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OCTOBER/NOVEMBER 2006
Case Study:
Infection Control of Varicella zoster virus (VZV)
Joseph Bick, MD
Chief Medical Officer California Medical Facility California Department of Corrections Assistant Clinical Professor Section of Infectious and Immunologic Diseases University of California, Davis Disclosures: The author has nothing to disclose. It is 5:00 p.m. on Friday afternoon, and you are looking forward to a well-deserved weekend with your family. As you prepare to leave the facility, you receive a frantic call from your Director of Nursing. A late bus has just arrived, and one of the prisoners on the bus has a vesicular rash. Also on the bus are six HIV-infected patients, a patient on high dose prednisone, and a patient who is status post bone marrow transplant. The nurse who is doing the intake screening just learned that she is six weeks pregnant. You: A. Call the warden, lock down the facility, and notify homeland security that you have just received a case of probable smallpox. C. Reassure your DON, and head to reception confident in your ability to differentiate between the common causes of vesicular rashes and to implement the appropriate management plan. Clinical Features Varicella zoster virus (VZV) is the cause of two distinct clinical syndromes: primary varicella, or chicken pox, and recrudescent varicella, also referred to as zoster or shingles. Prior to the widespread use of the varicella vaccine, virtually everyone became infected with VZV, with more than 90% of cases occurring before the age of fifteen. Following the licensing of the varicella vaccine in 1995, the number of varicella cases in the United States has declined by approximately 85%. In addition, hospitalizations for varicella-related illness have declined by more than 70%, and deaths attributable to varicella have decreased significantly. Most people who become infected with VZV will be symptomatic, and those who recall a history of chickenpox can be assumed to be immune to re-infection. Approximately 80% of adults will remember having had varicella, and among the 20% who do not recall having had the disease, serology will demonstrate prior infection in over 80%. Once infected with VZV, the incubation period prior to symptoms is 10-21 days. The most common symptoms of primary varicella are a low-grade fever, malaise, and rash. The rash classically begins as macules and papules on the face and trunk, and rapidly progresses to vesicles, which can involve the entire body. A hallmark of primary varicella is the development of successive crops of lesions over several days. The number of vesicles ranges from a few to more than a thousand, and tend to increase with the age of the patient. Immunocompromised individuals tend to have a larger number of lesions, and are also at increased risk for visceral involvement. Denuded lesions can become secondarily infected with bacteria, and rarely staphylococcus or group A streptococcus can cause serious secondary infections. Another very serious complication of chickenpox is varicella pneumonia, which can occur in up to 20% of adults who develop primary varicella. VZV can also involve the heart, liver, kidneys, and central nervous system (CNS). Primary varicella is highly contagious, and is most commonly transmitted by small droplet aerosols from the nasopharyngeal secretions of children in school or daycare who have active chickenpox. In the correctional setting, visiting children can be a source of varicella. VZV can also be transmitted from a person with zoster when a non-immune person comes into direct contact with the lesions of zoster or has exposure to aerosolized virus from clothing or linen. Those who have primary varicella are contagious beginning 48 hours before the development of a rash and continuing until all lesions have crusted. New lesions will most commonly continue to appear for several days, and complete crusting generally occurs within seven to ten days. After resolution of the initial illness, VZV remains dormant in the dorsal root ganglia. Once infected, individuals will harbor VZV for life. Herpes zoster (shingles) is due to reactivation of VZV from the dorsal nerve root ganglia. Approximately 300,000 cases of zoster develop in the United States each year. By the age of 75 years, 30-40% of persons will have experienced an episode of zoster. The incidence of zoster is markedly increased in those who have HIV infection, those receiving corticosteroids or other immunosuppressant therapy, and those who have a malignancy. Zoster or a history of zoster in a person who is not elderly or in anyone at increased risk for HIV infection (such as the incarcerated) should prompt a recommendation for HIV testing. Unlike chicken pox, zoster is characterized by a unilateral distribution of vesicular lesions in the distribution of a single or several adjacent dermatomes. A vesicular rash that crosses the midline is extremely unlikely to be due to zoster. Infrequently, a more disseminated form of zoster can develop. This variant is more likely to occur in persons who have profound immunosuppresion as in the setting of