Biology and Pathophysiology
The Herpesviridae family includes viruses that infect animals and humans (Siakallis 2009). Among these viruses, eight members are known to infect humans and are clinically important (Siakallis 2009). These viruses are herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and herpesviruses 6, 7, and 8 (Siakallis 2009; Odom 2012; Wolz 2012). Members of this family of viruses may cause a variety of diseases, including genital and oral herpes (HSV-1 and HSV-2), chickenpox/shingles (varicella-zoster virus), mononucleosis (human cytomegalovirus), and roseola (human herpes virus 6) (Roizman 2001; Siakallis 2009; Odom 2012). The focus of this protocol is typical manifestations of HSV-1 and -2, as well as shingles (varicella zoster).
Infection with any member of the Herpesviridae family involves multiple steps. First, the virus interacts with receptors on the external surface of human cells to gain entry into the cell (Jennsen 2005; Schnitzler 2010). Once inside the human cell, the virus uses the cell to make many copies of itself (replicate) (Mell 2008; Kinchington 2012). This stage is known as the primary infection, and while it can be accompanied by a period of illness, patients may also be completely asymptomatic and remain unaware that they have been infected.
In addition to using the cell to replicate, Herpesviridae viruses make a certain class of gene products known as latency-associated transcripts (LATs), which remain in the body and can reactivate the viral replication process (Block 1997; Kent 2003; Mell 2008; Kinchington 2012).
Members of the Herpesviridae family typically traverse sensory nerves until they reach large nerve clusters called ganglia, where they replicate undetected by the host (Mell 2008; Kinchington 2012; Zwaagstra 1990, 1991; Imai 2009; Hill 1990).
The varicella-zoster virus, which causes chickenpox in children, also causes shingles (herpes zoster), a disease that generally occurs in adulthood as a result of the reactivation of the virus (Wallmann 2011; Chisholm 2011).
The primary infection – chickenpox – is a childhood infectious disease that almost always causes symptoms. During this time, patients are extremely contagious (Wallmann 2011). Even people who have mild disease may spread the infection to others (Kaneshiro 2011). Chickenpox causes a characteristic rash that usually occurs 10 to 21 days after coming into contact with someone who had the disease, and typically presents as 250 to 500 small, fluid-filled, itchy blisters over the body (Kaneshiro 2011). Usually chickenpox affects patients for 5 to 10 days (CDC 2011). Chickenpox is highly contagious and can be spread via direct contact or in the air if an infected person coughs or sneezes. A person with chickenpox is typically contagious 1 – 2 days before they develop blisters, and remain so until all their blisters crust over (A.D.A.M. 2011; CDC 2012). Childhood vaccination against varicella zoster (Varivax®) can help protect against chicken pox, and is recommended by the Centers for Disease Control and Prevention (CDC) for most children (CDC 2008).
Once the virus establishes a dormant or latent infection, patients are no longer contagious and do not experience symptoms. However, the virus may become reactivated later in life, leading to shingles (Mayo Clinic 2011; Wallmann 2011; Gharibo 2011).
The varicella zoster virus can be spread from a person with active shingles to a person who has never had chickenpox. In such cases, the person exposed to the virus could develop chickenpox (rather than shingles). The virus is spread through direct contact with fluid from the rash blisters.
A person with shingles can spread the virus when the rash is in the blister-phase. A person is not infectious before blisters appear. Once the rash has developed crusts, the person is no longer contagious. Shingles is less contagious than chickenpox and the risk of a person with shingles spreading the virus is low if the rash is covered (Wallmann 2011).
Although shingles may occur at almost any time, it is more common in the elderly and in those with weakened immune systems. This suggests that reactivation may be triggered by impaired immunity to the virus, which occurs with advancing age (Sampathkumar 2009; Harpaz 2008).
Herpes infections can be caused by an infection with HSV-1 or HSV-2 (UMM 2011; Mell 2008; Urban 2009). Manifestations of herpes include: oral herpes (herpes labialis), or “cold sores”, herpes simplex keratitis, which causes sores to appear on the corneas of the eyes, and genital herpes. Another, less common, manifestation is erythema multiforme, which causes bull’s-eye shaped lesions to appear on the skin and can also cause lesions in or around the mouth (Kamala 2011; Sokumbi 2012).
HSV-1 is the usual cause of oral herpes and herpes simplex keratitis, whereas HSV-2 is usually associated with genital herpes. However, HSV-1 can also cause genital herpes, but HSV-2 is associated with more severe outbreaks (Urban 2009; Ehrlic 2011a; Mell 2008; Chirshom 2011; Chentoufi 2012).
HSV-1 is usually spread by skin-to-skin contact with an adult that has been infected with the virus. Many people initially contract this virus as an infant or child (American Academy of Dermatology 2012). HSV-2, on the other hand, is usually spread via sexual contact (American Academy of Dermatology 2012). In either case, the virus gains access to the body through mucous membranes or breaks in the skin (Ehrlic 2011a).
Infection with either HSV-1 or HSV-2 can initially manifest as small fluid-filled blisters on the skin (Mell 2008; Urban 2009; Chrisholm 2011). Once the initial infection subsides, the virus spreads to the nerve cells where it stays dormant until it is reactivated (American Academy of Dermatology 2012).
Factors such as stress, fatigue, sun exposure, surgery, fever, and menstrual periods can trigger the reactivation of HSV viruses. The frequency of these recurrent outbreaks varies from person to person; some individuals never experience any outbreaks (and are termed “asymptomatic carriers”), while others may have monthly outbreaks (Centoufi 2012). It is not known why some individuals remain asymptomatic while others have outbreaks, but both asymptomatic and symptomatic patients are able to infect others (Centoufi 2012).