Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

microbial pathogens > Microbial pathogens 1 > Flashcards

Microbial pathogens 1 Flashcards

1
Q

a pathogen

A

a microorganism that is able to cause a disease in a plant or animal or insect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

pathogenicity

A

the ability to produce disease in a host organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

more virulent ∝

A

more capable of causing disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

microbes express their pathogenicity by means of

A

virulence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

virulence =

A

term which refers to the degree of pathogenicity of the microbe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

determinants of virulence

A

any genetic, biochemical or structural features that enable it to produce disease in a host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Two main mechanisms underlying bacterial pathogenicity

A

-The ability to invade tissues (invasiveness)
-ability to produce toxins (toxigenesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

invasiveness =

A

-ability to bypass host defence mechanisms
-production of extracellular substances which facilitate invasion (like adherins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

toxigenesis the two types are

A

-two types of toxin EXO/ENDOtoxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

exotoxins

A

released from bacterial cells and may act at tissue sites removed from the site of bacterial growth

botulinum and cholera toxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

endotoxins

A

cell-associated substances that are structural components of the cell walls of GRAM NEGATIVE bacteria (capsule on LPS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

human pathogens can enter through (main sites)

A

-respiratory
-gastro-intestinal
-urinary or genital tracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

human pathogens can enter broken skin …

A

-by insect bites
-accidental surgical trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

opportunistic pathogens are carried as

A

part of the normal human flora
acts as ready source of infection in compromised host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

transmission of bordetella pertussis (more complex)

A

-respiratory
-requires contact with infectious material since the organisms survives poorly in environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

for pathogens where the primary source is environmental (infection follows ingestion) pathogens MUST

A

remain viable in different environmental conditions

the environment that can be colonised by a pathogen are critical in determining its reservoirs and potential modes of transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Psychrophile

A

grow best at low T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

psychotroph

A

able to grow at low T but prefer moderate T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

mesophile

A

most bacteria live in animals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

thermophile

A

amount all thermophiles is wide variation in optimum and maximum T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

growth rate curves for temperates effect

A

not symmetrical
-linear increase until optimum where the cell can’t function at high temps

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

cold shock adaptation

A

-inhibition of protein synthesis
-causes a growth lag known as the acclimation phase during this a group of cold shock proteins (Csp) are dramatically induced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

chaperone

A

protein that check other proteins are folding correctly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

cold shock proteins class 1

A

ensure ribosome/DNA/RNA synthesis is working correctly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

cold shock proteins class 2

A

conditioning ribosome to conduct protein synthesis in cold conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Listeria

A

-non spore forming gram positive bacilli

causes LISTERIOSIS
risk:pregnant/immunocomprimised

CAPABLE OF GROWTH OVER A WIDE RANGE FROM 2 TO 40°C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

how is listeria spread

A

infected foods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

listeria virulence factors-escape from single membrane vacuole

A

slide 16 for detail

proteins and enzymes that punch holes in membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

listeria virulence factors-cell to cell spread

A

slide 16 for detail

-Protein polymerising actin in wrong place (at base of cell allowing it to propel)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

listeria virulence factors-required for escape from double membrane vacuole

A

slide 16 for detail

a phospholipase that cleaves the head group from many different kinds of lipids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

listeria virulence factors-regulation of virulence factors

A

slide 16 for detail

positive regulator of virulence genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

how is listeria controlled in food

A

-high temps while cooking
-grow foods with 12% NaCL and with ph range of 4.4 to 9.8
-cook meat thoruoughly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Legionella pneumophila

A

-motile aerobic gram negative rod
-lives in phagocytic cells (macrophages)
-live in air conditioning units

CAUSES- pneumonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

temp and legionella

A

-humans are accidental hosts as CELLS EXPRESS MORE FLAGELLIN RNA and protein at 30°C than 37°C
-adherence is also temp dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Gram positive bacteria simple definition

A

only inner membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

pH of natural environments varies from

A

0.5(acid) to 10.5 (alkali)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

pH 0 = compared to pH 14 =

A

pH 0 = 1 mole per litre of Hydrogen ions (10^-14) moles per litre of OH^-

pH 14 = 10^-14 mole per litre of Hydrogen ions (1) moles per litre of OH^-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

most free-living prokaryotes can grow over a range of _ pH units

A

3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

pH growth rates are a _______ curve

A

symmetrical due to subtle effect of pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Acidophile =

