Urticaria pigmentosa

The aim of the present study was to assess the post-smallpox vaccination complication rate in a cohort of Israel Defense Force recruits enlisted in the calendar years 1991 to 1996 and to compare it with rates reported, in similar age groups, in large surveys during the 1960s. The overall complication rate was 0.4 per 10,000 vaccinees, and the rate of severe complications was very low, similar to previously published data. We conclude that among young healthy adults, vaccination with smallpox vaccine is relatively safe and is associated with a low rate of complications. Severe complications were very rare in this age group in our study. However, the complication rate is increasing with the increased percentage of primary vaccinees.

Introduction

In May 1980, the World Health Organization declared that smallpox had been eradicated from the world.1 The last documented indigenous human case was reported in Somalia in 1977.2 Despite this declaration, immunization against smallpox continues in many countries, especially among health care workers, laboratory workers exposed to orthopoxviruses, and military personnel potentially exposed to this virus as a biological warfare agent.2,3 In many countries, the routine immunization of infants was abandoned during the 1970s, so persons receiving this vaccine today are older and are usually exposed to it for the first time in their lives (primary vaccination). These facts are worrisome because it has been well established in several large national surveys in the United States and other countries that the complication rate is highest among primary vaccinees,4-8 with some authors reporting a particularly high rate of adverse effects among adults.9,10

Several complications have been described subsequent to the administration of smallpox vaccine, including fever, various skin rashes, inadvertent autoinoculation to other body sites, eczema vaccinatum, vaccinia necrosum, generalized vaccinia, and, most seriously, postvaccinial encephalitis. This complication is associated with a 15 to 25% mortality rate, and an additional 25% of the affected patients suffer from permanent neurologic sequelae.2,10

The present study describes the type and rate of complications among a cohort of vaccinees aged 18 years and older recruited to the Israel Defense Force (IDF) during the calendar years 1991 to 1996. Our findings are compared with those reported in earlier studies in the same age groups.

Methods

Study Population I

Study population I consisted of all recruits to the IDF in the calendar years 1991 to 1996 who received the smallpox vaccine. Smallpox vaccine is routinely administered to all IDF recruits for military reasons. According to the surgeon general's orders, any major adverse reactions (postvaccinial encephalitis, vaccinia necrosum, generalized vaccinia, eczema vaccinatum, inadvertent autoinoculation, and secondary infection) experienced after smallpox vaccination are reported to the Medical Corps Army Health Branch, where a central registry is kept concerning these complications and their sequelae. Excluded from vaccination are recruits with any of the following diagnoses: neurofibromatosis, atopic dermatitis, contact dermatitis, furunculosis, urticaria pigmentosa, lichen planus, psoriasis, keratodermia, epidermolysis bullosa, dermatitis herpetiforme, acrodermatitis chronica, keratosis follicularis, rheumatoid arthritis, systemic lupus erythematosus, dysproteinemias, agammaglobulinemia, agranulocytosis, Darier disease, morphea, discoid lupus, pregnancy, immunodeficiencies, known sensitivity to eggs, and acute febrile illness.

In Israel, vaccination of infants and of the general population was discontinued in 1978. Thus, most of the recruits during the calendar years 1991 to 1995 were revaccinees, and an estimated 20% of them received the vaccine for the first time. In 1996, a higher percentage of the recruits received the vaccine for the first time in their lives (50%). However, the precise vaccination status of these recruits was usually not known because smallpox vaccines were given during infancy and vaccination records were unavailable.

Adverse reactions were further categorized according to the possibility of their prevention.11 The categories were (1) severe and unavoidable, including postvaccinial encephalitis and generalized vaccinia; (2) severe and avoidable, including eczema vaccinatum and vaccinia necrosum; (3) mild and unavoidable, including local pain, local swelling, or erythema; and (4) mild and avoidable, including inadvertent autoinoculation and secondary infection.

