Minnesota Medicine

Published monthly by the Minnesota Medical Association
February 2002/Volume 85

Vaccines in Public Health Emergencies

By Kristen R. Ehresmann, R.N., M.P.H., and Heidi Kassenborg, D.V.M., M.P.H.

Vaccines have been identified as one of the top 10 public health achievements of the 20th century and are an important resource for the prevention of many diseases.1 They also are a key resource in responding to public health emergencies. Such emergencies may result from natural disease events, such as influenza pandemic, which tends to occur every 30 to 40 years, with the last pandemic occurring in 1968. And the events following September 11, 2001, have led us to realize the importance of vaccines in the face of a new disease threat: engineered public health disasters. This article will address the use of vaccine in pandemic influenza and in the case of a smallpox emergency.

Pandemic Influenza

Influenza viruses, first isolated in 1933, are particularly threatening because of their ability to give rise to a virulent novel strain that can cause sudden illness in all age groups around the world. The influenza viruses (orthomyxoviruses) that produce illness in humans are classified into two main types, influenza A and influenza B. Although influenza A and B viruses regularly cause epidemics, only the influenza A virus can cause pandemics. Influenza A viruses are divided into subtypes based on differences in the surface proteins neuraminidase (NA) and hemagglutinin (HA).2

Influenza viruses undergo two kinds of change, antigenic drift and antigenic shift. During nonpandemic periods, the HA and NA proteins mutate, producing a small change in the virus called antigenic drift. Consequently, new vaccine formulations are needed each year. Pandemic viruses appear by antigenic shift, which is characterized by a dramatic change in the HA and or NA of the virus. This results in a totally new virus for which the population has no immunity. 

Pandemic influenza has been associated with high rates of morbidity and social disruption. Influenza was first described by Hippocrates in 412 B.C., and the first likely influenza pandemic occurred in 1580. Thirty-one likely influenza pandemics have been described since that time. Three pandemics occurred in the 20th century, one of which—the infamous Spanish flu of 1918—was responsible for more than 20 million deaths worldwide, primarily of young adults.3

Planning for Pandemics

The federal government began planning for pandemic influenza in earnest in 1993.4 In 1998, the Minnesota Department of Health (MDH) received a small grant from the Council of State and Territorial Epidemiologists (CSTE) to begin pandemic influenza preparedness planning for Minnesota. The health department convened an all-day meeting of nearly 100 experts, including representatives from hospitals, public health agencies, utilities, schools, and the National Guard. The meeting had a twofold purpose: to educate participants about pandemic influenza and emergency planning and to solicit their input in the development of a draft pandemic influenza plan. Based on the comments and input of this group, a draft plan was developed, which includes a list of groups identified as high priority for vaccinations, such as essential service personnel. The plan was later tested at a tabletop exercise and further revised. A copy of the draft plan, which is a work in progress, can be found at www.health.state.mn.us/divs/ dpc/ades/vpd/pandemic.htm.

Inactivated influenza vaccine has served as the foundation of influenza prevention and control since the vaccine was developed more than 50 years ago. Approximately 90% of all doses given each fall are administered in the private sector; relatively small amounts of vaccine are administered through publicly funded programs. Despite recent frustrations caused by problems with supply and distribution, immunization rates for high-risk populations have improved under this system.

Vaccine Purchase and Distribution 

Because the widespread use of anti-viral agents, such as adamantanes and neuramindase inhibitors, is not likely during a pandemic, vaccination is expected to serve as the primary preventive strategy. However, vaccine delivery during a pandemic will be challenging. The population targeted for vaccination will be expanded to include the entire U.S. population. It is likely that the warning period preceding the spread of the pandemic strain in the United States will be short, which means that vaccine will need to be distributed and administered as quickly as possible. Current influenza manufacturing procedures require a minimum of 6 to 8 months lead time before vaccine is available for distribution. Because a pandemic strain can arise without warning, it is likely that a severe or moderate vaccine shortage will exist early in the pandemic while vaccine is being manufactured. It also might not be possible to produce vaccine in time to address the pandemic. Additionally, immunologic responses following influenza vaccination of unprimed (seronegative) individuals are generally poor, so the emergence of a novel pandemic strain is expected to require two doses of vaccine, with the second dose given 30 days after the first dose.

