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NYSNA has been granted provider status by the Florida State Board of Nursing as a provider of continuing education in nursing. (Provider number 50-1437).

About the Authors

This course was reviewed by Tener Goodwin Veenema, PhD, RN, MPH, MS a nationally recognized expert on bioterrorism.

Disclaimer

As stated above, this course was developed utilizing the most up-to-date information available, mainly from the Centers for Disease Control and Prevention (CDC). However, the subject of smallpox disease, smallpox vaccination and bioterrorism in general is rapidly evolving. For emerging information, consult the CDC website (www.cdc.gov), the New York State Department of Health website (www.health.state.ny.us) , or your state health department website for the most current changes.

Introduction

One of the most destructive potential threats is that of smallpox, if it were to be used as a biological agent of terror. Smallpox is a serious, highly contagious, and sometimes fatal infectious viral disease. The name is derived from the Latin word for "spotted" and refers to the raised bumps that appear on the face and body of an infected person.

Smallpox outbreaks have occurred episodically for thousands of years, but the disease was considered eradicated after a successful worldwide vaccination program. The last naturally acquired case of smallpox in the United States was in 1949, and the last naturally occurring case in the world was in Somalia in 1977. The last case of smallpox, acquired from a laboratory exposure, occurred in the United Kingdom in 1978. In the United States, routine vaccination against smallpox ended in 1972 (CDC, 2001d). Smallpox was declared globally eradicated on May 8, 1980 by the World Health Assembly, the supreme decision making body of the World Health Organization. After the disease was eliminated from the world, routine vaccination against smallpox among the general public was stopped because it was no longer necessary for prevention. However, it remains a biological threat because of its potential ease of large-scale production and subsequent use in a deliberate biological attack (CDC, October, 2002).

The use of the smallpox virus as a biological weapon may be less likely than other biological agents because of its restricted availability. However, over the last several years, multiple claims have arisen about terrorist groups or foreign governments having the smallpox virus.

Even one suspected case of smallpox is an international public health emergency. It will require rapid identification, a definitive diagnosis with rapid laboratory confirmation at the Centers for Disease Control and Prevention (CDC), and vaccination to contain and prevent further smallpox transmission. In the US, in 2003, volunteer healthcare providers were vaccinated in order to have a team of healthcare providers who could rapidly begin the vaccination process among the general public, if a smallpox outbreak occurred. These immunized healthcare workers had to have been vaccinated themselves prior to being able to give the vaccination.

Currently, specific therapies with proven treatment effectiveness for smallpox are unavailable. Medical care of more seriously ill smallpox patients would be resource intensive and would include primarily supportive measures and antiviral treatment. If the patient's condition allows, medical and public health authorities should consider isolation and observation outside a hospital setting to prevent healthcare associated smallpox transmission and overburden of healthcare resources.

Government and public health officials have been working on an organized, coordinated response to the threat of smallpox as a biological weapon. In December 2002, The CDC Smallpox Response Plan and Guidelines was released. This document outlines the public health strategies that would guide the public health response to a smallpox emergency and many of the federal, state, and local public health activities that must be undertaken in a smallpox outbreak. It can be accessed at http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp#annex.

This course will address the pre-event information needed by healthcare providers. It will include an overview of smallpox, including identification of smallpox, distinguishing it from other rash illnesses, vaccination, adverse reactions and their management. Additionally, the process of vaccination will be covered. This course is divided into three sections: Part I provides an overview of smallpox including information about its use as a weapon of terror; Part II addresses smallpox immunization benefits, risks, and the vaccination procedures; and Part III includes the role of healthcare providers in preparing for the potential use of smallpox as a weapon of mass destruction. It is expected that healthcare providers will follow-up this course with a locally available experiential educational activity that will allow them the opportunity to have hands-on practice with the vaccination process.

