Central Nervous System Infections Flashcards
1
Q
How does rabies differ from most CNS infections?
A
Infecting the CNS is an integral part of infection with 2 clear purposes.
- Needs to get from bite site to salivary glands
- Needs to change behaviour of animal (‘limbic system’)
- Specifically changes behaviour of cells with limited damage
2
Q
What occurs in most infections that infect the CNS?
A
Often the result of accidentally infecting the CNS
Typically not a good result for the pathogen
- Damages host
- Moves pathogen to area unlikely to assist transmission
- Disease symptoms of result from host (immune) response and/or cell damage
3
Q
Why is CNS homeostasis so important?
A
It is a highly sensitive tissue - non-renewable cells
Specialised privileged compartment
Highly metabolically active - solutes, waste products
Control of environment very important
4
Q
What are the 2 selective gateways that physically separate the CNS from the rest of the body?
A
Blood-brain barrier (BBB)
Blood-Cerebrospinal fluid barrier (BCSFB)
5
Q
What is the role of the BBB and BCSFB?
A
Protect the brain:
- Sudden changes in the blood/periphery
- Inappropriate immunity/inflammation
- Microbial infection
6
Q
What type of inflammatory environment is the CNS?
A
An anti-inflammatory environment
- Suppression of immunity
7
Q
What can be seen as a result of immune responses in the CNS?
A
- Can remove microbes but can also cause symptoms
- Major cause of symptoms of many infections
- Neurons do not regenerate
8
Q
What are the two outcomes of CNS infections?
A
Meningitis
Encephalitis
9
Q
What is meningitis?
A
Inflammation of meninges - layers surrounding the brain
10
Q
What is encephalitis?
A
Inflammation of brain ‘substance’ [tissues/paranchyma]
11
Q
What types of microbes cause meningitis?
A
Bacteria
Fungi
Protozoa
Viruses
12
Q
What types of microbes cause encephalitis?
A
Viruses
Prions
Parasites
Bacteria - toxins
13
Q
What physical feature is the brain protected by?
A
Skull
14
Q
What physical feature is the spinal cord protected by?
A
Vertebral column
15
Q
What is the brain surrounded by under the skull?
A
The meninges containing CSF
16
Q
What is the role of the meninges?
A
Mechanical support, protection and homeostasis
17
Q
What is the important of having contacts across the barriers?
A
Required for signalling, nutrients, metabolites
18
Q
What crosses the barriers of the CNS?
A
Blood vessels
Nerves
19
Q
What is the role of the BBB and BCSFB?
A
Selective regulated exchange
Maintain homeostasis
Protects from immunity
Protect from infection
20
Q
What is the major route of CNS infection and what pathogens use it?
A
Blood vessels
Bacterial species, Polio virus
21
Q
What are the 4 routes for CNS infection?
A
Blood vessels
Peripheral nerves
Invasion through ears/sinuses and olfactory nerve
Penetrating injury/surgery
22
Q
What are 2 pathogens that infect the CNS through peripheral nerves?
A
Rabies
Herpes simplex
23
Q
How much and where is the CSF contained?
A
Within the subarachnoid space (between the arachnoid mater and pia mater)
140ml
24
Q
What is the CSF produced by?
A
Produced by choroid plexus
25
What is the Blood Brain Barrier?
Endothelial cells of capillary
Tight junctions between capillary endothelial cells
Thick basement membrane surrounding capillary
"Feet" (processes) of astrocytes in brain surrounding capillary
No fenestrations
26
What is the BCSFB?
Endothelial cells of capillary
Basement membrane
Tight junctions between choroid plexus ependymal (epithelium) cells
27
What is the difference between BCSFB and BBB?
```
BCSFB is:
Less tight than BBB
Thinner basement membrane
Looser junctions
Vessel endothelium has fenestrations
```
28
Crossing the BBB results in what type of infection?
encephalitis
29
Crossing the BCSFB results in what type of infection?
Meningitis
30
What are 3 mechanisms by which pathogens can cross BBB/BCSFB and cause infection?
Transcellular
Pericellular
Trojan Horse
31
What is the mode of action of the transcellular mechanism?
- Infection (growing across ECs)
- Passive transport (not infection) through endothelium cells in vacuoles
- > receptor binding and endocytosis as for physiological cargos
32
What is the mode of action of the pericellular mechanism?