Vaccine purchase and distribution and the determination of priority groups for vaccination are important issues when considering vaccine use in a pandemic. Although a national decision has not been made regarding vaccine purchase, the Minnesota pandemic influenza plan assumes that if the federal government does not purchase the vaccine, the state will. Given the vaccine delays and distribution problems of the last several influenza seasons, allowing pandemic influenza vaccine acquisition and distribution to be driven by the free market would be unethical. By purchasing all needed vaccine for the citizens of Minnesota, the state could ensure equal access to vaccine, regardless of financial circumstances, and maintain control of vaccine supplies. The state also would consider seeking reimbursement from health plans for the cost of vaccine purchased on behalf of their enrollees. 

The Minnesota pandemic influenza plan calls for public sector distribution of vaccine. This decision has generated much discussion in national circles, because many states are planning for private sector distribution. There are two reasons for the Minnesota decision. The first is security, given the likely shortages and heightened public demand for vaccine. Vaccines will be distributed, stored, and secured at National Guard armories throughout the state. Public sector distribution will ensure equitable distribution to predetermined priority groups. The second reason is the scale of the problem. Even conservative estimates of disease attack rates suggest that private sector health care facilities will be overwhelmed by ill and hospitalized patients. The state public health department is uniquely qualified and prepared to conduct mass immunization clinics, track vaccinations, and ensure that the appropriate individuals are vaccinated.

Determining Priority Groups

Identifying priority groups for vaccination remains the most difficult and controversial aspect of the pandemic influenza preparedness plan. Priority groups will be identified based on a number of considerations, including the need to maintain those elements of the community infrastructure that are essential to carrying out the pandemic response plan; to minimize social disruption and economic losses; to reduce morbidity in the general population; and to limit mortality among high-risk groups. The U.S. Public Health Service, in conjunction with advisory committees, is in the process of formulating a rank-order list of priority groups for vaccination. This list will be modified to meet specific state needs (e.g. individuals involved in snow removal might be essential in Minnesota but not in Hawaii). Once a list is developed, it will be subject to change on short notice since it will need to be adapted to the epidemiologic and clinical features exhibited by the actual pandemic strain (e.g. with a particular strain, young adults rather than the elderly may be at highest risk of severe complications). Minnesota’s draft priority list is included in the state plan and reflects the discussions held by the group of experts.

The success of the pandemic vaccination program will be determined to a large extent by the strength of vaccination programs during periods when pandemics are not occurring. Public confidence in the benefits of influenza vaccine must continue to improve, along with increased emphasis on the use of pneumococcal polysaccharide vaccine (PPV) for those at high risk. The recent emergence of antibiotic-resistant strains of S. pneumoniae and the logistical issues that would preclude concurrent PPV vaccination during an influenza pandemic, highlight the importance of raising PPV coverage levels now.5

Smallpox Vaccination

Until recently, smallpox was considered a disease of only historical interest. Global eradication was achieved through systematic vaccination efforts. The last naturally occurring case of smallpox occurred in Somalia on October 26, 1977. Routine vaccination for smallpox was discontinued in the United States in 1971, and smallpox was certified as eradicated by the World Health Organization (WHO) Assembly on May 8, 1980.6

Following global eradication, all variola virus stocks were destroyed or transferred to one of two WHO reference laboratories (at the CDC in Atlanta, Georgia and the Institute of Virus Preparations in Moscow, Russia). There is concern that the smallpox virus exists in places other than these two laboratories and could be deliberately reintroduced to cause harm. For this reason, increased attention has been given to improving public health preparedness for bioterrorism events and, specifically, for smallpox infection. The CDC recently updated and released an interim plan for the handling of a smallpox emergency.7