Part I. Overview of Smallpox Disease

Early History of Smallpox

It was mentioned in writings from ancient Egypt dating back to approximately 3700 BC. The mummified body of Ramses V, a pharaoh, who died in 1157 BC, whose well-preserved remains are on display at the Cairo Museum, reveals a striking rash of yellow pustules on the face and hands -early physical evidence of the presence of smallpox. Traders carried smallpox from Egypt to India, where Sanskrit medical texts describe epidemics as early as 1500 BC. The disease arrived in China by 1122 BC, apparently imported by the Huns, since the Chinese called it "Hunpox". According to the Greek historian Thucydides, an epidemic suggestive of smallpox struck Athens around 430 BC, killing one third of the city-state's population and contributing to its defeat in the Peloponnesian War. In the 4th century BC, Alexander the Great's army suffered an outbreak of the disease in India. The Roman Emperor Marcus Aurielius died of smallpox in AD 165, accelerating the decline of the Roman Empire.

The use of smallpox as a biological weapon reportedly occurred during the French and Indian Wars 1754-1767. British troops allegedly distributed smallpox tainted blankets to Native Americans, with the intent of initiating an outbreak among them. In some of the epidemics that resulted, more than 50% of the infected tribes succumbed to the disease. The threat of smallpox as a bioweapon was greatly diminished with Edward Jenner's demonstration in 1796 that an infection resulting from inoculation with cowpox also provided protection against smallpox (Henderson, et al, 1999).

Concerns Regarding the Use of Smallpox as a Biological Weapon

Indications of intentional release of any biologic agent include

• An unusual temporal or geographic clustering of illness (e.g., persons who attended the same public event or gathering) or patients presenting with clinical signs and symptoms that suggest an infectious disease outbreak;

• An unusual age distribution for common diseases (e.g., an increase in what appears to be a chickenpox-like illness among adult patients, but which might be smallpox).

Smallpox is classified as a Category A agent by the Centers for Disease Control and Prevention (CDC). Category A agents are believed to pose the greatest potential threat for adverse public health impact and have a moderate to high potential for large-scale dissemination. Other Category A agents are anthrax, plague, botulism, tularemia, and viral hemorrhagic fevers.

In the event of an aerosol release of smallpox, all viruses will be inactivated or dissipated within 1-2 days. Buildings exposed to an initial aerosol release of the virus would not need to be decontaminated because by the time the first cases are identified, typically about 1 to 2 weeks after the release, the virus in the building will be gone. Infected patients, however, will be capable of spreading the virus and possibly contaminating surfaces while they are sick.

Much has been learned from previous outbreaks of naturally occurring smallpox. In 1972, in Yugoslavia, a smallpox outbreak occurred after a man who had been on Hajj, an Islamic pilgrimage to Mecca and Medina, became infected with smallpox virus while in Iraq. His infection was initially misdiagnosed as a penicillin-associated drug eruption and went undiagnosed. He brought the disease back to Yugoslavia and unknowingly infected 11 others, whose infections also went undiagnosed. It was not until the second generation of cases that the smallpox outbreak was recognized and control measures initiated. By that time there were 140 new cases of smallpox, with a transmission ratio of 1:13. Ultimately, a single index case caused 175 cases of smallpox and 34 deaths before the outbreak was brought to an end. This smallpox outbreak has been particularly instructive because it encompassed many of the concerns that would likely be expected if a smallpox outbreak occurred today:

• A large number of susceptible people - Since smallpox vaccination in the US was discontinued in 1972, the level of immunity, if any, among persons who were vaccinated before 1972 is uncertain; therefore, these persons are assumed to be susceptible. Some experts suspect that some level of immunity may be present although minimal, however the degree is not known. Although some healthcare workers have recently been immunized, there remains relatively few among the US population of almost 300 million people who have significant immunity to smallpox.

