Infectious Disease News: Results show more adverse events reported after << Td v>> s. << TT>>  Results show more adverse events reported after << Td v>> s. << TT>>  ACIP has had long-standing recommendations to administer Td for primary vaccination of adults or as boosters every 10 years.  
October 1997

ATLANTA ― Despite the need for adult protection against diphtheria, a significant number of providers continue to administer single antigen tetanus toxoids (TT) instead of the recommended tetanus-diphtheria (Td), according to the Centers for Disease Control and Prevention.

Between 1991 and 1995, approximately 18% of all tetanus-containing vaccine (TCV) indicated for use in adults was sold as TT, which is purchased exclusively by the private sector. This represents a significant change since 1974 when data showed that 69% of all TCV for adults was being sold as TT, but still goes against the long-standing recommendation by the Advisory Committee on Immunization Practices (ACIP) to administer Td to adults, according to Jennifer C Lloyd, National Immunization Program.

"There appears to be a slight downward trend since 1991 when 24% of the TCV for adults was sold as TT, until 1995, when 16% was sold," said Lloyd at a recent ACIP meeting.

Some investigators suggest that vaccine providers continue to use TT instead of Td because they believe it is safer. Although local reactions were more commonly reported after Td, overall adverse reporting rates are low after both Td and TT, suggesting both are safe and well-tolerated, Lloyd said.
Protection levels
Although childhood vaccination levels are at record levels, the coverage rates for adults varies. Most children are protected against diphtheria, but studies of diphtheria antitoxin levels in adults found that anywhere from 23% to 98% of U.S. adults were protected.

For tetanus protection, based on the NHANES 3 serosurvey of tetanus antitoxin levels. Overall, 70% of people in the United States 6 years and older carry protective levels of tetanus antitoxin. However, this varies by age, sex and race; 88% of people 6 to 11 years were protected against tetanus compared with 28% of people older than 70.

Men (79%) were more likely to be protected against tetanus than women (62%).

More complete results may be available by the end of the year for diphtheria antitoxin levels, Lloyd said, but they are likely to be 5% to 20% lower. This is probably attributable to the use of TT instead of Td.
Safety
Three studies conducted in the 1980s compared the reactogenicity of << Td v>> s. << TT>> . The first study in 1982 used participants randomly chosen to receive either Td or TT and found no difference in the reporting of local or systemic reactions after the two vaccines. However, the study population was small, Lloyd said.

A larger study conducted in 1985 involved 193 participants. This study indicated local reactions were more commonly noted in Td recipients when compared with TT recipients, but no difference was noted in the reporting of systemic symptoms.

The third and largest study conducted in 1986 included 1,426 participants and significant differences were noted in the occurrence of redness, swelling and other reactions. Fewer reaction rates were reported from participants who received TT than those who received Td. However, the differences between Td and TT were not statistically significant for the other events. Systemic or serious events could not be evaluated because of the relatively small population.

Each of the three studies concluded that although more adverse events were reported after administration of Td than TT, the events themselves were local in nature and self-limiting, Lloyd said. Therefore, the benefit of diphtheria protection would outweigh concerns about the local adverse events.
VAERS
---Reporting rates for select serious events after Td and TT, VAERS, 1991-1995.



Lloyd said postmarketing surveillance data for both vaccines from the Vaccine Adverse Event Reporting System (VAERS) was reviewed to better assess the relative safety of Td and TT in a larger population and to look at more serious adverse events.

Included in the VAERS review were reports that listed a date of vaccination between Jan. 1, 1991, and Dec. 3, 1995, and the vaccinees’ age as 7 years or older, Lloyd said.

A total of 1,924 VAERS reports listed Td, or 36 reports per million net doses of vaccine distributed; 339 reports listed TT, 23 reports per million net doses.

"This translates to a relative risk for the reporting of any adverse event after TD when compared to TT of 1.6 with a 95% confidence interval of 1.4 to 1.8," Lloyd said.

A total of 113 VAERS reports that listed Td described a serious event, which equals a reporting rate of 2.1 reports per million net doses; 23 reports which listed TT also described a serious event, which translates to a reporting rate of 1.5 per million net doses.

The most common adverse events associated with Td and TT include redness, swelling, pain, tiredness, headache, arthralgia and fever. A statistically significant difference in reports for injection site reactions, redness, pain and fever were noted, with fewer reports following TT. Lloyd said the five most common events described on serious VAERS reports were also the same five events most commonly reported overall.

Although age-specific denominator data is not available, a difference in age distribution of patients was noted. The distribution of serious reports by age group is similar to all other reports; nine of 14 serious reports of syncope were from people 7 to 29 years. It was later revealed that 77% of these reports described patients younger than 20, Lloyd said.

"So if younger people are both more likely to receive Td and to experience syncope regardless of which vaccine they receive, this may explain some of the difference in the reporting rates for syncope," she said.