Mass smallpox immunization program in a deployed military setting

Abstract

A prospective, observational study of immunizing over 6,000 active-duty troops against smallpox in a 4-week time period was conducted. It focused on the complications of the vaccine and lost workdays. Comparison is made to the complication rates of earlier smallpox immunization programs. In direct response to elevated bioterrorism concerns, the United States military and civilian first-responders have begun a mass smallpox immunization program. This article reviews the experience with implementing such a program in a forward-deployed location while maintaining military readiness. The objectives were to assess the impact of a mass smallpox immunization program on operations in a forward-deployed military setting and to comment on lessons learned in the screening and immunization process. From January 16, 2003 through February 11, 2003 6,002 members of the United States military were immunized in a forward-deployed location. Information was obtained using data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan to calculate the following Main Outcome Measures data: (1)Percentage of individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC criteria, (3) Number of serious complications, (4) Number of life-threatening complications, and (5) Number of manpower days lost as a complication of the vaccine. A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. The "take" rate for the vaccine was 98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The immunization program produced an additional 156 medical visits (2.6% of patients required one visit). A total of 0.55% of immunized individuals lost one or more work days. In conclusion, a mass smallpox vaccination program can be effectively administered in a forward-deployed military setting despite high tempo military operations with minimal operational impact.

Complication	Ten State Survey	Rate per Million	Rate Expected at PSAB	Rate Observed at PSAB
Inadvertent inoculation	532	3.2	None
Generalized vaccinia	222.8	1.4	None (2 Cases later deemed probable EM)
Erythema multiforme	131.3	0.78	2 Presumed
All nonlife-threatening complications	935.3	5.6	None
Postvaccinal encephalitis	8.6	0.05	None
Progressive vaccinia	1.7	0.01	None
Eczema vaccinatum	41.5	0.25	None
Total life-threatening reactions	52.3	0.31	None
Death	1	0.006	None

TABLE 1 - Estimated Rates of Complications

The political and military landscape of the United States was changed forever with the terrorist bombings of September 11th and the anthrax bioterrorism of 2001. In an effort to confront the terrorism threats, President George W. Bush instituted a mass smallpox vaccination program on December 13, 2002. The program included members of the military and civilian medical first responders. This decision came during a time of increased operational tempo and a massive deployment of military members to forward-deployed locations in preparation for possible military conflict in the Middle East. This placed a seemingly enormous task on the field medical services. The smallpox immunization program as directed by the Department of Defense required that each individual be briefed on smallpox and the vaccination program and be fully screened for medical contraindications. Each qualified individual would be vaccinated and then re-evaluated in 6 to 8 days to determine if an adequate local response had occurred.

This study evaluates the implementation of this program at one forward-deployed military setting and how it affected the military operations.

Methods

This prospective observation study used data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) from January 16 through February 11, 2003, we calculated the following data:

1. The percentage of individuals eligible to receive the vaccine

2. The take rate for the vaccine

3. The number of medical and administrative exemptions

4. The number of serious, but non-life threatening complications

5. The number of life-threatening complications

6. The number of patient care visits due to the vaccine

7. The number of manpower days lost as a complication of the vaccine.

No patient identification was used in this study. The summary reports from the tracking applications listed above do not generated specific patient information in the summary reports. The medical encounters all involved the patient being evaluated by a licensed physician who determined if the patient's symptoms and time course relative to their vaccination supported the symptoms being due to the smallpox vaccine. All physicians were educated using the clinical criteria from the CDC website to determine confirmed, probable or suspected vaccinia complications.

Demographic data

No individual demographic data were obtained. The patients were all between the ages of 18 and 54, but no analysis of age distribution was possible. All of the individuals met their military service specific medical requirements to be eligible to deploy which ensures a healthy population. All of the individuals were screened for the following relative smallpox vaccine contraindications:

1. Pregnancy

2. History of adverse reaction to previous smallpox vaccine

3. History of atopic dermatitis or eczema

4. Active skin lesions of: psoriasis, acute burns, impetigo, uncontrolled acne, varicella

5. Immune deficiencies: leukemia, lymphoma, cancer, HIV, rheumatoid arthritis, Crohn's disease, lupus, hepatitis, organ/bone marrow transplant, immune altering medications

6. Return to home with a family member with any of the above contraindications in the next 21 days

7. Allergy to tetracycline, streptomycin, polymyxin B, neomycin or latex. (the vaccine contains trace amounts of these antibiotics and the allergy to latex is to alert the individuals giving the vaccine not to wear latex gloves.)

