Emerging infectious diseases - Pathogens Flashcards
1
Q
To which group of viruses does Mpox belong?
A
Poxviridae
2
Q
Which groups of animals can be infected by poxviridae?
A
- Vertebrae
- Insects
3
Q
Which two obligate human pathogens can be found in the family of poxviridae?
A
- Variola virus (smallpox)
- Molluscum contagiosum virus
4
Q
What are common zoonotic pathogens of the poxviridae? (3)
A
- Cowpox
- Vaccinia virus
- Monkeypox
5
Q
What are the genomic characteristics of poxviridae?
A
Large and complex linear dsDNA viruses
6
Q
What is the prototypic shape of poxviridae?
A
Brick-shaped tagument surrounded by an envelope
7
Q
Where in the cell do poxviridae replicate?
A
Cytoplasm
8
Q
Which stages of gene transcription are there during poxvirus replication?
A
- Early gene transcription
- Intermediate gene transcription
- Late gene transcription
9
Q
During particle production of poxviridae, different types of particles are produced. Which? (3)
A
- Intracellular mature viruses particles (IMV)
- Intracellular enveloped particles (IEV)
- Extracellular enveloped particles (EEV)
10
Q
Immature virions of poxviridae are much [smaller/larger] than mature virus particles
A
Immature virions are larger than the mature particles
11
Q
When was smallpox declared eradicated by WHO? When did smallpox vaccination stop?
A
Eradication: 1980
Vaccination stopped in 1985
12
Q
When was Mpox first identified?
A
1958
13
Q
What is the animal reservoir of Mpox?
A
Unknown, detected in various species
14
Q
When was the large Mpox outbreak?
A
2022
15
Q
Were there cases of Mpox in humans before 2022?
A
Yes, but only sporadic
16
Q
How many clades of Mpox are there? Where are these clades indigenous?
A
Clade I: Congo
Clade II: West-Africa
17
Q
Which of the Mpox clades is more pathogenic?
A
Clade I
18
Q
Which clade of Mpox was responsible for the 2022 outbreak?
A
II2b
19
Q
Mpox is genetically [unstable/stable]. Why?
A
Stable, due to Pol-proofreading
20
Q
What is the most common cause of death in humans that have been infected by Mpox?
A
Brainstem encephalitis
21
Q
How is Mpox transmitted from animal to human? (3)
A
- Hunting/consumption of infected animals
- Bite/scratch from infected animals
- Contact with infected secretions/lesions
22
Q
How is Mpox transmitted from human to human? (3)
A
- Respiratory droplets in close contact
- Direct contact with lesions
- Contaminated objects
23
Q
Why is Mpox less transmissible than smallpox?
A
Smallpox was very transmissible via aerosols, Mpox less so
24
Q
What is the incubation period of Mpox?
A
7-21 days
25
Which phases can be distinguished after Mpox infection?
1. Incubation period
2. Prodormal phase = fever-like symptoms
3. Rash phase
26
How long does the prodromal phase of Mpox last? What are its symptoms? (8)
1-4 days, with flu-like symptoms
1. Headache
2. Myalgia
3. Fever
4. Chills
5. Sore throat
6. Malaise
7. Fatigue
8. Lymphadenopathy
27
How long does the rash phase of Mpox last? What are its symptoms?
2-4 weeks, during which a skin rash forms that develops into papules and vesicles
28
Mpox causes a centrifugal rash. What does this mean?
Develops in the extremities, then migrates towards the rump
29
How can the migration pattern of Mpox be used to distinguish it from chickenpox?
Mpox has a centrifugal pattern (extremities to rump), whereas chickenpox is the other way around (rump to extremities)
30
True or false: chickenpox is a virus belonging to the poxviridae
False; chickenpox is not a poxvirus!
31
What are the proposed pathogenic phases in Mpox? (3)
1. Virus entry, starts replication in draining lymph nodes and causes primary viraemia
2. Primary viraemia allows more lymphoid organs to be infected -> massive viral replication -> secondary viraemia
3. Infection of tertiary organs/skin -> clinical manifestations
32
Why was the clinical presentation of the 2022 Mpox virus atypical? (2)
1. Presented as solitary genital lesions, causing delayed diagnosis due to a differential diagnosis of many STDs
2. Lesions involving palms & soles
33
Why does the long incubation/asymptomatic phase of Mpox increase transmission?
Individuals can transmit a lot of virus in this period, usually via sexual contacts
34
What are Mpox risk factors in endemic areas? (4)
1. Living in forested areas
2. Disease burden in children & females
3. Human-to-human transmission through close contact
4. Nosocomial infection of females
35
What was the major risk factor in the 2022 Mpox outbreak?