A

acid loving

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

most cells are _____philes

A

neutro

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Thiobacillus species

A

-Acidophiles
-require low pH for growth because their membranes dissolve and the cells lyse at neutrality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

obligate alkali-holes can grow around pH

A

10

-in an alkaline bacillus species a Na+ gradient (instead of pmf) supplies the energy for transport and motility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

pmf

A

proton motor force

-electrochemical gradient forced due to ETC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

optimal growth pH is the pH of the

A

extracellular environment
-extremes are 4.6 (acidophil) and 9.5 for (alkaliphile)

most are NEUTROPHILES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

problems posed by acidic conditions

3

A

-capacity for nutrient acquisition and energy generation
-cytoplasmic pH homestasis
-protection of proteins and DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

acidic conditions effecting protection of proteins and `DNA two mechanisms that can help achieve this

A

chaperone proteins

alkalisation of the periplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

helicobacter pylori

A

-gastric pathogen

-gram negative curved rod
highly motile due to flagella

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

helicobacter pylori causes what

A

-gastric and duodenal ulcers
-ulcers associated with development of gastric cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

helicobacter pylori main virulence factors

A

-flagella
-urease = helps neutralise the acidic pH of the stomach
-adhesins
-vacuolating toxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Koch’s postulates

A

-the organism is always present in animals suffering from the disease but not in healthy

1)organism cultivated in pure culture away from the animal
2)susceptible animals should initiate the disease characteristics
3)organism re-isolated from experimental animals and cultured (same as ORIGINAL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Barry Marshall

A

-drank culture of helicobacter pylori and shown to have an inflamed stomach two weeks later

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

how does H. Pylori survive in the acidic pH of the stomach - WHERE DOES IT GO

A

colonises mucin layer that covers the gastric mucosa
-mucus resists diffusion of protons from stomach acid because it is composed of negatively charged sulphated polysaccharides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

how does H. Pylori survive in the acidic pH of the stomach - short term pH protection during motility

A

urease hydrolyses the urea secreted by gastric cells to produce ammonia and CO2- the ammonia neutralises stomach acid in its immediate vicinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

how does urease work?

A

urease is intracellular so the organism takes up urea and exports ammonia very efficiently to the periplasm where the pH can rise to approx 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

H. Pylori adhesions and neutrophils

A

BabA: adhesin recognising lewis b antigens which binds sulphated mucin sugars on epithelial cells

-NAP: neutrophil leads to inflammation
-VacA: vacuolating cytotoxin produces large vacuoles in mammala cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

UreI is a H.Pylori sensor

A

-an inner membrane protein that facilitates urea entry in a pH-controlled way
-UreI consists of 6 transmembrane regions
-Periplasmic loops and carboxy terminus contain a number of histidine and acidic residues that act as pH sensors through their ionisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Salmonella typhimurium characteristics

A

-Gram negative rod
-motile

-causes gastroenteritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Salmonella typhimurium main virulence factors

A

-acid tolerance responses
-adhesins
-invasion of mucosal cells
-type III secretion system = contact dependent (like a syringe)
effectors that pathogens produce are proteins (hard to diffuse through membrane)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Salmonella typhimurium acid tolerance response type III is induced when …

A

within acidified phagosomes of macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

cultured Salmonella typhimurium grown at neutral pH and shifted to lower pH survives well at pH values down to 4 but …

A

if cells are able to ADAPT (by growth at pH 6 for a generation) they can survive down to pH 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

DNA-binding protein fur

A

regulates a subset of acid shock proteins so fur senses pH as well as iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

mechanisms of acid resistance in gram positive - proton pumps

A

F1/F0 -ATPases from tolerant bacteria are less sensitive to low PH
-glutamate decaboxylases (GAD) : consume protons via glutamate decarboxylation the reaction product (GABA) is exported

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

mechanisms of acid resistance in gram positive - regulators

A

often of glycolytic enzymes to facilitate rapid growth recovery when pH stress is removed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

mechanisms of acid resistance in gram positive - CELL DENSITY

A

a quorum sensing system and biofilm growth allow for increased acid tolerance in S. mutans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

mechanisms of acid resistance in gram positive - envelope alterations

A

s mutans has increased levels of monounsaturated and longer chain fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Obligate aerobes

A

-require O2 for growth; they use O2 as final electron acceptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

obligate anaerobes/aerophobes

A

-do not need or use O2 as a nutrient
-O2 is TOXIC
-kills or inhibits growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

obligate anaerobes may live by

A

-fermentation
-anaerobic respiration
-bacterial photosynthesis (H sulphate as terminal e acceptor)
-methanogenesis (methane from acetate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

facultative anaerobes/ facultative aerobes

A

-organisms that can switch between aerobic and anerobic types of metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

aerotolerant anaerobes

A

-bacteria with an exclusively anaerobic (fermentation) type of metabolism but they are insensitive to the presence of O2 they live by fermentation alone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

