Poxviridae disease

Objective: To determine the feasibility of implementing a smallpox vaccination program aboard an aircraft carrier in conjunction with anthrax vaccination. Methods: Retrospective review of smallpox vaccination program conducted from January 17, 2003 to February 19, 2003. Morbidity and loss of manpower were the major endpoints. Results: There were 5,204 sailors available for vaccination. There were 243 (4.7%) medical exemptions and 24 administrative exemptions. During the program, 4,931 sailors were vaccinated. There were five reportable complications. Three sailors had autoinoculation, one sailor had localized cellulitis, and one patient had a positive [beta] human chorionic gonadotropin during vaccination. None of the complications required medical evacuation. Only two sailors required time off from duty. Conclusions: Smallpox vaccination can be accomplished rapidly and safely aboard an aircraft carrier. There was not an increase in adverse events compared to historical data despite the close-quarter conditions. Smallpox and anthrax vaccinations can be completed simultaneously with minimal morbidity.

Introduction

On December 13, 2002, the President of the United States implemented a nationwide smallpox vaccination program in response to events occurring in September and October 2001.1 Although smallpox was declared eradicated from the earth in 1980 by the World Health Organization, stores of the virus that cause smallpox, variola, remain.2 The President's directive reflected the threat to troops stationed abroad and at sea from bioterrorism. To our knowledge, there has never been a smallpox vaccination program initiated and completed on an aircraft carrier. Although we had recent experience with anthrax vaccination, the risks posed by a live-virus vaccine, including autoinoculation and contact transmission, were obvious. This report is an account of our planning and implementation of a smallpox vaccination program, with particular emphasis on the actual vaccination schedule and major adverse events. Lessons learned on wound care and adverse event prevention are discussed.

Background

It is speculated that smallpox began around 10,000 BC with the first agricultural settlements. Written descriptions of the disease first appeared in 4th century AD China and by the 16th centuiy, smallpox had spread to the Western Hemisphere, where it decimated American Indian tribes such as the Aztecs and Incas.3 Humans are the only known reservoir, with transmission usually accomplished by direct face-to-face contact. Infection caused by indirect contact, through blankets and other fomites, is rare.

Vaccination programs began in India around 1000 AD. At that time, material from smallpox scabs was inoculated into skin or nasal passages. It was noted that the ensuing infection was less severe than primary smallpox infection and conferred immunity against further attacks. This process of using pustular or scab material was called variolation. In 1796, Edward Jenner was credited with developing the process we know today as vaccination.4 Using cowpox virus, material was injected into the skin of individuals and it conferred smallpox immunity. Cowpox and vaccinia virus are members of the Orthapoxuirus genus, Poxviridae family. Immunity is conferred to all members of the family, including variola, which causes smallpox. Vaccinia eventually became the primary virus used for smallpox vaccination. It was grown and harvested from calf flanks, creating a more readily available supply of vaccine. Methods for developing a stable, long-lasting vaccine were started in the 1940s and were perfected by Collier.3 Routine vaccination was stopped in the United States in 1971, except for certain medical personnel and the military. Military personnel stopped receiving the vaccination in 1990, although some branches stopped sooner. As of 1985, there were only two stockpiles of variola virus: one in the USSR and one in the United States. There is concern today that stockpiles of variola might exist outside these locations and may be used as a weapon of bioterrorism.

The symptoms of smallpox vary depending on the stage of infection. In the first stage, which usually begins anywhere from 7 to 17 days after exposure, the patient experiences fever, malaise, and headache. A maculopapular rash appears soon afterward. This rash develops into the classic papulovesicular rash, which scabs over after about 1 week.5 The rash has a typical spread from the face, oral cavity, and forearms to the trunk and legs. This is known as centrifugal spread. all of the lesions are usually in the same stage of development, in contrast to varicella, which causes chickenpox. Once the scabs fall off in 3 to 4 weeks, the patient is no longer infectious. The greatest risk of spread comes when the lesions in the oral cavity ulcerate, causing a large load of virus to be concentrated in the saliva. This usually occurs when the rash first appears. This can then be spread to other persons through coughing and direct face-to-face contact.