• Delayed diagnosis - Because smallpox is a threat that few healthcare providers have seen due to its eradication decades ago, it may go undiagnosed or be misdiagnosed as another eruptive illness. However, since September 11, 2001, the index of suspicion regarding possible bioterrorism related illness has increased. Additionally, diagnosis will likely be delayed because of the time it takes for the index case to develop the symptoms and seek medical care. During that time many others can be infected with the smallpox virus and include:
  • Both hospital and community transmission.
  • Wide geographic dispersion of cases - The high level of mobility of the US population will contribute to the dispersion of cases, particularly if a smallpox outbreak were calculated to start in an airport or other mass transportation area.
  • Difficulty in contact tracing - Because of the high level of mobility in the population, tracing contacts will be difficult. Other issues include fear, confidentiality and trust.

Pathogenesis

After smallpox virus infection, the virus remains localized and replicates for up to 3 days. The initial steps in viral dissemination in the body involve a primary viremia in which the virus moves to the draining lymph nodes, spleen and sometimes bone marrow. In smallpox the virus replicates further in lymphoid organs then migrates via the lymphatics to the bloodstream producing a secondary viremia followed by fever and toxemia. The secondary viremia carries the virus to the basal layer of the oropharyngeal region and epidermis by the 10th to 14th day after the initial infection. Just after the fever peaks, the development of oropharyngeal lesions begins (the enanthem), and is soon followed by the development of skin lesions (the exanthem). Lesions occur first on the mucous membranes of the mouth, tongue, pharynx, larynx, and upper part of the esophagus. Transmission by large-particle, airborne droplets is maximal at the time of the appearance of skin lesions. The disease can be spread by these large-particle, airborne droplets until the skin scabs fall off, however, droplet transmissibility decreases significantly after the 2nd week of disease as the oral lesions of the enanthem heal and viral titers in the saliva decrease.

The characteristic pathologic feature of smallpox is the skin rash. Initially, the capillaries in the dermal papillae dilate, followed by swelling of the endothelium and infiltration of lymphocytes and histiocytes (macrophages present in connective tissue). Polymorphonuclear leukocytes enter skin vesicles from the dermis to produce the pustular lesions. The pustular fluid eventually dries up as the disease disappears and the lesions become filled with granular tissue, which forms scabs consisting of degenerated epithelial cells and leukocytes. Virus particles can be present in large numbers in the scabs but are generally not highly infectious because they are enclosed within the hard, dry scab. Lesion scars or pockmarks are sequelae caused mainly by destruction of infected sebaceous glands and are most prominent on the face.

Types of Smallpox Disease

Modified smallpox most often occurs in previously vaccinated individuals. Modified refers to the character of the eruption and the rapidity of its development, progression and resolution of lesions. In general, the prodrome stage may still consist of severe headache, backache, and fever, and the duration may not be shortened. However, once the skin lesions appear, they generally evolve more quickly with crusting completed within 10 days. The lesions may be fewer in number and are more superficial than those seen in ordinary-type smallpox. Fever during the evolution of the rash is also usually absent during this modified clinical course. Modified smallpox is rarely, if ever, fatal.

Flat-type smallpox is also referred to as malignant smallpox; it is a more severe form of smallpox and has a high mortality rate (97 percent in unvaccinated cases). Flat-type smallpox is so called because the lesions remained more or less flush with the skin at the time when raised vesicles formed in ordinary smallpox. It's not known with certainty why some people develop this type of disease, but many cases occurred in children. The prodrome and constitutional symptoms are severe, and last three or four days. The fever remains elevated throughout the course of the illness and the patient has severe toxic symptoms. The rash on the tongue and palate is usually extensive, and the skin lesions develop very slowly. By the seventh or eighth day the lesions are flat and appear to be buried in the skin. Unlike ordinary type smallpox the vesicles contain very little fluid and do not appear umbilicated. The lesions are soft and velvety to the touch. Lesions may contain hemorrhages. The prognosis for this form of smallpox is grave and most cases are fatal. Flat type smallpox can be difficult to diagnose, mainly because the typical skin lesions do not develop.

