Herpes Flashcards

Question

Describe neonatal herpes

Answer 1

-Rare - 1.65 per 100,000 live births in the UK -Without therapy, carries high mortality (60%) and significant morbidity -HSV (often HSV-2) acquired by passage through an infected genital tract -Transmission rate =50% if mother suffers primary HSV at time of delivery =5% if mother suffers recurrence at time of delivery -Three clinical forms =Skin, eye and mucous membrane (SEM) =10-12 days post-partum =Vesicles on presenting part =75% will progress to disseminated disease -Disseminated disease =During first few days of life =Pneumonitis and hepatitis with/without – Aseptic meningitis – Encephalitis -Encephalitis (with/without dissemination) =In first 2-3 weeks of life =Severe neurological morbidity or death -Recurrence =Can occur, especially at skin sites, in the first year of life

Answer 2

-Aciclovir (ACV) =Available for topical, oral and intravenous (iv) use =Topical ACV is suitable for mild epithelial lesions =Any lesions that are not simply mild and superficial ones =HSV-associated disease in the immunocompromised host =CNS and systemic infection (iv therapy is required) =Any of the serious manifestations of HSV disease -Dosage depends on site of infection (see BNF) -Therapy must be maintained until clinical response is achieved -Serious systemic disease necessitates iv therapy for 2-3 weeks (sometimes followed by suppressive oral treatment) -Valaciclovir (oral pro-drug of ACV) produces significantly higher plasma levels after oral dosing than ACV -Famciclovir (oral pro-drug of penciclovir) is another ACV derivative -Valaciclovir and famciclovir can be administered less frequently than aciclovir ! Resistance can develop: f resistance emerges, foscarnet can be used

Answer 3

-Partly seasonal: respiratory spread in winter and early spring -Highly infectious -Past history is a good indicator of immunity -Approx 90% of adults have been infected with VZV (lower % in sub-tropical countries for unknown reasons)

Answer 4

1. Primary infection: varicella (or chickenpox) is a generalized eruption 2. Reactivated infection: zoster (or shingles) is localized to one (or a few) dermatomes

Answer 5

Smallpox: =Fever 2 to 4 days before rash =Rash: pocks in same stage =Slow development =More pocks on arms and legs =Usually present on palms and soles =1 in 10 die Chickenpox: =Fever at all time of rash =Pocks in several stages =Rapid development =More pocks on body =Usually absent on palms and soles =Ver uncommon death

Answer 6

-Virus enters through upper respiratory tract or conjunctivae; may multiply in local lymphoid tissue for a few days before entering blood and disseminating throughout body -After replication in reticuloendothelial sites, a second viraemic stage precedes the appearance of the skin and mucosal lesions -The vesicles lie in the middle of the epidermis and contain infectious virus; they dry up and scabs form that desquamate -Lesions in all stages are present at any one time

Answer 7

-Latent virus is found in neurones and satellite cells in sensory ganglia -Reactivation of VZV as zoster can occur at any age but is most often seen in individuals >60 years of age - Shorter latent period is seen in immunocompromised patients and those who acquired VZV in utero or in the first year of life -Stimulus to reactivation is largely unknown (sometimes it is trauma) -Zoster is usually limited to one dermatome; in adults, this is usually the thoracic or upper lumbar regions, or in the area supplied by the ophthalmic division of the trigeminal nerve -Viraemia may occur but is unusual in the immunocompetent host

Answer 8

-Incubation period of 10-21 days (ave 14 days) -Individual is infectious from up to 1-2 days before, and for some days after, onset – while new vesicles are appearing and until all vesicles have crusted over -Rash

Answer 9

-Centripetal -Most dense on the head and trunk -Generally not on palms of hands or soles of feet -Macular through papular to vesicular -Main differential diagnosis used to be smallpox but is now either HSV or, rarely, monkeypox (for example, from exotic African pets such as the Gambian rat)

Answer 10

-Secondary bacterial infection (resulting in scarring) -Thrombocytopenic purpura (may lead to fatal haemorrhagic chickenpox) -Arthritis, myocarditis, hepatitis, glomerulonephritis, appendicitis -The most frequent problems relate to the lungs and CNS

Answer 11

- VZV pneumonitis is a serious (even fatal) complication =1:200 in otherwise healthy adults =1:200,000 in otherwise healthy children -More likely in =Adults =Smokers =Pregnant women =Immunocompromised host -Cough, dyspnoea, tachypnoea and chest pains begin a few days after the vesicular rash -Nodular infiltrates are seen on CXR -Prompt antiviral therapy is required

Answer 12

-Common complications include =Cerebellar ataxia syndrome =Aseptic meningitis -Acute encephalitis is rare but more serious -Differential diagnosis include the immunologically-mediated =Post-infectious encephalopathy =Transverse myelitis =Guillain-Barrė syndrome