The mortality rate from previous studies is approximately 30% for the typical forms of smallpox. Rare forms of smallpox, flat-type and hemorrhagic, may have a higher mortality. Treatment usually involves isolation, supportive care, and early vaccination if known exposure has occurred. Newer therapies, including the antiviral drug Cidofovir, are being tested. Vaccinia immunoglobulin has no efficacy against active smallpox.2

Methods

The message to implement the smallpox vaccination program was received on January 9, 2003.6 It was recommended that vaccinations commence by January 15th. Our first step was to educate our medical department on the risks of smallpox and the vaccine. Medical personnel were an obvious choice as the first to be vaccinated, as we could gain experience with the process and provide medical care in the event of an actual smallpox attack. The current vaccine in use is the Dryvax vaccine by Wyeth Laboratories (Marietta, PA). This vaccine is approved by the Food and Drug Administration and is made from dried calf-lymph virus. Because it is a live-virus vaccine, the risks of autoinoculation and direct transmission are greater than other vaccines. Information was obtained from the Department of Defense (DOD) website, and videos created for health care providers by the Centers for Disease Control were reviewed. Once appropriate education of the medical department was performed, the appropriate two-page prescreening questionnaire was completed and the medical department vaccinated. This was accomplished on January 17th, 1 week after we had been given the implementation message. The corpsmen and providers who were designated to give vaccinations observed three vaccinations and then performed three vaccinations under supervision. At this point in time, we used common adhesive bandages and dry gauze with tape to cover the wounds. During this time, we also vaccinated the dental department, who are our triage officers in mass casualty events.

We had three major objectives to achieve before vaccination: to educate the crew on the vaccination process, to design a system of vaccination that would cause the least disruption in carrier operations, and to locate appropriate medical facilities in the case of adverse events.

The education process began with a live television presentation that was introduced by the Commanding Officer. The Commanding Officer and the Command Master Chief were vaccinated during this program and then a 1-hour presentation was given. The presentation was simple in nature, explaining the fact that the smallpox vaccine had been present for many years and that the vaccine was the same one used by the U.S. military in the past. A Power Point presentation edited from the one provided by the DOD web site (www.smallpox.army.mil) was then shown. This video presentation was shown throughout the week in preparation for the actual vaccination process. On the same day as the television program, a StarScope article (Constellation newspaper) was distributed, explaining the myths of smallpox vaccination and expected side effects. The last part of the educational process was a one-page handout provided by the DOD, which was attached to the two-page prescreening form provided from the website. A departmental representative who was responsible for all paperwork in each department picked up the forms. We felt this would minimize the paper trail and prevent sailors who might not be vaccinated for weeks from losing their prescreening forms. These handouts/prescreening forms were dispersed on January 20th, the same day the television program aired and newspaper article ran.

The screening process began after the sailors had 48 hours to read the forms carefully and review the video and newspaper article. They were then instructed to return the forms to their departmental representative. Those sailors who answered "yes" to any of the prescreening questions were instructed to report to medical during a specifically designed screening clinic. Their medical charts were reviewed, a physical examination was performed, and a decision was made as to whether or not they should be vaccinated. Most exemptions from vaccination were sailors who had chronic skin conditions such as psoriasis, severe acne, eczema, or atopic dermatitis. The medical exemptions were in accordance with the Advisory Committee on Immunization Practices and the Health care Infection Control Practices Advisory Committee.5 We also had several sailors who were exempt because of unknown human immunodeficiency virus (HIV) status. We used guidelines provided by Commander, Naval Air Force, U.S. Pacific Fleet for HIV status. If the patient had a negative HFV test within the past 2 years and a test drawn within the last year, we proceeded with vaccination if there was no other contraindication. If the sailor reported contact with a possible HIV-positive patient, we erred on the side of not vaccinating until documentation of status could be provided. Administrative exemptions included reasons such as retirement within 30 days or reservists going to nonparticipating individual ready reserve units. The prescreening process lasted 3 days, with immunizations beginning on the January 25th.

We made the decision to complete the vaccination program over 4 weeks to minimize the impact on each department. We also decided to vaccinate the crew by rank, starting with officers and Chief Petty Officers (CPOs). Many of the officers and CPOs had received the vaccine before. This would hopefully provide a good example for the younger sailors who had never received a vaccine of this type. The ranks were divided as follows: Officers and CPOs, E6-E5, E4s, and El-ESs. Laundry personnel and those sailors working in exercise facilities were vaccinated during the first wave with the officers and CPOs. The only exceptions to this schedule were pilots and flight officers, who were allowed to come down several at a time throughout the 4-week period to minimize any possible downtime in flying. This decision was made after consultation with the Carrier Air Wing Commander, who was coordinating efforts in Operation Southern Watch. Three to 4 days were allowed for each rank, with one "night-check" vaccination provided for the night crew during the 3- to 4-day period. Each vaccination cycle lasted 4 to 5 hours. The night check period lasted only 2 hours.

Exercise areas were provided with common cleaning disinfectants that were to be used after each exercise evolution. Bleach solution was unavailable on the ship. Sailors were instructed to spray the equipment with disinfectant and then wipe it down with paper towels before the next person used the machine. No one was allowed into the gym without a towel, a dressing on his or her vaccination site, and a T-shirt with sleeves.

