5. Viral, Protozoal infections Flashcards
(21 cards)
Describe viral replication
- For entry viruses use their protein coat to bind to the cell surface proteins and transfer viral material to the cell
- once uncoated viral DNA enters nucleus of cell where replication of the viral DNA takes place. Enzymes such as DNA and RNA polymerases are involved in replication
- Once replicated, the viral material is then transcribed and transferred back into the cytoplasm where protein synthesis occurs from RNA template.
- Once synthesised these proteins including capsid proteins are then assembled in the nucleus. The viral particles are exocytosed and leave the cell to go and infect more cells.
What are the DNA viruses?
DNA viruses affect mostly ocular surfaces.
- Herpes simplex virus
- Varicella zoster
- Cytomegalovirus
- Adenovirus
What are the RNA viruses?
RNA viruses affect the area or skin around the eyes rather than the eye structures.
- Rubeola (measles)
- Rubella (German measles)
- Variola (small pox)
- SARS CoV 2 (COVID-19)
What are the symptoms of viral infections?
- Redness
- Itching, burning
- Watery eye
- Blisters on or near the eyelid
- Photophobia
- Blurred vision
Describe the mechanism of herpes simplex virus infection.
- Infection first occurs usually in childhood.
- The initial infection is asymptomatic or is very mild and resolves itself in days.
- The virus transports itself down nerve ending into cell body, travels through opthalmic branch of trigeminal nerve.
- Virus then lies dormant in the sensory ganglia
- Until a trigger activates virus replication. A trigger could be stress or reduced immunity.
- This activation then results in recurring infections due to repeated viral infections.
Why is there inflammation with viral infections?
This is because of the adverse effects of our immune system whilst it is trying to fight off the infection.
This is because viral proteins are similar to human protein so the immune system attacks both.
For example:
Virus coat has protein UL6 which is similar to proteins in the cornea. UL6 protein activate certain inflammatory cells such as CD4 and T cells which attact inflammatory mediators such as cytokines, causing inflammation cascade in the infected area.
Another example is the viral protein glycoprotein K which activates inflammatory cells such as CD8+ that is responsible for scarring we get with ocular infections.
Describe the mechanism of Herpes varicella zoster infections.
These infections are secondary to childhood chicken pox infection. After the initial infection during childhood, they lay dormant in different parts of the ophthalmic nerve. Once activated it can cause hyperesthesia and then vesiclular rash, and is contagious at this stage. Once the vesicles crust over then infection is less contagious. There are major risks of corneal scarring, uveitis ,cataract, glaucoma, macular oedema and necrosis (cell death) of the retina.
What happens in Cytomegalovirus infections?
Infection mostly observed in immuno compromised people such as those infected with HIV. This infection can lead to CMV retinitis. Progressive damage to retina leading to blindness and increased risk of retinal detachment.
What are the availability of anti-viral drugs and side effects?
Topical anti-viral drugs:
1. Ganciclovir
Side effects are rare.
Systemic anti-viral drugs:
1. Famciclovir
2. Penciclovir
Side effects: resolve after treatment
*fever
*rash
*diarrhoea
Describe the mechanism of action of Ganciclovir
These drugs have similar structure to DNA building blocks. They have an altered end so stop the DNA synthesis.
There will be selective toxicity because the initial phosphorylation of the drug is mediated by the enzyme viral thymidine kinase. Because thymidine kinase is viral, the phosphorylation and incorporation of the drug only happens in infected cells. So cells without infection won’t be affected by the drug.
What is the approach to treat viral infections?
- Topical and systemic anti virals are used every couple of hours for a week. If need be then can use topical anti virals up to 14 days.
- Rarely but if need be, topical steriods may be used at the same time to reduce inflammation.
What is RNA retrovirus and what are the treatment methods?
HIV-
Enzyme reverse transcriptase makes DNA copy of viral RNA.
