COD infectious diseases Flashcards
Describe AIDS
Acquired Immune Deficiency Syndrome WHO 2014: HIV prevalence among adults 15–49 years old • 38 million people infected • 33 million deaths since 1980s Incidence: • 2.6 per 1000 population 4th greatest cause of global deaths
What viruses is AIDS caused by?
2 viruses
HIV-1 = common
HIV-2 = less common (African)
What was the general clinical epidemiology of AIDS?
First 2000 cases (US) Homosexual men = 72% IV drug abusers = 17% Haitians = 5% Haemophiliacs = 1%
What sort of virus is HIV?
A retrovirus
Lentivirus
9kb RNA genomes
Converted to DNA upon infection
Integrated into host cell genome so it is a permanent infection
New viral RNA produced by host RNA polymerase
Lipid viral envelope also derives from host cell
What is the consequence of the HIV replication cycle?
T4 lymphocytes =
Helper cells =
Underpin normal immune function
B lymphocytes are stimulated to produce antibodies
Macrophages are activated to enter infected or damaged tissues
Other T cells are stimulated eg Cytotoxic killer cells
Assist in the elimination of cancer cells
Active HIV replication = depletion of T4 cell count
What are some Clinical signs & AIDS indicator diseases?
- Multiple and recurrent bacterial infections
- Mycobacterial infections
- Pneumocystis pneumonia
- Lymphoma
- Wasting, night sweats
How is HIV diagnosed?
ELISA
Detects circulating anti-HIV antibodies
• Positive 4 - 8 weeks after initial infection
What are some HIV drug treatments?
Antiretroviral protease inhibitors:
• HIV protease is essential
• Required for long protein processing
• Saquinavir
Entry inhibitors
• Bind CCR5 chemokine receptor
• Block HIV entry
• Maraviroc
Fusion inhibitors
• block HIV fusing with T4 cell membrane
• Enfuvirtide
Integrase inhibitors
• Inhibits the HIV integrase action
• Integration of viral DNA blocked
• Raltegravir
What is Antiretroviral Therapy (ART)?
ART prevents resistance (multiple drugs/cycled)
• Also most potent means of killing virus
Keep circulating virus low
• Less progression to AIDS
• Combinations of drugs are used
Describe HIV-1 RNA quantitation
• viral load assays • number of RNA genomes • correlates to number of viral particles in blood • statistical correlation: < 4530 copies of viral RNA/ml • clinically stable • slow progression to AIDS > 36, 720 copies of viral RNA/ml • rapid disease progression • early AIDS onset
Describe HIV-1 Therapy
Hit high viral load with sustained drug therapy
• Combined ART drugs
• Keep viral copies low (50 or less per ml serum)
What are viral load assays?
Quantitate HIV-1 RNA in blood plasma
• A surrogate marker for HIV treatment = viral burden/titre
• HIV RNA genomes equivalent to virus particle per mL blood
• Nucleic acid-based tests (NATs)
What is the best tool for HIV Molecular Epidemiology?
- HIV full length genome sequence
* Use phylogenetic clustering
What is the origin of HIV?
Related to Simian Immunodeficiency Virus (SIV) • Are chimpanzees the source? Multiple simian lentiviruses • HIV moved into humans Bush meat trade • Infected blood
While there is no cure for HIV infection, its preventable by:?
Interrupting transmission: surveillance, testing & counselling
• Interventions: Condom use & male circumcision
• Pre- & Post-exposure prophylaxis
• Blood donor screening
• Stop mother to child transmission
Describe coronavirus
Positive-single-strand RNA viruses
S: Spike → homotrimeric class I fusion glycoproteins
Two function: (i) Bind cell surface receptors and (ii)
induce fusion of viral and cellular membranes
• E: Envelope
virus morphogenesis, assembly and bud-ding
• M: Membrane glycoprotein
• N: Nucleocapsid
binds the RNA genome in a beads-on-a-string fashion
What is the life cycle of coronavirus?
Entry:
• Bind ACE2
• Need protease: TMPRSS,
cathepsin B and L
Viral gene expression: • Translation of ORF1a and ORF1b → polyproteins pp1a (nsp1–11) and pp1ab (nsp1–10) • Cleavage by two cysteine proteases nsp3 and nsp5
SARS-CoV-2 can cause gastrointestinal
symptoms such as what?
vomiting, diarrhea, or abdominal pain during the early phases of the disease
What is a variant?
A virus with one or more new mutations is referred to as a “variant” of the original virus
A variant become a new strain when it acquired distinct properties and has a particular immune
response
Describe some treatments used for covid-19
Dexamethasone (corticosteroid): reduced death by one third
• Remdesivir (adenosine analogue which terminates viral replication ): may reduce the recovery time.
• Convalescent plasma serum
Describe Convalescent plasma serum
Buying time for the patient: • Antibodies (IgG and IgM) are administered to protect or treat another person • Short-term strategy: antibodies have a short life
Describe some treatments used for covid-19 that did not work
Hydroxychloroquine (treatment of rheumatic diseases): no clinical benefit
• Chloroquine: no conclusive clinical trial has proved efficacy of the drug
Describe the 3 main problems with in vitro transcribed mRNA
1- mRNA instability
2- high innate immunogenicity
3- inefficient in vivo delivery
Describe the 3 main advantages with in vitro transcribed mRNA compared with attenuate vaccine
1- mRNA are non-infectious → no potential risk of infection or insertional mutagenesis.