Transport between cells (if tight junctions weakened by inflammation)
-> bystander effect
33
What is the mode of action of the trojan horse mechanism?
Inflammation can allow infected white blood cells to enter CNS
34
How does Rabies get into the CNS?
Rabies viruses -> muscle -> enters peripheral nerves -> travels to CNS
35
Do peripheral nerves cross the BBB/BCSFB?
No they entirely circumvent it
36
How does HSV get into the CNS?
HSV skin lesion -> enters peripheral nerve -> moves to dorsal root ganglia; becomes latent -> on reactivation usually returns to lesion, sometimes enters CNS
37
How are cellular cargos (sometimes our pathogen) moved from the peripheral nerves to the CNS?
Use molecular motors (Dynein) that move along microtubules in neurons toward the CNS
38
What is the mode of action of invasion via the olfactory route?
Nasal passages -> olfactory tract -> mengingitis/encephalitis
e.g. protozoa Naegleria fowleri
amoeba that lives in stagnant water
39
Which entry pathway does Naegleria fowleri use to enter the CNS?
Olfactory route
40
What is the immune status of normal CNS?
- Quiescent but can mount a response
- has immune cells but fewer than other tissues
- protected by immune cells, macrophages (meninges), microglia (brain parenchyma)
- small number of resident T cells perform immune surveillance
41
Which immune cell protects meninges?
Macrophages
42
Which immune cell protects brain parenchyma?
Microglia
43
What is the immune status of the CNS during infection?
Resident macrophages activate T cells
- pro-inflammatory cytokines released: causing loosening of tight junctions, recruiting immune cells (pericellular)
- more immune cells enter CNS
- large number of immune cells crossing into CNS caue capillaries to become leaky
BBS/BCSFB is compromised
44
Through which mechanism do immune cells enter the CNS?
Pericellular mechanism
45
Which immune cells are recruited for free living bacteria in the CNS?
neutrophils
46
Which immune cells are recruited for viruses in the CNS?
lymphocytes
47
What are some disadvantages of the immune response?
- Can cause damage to the host
| - May develop low blood pressure and/or swelling of the brain within the skull
48
Compare the immune responses for bacteria vs viruses
```
Bacteria:
Rapid immune response
Highly inflammatory
Causes a lot of damage
Viruses:
Less rapid
Less inflammatory
Less damage
```
49
After recovery from initial infection in CNS, what can occur?
autoimmunity, may happen years later
50
What is the pathogenesis of a CNS infection?
It is the combination of pathogen and host immune response
51
What are the 4 sources of pathogenesis in CNS infection?
1. Cell death/damage
2. Cellular dysfunction
3. Immune response
4. Neurons are non-regenerative - can see permanent damage
52
What source of pathogenesis does Rabies use?
Cellular dysfunction
53
What source of pathogenesis does Polio use?
Cell death/damage - lyses neurons for release
54
What cell type does rabies infect?
Neurons
55
What cell type does Polio infect?
Neurons
56
What cell type does JC virus infect?
Oligodendrocytes
57
What source of pathogenesis do bacteria tend to incur?
Immune response
58
How do we monitor CNS?
Through testing CSF, can provide information on the nature of potential infections of CNS
- Lumbar puncture
59
What is the gold standard for diagnosis of bacterial meningitis?
CSF examination
| Positive CSF signs in 80-90% of cases of confirmed bacterial meningitis
60
```
Compare
normal CSF
aseptic meningitis (viral) and
pyogenic; bacterial meningitis
in terms of immune cells
```
```
Normal CSF:
- quiescent
- very few WBCs
- all are lymphocytes or monocytes
- NO neutrophils
Viral:
- Increase in lymphocytes (mostly T cells)
- Neutrophils: usually in low numbers
Bacterial:
- Really high numbers of neutrophils (90% of acute cases)
- NOT for TB
```
61
```
Compare
normal CSF
aseptic meningitis (viral) and
pyogenic; bacterial meningitis
in terms of protein
```
```
Normal:
170-550 mg/L
Viral:
Moderately high, 500-1000 mg/L
Bacterial:
High to very high; >1000-5000 mg/L
NOT for TB
```
62
```
Compare
normal CSF
aseptic meningitis (viral) and
pyogenic; bacterial meningitis
in terms of glucose
```
```
Normal:
500-800 mg/L
Ratio of normal CSF/blood - c. 0.6
Viral:
Normal or slight increase
Bacterial:
Low glucose
Ratio CSF/blood c. 0.4
NOT for TB
```
63
```
Compare
normal CSF
aseptic meningitis (viral) and
pyogenic; bacterial meningitis
in terms of CSF appearance
```
Normal:
clear, no bacterial growth in bacteriological culture
Viral:
Clear, no microscopic evidence, no bacterial growth in bacteriological culture
Bacterial:
often cloudy, bacteria can be observed (microscopy - gram stain) and/or cultured
64
What accounts for the difference in protein and glucose levels between viral and bacterial CNS infections?
