Infectious Disease Flashcards
1
Q
What are global risk factors for infectious disease?
A
Poverty War Lack of clean and food water supply Environment Under resourced health care services Life style Illiteracy Political instability International Travel
2
Q
Why it is important to understand the epidemiology of communicable diseases?
A
Globalisation
Emerging diseases
Natural disasters
Economic costs
3
Q
What causes malaria?
A
Parasites from the plasmodium genus
P.falciparum, P.ovale, P.malaria and P.vivax
4
Q
Describe the stages of malaria infection
A
Mosquito takes blood meal
Infects liver cells which become schizont and then rupture
From here it enters blood and forms gametocytes
A non infected mosquito could then bite here and ingest gametocytes
5
Q
Who is most likely to die from malaria?
A
Mostly children
6
Q
What can be a problem with malaria treatment?
A
Resistance to chloroquine
7
Q
What is the most common infectious disease in the world?
A
TB
8
Q
What is the second leading cause of disease burden worldwide?
A
AIDS
9
Q
What are the causative agents of Bilharziasis?
A
Schistosomiasis species of parasitic worms spread in contaminated water - freshwater snails
S.mansoni, S. haematobium and S. japanicum
May infect urinary tract or intestines
Abdo pain, diarrhoea, bloody stool/urine
Long term liver damage, kidney failure etc
10
Q
What is yellow fever?
A
Viral disease transmitted by several species of mosquito
Caused by yellow fever virus, which belongs to genus flavivirus
Humans and monkeys are the principle reservoirs for the virus
Most common types of mosquito that transmit yellow fever virus are Aedes aegypti or Haemagogus spp
Symptoms: high temp, headache, N&V, muscle pain, loss of appetite
Can develop into more serious: jaundice, kidney failure, bleeding from mouth, nose, eyes, stomach
11
Q
What is bronchiolitis?
A
Common lower respiratory tract infection, affects babies and children under 2. Viral, 70% respiratory syncytial virus (RSV)
Major cause of admission to hospital in children under 1
Highly infectious, epidemic in winter months. 80% of 2 year olds have antibodies
Most cases mild and clear up without need for treatment in 2-3weeks, some children have severe symptoms and need hospital treatment
Early symptoms similar to those of a cold: runny nose, cough
Further symptoms develop over next few days: high temperature, dry and persistent cough, difficulty feeding, rapid or noisy breathing (wheezing)
12
Q
What are symptoms and signs of Bronchiolitis?
A
Distressed child (and parents!)
Respiratory distress, wheeze
Poor feeding, lethargy
Apnoea
13
Q
What are management steps for Bronchiolitis?
A
Supportive: majority managed in community, recover in 7-10d
Fluids, nutrition, antipyretics, Careful safety netting
Admission required if markers of severity: RR high, low sats
Oxygen, NG feeding, tiny minority ventilated
Remember infection control: isolation, PPE, careful handwashing
14
Q
What can be done to prevent Bronchiolitis?
A
Hygiene
RSV vaccine made disease worse
Passive immunisation may have a role in the patients at highest risk of severe disease
15
Q
What are outcomes of Bronchiolitis?
A
Most make full recovery
up to 50% will wheeze recurrently
Mortality 8/100k, mostly in under 6m and with cardiac/pulmonary disease
16
Q
What is an infective exacerbation of COPD?
A
More sputum, more purulent sputum and more breathless
Sustained worsening of patient’s symptoms from his or her usual stable state, which is beyond normal variations and acute in onset
Caused by: Viruses 20-40% Rhinovirus, Adenovirus, RSV, Influenza
Bacteria: >= 50% Haemophilus, Streptococcus pneumoniae, Moraxella, Gram negatives including E. coli, Pseudomonas
17
Q
What are management options for an infective exacerbation of COPD?
A
Bronchodilators
Steroids
Antibiotics: Amoxicillin PO, Doxycycline PO
18
Q
What are preventative measures against infective exacerbations of COPD?
A
Influenza and pneumococcal vaccination
NO role for prophylactic antibiotics
19
Q
What organisms can cause influenza like illnesses? And what would be initial symptoms?
A
Influenza, parainfluenza viruses Adenovirus RSV Coronavirus Sudden onset fever, chills, Dry cough, runny nose, Headache, Myalgia
20
Q
What are antibiotic management options for community acquired pneumonia?
A
Amoxicillin +/-clarithromycin
21
Q
What’s atypical pneumonia?
A
Presents other than with symptoms of “typical” pneumonia caused by Streptococcus pneumoniae
caused by “atypical” bacteria, also viruses
Often used to mean lacking lobar consolidation on chest X ray
22
Q
What’s an “atypical?”
A
(Usually) No cell wall
Intracellular pathogens
Relevant because no antibiotic acting on the cell wall will work
Also, generally not amenable to regular culture
23
Q
What are important atypical causes of pneumonia to be aware of?
A
Mycoplasma pneumoniae
Chlamydophila pneumoniae and psittaci
Legionella
Respiratory viruses
24
Q
What is Legionella?
A
Gram negative, standard cell wall Intracellular pathogen Sporadic and outbreaks Mild illness “Pontiac fever” Severe illness esp in older male smokers: “Legionnaire’s disease”, mortality 10%
25
How do you treat Legionella infection?
