L4 - Picornavirus II (Poliovirus and Rhinovirus) Flashcards
(136 cards)
1
Q
What surprising personal connection did the lecturer mention regarding Type 1 Diabetes?
A
He was diagnosed with Type 1 Diabetes after an enterovirus infection, possibly triggered by a series of COVID infections, suggesting he may have had a genetic predisposition.
2
Q
When do most people acquire poliovirus?
A
When they are a child and most child cases don’t result in symptomatic disease (but some cases can result in serious illness)
3
Q
What family is poliovirus apart of?
A
Picorna family
4
Q
how many types of human poliovirus are there?
A
3 :
Human poliovirus 1
Human poliovirus 2
Human poliovirus 3
5
Q
how do poliovirus type 1-3 spread?
A
Via the faecal oral route
6
Q
What typically happens in 2 days after infection?
A
- Invasion
- Multiplication of the virus
- Final excretion in faeces through the large intestines
(usually the patient doesn’t show any symptoms)
7
Q
What happens after 2 days if poliovirus enters the bloodstream?
A
- Within the first 24 hours, the virus invades the regional lymph nodes. Over the next 24–48 hours, it enters the bloodstream, leading to viremia as it spreads to secondary replication sites in other organs.
- During viremia, the virus can reach the central nervous system (CNS) within 6 days in approximately 1–2% of infected individuals.
- In the CNS, poliovirus replicates in motor neurons. If a critical number of these neurons are destroyed, the individual may develop partial or complete paralysis within 10 days, occurring in 0.3–1% of cases.
8
Q
What are the progressive symtoms of an individual getting paralysis
A
Illness often begins with a headache, fever (ranging from mild to moderate) and a stiff neck and back (muscles become rigid and painful) followed by paralysis of the voluntary muscles previously controlled by the destroyed neurons of either the spinal cord or the brainstem
9
Q
What was the era of the iron lungs
A
late 1920s to early 1960s which was the perioid of peak poliomyelitis epidemics before the use of widespread availability and use of effective vaccines. This lead to many being hospitalised and widespread use of iron lungs
10
Q
What is the Oral Polio Vaccine (OPV)?
A
The OPV is a live attenuated vaccine given in droplet form, making it easy to administer, especially in large-scale immunization efforts.
11
Q
Why has polio eradication been delayed despite global efforts?
A
- Health inequalities
- civil unrest
- the COVID-19 pandemic
- political instability (wars) and indifference
- vaccination fatigue (by parents whose children have recieved more than 15 doses)
- evolution of the vaccine strains (vaccine derived poliovirus)
- escape from labs (bioterrorism)
- Hostility to vaccination : misinformation in Pakistan and violence against vaccinators
- maintaining the potency of live vaccines in extremely hot areas
12
Q
what temperature does the vaccine need to be kept at to be successful
A
2-8*c
13
Q
What is the primary mode of transmission for poliovirus?
A
It is transmitted via the faecal-oral route, typically acquired in childhood.
14
Q
What disease is poliovirus the causative agent of ?
A
Poliomyelitis
15
Q
What are the neurological consequences of poliovirus infection?
A
Outcomes range from mild limb paralysis to total body paralysis requiring respiratory support and in some cases death
16
Q
How did improved sanitation affect polio outbreaks in developed countries?
A
improved sanitation initially reuced cases, but sporadic outbreaks still occurred due to lapses in hygiene or contaminated food, especially in the 20th century
17
Q
What was the historical impact of polio outbreaks in the 20th century?
A
Outbreaks, especially in the 1950s had devastating impacts, with close to 4 million reported cases of which up to 1% of infected individuals becoming paralysed, severely straining healthcare systems
18
Q
What is the March of Dimes and how is it related to polio?
A
this was one of the first major public fundraising efforts in the U.S to support medical research, specifically focused on combating polio
19
Q
Why did poliovirus gain significant public attention in the early 20th century?
A
Polio gained attention partly because it was widespread and debilitating and even affected high-profile figures like supposedly U.S President Franklin D.Roosevelt, who was believed to be paralysed by it. Because of the the public attention it was increasingly present in the media, their was increasing funding and intensive research into the vaccines
20
Q
What was a major scientific breakthrough that enabled polio vaccine development?