In August 1995, after several cases of complications occurred in soldiers who had mistakenly received the vaccine despite contraindications to vaccination, regulations were updated to detect soldiers who have contraindications to the vaccine and prevent subsequent avoidable complications. This gave us the opportunity to compare the complication rate from 1991 to 1995 with the complication rate in 1996.

Study Population II

A survey of 2,480 new recruits who were given the smallpox vaccine (study population II) sought information on minor postsmallpox vaccine complications, including fever, skin rashes, headache, malaise, lymphadenopathy, sick days, and hospitalization in sick rooms as a result of complaints appearing after vaccination. Exclusion criteria were the same as for study population I.

Data Analysis

Data analysis was performed by reviewing all of the complications reported to the Army Health Branch during the calendar years 1991 to 1996 and calculating the rates of various complications, We compared the IDF post-smallpox vaccine complication rate with rates reported in other large surveys to investigate possible explanations for the differences. The significance of the differences between complication rates in 1991 to 1995 versus 1996 was determined using Fisher's exact test. Two-tailed p values are reported.

Results

Study Population I

The total complication rate among IDF vaccinees during the calendar years 1991 to 1996 was 0.4 per 10,000 vaccinees. No case of postvaccinial encephalitis or mortality was noted. The most frequent complications were eczema vaccinatum (0.15 per 10,000) and generalized vaccinia (0.09 per 10,000).

Comparison with Previously Published Surveys

The rates of postvaccinial encephalitis and vaccinia necrosum in our registry were comparable with rates reported in the other surveys (Table I). The rates of eczema vaccinatum, generalized vaccinia, and inadvertent inoculation were higher in IDF recruits than in similar surveys conducted in the 1960s (Table I).

Avoidable Complications

Two-thirds of all postvaccination complications were potentially preventable.

Complication Rate during the Years 1991 to 1995 Compared with 1996

The complication rate was 0.36 per 10,000 vaccinees during the calendar years 1991 to 1995. The rate increased by 94%, to 0.7 per 10,000 vaccinees, in 1996. However the avoidable complication rate decreased from 0.26 per 10,000 in 1991 to 1995 to 0 in 1996 (statistically not significant).

Study Population II

Among 2,480 vaccinees, 36 (1.5%) complained of minor medical complaints: local pain, local swelling, fever, and lymphadenopathy. None required hospitalization or more then 1 day of sick leave.

Discussion

The overall complication rate reported in the present study is similar to the complication rate reported in persons 15 years or older (0.46 per 10,000 vaccinees) in a four-state survey in the United States in 1963 7 but higher than the rates reported in larger national surveys in the United States in 1963 and 1968.4,5 In the national survey conducted in the United States in 1963, the overall reported complication rate among persons older than 15 years was 0.06 per 10,000 vaccinees4 which was eight times lower than the rates reported in the present study and in the four-state survey conducted in the same year.7 In the national survey conducted in the United States in 1968, the reported complication rate among vaccinees older than 15 years was 0. 12 per 10,000.

The higher complication rate in the present study could be partially explained by the fact that the number of primary vaccinees in our study was approximately 23%. In the U.S. national survey in 1963, only 8% of the vaccinees 15 years or older were primary vaccinees, with a postvaccination complication rate of 0.5 per 10,000 among primary vaccinees and a very low rate (0.015 per 10,000) among revaccineeS.4 The relatively low rate of complications in the 1968 U.S. survey is explained by the very low complication rate among revaccinees (0.04 per 10,000) compared with primary vaccinees (0.98 per 10,000) and the low rate of primary vaccinees (7%) compared with that in our study population (23%).

Another explanation for the lower complication rate reported in the U.S. national surveys is that secondary infection was not included in those reports.

In addition, it is possible that many complications went unnoticed in the 1963 and 1968 national U.S. surveys,7 and the authors themselves suggested that their published rates are probably underestimations.5 Underreporting of severe complications is highly unlikely in the IDF because military physicians are ordered to report any such complications to the Army Health Branch. Civilian hospitals that care for ill soldiers report promptly to the IDF Medical Corps about hospitalized soldiers.