This DNA then becomes integrated into host genome
This directs generation of new viral material
Treatment:
- Reverse transcriptase inhibitors -
Can use either
a) Nulceotide RTIs - analogues of endogenous nucleotides
b) Non nucleotide RTIs - Denature the catalytic site of RT. - Protease inhibitors -
Inhibit viral proteases which cleave precursor polyproteins. This disrupts structural and functional proteins of new virions.
Effective treatment requires combination of these treatments to prevent recurrence or tolerance.
What is acanthamoeba keratitis and why are contact lens wearers more prone?
They are free living, parasitic protozoa.
There are multiple acanthamoeba species. They are most common in south of UK as acanthamoeba feed on gram negative bacteria which proliferates better in hard water as it likes limescale.
More common in CL wearers because:
*Less oxygen reaching cornea
* Build up of bacteria on lens
*Could get corneal abrasions from CL wear
What are the symptoms of Acanthamoeba keratitis?
- Decreased VA
- Pain and redness
- Foreign body sensation
- Photophobia
- Ring infiltrate round cornea
- Ground glass epitheliopathy
Why is it difficult to treat acanthamoeba keratitis?
Can be in two forms:
1. Dormant form (Cyst)
2. Active form (Trophozoite)
The dormant form is hard to treat because it has an extra layer. It’s metabolically inactive enclosed within a hard shell. Therefore the cyst can come out at any time and cause recurrence which is why it takes so long to treat.
If Acanthamoeba is stressed it can switch between dormant and active form.
What is the treatment of Acanthamoeba keratitis?
Very intense treatment: Hourly administration for 2-3 days. Treatment for a minimum of 2 weeks, commonly lasts between 6-12 months.
Detergents used as treatment:
1. Chlorhexidine (0.02%)
2. Polyhexamethylene biguanide (PHMB 0.02%)
3. Propamidine isoetrionate (Brolene 0.1%)
4. Hexamidine (0.1%)
These detergents work by penetrating the cell membrane and disrupting the cell wall, causing leakage. This activates autolytic enzymes leading to cell death. These drugs can compromise the extra layer of the dormant form.
Anti-biotics used as treatment:
*Neomycin
The anti-biotics kill of the bacteria so Acanthamoeba can’t feed.
Warning:
Use of topical steroids can worsen condition
What is fungal keratitis?
Fungi are non motile eukaryotic cells. Many fungi are parasitic. Fungal keratitis can be caused fungi named:
*Fusarium
*Aspergillus
*Candida
They gain access through damaged epithelium. So there is increased chance of happeining if:
*Topical steroid overuse
*Immuno-compromised individuals
*Overuse of anti-biotics
*Soft contact lens users
What are the symptoms of fungal keratitis?
- Foreign body sensation
- Increasing eye pain
- Sudden blurry vision
- Redness
- Excessive tearing and discharge
- Photophobia
What are the clinical features of fungal keratitis?
- Fine or coarse granular infiltrate
- Rough corneal surface, may appear elevated
- Irregular feathery edged infiltrate
- White ring in the cornea, satellite lesions near edge of primary infection.
Describe the mechanism of action for anti-fungal drugs.
Anti-fungals target synthesis of ergesterol.
Enzyme Cytochrome P450 3A is responsible for ergosterol synthesis.
Ergesterol is an important protein found on cell membrane. It has fat molecules which gives flexibility to cell membrane. And ergesterol makes transmembrane ion channels.
By targeting ergesterol this disrupts the cell membrane causing leakage and cell death.
What are the available anti-fungal drugs and their side effects?
Polyenes:
1. Amphotericin B 0.15% eye drops
2. Nystatin oral
These bind to ergesterol and disrupt ion balance (mostly K+)
Side/adverse effects:
*No urine - Renal toxicity
*Nausea
*Diarrhoea
Azoles:
1. Voriconazole 1% eye drops
2. Fluconazole oral
These inhibit cytochrome P450 3A enzyme preventing formation of ergosterol. This alters fluidity of membrane, interferes with membrane bound enzyme activity and inhibits replication
Side/adverse effects:
*80% patients kidney impairment
Other anti-fungals:
1. Terbinafine oral
2. Flucytosine oral