A
Poliovirus became the first virus to be grown in cultured cells, which allowed for large scale vaccine development and testing
21
Q
What are the two types of polio vaccine developed and who created them?
A
The Salk vaccine (inactivated virus) and the Sabin vaccine (live attenuated virus)
22
Q
what are the key differences between the Salk and Sabin vaccines?
A
- The Salk vaccine requires intramuscular injection by trained personnel and is more costly, while the Sabin vaccine is oral, cheaper, and easier to administer, making it ideal for mass immunisation.
-The Salk vaccine induces a strong systemic IgG immunity which protects against severe disease - prevents the virus from replicating in the CNS and causing paralysis but does not prevent initial infection or viral shedding from the gut whilst sabin vaccine induces both mucosal (IgA) and systemic immunity (IgG) offering protection at the site of viral entry blocking infection and transmission
23
Q
What are the dosage requirements for the SALK and SABIN vaccines?
A
SALK = 3 univalent injections
SABIN = 3-4 multivalent doses
(both provide lifelong protection)
24
Q
Why does the Sabin vaccine carry a risk of complications?
A
Because it is a live attenuated vaccine, Sabin can sometimes revert to a virulent form due to mutations during replication, potentially causing vaccine-derived polio.
25
What is "blind passaging" and how was it used in developing the Sabin vaccine?
Blind passaging is a process where the virus is repeatedly passed through animals (monkey strains) or cell cultures to accumulate spontaneous mutations that reduce virulence, ultimately producing an attenuated strain.
26
How many mutations / nucleotide substitions were made in attenuating the Sabin vaccine strains?
SABIN 1 : 57 substututions (of these 21 resulted in changes to aa in viral proteins)
SABIN 2 : 2 substitutions
SABIN 3 : 10 substitutions
The smaller the number of mutations, the more likely the virus can revert back to a more virulent form during replication posing a risk for vaccine-derived outbreaks.
27
which structural proteins had mutations in SABIN 1
VP1, VP3 and VP4
28
Which structural proteins were mutated in SABIN 2`
VP1
29
What strutcural proteins were mutated in SABIN 3
VP1
30
What major public health success inspired the WHO to attempt polio eradication?
The successful eradication of smallpox in 1980 motivated the WHO to attempt global eradication of poliovirus using available vaccines.
31
What os the issue with live SABIN strains?
Although they are less virulent, because they are alive, they could mutate and revert back to their original virulent forms which become more likely the fewer mutations they have e.g. SABIN 2 has the highest likelihood
32
Why is the Sabin vaccine preferred in global eradication efforts despite its risks?
The Sabin vaccine is cheap, easy to administer, and induces mucosal immunity, making it suitable for mass vaccination campaigns in resource-limited settings.
33
What were the two vaccination strategies to try and eradicate poliovirus?
1. Mass vaccination
2. Routine immunisation
34
How does mass vaccination strategy work for eradication
Involves national immunisation days which abruptly reduces the number of susceptible individuals. This interrupts virus transmission including silent transmissions which is important as many infected are asymptomatic
35
What is the concept of “National Immunisation Days” in the context of polio eradication?
National Immunisation Days involve mass administration of the oral polio vaccine to all children in regions where the virus circulates, aiming to stop transmission and achieve regional elimination.
36
How does routine immunisation strategy work?
protects the individual but generally doesn;t stop the virus from circulating. (not as good as mass vaccination)
37
What is the ultimate goal of using the oral polio vaccine in eradication campaigns?
The goal is to achieve herd immunity in endemic areas, stopping virus circulation and ultimately leading to the global eradication of poliovirus.
38
Why is routine immunisation coverage low in many developing countries?
Stroage of the vaccine is difficult in hotter climates (needs to be kept at 2-4*c) , and there is year-long transmission leading to a higher likelihood of individuals being infected before routine immunisation is possible
39
Why might some children require up to 12 doses of polio vaccine in certain regions?
In regions with high prevalence of gastrointestinal infections, vaccine efficacy may be reduced, requiring more doses to establish effective immunity.
40
what are poliovirus trens in 1988 vs now
1988 : 350,000 cases with 125 endemic countries
2016 : 34 cases with 3 endemic countries (Afghanistan, Pakistan and Nigeria)
2000 : 719 cases (going up?)