Antibiotics active against intracellular bacteria: macrolides (clarithromycin), tetracyclines, quinolones (e.g levofloxacin)
26
What is empyema thoracis? And what organisms can cause it?
Pus in pleural cavity
Spontaneous: complication of pneumonia
Streptococcus milleri, Streptococcus pneumoniae, Staphylococcus
aureus, anaerobes e.g Fusobacterium
Tubercular: spontaneous but more chronic presentation
Iatrogenic: following pleural incision, including pleural drain Staphylococcus aureus, Gram negatives e.g E. coli
27
Who is most likely to be affected by bronchiectasis?
F >>M, May present at any age, but prevalence highest in older women
No identifiable underlying cause approx 50%
If underlying cause identified, most commonly post-infective (pneumonia, TB, pertussis, childhood respiratory virus including measles)
28
How do you diagnose bronchiectasis?
Radiological diagnosis: High resolution CT thorax shows bronchial wall thickening
Sputum culture usually positive, may not be helpful in determining whether antibiotics needed
29
What are usual causative organisms of bronchiectasis?
Haemophilus influenzae
Staphylococcus aureus
Gram negatives e.g E. coli, Klebsiella
Pseudomonas aeruginosa
30
What is an important cause of bronchiectasis?
Cystic fibrosis
31
What would you call a severe, localised pyogenic (pus-forming) infection in lung tissue?
Lung abscess
32
What are some causes of lung abscesses?
```
Aspiration of pyogenic organisms
Streptococcus milleri
Anaerobes
Unresolved pneumonia
Staphylococcus aureus
Klebsiella
Septic emboli from endocarditis
Staphylococcus aureus
Seeding of bacteraemia
Penetrating trauma
Infected tumour
Infected foreign body
```
33
What are alternative options if you can't see, grow and kill a microbe?
Detect the organism
Antigen
Nucleic acid (PCR)
Detect the immune response to the organism, usually antibody
34
What things do you need to specifically ask to be tested for in a sputum sample?
TB: Mycobacterium tuberculosis and non-tuberculous mycobacteria
Legionella
Bordetella (whooping cough)
Fungi
35
What organisms might you detect rather than grow? And why?
Seeing them is hard (viruses)
We can’t grow them e.g Pneumocystis
It takes too long to grow them e.g most viruses, intracellular bacteria, Legionella
It’s cheaper to do it another way e.g most viruses
36
What are ways of detecting an organism?
Antigen detection: Uses specific antibody to identify pathogen of interest
Nucleic acid detection: No antibody needed, Pathogen may not be alive (can be done on formalin-fixed specimens), Quick, relatively cheap, highly specific, multiplex
37
Name some organisms that you might detect using Nucleic acid detection
Viruses: influenza, RSV
Bacteria: tuberculosis, pertussis
Fungi: Pneumocystis
38
What are some disadvantages to using direct detection of organisms?
No sensitivity testing results (some genomic sensitivity available for TB)
Multiplex increases chance of finding something, but relevance of that may be harder to interpret
No typing data if simple yes/ no detection
39
How can you detect an immune response to an organism?
Usually antibody to pathogen of interest
Not timely e.g. need 4 week convalescent specimen to see rising antibody titres in “atypical” pneumonia
Activation of T cells: the IGRA tests for TB
40
What are the general principles of management of severe infection?
Treat the patient: ABCDE and sepsis six
Cultures before antibiotics if well enough
Start SMART then focus: appropriate empirical antibiotics (local guidelines)
41
What principles should be applied to Smart antibiotic use?
Right drug
Right dose
Right time: lifesaving early treatment of sepsis
Right duration: most eminence not evidence based!
Do not use antibiotics where other therapy more appropriate
42
Describe alternative management of infections
If there’s pus drain it!: Empyema requires drainage and possible surgical clearance
If there’s a foreign body, get it out: Aspirated objects a cause of persistent cough in children
If there’s dead tissue, cut it off Lobectomy or partial pneumonectomy still sometimes used for refractory TB
43
How do you know if you have the right antibiotic drug?
Effective against likely or known pathogen
Local guidelines take into account common organisms and resistance patterns
Specific culture and sensitivity results
Safe
Check allergy history, renalfunction, liver function and other meds
44
Give some examples of broad spectrum antibiotics
Cephalosporins (ceftriaxone)
Aminoglycosides (gentamicin)
Quinolones (ciprofloxacin)
Extended spectrum penicillins (piperacillin-tazobactam)
45
Give an example of a drug which only works on gram positive bacteria
Vancomycin
46
Give an example of drug which only acts on gram negative bacteria
Aztreonam
47
What sort of spectrum drug is flucloxacillin?
Narrow spectrum in gram positive range
48
What bacteria can be killed using macrolides (erythromycin and clarithromycin), tetracyclines, rifampicin?
Mainly gram positive, also intracellular bacteria
49
What sort of range of bacteria can be killed by amoxicillin?
Medium range mainly gram negative but including some gram positive bacteria
50
What do you use to treat non complicated community acquired pneumonia?
Amoxicillin plus clarithromycin
51
What do you use to treat aspiration pneumonia?
Co-amoxiclav
52
What do you use to treat hospital acquired pneumonia?