stem cell transplant. A prodrome of pain, numbness, or pruritus can occur for hours to days before the appearance of lesions. New vesicles typically continue to form for three to five days, scabbing generally occurs by seven to ten days, and complete healing may require two to four weeks. Although any dermatome can be involved, those most commonly affected are from the mid-thoracic to the lower lumbar area. Zoster involving the ophthalmic branch of the trigeminal nerve is referred to as zoster ophthalmicus, and is an ophthalmologic emergency. Any involvement of the trigeminal nerve requires urgent ophthalmologic referral. Ophthalmic zoster can result in uveitis, keratitis, scleritis, and/or optic neuritis. Zoster can lead to bacterial infection or scarring at the site of the skin lesions. Careful attention to skin hygiene can decrease the risk of secondary infection. Uncommon complications include cutaneous dissemination, pneumonitis hepatitis, encephalitis, myelitis, motor neuropathies, and granulomatous CNS vasculitis. Zoster is commonly accompanied by acute neuritis and/or postherpetic neuralgia. Both can be severe, disabling, and refractory to treatment. The frequency of postherpetic neuralgia increases in those who develop zoster at an older age. Pain lasting more than one month is uncommon in those less than 30 years old, but is seen in 60-70% of those over age 60. A common sequela is hyperesthesia. Patients may report that gusts of wind or the pressure of thin bed sheets leads to sharp intense pain. Differential Diagnosis Prior to the last reported indigenous case of smallpox in 1977, it was important to include this virus in the differential diagnosis of a vesicular rash. An important difference between the two illnesses is that the rash of varicella has macules, papules, vesicles, and scabs in varying degrees of evolution. In smallpox, all lesions are in the same stage. Other illnesses that should be considered in the differential diagnosis of varicella include impetigo, disseminated herpes simplex, disseminated herpes zoster, dermatitis herpetiformis, and disseminated coxsackievirus. These conditions are detailed in Table I on page 7. Treatment The risk for secondary bacterial infection of the skin during VZV disease can be diminished with good skin hygiene. Fingernails should be cut short to decrease the likelihood of inoculating the skin with endemic bacteria such as MRSA. Outside of the correctional setting, daily soaks are commonly recommended. This is not practical in the correctional setting, but access to showers and soap should be facilitated. Antipruritic medications can provide some relief. Antiviral treatment of adults who have primary varicella leads to small but statistically significant improvement in the days of new lesion formation, the time to onset of cutaneous healing, the time to 100% crusting, and the total number of lesions. Studies have yielded conflicting data concerning whether antiviral therapy decreases the likelihood of chronic pain and the time to cessation of zoster associated pain. To be of benefit, treatment should be initiated as soon as possible after the development of rash, preferably within 24 hours. Regimens that have demonstrated efficacy in the treatment of acute varicella and zoster include acyclovir (800 mg by mouth five times per day), famciclovir (500 mg orally three times daily) and valacyclovir (1000 mg by mouth two to three times daily). Intravenous treatment should be offered to those who develop visceral disease, those with disseminated zoster, and immunocompromised persons who develop varicella or disseminated zoster. Medications that may provide some relief for zoster associated pain include nonsteroidal anti-inflammatory medications, tramadol, narcotics, and medications that interfere with the transmission of painful impulses such as tegretol, amitryptiline, and gabapentin. Several studies have demonstrated a benefit of prednisone treatment during zoster in terms of accelerating resolution of acute neuritis, return to normal sleep, return to unaroused sleep, and cessation of analgesic use. The risk, benefit ratio of prednisone should be weighed carefully and most patients can be managed without corticosteroids. The data on decreasing the prevalence of chronic pain with corticosteroids is less conclusive. Prevention Primary Varicella. A live attenuated varicella vaccine (VarivaxT, Merck and Company, Inc.) was licensed in 1995 by the Federal Drug Administration (FDA) for use in healthy persons 12 months of age or older who have not had varicella. One dose of the vaccine is highly immunogenic, leading to the development of protective antibody titers in 95% of healthy children and 88% of healthy adults. Mild vaccine associated symptoms (fever, rash, and/or local symptoms) occur in 4-8% of individuals. Individuals with a history of varicella (i.e. chickenpox as a child) do not need to receive the vaccine, as prior infection confers protection against re-infection. Pregnant women with a history of previous varicella infection should be considered immune. Pregnant women without a history of previous varicella infection are at risk of infection, which can lead to severe complications of the pregnancy. For this reason, particular attention must be paid to prevent non-immune pregnant women from exposure to individuals with active varicella disease. As preventive use of the VZV vaccine has become increasingly common, more persons have reached adulthood without having been either infected or vaccinated. In addition, immunity following vaccination may wane over time, leaving some adults at risk for acquiring VZV at a later age. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has recently added a recommendation for a second dose of varicella vaccination. The first dose should be offered between the ages of 12 and 18 months, and the second between the ages of 4 and 6 years. In addition, ACIP now recommends that persons over 13 years old who do not have a history of varicella infection or of vaccination should receive two doses of varicella vaccine at an interval of 4-8 weeks. The ACIP is also recommending that adolescents and adults who previously received one dose of the vaccination should receive a booster, regardless of how long ago the initial dose was. Adults who are vaccinated for VZV can develop a rash within 2 to 6 weeks of receiving the vaccine. The rash can be vesicular, macular, or papular, and can be localized to the site of the vaccination or disseminated. Employees should be educated that they may develop a rash following vaccination and instructed to inform employee health staff if a rash is seen. Employees who develop a rash are potentially contagious to non-immune individuals, and should be medically furloughed until the rash resolves. Lesions will typically heal in 2 to 3 days. Zoster Recently, a trial was performed to determine if vaccination of VZV infected adults would decrease the incidence of zoster. Over 37,000 volunteers >60 years old participated in this study and were followed up for an average of three years. Those who were vaccinated had a 52.3% decrease in the incidence of zoster. Those who were vaccinated and developed zoster had a 61.1% decrease in the incidence post herpetic neuralgia. In May of 2006 the FDA approved the use of this live attenuated varicella vaccine (ZostavaxT, Merck and Company, Inc.), a stronger version of the chickenpox vaccine, for the prevention of zoster in people > 60 years of age who have previously been infected with VZV. The vaccine is given as a single injection under the skin, preferably in the upper arm. Both varicella virus vaccine and zoster vaccine live are contraindicated in persons with a history of anaphylactic or anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine, a history of primary or acquired immunodeficiency states including leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system. They are also contraindicated in persons with AIDS or other clinical manifestations of infection with human immunodeficiency viruses, persons on immunosuppressive therapy including high-dose corticosteroids, and in women who are or may be pregnant. Infection Control Transmission of varicella from health care workers to patients is a well-recognized phenomenon that can have devastating consequences. Providing varicella vaccination to non-immune employees can decrease the likelihood of transmission in either direction between staff and inmate/patients. Vaccination is especially important for employees who are in contact with those inmate/patients who are at greatest risk for varicella-related complications. This includes pregnant inmates and those who are immunocompromised (for example, those who are HIV-infected). Another benefit of an active varicella vaccination program is that it simplifies the required response to the diagnosis of varicella within the facility. Employees who are known to be immune to VZV (either naturally or via vaccination) will not be subject to medical furlough following possible exposure episodes. Because varicella is spread through the air, it is essential to isolate those who have contagious VZV disease. Inmate-patients with active VZV should be placed in a private room that has negative air pressure relative to the hallway and kept there until all vesicular lesions have dried. Employees who have active VZV should be medically furloughed for a similar period of time. If negative pressure rooms are not available, it may be acceptable to confine the inmate-patient in a cell or dormitory with inmates who are known to immune by virtue of having had VZV in the past. Employees who are not known to be immune should not participate in the care of persons who have VZV unless wearing a respirator. A contact investigation should be performed to identify non-immune persons who may have shared the air with the person who has active varicella. Because of the highly immunogenic nature of the vaccine, testing to demonstrate immunity is not recommended among those who have been vaccinated. If an exposed person does not recall a history of vaccination or active VZV disease, stat serology (results within 72 hours) should be obtained. Persons who are VZV IgG negative can be considered to be non-immune. Exposed susceptible inmate-patients should be