ROS

A

reactive oxygen species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

what is generated by cells in the presence of O2

A

oxygen radicals can kill the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

FAD

A

flavodeninedinucleotide

-cofactors involved in oxidation reactions therefore can be inhibited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

all cells contain enzymes capable of reacting with O2

A

-oxidation of flavoproteins by O2 invariably results in the formation of H2O2(hydrogen peroxide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

singlet oxygen

A

-produced by chlorophyll and other pigments in cells that react with O2 in the presence of light

ANOTHER RADICAL which is potent oxidising agent in biological systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

superoxide dismutase (SODS)

A

enzyme
-all organisms that can live in teh presence of O2 contain superoxide dismutase prevents lethal accumulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

catalase

A

decomposes H2O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

certain aerotolerant bacteria such as lactic acid bacteria lack catalase so instead

A

they decompose H2O2 by means of peroxidase
enzymes which derive electrons from NADH2 to reduce peroxide to water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Obligate aerobes lack

A

superoxidase

dismutase
catalase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

all photosynthetic and some non are protected from lethal oxidations of singlet oxygen by their possession of

A

carotenoid pigments which physically react with the singlet oxygen radical and lower it to its non-toxic triplet state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

clostridium spp. - obligately anaerobic pathogens

A

-most clostridia lack respiratory chain cytochromes and the ENZYMES
-they obtain ATP by substrate-level phosphorylation
-a number of clostridia ferment sugars producing butyric acid ; other ferment amino acids
-clostrdia are in soil and some in human flora

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

substrate-level phosphorylation

A

the formation of ATP from ADP and a phosphorylated intermediate

-due to high energy phosphate bonds from organic intermediates are transferred to ADP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Clostridium botulinum

A

-most fatal food poisoning
-commonly found in soil and aquatic sediments
-extremely potent (1mg of pure toxin can kill 1 million guinea pigs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Clostridium botulinum how can it be in food

A

-poorly canned foods create an anaerobic environment unfilled spores germinate and produce toxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Clostridium botulinum different strains produce …

A

7 exotoxin types (A,B,C1,D,E,F,G)

types C and D are encoded by lysogenic bacteriophage that infect the bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

lysogenic bacteriophage =

A

inserts itself into genome

bacteriophage = viruses that target bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

botulism =

A

results from the ingestion of bacterially produced neurotoxins

89
Q

exotoxin - types A, B, E and F are

A

the most toxic for humans these protein exotoxins are often released in an inactive form ; proteolytic cleavage activates them

90
Q

type A exotoxin

A

the most potent known

10 ng can kill a normal adult

91
Q

exotoxins block

A

the release of the neurotransmitter acetylcholine resulting in

-double vision general weakness

92
Q

botulism- paralysis with accompanying respiratory failure

A

can be fatal in 20% of those affected

93
Q

botulism food poisoning can be observed about

A

18-36 hours after ingestion which is heat labile(one that is capable of changing or destruction when subjected to heat)

94
Q

action of botulinum toxin from Clostridium botulinum

A

-acts at motor end plates and prevents release of acetylcholine from vesicles resulting in a lack of stimulation of muscle fibres leading to flaccid paralysis

95
Q

botulinum toxin is expressed as an

A

-inactive 150 kDa polypeptide
-comprising a 100kDa heavy chain (HC)
-50 kDa light chain(LC)
-linked through a disulphide bridge

96
Q

botulinum toxin process

A

1)Hc binds the toxin to the presynaptic receptor
2)toxin enters the cell and the disulphide bond is cleaved
3)cleavage liberates the LC into the cytoplasm and endosomal compartment
4)LC acts as zinc endopeptidase cleaving SNAP/VAMp and syntaxin

prevents fusion of AC vesicles at membrane

97
Q

clostridium tetani

A

-causative agent of tetanus
-from trauma or a puncture wound
-tetanus caused by the release of a SINGLE EXOTOXIN
-adheres to neuronal receptors

98
Q

what does clostridium tetani fit to

A

-gangliosides thereby blocking the release of the neurotransmitters glycine and gamma-amino butyric acid(GABA)
-glycine normally prevents contraction of muscles therefore muscle spasms and convulsions occur