Co-amoxiclav plus gentamicin or
| Piperacillin-tazobactam plus gentamicin
53
Why must you be careful with gentamicin and vancomycin?
Toxic and need levels monitoring
54
According to WHO data what are the 3 biggest killers in Europe and how does this compare to Africa?
Europe: ischaemic heart disease, stroke, lung cancer
Africa: lower respiratory tract infections, HIV/AIDS, diarrhoeal diseases
55
What is surveillance?
Ongoing systematic collection, collation, analysis and
| interpretation of data, and dissemination of information (to those who need to know) in order that action may be taken
56
Give some examples of surveillance systems in hospital?
Notifications of Infectious Disease
Laboratory notifications
Other disease specific systems
Primary care surveillance systems: Remote health advice (NHS 111), GP in hours and GP out of hours, RCGP, COVER (immunisation data)
Secondary care surveillance systems: Emergency Department Syndromic surveillance
57
What is the role of public health England in communicable disease control?
Statutory responsibility to take notifications of infectious disease and manage outbreaks/chemical or environmental incidents
58
What is the responsibility of NHS England in communicable disease control?
Lead and co-ordinate NHS response to an outbreak
59
What are the roles of clinical commissioning groups in communicable disease control?
Support role of NHS England and work with community and acute trust providers to support outbreak response
60
What is primary cares role in communicable disease control?
Support outbreak investigation and management, through taking samples (nose/throat swabs, stool samples, blood samples, oral swab samples) and organising treatment and prophylaxis (latter being either medications or vaccinations)
61
What are roles of acute hospital trusts in communicable disease control?
Provide microbiological advice regarding single cases of communicable disease/outbreaks
In a hospital incident, Director of Infection Prevention and Control (often a microbiologist) leads outbreak management
62
What is the role of local authorities in communicable disease control?
Environmental Health Officers support investigation of certain communicable disease cases/outbreaks which may have an environmental source, e.g. gastrointestinal infections, Legionella etc. Organise food questionnaires and stool samples in an outbreak of
gastrointestinal disease, as well as inspection of food premises/kitchens which may be implicated. Have powers to prosecute as necessary
Director of Public Health (and teams) in Local Authority has statutory responsibility to ensure there are plans in place to protect the health of the population, and will support outbreak response
63
What 3 things may affect the outcome of a communicable disease?
Agent: organism which produces infection e.g.: Virus, Bacteria, Fungus, Rickettsia, Protozoa
Host factors: Age, Gender, Socio-economic status, Ethnicity, Lifestyle factors (e.g. drug use, sexual behaviours, diet, personal hygiene), Level of inherent resistance, Immunological status: Immunosuppression due to disease or treatment, Previous exposure to infection, Immunisation
Environmental factors: Climate and temperatures, Physical surroundings, Crowding, Sanitation, Availability of health services
64
Define infection or colonisation
Entry and development or multiplication of an infectious agent in/on the body of man or animals (not synonymous with disease)
65
Define communicable or infectious disease
Disease which occurs following direct or indirect transmission of an infectious agent or its toxic products
66
Define contagious
Describes an infectious transmitted by direct contact
67
Name some direct modes of transmission of disease
Touching (scabies), kissing (oral infections), sexual intercourse (Chlamydia, Gonorrhoea, Syphilis, HIV, Hepatitis B)
Droplet spread (e.g. measles, mumps, flu, meningococcal disease)
Transplacental (bloodborne viruses such as Hep B and HIV)
Faeco-oral (campylobacter, salmonella, E Coli 0157, Hepatitis A)
68
What is surveillance?
Ongoing systematic collection, collation, analysis and
| interpretation of data, and dissemination of information (to those who need to know) in order that action may be taken
69
Give some examples of surveillance systems in hospital?
Notifications of Infectious Disease
Laboratory notifications
Other disease specific systems
Primary care surveillance systems: Remote health advice (NHS 111), GP in hours and GP out of hours, RCGP, COVER (immunisation data)
Secondary care surveillance systems: Emergency Department Syndromic surveillance
70
What is the role of public health England in communicable disease control?
Statutory responsibility to take notifications of infectious disease and manage outbreaks/chemical or environmental incidents
71
What is the responsibility of NHS England in communicable disease control?
Lead and co-ordinate NHS response to an outbreak
72
What are the roles of clinical commissioning groups in communicable disease control?
Support role of NHS England and work with community and acute trust providers to support outbreak response
73
What is primary cares role in communicable disease control?
Support outbreak investigation and management, through taking samples (nose/throat swabs, stool samples, blood samples, oral swab samples) and organising treatment and prophylaxis (latter being either medications or vaccinations)
74
What are roles of acute hospital trusts in communicable disease control?
Provide microbiological advice regarding single cases of communicable disease/outbreaks
In a hospital incident, Director of Infection Prevention and Control (often a microbiologist) leads outbreak management
75
What is the role of local authorities in communicable disease control?
Environmental Health Officers support investigation of certain communicable disease cases/outbreaks which may have an environmental source, e.g. gastrointestinal infections, Legionella etc. Organise food questionnaires and stool samples in an outbreak of
gastrointestinal disease, as well as inspection of food premises/kitchens which may be implicated. Have powers to prosecute as necessary
Director of Public Health (and teams) in Local Authority has statutory responsibility to ensure there are plans in place to protect the health of the population, and will support outbreak response
76
What 3 things may affect the outcome of a communicable disease?