2- mRNA are degraded as a normal process, and this degradation can be regulated → increased safety
3- Formulating mRNA into carrier molecules: anti-vector immunity is avoided, and mRNA vaccines can be administered repeatedly.
4- Production: extremely fast.
Describe the Pfizer vaccine
Lipid nanoparticle-formulated nucleoside-modified mRNA:
encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein
• T4 fibritin-derived foldon trimerization domain: increase immunogenicity
• Cap analogue, 5’-UTR, 3’UTR and poly(A) tail: increase mRNA stability
What is a live attenuated vaccine?
An attenuated vaccine consists of live, whole bacterial cells or
viral particles that are treated in such a way that they have reduced virulence
within the host but retain their ability to provoke an immune response
eg polio vaccine
What is an Adenovirus based
vaccine?
Human Adenovirus: high prevalence in human population
→ impaired B and T cells response again the transgene product.
• Chimpanzee Adenovirus: low prevalence in human population
(Europe and US but not Africa!). No cross neutralisation with
the human adenovirus. Induce T- and B-cell immune responses
• Oxford/AstraZeneca: AZD1222
Chimpanzee adenovirus vectored vaccine expressing the SARSCoV-2 spike protein
What is Salmonella?
An acute diarrhoeal infection caused by
ingestion of food contaminated with the bacterium
belonging to the genus Salmonella
What are the clinical symptoms of salmonella?
- Incubation (time between ingestion and first symptoms): 12 hours to 36 hours
- Target:
Children and adults - Stomach cramps
- Watery diarrhoea
- Fever
- Sometime vomiting
What are serotypes?
Serotypes are groups within a single species of microorganisms, such as bacteria or viruses, which share distinctive surface structures.
Describe salmonella enterica
eg gram….neg or pos
what does it grow on
Gram negative • Xylose-lysine-deoxycholate agar (XLD) agar and Brilliant Green agar (BGA) • Motile • Facultative Anaerobe
Describe Xylose-lysine-deoxycholate agar (XLD)
Salmonella and E.coli ferment xylose (acidification): media become yellow BUT after xylose been consumed,
Salmonella decarboxylate lysine (alkalization): media
turn red
Salmonella metabolise thiosulfate: production of
hydrogen sulfide (black colony)
What is a facultative anaerobe?
an organism which can survive in the presence of oxygen, can use oxygen in aerobic respiration, but can also survive without oxygen via fermentation or anaerobic respiration
How do you prevent salmonella?
- Keep clean
- Separate raw and cooked
- Cook thoroughly
- Keep food at safe temperature
- Use safe water and raw materials
How do you control the salmonella infection?
Rehydration: Drink plenty of fluids Manage fever: Paracetamol Antibiotics: No except if bacteria reach the blood streams or compromised immune system Loperamide: No as it prolongs the diarrhoea
What is Cholera?
an acute diarrhoeal infection caused by ingestion
of food or water contaminated with the bacterium Vibrio
cholerae
Infectious dose:
• if ingested with water: 103 -106 organisms
• If ingested with food: 102 -104 organisms
What are the clinical symptoms of cholera?
Clinical symptoms: 1. Incubation (time between ingestion and first symptoms): 12 hours to 5 days 2. Target: Children and adults 3. Acute watery diarrhoea: Up to 1L/h Rice-water stools 4. Vomiting 5. Leg cramps
Describe vibrio cholerae
eg gram neg/pos
Gram negative • Motile • Oxidase positive • Growth on Thiosulfate-citratebile salts-sucrose agar (TCBS) • Growth in media with high salt (6% NaCl)
What is The reservoir of an infectious agent?
the habitat in which the agent normally lives, grows, and multiplies.
Reservoirs include humans, animals, and the
environment. The reservoir may or may not be the
source from which an agent is transferred to a host
What are Toxin-Coregulated Pili (TCP)?
Type IV pili that self-aggregate, bringing the bacteria together in microcolonies that protect them from host defenses and concentrate their secreted cholera toxin
What is type IV pili?
And what are the 2 types?
Filamentous structure found in numerous bacteria
type IVa pili: widespread, involved in cell motility, DNA transfer,
host predation and electron transfer
• type IVb pili: less prevalent and mainly found in enteropathogenic
bacteria. Involved in host colonisation
How do you prevent cholera?
Access to safe drinking-water;
• Use of improved sanitation;
• Exclusive breastfeeding for the first six months
of life;
• Good personal and food hygiene;
• Health education about how infections spread
Vaccinations
How do you control cholera?
Rehydration:
Oral rehydration salts (ORS) solution (clean water, salt and sugar).
Intravenous fluids in case of severe dehydration or shock.
• Antibiotics:
Reduce the duration of a diarrhoea episode by 25% and are
associated with a 30% reduction in stool volume. Azithromycin
and ciprofloxacin are commonly used.
• Loperamide
It can help with short-term diarrhoea or irritable bowel syndrome
