Herpes and therapy

Question 1

What are the 5 notable herpes viruses?

Answer 1

Herpes simplex type 1, herpes simplex type II, Epstein barr virus, Varicella-zoster virus & Kaposi’s sarcoma herpes virus

Question 2

What happens during primary infections of HSV I and II?

Answer 2

initial infection may be asymptomatic, may be minor local vesicular lesions, during primary infection virus enters peripheral sensory nerves and moves along axons to sensory nerve ganglia CNS

Question 3

How does the reactivation of latent virus case disease?

Answer 3

virus travels back down sensory nerves to surface of body and replicates, causing tissue damage

Question 4

Describe the clinical manifestation and treatment of HSV 1 infections

Answer 4

cold sores, acyclovir or similar antiviral used

Question 5

What is EBV?

Answer 5

Epstein barr virus, a virus shed in saliva which is also its route of transmission. Causes glandular fever. Can persist in symptomatic state and has T cells controlling it

Question 6

Describe the clinical manifestation of glandular fever

Answer 6

fever, sore throat, fatigue, swollen glands

Question 7

What is the Varicella Zoster virus?

Answer 7

Varicella is chicken pox, highly contagious, infection occurs via respiratory tract or conjunctiva, produces vesicles filled with high titres of infectious virus, after primary infection virus persists in sensory ganglia of CNS. Zoster is shingles, reactivation takes place after many years leading to infection and tissue damage in skin areas served by infected ganglia, where the cranial nerves (eye) involved can cause blindness. Both treated with acyclovir or related antiviral

Question 8

What happens within 1-2 days of varicella infection and after days 3 or 4?

Answer 8

1-2 days fever and malaise, vesicles start to appear. After 3-4 days vesicles dry with granular scab

Question 9

When is the infectious period for varicella?

Answer 9

1-2 days before the rash appears until the vesicles dry up is the infectious period. Various plentiful in nasopharynx and vesicles before they dry up.

Question 10

What is the risk to a foetus and neonate from maternal chicken pox at different stages of pregnancy?

Answer 10

first 20 weeks – congenital varicella syndrome, limb hypoplasia, microcephaly, cataracts, growth retardation. Second/third trimester – herpes zoster in infancy, sometimes fetal damage causing chorioretinal damage, microcephaly. Week before, to a week after delivery – severe, even fatal disease in neonate

Question 11

Describe the Varicella vaccine and who is currently offered it

Answer 11

lyophilised preparations containing live, attenuated virus from Oka strain of varicella zoster virus, don’t contain thiomersal, 2 doses currently offered on NHS to people in close contact with someone vulnerable and also HCW who haven’t previously had it including hospital cleaners, catering staff, ambulance staff, receptionists

Question 12

What causes shingles and what happens after primary infection?

Answer 12

caused by reactivation of latent varicella zoster infection, usually decades after primary infection. After primary infection, virus enters sensory nerves and travels along nerve to sensory dorsal root ganglia and establishes permanent latent infection

Question 13

What is the clinical manifestation of Shingles?

Answer 13

First signs begin with abnormal skin sensations and pain in affected area, headache, photophobia, malaise, within days/weeks a unilateral rash appears and in immunocompromised people a rash involving multiple dermatomes appear. Following rash, persistent pain at site known as post herpetic neuralgia can develop

Question 14

Describe the shingles vaccine

Answer 14

contains live, attenuated virus from Oka/ Merck strain, much higher dose than Varicella vaccine

Question 15

What drugs are used in treatment of herpes viruses?

Answer 15

idoxuridine, acyclovir, famciclovir, valaciclovir

Question 16

How do these antivirals work?

Answer 16

They target nucleic acid synthesis

Question 17

What is Idoxuridine used for?

Answer 17

herpes simplex, used topically for herpes eye infections and cold sores

Question 18

Describe Acyclovir MoA and its uses

Answer 18

purine analogue, active form is selective inhibitor of herpes simplex viral DNA polymerase, it’s incorporated into growing DNA strand causing premature termination, healthy cells don’t activate drug, used for HSV 1 and 2 as well as varicella zoster virus, used topically or injected

Question 19

What is Ganciclovir used for?

Answer 19

to treat cytomegalovirus, more toxic than acyclovir

Question 20

How do Penciclovir and Famciclovir work?

Answer 20

penciclovir is a bioisostere of ganciclovir with similar activity to acyclovir. Famciclovir is a pro drug of penciclovir, an ester but also reduced. Needs to be oxidised and the esters hydrolysed

Question 21

What is Valaciclovir used for?

Answer 21

Valine ester of acyclovir, a pro drug, used to treat infections of skin and mucous membranes including genital herpes

Question 22

Why is the monophosphate bioisostere phosphonomethylene prepared?

Answer 22

for viruses that lack thymidine kinase and are therefore resistant to acyclovir, so thymidine kinase reaction must be part of drug eg. Cidofovir