Agent: organism which produces infection e.g.: Virus, Bacteria, Fungus, Rickettsia, Protozoa
Host factors: Age, Gender, Socio-economic status, Ethnicity, Lifestyle factors (e.g. drug use, sexual behaviours, diet, personal hygiene), Level of inherent resistance, Immunological status: Immunosuppression due to disease or treatment, Previous exposure to infection, Immunisation
Environmental factors: Climate and temperatures, Physical surroundings, Crowding, Sanitation, Availability of health services
77
Define infection or colonisation
Entry and development or multiplication of an infectious agent in/on the body of man or animals (not synonymous with disease)
78
Define communicable or infectious disease
Disease which occurs following direct or indirect transmission of an infectious agent or its toxic products
79
Define contagious
Describes an infectious transmitted by direct contact
80
Name some direct modes of transmission of infectious disease
Touching (scabies), kissing (oral infections), sexual intercourse (Chlamydia, Gonorrhoea, Syphilis, HIV, Hepatitis B)
Droplet spread (e.g. measles, mumps, flu, meningococcal disease)
Transplacental (bloodborne viruses such as Hep B and HIV)
Faeco-oral (campylobacter, salmonella, E Coli 0157, Hepatitis A)
81
Name some indirect modes of transmission of infectious disease
```
Vehicle borne (flu) – inanimate objects, food/water, biological products e.g. blood, tissues
Vector borne (malaria) – an insect or living carrier which carries disease from an infected individual to a susceptible individual
Airborne (aerosols e.g. TB and dust e.g. fungi and respiratory viruses)
```
82
What is an incubation period?
Time from exposure to development of symptoms
83
What is a latent period with an infectious disease?
Time from exposure to being infectious to others
84
What is sporadic occurrence with infectious disease?
Irregular pattern of disease, occasional cases at irregular intervals
85
What is endemic occurrence in infectious disease?
Persistent, low or moderate level of disease
86
What is hyper endemic occurrence in infectious disease?
A higher persistent level of disease
87
What is cluster occurrence with infectious disease?
Occurrence exceeds the expected level for a given population and/or in a given geographical area and/or in agiven time period (cases have a possible but unconfirmed link)
88
What is an epidemic/outbreak in infectious disease?
Occurrence exceeds the expected level for a given population and/or in a given geographical area and/or in agiven time period (cases have a highly probable or confirmed link)
An outbreak is a localised epidemic, two or more linked cases, or a single case of a rare disease e.g. rabies, diphtheria, botulism, polio
89
What is pandemic occurrence in infectious disease?
Epidemic occurring worldwide or over a very wide area, crossing international boundaries, and usually affecting a large number of people
90
How can you break the chain of transmission of infectious disease?
Control the source
Interrupt transmission
Protect susceptible population by immunisation or chemoprophylaxis
91
What are the 8 steps to managing an outbreak of an infectious disease?
Confirm (verify diagnosis)
Immediate control
Convene an Outbreak Control Team
Review epidemiological (time, place and person) and microbiological information
Case finding
Descriptive Epidemiology (epidemic curves)
Analytical study (case control or cohort)
Declare outbreak over – lessons learnt, prevention measures in place, ongoing monitoring
92
What different patterns of epidemic curves are there?
Point source: all cases appear to occur within one incubation period, suggesting that cases did not arise from person-to-person spread. Outbreak of short duration, single, brief exposure that did not persist over time
Propagated: begins with a single index case that infects a number of other individuals. One or more of people infected in initial wave infects a group of people who become the second wave of infection. Transmission is person-to-person, rather than common source. Propagated epidemic in which one or more of the first wave of cases serves as a source of infection for subsequent cases
Continuous source: group of people are exposed to a single noxious influence. Exposure continues over a longer time (contaminated water supply that doesn't get fixed), so outbreak persists for longer. Abrupt beginning of outbreak, many people exposed simultaneously, rather than spreading via transmission from one case to another. No cases arise beyond one incubation period following the termination of exposure
Mixed picture
93
Who is protected by vaccination?
Protection of individual, but also population protection (herd immunity)
94
Who is protected by post exposure chemoprophylaxis,e.g. in meningococcal disease?
Chemoprophylaxis (ciprofloxacin) may protect individual to some extent, but also eliminates nasal carriage in contacts so they cannot pass on to others
95
How long are people excluded from work/school or nursery (e.g. if case of E.Coli 0157 and work in healthcare /food preparation industry/nursery or if case is young child)?
Not allowed to return to work until clear stool samples (can be long periods of time)
96
When might you use Part 2A order legislation?
When investigation and detention of individual who poses a risk to the public is required
97
How is TB spread?
Spread via airborne particles: droplet nuclei
Expelled when person with infectious TB coughs, sneezes, shouts, or sings
Transmission occurs when droplet nuclei inhaled and reach
alveoli via nasal passages, respiratory tract, and bronchi
98
What factors influence the likelihood of TB being spread?