cohorted and medically confined to a housing unit beginning 10 days after exposure and ending 21 days after exposure. Exposed susceptible staff should be medically furloughed during the same time frame. Post Exposure Prophylaxis Non-immune persons who have been exposed to varicella and who are considered to be at high risk for severe disease and complications should be offered varicella zoster immunoglobulin. High risk non-immune adults include pregnant women and those who are immunocompromised (HIV infected, recipients of organ transplants, those receiving immunosuppressive agents, etc). Varicella zoster immunoglobulin should be administered as soon as possible, within 96 hours of exposure. Non-immune adults should also be vaccinated for varicella unless contraindicated (HIV infection with CD-4 counts < 200 or 15%). Varicella vaccine should not be given until at least five months after varicella immunoglobulin. In 2004, the only U.S. licensed manufacturer of VZIG discontinued production. In 2006, an investigational VZIG product, VariZIGT (Cangene Corporation, Winnipeg, Canada) became available under an investigational new drug application (IND). This investigational drug is distributed by FFF Enterprises (Temecula, California; 24-hour telephone, 800-843-7477). Conclusion 5:16 p.m. You take a deep breath, and enter the bus screening area. Since you had chickenpox as a child, you know that you do not need to worry about "catching" it again. The triage nurse is in tears, and her union rep is helping her fill out a stress claim. While evaluating the 20 year-old inmate who has a rash, you learn that two weeks ago his girlfriend and their two year-old child visited him in the county jail. He recalls that the child had a fever, and was not her usual playful self. Neither he nor his girlfriend has vaccinated the child, because they believe that immunizations are dangerous. You examine the patient and find that he has over 100 scattered skin lesions on his face, chest, back, and arms. The lesions include macules, papules, vesicles, pustules, and scabs. He has a temperature of 101.6, malaise, anorexia, and pruritus. He does not recall having had chickenpox as a child. You diagnosis him with primary varicella, and have him separated from the rest of those who need evaluation. You ask the Nursing Director to contact your local referral hospital and arrange for a negative pressure respiratory isolation room. You also ask her to ensure that those assigned to transport the patient have all had chicken pox. 5:31 p.m. You turn your attention to the bus screening nurse. Your pulse quickens when she tells you that she does not remember having had chicken pox. You know that chickenpox is one diagnosis for which the sensitivity and specificity of a mother's history is superb, and so you ask the nurse to call her mom. You resume the investigation of those who traveled on the bus with your chickenpox patient. 5:42 p.m. There are a total of 12 new arrivals, including the 6 patients who are known to be HIV infected, one who is receiving 60 mg per day of prednisone for some type of kidney disorder, and one who is 18 months post stem cell transplant for ALL. You are informed that all the patients' charts were mistakenly left at the last institution. The inmates are working together on some paperwork; one of them asks you if you know how to spell "deliberate indifference". Ten of the inmate-patients recall having had chicken pox as a child. You advise them that they are immune, have no risk of being re-infected, and that they do not need any special treatment related to this exposure. You inform custody that these ten inmates can be housed without regard to this exposure. Two of the patients do not recall a history of chickenpox; one is HIV infected and the other is your stem cell transplant patient. You order a stat blood draw for varicella zoster serology (IgG) to be obtained from both of these patients. You authorize overtime for the phlebotomist to personally drop the specimens off at the local reference lab that evening, with instructions that you need results back no later than Monday afternoon. You place a medical hold on these two patients, and inform custody that although these patients are not contagious and do not need special housing, they must not leave the institution until they have been evaluated further. 6:02 p.m. Returning to the reception nurse, you are immensely relieved to learn that her mother clearly recalls nursing her through chickenpox when your employee was four years old. You reassure the nurse that there is no risk to her or her unborn baby from this exposure, write her a brief note, and suggest that she follow-up with her physician for good measure. 6:15 p.m. You stroll confidently to the parking lot, hoping to salvage some of the evening with your family. As you pull out of the parking lot, you answer a new page from the watch commander. She informs you that one of her sergeants has determined that an inmate has scabies, has quarantined the man's 300 man dorm, and is demanding that all 300 inmates be treated immediately with DDT.
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