An early method for protection against smallpox was first used in India prior to A.D. 1000. Scabs or pustular material from lesions of smallpox patients were used to deliberately inoculate the skin or nasal passage of an uninfected person. This practice, referred to as variolation, produced an infection that was usually less severe than natural infection acquired by droplet inhalation. In 1796, the English physician Edward Jenner demonstrated that material could be taken from a human cowpox lesion and used to inoculate the skin of another person to produce a similar infection. After recovery, the inoculated individual was protected from smallpox.8

Administration

Vaccinia vaccine is used for vaccination against smallpox. Current recommendations for routine, nonemergency smallpox vaccination are limited to laboratory workers who directly handle cultures or animals contaminated or infected with nonhighly attenuated vaccinia virus, recombinant vaccinia viruses derived from nonhighly attenuated vaccinia strains, or other closely related orthopoxviruses that infect humans (e.g. vaccinia, monkeypox, cowpox, and variola). Because of the theoretical risk of infection, vaccination can be offered to health care workers whose contact is limited to materials contaminated with nonhighly attenuated vaccinia virus. Vaccination is not recommended for persons who do not directly handle nonhighly attenuated vaccinia virus cultures or materials or who do not work with animals contaminated or infected with these viruses.9 
Unlike other vaccines, the smallpox vaccine is administered intradermally using a bifurcated needle. Approximately 0.0025 ml of vaccine adheres to the tines of the needle when it is dipped into the vaccine. The needle is held perpendicular to the skin surface, and the vaccine is administered with 15 rapid strokes. These strokes should be vigorous enough to produce a trace of blood at the vaccination site within 15 to 20 seconds. Successful primary vaccination results in proliferation of the virus in the basal cells of the epidermis, producing a vesicular or pustular lesion at the site of vaccination.10

Complications and Contraindications

The frequency of complications associated with the New York Board of Health strain of smallpox that is used for vaccine throughout the United States and Canada, while the lowest for any established vaccine, is not insignificant. Vaccine complications include post-vaccinial encephalitis (1 in 300,000 vaccinations) with a 15 to 25% case-fatality rate, progressive vaccinia, eczema vaccinatum, generalized vaccinia, and other rashes.11 The only product available for treatment of complications of vaccinia vaccination is vaccinia immunoglobulin (VIG). VIG is contraindicated for treatment of vaccinial keratitis (because of the increased potential for scarring), is not effective in treating post-vaccinial encephalitis, and has no role in treating smallpox. Current supplies of VIG are severely limited, and should be reserved for treatment of the most serious vaccine complications, such as eczema vaccinatum and severe generalized vaccinia.

If smallpox exposure has occurred, there are no contraindications for vaccination. All persons with a high risk of exposure to smallpox virus should be vaccinated because their risk for serious disease outweighs their risk for potential adverse reactions to the vaccine. Vaccination administered within 4 days of exposure has been shown to offer some protection against acquiring infection and significant protection against death. 

Nonemergency smallpox vaccination is contraindicated for the following groups of individuals:

1. Persons with, persons with a history of, or persons with household contacts who have a history of eczema or other significant exfoliative skin conditions;

2. Persons with or persons with household contacts who have leukemia, lymphoma, or generalized malignancy or who are receiving therapy with alkylating agents, antimetabolites, radiation, or large doses of corticosteroids;

3. Persons with HIV infection;

4. Persons with hereditary immune disorders; 

5. Pregnant women;

6. Persons with a history of anaphylactic reaction to vaccine components; and

7 . Infants and children.9

The immunity of individuals who were vaccinated prior to 1972, when routine vaccination in the United States was stopped, is uncertain because duration of immunity has not been adequately measured. Persons vaccinated only once are expected to experience waning immunity and lack lifelong protection from vaccination. A study of persons vaccinated three times (at birth, 8 years, and 18 years) showed that they had stable antibody over a 30-year period. However, because very few persons received more than one smallpox inoculation, the U.S. population is considered virgin and without immunity to smallpox.

