Herpes simplex virus belong to alpha- sub family of Herpesviridae.
- They are extremely widespread and exhibit a broad host range; can infect many types of cells and different animals. However, the human herpesviruses infect exclusively man.
- They replicate fast (12-18 hours cycle), spread fast and are cytolytic.
- Herpes simplex viruses (HSV) are of two distinct types: HSV-1 and HSV-2. They differ from each other in many aspects .
- They can cause a spectrum of diseases, involving skin, mucosa and various organs.
- They undergo latency in nerve cells; reactivate later causing recurrent lesions.
PATHOGENESIS:
Primary Infection
Transmission occurs through abraded skin or mucosa from any site, but more commonly by:
• HSV-1: Oropharyngeal contact with infected saliva or direct skin contact
• HSV-2: Sexual contact or rarely vertical mode (from mother to fetus).
Site of infection: HSV replicates at the local site of infection and produces lesions anywhere, but more commonly in:
• HSV-1 lesions are confined to areas above the waist (most common site-around mouth)
• HSV-2 produces lesions below the waist (most common site-genital area).
Spread via nerve: Virus then invades the local nerve endings and is transported by retrograde axonal flow to the dorsal root ganglia, where it replicates further, and then undergoes latency.
Primary HSV infections are usually mild; in fact, most -are asymptomatic.
However in immunocompromized hosts, viremia occurs that leads to widespread organ involvement and systemic manifestations.
Latent Infection
1-HSV has a tendency to undergo latency in neurons:
• HSV-1: undergoes latency in trigeminal ganglia
• HSV-2: undergoes latency in sacral ganglia.
–Nonreplicating state: HSV does not replicate in latent stage except for a small RNA, called micro-RNA ( encoded by a latency-associated viral gene) which maintains the latent infection and prevents cell death.
–The virus can not be isolated during latency.
Recurrent Infections-
Reactivation of the latent virus can occur following various provocative stimuli, such as fever, axonal injury, physicalor emotional stress, and exposure to ultraviolet light.
- Via the axonal spread, virus goes back to the peripheral site and further replicates in skin or mucosa producing secondary lesions
- Recurrent infections are less extensive and less severe because of presence of pre-existing host immunity that limits the local viral replication
- Recurrent infections are usually asymptomatic; but the virus continues to shed in the secretions.
Clinical Manifestations
Both HSV-1 and 2 have been isolated from nearly all mucocutaneous sites and viscera; however, in general, oral-facial infections are common with HSY-1, whereas HSY-2 frequently causes genital infections and intrauterine . The incubation period ranges from 1 to 26 days (median, 6-8 days).
Oral-facial Mucosal Lesions
- Oral-facial mucosal lesions are the most common manifestation of HSV infections.
- Most common affected site is buccal mucosa
- Most frequent primary lesions are gingivostomatitis and pharyngitis Most frequent recurrent lesion is herpes labialis (painful vesicles near lips)
- Other lesions produced are- ulcerative stomatitis and tonsillitis
- Many cases are asymptomatic but can predispose to secondary bacterial infection.
Nervous System
HSV causes various neurological manifestations.
1.Encephalitis: HSV is the most common cause (10-20%) of acute sporadic viral encephalitis, most frequently involving temporal lobe. HSV-1 is more common (95%) than HSV-2
Children get primary infection: HSV is acquired exogenously and invades CNS via the olfactory bulb
Adults get recurrent infections due to reactivation of HSV in trigeminal nerve.
2.Meningitis: HSV can cause recurrent lymphocytic meningitis called Mollaret’s meningitis
3.Other neurological manifestations:
• Autonomous system involvement (sacral region)
• Transverse myelitis
• Guillain-Barre syndrome
• Peripheral nervous system involvement
• Cranial nerve involvement (e.g. facial nerve in Bell’s palsy).
Cutaneous Lesions
HSV usually infects through abraded skin and causes various cutaneous lesions.
Herpetic whitlow: Lesions present on the fingers of dentists and hospital personnel
Febrile blisters (herpes febrilis ): Fever due to any other cause can provocate HSV to cause recurrent blisters Herpes gladiatorum: Mucocutaneous lesions present on the body of wrestlers
Skin lesions are often severe on underlying eczema or burns which permit extensive local viral replication and spread
Eczema herpeticum: Caused by HSV-1 in patients with chronic eczema. Similar lesions are also produced by vaccinia virus or coxsackievirus Al6 infection; these conditions together are designated as Kaposi’s varicelliform eruptions
Erythema multiforme: HSV is commonly associated with this condition. Herpes antigens have been detected in the immune complexes found in serum or skin biopsies.
Ocular Lesions
HSV-1 is more common than HSV-2 to infect eyes.
- Severe conjunctivitis is the most common manifestation
- Recurrent lesions develop into dendritic ulcers of cornea or vesicles on the eyelids
- Acute keratoconjunctivitis
- Follicular keratoconjunctivitis with vesicles on eyelid
- Corneal blindness: Involvement of corneal stroma may cause opacity and blindness. HSV-1 infections are the second common cause of corneal blindness (next to trauma).
Genital Lesions
HSV-2 is more common than HSV-1 to cause primary as well as recurrent genital lesions.
Genital lesions are described as bilateral, painful, multiple, tiny vesicular ulcers
This may be associated with fever and inguinal lymphadenopathy.
Visceral and Disseminated Herpes
HSV viremia results in disseminated infection; involving multiple organs.
Risk factors: Immunocompromized patients, underlying malnutrition or AIDS, pregnant women and transplant recipients are at a higher risk of disseminated infection Common manifestations include: Pneumonitis, tracheobronchitis and hepatitis.
Neonatal Herpeshttp://Medihealthserve
HSV is one of the common causes of congenital infections, along with the other TORCH agents . Transmission: Newborns acquire HSV infection most commonly during birth from the maternal genital tract. However, transmission can also occur in utero or after birth Risk of developing neonatal herpes is maximum (10 times more) if the mother recently acquires the virus (primary infection) than those who present with recurrent infection HSV-2 is more common to cause neonatal herpes (50-70% of total cases) than HSV-1
Clinical features: Babies are almost always symptomatic and present in one of the two forms:
• Local lesions involving skin, eye and mouth are the most frequent manifestations
• Systemic: Among all HSV-infected people, neonates are at highest risk of visceral and/ or CNS (encephalitis) infection.
Mortality: Neonatal herpes is associated with high mortality (65% without treatment).
Treatment: Neonates with presumed herpes should be treated with antiviral drug acyclovir for 6- 12 months.
REFERENCES-
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