Bacteria are free-living organisms, they require glucose for metabolism so steal from host lowering the blood glucose, they also multiply and to do that create more protein thus increasing protein levels that can be detected.
Viruses cannot grow independently and survive in host cells. Therefore, they don't require glucose from the host and the host cells use glucose as normal. In terms of protein more viruses are being produced and viruses have protein components therefore it makes sense that more virions means more protein.
65
Why are some 'aseptic' CSF samples misleading?
They may contain slow-growing bacteria/fungi
e.g. TB, partially treated bacteria
Due to low numbers or species of microorganism CSF changes are subtle and/or bacteria/fungi can't be observed or cultured
66
How many cases of bacterial meningitis in US each year?
100,000
67
How many cases of bacterial meningitis in Sub-Saharan Africa each year?
100-1000 cases per 100,000 people
68
Can bacterial meningitis be treated?
Yes but only with prompt administration of appropriate antibiotics
69
What are the most common causes of bacterial meningitis in high income countries prior to specific vaccines?
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis
70
What are the most common causes of bacterial meningitis in high income countries after specific vaccines?
```
Streptococcus pneumoniae (many serogroups)
Neisseria meningitidis (different serogroups, geographical)
```
71
What is the clinical presentation of acute bacterial meningitis?
1. fever (77% of cases)
2. stiff neck (83% of cases)
3. altered mental state (69% of cases)
4. headache (87% of cases)
72
What is the classical triad of acute bacterial meningitis?
Fever, stiff neck, altered mental state
73
What causes a stiff neck in acute bacterial meningitis?
Body response: rigidity protects subarachnoid space
74
What is meant by altered mental state in acute bacterial meningitis?
- Nausea/vomiting
- irritability/excitability
- decreased level of alertness or consciousness
75
What percentage of adults present with the classical triad in acute bacterial meningitis?
44%
76
What percentage of adults present with 2 of the 4 signs of acute bacterial meningitis?
95%
77
How do babies/small children present with acute bacterial meningitis?
May only be irritable/less alert and look unwell
78
What percentage of adults show a rash/septicaemia in acute bacterial meningitis?
25%
79
How is acute bacterial meningitis diagnosed?
History of patient:
- knowledge of current illness/treatment, living environment and region, vaccination status, contact with children, recent travel
Physical examination:
- skin rash, septicaemia - late stage
Check if blood culture already available:
- 10-15% meningitis cases have septicaemia first
CSF examination
80
How is CSF examined in acute bacterial meningitis?
Look for CSF indicators
PCR to amplify bacterial DNA from CSF sample
Microscopy - gram stain
Positive bacterial culture
- used to identify species and antibiotic susceptibility
81
How should acute bacterial meningitis be treated?
It is a medical emergency
Antibiotics need to be given IMMEDIATELY if meningitis is suspected: before going to hospital, before confirmation, before identification of pathogen
82
What type of bacteria is Neisseria meningitidis?
Gram-negative diplococcus bacterium
83
What virulence factors does N. meningitidis have?
LPS (endotoxin) causes inflammatory response
| Thick capsule prevents phagocytosis by immune cells and confers survival in blood
84
How many serogroups does N. meningitidis have?
13
85
What happens if you don't treat N. meningitidis?
Host immune response (inflammatory cascade) leads to septic shock
86
What percentage of the population carry N. meningitidis asymptomatically in nasopharynx?
20%
87
Can N. meningitidis infect blood and meninges?
Yes but it is rare
88
Who is most susceptible to N. meningitidis infection?
Children >3 months (decreased maternal Ab)
| Adolescents with no prior exposure to the infecting serotype (no type-specific immunity)
89
How is N. meningitidis transmitted?
