By

Aminu Arzet

Department of Internal Medicine,

Nelson Mandela School of Medicine,

University of Kwazulu Natal

Durban.

CONTENTS

INTRODUCTIONEPEDEMIOLOGYTRANSMISIONPATHOGENESISCLINICAL MANIFESTATIONDIAGNOSISTREATMENTPROGNOSISCONTROL AND PREVENTION

28th October,2014

Introduction Herpes simplex encephalitis(HSE) is a rare, but severe viral infection of the human CNS, which has high mortality if untreated or if treatment delayed.

HSV Account for about 10 % of all cases of encephalitis.

70-85 % of cases of HSE are caused by herpes simples virus-1 .

Introduction Continuation

Herpes simples Virus-2 account for About 10-15 % of the cases of HSE.

The disease is characterized by the rapid onset of fever, headache, vomiting, psychiatric symptoms , seizures, focal weakness, impaired consciousness , and death.

Epidemiology

Human is the natural host of the virus.

transmission is via direct contact between mucocutaneous surfaces.

All infected individuals harbor latent infection with recurrent infections, which may be asymptomatic, and are periodically contagious.

Epidemiology continuation

HSV-1 and HSV-2 are capable of causing infection at any part of the body, but HSV-1 causes more oral infections,HSV-2 causes more genital infections.

HSV-1 infection is commoner during childhood and adolescence.

HVS-1 mostly cause cold sores on the lips (herpes labialis),herpetic whitlow, eczema herpeticum, and herpes simplex keratitis (cornea of the eye ).

Herpes labialis Eczema herpeticum

Herpes keratitis Herpes whitlow

Epidemiology Continuation

HSV-1 overall prevalence is 55%

prevalence increase with age:- 44% in adolescents 12–19 yr- 90% >70 yr of age.

HSV-2 overall prevalence is 21.9%.

Prevalence of HSV-2 increases with:- age - illiteracy - gender(more in females)- poverty -multiple sexual partners- drug use

Epidemiology Continuation

HSV-2 mostly causes genital herpes.

Epidemiology Continuation

Both HVS 1 and 2 are seen in HSE.

pre-existing HSV-1 antibodies, decreases incidence of HSV-2 infections.

Transmission

Humans are the only natural reservoirs

Infection occurs by way of inoculation of the virus into mucosal surfaces.

HSV-1 is transmitted chiefly by contact with infected saliva.

HSV-2 is transmitted sexually or mother-child.

HSV is inactivated at room temp or by drying.

Pathogenesis

HSV is an enveloped, double-stranded DNA virus.

Viral infection begins at the point of entry:-oral cavity-genital mucosa -ocular conjunctiva-breaks in the skin.

Virus replicates locally, resulting in tissues damage and inflammatory response, which present as vesicles and ulcers.

Pathogenesis Continuation

It then enters nerve endings and spreads to sensory ganglia by intraneuronal transport.

Finally reach brain via trigeminal or olfactory nerve.

It continue to replicate, and multiply in the neuronal tissues, causing extensive damage.

It causes necrotizing infection, involving the frontal and/or temporal cortex and the limbic system.

Clinical Presentation

It present with nonspecific findings, including: fever, headache, vomiting, delirium, seizures, and alteration of consciousness.

Injury to the frontal or temporal cortex or limbic system may present with:anosmia, memory loss, expressive aphasia and

other changes in speech, hallucinations, and focal seizures.

Clinical Presentation continuation

It can present as meningitis(less common), and is the most common cause of recurrent aseptic meningitis (Mollaret meningitis).

Untreated infection progresses to coma and death in 75% of cases.

Diagnosis1. Polymerase chain reactions(PCR); DetectsHSV DNA. Highly sensitive and specific.

2. Immunofluorescent staining;Distinguishes between types of HSV virus.

3. Direct Fluorescent Antigen: Staining with fluorescent antibodies. May distinguish between HSV types.

4.Viral culture/ isolation(gold standard)

Diagnosis Continuation

5.HSV IgM tests are unreliable. A demonstration of a 4-fold or greater rise in HSV IgG titers between acute and convalescent serum samples is only useful in retrospect.