41
Annual expenditure on poliovirus from 1988 to present
1988 - low
2000 - $150 million
2010 - $400 million
( initially cases dropped as expenditure increased, but more recently despite increasing epensidure cases remain relatively stable / increasing slightly showing how eradictaion has been more challenging than originally predicted and doesn't always relate to how much is invested)
42
Which poliovirus vaccines is offered in the UK
the inactivated poliovirus vaccine (IPV) AKA the SALK vaccine. This will be offered as a component of the 5 in 1 vaccine DTaP/IPV/Hib
Diptheria (D) , Tetanus (T), Pertussis(aP), Polio (IPV), Haemophilus influenza tybe b (Hib) - usually given in a series of 5 doses starting from 8 weeks / 2 months
43
when was type 2 poliovirus last detected and declared eradicated globally
last detected = 1999
eradicated = 2015
44
When was type 3 poliovirus last detected and then declared eradicated globally
last detected = 2012
eradicated = 2019
45
which type of poliovirus now remains
type 1 wild poliovirus (endemic to Afghanistan and Pakistan)
46
which vaccine was the trivalent poliovirus vaccine replaced by in 2016
the bivalent vaccine which includes type 1 and 3
47
What was the poliovirus immunisation setback in Nigeria in 2003
Rumours that the vaccine caused sterility in girls preventing people getting immunised and leading to a dramatic rise in cases in an already endemic country. because the spread was uncontrolled it eventually led to re infection to 8 poliovirus free countries
48
when/ where was the trivalent poliovirus vaccine re introduced and why?
the trivalent poliovirus was reintroduced in Nigeria to control an outbreak of circulating vaccine derived poliovirus type 2 which had emerged despite the use of monovalent vaccines for type 1 and 3. The re-introduction aimed to provide population-level immunity against the re-emergent neurovirulent type 2 strain
49
What was the recent poliovirus immunisation setback in Afghanistan?
The taliban suspeded a national vaccinaton campaign and wanted to impose taxes on humanitarian groups and their activities. That year the WHO detected 18 new poliovirus cases (up from only 6 cases in 2023)
50
by what percentage have poliovirus eradication efforts reduced the number of annual diagnosed cases by ?
99.9%
51
What does cVDPV stand for?
Circulating vaccine-derived poliovirus
52
How can cVDPV arise
the excreted OPV vaccine virus can mutate and accumulate genetic from other enteroviruses. In some cases, the vaccine virus can change into a paralytic form of cVDPV
53
what is Vaccine-Associated Paralytic Poliomyelitis (VAPP)
VAPP is a rare but serious adverse event linked to the use of the Oral Poliovirus Vaccine (OPV). It involves the development of paralytic polio in individuals who have received the OPV or in their close contact
54
what is the estimated incidence rate of VAPP in primary OPV vaccine recipents
incidence rate of VAPP in primary (first-time) OPV vaccine recipents is ~ 1 in 750,000 (very rare)
55
What are characteristic VAPP symtoms?
VAPP patients typically display polio symtoms which include acute flaccid paralysis (sudden weakness or paralysis of the limbs), muscle weakness and potential respiratory difficulties if the paralysis affects the breathing muscles. Most importantly it is still transmissible
56
what is the issue with cVDPV and outbreaks?
Many outbreaks in areas where poliovirus were previously eradicated have occurred. Sequence analysis has shown that the virus isolated from patients were found to be very similar to the vaccine strains of poliovirus
57
What is the genetic composition of cVDPVs
they can have structural genes from polio (determining the viral particle) and nonstructural genes from other enterviruses (through recombination) or mutated vaccine virus genes.
58
How is transmission believed to take place in VAPP cases?
It is believed to be shed in the stool of the vaccinated individuals. Close contacts, particularly household members who are not fully immunised can become infected with the shed virus
59
how long was the new cVDPV found to have circulated for?
around 2 years
60
What are immune deficient vaccine-derived polioviruses (iVDPVs)
Immune-Deficient Vaccine-Derived Polioviruses (iVDPVs) are poliovirus strains derived from the live attenuated viruses in the Oral Poliovirus Vaccine (OPV) that undergo significant genetic evolution and can become neurovirulent after prolonged replication in individuals with compromised immune systems.
