrolide antibiotics
33
What is the vaccine for NTHi and what is the 6-1 vaccine?
* everyone is vaccinated since 1992
* 3 separate doses at 8, 12 and 16 weeks of age
* as part of the combined 6 in 1 vaccine (diphtheria, hepatitis B, Haemophilus influenza type b, polio, tetanus, pertussis)
34
What are the 4 genuses of the influenza virus?
Family: Orthomyxoviridiae
4 genus:
* influenza A (genus influenza virus A) - human and other mammals (domestic animals, pigs, horses and poultry and in wild migratory birds)
* influenza B (genus influenzavirus B) - human
* influenza C and D
35
What is the incidence for the influenza virus?
* 2 influenza seasons per years during winter: northern hemisphere and southern hemisphere
* children are the main transmitters
* incubation period: 1 to 4 days
* 1 billion infections (affects 5-15% of the population)
* 3-5 million cases of severe illness
* 300,000-500,000 deaths (death rate: 0.1%)(1918: >40 million deaths worldwide)
36
What are the 8 RNA negative-sense single strand RNA viruses?
1-3 = RNA dependant RNA polymerases (RNA synthesis and replication in infected cells)
4 = viral glycoproteins haemagglutin (HA) (mediates binding to sialic acid-containing receptors)
5 = viral nucleoprotein (NP) (bound RNA genome)
6 = neurominisase (NA) (release viruses bound to
non-functional receptors and help viral spread)
6-8 =-2 other proteins
37
What is antigenic shift and drift?
Influenza viruses change through 2 main processes:
Antigenic drift is a gradual accumulation mutations in the genes of influenza viruses, leading to minor changes in their surface proteins (HA and NA).
This happens in all influenza types and results in localised outbreaks.
Antigenic shift is a more dramatic change that occurs in influenza A viruses, involving a major swap of HA and/or NA proteins, potentially from a different virus type. This can lead to widespread epidemics and even pandemics, as there’s limited immunity to the new virus in the population.
38
Briefly describe the influenza lifecycle.
The influenza virus cycle involves serveral key stages:
- entry into a host cell
- replication
- transcription of viral genome in nucleus
- assembly of new viral particles
- release from host cell
39
What is post influenza bacterial superinfection?
Occurs when a bacterial infection develops after a person has recovered from the flu.
This superinfection can lead to increased morbidity and mortality compared to infliuenza alone. It’s often caused by bacteria like staphylococcus or strept pneumonia
The influenza infection disrupts the bodies immune response, making it more vulnerable to bacterial infections.
40
What is the inactivated influenza virus vaccine manufacture?
Production time -
- egg based vaccine: 6 months
- cell based vaccine: 3 months
41
What is SARS-Cov2?
Coronavirus (SARS - CoV-2)
Incidence:
* incubation period: 2 to 14 days
* today: 131/100,000
* 6985004 deaths in the world
Ro of Covid-19: 3.28
42
What is Ro (R-naught)?
Ro (R - naught) of an infection -
* a mathematical term that indicates how contagious an infectious disease is. The Ro is defined by the average number of secondary cases arising from a typical primary case in an entirely susceptible population of size So.
43
What is corona virus and what are its coding regions?
- positive single stranded RNA viruses
- at least 12 coding regions predicted (1ab, S, 3, E, M, 7, 8, 9, 10b, N, 13 and 14)
1ab = replicate proteins with proof reading activity
S = spike (bind to cell surface receptor)
E =envelope (virus morphogenesis, assembly and budding)
M = membrane glycoprotein
N = nucleocapsid (binds RNA to the genome in a string on beads fashion)
44
What is RaTG13 and pangolin CoV MP789?
* RaTG13 from Rhinolophus affinis showed the highest nucleotide similarity of 96.2%
* sequence identity show frequent recombination events in natural reservoir hosts
* pangolin CoV MP789: shared five essential amino acids for ACE2 binding in the S with SARS-CoV-2
45
What is the definition of diarrhoea?
Definition - Diarrhoea is the passage of unusually lose or watery stools, usually at least 3 times in a 24hr period
46
What are the 4 clinical types of diarrhoea?
1) Acute watery diarrhoea (osmotic diarrhoea, secretory diarrhoea)
2) Acute bloody diarrhoea (dysentery; mucus and blood in the faeces)
3) Persistent diarrhoea (which last 14 days or longer)
4) Diarrhoea with severe malnutrition (maramus or kwashiorkor)
47
What are the statistics for diarrhoeal disease?
Children- 1.7 billion cases of diarrhoeal disease every year (twice the population of Europe 742 million)
Adult - one episode every 2 years
Diarrhoea is the leading cause of maltnutrition in children under 5
48
What is the leading cause of diarrhoea?
* effective vaccine
* Rwanda: 61-70% reduction of rotavirus diarrhoea
49
What are the other 4 main pathogens causing diarrhoea?