Hemorrhagic smallpox is also a severe and uncommon form of smallpox that is almost always fatal. In patients with a highly compromised immune response, there is extensive multiplication of the virus in the spleen and bone marrow to produce this rare form of smallpox. It involves extensive bleeding into the skin, mucous membranes and gastrointestinal tract. Megakaryocyte destruction in the bone marrow is believed to lead to defective blood coagulation. The rare hemorrhagic-type smallpox is associated with petechiae in the skin and bleeding from the conjunctiva and mucous membranes.

The prodrome, which can be prolonged, is characterized by fever, intense headache and backache, restlessness, a dusky flush or sometimes pallor of the skin, extreme prostration, and toxicity. There is little or no remission of fever throughout the illness. Hemorrhagic manifestations can occur early or late in the course of the disease. Hemorrhagic manifestations appear on the second or third day as subconjunctival bleeding and bleeding from the mouth and gums, or other mucous membranes, petechiae in the skin, epistaxis, and hematuria. Death often occurs suddenly between the 5th or 6th day of the rash, when only a few insignificant maculopapular cutaneous lesions are present. In patients who survive for eight to 10 days the hemorrhages appear in the early eruptive period. The rash is flat and does not progress beyond the vesicular stage. Hemorrhagic smallpox could be easily misdiagnosed as meningococcal bacteremia because of the hemorrhages and lack of typical smallpox vesicles and pustules. Hemorrhagic-type smallpox occurs among all ages and in both sexes but is more common in adults. Pregnant women also seem to be more susceptible to developing this form of smallpox than other adults. The underlying molecular biologic reasons for the toxemia and other effects are unclear.

Clinical Manifestations of Classic Smallpox

Crusts begin to form about the eighth or ninth day. When the scabs separate, pigment-free skin remains, and eventually pitted scars form (Johns Hopkins University, 2000). The scars result from the destruction of sebaceous glands that is followed by shrinking of granulation tissue and fibrosis. Scars are most evident on the face (Henderson, et al., 1999).The lesions on the mouth and pharynx ulcerate quickly, releasing large amounts of virus into the saliva. Patients are most infectious during the first week, which corresponds with the high virus titers in the saliva (Henderson, et al., 1999). Patients are no longer infectious after all scabs have separated, approximately 3-4 weeks after the onset of the rash (ACIP, 2001).

Diagnosis of Smallpox Disease

Another tool that the CDC developed to assist with the diagnosis of smallpox is a worksheet, Evaluating Patients for Smallpox, that can also be accessed online at http://www.bt.cdc.gov/agent/smallpox/diagnosis/index.asp#diagnosis. It appears in Appendix A. The CDC also developed the Poster: Evaluating Patients for Smallpox, to be used in conjunction with the worksheet (Appendix A). The poster appears in Appendix B.

Case Definitions/Classifications

Thus, in the absence of smallpox disease in the world, the suggested approach to surveillance relies on a highly specific clinical case definition, which is focused on identifying the classic case presentation (ordinary type) of smallpox. (Before eradication, classic (ordinary type) smallpox generally accounted for approximately 90% of smallpox cases in previously unvaccinated individuals and 70% of cases that occurred in previously vaccinated individuals who were no longer fully protected by vaccination.)

Smallpox clinical case definition - An illness with acute onset of fever >101°F (38.3°C) followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause.

Laboratory criteria for confirmation - Laboratory diagnostic testing for variola virus should be conducted in a CDC Laboratory Response Network (LRN) laboratory utilizing LRN-approved PCR tests and protocols for variola virus. Initial confirmation of a smallpox outbreak requires additional testing at CDC. Generic orthopox PCR and negative stain electron microscopy (EM) identification of a pox virus in a clinical specimen are suggestive of an orthopox virus infection but not diagnostic for smallpox.