Horizontal (person-to-person)
- via droplets of respiratory/throat secretions
Close contact
- confinement/crowding (prisons, dorms), sneezing/coughing, kissing, sharing utensils or drinks
90
When are N. meningitidis outbreaks most common in the US?
Late winter and early spring due to confinement and increased secretions due to respiratory diseases (colds/flu)
91
Where in the world is the highest rate of N. meningitidis infection?
Meningitis belt - Sub-Saharan Africa
During dry season: dust/wind/cold temperature/upper respiratory tract infections are thought to damage the nasopharyngeal mucosa
Pilgrimages and travel markets result in large, confined crowds
92
Are all N. meningitidis vaccines the same?
No, they contain the most prevalent serotypes for their geographical area
93
What type of bacteria is Streptococcus pneumoniae?
Gram-positive coccus, forms chains
94
What is a virulence factor of S. pneumoniae?
Thick polysaccharide capsule, prevents phagocytosis, enables it to survive in blood
95
How many serogroups of S. pneumoniae are there?
>85
96
What is the mortality rate of S. pneumoniae infection?
20-60%
97
How is S. pneumoniae diagnosed?
Does patient have predisposing factors?
| Ear, sinus, or lung infections precede pneumococcal meningitis in ~40% of patients
98
Who predominately becomes infected with S. pneumoniae?
Children <2 and the elderly
99
Is there a vaccine for S. pneumoniae?
Yes, Prevenar which protects against 13 serogroups
100
Is S. pneumoniae predominant in developed or developing nations?
Developed
101
What type of bacteria is Haemophilus influenzae?
Gram-negative coccobacillus
102
Is H. influenzae predominant is developed or developing nations?
Developing
103
What are some viral factors of H. influenzae?
LPS, causes inflammatory response
| Capsule, anti-phagocytic
104
Is H. influenzae carried asymptomatically?
Yes in most people in their throat
105
Is there a vaccine for H. influenzae?
Yes, Hib
106
What is the mortality rate of H. influenzae?
5% in treated cases
| 9% present with sequelae
107
What is neonatal meningitis?
It is meningitis that occurs in newborns up to 4 weeks old.
| - They have an immature immune system (brain and periphery)
108
In adults, what percentage of bacteraemia cases develop into meningitis?
<1%
109
In newborns, what percentage of bacteraemia cases develop into meningitis?
33%
110
What is the mortality rate of neonatal meningitis?
10-15%
| 50% disability (cerebral palsy, epilepsy, mental retardation)
111
What are the main 3 causes of neonatal meningitis?
Group B Streptococcus
E. coli
Listeria monocytogenes
112
If the mother is infected with Group B Streptococcus or E. coli what should be done to prevent neonatal meningitis?
Treat the mother with antibiotics
113
What is the best treatment to give a patient with bacterial meningitis intially?
3rd generation Cephalosporin as it is broad spectrum
114
What treatment should be given for N. meningitidis bacterial meningitis?
3rd gen. cephalosporin or benzylpenicillin for 7 days
115
What treatment should be given for H. influenzae bacterial meningitis?
3rd gen cephalosporin for 10 days
116
What treatment should be given for S. pneumoniae bacterial meningitis?
3rd gen cephalosporin or benzylpenicillin for 10 days
| Since many strains are penicillin resistant, sometimes vancomycin or rifampin are used in combination with cephalosporin
117
What is given to adults and children over 2 years to reduce the inflammatory response in bacterial meningitis?
Steroid Dexamethasone
118
Should close contacts of those with bacterial meningitis be treated?
Yes
119
Does Mycobacterium tuberculosis meningitis occur alone?
Typically there is a focus of infection elsewhere in the body e.g. lungs
However, in 25% of cases there may be no previous evidence of TB disease symptoms
120
Who does meningitis occur in more commonly in TB endemic countries?
Children 0-4 years
121
In low TB incidence countries who does meningitis more commonly infect?
Adults with pre-disposing factors: HIV, impaired immunity
122
How does TB meningitis present?
Gradually over several weeks
| Malaise, apathy, anorexia, photophobia, neck stiffness
123
What is CSF like in TB meningitis?
Clear
High protein
Low glucose
High WBCs mainly lymphocytes
124
Why is detection of TB meningitis so hard?
Low numbers of bacteria:
| - large and multiple samples of CSF required to perform acid-fast staining which can detect TB
125
How is TB meningitis treated?