61
How long can does excretion of vaccine derived poliovirus strains typically last in individuals with a normal immune function vs how long can iVDPVs be secreed by individuals with compromised immune systems?
VDPV in normal immune function = several weeks
iVDPVs in immunocompromised = for years
62
how does the sequence of iVDPVs change over time compared to the original vaccine strain?
the sequence significantly drifts from the original vaccine over the extended period of replication potentially regaining virulence and transmissibility
63
What is a critical implication of the eventual eradication of wild-type poliovirus regarding the source of paralytic polio?
When wild-type poliovirus is eradicated globally, vaccine-derived polioviruses (both cVDPVs and iVDPVs) will be the only remaining source of paralytic polio posing a large threat (necessitating the eventual global cessation of OPV use in favour of the safer IPV to achieve a truly polio free world.)
64
What was the SV40 contamination issue with the polio vaccine around 1960?
In the 1960s, it was discovered that the rhesus monkey kidney cells used to prepare some polio vaccine batches. These Kidney cells were infected with Simian Virus 40 (SV40) which Is known to cause cancer in some animal models. ~10-30 million Americans received doses of the contaminated vaccine although no relationship was found with immunisation and cancer.
65
which strain is most associated with cVDPV
type 2 becuase it was the first to become eradicated and the bivalent vaccine replaced only covered type 1 and 3 meaning that when cVDPV regains neurovirulent properties, it was able to spread amongst the unimmunised
66
what is the novel type 2 OPV (nOPV)
a promising genetically engineered vaccine
67
what is the novel type 2 OPV (nOPV2)?
nOPV2 is a genetically engineered version of the type 2 oral poliovirus vaccine designed with improved genetic stability especially at the 5' UTR (known to be important for attenuation), imrpved fidelity of the viral polymerase (reducing the likelihood of mutations during replication) and safety features.... used to prevent cVDPV2 outbreaks
68
when was the nOPV2 introduced?
In 2021
69
whow many doses have been given out since nOPV2s introduction
500 million doses across 25 countries
70
after nOPV2s success what is currently undergoing clinical trials?
nOPV1 and NOPV3 which are being designed to be more temperature stable, better for hotter climates where outbreaks are more common or where cold chain can't be maintained as easily
71
what is the "abrupt" cessartion stretegy for OPV vaccination and what is the rationale behind it?
An "abrupt" cessation strategy involves a sudden and complete stop to all OPV use globally after a mass immunisation campaign. the rationale is that since excretion of the vaccine virus typically lasts no longer than 6 months in immunocompetent inviduals, a synchronised global stop after high coverage could prevent the emergence of new cVDPVs
faecal samples in lab freezers would have to be completed destroyed to prevent accidental lab escape / spread.
72
what is a key uncertainty associated with an abrupt cessation of OPV?
the status of iVDPVs is uncertain under an abrupt cessation strategy - they could potentially continue to shed neurovirulent viruses for years after a global OPV cessation posing risk for outbreaks in susceptible individuals.
73
why could it potentially be feasable for complete eradication once it is eradicated in people
there are no other animal hosts for poliovirus, so once it is eradicated in humans, it is potentially fully eradicated
74
How is inactivated polio vaccine (IPV) currently used in most countries?
most countries use IPV (containing killed poliovirus - therefore carries no risk of VAPP or the generation of cVDPVs or iVDPVs) for routine immunisation against polio
75
What are the chalenges associated with a global shift to IPV
involve cost and supply issues as it is expensive so it would have to be subsidised by other countries and like with any vaccine there needs to be good coverage otherwise susceptible people can cause outbreaks (especially since IPV does not prevent transmission of poliovirus)
76
since Jan 2013 which countries have introduced IPV
Kazakstan
Peru
Micronesia
Libya
Albania
Panama
Nepal
Tunisia7Senegal
Servua
Columbia
Nigeria
Bangladesh
Maldives
DR Congo
Korea
Cote D'Lvoire
Cameroon
Niger
Pakistan
Sri Lanka
77
how many countries induduced IPV as of 2015
97
78
how many countries introdueced IPV as of 2018
176
79
What are the potential sources for the re-emergence of poliovirus after eradication?
- Persistence of wild-type strains in undetected reservoirs.
- Evolution of vaccine strains (leading to cVDPVs or iVDPVs).