- e.coli (a loaddd of different types)
- vibrio cholerae
- clostridium difficile
- toxigenic staphyloccus aureus
50
What bacteria targets the liver?
Hepatitis B
51
What bacteria targets the gallbladder?
Salmonella typhi
52
What bacteria targets colon?
Clostridium difficile
53
What bacteria targets the small intestinal region?
Vibrio cholera
54
What bacteria targets the stomach and duodenum?
Helicobacter pylori
55
What is the difference between osmotic and secretory diarrhea?
Osmotic diarrhoea occurs when poorly absorbed substances in the intestines draw out water into the gut, while secretory diarrhoea results from an increased secretion of fluids and electrolytes into the intestine, often with reduced absorption.
56
What are the brush border enzymes found in the small intestine?
A-dextrinase
Enteropeptidase
Lactase
Maltase
Nucleosidases and phosphatases
Peptidases
Sucrose
57
Main cause of osmotic diarrhoea?
E.coli
58
Main cause of secretory diarrhoea?
Cholera
59
Sources of transfer for diarrhoea?
- contaminated water and food
- outbreaks linked to vegetables (US)
- other humans
60
Prevention of diarrhoea?
* access to safe drinking water
* use of improved sanitation
* exclusive breastfeeding for the first 6 months of life
* good personal and food hygiene
* vaccination (rotavirus, cholera)
* health education about how infections spread
61
Why is hand washing with soap so important?
* reduces the number of people who get sick with diarrhoea by 23-40%
* reduces diarrhoeal illness with weakened immune systems by 58%
* reduces respiratory illnesses like colds in general population by 16-21%
* reduces absenteeism due to gastrointestinal illness in school children by 29-57%
62
How can someone rehydrate after having diarrhoea?
* oral rehydration salts (ORS) solution (clean water, salt and sugar). Costs: few cents per treatment. ORS is absorbed in the small intestine and replace the water and electrolytes lost in the faeces. ATTENTION: osmotic diarrhoea
* intravenous fluids in case of severe dehydration or shock
63
How can zinc supplements and nutrient rich foods be implemented for diarrhoea?
* reduce the duration of diarrhoea episode b 25% and are associated with a 30% reduction in stool volume
Nutrient rich foods:
* reduce malnutrition induce diarrhoea. ATTENTION: osmotic diarrhoea
64
What does loperamide do?
Control and relieve symptoms of diarrhoea
- used in patients with inflammatory bowel disease
- helps stop diarrhoea by slowing down movement of the intestines
65
What is the original definition of an antibiotic?
Original definition: 1930 - Waksman defined an antibiotic as a compound made by a microbe to destroy other microbes
66
What is meant by ‘antimicrobial’?
compounds which kill any type of microbes (not just bacteria) and could be a mix of active components
67
What are antibiotics?
Chemical compounds with a single mode of actions and only active against bacteria
68
What is Alexander Fleming remembered for?
In 1928 he discovered Pencillium notatum inhibiting Staphyloccocus aureus on a agar plate
69
What are bacteriostatic agents?
- inhibit important biological processes, eg protein synthesis
- weak target binding
- if the agent is removed the cell will continue growing
- many antibiotics fall into this category
70
What are bactericidal agents?
- kill the cell
- strong target binding
- cell is not lysed; therefore, total cell count remains constant
- viable cell count (the number of live bacteria) decrease
71
What are bacteriolytic agents?
- kill and lyse the cell, releasing their cytoplasmic contents, eg detergents
- rupture cytoplasmic membrane
- because the cell is lysed, the total cell count and viable cell count both decrease
72
What is the activity spectrum?
Activity depends on whether the target is present in only certain types of bacteria (eg Gram-positive or Gram-negative) or in all.
73
What is narrow spectrum activity and an example of this?
* advantage - potential to limit selection for and spread of resistance, and to elicit a lesser detrimental effect upon the host microbiome
* challenge: require rapid, accurate and sensitive diagnostic assays for the identification of bacterial pathogens
* examples; Azithromycin (Macrolide to treat pneumonia)
74
What is broad spectrum activity and an example of this?
* advantage - can be used quickly before the formal identification of the causative bacteria
* challenge - selection for and spread of resistance across multiple bacterial species
* example - amoxicillin
75
What are the 8 most common classes of antibiotic and what 3 areas do they target?
1) Betalactams (penicillins, cephalosporins, carbapenems) - bacterial cell wall synthesis
2) Sulfonamides
3) Fluoroquinolones (DNA synthesis)
4) Macrolides
5) tetracyclines
6) Aminoglycosides (protein synthesis)
76
What are beta lactams?