Although it was initially recommended to us that medical exemptions be berthed in separate living areas, we decided not to separate the exemptions unless they specifically requested moving. This was done for two reasons. First, living spaces on the ship were extremely limited because of civilian and media personnel onboard. Second, there was strong input from the departments that the sailors did not want to be moved from their berthing mates, who they had come to know and live with over the course of the deployment. We felt that proper hygiene and contact precautions could prevent any unwarranted contact transmission, but if the sailors desired, they could move their rack to a separate part of the berthing. This was coordinated by the Leading Petty Officers of each division. Sharing of bunks, clothing, and laundry was discouraged.

We did not dedicate any specific waste receptacles for the disposal of bandages and dressings. We instructed the crew to dispose of bandages in common paper trash bags and to immediately wash their hands afterward per instruction from the Navy Environmental and Preventive Medicine Unit.

On the day of vaccination, sailors obtained their prescreening and vaccination forms from their departmental representative and reported to the hangar bay. The schedules were posted on the Plan of the Day and also announced over the 1MC announcing system at the beginning of the vaccination period. A schedule was also given to departmental CPOs to encourage departmental accountability.

At the vaccination area, two health care providers reviewed the prescreening forms and decided whether the sailor was to receive three or 15 punctures. Sailors with no previous history of vaccination were given an initial three punctures. When there was a question of possible previous vaccination, for example, a sailor born in the Philippines or South America, but who could not recall vaccination, 15 punctures were given. All efforts were made to evaluate the patient's arms for Jennerian scars. The sailor then reported in assembly-line fashion to the vaccination table where he or she was vaccinated. He/she then received a supply of bandages, forms were turned in, and further instruction on hygiene and local wound care was given at the last station. The process took about 5 minutes after being screened by the provider. The sailors were instructed to return in 7 days for a site check and to fill out the follow-up sheet provided by the DOD at that time. Paperwork for the vaccinations was handled by the Preventive Medicine Department for ship's company and by squadron corpsmen for the airwing.

The dressing we chose was a self-adhesive 2- × 3-in coverlet bandage, which in actuality is a large self-adherent bandage. We felt this would stay on the vaccination site despite the activity and sweating experienced by many of the crew. Sailors were instructed to change the bandage at least once daily, usually after showering. When a well-formed scab was noted, they were instructed to leave bandages off and keep the site covered with a t-shirt. The usual precautions of not touching the vaccination site and proper hand washing were reinforced. Appropriate military facilities for treating complications requiring medical evacuation were identified.

Results

The vaccination program lasted 26 days. Four of these were for the second dose of anthrax, 2 days were "off " days for the vaccination crew, and 5 days were in port. Thus, there were 15 actual vaccination days for the crew other than medical and dental. There were 5,204 sailors available for vaccination. We vaccinated 4,931 sailors during the program. There were 243 (4.7%) medical exemptions, 9 of which were temporary and 24 administrative exemptions, for a total of 267 exemptions. One sailor refused vaccination. Three sailors were lost to follow up during the vaccination program because of Permanent Change of Station orders.

The vaccination cycles usually saw the most people on the first and second days, usually around 350 to 400 a day. Thereafter, the numbers dropped significantly. On average, 329 sailors were vaccinated per day. Four to 5 hours a day was more than adequate time, and we could have vaccinated close to 600 during this 4- to 5-hour period.

Complications and side effects were rare. The most common side effect seen was a "flu-like" syndrome on days 6 to 9, which usually consisted of low-grade fever, malaise, and body aches. Axillary and supraclavicular lymphadenopathy were also common. This is consistent with previous reports.7 Severe fatigue was noted among a large portion of the crew, although only two sailors required Sick-In-Quarters because of illness. No aviators were grounded during the program. However, there was a mandatory 24-hour grounding for pilots and flight officers immediately after the vaccination per instruction from the DOD. Data on common side effects was hard to track because of the nature of the follow-up survey. The survey was somewhat confusing to many of the sailors and we gained little additional insight into problems from the vaccination. A macular and sometimes vesicular rash was often seen at about 1 week after vaccination. This rash usually appeared on the arms and upper torso, was nonpruritic, and usually disappeared in 48 hours. An estimate would be that 10% of the crew had some type of benign rash that resolved in 1 to 2 days occurring about 1 week after vaccination.