- "Escape" of the virus from laboratories.
- Intentional release through bio-terrorism.
80
What ky strategies have been proposed to prevent or manage poliovirus re-emergece in the post-eradication era?
- Proper containment of the virus in laboratories to prevent accidental release or intentional misus of poliovirus stocks held in laboratories which could lead to new outbreaks
- Robust disease surveillance to rapidly detect and contain (stop) any re-emergence
- Effective outbreak response capabilities.
- Continued vaccination using IPV to maintain population immunity and protect individuals against paralytic disease in the event of re-emergence
- Development of new vaccines or antiviral drugs.
81
What is an example of disease surveillance
waste water surveillance e.g. London
82
What is Pleconaril and why is it relevant in the context of post-polio preparedness?
Pleconaril is a capsid-binding broud-spectrum antiviral drig that was under renewed development and is effective against polioviruses (and entero/rhinoviruses). It is relevant as a potential antiviral treatment option in the event of a poliovirus outbreak
83
how does pleconaril work?
Pleconaril works by binding to a hydrophobic pocket within the capsid. this binding stabilises the capsid and prevents the conformational changes necessary for the virus to uncoat ts RNA genome inside the host cell. By inhibiting uncoating, Pleconaril effectively blocks viral replication
84
What is the overall significance of rhinoviruses in human health?
Rhinoviruses (belonging to 3 species) are the causative agents of the most common cold infections in humans (resulting in worldwide infections)
85
what proportion of acute respiratory illnesses are estimated to be caused by rhinovriuses?
at least 50% of all acute respiratory illnesses
86
How are rhinoviruses classified?
into 3 groups : A,B and C. Within these groups there is a high degree of antigenic diversity with over 100 serotypes in groups A and B and over 60 serotypes in group C
87
what is the primary site of rhinovirus infection?
the nasal mucosa ( Rhinoviruses are well adapted to the slightly coolore temperatures found in the nasal passages (around 33-35*c)
88
What are the key receptors that rhinoviruses use to enter host cells in the nasal mucosa?
- ICAM-1 (Intercellular Adhesion Molecule 1): The major receptor for most rhinovirus serotypes (primarily in groups A and B). Its expression can be upregulated by inflammatory cytokines.
- LDLR (Low-Density Lipoprotein Receptor) family: Used by a smaller subset of rhinovirus serotypes (mainly in group B).
- CDHR3 (Human Cadherin-Related Family Member 3): A key receptor, particularly for many rhinovirus C serotypes, and has been linked to asthma susceptibility and severity.
- Others: Research continues to identify additional receptors that may be used by specific rhinovirus serotypes.
89
What is notable about the amount of rhinovirus required to initiate an infection?
Infection can be initiated with less rhinovirus than is detectable in optimal assay systems (highlighting its high infectivity and contributes to the ease at which colds can spread)
90
How are rhinoviruses primarlity spread?
by virus-contaminated respiratory secretions e.g. droplets released by sneezing or coughing. These can then be directly inhaled or survive on surface which then get touched
91
How do rhinovirus infection and illness rates vary with age?
Infection and illness rates are highest among infants and children (>1 infection per year / 26% of children under 5 yo were rhinovirus positive) and decrease with increasing age.
92
How many rhinovirus subtypes are there?
167 - very diverse and an issue is that if you get infected by one subtype you don't get immunity to the other 166
93
What proportion of infected get clinically apparaent symptoms
2/3
94
what are the typical clinical symtoms for rhinovirus
dry throat, followed by sneezing, unilateral or bilateral nasal obstruction (stuffy nose from inflammation of the nasal linking) and the onset of nasal discharge (runny noise in attempt to clear the virus). OIther symptoms can also include headaches, coughs, fever and general malaise. These symptoms are very general
95
What percentage of people infected with rhinovirus get a fever?
10-20%
96
what is the typical duration of maximal illness and the overall duration of rhunvius infection symptoms?
maximal illness (when symtoms are most severe) typically last for 2-3 days, and the overall duration of symptoms is for around 7 days
97
what complications can be facilitated by rhinovirus infection
Rhinovirus infections can facilitate the development of bacterial sinusitis (inflammation of the sinuses) and otitis media (middle ear infection).