• Polymerase chain reaction (PCR) identification of variola DNA in a clinical specimen, OR
• Isolation of smallpox (variola) virus from a clinical specimen (WHO Smallpox Reference laboratory or laboratory with appropriate reference capabilities) with variola PCR confirmation.

• Confirmed case - A case of smallpox that is laboratory confirmed, or a case that meets the clinical case definition that is epidemiologically linked to a laboratory confirmed case.

• Probable case - A case that meets the clinical case definition, or a case that does not meet the clinical case definition but is clinically consistent with smallpox and has an epidemiological link to a confirmed case of smallpox. Examples of clinical presentations of smallpox that would not meet the ordinary type (pre-event) clinical case definition are: a) hemorrhagic type, b) flat type, and c) variola sine eruptione.

• Suspect case - A case with a febrile rash illness with fever preceding development of rash by 1-4 days.

Differential Diagnosis

• The most obvious distinction between the two infections is the period of time over which the lesions appear. In chickenpox, the lesions occur in successive "crops". Physical examination will reveal several different stages of lesion maturation and development at the same time. Smallpox lesions however, appear more or less simultaneously.
• Another diagnostic clue resides in the density and location of the lesions. Chickenpox lesions are denser over the trunk (central distribution) and smallpox lesions are denser on the face and extremities (centrifugal distribution).
• Finally, the physiology of the lesions is diagnostic as well, with chicken pox lesions being more superficial.

Exposure and Transmission

The most frequent mode of transmission is person-to-person, spread through direct deposit of infective droplet nuclei onto the nasal, oral, or pharyngeal mucosal membranes, or the alveoli of the lungs from close, face-to-face contact with an infectious person. Only rarely has airborne transmission been documented (ACIP, 2002a). Transmission does not occur during the prodromal period, before the rash appears. Epidemiologic studies have shown that smallpox has a lower rate of transmission than diseases such as measles, pertussis, and influenza (ACIP, 2002a). The greatest risk of infection occurs among household members and close contacts of persons with smallpox, especially those with prolonged face-to-face exposure. Vaccination and isolation of contacts of cases at greatest risk of infection has been shown to interrupt transmission of smallpox. However, poor infection control practices resulted in high rates of transmission in hospitals (ACIP, 2002a).

Indirect spread (i.e., not requiring face-to-face contact with an infectious person) through fine-particle aerosols or a fomite containing the virus is less common (ACIP, 2001). Persons with smallpox are most infectious during the first week of illness, because that is when the largest amount of virus is present in saliva. However, some risk of transmission lasts until all scabs have fallen off. Droplet and airborne precautions are needed for a minimum of 17 days following exposure for all persons in direct contact with the index case, especially the unvaccinated. In the non-military setting strict quarantine of asymptomatic contacts may prove to be impractical and impossible to enforce. The United States Army Medical Research Institute of Infectious Diseases (USAMRIID, 2001) suggests that a reasonable alternative would be to require contacts to check their temperatures daily. Any fever above 38 C (101 F) during the 17-day period following exposure to a confirmed case would suggest the development of smallpox. The contact should then be isolated immediately, preferably at home, until smallpox is either confirmed or ruled out. Patients should be considered infectious until all scabs separate. Immediate vaccination or revaccination should also be undertaken for all persons exposed to either weaponized variola virus or a clinical case of smallpox.

The potential for airborne spread to other than close contacts has occurred. In general, close person-to-person contact is required for transmission to reliably occur. However, variola's potential in low relative humidity for airborne dissemination was alarming in two hospital outbreaks. Smallpox patients were infectious from the time of onset of their eruptive exanthem, most commonly from days 3-6 after onset of fever. Infectivity was markedly enhanced in these patients who manifested a cough which allowed for the aerosol release and transmission of smallpox. Indirect transmission via contaminated bedding or other fomites was infrequent. Some close contacts harbored virus in their throats without developing disease, and hence might have served as a means of secondary transmission (USAMRIID, 2001).Vaccination with a verified clinical "take" (vesicle with scar formation) within the past 3 years is considered to render a person immune to smallpox (USAMRIID, 2001).