We had five reportable adverse events. The first patient was a 32-year-old Caucasian man who presented with erythema and swelling around the vaccination site on postvaccination day 9. This patient had a history of documented, recurrent methicillin-resistant Staphylococcus aureus cellulitis previously requiring Vancomycin. He was initially observed for 48 hours under the diagnosis of a "robust" take. After the brief observation, he was given oral Cephalexin. He subsequently was started on 1.0 g of Vancomycin intravenously bid and the cellulitis resolved.

The second patient was a 26-year-old Caucasian woman who was found to have a positive [beta] human chorionic gonadotropin 3 weeks after vaccination. She had a negative [beta] human chorionic gonadotropin 1 day before vaccination. As of this report, there is no evidence of complication to the fetus. She was given counseling on close monitoring of the pregnancy and has since been transferred to another command.

The third complication was a 22-year-old Caucasian man that had apparent autoinoculation to the left groin. he presented 9 days postvaccination. The lesions were painful and in a dermatomal distribution in the S1 area. The lesions spared the scrotum and involved the left crural fold. He was admitted to the ward, started on acyclovir with a tentative diagnosis of herpeszoster versus autoinoculation. The lesions were similar in appearance to the arm lesion but more exudative. He recovered after a 4-day hospitalization and required no further treatment. The acyclovir was stopped after 3 days. The lesions are pictured in Figure 1.

The fourth complication was a 28-year-old Caucasian man with possible groin autoinoculation. The original diagnosis was folliculitis. The patient related meticulous care of his vaccination site and had only one lesion in the area. This responded to conservative therapy and did not look similar to his vaccination site, but was reported because of the timing of the lesion. The lesion is pictured in Figure 2.

Satellite lesions underneath the dressing were noted. An estimate based on the follow-up site check is that 2% of the crew had satellite lesions. Most of these were self-limited and resolved without incident. When severe, sailors were instructed to report to the emergency room daily for a gauze dressing to allow the vaccination site to dry and heal faster. Our fifth complication had autoinoculation to his left ear after he was noted to have significant satellite lesions underneath the dressing. He reported changing the dressing every 3 days. His lesions also resolved without incident. This patient was a 30-year-old African-American man and the satellite lesions on his arm can be seen in Figure 3.

The bandages we chose created a localized dermatitis in a large percentage of the crew, approximately 50%. This resolved once the bandages were removed, but were a source of severe pruritis and discomfort for many. A picture of one of the more severe cases of dermatitis with fibrin deposition can be seen in Figure 4.

At the beginning of the program, there was some confusion about how many revaccinations should be attempted. At first, we were giving two revaccinations of 15 punctures for anyone who failed their primary vaccination. This was subsequently modified to only one revaccination dose of 15. The original message from the DOD was interpreted to mean that the patient should get two revaccinations after a failed first attempt. Information from our Environmental and Preventive Medicine Unit subsequently led us to revaccinate only once. Therefore, several of our sailors received more punctures than necessary.

Overall, we revaccinated 142 sailors out of 4,931 vaccinations (2.9%). Ship's company data were complete as to cause and number of revaccinations, and was therefore analyzed for the purposes of this paper. There were 100 revaccinations among 3,040 ship's company (3.3%). The average age of those revaccinated was 28. Data for ship's company revaccinations are presented in Table I.

Of the 33 patients (33%) with no or equivalent responses, 10 of these were patients who had previous vaccinations and therefore were likely immune. The previous vaccination was discovered after more intensive examination and questioning at the revaccination follow-up. Therefore, only 23 (23%) of 100 revaccinations had no response with no previous history of vaccination. Of the 19 patients who started with three punctures and who were revaccinated twice, eight (42.1%) had "major takes" after their second dose of 15 punctures.

Of the two patients who started with 15 punctures and were revaccinated twice, there were no major takes. Our overall major take on first vaccination was 97.1%.

Discussion

The goal of our vaccination program was to quickly vaccinate the crew against smallpox with minimal morbidity. Although, historically, the rate of major complications for all first-time vaccinnees is 125 events of 100,000 vaccinations (0.13%), we expected more on the aircraft carrier because of the close living conditions.8 Multiplying this percentage times the 5,204 personnel on board would give an expected seven major complications. From the above report, we expected that approximately 30% of the crew would get a "flu-like" syndrome at about 7 to 9 days postvaccination, with 21% seeking medical attention. Our experience with smallpox vaccination was similar to this. Our major complication rate was 0.10%.

Data regarding contact transmission from vaccinia have been well described by Sepkowitz.9 In his review of contact transmission, he noted only 85 reported cases of nosocomial spread and 27 cases of spread within families. Most cases occurred among young children living in the same household. Other reports confirm the finding that secondary transmission occurs infrequently, especially in adults. Data from the 1960s revealed a contact transmission rate of 2 to 6 events per 100,000 vaccinations.10 Although we did not actually segregate the 243 medical exemptions, we had no reportable direct transmissions. If a sailor was berthing with someone who had a contraindication to vaccination, precautions to not share bunks, clothing, or laundry were reinforced.