Susceptibility of the exposed person
Infectiousness of person with TB (number of bacilli TB patient expels into air)
Environmental factors that affect concentration of TB organisms
Proximity, frequency, and duration of exposure (e.g., close contacts)
99
Describe the pathogenesis of TB
Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to alveoli where they multiply
Small number of tubercle bacilli enter bloodstream and spread throughout body. They may reach any part of body, including areas where TB disease is more likely to develop (brain, larynx, lymph
node, lung, spine, bone, or kidney)
2 to 8 weeks, macrophages ingest and surround tubercle bacilli. Cells form a granuloma, keeps the bacilli contained and under control (LTBI)
If immune system cannot keep tubercle bacilli under control, they multiply rapidly (TB disease). This can occur in different areas in body, such as the lungs, kidneys, brain, or bone
100
How can you test for latent TB?
TST (tuberculin skin test) or interferon-gamma release assay (IGRA)
101
How can latent TB progress to TB disease?
Granulomas may persist (LTBI)
| Break down to produce TB disease, bacilli escape and multiply
102
How do you confirm TB diagnosis?
Positive M. tb culture
103
What are the sites of TB disease?
Lungs: most common site; usually infectious
Miliary: occurs when bacilli spread to all parts of body; rare, but fatal if untreated
Central nervous system: usually occurs as meningitis, but can occur in brain or spine
104
Which examples of extrapulmonary TB will still be infectious?
Concomitant pulmonary disease
Extrapulmonary disease in the oral cavity or larynx
Extrapulmonary disease with open site, especially with aerosolised fluid
105
What is the risk of developing TB in a person with a normal immune system?
Untreated, 5% of infected persons with normal immunity
develop TB in first 1–2 years post infection, another 5% later in life
About 10% of infected persons with normal immunity will develop TB at some point in life if not treated
106
What is the risk of developing TB in a person with a compromised immune system?
Untreated HIV infection highest risk factor: risk of developing TB disease is 7%–10% each year
Children
107
What will investigations show in a person with latent TB? And what treatment would you give?
Usually, skin test or TB blood test reaction indicating infection
Radiograph typically normal
Sputum smears and cultures are negative
Should consider treatment for LTBI to prevent TB disease
Does not require respiratory isolation
108
What set of symptoms might point towards to TB?
```
Cough – more than 3 weeks
Fever – more than 3 weeks
Weight loss - unexplained
Night sweats
Anorexia
```
109
What do you do if you suspect a case of TB?
Take sputum for AFB smear and culture
Do a chest x-ray
Ensure follow up is in place
110
How do you diagnose TB?
Clinical awareness
Microbiology of pathological samples - discharged pus or biopsy material: direct staining, culture = gold standard, PCR
Histopathological pattern of inflammation
Tuberculin skin testing
Interferon gamma release assays
Radiographic appearance
111
Why does TB treatment require combinations of drugs?
Guard against the development of antibiotic resistance
112
Why does TB treatment have to be so prolonged? And how long is it?
Dormant bacilli are hard to kill
| Minimum 6 months but depends on characteristics of individual antibiotics
113
What are problems with TB treatment?
Non-compliance, drug resistance, side effects
114
What is the first line treatment for TB?
```
Isoniazid (INH)
Rifampicin (RMP)
Pyrazinamide (PZA)
Ethambutol (EMB)
For 2 months
```
115
What treatment is given in the continuation phase of TB treatment?
Two drugs to which the organism is sensitive
INH and RMP (Isoniazid and Rifampicin) for 4 months
To complete 6 months treatment in total
116
What strategies are in place to control TB spread?
Case finding: Active - eg examination of contacts, Passive - education all round
Treatment services: Especially supervision
Prevention: BCG immunisation, Prophylactic use of chemotherapy
117
Describe differences between viruses and bacteria
Viruses: Obligate intracellular parasites, No ribosomes, DNA or RNA, not both, seen by EM, 10-100s of genes
Bacteria: Usually free-living, but can be parasites, including
intracellular, Ribosomes, DNA and RNA, seen by LM, 100s-1000s of genes
118
Describe the structure of a virus
Genetic core: DNA or RNA (never both)
Protein coat: Capsid, Individual units, capsomeres
Envelope: only some viruses
119
What does H1N1 mean in relation to the flu virus?
Cell surface receptors - antigenic sites
120
Describe the life cycle of viruses
```
Receptor binding - attachment
Cell entry - penetration
Uncoating
Genome transcription
Protein translation
Virion assembly
Release - cell lysis or budding through plasma membrane
```
121
Describe different mechanisms that viruses have to penetrate cells
Translocation - e.g. polio
Endocytosis - e.g. influenza
Fusion - e.g. Parainfluenza and HIV
122
What can be outcomes of cell contact with viral particles?
Failed infection
Cell death (cell lysis by virus or immune response to virus)
Viral replication without cell death (productive)
Presence of virus without replication (latency) but with potential for reactivating at a later date (recurrent)
123
What different states can persistent infections be?
Chronic (non-lytic, productive)
Latent (some synthesis of viral nucleic acid/ protein but no intact virions produced)
Recurrent (latency then periods of active replication)
Transforming (immortalising)
124
Describe some mechanisms of persistence of viral infection
```
Genome integration: retroviruses
Immune suppression (local or systemic): herpesviruses, HIV
Immune evasion by infecting immune-privileged areas: papillomaviruses (warts)
Mutation in host to avoid immune response (HIV)
```
125
What is the acute secondary infection that an adult gets if chickenpox (herpes zoster) virus is reactivated?