Control of Smallpox

Because of the problems encountered with imported cases, health officials should be diligent regarding use of adequate isolation facilities and precautions. Isolation of confirmed or suspected smallpox patients will be necessary to limit the potential exposure of nonvaccinated and, therefore, nonimmune persons. A problematic situation regarding poor infection control practices occurred in Germany in 1970, a German who was returning from visiting Pakistan was diagnosed with smallpox and admitted to the hospital. Nineteen subsequent cases of smallpox were diagnosed in that hospital as a result.

Since the numbers of immunized persons, at this time is very low, most of the population is at risk, and all children and infants are at risk. Although droplet spread is the major mode of person-to-person smallpox transmission, airborne transmission through fine-particle aerosol can occur. Therefore, airborne precautions using correct ventilation (e.g., negative air-pressure rooms with high-efficiency particulate air filtration) should be initiated for hospitalized confirmed or suspected smallpox patients, unless the entire facility has been restricted to smallpox patients and recently vaccinated persons.

Healthcare providers should observe standard and contact precautions (i.e., using protective clothing and shoe covers) when in contact with smallpox patients or contaminated materials to prevent inadvertent spread of variola virus to susceptible persons and potential self-contact with other infectious agents. Personnel should remove and correctly dispose of all protective clothing before contact with nonvaccinated persons. Standard hospital grade disinfectants such as quaternary ammonias are effective in killing the virus on surfaces should be used for disinfecting hospitalized patients' rooms or other contaminated surfaces. Although less desirable because it can damage equipment and furniture, hypochlorite (bleach) is an acceptable alternative (CDC, 2001d).Contaminated clothing or bed linen could also spread the virus. In the hospital setting, patients' linens should be autoclaved or washed in hot water with bleach added. Laundry handlers should be vaccinated before handling contaminated materials. Infectious waste should be placed in biohazard bags and autoclaved before incineration. Special precautions need to be taken in the community, to ensure that all bedding and clothing of patients are cleaned appropriately with bleach and hot water. Disinfectants such as bleach and quaternary ammonia can be used for cleaning contaminated surfaces (CDC, 2001d).

Treatment

Multiple studies of antivirals during the smallpox eradication failed to show significant benefit in the treatment of smallpox. Evaluation of modern day antivirals at CDC is ongoing. One current antiviral, Cidofovir, has shown some in-vitro and in-vivo (animal studies) activity against orthopoxviruses. However, its effectiveness for treating clinical smallpox or vaccine adverse events is not known. This medication is labeled for the treatment of CMV retinitis and has been associated with renal failure. Were an outbreak of smallpox to occur, this medication would be made available through the CDC or National Institutes of Health (NIH) under an Investigational New Drug (IND) protocol for the potential treatment of smallpox or vaccine adverse events.

Reporting Suspected Smallpox

Any confirmed case of smallpox should be considered an international emergency; even suspected smallpox should be reported immediately by telephone to state or local health officials and advice obtained regarding isolation and laboratory specimen collection.

Medical personnel should notify their state and local public health authorities about suspected cases of smallpox.

State or local health officials should notify the CDC immediately at: 770.488.7100, CDC's Emergency Response Hotline (24 hours), or at (404) 639-2184, (404) 639-0385 if:

• A suspected case of smallpox with request for clinical specimen testing is identified;
• An outbreak of illness that is clinically compatible with smallpox;
• A request to test an environmental sample, package, distribution device or other device associated with potential human exposure for smallpox virus.

Part II. Smallpox Vaccination

The smallpox vaccine contains the "live" vaccinia virus, not dead virus like many other vaccines. Other live virus vaccinations include those for measles, mumps, rubella and chickenpox. "Live" vaccine contains "living" virus that is able to give and produce immunity, usually without causing illness. Smallpox vaccine is a highly effective immunizing agent. When the superficial layers of the skin are inoculated with the vaccinia virus, it grows and induces an immune reaction that protects against smallpox. Vaccinia vaccine enabled the global eradication of smallpox through a focused ring vaccination campaign, intensive surveillance, and contact-tracing (ACIP, 2001).

