Varicella Zoster Virus Pathophysiological Impact and Vaccine
Purdue Global University
Varicella-zoster-virus (VZV) or more commonly, the Chicken Pox, is a highly contagious virus that is spread from person to person by direct contact or through the air by sneezing or coughing (CDC, 2016). The term chickenpox is said to come from the French word “chiche–pois” for chick-pea which described the size of the vesicle to help distinguish the disease from smallpox (Rockley & Trying, 1994). This virus causes a blister-like rash, itching, fever and tiredness. Chickenpox can be a very serious disease, especially in elderly, babies and individuals with weakened immune systems. VZV can cause potentially fatal superinfections from scratching at the blisters and introducing streptococcal or staphylococcal bacterium (Gershon & Gershon, 2016).
Most cases of chickenpox are mild and will last 5-10 days but deaths can occur. In 1995 the varicella vaccine became available and was added to the vaccination schedule. (Immunization Action Coalition, 2013). Although the vaccine reduced the death rate by 90% there was still some resistance. Parents preferred to purposely seek out other infected children to infect their child. The idea was to build an immunity from something “natural” (the disease) as opposed to something “artificial” (the vaccine) (Immunization Action Coalition, 2013). Currently, the vaccine is recommended by the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) and tens of millions of vaccines have been given since being licensed (Immunization Action Coalition, 2013).
Chickenpox is described as: “an acute contagious disease especially of children marked by low-grade fever and formation of vesicles and caused by a herpesvirus” (Merriam-Webster, 2018). The blisters typically first appear on the stomach, back and face and can spread over the entire body (CDC, 2016). At its peak, there can be 250 to 500 itchy blisters (CDC, 2016). Prior to the vaccine 100 people died every year from the chickenpox (Immunization Action Coalition, 2013). In the early 1990’s an average of 4 million people was infected with VZV (CDC, 2016). Since the vaccine more that 3.5 million cases have been prevented (CDC, 2016).
The transmission of the Varicella-zoster-virus (VZV) comes from a host cell invading a healthy cell. This is thought to happen through the upper respiratory tract (Gershon & Gershon, 2016). Once the infected virion is inhaled it then proliferates within local lymphoid tissues (Gershon & Gershon, 2016). In the lymphoid tissues the VZV infects the T lymphocytes and programs them to target the skin at which point the infection is shifted to the epidermis (Gershon & Gershon, 2016).
Homeostasis is defined as the “tendency of an organism or cell to regulate its internal conditions, usually by a system of feedback controls, so as to stabilize health and functioning, regardless of the outside changing conditions (Biology Online, n.d.).” A great example of how the body maintains homeostasis is a healthy blood pressure. The heart is able to sense changes in the blood pressure, it then sends signals to the brain, which then sends back signals to the heart telling it how to respond. If the blood pressure is too low the heart will speed up and vice-versa if the blood pressure is too high the heart will slow down.
Homeostasis: Body System-Healthy State
The main systems affected by the VZV is the lymphatic and integumentary systems via the respiratory system. These systems in a healthy state work together to remove pathogens from the body, protect organs and circulate oxygen through the blood.
The lymphatic system is an organized network that is made up of interrelated tissues such as lymph nodes whose main components are macrophages, lymphocytes and migrating dendritic cells (Olszewski, 2004). In a healthy body the lymphatic system maintains fluid balance, fights pathogens, filters blood and much more (Encyclopedia Britannica, 2017). Fluid balance is achieved through the absorption of excess fluid and particulate matter from tissues. It is then deposited into the bloodstream preventing a fluid imbalance which would result in organism death (Encyclopedia Britannica, 2017). The lymphatic system helps to protect the body by producing white blood cells called lymphocytes. Lymphocytes help fight disease-causing microorganisms with two different types of lymphocytes: T cells and B cells (Encyclopedia Britannica, 2017).