It is difficult to treat
Initial treatment at least 2 months with antibiotic combination, isoniazid, rifampin, pyrazinamide, and ethambutol
Treatment needs to be prompt to prevent serious complications
Corticosteroids can also be administered
126
Is there a vaccination to prevent TB meningitis?
Yes BCG vaccine
| Only 75% effective
127
Does fungal meningitis occur?
Yes but it is very rare
128
How do fungi cause meningitis?
Enter the lung -> blood -> meningitis
| Sometimes from injections of painkillers into CSF in US
129
Who is mainly affected by fungal meningitis?
Low birth weight babies
| Adults with suppressed cell-mediated immunity
130
Where do the fungi that cause fungal meningitis come from?
Bird/Bat droppings
| Certain soil types
131
What are the 2 main causes of fungal meningitis?
Cryptococcus neoformans
| Coccidioides immitis
132
Describe Cryptococcus neoformans
Capsulated yeast
Cells visible in CSF stained with India-Ink
Can be cultured
133
What is the progression of meningitis caused by C. neoformans like?
Slow over days or weeks
134
What is the treatment for C. neoformans meningitis?
Long course/High dose intravenous antifungals
| e.g. amphotericin B and flucytosine combination
135
What type of infection do protozoa in the CNS cause?
Meningitis and/or encephalitis
136
What is the likelihood of protazoal infection of the CNS?
very rare
137
What is the progression of CNS infection caused by protozoa like?
Rapid and usually fatal
138
What is the primary cause of amoebic meningoencephalitis?
Protozoa
139
Where do free-living amoeba come from?
Stagnant fresh water pools and lakes in warm countries
140
How do free-living amoeba infect the CNS?
Enter through nose usually during water recreation, travels from olfactory tract directly to meninges
141
Who is infected by Naegleria amoeba?
Healthy individuals
142
How is protozoal meningitis treated?
Drug treatment is sometimes available but rarely successful
| Almost always fatal
143
What is the most common pathogen type to cause meningitis?
Viruses
144
Compare bacterial meningitis and viral meningitis in terms of disease?
Viral is milder
145
What are the symptoms of viral meningitis?
Headache
Fever
Photophobia
146
What is the main group of viruses responsible for viral meningitis?
Enteroviruses
| e.g. polio, Coxsackie, echo
147
Is viral meningitis seasonal?
Yes
148
How is viral meningitis diagnosed?
Batteries of PCR specific for each probable infecting virus very important for diagnosis
Each PCR amplifies specific viral nucleic acids
149
How is viral meningitis treated?
Few antiviral drugs
Usually complete recovery without drugs
Rest and support (home/hospital)
150
What type of pathogen is the main cause of encephalitis?
Viruses
151
Additional to the signs displayed in meningitis, what is seen in encephalitis?
Cerebral dysfunction: abnormal behaviour, seizures
Confusion
Focal neurological effects depending on site of infection: loss of sensation, muscle weakness, partial paralysis
Speech/hearing, hallucinations, personality changes
Altered consciousness
Vomiting/nausea
Fever
152
What are 5 groups of virus and an example that can cause viral encephalitis?
```
Herpesviruses (HSV-1)
Enteroviruses (Polio)
Paramyxoviruses (Mumps)
Rhabdoviruses (Rabies)
Arboviruses (different families Arthropod-borne viruses)
Retroviruses (HIV)
```
153
How do viruses most commonly enter the CNS?
Through the blood
154
What are the steps of pathogenesis of viral encephalitis?
1. 'free' virus or virus in blood cell
2. leaves blood via BBB
3. infects glial cells such as astrocytes or neurons
4. causes death/damage/dysfunction
155
What does Polio do in the CNS?
Lyses and destroys nerves for release (permanent damage)
156
What is the immune response to viral encephalits?
Monocytes, lymphocytes (T cells, B cells/antibodies) move from the blood into the brain
Can clear virus, but also cause immune pathology
Can control primary infection, but cause delayed autoimmune pathology years later
157
How is viral encephalitis managed?
Exclude other causes for symptoms displayed (e.g. head injury)
If encephalitis suspected start therapy IMMEDIATELY
Typically give acyclovir (Zovirax) before confirmation.
Acyclovir is a HSV therapy, it is used as most viral encephalitis is caused by HSV
Restrict fluids to lower pressure in brain
Give anti-seizure medication
Ventilation if required
158
What is the most common cause of viral encephalitis?