99
Q

the action of tetanus toxin

A

blocks release of glycine (an inhibitory neurotransmitter) so that Acetylcholine release cannot be inhibited therefore muscle is irreversibly contracted

100
Q

tetanus toxin physiology

A

-synthesised as 150 kDa polypeptide chain
-100 kDa HC = c terminal domain binds to gangliosides whilst teh n terminal domain of teh HC allows the LC to cross into the cell cytoplasm
-50 kDa LC

101
Q

tetanus vs botolism

A

-one exotoxin compared to many

102
Q

clostridium tetani how does the host die

A

-from respiratory paralysis though teh underlying tetani infection is elsewhere
-toxin secretion occuring

-the killing of the human host allows C.tetani to multiply as these anaerobic microbes can only grow in tissues that are anaerobic

103
Q

most at risk of tetanus

A

herion addicts

104
Q

clostridium difficile

A

-gram positive, obligately anaerobic, spore former
-antibiotic use reduces concentrations of normal microbiota C.difficile overgrows produces toxins A and B

105
Q

clostridium difficile toxins causes

A

-diarrhoea and lesions on colon surface which coalesce- forming extensive tissue damage known as pseudomembranous colitis
-can be fatal

106
Q

clostridium difficile toxins A and B are

A

large exotoxins that modify host cell membrane G proteins
-mode of action is to alter actin cytoskeleton of mammalian cells

107
Q

clostridium difficile G-proteins

A

-mediated by toxins glucosylating G-proteins

-Glucosyl groups (from UDP-glucose) added to specific threonine residue on the G protein

108
Q

flagellated protozoa

A

African trypanosomes

109
Q

vector borne disease

A

-have arthropod /insect/vector which transmits parasites

110
Q

African tryps-

A

trypanosoma brucei species HAT(human african trpanosoiasis

111
Q

american tryps

A

trypanosoma cruzi and chagas disease

112
Q

communicable disease =

A

infectious

113
Q

vector of disease can be

A

biological or mechanical

114
Q

zoonotic

A

transmissible from animals

115
Q

arthroponotic

A

transmissible from human to human

116
Q

a biological vector includes an

A

extrinsic incubation period which forms part of vectorial capacity

117
Q

horse flies transmit

A

mechanically (interruptive feeding)

-where the fly sucks upinfected blood and injects bacteria on next feed

118
Q

non-resevoir host

A

-dead end host
-parasite goes in but doesnt come out
-may not be susceptible but do provide blodd
-strong evolutionary force to find blood source

119
Q

global warming assits the

A

extrinsic incubation period (ideal temps)

120
Q

kinetoplastids-DIAGNOSTIC TOOL

A

-flagellated forms (locomotion by flagella)
-kinetoplastids distinguished by kinetoplast - a large DNA containing structure

121
Q

morphological forms of hemoflagellates

A

-some forms are highly motile pulled by FLAGELLUM

122
Q

HAT morphological form

A

epimastigot when developing in vector
-trypomastigote when blood form in host

123
Q

epidemiology and distribution of African trypanosomes

DISEASES

A

-sleeping sickness in humans
-lagana in cattle

124
Q

trypanosoma brucei
GAMBIAN

A

-central and W.Africa
-humans
-sleeping sickness (CHRONIC)
-glossina palpalis

125
Q

trypanosoma brucei
RHODESIENSE

A

-East and S.Africa
-humans (zoonosis)
-sleeping sickness (ACUTE)
-glossina morsitans

126
Q

nagana in cattle results in

A

-subacute,acute or chronic disease: anaemia, intermittent fever, diarrhoea, rapid loss of condition and often death

127
Q

Nagana in cattle- T.b Brucei

A

-chronic to mild in cattle

-incubation 5-10 days
-acute in donkeys, horses
NO AQUIRED IMMUNITY WITH AGE

128
Q

Nagana in cattle- T. congolense

A

-severe
-incubation 4-24days
-single important cause in E. AFrica
-major cause in W. Africa
-NO AQUIRED IMMUNITY WITH AGE

129
Q

Nagana in cattle- T vivax

A

-less pathogenic than T.congolense:
-incubation 4-24 days
-most important in cattle in W. Africa
-partial immunity with age

130
Q

emaciation

A

the state of being abnormally thin or weak.