The integumentary system is made up of 3 layers, epidermis, dermis and subcutaneous (McLafferty, Hendry, & Farley, 2010). The skin is the largest organ in the body and is responsible for sensation, thermoregulation, protection and synthesis of vitamin D (McLafferty, Hendry, & Farley, 2010). The skin has roughly one million nerve endings which allows an individual to react to external stimuli such as: cold, heat, pain, touch and pressure (McLafferty, Hendry, & Farley, 2010). Thermoregulation is the regulation of temperature and is a critical component of a body’s ability to maintain homeostasis. Receptors in the skin monitor the external conditions and communicate with the hypothalamus, in the brain, whether it is too hot or too cold (McLafferty, Hendry, & Farley, 2010). When the body gets too hot, the hypothalamus activates the autonomic nervous system to induce sweating through eccrine glands and increase blood flow to help cool the body. When the body gets too cold, heat loss is reduced through the process of vasoconstriction, which reduces the flow of blood to the extremities and keeps the core warm (McLafferty, Hendry, & Farley, 2010). The body will also begin to shiver in an attempt to create heat.
The skin acts as a protective barrier for all the internal organs, and is lined by subcutaneous adipose tissue. This barrier prevents fluid loss and plays an important role in electrolyte balance (McLafferty, Hendry, & Farley, 2010). Lastly, it is a critical component in vitamin D synthesis. Vitamin D is necessary for controlling the amount of calcium and phosphorus that is absorbed in the small intestine and mobilized from the bone (McLafferty, Hendry, & Farley, 2010).
The respiratory system is critical for oxygen perfusion to the body and the blood. It also acts as a defense mechanism to invaders such as VZV. The average person will breath about 20,000 liters of air every 24 hours (Lechtzin, n.d.). It is inevitable that we inhale dangerous pathogens that can cause disease and illness. The body has a certain defense system to help ward of invaders and maintain homeostasis. Cilia, are tiny hairs that line the airway and propel a liquid layer of mucus that covers the airway (Lechtzin, n.d.). This mucus traps pathogens and other particles preventing them from reaching the lungs (Lechtzin, n.d.). Alveolar macrophages act as a second line of defense. They are a type of white blood cell (WBC) on the surface of the alveoli in the lung (Lechtzin, n.d.). These macrophages seek out foreign particles, bind to them, ingest them, and kill any that are living (Lechtzin, n.d.). If there are more particles than these WBC’s can handle, additional WBC’s called neutrophils will be recruited to assist with neutralizing any threat (Lechtzin, n.d.).
Homeostasis: Body System- Disease-State
Varicella zoster virus typically enters the human body through the respiratory system by being inhaled. The initial response is from the immune system and is the trigger of antiviral cytokines and the activation of natural killer (NK) cells (Arvin, 2008). NK cells have the ability to lyse VSV infected targets and inhibit replication in vitro, therefore reducing the severity of the VSV infection (Arvin, 2008).
Epidemiological evidence indicates that the infection begins with replication in the epithelial cells of the upper respiratory mucosa (Zerboni, Sen, Oliver, & Arvin, 2014). Then, after a 10-21 day incubation, a vesicular rash appears on the body (Zerboni, Sen, Oliver, & Arvin, 2014). This path shows the virus spreads to the tonsils and other local lymphoid tissues, from where infected T cells will transport the virus through the bloodstream to the skin (Zerboni, Sen, Oliver, & Arvin, 2014).
Once an infection has invaded the body, the process to fight it off is immediate. The immune system unleashes WBC’s called macrophages whose job is to find and destroy infected cells. In a more severe infection T and B lymphocytes are released. B lymphocytes make a special protein called antibodies that are able to bind to a virus to stop it from replicating (BBC Science, 2013). This also tags the cell so other blood cells know to destroy it. T cells have a different role, they can initiate a response when they detect an infected cell or help B cells produce antibodies (BBC Science, 2013). One of the most important jobs of these B and T lymphocytes is to retain an accurate memory of the destroyed virus (BBC Science, 2013). This memory means that if another attack from the same virus were to occur the body would have what is known as “acquired immunity” (BBC Science, 2013). During the initial phase of an infection molecules called pyrogens are released which alerts the brain to increase body temperature (Nguyen, 2017). This fever inhibits the movement of the virus which allows more time for the immune cells to find and eliminate the invaders (Nguyen, 2017).