Supply and Distribution

The current smallpox stores in the United States are limited to a reserve supply of vaccine produced by Wyeth Laboratories in the 1970s. This supply is estimated to be sufficient to vaccinate between 6 and 7 million people. Studies are currently underway to determine whether dilution of the current vaccine will provide sufficient protection and could be a way to increase available vaccine. Supplies of VIG are also limited. VIG has been given in conjunction with vaccination to protect persons in need of vaccination but who are at risk of vaccine-related complications. The United States has established a contract with Acambis Inc. to produce smallpox vaccine in sufficient quantities to vaccinate the entire population. This vaccine is expected to be available by the end of 2002. The current plan does not call for mass vaccination in advance of a smallpox outbreak because the risk of side effects from the vaccine outweighs the risk of someone actually being exposed to the smallpox virus.

The first and foremost public health priority during a smallpox outbreak is control of the epidemic. The focal point of the current smallpox response activities includes “ring vaccination” or what is also referred to as “search and containment.” It is important to note that this method was successfully used to eradicate smallpox from the world. This method was adopted after attempts at mass vaccination failed to eradicate the virus. Ring vaccination involves isolating people with confirmed or suspected cases of smallpox, identifying and locating their contacts, and vaccinating and monitoring a ring of people (including contacts) around each confirmed or suspected case of smallpox. This method forms a buffer of immune individuals and prevents the spread of smallpox.

Like pandemic influenza, the smallpox plan calls for public sector vaccination in part because vaccination is linked to case investigation and disease containment. Vaccination in the public sector will ensure that security is maintained; that vaccine (which comes in 100-dose vials) is not wasted; that distribution is equitable and according to public health recommendations; and that tracking and follow-up occur. 

Successful use of vaccines during a public health emergency requires collaboration between federal, state, and local health authorities as well as local providers. The physician has a key role in educating patients about the plan and rationale for use of vaccines in public health emergencies. The MDH will continue to provide information to physicians to facilitate provider-patient communication. 

Kristen Ehresmann is an epidemiologist and chief of the Immunization, Tuberculosis, and International Health (ITIH) section of the Minnesota Department of Health and is in charge of pandemic influeza planning for Minnesota. Heidi Kassenborg is the state bioterrorism coordinator at the Minnesota Department of Health.

References 

1. CDC. Ten great public health achievements—United States, 1990-1999. MMWR Morb Mortal Wkly Rep. 1999;48:241-3.

2. CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep.2001;50 (No. RR-4):2-3.

3. Oxford JS. Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology, and epidemiology. Rev Med Virol. 2000;10:119-133.

4. Centers for Disease Control and Prevention. Pandemic influenza: a planning guide for state and local officials (draft 2.1). Available at www.cdc.gov/od/ nvpo/pandemicflu.htm.Accessed Jan. 11, 2002.

5. Butler JC, Dowell SF, Breiman RF. Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention. Vaccine. 1998;16(18):1693-7.

6. World Health Organization. The global eradication of smallpox. Final report of the global commission for the certification of smallpox eradication. In History of International Public Health No. 4. Geneva, WHO, 1980.

7. CDC. Interim smallpox response plan and guidelines. Available at: www.bt.cdc.gov/DocumentsApp/Smallpox/RPG/index.asp. Accessed Jan.11, 2002.

8. Henderson DA, Moss B. Smallpox and Vaccinia. In Plotkin S, Orenstein W, eds. Vaccines. 3rd ed.W.B. Saunders Company. 1999:74-97.

9. CDC. Vaccinia (smallpox) vaccine: recommendations for the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Morb Mortal Wkly Rep. 2001;50 (RR-10):1-26.

10. Henderson DA, Ingelsby TV, Bartlett JG, et al. Smallpox as a biological weapon: Med and Public Health Manage. JAMA.1999;281:2127-37.

11. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970;122:303-9.