131
Q

Tsetse belt significant to africa

A

-1.6 million DALYs
-agricultural production losses worth US 4.75 bill
-when shipping out cows died within months

132
Q

distribution of trypanosoma congolense and subgroups causing bovine trypanosomiasis

(Nagana-_______)

A

chronic
predominantly in east africa

133
Q

distribution of trypanosoma vivax and subgroups causing bovine trypanosomiasis

(nagana-______)

A

acute
in south america and south africa

134
Q

distribution of trpanosoma evansi causing

A

sura

across globe

135
Q

epidemiology and control of human african trypanosomes

A

-60 million at risk
-in 36 countries
-500,000 cases pa
-deaths 50,000 pa

136
Q

trypanosoma brucei

gambiense vs rhodesiense

G

A

G
-endemic in 24 countries of west and central africa
->90% of reported cases of sleeping sickness worldwide
-chronic disease lasts for several years
-athroponotic transmission (human resevour and vector borne)
-rivereine tsetse vector
-FATAL if untreated

137
Q

trypanosoma brucei

gambiense vs rhodesiense

G

A

R
-endemic in 13 countries of east and south africa
-<10% of reported cases globally
-acute disease lasts for months
-zoonosis transmission (domestic and wildlife reservoirs, vector-borne)
-savannah tsetse vector
-FATAL if untreated

138
Q

tsetse fly -
morsitans group

A

-savannah woodland
-highly mobile
-visual/olfactory cues

139
Q

tsetse fly -
fusca group

A

-humid forest ecology

140
Q

tsetse fly -
palpalis group

A

-riverine woodlands
less mobile
visual cues

141
Q

HAT pathology

A

-two phases
-early stage (haemolymphatic or stage
-late stage (encephalitic or stage 2) SLEEPING SICKNESS

142
Q

sleeping sickness

A

biological clock interrupted and oly sleep during day

143
Q

the early stage of infections

A

parasite spreads through lymphatic system and invades the bloodstream
-chancre arises at site of bite in 50% of R infections (rarely in gamb)

144
Q

early general symptoms

A

-enlarged lymph glands
-local oedema
-cardiac abnormalities
-general malaise
-headaches
-fever

145
Q

late stage neuropathology

A

acute haemorrhagic leucoencephalopathy (AHL)

there is widespread fibrinoid necrosis in the walls of small blood vessels in teh affected regions of the brain

146
Q

T.b gambiense (C and W africa)

pathology

A

-long asymptomatic period (months to years) emergent disease advanced

necessitates early diagnosis

147
Q

T.b grhodesiense (E and S africa)

pathology

A

-acute virulent infection
-incubation 1-4 weeks

quickly detectable

no aquired immunity no vaccine
fatal without treatment

148
Q

mechanisms of HAT

variant surface glycoprotein (VSG) the decoy antigen

A

-covers entire parasite surface including flagellum
-10^6 produced per cell
-molecule is highly immunogenic
-elicits highly strong antibody responses from infected host
-stage-specific

149
Q

VSG the decoy antigen how does it work?

A

-parasite is able to switch VSG expression

-there are&raquo_space;200 VSG genes
-under transcriptional control

150
Q

VSG expression switching leads to

A

undulating fever which can last for months
-parasites from each peak of infection are antigenically distinct

151
Q

diagnosis of HAT

A

-serological test:card agglutination (CATT) for gambiense only
-rapid serological tests (sticks in blood samples)
-microscopy

152
Q

on clinical or serological positive evidence

A

-diagnosis of the stage is necessary step to identify appropriate treatment
-inspection of CSF obtained by lumber puncture to define disease stage
-trypanosomes (or high WBC count) demonstrated in CSF indicates 2nd stage of disease

153
Q

different approaches to control HAT

GAMBIENSE

A

-reduce person to person transmission
- requires active identification of cases
-active or passive case detection and treatment
-vector control plays little to no part of control (low cost effectiveness)
-large scale epidemics in 20th century controlled by 1960s by active case detection and treatment programmes

154
Q

different approaches to control HAT

RHODESIENSE

A

-to reduce transmission from zoonotic reservoirs
-vector control is central (NEED TO INTERRUPT TRANSMISSION CYCLES)
-cattle treatment becoming more common
-case screening conducted for humanitarian reasons

155
Q

vector control prevents initial infection

A

whereas case treatment reduces circulation of parasites

both should reduce disease

156
Q

vector control rationale

A

-low density
-low reproductive potential
-4% sustained mortality of females per day should cause extinction

157
Q

K strategists

A

-dont have millions of offspring
-produce large larvae

158
Q

insecticide applications

A

-traps/targets
-dips or pour on topical treatment
-ultra low volume (ULV) spraying
NOT USED ANYMORE, COSTLY AND ENVIRONMENTAL IMPLICATIONS
-sterile insect technique