Shingles
126
Describe the determinants of pathogenesis of viral infection
```
Host cell binding and entry
Stability in the body/ compartment
Contiguous infection of adjacent cells
Cytopathy
Host protective responses
Immunopathology
```
127
Describe the determinants of pathogenesis of influenza
Host cell entry: specific binding to receptors in respiratory tract
Cytopathy: cell lysis of ciliated and mucus-secreting respiratory epithelial cells
Host protective responses: antibody important in future protective immunity (vaccination)
Immunopathology: interferon and other cytokines cause characteristic chills and aches
128
Describe some determinants of pathogenesis of varicella
Host cell binding and entry: inhalation, infects tonsils and
mucosa of URT
Stability in the body/ compartment: infects T cells which deliver virus to skin
Contiguous infection of adjacent cells: bloodstream and lymphatic spread
Cytopathy: syncytia form in epithelia
Host protective responses: virus cleared by cell-mediated immunity, latently infected cells are not recognised by immune system
Latent infection in neurons, usually dorsal root and cranial ganglia
129
What does the varicella zoster virus cause?
Chickenpox in children
| Shingles in adults
130
List some viral skin infections which do not have systemic spread
Human papilloma virus: warts
Molluscum contagiosum: red papules, itchy in children
Orf: contagious pustular dermatitis from sheep and goats
131
List some viral skin infections which can cause systemic infections
Herpes simplex, Varicella
Coxsackie (Hand, foot and mouth)
Parvovirus B19 (Slapped cheek): in pregnancy, foetal loss
HHV6 (“exanthem subitum”): sudden rash
Measles
Rubella: birth defects, hearing loss, cardiac problems
Dengue
132
Name some viruses which can cause pharyngitis/tonsillitis
Epstein Barr
| Cytomegalovirus
133
Name a virus which can cause parotitis
Mumps
134
Which common viruses can affect the GI system?
Rotavirus in children
| Norovirus in adults
135
Which forms of hepatitis will cause GI symptoms and jaundice?
Hep A and E
136
What pathology is seen with hepatitis B and what is there a risk of long term?
Acute hepatitis followed by chronic carriage with progressive
liver damage
Hepatocellular carcinoma risk long term
137
In which form of hepatitis would you expect to see chronic liver damage and hepatocellular carcinoma, but not an acute illness?
Hep C
138
List some viruses which can cause antenatal and congenital infections
```
CMV: congenital malformation
Parvovirus: foetal anaemia
HSV: neonatal herpes
Rubella: congenital malformation
HIV
HPV
```
139
List some viruses which can affect the CNS
Enteroviral meningitis
Herpes simplex encephalitis and meningitis
Varicella encephalitis
Measles: primary encephalitis and SSPE
Encephalitis viruses (vector-borne, non-endemic)
Polio
Rabies
140
List the major viruses which cause systemic infections
```
EBV, CMV
HIV
Tropical vector-borne infections
Dengue and Chikungunya
Yellow fever
Viral haemorrhagic fever
```
141
How can you diagnose viral infections?
Antigen detection: early HIV (p24), HBV
Nucleic acid detection: most viral diagnosis
Immune response: IgM to detect acute infection (though increasingly replaced by PCR)
Immune response: IgG to detect immunity
142
What principles of transmission prevention can be applied to viruses?
Remove reservoirs & sources
Interrupt transmission
Increase host resistance
143
Describe some preventative mechanisms to control viral infection spread
Hygiene
Vaccination: decreases reservoirs and transmission
Human reservoirs e.g. Rubella virtually eliminated from UK
Animal reservoirs e.g. rabies
Culling reservoir animals in outbreaks
144
Describe control measures for preventing spread of influenza
Interrupt chain of transmission: hygiene, especially handwashing and tissue etiquette
Decrease the reservoir and increase host resistance: vaccination
145
Describe control measures to prevent spread of varicella
Interrupt chain of transmission: hygiene, quarantine rules for
schools/ healthcare facilities, vaccination
Decrease reservoir and increase host resistance: vaccination
Increase host resistance
Passive immunisation: pregnancy and immunocompromised
146
Describe the mechanisms of action of anti-viral drugs
Use of host cell metabolism, so high toxicity to host
Difficulties of ex vivo culture and so testing drug candidates
Rapid mutation rates
Many viral infections show symptoms only when viral replication has already ceased; no virus to kill
147
How do immunoglobulins work as anti viral drugs?
Neutralising antibodies against free virus, so act pre-replication
148
How do interferons work as anti viral drugs?
Increases cell surface presentation of viral peptides activating cytotoxic T lymphocytes to kill infected cells
149
Name 2 drugs which act to augment the immune response to viruses
Immunoglobulins and interferons
150
What is maraviroc?
Entry inhibitor used to treat HIV
151
What is enfuvirtide?
Fusion inhibitor used to treat HIV
152
What is amantidine?
Inhibits uncoating
| Used to treat influenza
153
How does aciclovir work?
Interferes with DNA replication
154
Name some important RNA viruses
Influenza
RSV (respiratory syncytial virus)
Hepatitis C
HIV and other retroviruses (have reverse transcriptase)
155
What is Ribavirin?
Nucleoside inhibitor
Stops viral RNA synthesis
Used for RSV and hep c
156
How do reverse transcriptase inhibitors work as anti virals?