6.CSF analysis;-shows a moderate number of mononuclear cells and polymorphs-Mildly elevated protein concentration, -Normal or slightly decreased glucose concentration.-Often a moderate number of erythrocytes.

Diagnosis Continuation

MRI of the brain: Is the preferred imaging study.

CT scanning of the brain: Less sensitive than MRI.

EEG: Low specificity (32%) but 84% sensitivity to abnormal patterns in HSE

Differential Diagnosis Chancroid: STD caused by Haemophilus Ducreyi.

Hand-foot-and-mouth Dx: transmitted feco -orally, mostly caused by Coxsackie virus A16

Herpes Zoster (Shingles)

Syphilis: STD caused by Treponema Pallidum

Candidiasis: Fungal infection.

Treatment

Mainstay of RX is prompt initiating of empiric Acyclovir therapy in pts with suspected HSE pending confirmation of the diagnosis, because Acyclovir, is relatively nontoxic and delay Rx has poor prognosis. 10mg/kg/dose 8hrly IVI over 1 hour for 2-3/52.

Valacyclovir, a pro-drug of Acyclovir can be used as well. 1g bd for 2/52.

Acyclovir is converted to acyclovir triphosphate, a potent HSV DNA polymerase inhibitor. It stopped viral replication

Treatment Continuation

Because of its high pH, IV acyclovir may cause phlebitis and local inflammation if extravasation occurs.

GI disturbances, headache, and rash are among common adverse reactions.

Its excreted by the kidney, as such doses should be modified in pts with renal impairment.

Treatment Continuation Nephrotoxicity is reduced by adequately hydrating the pt.

Acyclovir resistance is insignificant in immunocompetent pts(<1 %)/, but can be serious in immunocompromised pts(up to 6 %).

Acyclovir resistance is strongly related to degree of immunosuppression and duration of exposure to acyclovir.

Treatment ContinuationRelapse occur within 3 months of completing initial course of IV acyclovir, as such prolonged course of an oral valacyclovir for 3/12,has been suggested after initial treatment.

Oral acyclovir or Famciclovir can be used for long term suppressive therapy as well.

Treatment ContinuationSeizures control; Use of anti epileptic drugs.

Diuretics/steroid; To manage increased intracranial pressure and reduce neuronal inflammation.

Supportive therapy;-Airway, breathing, circulatory support-Nutritional and fluid support-Universal precautions-ICU admission if needed

PrognosisUntreated HSE is progressive and often fatal in 7-14 days.

Mortality is up to 70% in untreated pts, with severe neurologic deficits in most of the survivors.

Mortality in pts treated with acyclovir is about 19%, though recent trials report lower mortality: 6-11%

Prognosis Sequelae among survivors are significant and depend on the patients age and neurologic status at the time of diagnosis.

Patients who are comatose at diagnosis have a poor prognosis regardless of their age.

In noncomatose pts, prognosis is better among those younger than 30 years.

Prognosis Continuation Neurologic outcomes in survivors treated with acyclovir are as follows:-No deficits or mild deficits - 38%-Moderate deficits - 9%-Severe deficits - 53%

Anterograde memory lost is common, even with successful treatment.

Retrograde memory, executive function, and language ability may be impaired.

Prognosis Continuation A study by Utley et al showed that pts who had a shorter delay (< 5 d) between presentation and Rx had better cognitive outcomes.

Elbers and colleagues followed properly treated children for 12 years after the HSE. They found seizures in 44% of the children and developmental delay in 25% of the children.

They concluded that HSE has poor long term neurologic outcomes despite appropriate RX.

Prognosis Continuation Relapses have been reported to occur in 5-26% of patients, with most relapses occurring within the first 3 months after completion of RX.

It is unclear whether such relapses are due to recurrence of viral infection or an immune-mediated inflammatory process.

Recent studies suggest that immune-mediated events, rather than direct viral invasion, may predominate in relapses.

PreventionProper hand washing

Universal precautionary measure while attending to patients.

Safe sex; sticking to only one partner and use of condoms.

Patients education.

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References Continuation

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