159
Q

standard tsetse traps

A

-electrified black target with flanking net
-biconical trap with flanking electrified grid

160
Q

sterile insect techniques
8 million

A

-zanzibar
-1988 tsetse population suppressed using insecticide treated cattle and traps
-seriel release of sterlizid males by aircraft per week
1994-1997 8.5 mill males released

-1995 sterile to normal male ratio 100:1 >70% barren females

1996-7 tsestse population crashed glossina austeni eradicated

161
Q

current gambiense situation in africa

A

-control seems to be working in many places with active foci being generally well known and reducing in size
-political instability makes monitoring less of a priority therefore may hide scale of problem
-most important areas of disease burden in DRC with 85% transmission

162
Q

model predictions of gambiense to achieve elimination

A

-active screening to treat reduced incidence of new human infections by 52-53% over a 15 year period
-model projections indicate elimination goal may not be met until later this century under the current strategy

163
Q

Flagellated protozoa African _____

A

trypanosomes

164
Q

trypanosomes- Uganda two subspecies overlap…

A

making diagnosis essential for treatment

165
Q

Geographical distribution of two HAT subspecies

A

-T.b gambiense west african tyrpanosmiasis
-T.b rhodesiense East african

166
Q

Major epidemics of sleeping sickness in last century

modelling sleeping sickness in SE uganda

A

-human sleeping sickness SRA analysis (0.6%)
-fly biting prefernce human 9% cattle 23%
-cattle 234x more likely to be source of human rhodesiensis than humans
-predicted that 20% of cattle need treatment to achieve R0<1

167
Q

through time subspecies of Rhodesiense are getting

A

closer together

168
Q

Stamp out sleeping sickness (SOS) initiative

A

-public-private partnership launched in uganda 2006
-response to possible convergence of rhodesiense and gambiense in N.Uganda because treatment where human infections are mixed is more difficult

169
Q

SOS drugs early stage disease 1st line drugs

A

-Suramin efficacious against rhodesiense
-pentamidine efficacious against gambiense
-pentamidine is not effective against early stage rhodesiense

170
Q

SOS drugs late stage 1st line

A

-melarsoprol (arsenic so side effects) efficacious against both
-late stage treatment failures of gambiense increasing
-an alternative is eflorinithine but not effective against rhodesiense

171
Q

Restricted application protocol (RAP)

A

cows dipped in insecticide
-convenient however large amount required $$$
-need knowledge of other ticks to kill off multiple things

172
Q

Babesiosis in cattle

A

-incubation 3-21 days
-high fever anorexia, seek shade, weight loss, abortion, poor milk production
-extensive erthrocytic lysis :75% erthrocytes destroyed in a few days
-most survive but mortality up to >50% known slow recovery (AGIRCULTURE QUESTION IF WORTH TREATING)
-carrier status (low parasitaemia) for years

173
Q

cattle babesiosis tick vectors

A

-Babesia pass into ovaries/eggs - vertical or transoverial transmssion
-migrate into salivary glands to reproduce in larvae
-larvae await on grass stalks to attach
-babesia from salivary glands injected into mammals bloodstream

174
Q

___ _______ cattle in tropical and subtropical regions of the world are at risk to infection with babesia bovis and babesia bigemina

A

300 million

175
Q

complexcity of insecticide treatment of cattle

A

-insecticides kill both ticks + tsetse
-need to maintain tick exposure while preventing tick bites
-insecticide costs

176
Q

TBD endemic.enzootic stability CRITERIA

A

1)disease is more likely or more severe in older rather than younger susecptibles
2)following infection the probability that subsequent infection results in disease is REDUCED

177
Q

endemic stability descrbes

A

a dynamic epidemiological state in which clinical disease is rare in spite of a high incidence of infection within a population

178
Q

Criteria met by babesiosis

A

-1-2 met by babesiosis, cowdriosis and anaplasmosis
-uncertain for theileria
-nagan (t.b brucie, t.b congolense, t vivax) age not related to severity and no conferred immunity

179
Q

Cattle age-dependent tick fever severity

A

-calf exposure to infected ticks is key to immunity
-the age of first exposure determines severity
-if exposed by 9 months long lasting immunity

180
Q

measure to maintain endemic stability

A

WHERE TO TARGET INSECTICIDe
1)Tsetse more suspecitble to pyrethroid-treated cattle than are ticks - increasing intervention interval lowers impact on ticks
2)tsetse preferentially feed on different sites of body particularyly legs- avoid tick attachment sites