HSV
159
How does HSV cause viral encephalitis?
Primary infection: lesion or cold sores
Then enters sensory nerves and travels to dorsal root ganglion (spinal column) or trigeminal ganglion (face) and enters the latent stage
Can be reactivated by stress and/or illness
Ganglion typically returns to lesions; but can travel up nerves to CNS causing encephalitis
160
Which HSV, HSV-1 or HSV-2, typically causes viral encephalitis?
HSV-1
161
Who most commonly contracts HSV-1 viral encephalitis?
Older children and adults infected with HSV-1
162
Who most commonly contracts HSV-2 viral encephalitis?
Neonates and newborns
163
What signs show that the temporal lobe is infected?
Speech and understanding affected (aphasia)
| May display bizarre behaviour, hallucinations
164
How is HSV viral encephalitis diagnosed?
CSF samples may have an increase in lymphocytes, red blood cells also seen
Imaging: CT, EEG or MRI scan (typically of temporal lobe)
PCR on CSF
165
What part of the brain does HSV usually target?
Temporal lobe
166
How is HSV viral encephalitis treated?
Prompt treatment with acyclovir before diagnosis confirmed
167
What is the mortality rate of HSV viral encephalitis?
Untreated = 70% mortality rate
| Survivors usually have secondary complications
168
What is the main cause of enterovirus encephalitis?
Poliovirus
169
What transmission route do enteroviruses use?
```
water borne (faecal oral route)
water -> gut -> blood -> brain
```
170
What was the most common cause of viral encephalitis prior to vaccinations?
Poliovirus
171
What percentage of people suffer from encephalitis when infected with Poliovirus?
<1%
172
Why is CNS infection unlikely in Poliovirus infection?
Because the brain is not a productive/required part of infectious cycle
173
What is the pathogenesis of Poliovirus encephalitis?
1-4 days of fever, sore throat
Followed by meningeal symptoms then encephalitis affecting motor neurones.
Destruction of neurons: permanent paralysis
174
How is poliovirs treated?
It isn't
| It can only be prevented through vaccine
175
What type of vaccine is the Polio vaccine?
Inactivated and then live oral vaccine
| Due to this it has been eliminated in most countries
176
Which 2 viruses are the main causes of Hand, Foot and mouth disease?
Coxsackie virus
| Enterovirus 71
177
Which of Coxsackie and enterovirus 71 is more severe?
Enterovirus 71 as it is more likely to be neurological
178
What severity of disease does Enterovirus 71 cause in different demographics?
Mild disease: adults and children
| Severe disease: young children and immunocompromised adults
179
How is enterovirus 71 resolved?
Usually spontaneously
180
What happens in severe enterovirus 71 cases?
There is brainstem involvement leading to permanent neurological damage
181
When was there an outbreak of enterovirus 71?
1998 in Taiwan, 405 patients, most under 5
| Mortality rate 19%
182
Is there a vaccine for enterovirus 71?
No
183
What viruses can causes paramyxovirus encephalitis?
Mumps virus
Nipah virus
Hendra virus
184
In what percentage of mumps cases does mild meningitis occur?
10%
| 10 days after onset of parotitis (inflammation of salivary gland)
185
What is parotitis?
Inflammation of salivary gland
186
What is the outcome of mumps encephalitis?
Usually complete recovery but rarely deafness may occur
187
Is there a vaccine for mumps virus?
Yes, MMR vaccine
188
What is the case fatality of Nipah/Hendra virus?
40-70%
189
Where in the world is Nipah seen?
Asia
190
Where in the world is Hendra seen?
Australia
191
What is the natural reservoir of Nipah/Hendra?
Fruit bats
192
What is the chain of infection for Nipah?
Bat -> Pig -> Human
193
How do humans contract Nipah?
Eat palm-sap
| Human to human
194
Is there a vaccine for Nipah?
No
195
How is Nipah infection treated?
There are no antivirals
196
Are there outbreaks of Nipah?
Yes annually in Asia
197
Are there outbreaks of Hendra?
Yes in horses since 1998 in Queensland and New South Wales
198
Has there been horse to human transmission?
Yes there have been 4 cases of it, with 7 infected and 4 dead
199
What is the terminal host in Hendra?
Humans
200
What is the chain of infection of Hendra?
There isn't one
| Although in human infection it has been shown as bat -> horse -> human
201
Is there a vaccine for Hendra?