Smallpox vaccination differs from other vaccines because the "live" vaccinia virus inoculation causes a vaccinia infection on the skin surface. It is important to remember that the vaccinia virus in not the same as variola virus; the vaccine does not contain variola, or smallpox, virus. In order for the vaccination to be successful, a vaccinia infection must occur. This successful vaccination is often called a "take". The vaccination site or "take" requires specific care on the part of the person being immunized, or that person's caretaker.

A number of adverse reactions, as well as secondary infection can occur. Because of these special care requirements and possible adverse reactions, prevaccination counseling is advised prior to immunization (Sibley, 2002) (more information of prevaccination counseling and patient education appears later in this course).

The Smallpox Vaccine

Dryvax is prepared from calf lymph with a seed virus derived from the New York City Board of Health strain of vaccinia virus and has a minimum concentration of 108 pock-forming units (PFU)/ml. Dryvax is a lyophilized (freeze-dried), live-virus preparation of infectious vaccinia virus and must be reconstituted before use. Studies conducted among young adults with no previous smallpox vaccination history showed that a 1:5 dilution of Dryvax (Wyeth Laboratories, Inc.) produced take rates among vaccinees equivalent to those of the undiluted vaccine (Wharton, et. al., 2003). The CDC therefore recommends that the vaccine be reconstituted to a 1:5 dilution; the diluent contains 50% glycerin and 0.25% phenol. The vaccine is packaged in multiple dose vials (100 doses) which, when diluted, will yield 500 doses. The 1:5 dilution is equivalent to full strength in terms of take rates.

Contraindications to Vaccinia Vaccine

This is important in order to avoid accidental transplantation to anyone with contraindications to the vaccine. It is also important to ensure that the vaccinee breaks contact with the susceptible individuals until scar formation, generally in 2-3 weeks, indicating a lack of infectivity. The vaccinia vaccine should not be administered for nonemergency indications if any of the conditions below are present or if the vaccinee will be in close contact with someone, either in their household, or in a healthcare setting, who has one of these conditions.

Please note however, that in the event of a smallpox outbreak where there is a high risk of contact with a patient, these contraindications would not apply. Further information will be provided in the "prevention" section of the progressive vaccinia content.

Eczema or atopic dermatitis and other acute, chronic, or exfoliative skin conditions

• Persons who have ever been diagnosed with eczema or atopic dermatitis should not be vaccinated, even if the condition is not currently active. These patients are at high risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication. Additionally, persons with household contacts that have a history of eczema or atopic dermatitis, irrespective of disease severity or activity, should not be vaccinated.

• If the potential vaccinee or any of their household contacts have other acute, chronic, or exfoliative skin conditions (e.g., burns, impetigo, chicken pox, contact dermatitis, shingles, herpes, severe acne, severe diaper dermatitis with extensive areas of denuded skin, or psoriasis), they are at risk for inadvertent autoinoculation of the affected skin with vaccinia virus and should not be vaccinated until the condition(s) resolves.

• Persons with Darier?s disease can develop eczema vaccinatum and therefore should not be vaccinated.

• The size and extent of the skin disorder may be sufficiently small that vaccination can be safely performed. However, all such patients must be counseled to take great care to avoid any transfer from the primary site to the affected skin. Disruptive or eruptive, for example:
  • Acne
  • Burns
  • Wounds
  • Contact dermatitis
  • Current surgical incisional wounds

Diseases or conditions which cause immunodeficiency or immunosuppression

• If a potential vaccinee or any of their household contacts have conditions such as HIV/AIDS, solid organ or stem cell transplant, generalized malignancy, leukemia, lymphoma, or agammaglobulinemia, they should not be vaccinated. People with these conditions are at greater risk of developing a serious adverse reaction resulting from unchecked replication of the vaccine virus (progressive vaccinia).