Increased mucus production can also bring bacteria from the normal flora into the lungs where they can contribute to more serious bacterial infections e.g. pneumonia that can require antibiotics
Some people are also more prone to getting chronic bronchitis or asthma
98
What is the role of rhinovirus and asthma
It can induce inception of asthma in healthy infants and exacerbation of asthma in children or adults with asthma already.
99
Rhinovirus inception in healthy infant pathway
infections with human rhinovirus (as well as RSV or other viruses such as influenza) can decrease lung function, reduced and changed IFN responses e.g. Epithelial cells produce less Type I (IFN-α/β) and Type II (IFN-γ) interferons in response to human rhinovirus infection reducing viral clearance. This means that the individal will get more severe symptoms that can lead to wheezing illness which can either resolve, or otherwise develop into asthma. At this point the patients airways would have remodelled and they can then get exacerbations when reinfected
100
what happens in exacerbation of asthma
when a child or adult who already has asthma gets infected, this can result in exacerbations, acute care visits and hospitalisations
101
what was the link found between severe rhinovirus infections in early childhood and the development of asthma according to a cohort study
the cohort study conducted, followed 259 children from birth and found that ~90% of children who had severe rhinovirus infections before the age of 3, developed asthma by the age of 6. Additionally children who developed asthma were found to have more prolonged and pronounced rhinovirus infections. (this is one of the best ways to make epidemiological links)
102
In general what porportioon of asthma exacerbations are associated with respiratory infections?
it is estimated that ~80-85% of asthma exacerbations are associated with respiratory infections. Of which 60% are associated with rhinovirus viral infections
103
How does rhinovirus infection differ in non-predisposed host versus an asthma-predisposed host?
In a non-predisposed host, rhinovirus infection leads to an appropriate immune response and resolution, resulting in healthy lungs. In an asthma-predisposed host, rhinovirus infection triggers an inappropriate immune response characterised by airway inflammation, potentially leading to chronic lung injury and permanent remodeling over time.
104
what is a non-predisposed host vs a predisposed host
non-predisposed host - someone who is more resistant against rhinovirus infection. Mosly to do with genes in their interferon responses
predisposed host - someone who is genetically predisposed to asthma
105
What is the likely primary mechanism of recovery from a primary rhinovirus infection?
Recovery from a primary rhinovirus infection is unlikely to be mediated primarily by antibodies (Ab) or cellular immune responses. Instead it is largely though to be due to innate immune responses e.g. interferon production and the shedding of infected epithelial cells. The adaptive immune response takes longer to develop and may play a more significant role in subsequent protection
106
what happens to IgA and IgG antibody levels after a rhinovirus infection and what is their role in protection?
Both IgA and IgG antibody levels increase after a rhinovirus infection and provide protection for several months against the homologous virus (the specific serotype that caused the infection).
107
Which antibody class appears to be the most important in protection against rhinovirus reinfection, and what is its temporal pattern?
IgA, although its levels decrease over time
108
How does the numer of serotype-specific antibodies change with increasing age?
With increasing age, there is an increase in the number of serotype-specific antibodies as individuals are exposed to a greater variety of rhinovirus serotypes, leading to the development of specific antibodies against each encountered strain. This accumulated immunity contributes to the decrease in the frequency of colds as people get older, although new serotypes can still cause infection.
109
How effective were inactivated rhinovirus vaccines in early studies?
Inactivated rhinovirus vaccines were shown to reduce virus shedding and illness in vaccinated individuals.
110
What are the major factors complicating the development of a successful rhinovirus vaccine?
- Multiplicity of serotypes: The sheer number of distinct rhinovirus strains (over 160) makes it impractical to include them all in a single vaccine.
- Minimal cross-reactivity between different serotypes: Immunity to one serotype generally does not protect against infection with other serotypes.
- Difficulty in maintaining IgA levels: Achieving long-lasting protective IgA responses in the nasal mucosa through vaccination has proven challenging.
- Development of drug-resistant strains: Like with other viruses, rhinoviruses can potentially develop mutations that confer resistance to antiviral drugs.
- Treating the illness at the optimal time: Colds typically have a rapid onset, and maximal viral shedding occurs early in the infection, often before symptoms are severe enough for individuals to seek treatment. Antivirals may be most effective if administered very early in the course of the illness.