* bactericidal, broad spectrum
* targets cell wall synthesis
Side effect: No side effects in humans apart from occasional allergies
* most used molecules - ampicillin, cephazolin, imipenem
77
What are sulfonamides?
history - introduced in 1935, Prontosil (Bayer) was the first ever antibiotic to treat a range of bacterial infections
* bacteriostatic, broad spectrum
Target - Competitive inhibitors of the enzyme dihydropteroate synthase (DHPS), an enzyme involved in folate synthesis (required for purine and DNA synthesis)
78
Side effects of sulfonamides? Most used molecules?
Side effects -
* hypersensitivity reactions
* hematologic reactions
* neurological effects, such as insomnia and headaches
Most used molecules - Sulfamethoxazole (use with Trimethoprim)
79
What are floroquinolones?
History - dervied from Nalidixic acid discovered in 1960 as a by-product if an antimalaria quinine compound
* bacteriocidal, broad spectrum activity
Target - inhibit bacterial topoisomerases II and IV
80
Side effects of fluroquinolones? Most used molecules?
* tendinopathy
* hyperglycaemia and hypogylcemia
Most used molecules: ciprofloxacin, norfloxacin and moxifloxacin
81
What are macrolides?
History - isolated from a strep strain in 1950 (erythromycin), derivatives
Have been synthesised, leading to the development of 3 generations
Of macrolides
* bacteriostatic, broad spectrum activity
target - bind the bacterial 50S ribosomal subunit causing the cessation of bacterial protein synthesis
82
What are the side effects of macrolides? Most used molecules?
Side effects:
* cardiac arrhythmias
* hepatotoxicity
Most used molecules: azithromycin, clathromycin and erythromycin
83
What are tetracyclines?
history - isolated from an Actinomycetes soil bacteria in 1948. Derivatives have been synthesised leading to the development of 3 generations of tetracyclines
* bacteriostatic, broad spectrum activity
target - bind the bacterial 30S ribosomal subunit causing the cessation of bacterial protein synthesis
84
What are the side effects for tetracyclines? Most used molecules?
* discolouration of teeth and inhibition of bone growth in children
* photosensitivity
* hepatoxicity
Most used molecules - tetracycline, doxycycline, minocycline
85
What are aminoglycosides?
History: isolated initially from a strep strain and made clinically available in 1944 (streptomycin). Derivatives have been isolated from other species: neomycin (1949, S fradiae), kanamycin (1957, S kanamyceticus) gentamicin (1963, micromonospora purpurea), tobramycin (1967, s tenebrarius)
* bacteriocidal, broad spectrum
target - bind the bacterial 30S ribosomal subunit causing the cessation of bacterial protein synthesis
86
What are the side effects of aminoglycosides? Most used molecules?
Side effects -
* nephrotoxic
* ototoxic
* neuromuscular blockade
Most used molecules (IM or IV)
* streptomycin, gentamicin, neomycin
87
What are the principles of antibacterial therapy?
* viral infections can’t be treated with antibiotics, however, they may be used to treat secondary bacterial infections (eg bacterial pneumonia secondary to influenza)
* organism prevalence and their current sensitivity
* dose depends on age, weight, hepatic function, renal function and severity of infection
* route: oral vs intravenous, some antibtiocs cannot be absorbed orally
* duration: too long can increase resistance and side effects. However some infections will require months of treatment due to the slow growing nature of the bacteria (tuberculosis)
88
Describe agricultural use of antibiotics.
* disease treatment of animals
* subtherapeutic levels in concentrated animal feed for growth promotion, improved feed conversion efficiency and the prevention of diseases
89
What has led to a high level of antibiotic resistance?
* misuse and overuse of antibiotics in medicine and agriculture
* patients not taking antibiotics as prescribed
* poor infection control in hospitals/clinics
* lack of rapid laboratory tests
* poor hygiene and sanitation practices
90
Why has big pharma abandoned antibiotics?
* lack of financial incentive/ profit
* the last entirely new class of antibiotics was discovered in the late 1980s
* cost of developing a new antibiotic US$1.5 billion
* average revenue generated from antibiotic sales is $46 million per year
* government agencies (eg NICE in the UK) ensure drug prices are kept low
* deaths caused by infectious diseases have fallen by 70% since antibiotics were introduced in the 1940s
* physicians are avoiding the over-prescription of antibiotics to curb resistance
91
What are the top 3 WHO list of antimicrobial resistant priority pathogens?
All gram negative
Acinetobacter baumannii - Nosocominal/opportunistic infections of the skin, bloodstream, urinary tract and other soft tissues
Pseudomonas aeruginosa - Opportunistic urinary tract and respiratory system infections, dermatitis, soft tissue infections, bacteraemia, bone and joint infections and a variety of systemic infections
Escherichia coli - Gastroenteritis. Strains range from avirulent to highly pathogenic eg enteropathogenic (EPEC), enterotoxigenic (ETEC) and enteroharmorrhagic (EHEC) strains