Unprotected sexual contact, mainly among MSM
36
What are available preventions & treatments for Mpox? (4)
1. Supportive care during infection
2. Vaccinia immunoglobulin (crossreactive)
3. Vaccines (crossreactive from smallpox)
4. Antivirals effective against orthopoxviruses
37
In which group was vaccinia immunoglobulin used for treatment of Mpox?
Immunocompromised individuals, unable to generate a humoral immune response
38
How many generations of smallpox vaccines are there?
4 (0, 1, 2, 3)
39
What is considered to be the 0th generation of smallpox vaccines?
Variolation
40
What is variolation?
Transfer of a small amount of smallpox/cowpox virus into uninfected individuals
41
What is the 1st generation of smallpox vaccines?
Unattenuated vaccinia virus grown on the skin of live animals, then freeze-dried
42
What is the 2nd generation of smallpox vacines?
Vaccinia virus purified from cell lines
43
What is the 3rd generation of smallpox vaccines?
Modified vaccinia virus, grown in primary chicken fibroblasts
44
Why are vaccines against smallpox also protective for Mpox?
Crossreactivity, with similar antibodies against the two viruses
45
Which antivirals against smallpox are available? What is their target? (3)
1. Tecovirimat: viral protein p37
2. Cidofovir: DNA polymerase
3. Brincidofovir: prodrug of cidofovir
46
What is the disadvantage of cidofovir?
Nephrotoxicity
47
How can antivirals against smallpox be developed, despite the virus being eradicated? (no human testing possible)
FDA animal rule: allowing for the approval of drugs/biologial products based on animal studies only when human efficacy studies are not ethical/feasible
48
Why do compounds approved under the FDA animal rule still need to be tested in humans?
To establish their pharmacokinetic properties
49
To which family and genus does poliovirus belong?
Family: picornavirales
Genus: enterovirus
50
What is the genetic structure of poliovirus?
RNA+ virus
51
How many species of enterovirus are there?
~350
52
Which enteroviruses are human pathogens? (4)
A, B, C, D
53
Which groups of clinical manifestations of poliovirus can be distinguished? (5)
1. Asymptomatic
2. Non-paralytic polio
3. Non-paralytic CNS disease
4. Paralytic poliomyelitis
5. Bulbar paralytic poliomyelitis
54
What are symptoms of non-paralytic polio? (7)
1. Fever
2. Sore throat
3. Headache
4. Vomiting
5. Fatigue
6. Pain/stiffness in back, neck, arms or legs
7. Muscle weakness or tenderness
55
What is the most frequent non-paralytic CNS disease caused by poliovirus?
Meningitis
56
What symptomatology does paralytic poliomyelitis cause?
Acute flaccid paralysis
57
What is bulbar paralytic poliomyelitis?
Acute flaccid paralysis with involvement of the brain stem
58
There [is/is not] a treatment for polio available
No treatment available; only supportive therapy
59
What increases the chance of severe symptomatology in polio infection?
Higher age
60
What are the clinical outcomes after paralytic poliomyelitis (%)?
~10% = complete recovery
~80% = permanent paralysis
~10% = fatal (higher in case of bulbar involvement)
61
What is post-polio syndrome?
A syndrome that occurs 15-60 years after initial polio infection, in 20-75% of polio survivors
62
What are the sypmtoms of post-polio syndrome? (5)
1. Muscle atrophy and weakness
2. Pain
3. New disabilities
4. Fatigue
5. Sleeping problems
63
Which two vaccines for polio are available?
1. Salk-inactivated polio vaccine
2. Sabin live-attenuated vaccine
64
What are the advantages of the Salk polio vaccine? (2)
1. Almost 100% seroconversion, prevents severe disease
2. No severe side effects
65
What are the disadvantages of the Salk polio vaccine? (4)
1. Requires a cold chain
2. Expensive
3. Needles required
4. Low intestinal immunity -> only reduced viral shedding
66
What are the advantages of the Sabin polio vaccine? (5)
1. Cheap
2. Provides intestinal immunity
3. Passive immmunisation of unvaccinated persons by shedding vaccine virus
4. No cold chain required
5. Oral drops -> easy to administer
67
What are the disadvantages of the Sabin polio vaccine? (3)
1. Can acquire virulence mutation
2. Can cause vaccine-associated paralytic poliomyelitis (VDVP)
3. Can lead to circulation of VDVP virus
68
What is the global polio eradication initiative?
An effort to complete the eradication and containment of all wildtype and vaccine-related polioviruses
69
How much has the global incidence of polio declined since the global polio eradication initiative started?
99%
70
Which types of polio have been eradicated?
WPV2, WPV3
71
Where does the WPV1 polio type still circulate?
Pakistan & Afghanistan
72
Why are there still outbreaks of poliovirus from time to time outside of areas in which the wildtype virus circulates?