- some strains e.g. RV-C lacking a hydrophobic pocket
111
How successful have antiviral compounds with in vitro activity against rhinoviruses been in clinical trials?
Many compounds have shown antiviral activity against rhinoviruses in cell culture, but few have demonstrated effectiveness at the clinical level in humans. Testing for effectiveness in humans has been almost uniformly discouraging. With that said antivorals can be made more effective when they are given in combination with other antivirals
112
How has understanding the three-dimensional structure of rhinoviruses aided in antiviral drug development?
The description of the three-dimensional structure of rhinoviruses has permitted precise assessment of drug interaction with capsid proteins. Examples include drugs like Pirodavir and Pleconaril.
113
What is a major challenge in achieving effective antiviral treatment for rhinovirus infections?
A major challenge lies in achieving optimal administration of the drug to the nasal mucosa, the primary site of infection.
114
which rhinovirus strains aren't amenable to antiviral drugs and why
RV-C strains as they lack the hydrophobic pocket
115
What is a defining characteristic of the Hepatitis A Virus (HAV) in terms of its global impact?
HAV is responsible for over 90% of viral hepatitis cases worldwide, highlighting its significant global health burden. This high percentage underscores the importance of understanding its transmission and prevention.
116
What is the spectrum of clinical symptoms associated with a Hepatitis A Virus (HAV) infection?
Clinical symptoms can range from being completely asymptomatic to developing acute hepatitis, which involves inflammation of the liver and can cause symptoms like jaundice (yellowing of the skin and eyes), fatigue, abdominal pain, nausea, vomiting, and dark urine. The severity can vary greatly between individuals.
117
Does Hepatitis A Virus (HAV) establish a long-term, persistent infection in individuals?
No, HAV is not shed chronically. This means that once the acute infection resolves, the virus is typically cleared from the body, and individuals do not continue to transmit the virus long-term. This is a key difference between Hepatitis A and some other forms of viral hepatitis (like Hepatitis B and C).
118
What is the primary route of transmission for Hepatitis A Virus (HAV), and what other virus shares a similar epidemiological pattern?
HAV is spread through the faecal-oral route. This means the virus is shed in the faeces of an infected person and can be ingested by another person, often through contaminated food or water, or poor hygiene practices. This is similar to the epidemiology of poliovirus, which also spreads via the faecal-oral route, emphasizing the importance of sanitation and hygiene in preventing both infections.
119
Where does HAV primarily replicate within the body?
HAV primarily replicates in the liver. After ingestion, the virus replicates in the gut where it then travels to the liver (main site of replication) via the bloostream, where it infects hepatocytes (liver cells) and multiplies. This replication process leads to liver inflammation and the symptoms associated with hepatitis.
120
How does the Hepatitis A Virus (HAV) leave the liver to be shed from the body?
HAV is excreted in bile, a fluid produced by the liver that aids in digestion. Bile containing the virus is then released into the intestines and eventually eliminated in the faeces, facilitating the faecal-oral transmission route.
121
What challenges are associated with growing Hepatitis A Virus (HAV) in a laboratory setting using cell culture?
- It replicates slowly, making it challenging to produce sufficient quantities of the virus for research and diagnostic purposes.
- It does not alter host macromolecular synthesis in a significant way that is easily detectable in cell culture. Many other viruses disrupt the host cell's normal processes, making their growth easier to monitor.
122
what is the course of a typical HAV infection
after exposure, viral levels will continue to increase and it will be detectable in faecal samples after a couple of days which is when you can spread it to others. Within a week patients get viraemia and after 2 weeks clinical symptoms appear.
By 4.5 weeks, there will be a peak in liver enzymes which coincides with liver damage. At the same time there is a good immune response but it can take time to develop
123
Hepatitis A (HAV) clinical features in young ages
HAV clinical features are age dependent with children being more likely to have asymptomatic infection and jaundice being rare in children under the age of 6
124
After the onset of jaundice in a typical Hepatitis A Virus (HAV) infection, when is an individual generally considered non-infectious?
An individual with a typical HAV infection is generally considered non-infectious 1 week after jaundice develops. This timeframe is important for public health recommendations regarding isolation and preventing further spread of the virus. The decline in infectivity is associated with the clearance of the virus from the stool.