The primary VZV infection is acquired by direct contact with infected skin lesions (Rockley & Trying, 1994). As the infected person scratches their lesions, infected epithelial tissue is released and then inhaled by a new host. The new site of infection is now the conjunctivae and/or the mucosa of the upper respiratory tract (Rockley & Trying, 1994). The first invasion and replication happens in the local lymph tissue, most commonly the tonsils. The VZV gains access to the T cells where the virus is able to infect and replicate.
Enveloped VZV particles attach to cell membranes, fuse and release the viral matrix proteins (Zerboni, Sen, Oliver, & Arvin, 2014). Uncoated capsids dock at nuclear pores, where genomic DNA is injected into the nucleus and infects (Zerboni, Sen, Oliver, & Arvin, 2014). Nucleocapsids are then assembled and contain newly synthesized genomic DNA (Zerboni, Sen, Oliver, & Arvin, 2014). This new DNA moves to the inner nuclear membrane and bud across the nuclear membrane entering the cytoplasm (Zerboni, Sen, Oliver, & Arvin, 2014). Once in the cytoplasm, virion glycoproteins mature in the trans-Golgi region and tegument proteins assemble in vesicles (Zerboni, Sen, Oliver, & Arvin, 2014). The last step is the capsids undergo secondary envelopment and are transported to cell surfaces, where newly assembled virus particles are released (Zerboni, Sen, Oliver, & Arvin, 2014). This first cycle of replication occurs on day 2 through 4 in regional lymph nodes (Rockley & Trying, 1994). The newly infected T cell is then released into the blood and a second replication cycle takes place in the liver, spleen and possibly other organs (Rockley & Trying, 1994). The blood released from those organs then sends the infected cells through the body, the virus then invades the capillary endothelial cells, exits the capillaries, and spreads to the epidermis by day 14 through 16 (Rockley & Trying, 1994).
After the initial infection has run its course, most individuals usually have immunity for life (CDC, 2016). The exceptions are re-exposure to a “wild-type” of varicella or individuals who are immunocompromised (CDC, 2016). This lasting immunity is through the ability of T lymphocytes to establish a memory to the virus. If the host where to be exposed again the T cells would inhibit any initial replication of the virus. Although the T cells keep the body immune to a reoccurrence of VZV, there is a strong possibility of developing the Herpes Zoster virus (shingles) later in life. After a person recovers from VSV, the virus can stay dormant in the body (CDC, 2018). There is still very conflicting evidence as to why this happens and almost 1 out of every 3 people in the United states will develop shingles (CDC, 2018).
The VZV vaccine was first licensed in the United States in March of 1995 and is a live-attenuated vaccine derived from the Oka strain of VZV (CDC, 2015). The vaccine names are Varivax and Merck (CDC, 2015). The CDC recommends that the first does be given at 12-15 months and a second dose at 4-6 years old (CDC, 2015). After the first dose of the single-antigen varicella vaccine, 97% of children developed detectable antibody titers and 99% after the second dose (CDC, 2015). Common side effects of the vaccine include: sore injection site, fever, mild rash and temporary pain and stiffness in joints (CDC, 2016). Serious side effects are very rare, the few that have been reported include: severe rash, infections of the lungs or liver, meningitis, seizures, pneumonia or general severe infection with the virus strain from the vaccine (CDC, 2016).
A live-attenuated vaccine means that it contains a weakened form of the germ that causes the disease (U.S. Department of Health and Human Services, n.d). The immune response to the VZV vaccine is the proliferation of interferon production by peripheral blood mononuclear cells (PBMC) and T cell specification. The injection of the virus allows the body to develop immunity through the imitation of an infection. This infection does not actually cause the illness but allows the body to build a memory. Although this vaccine is very effective, not everyone can receive it. Individuals who are immunocompromised cannot receive the vaccine due to their inability to fight infection (National Institute of Allergy and Infectious Diseases, Understanding Vaccines, 2013).
The chickenpox, although considered a mild virus, has a long-term effect on individuals. Through intervention with the vaccine the virus is almost 100% contained. The ability of science to create a vaccine has had an enormous effect on the 21st century mortality and morbidity rates. Continued efforts are currently underway to help revolutionize how science combats disease. As effort continue and discoveries are made, eradication is a possible outcome.
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