Vaccine-associated paralytic poliomyelitis due to use of the Sabin vaccine
73
Why has the triple oral polio vaccine been changed into a bivalent vaccine?
WVP2 has been eradicated since 2015 -> no longer a need to vaccinate
74
Why is removal of WVP2 from the polio vaccine advantageous?
WVP2 caused the majority of VDVP-cases
75
Why does eradication of poliovirus not mean eradication of all acute flaccid paralysis?
There are more viruses/pathogens that can cause acute flaccid paralysis, such as neutrotropic enteroviruses
76
How does enterovirus D68 present itself?
Severe respiratory illness, followed by acute flaccid paralysis 4-5 days after respiratory disease in some patients
77
How long after respiratory disease does enterovirus D68 cause acute flaccid paralysis?
4-5 days
78
When is the number of enterovirus D68-caused acute flaccid paralysis highest?
Along with the seasonal pattern of enterovirus D68, on a biannual cycle
79
What are the main complications of enterovirus D68 infection? (2)
1. Predominantly severe respiratory disease
2. CNS diseases such as acute flaccid paralysis, cranial nerve dysfunction & encephalomyelitis
80
In which group does enterovirus D68 (mainly) cause severe respiratory symptoms? Which group is even more severely affected?
Children, with asthma being an exacerbating factor
81
In which respect does the replication of enterovirus D68 differ from other enteroviruses?
It replicates in the respiratory tract -> behaves more like a rhinovirus
82
What are characteristics of enterovirus D68 that do not allow it to replicate in the intestine? (2)
1. Acid sensitivity
2. Replication optimal at 33 °C (other enteroviruses @37 °C)
83
Which part of the respiratory tract is infected by mild infections of enterovirus D68? Which cell types?
URT -> infection of respiratory epithelial cells
84
When does enterovirus D68 cause severe respiratory symptoms?
When it infects the LRT, causing pneumonia and severe asthma exacerbations
85
How does enterovirus D68 disemminate systemically?
Infection of lymphoid tissues, after which viraemia occurs
86
How does enterovirus D68 enter the CNS to cause pathology?
Mechanism largely unknown
86
What are CNS complications of enterovirus D68 infection? (5)
1. Acute flaccid myelitis = most common
2. Cranial nerve dysfunction
3. Encephalitis
4. Aseptic meningitis
5. Meningo-encephalitis
87
What are the proposed routes of CNS infection by enterovirus D68? (4)
1. Cranial nerves
2. Viraemia
3. Infection of endothelium of blood-brain barrier
4. Trojan horse -> infection of leukocytes that travel into the CNS
88
How does poliovirus enter the CNS?
Infection of skeletal muscles, after which the virus can infect motor neurons through the motor end plate
89
How can acute flaccid myelitis due to enterovirus D68 infection be prevented?
Antibodies against EV-D68 -> vaccination or monoclonals
90
When was MERS-coronavirus identified?
2012
91
Why does the incidence of MERS follow a characteristic peak pattern?
Every peak is due to a seperate zoonotic event, after which the infection dies down
92
Why are there no vaccines needed to stop MERS outbreaks?
Quarantine & isolation very effective
93
What are MERS-vaccines currently used for?
Vaccination of dromedaries to prevent zoonosis
94
True or false: there is no human MERS-vaccine available
False; a vaccine has been available since 2018
95
Which aspects are needed for MERS outbreak control? (3)
1. Identification & characterisation of pathogen
2. Development of diagnostics
3. Identify & isolate infected individuals & place contacts in quarantine
96
From which viruses does MERS originate?
Bat CoVs
97
What is the animal reservoir of MERS coronaviruses?
Dromedary camels
98
What is the entry receptor for MERS?
DPP4
99
Where is the DPP4 receptor (used by MERS to enter cells) located in dromedary camels vs. in humans?
Dromedary camels: URT
Humans: LRT -> causes pneumonia
100
When was SARS-CoV first detected?
2003
101
How many days post-infection do respiratory symptoms start to deteroriate in SARS?
~9 days
102
What happens to the viral load as SARS respiratory symptoms worsen?
Viral load decreases
103
What causes fatalities of SARS-CoV infections?
ARDS
104
In how many % of SARS-CoV infected individuals does ARDS occur?
15%
105
How is SARS-CoV transmitted?
Direct or indirect contact
Possibly droplets
106
Which receptor do SARS-viruses use to enter cells?
ACE2
107
Why were no vaccines needed to contain SARS? (2)
1. Virus-excretion in SARS-patients peaked after LRT symptoms -> patients easy to recognize, diagnose & quarantine
2. Few asymptomatic cases
108
Why did SARS-CoV-2 infect many more individuals than the original SARS-virus? (2)
1. Virus release peaks before symptoms
2. Many asymptomatic individuals