125
What is meant by "inapparent" Hepatitis A Virus (HAV) infection, and what liver enzyme levels are typically observed?
An inapparent HAV infection is asymptomatic, meaning the individual does not experience any clinical signs of illness. Importantly, in these cases, there is no increase in ALT (alanine aminotransferase) levels. ALT is a liver enzyme, and its elevation usually indicates liver damage. The absence of elevated ALT suggests that even with infection, significant liver inflammation may not occur in some asymptomatic individuals.
126
Describe the features of "clinically evident" Hepatitis A Virus (HAV) infection.
Clinically evident HAV infection involves liver dysfunction, leading to symptoms such as dark urine and jaundice (yellowing of the skin and eyes due to bilirubin buildup). However, it's important to note that infection without jaundice may also occur. Other common symptoms include fever, aches, nausea, fatigue, and diarrhoea.
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What is the typical duration of symptoms in a Hepatitis A Virus (HAV) infection, and what is a less common but possible longer-term outcome?
Symptoms of HAV infection do not normally last longer than 2 months. However, in some cases, a relapsing HAV infection can occur, where symptoms reappear after an initial improvement. Full recovery, even with relapsing HAV, typically takes around 1 year.
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What is a rare but severe complication of Hepatitis A Virus (HAV) infection, and what is the potential outcome?
: In rare cases, HAV infection can lead to fulminant hepatitis, which is a sudden and severe form of liver failure. This is a life-threatening condition and can result in death
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According to Robertson & Bell (2001), how are worldwide Hepatitis A Virus (HAV) endemicity patterns typically categorized?
Robertson & Bell (2001) distinguished 4 patterns of worldwide HAV endemicity: green - very low endemecity, orange - low endemicity, yellow - intermediate endemicity, pink - high endemicity. These patterns reflect the prevalence of HAV infection in different populations based on factors like sanitation, hygiene, and socioeconomic status. (While the specific patterns aren't detailed in your provided text, this highlights the geographical variation in HAV risk).
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Why is serological detection crucial for diagnosing Hepatitis A Virus (HAV) infection?
HAV symptoms are not distinct, meaning they can resemble those of other viral illnesses. Therefore, diagnosis requires serological detection, which involves blood tests to identify specific antibodies (like anti-HAV IgM for acute infection and anti-HAV IgG for past infection or immunity) produced by the body in response to the Hepatitis A virus.
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What are the key strategies for the prevention of Hepatitis A Virus (HAV) infection?
Personal hygiene: Emphasizing thorough handwashing, especially after using the toilet and before preparing or eating food, is crucial in interrupting the faecal-oral transmission route.
Pre- or post-exposure passive immunoprophylaxis with immune globulin: This involves administering antibodies (immune globulin) to provide immediate, short-term protection against HAV.
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How effective is immune globulin (passive immunoprophylaxis) in preventing Hepatitis A Virus (HAV) infection, and what is the optimal timing for administration?
Immune globulin is >85% effective in preventing HAV when given prior to or within 2 weeks of exposure to the virus. Administration 2-4 weeks after exposure may still result in no or asymptomatic infection, suggesting some benefit even later in the incubation period.
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What type of vaccine is used to prevent Hepatitis A Virus (HAV) infection, and how effective is it in inducing an immune response?
The preferred vaccine for HAV prevention is an inactivated whole virus vaccine. This vaccine is highly effective, inducing protective antibodies in >95% of vaccinees within 2-4 weeks after the first dose. A second (booster) dose extends the duration of protection, providing long-term immunity.
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What are the mechanisms by which Hepatitis A Virus (HAV) vaccination prevents infection and transmission?
Preventing liver replication: The induced antibodies neutralize the virus, preventing it from effectively replicating in the liver.
Preventing faecal shedding: By inhibiting viral replication in the liver, the vaccine also prevents the virus from being excreted in the faeces, thus breaking the chain of transmission.
Consequently, vaccination should prevent transmission of the virus within communities.
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When can the Hepatitis A Virus (HAV) vaccine be administered in relation to potential exposure?
The HAV vaccine can be given pre-exposure to provide long-term protection for individuals at risk. It can also be administered post-exposure (within 2 weeks) to potentially prevent or lessen the severity of infection after known exposure to the virus.
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