181
Q

porportion of tsetse blood meals on cattle increases with

A

cattle weight

182
Q

daily probability of tryp infection if in a mixed cow age herd

A

-more liekly to be infected if ox than cow than calf

183
Q

solution towards sustainable control by farmers

A

-tsetse preferentially feed on older and larger herd members - leave young cattle untreated to become exposed to ticks
-treating half the herd (insecticide to larger individuals) would only be slightly less effective and cheaper
-selective treatments of hosts with restricted application protocol (RAP) reduce insecticide costs by 90% compared with teh current regime of treating entire herd)

184
Q

vector control in absense of cattle

A

-minimum densities of 10 cattle/km^2 are necessary for cattle to be an important part of tsetse blood source depending on availability of zoonotic hosts
-precludes the use of RAP in many gambian HAT foci
-traditional biconial traps and deplyment is expensive costing an estimated US556 dollows per kilometre squared
-one recent disovery is theuse of tiny insecticide impregentaed targets against gambian transmission)

185
Q

Tiny traps

A

look on slides lecture 6

186
Q

Apicomplexan parasites

A

-Eukaryotic
-obligate parasites (have to have a host)
-one or multiple hosts depending on the species
-extremely important as disease agents
-malaria parasites (plasmodia)
-coccidia
-Prioplasms

187
Q

Apical complex

A

-distinctive to apicomplexans
-key cellular machinery for host cell invasion
-some apicomplexans are motile and apical complex is essential for movement
-includes secretory organelles
-subpellicular membranes enable parasite feeding from host

188
Q

host cell invasion

A

-conoids protrude into host cells in response to calcium
-rhoptries are secretory organelles releasing rhoptry protein sinto host during invasion
-micronemes also secrete proteins into host cell
-parassitophorus vacuole is formed
-parasite moves into parasitophorus vacuole
-polar ring is a microtubule organising centre

189
Q

Apicomplexan life cycles

A

-can involve one or more hosts (human and mosquito)
-sexual - gametes fuse to form zygote
-asexual - sporozoites differentiate to form merozoites
-merozoites undergo multiple rounds of replication
-some merozoites differentiate into gamonts
-gamonts differentiate into gametes

190
Q

malaria intro

A

-life thretening
-caused bt PLASMODIAN APICOMPLEXAN PARASITES
-mosquito vectors are becessary for disease transmission
-half of worlds population at risk - mainly in tropical areas
-disease can acuse considerable morbidity and mortality

191
Q

morbidity =

A

having disease or illness

192
Q

malria most often occurs in

A

tropics

193
Q

malaria - causative agents and vector

A

majority of morbidity and mortality is caused by Plasmodium falciparum and vivax

-vector is female anopheles mosquito

194
Q

plasmodium life cycles

A

-always involves mammal and female mosquito as hosts
-in insects -> gametes fuse to form zygote which forms oocyst
-in humans
sporozoites differentiate to form merozoites
-merozoites undergo multiple rounds of replication
-some merozoites differentiate into gamonts
-gamonts differentiate into GAMETES

195
Q

disease presentation
-asymptomatic malaria -

A

circulating parasites but no symptoms (could be due to previous immunity)

196
Q

disease presentation
-uncomplicated malaria

A

-nonspecific symptoms
-fever,shaking chills, profuse sweating, headache, nausea, vomiting, diarrhoea and anaemia (due to RBCs popping)

197
Q

disease presentation
complicated malaria

A

-as above with additional organ damage and anaemia associated with hyperparasetemia and increased mortality
-extreme tiredness and fatigue
– impaired consciousness
– multiple convulsions
– difficulty breathing
– dark or bloody urine
– jaundice (yellowing of the eyes and skin)
– abnormal bleeding

198
Q

hyperparasetemia

A

higher parasite load

199
Q

Plasmodium falciparum specific complications
-cerebral malaria

A

(often fatal) high temps with convulsions and coma infected erythrocyte’s adhere to capillary endothelial cells-erythrocytes become knobbly, as a result of parasite proteins exported to the membrane these bind to ligands on host cells

200
Q

Plasmodium falciparum specific complications
-blackwater fever

A

-massive lysis of erythrocytes causes high levels of free haemoglobi. in the blood and renal failure
-presence of haemoglobin in the urine gives the condition its name

201
Q

Co-evolution of plasmodia and humans results in arms race
plasmodia

A

-plasmodia adaptations include array of hypervariable membrane proteins to switch between and evade immune system