In our study, we found that roughly two-thirds of the complications could be prevented by strict adherence to the regulations regarding contraindications to vaccination. Similar estimates have been given by other authors.4,5,11 Moreover, subsequent adherence to these regulations eliminated completely the avoidable complications. The increased complication rate seen in 1996 probably results from improved surveillance and reporting after implementation of the new regulations in 1996 and the steadily increasing percentage of primary vaccinees.

Limitations of the Study

We cannot exclude the possibility that not all of the complications were reported to the Army Health Branch; however, this is highly unlikely with regard to severe complications. As for minor complications, it is possible that many of them were not reported by the vaccinees and therefore did not come to our attention. However, in the second survey, which included intense surveillance in the week after vaccination, the minor complaint rate was only 1.5% among 2,480 vaccinees.

Conclusions

We conclude that among young healthy adults, vaccination with smallpox vaccine is relatively safe and is associated with a relatively low rate of complications. Severe complications are very rare in this age group. The complication rate is increasing with the increase in the percentage of primary vaccinees. Together, these data suggest that stricter implementation of existing regulations may decrease the rate of avoidable complications after smallpox vaccine. Surveillance will continue for further monitoring of postvaccination adverse effects.

References

1. World Health Organization: Declaration of global eradication of smallpox. Weekly Epidemiol Rev 1980; 55: 145-52.

2. Centers for Disease Control: Vaccinia (smallpox) vaccine: recommendations of the immunization practices advisory committee (ACIP). MMWR 1991; 40: 1-10.

3. Capps L, Vermund SH, Johnsen C: Smallpox and biological warfare: the case for abandoning vaccination of military personnel. Am J Public Health 1986; 76: 1229-31.

4. Neff JM, Lane M, Pert JH. Moore R, Millar JD, Henderson DA: Complications of smallpox vaccination. I. National survey in the United States, 1963. N Engl J Med 1967; 276: 125-32.

5. Lane JM, Ruben FL, Neff JM, Millar JD: Complications of smallpox vaccination, 1968: national surveillance in the United States. N Engl J Med 1969; 281: 1201-7.

6. Lane JM. Ruben FL, Neff JM, Mlllar JD: Complications of smallpox vaccination, 1968: results of ten-state wide surveys. J Infect Dis 1970; 122: 303-9.

7. Neff JM, Levine RH, Lane JM, Ager EA, Moore H, Rosenstein BL, Mollar JD, Henderson DA: Complications of smallpox vaccination, United States 1963. II. Results obtained by four statewide surveys. Pediatrics 1967; 39: 916-23.

8. Ratner LH, Lane JM, Vicens CN: Complications of smallpox vaccination: surveillance during an island-wide program in Puerto Rico, 1967-1968. Am J Epidemiol 1970; 91: 278-85.

9. Gurvich EB: The age-dependent risk of postvaccination complications in vaccinees with smallpox vaccine. Vaccine 1992; 10: 96-7.

10. Fenner F, Henderson DA, Arita I, Jezek E, Ladnyi LD: Smallpox and Its Eradication. Geneva, Switzerland. World Health Organization, 1988.

11. Baxby D: Indications for smallpox vaccination: policies still differ. Vaccine 1993; 11: 395-3.

Guarantor: MAJ Moti Haim, MC IDF

Contributors: MAJ Moti Haim, MC IDF; MAJ Michael Gdalevich, MC IDF; CPT Daniel Mimouni, MC IDF; COL Isaac Ashkenazi, MC IDF; MG Joshua Shemer, MC IDF

Army Health Branch, Medical Corps, Israel Defense Force, Military Post 02149, Israel.

This manuscript was received for review in August 1998. The revised manuscript was accepted for publication in October 1999.

Reprint & Copyright (C) by Association of Military Surgeons of U.S., 2000.

Copyright Association of Military Surgeons of the United States Apr 2000
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