Answer 13

-Congenital varicella syndrome (CVS): a rare consequence (1% in first trimester) of fetal infection in first half of pregnancy =Scarring of skin =Damage to musculoskeletal system: Muscular atrophy, limb hypoplasia, rudimentary/missing digits =CNS damage: Cortical atrophy, psychomotor retardation =Damage of eyes: Chorioretinitis, cataracts -Neonatal varicella: varicella in first 4 weeks of life (usually from maternal varicella in late pregnancy) =Serious (even fatal) disseminated VZV disease: Pneumonitis, Encephalitis =Greatest risk if maternal varicella occurs within 6 days of, or up to 2 days after, delivery (no maternal IgG transferred to baby) =Silent infection may only manifest as zoster in first year of life

Answer 14

-Reactivation of VZV =Localised eruption, usually confined to one dermatome =Prodrome (pain and paraesthesia) in the area supplied by the affected sensory nerve =Evolution of rash is similar to varicella except for confinement to dermatome =Occasionally, there are no skin lesions: zoster sine herpete -Occurs with increased incidence in =Old age =Immunocompromised individuals -Disseminated zoster resembles varicella and may involve internal organs =Pneumonitis =Meningitis =Encephalitis =Myelitis =Internal organ zoster may not be accompanied by a typical skin rash

Answer 15

-Involvement of the ophthalmic division of the trigeminal nerve -Occurs in up to 25% of zoster episodes with ocular complications in >50% of the patients -Complications include =Corneal ulceration =Stromal keratitis =Anterior uveitis =Scarring =Acute retinal necrosis =Granulomatous cerebral angiitis =Ramsay-Hunt syndrome (facial palsy with aural zoster vesicles)

Answer 16

-The most common complication of zoster -Intractable pain persisting for 1 month or more after the skin rash -Constant pain at site or paraesthesia may continue for 1 year or longer -Exhausting and disabling

Answer 17

-Aciclovir (ACV) =VZV is less sensitive to ACV than HSV; needs frequent iv high dosage =Oral ACV accelerates healing and reduces new lesion formation during zoster in the immunocompetent patient; may lower rate of PHN =Oral ACV should be considered for all adult cases of varicella -Valaciclovir or famciclovir require less frequent dosing -The following groups should receive oral or iv aciclovir therapy =neonates (within first 4 weeks of life) =immunocompromised patients =ophthalmic zoster =healthy individuals with varicella and a complicating factor -A live-attenuated varicella vaccine is available -The vaccine strain (Oka strain) can be distinguished from wild-type VZV -Immunisation does not prevent latency, but incidence of zoster is not increased whereas incidence of varicella is significantly reduced -Primary course consists of two vaccine doses administered intramuscularly 4-8 weeks apart; a booster dose may be required (not current guidance) - In UK, the vaccine is not offered as part of the childhood immunisation programme but to 70/78yos as well as susceptible individuals who are in regular contact with those at risk of developing serious VZV illness =Non-immune healthcare workers =Healthy contacts of immunocompromised patients

Answer 18

-Is most often acquired in childhood when it is generally asymptomatic -Gives rise to infectious mononucleosis (IM; also known as glandular fever) in up to a quarter of individuals when infection is delayed into adolescence -Rare but serious complications of IM include airway obstruction, splenic rupture and neurological complications (including aseptic meningitis, encephalitis and the Guillain–Barré syndrome)

Answer 19

-Link between EBV and a variety of epithelial/lymphoid tumours is clear =EBV is an oncovirus; in particular, it can drive uncontrolled (tumoriforming) B cell proliferation -There is no antiviral drug treatment -There is no EBV vaccine in routine use, yet -Approx 90% of adults have acquired the virus which is transmitted in saliva (and perhaps in genital secretions) -Latency is established in resting memory B lymphocytes

Answer 20

-Primary infection is usually mild and unrecognised in childhood -Infectious mononucleosis (IM) is seen when primary infection is delayed to young adulthood - Incubation period is 30-50 days -IM consists of a triad of sore throat (often severe pharyngitis/ tonsillitis), cervical lymphadenopathy (becomes generalised often with splenomegaly) and intermittent fever -Often accompanied by malaise, headache, sweating (particularly at night), gastrointestinal discomfort, fatigue, and poor concentration -Atypical mononucleosis is seen in blood and biochemical hepatitis may also be observed -A faint maculopapular rash may become apparent (for example, following amoxicillin)

Answer 21

-Approx 60% of individuals at 40 years of age have acquired CMV, and most by 60 years of age -Incubation period is 4-6 weeks -Mononuclear cells carry the latent CMV genome, and bone marrow progenitor cells may be the prime site of latency -CMV replicates in vivo in epithelial cells in – salivary glands – the kidney – the respiratory tract – other epithelial (or endothelial) sites -Aciclovir is not effective against CMV; alternative agents are ganciclovir, foscarnet and cidofovir (all have serious side effects that limit their use) -No CMV vaccine is licensed for routine use yet