Nucleoside RTIs: Nucleoside and nucleotide analogues compete with cellular building blocks of nucleic acids so blocking replication
Non nucleoside RTIs: bind allosterically at distinct site on enzyme
157
Name some reverse transcriptase inhibitors used in HIV treatment
Azidothymidine - nucleoside RTI
| Nevirapine - non nucleoside RTI
158
What is ritonavir?
Protease inhibitor used to treat HIV
159
What is oseltamivir?
Tamiflu
| Neuraminidase inhibitor used for flu
160
What is a retrovirus?
RNA virus that replicates and produces its viral RNA from a DNA copy that is spliced into the host cell DNA
This requires the enzyme reverse transcriptase
161
How is HIV transmitted?
Virus is found in blood, semen, cervical and vaginal secretions Transmission is most likely when the virus load is highest
Major modes of transmission: unprotected penetrative sexual intercourse (particularly high in anal sex), via infected blood and blood
products (sharing contaminated needles) and vertical transmission
162
What does vertical transmission mean? How likely is it?
Passing of disease from mother to child
Mostly in late pregnancy or during delivery
Likelihood depends on maternal viral load; if mother’s HIV is suppressed, then transmission is
163
How does the HIV virus cause disease?
HIV has specific tropism for CD4 positive T lymphocytes and also infects monocyte-macrophage lineage cells
Infection and then destruction of immune system cells responsible for the clinical manifestations
Viral replication, killing of infected cells by cytotoxic T lymphocytes and natural killer cells and increased apoptosis in infected and uninfected CD4 T cells all leads to decline in CD4 positive T lymphocytes
164
How do you stage a HIV infection?
Absolute CD4 cell count is used for staging HIV infection for surveillance purposes but also for clinical management as it is a guide to the susceptibility of the patient to opportunistic infection
A count of
165
What are the stages of HIV infection?
Primary HIV infection, often called seroconversion, happens 10-30 days after exposure
Symptoms: fever, pharyngitis, flu-like symptoms, generalized lymphadenopathy and maculopapular rash
Infection enters asymptomatic phase: may last up to 10 years or more, virus is replicating in this time but not causing clinically overt disease. Sometimes persistent, generalized lymphadenopathy is present during this ‘asymptomatic” stage
Development of clinically overt symptoms signals the entry to category of AIDS
166
What is AIDS and how is it defined?
Acquired immune deficiency syndrome
| Present if HIV infection is confirmed and one or more AIDS-defining illness is present
167
What are the principal infectious and non-infectious complications of HIV?
Infectious: Tuberculosis, Cytomegalovirus, Candidiasis, Cryptococcus meningitis, Toxoplasmosis, Cryptosporidiosis
Non infectious: Kaposi's sarcoma, lymphomas, wasting syndrome, neurological complications, kidney disease
168
What can be a complication of HIV therapies?
Immune reconstitution inflammatory syndrome
When HIV replication is suppressed and CD4 T cells become more active, there is a generalized response to pathogens present in the body
169
How do we diagnose HIV? Why might the diagnosis be missed?
Old HIV test: detection of antibody to HIV, using ELISA. Seroconversion to antibody positivity takes 1-2 months leading to the “seroconversion window” when diagnosis could be missed because no antibody is present. Testing strategy requires 1 screening test followed by 2 confirmatory tests on the same sample using different targets, plus a 2nd specimen from the patient.
Newer tests and testing strategies detect HIV antigen, usually the p24 envelope protein, they are therefore positive earlier than the antibody based tests. HIV RNA can also be detected in blood using PCR. This can be quantitative and is used for monitoring viral loads
170
What are the principles of HIV management?
Manage in multidisciplinary way, specialist-led, patient-centred
Aim to stop and if possible reverse damage to immune system
Improve physical and psychological well-being
171
What are the major modes of action of anti retroviral drugs?
Blocking adsorption and entry to cells: maraviroc (CCR5 blocker)
Inhibit entry to cell by envelope fusion e.g enfuvirtide
Inhibit replication by inhibiting reverse transcriptase either by nucleoside/nucleotide analogues (NRTIs) e.g. AZT or by blocking the active site (NNRTIs) e.g nevirapine
Inhibit replication by stopping viral nucleic acide integrating into host DNA: integrase inhibitors
Inhibit viral maturation: protease inhibitors
172
Why are anti retroviral drugs used in combination?
Delay development of resistance and maximize effectiveness
| HAART (highly active antiretroviral therapy) uses at least 3 drugs
173
What is primary chemoprophylaxis as applied to HIV and how is it different from secondary chemoprophylaxis?
Primary chemoprophylaxis is use of antimicrobials to prevent secondary viral, bacterial or fungal infections before they occur
Secondary chemoprophylaxis is the use of antimicrobials to prevent recurrence of an infection that has already occurred
174
Who produces UK guidelines on HIV management and treatment?
BHIVA (British HIV association)
175
How is transmission of HIV stopped?
Intervening with the transmission cycle
Safer sex, maternal antiretroviral therapy, good infection control practices, needle exchange schemes
No vaccine yet clinically available; vaccine development is severely hindered by the ability of the virus to vary its surface antigens
176
What is PEP and when might it be used?