• Before vaccination, potential vaccinees should be educated about the risk of severe vaccinial complications among persons with HIV infection or other immunosuppressive conditions; persons who think they may have one of these conditions should not be vaccinated.

• It is also reported that some patients with severe clinical manifestations of some autoimmune diseases (e.g., systemic lupus erythematosus) may have some degree of immunocompromise as a component of the disease. These patients should not receive smallpox vaccine during the pre-event vaccination program.

• ACIP does not recommend mandatory HIV testing prior to smallpox vaccination, but recommends that HIV testing should be readily available to all persons considering smallpox vaccination. HIV testing is recommended for persons who have any history of a risk factor for HIV infection and who are not sure of their HIV infection status. Anyone who is concerned that they could have HIV infection also should be tested. HIV testing should be available in a confidential or, where permitted by law, anonymous setting with results communicated to the potential vaccinee before the planned date of vaccination. Persons with a positive HIV test result should not receive the smallpox vaccination.

• Information about local HIV testing options should be provided to all potential vaccinees, including sites where testing is performed at no cost.

Treatments which cause immunodeficiency or immunosuppression

• If a potential vaccinee or any of their household contacts are undergoing treatment with radiation, antimetabolites, alkylating agents, high-dose corticosteroids (i.e., > 2 mg/kg body weight or 20 mg/day of prednisone for > 2 weeks), chemotherapy agents, or organ transplant medications, they should not be vaccinated. People who are receiving these therapies are at greater risk of serious adverse reactions to the smallpox vaccine.

• People undergoing treatment with high dose corticosteroids, or who have household contacts undergoing such treatment, should not be vaccinated within one month of completing corticosteroid therapy. Persons undergoing other treatments which cause immunosuppression or who have household contacts undergoing such treatment should not receive smallpox vaccine until they or their household contact have been off immunosuppressive treatment for 3 months.

Pregnancy

• Live virus vaccines are generally contraindicated during pregnancy. Pregnant women who receive the smallpox vaccine are at risk of fetal vaccinia. Although this is a very rare condition (fewer than 50 cases have ever been reported), it usually results in stillbirth or death of the infant shortly after delivery.

• Before vaccination, people should be asked if they or any of their household contacts are pregnant or intend to become pregnant in the next 4 weeks; those who respond positively should not be vaccinated. In addition, women who are vaccinated should be counseled not to become pregnant during the 4 weeks after vaccination, and abstinence or highly effective contraceptive measures should be recommended to reduce the risk of pregnancy within four weeks of vaccination.

• Routine pregnancy testing of women of child-bearing age is not recommended.

• To further reduce the risk of inadvertently vaccinating a woman who is pregnant, at the time of pre-screening, women of child-bearing age should be educated about fetal vaccinia, and abstinence or contraception to reduce the risk of pregnancy before or within four weeks after vaccination. Any woman who thinks she could be pregnant or who wants additional assurance that she is not pregnant should perform a urine pregnancy test with a "first morning" void urine on the day scheduled for vaccination. Such tests could be made available at the pre-screening and vaccination sites to minimize cost or access barriers to testing. However, women should be informed that a negative urine pregnancy test cannot exclude a very early pregnancy and therefore they and their healthcare providers should not base a decision about their pregnancy status solely upon a urine pregnancy test result.

• If a pregnant woman is inadvertently vaccinated or if she becomes pregnant within 4 weeks after vaccinia vaccination, she should be counseled regarding the basis of concern for the fetus. However, vaccination during pregnancy should not ordinarily be a reason to terminate pregnancy.

• To expand understanding of the risk of fetal vaccinia and to document whether adverse pregnancy outcome may be associated with vaccination, a pregnancy registry should be maintained and any adverse outcomes carefully investigated.