Results

A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. There were 355 (5.3%) individuals who were medically excluded. The most common exclusion was a history of atopic dermatitis. There were 36 (0.7%) individuals who were administratively excluded because they would be returning home to a family member with a contraindication in less than 21 days. A total of 6,002 (95%) of the 6,328 received the vaccine. Three hundred forty-six (5%) had not yet presented for their immunizations. The "take" rate for the vaccine was 98.6%. The immunization of 6,002 individuals produced an additional 156 medical visits (2.6% of patients required one visit). In total, 52 manpower days were lost. This equates to 0.009 workdays lost per individual immunized. Two inpatient hospitalizations accounted for 19 of those 52 days. All of the individuals who missed work due to the vaccine were absent for 24 hours or less. Only 5 manpower days of operational flying duties were lost. There were 32 patients who presented with a rash after the vaccination (0.5% of all vaccine recipients and 20.5% of all individuals who presented for medical concerns status postvaccination). The majority of these rashes were maculopapular. Urticarial lesions with intense pruritis were seen in 12% of the patients who developed rashes, but no life-threatening urticaria was noted. A few patients displayed significant viral lympangitis. No cases of inadvertent inoculation or erythema multiforme were identified. There were 2 patients (0.005%) with generalized vaccinia. Both of these patients recovered fully and did not require aeromedical evacuation from our facility.

There were no cases of life-threatening illness due to the vaccine such as postvaccinal encephalitis, progressive vaccinia or eczema vaccinatum.

Comment

Smallpox is one of several biological agents which can be weaponized and used both as an offensive weapon as well as a weapon of bioterrorism. Several nations are suspected of retaining smallpox for use as an offensive weapon, including Russia, the United States, Iraq, and North Korea, according to Jonathan Tucker, a senior fellow at the United States Institute of Peace. The Iraqi government is known to have worked with camel pox as a biological warfare agent. Elaborate models have been developed to assess how effective smallpox would be as a biological weapon or a weapon of biological terrorism. Some have found that mass immunization along with surveillance and vaccination of contacts is an effective strategy.1 Others models have had conflicting results.2

On December 13, 2002, President George Bush announced a national plan that focused on vaccinating military members and civilian "first responders" to neutralize the threat of smallpox as a bioterrorism weapon. In the first phase, all the active duty members were screened for atopic dermatitis and other relative contraindications for the vaccine. Based on the literature, it is generally expected that the prevalence of atopic dermatitis is approximately 10% to 15% in the general population.3 Some recent literature has speculated that up to half of the general population may be excluded due to having a history of atopic dermatitis or living with someone who has such a history.4 The military population is quite different from the general population. Military populations are primarily young and healthy individuals who have been medically screened before being accepted into military service.

We can roughly extrapolate from vaccinia vaccination complication rates from the United States, published in 1968, to what number of complications would be expected at our location.1,2 These estimates are limited by several factors. The data from 1968 involved a universal immunization program without screening. Our population was screened for vaccine contraindications using a DoD overprint form 600.5 Also, a review of the literature with analysis of individuals responsible for the transmission of vaccinia causing secondary cases in the 1964-1968 period indicated that 63% were younger than 4 years of age.6 Our population age characteristics are obviously quite different from the civilian population of the United States in the 1960s.

Using the estimated population, we can roughly summarize the estimated rates of complications (see Table 1).

Simply stated, based on the 10 state surveys we would have expected 2 to 3 cases of inadvertent inoculation, 1 to 2 cases of generalized vaccinia, 1 case of erythema multiforme, no life threatening complications and no deaths attributed to the vaccine.

Our results showed only 2 serious but nonlife-threatening complications, both of which were presumed to be generalized vaccinia. Neither individual had any relative contraindication to the vaccine or any relevant family history. Only 1 of the patients developed noticeable scarring to the sites of his lesions. Unlike smallpox, however, these lesions spared the face and did not produce cosmetic disfigurement. The scarring was noted only on the chest and arms. Our 2 patients differ from the published literature profile in that most cases of generalized vaccinia in the literature occurred among young children. There was one case report of a military recruit with generalized vaccinia who was found to have undiagnosed HIV.7 Both of our patients were negative on screening tests for HIV. Both patients recovered fully and neither required return from our deployed setting.