The usual sites of autoinoculation include the eyes, genitals, face, and rectal area. The inadvertent inoculation rate from previous reports noted 529 autoinoculations out of 1,000,000 first-time vaccinees for an incidence of 0.05%.B Therefore, we should have expected roughly three autoinoculations, which is what we reported. We had no ocular implantations and none of the autoinoculations required transfer off the ship.

Approximately 10% of the crew had a benign rash that appeared anywhere from 5 to 9 days after vaccination. This was usually maculopapular or vesicular and was usually noted oh the chest, shoulders, and back. This benign rash was also noted by Frey et al.7 who reported that 14.3% of their 665 vaccinees had a rash at sites other than vaccination.

Dermatitis at the bandage site was our most common complication. A combination of the adhesive on the bandage and moisture likely led to the dermatitis. Most often, the sailors would have a square, eiythematous, pruritic area where the dressing was located. The dermatitis resolved after the bandages were removed. In retrospect, we might have chosen a different dressing. Although some sources recommend placing no dressing on the site, most of our sailors wanted to wear a dressing for fear of contamination and autoinoculation.

In summary, our vaccination program went smoothly with few complications. Most of our problems were from local reactions to dressings and the expected flu-like syndrome after vaccination. We were able to complete the anthrax vaccination program in conjunction with the smallpox program without untoward effects. From our experience, we would probably do some things differently in the future. We would recommend vaccinating the crew over a shorter period of time, as the side effects and downtime we experienced were minimal. We would also suggest having one or two persons in charge of vaccination paperwork to assist with data analysis. We like the idea of vaccinating by rank. Although it is unclear if this helped decrease the actual number of adverse events, it did allay many of the fears the younger sailors had upon commencement. We hope this data provides some insight for future vaccination programs aboard aircraft carriers.

Acknowledgments

We thank the efforts of the following individuals in the preparation of this article: HMCS Jose Mendez, USN, and LT David Groom, MSC USN. In addition, we thank all corpsmen of the USS Constellation for their efforts in the vaccination program.

References

1. Presidential Directive: Commencement of Smallpox Response Plan. December 13, 2002.

2. Breman JG, Henderson DA: Diagnosis and management of smallpox. N Engl J Mecl 2002; 346: 1300-8.

3. Henderson DA: Smallpox and Vaccinia in Vaccines, pp 8-30. Philadelphia, PA, W.B. Saunders Company, 1988.

4. Jenner E: An inquiry into the causes and effects of the variolae vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and known by the name of the cowpox. London, 1798. [Reprinted in Classics of Medicine and Surgery. Edited by Camac CNB. New York, Dover, 1959.]

5. Centers for Disease Control and Prevention: Vaccinia [smallpox] vaccine: recommandations of the Advisory Commitlee on Immunization Practices [ACIPl, 2001. Morb Mortal WkIy Rep 2001; 50: 1-25.

6. NAVADMIN 007/03. January 9, 2003.

7. Frey SE, Couch RB, Tacket CO, et al; Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med 2002; 347: 1265-74.

8. Lane J, Ruben F, Neff J, Millar J: Complications of smallpox vaccination, 1968: results often statewide surveys. J Infect Dis 1970; 122: 303-9.

9. Sepkowitz KA: How contagious is vaccinia? N Engl J Med 2003; 348: 439-46.

10. Neff JM, Lane MM,Fulginiti VA, HendersonDA: Contact vaccinia-transmission of vaccinia from smallpox vaccination. J Am Med Assoc 2002; 288: 1901-5.

Guarantor: LT Jeff Apple, MC USNR

Contributors: LT Jeff Apple, MC USNR; LTJG Patrick Hare, MSC USN; LT Chris Crerar, NC USN; LT Errika Walker, MC USNR; LT Joe Wilson, MC USNR; LT Christin Brown, MC USNR; LT Kennett Moses, MC USNR; HMC Thomas Hendrickson, USN; HM1 Daniel Field, USN; HM2 Francis Hoffman, USN; HM2 Patrick Pedrus, USN; CAPT John Miller, USN; CDR Brad Smith, MC USN

USS Constellation, Medical Department, San Diego, CA, FPO AP 96635-2780.

This manuscript was received for review in April 2003 and accepted for publication in June 2003.

Reprint & Copyright © by Association of Military Surgeons of U.S., 2004.

Copyright Association of Military Surgeons of the United States Jun 2004
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