Yes but only for horses
202
What viruses can cause lyssavirus encephalitis?
Rabies
| Australian Bat Lyssavirus
203
In which animal reservoir can rabies be found?
Virus in infected saliva of dogs, foxes, skunk, raccoons, bats
204
Who can rabies infect?
All warm-blooded animals
205
What is the fatality rate of rabies?
100% in all symptomatic cases
206
What is the terminal host of rabies?
Humans
207
What is the chain of infection of rabies?
There isn't one
208
How often do humans die from rabies infection?
1 every 10 minutes worldwide
209
What demographic is most commonly affected by rabies?
Children
210
Where does rabies rank on the most important global infectious disease chart?
7th
211
Can dogs be infectious before they show symptoms?
Yes
212
How do humans contract rabies?
via bite or saliva or skin abrasion
213
What percentage of rabies cases are caused by unvaccinated dogs per year?
99%
214
Which islands have excluded rabies via quarantine?
Australia and UK
215
What is the incubation period for rabies?
Slow incubation period; 4-13 weeks up to 6 months/years
216
How does rabies travel to the CNS?
Virus must first reach peripheral nerves
Travels through peripheral nerves from site of bite to CNS
Peripheral nerves -> CNS -> encephalitis
217
What is the immune response to rabies?
There is none as rabies is hidden in muscle/nerve
218
How can we induce active immunity against rabies?
Can passively immunise post-exposure with human rabies immunoglobulin together with vaccine
219
What happens to an unvaccinated persons brain when infected with rabies?
Virus migrates to brain, spreads from cell to cell, with few cytopathic effects or immune inflammatory response
- It maintains BBB
- Causes dysfunction of neurons
220
After rabies has infected the brain what does it do?
It spreads back to the body via nerves, including to the salivary glands
221
What are the clinical features of rabies infection?
Aggressive behaviour (due to limbic dysfunction)
Flu-like symptoms: sore throat, headache, fever
Spasms, fits, hallucinations, hydrophobia, paralysis, delirium
Coma, respiratory failure
222
What does dysfunction of the limbic system lead to?
Aggressive behaviour
223
How is rabies virus diagnosed?
Detection of viral antigen by immunofluorescence
or
RT-PCR
- skin biopsies, saliva, CSF
Serology for rabies antibody (blood, CSF)
Intracytoplasmic inclusions called Negri bodies are seen in neurones
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How is rabies virus treated?
Once symptomatic there is not treatment
225
How is rabies prevented?
Controlling dogs, wildlife and pets
| Human prophylaxis: vaccine
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How do we prevent rabies in high risk individuals?
3 vaccinations, with antibody confirmed
| Still need 2 follow up boosters after exposure
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How to we prevent rabies in non-vaccinated individuals after exposure?
Washing wound
If possible, determine rabies status of animal
Prophylactic treatment - immunoglobulin (RIG), 5 vaccinations
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When was Australian bat lyssavirus first detected?
1996 in a flying fox in New South Wales
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How many cases of Australian bat lyssavirus have there been?
3 cases in total, all fatal
1996 women was bitten, died two years later
1996 animal carer was bitten, died within 8 weeks
2013 boy bitten, died 2 and 1/2 months later
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How to prevent Australian bat lyssavirus infection?
Avoid handling bats
| Wildlife/bat handlers should be vaccinated
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What is the treatment for Australian bat lyssavirus?
Same as for rabies:
| Rabies immunoglobulin and rabies vaccine
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What is arboviruses short for?
Arthropod borne viruses
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How are arboviruses spread?
Spread by mosquito/tick (arthropod) vectors
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How to control arbovirus spread?
Wear protective clothing
Wear insect repellent
Eradicate mosquitos
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What are 3 main arboviruses that cause encephalitis?
Flaviviridae
Togaviridae
Buyaviridae
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Where can you find Zika virus in the world?
Uganda
South east Asia
Pacific islands
Brazil
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Where can you find Japanese encephalitis virus?
Asia with outbreaks worldwide
238
Where can you find Murray Valley encephalitis?
Australia
| Paupa New Guinea
239
Where can you find Chikungunya virus?
Africa
India
South east Asia
240
Where can you find rift valley virus?
Africa
241
How can HIV cause encephalitis?