Our experience shows that it is quite feasible to institute a mass smallpox-screening program in a forward-deployed setting without significant impact on the medical resources and without significant interruption of military operations. We experienced only a minimal workforce loss during the immunization of more than 6,000 individuals. Our population characteristics are quite different from the general United States population, which limits the comparison to the 10 state surveys. However, the reduced rate of complications does appear to indicate that screening decreases the complication rate from the vaccine. It should also be noted that our population is similar to the population of first responders and emergency physicians who are called on to take this vaccine. The possible association between cardiovascular events and the smallpox vaccine are also worrisome.

There has been reluctance shown by physicians and first responders who have been asked to submit to this vaccine. Much of these concerns are based on the complication rates documented in the smallpox immunization program in the 1960s. Much is also related to the complications noted in the number of civilians immunized in the United States since President Bush directed the nation to start the immunization process again. The CDC reported that there were 25,645 people immunized as of April 14, 2003 with 29 cases of inadvertent inoculation, 10 cases of myopericarditis, 8 cases of generalized vaccinia, and 2 cases of ocular vaccinia. The issues related to a possible link to ischemic heart disease are also quite troubling. The concerns over vaccination have not been helped by the delay in discussing a vaccine compensation package by the federal government for individuals who experience these complications. At the time this manuscript was submitted for publication the federal government's approach was outlined by Stewart Simonson, JD, a member of the Department of Health and Human Services' General Counsel's office.8 He provided the following input:

If the physician dies, the family may sue the federal government in federal court.

If the vaccinated physician accidentally transmits the vaccinia to a family member, the government provides presumptive liability and the family member can sue the federal government.

If the physician becomes ill and cannot work for several days or months, the physician's own health plan, workman's compensation, and/or personal disability would cover lost wages.

If the physician were permanently disabled, the physician's private disability policy, workman's compensation, social security disability payments, and eventually Medicare payments would provide compensation.

This approach has done little to allay the fears of medical personnel tasked with risking their own health for the sake of the national emergency medical response capability. As our study shows the risks of the smallpox vaccine, however, may be significantly less than that experienced in the 1960s. The studies were done when the vaccine was administered to an unscreened population. The experience of the Israeli Defense Forces in the 1990s shows a significantly reduced rate of complications in individuals who are properly screened.9 It should be noted that the Israeli's defense ministry used a different smallpox vaccine.

In summary we found that a mass smallpox immunization program could be accomplished with minimal impact on our military mission despite the base having a high operational tempo. It shows that the rate of complications in a properly screened population is lower than expected based on the data from the 1960s. This may be quite significance to many physicians and first responders as they decide whether or not to volunteer for this vaccination.

Acknowledgements

This work benefited greatly from the assistance of the 363EMDG, Prince Sultan Air Base, Kingdom of Saudi Arabia.

References

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Bozzette SA, Boer R: A Model for a Smallpox-Vaccination Policy . N Engl J Med 348 (5): 2003.

Schultz Larsen F, Hanifin JM: Epidemiology of atopic dermatitis . Immunol Allergy Clin North Am 22 1-24, 2002.

Engler, Kenner and Leung . J Allergy Clin Immunol 110 (3): 357-365, 2002.

US Army Vaccination Website: 2003. Available at http://www.smallpox.army.mil/ (2 page short screening form). Accessed June 23

Neff JM, Lane JM, Fulginiti VA: Contact Vaccinia-Transmission of Vaccinia From Smallpox Vaccination . JAMA 28815 1901-1905, 2002.

Redfield RR, Wright DC, James WD: Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease . N Engl J Med 316 673- 1987.

American College of Emergency Physicians Website: 2003. Available at http://www.acep.org/1,32610,0.html. Accessed June 23, 2003

American College of Emergency Physicians Website: 2003. Available at http://www.acep.org/download.cfm?resource=775. A report by Leonard Marcus, PhD, of the Harvard School of Public Health published on the ACEP website. Accessed June 23