Post-exposure prophylaxis
Main indications are after occupational exposure (needlestick), and after high risk sexual contact
Risk of acquiring HIV from an infected patient after an inoculation injury with a hollow-bore needle is quoted as approximately 3 in 1000
Important to remember that other viruses can be transmitted via such injuries, notably hepatitis B, with a risk of approximately 30% and hepatitis C with a risk of 1.5-3% (no PEP available)
177
How is hepatitis B spread?
Body fluids: contaminated transfusion products, reused needles, sex, vertical transmission
178
What needs to be put in place for hepatitis B positive patients who are asylum seekers?
Refer to hepatology specialist at Univ Hospital
Levels of virus checked; if high and liver damage may need antiviral treatment
Spouses and children need screening and imms
179
What needs to be done annually for people with sickle cell or thalassaemia traits?
Annual flu vaccs, pneumococcal vacc, hep A and B
180
Describe how retroviruses work
Enveloped viruses, replicate in host cell via reverse transcription
Have single stranded RNA and use their own reverse transcriptase enzyme to turn this into DNA within a host cell
DNA is incorporated into host chromosome, then referred to as provirus and uses usual transcription-translation processes of the cell
181
Describe the genetic variability of the HIV virus
Fast replication cycle
High mutation rate
Retroviral recombination: Strand switching, Infected with >1 virus
182
When do HIV levels rise to their biggest peak after an infection?
Weeks 3-6
| Wide dissemination of virus, seeding of lymphoid tissue
183
What may be symptoms of acute HIV infection?
```
Fever, malaise, myalgia
Non-tender lymphadenopathy
Sore throat/glandular fever, esp ulcers
Generalised rash
Nausea, diarrhoea, weight loss (average 5kg)
Headache, viral meningitis
```
184
When do HIV levels stabilise after infection?
Within 6 months
185
What conditions put HIV into the B category of severity? (Symptomatic)
Oropharyngeal candidiasis, pelvic inflammatory disease, cervical dysplasia, oral hairy leukoplakia, shingles (2+ episodes or >1 dermatome), diarrhoea >1 month, peripheral neuropathy
186
What conditions put HIV into the C category of severity? (AIDS indicator conditions)
Recurrent pneumonia, candidiasis of bronchi or oesophagus, cervical carcinoma, cryptococcosis, chronic cryptosporidium, CMV disease, HIV encephalopathy, histoplasmosis, karposi sarcoma, lymphoma, Progressive multi focal leukencephalopathy, pneumocystis pneumonia, tuberculosis, toxoplasmosis
187
What prophylaxis is available for people with HIV?
Vaccination (e.g. hepatitis)
PCP – co-trimoxazole
Toxoplasma – co-trimoxazole
Mycobacterium aviumcomplex - azithromycin
188
How can you diagnose HIV?
Serology: IgG at 6-12 weeks in most and by 6 months in 95%
Antigen testing (p24)
Viral detection: Not for diagnosis but may be useful in acute HIV,
neonates
189
What tests would you do for a neonate to check for HIV?
HIV-1 DNA PCR for provirus (maternal ab interferes with sero)
190
What test would you do for suspected HIV in a patient presenting with seroconversion illness?
HIV RNA test
| Caution in believing if low level (false positive)
191
What test would you do for someone with established HIV?
4th generation Ab/Ag test
192
Name some Nucleoside/tide reverse transcriptase inhibitors
Azidothymidine, dideoxythymidone, didanosine, abacavir, lamivudine, emtricitabine, tenofovir
193
Why do reverse transcriptase drugs have some of the side effects that they do?
Limited effect on human cells which can repair their own DNA if drug acts on them
At higher doses can inhibit the mitochondrial DNA polymerase (lactic acidosis, myopathy, anaemia)
Other side effects include body fat changes, neuropathy
194
What drugs except reverse transcriptase inhibitors are available for HIV treatment?
Protease inhibitors: indinavir, lopinavir, ritonavir, dalrunavir
Non-nucleoside RT inhibitors: Nevirapine, efavirenz, rilpivirine
Fusion inhibitors: Maraviroc (CCR5 blocker), Fuzeon
Integrase inhibitors: Raltegravir, prevents viral DNA integrating into host cell
195
When do you treat people with HIV?
British HIV Association 2015 guidelines: Now recommend treatment of all HIV positive patients regardless of CD4 including those with acute HIV
196
What is untreated HIV a risk for?
Coronary and renal disease, neurocognitive decline, malignancy
197
What does BHIVA recommend as treatment for HIV?
Tenofovir, emtricitabine and a Protease inhibitor, integrase inihibitor or NNRTI
198
What are some problems with HIV testing and treatment?
```
Stigma about testing
Practicalities of testing
Denial about result
Infrastructure: Clinic size and site, Nurse and doctors, Transport of specimens, keeping drugs, communicate results
Monitoring
Adherence
Emergence of resistance
```
199
What are important prevention strategies for HIV?
Education and behaviour: ABC (abstinence, be faithful, condom), Concurrent partnerships
PMTCT (prevention of mother to child transmission): Early anti-retroviral drugs to mother, Prophylaxis to child
Male circumcision: Reduces risk by 50-60% in Africa
Treatment as prevention
Vaccine
200
What is HAART?
Highly active anti retroviral therapy