Soon after HIV infection, HIV can invade the CNS
First causing mild meningitis
As the disease progresses subacute encephalitis with dementia may occur
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Define delayed onset encephalitis? (post vaccinial/post infectious encephalitis)
Encephalitis after infectious or non-infectious vaccine
| Usually immune driven: against virus and host
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What is a virus that may cause delayed onset encephatlitis?
Measles
244
How does measles cause delayed onset encephalitis?
Measles is cleared
Influenza-like illness 1-2 weeks later, with encephalitis
Usually no virus recovered from CSF
Most likely an autoimmune response triggered by vaccination/infection
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What is subacute sclerosing panencephalitis?
Infection of CNS by 'slow virus' years after infection
246
What virus can cause subacute sclerosing panencephalitis?
Measles 5-10 years after initial infection
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What is encephalopathy?
disorder or disease of brain
| pathological change, not inflammation
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What is spongiform encephalopathy?
disorder or disease of brain resulting in appearance of gaps in brain tissue
249
What is a disease that causes spongiform encephalopathy?
Bovine spongiform encephalopathy (BSE)
250
How do you treat encephalopathy?
It is incurable and invariably fatal
251
What causes infectious encephalopathy?
prions - proteinaceous infectious agents
252
What is happening inside the brain to cause encephalopathy?
Single malfunctioning host protein; misfolded version of PrP (prion protein)
Changes in conformation from normal to dysfunction infectious protein
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What are the 3 causes of encephalopathy?
Genetic (mutation)
Sporadic
Acquired (infectious)
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What is the incubation period for encephalopathy?
Can be up to 50 years before dementia, wasting, lack of motor control
255
What is a disease that infects humans causing encephalopathy?
Creutzfeldt-Jakob disease
256
What is Creutzfeldt-Jakob disease?
Can be genetically acquired, transmitted via medical treatment, blood transfusion, or ingestion of infected meat
257
What type of pathogen is toxoplasma gondii
Parasite
258
Where is Toxoplasma gondii found?
Found globally
259
How does Toxoplasma gondii get inside the host?
Undercooked meat
Contaminated water
Cat faeces
Objects contaminated by any of the above
260
What is congenital toxoplasmosis?
When a newborn acquires toxoplasmosis from the mother.
T. gondii localises in the brain
Causes damage to eyes and hydrocephalus (excess CSF within the skull)
261
What is hydrocephalus?
Excess CSF within the skull
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How does T. gondii typically present?
Most disease is latent, with no obvious symptoms
- may have flu-like symptoms (month or more)
- sometimes ocular symptoms
263
What happens in T. gondii infection in healthy patients?
Usually kept under control
264
What happens in T. gondii infection in immunocompromised patients?
encephalitis
265
What disease does Plasmodium falciparum cause?
malaria
266
What percentage of cases of malaria develop into cerebral malaria?
20-50%
267
What happens in the body during malaria infection?
Red blood cells become infected
- become sticky, bind to capillaries in the brain
- block, slow/stop blood flow
Increased cranial pressure and seizures, coma, respiratory arrest
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What is the mortality rate of malaria?
High
one million African children die annually
Of those that survive, 10% have neurological problems
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What bacteria produces the toxin, tetanospasmin?
Clostridium tetani
270
Can Clostridium tetani infect the CNS?
No, but the tetanospasmin toxin can cause CNS symptoms
271
What type oxygen conditions does C. tetani require?
Anaerobic
272
Where does C. tetani reside in the human body?
Deep puncture wounds
| Within umbilical stump of newborns
273
What disease does C. tetani cause?
tetanus
274
Where does tetanospasmin go in the human body?
travels to CNS via retrograde transport up motor neurons to the neurons in the CNS
Binds to neurons and blocks the release of inhibitory mediators
275
What CNS symptoms does C. tetani infection cause?
Overactive motor neurons: exaggerated reflexes, muscle rigidity (lock jaw), uncontrolled muscle spasms
Overactive sympathetic nerves: tachycardia and excessive sweating
276
How is C. tetani infection treated?
Wound requires thorough cleaning
- excise/open closed wound to enable oxygen to enter to kill C. tetani
Antibiotic treatment
Passive immunisation with tetanus immunoglobulin (antitoxin)
Active immunisation with toxoid (inactivated toxin) vaccine to induce active immunity, lasts 10 years
Muscle relaxants to relieve symtpoms
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What is the mortality rate of tetanus?
50%