202
Q

Co-evolution of plasmodia and humans results in arms race
human

A

-higher proportions of people lacking duffy (dont have receptor for p vivax to bind to) therefore cant invade cells
-several inherited erthrocyte disorders in endemic areas offering protection against infection
-Eg sickle cell anaemia in malarial endemic aress as having heterozygous alleles offers protection from plasmodia

203
Q

apicomplexian - an arms race

A

-the plasmodium falciparum genome contains a large family of 60 var genes that encode hypervariable. P. falciparum erthrocute membrane protein 1(PfEMP1)
-during the erythocytic stage each parasite expresses one of its var genes at a time
-by switching between different var genes during the course of infection the parasite is able to evade destruction by host immunity
-protective immunity lasts only as long as residual population of parasites is present, if the person is completly cured susceptibility returns (this is the reason most vaccines are ineffective)

204
Q

arms race continued

A
  • P. vivax can only enter erythrocytes with genetically determined receptor sites known as Duffy blood groups.
  • Individuals which lack these antigens are refractory.
  • A large proportion of the populations in western Africa are Duffy negative,
    accounting for the low levels of P. vivax in west Africa.
  • This innate resistance led to the identification of the Duffy antigen as the
    erythrocyte receptor for merozoite invasion.
  • Several inherited erythrocyte disorders are found predominantly in malaria endemic areas and at frequencies much higher than expected.
205
Q

sickle cell anaemia

A

-sickle cell anaemia is protective against malaria a glutamic acid residue is in the amino acid sequence of haemoglobin is replaced by a valine which reduces oxygen carrying capacity
-those with homozygous alleles often die before 30 but those with heterozygous alleles have some normal haemoglobin and have 80-95% protection against p.vivax
-sickled cells tend to get stuck in narrow blood vessels, blocking flow of blood

206
Q

malaria diagnosis

A

-WHO criteria: fever and presence of parasites
-light microscopic examination of a blood smear
-rapid diagnostic test

207
Q

treatment recommendations

A

-P.falciparium- artmisinin combination (ACT) artemisinin derivative plus quinine derivation
-p vivax and p ovale- chloroquine unless drug resitance issue in area then ACT
-drug resistance is a major concern

208
Q

malaria vector control

A

-widespread insecticide/ larvicide
-destruction of breeding grounds
-indoor residual spraying (IRS)
-long acting insecticide treated bednets (ITN)
-experimental methods in pipeline

209
Q

insecticide treated bednets (ITNs)

A

-shown to reduce devere disease and mortality due to malaria in endemic regions
-reduce mortality by 20%
-currently only pyrethroid insecticides ae appropved due to low mammalian toxcity and may have knock on effect on insects
-Long-lasting insecticidal nets (LLINs) are the preferred form of ITNs for public health programmes.

210
Q

Pyrethroids

A

have a high residual effect: they do not rapidly break down unless washed or exposed to sunlight.
*The need for frequent retreatments (6-12 months) was one of the most difficult barriers to full implementation of ITNs in endemic countries.

211
Q

drugs used for malaria prophylaxis can work in one of three ways

A

1)kill parasites in liver (causal prophylaxis)
2)kill asexual parasites in RBCs suppressive prophylaxis
3)kill sexual parasites (gametophytes) in RBCs gametocytocidal prophylaxis

212
Q

malaria vaccines

A

-recent vaccine developments offer hope

-RTS, S
-virus like particle (VLP) vaccine based on teh P falciparum circumsporozoite protein (CSP)
-tagets sporozoites injected by mosquito
-three primary doses plus booster
-efficacy 55%

213
Q

R21 vaccine

A

-based on the falciparum cicumsporozite protein (CSP)
-three primary doses plus booster
-efficacy 75%

214
Q

malaria impact of covid

A

-fragile health system capacity overwhelmed
-misdiagnosis as covid-19 or flu
-decreased funding
-malaria controld delivery systems impact by supply chain disruption

215
Q

experimental approaches to control

A

-endectocides (systemic insecticides to kill mosquito feeding of them)
-sterile insect techniques
-CRISPR/CAS9 gene drives
-biocontrol using bacteria or fungi that infect the mosquito and prevent development of the plasmodium

216
Q

sterile insect techniques

A

-irradiated males
-GM spermless males
-are not as competitive in mating flights

217
Q

gene drive

A

-all male off-spring
-females sterile
-mosquitos resistant to plasmodium parasite
-ethics concern about relase and food chains

218
Q
A

microbial pathogens (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions