SEATTLE – Inadvertent freezing of the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine while it is being stored in vaccine refrigerators may be contributing to the rise in pertussis in the community, new data suggest.

Using continuous data loggers, investigators at the Baylor College of Medicine in Houston found that one-quarter of 54 vaccine refrigerators in the city’s community health centers had temperatures that dipped into the freezing range, most commonly at night and on weekends.

There was a significant 76% correlation between the percentage of vaccine refrigerators in a health region experiencing prolonged freezing temperatures and that region’s rate of pertussis, the investigators reported at the annual meeting of the North American Primary Care Research Group.

The study establishes only correlation, and there are many possible confounders and explanations, acknowledged lead investigator Dr. Patrick J. McColloster, an associate professor of family medicine at the college.

"But I think though that one thing that has been neglected in looking at the pertussis outbreaks in the United States is inadvertent freezing and the instability of DTaP – back to the cold chain again," he said, referring to the practice of ensuring that the vaccine is continuously kept at the recommended temperature.

In interviews, nursing staff at the centers were skeptical of the freezing because they more often noticed warm temperatures during the workday, he commented. "Whenever they would open and close the refrigerator doors, they always made sure [the temperature] was within normal range, and if it was a little too hot, they would just crank the refrigerator up a little bit more. So basically, they were freezing the vaccines like crazy."

Explaining the rationale for the study, Dr. McColloster noted that the incidence of pertussis fell in the 10 years after introduction of the DTP (diphtheria, tetanus, pertussis) vaccine, but it actually rose in the 9 years after subsequent introduction of the DTaP vaccine.

"Currently, all the studies that are out there are saying it’s due to seasonal variation, unvaccinated pediatric clusters, and declining adult immunity," he said. "Gee, it doesn’t have anything to do with DTaP, does it?"

The impact of failure of the vaccine cold chain on the occurrence of pertussis has not been studied in the United States. "DTaP uses aluminum as an adjuvant (just like DTP does), but it’s a little bit different in that it’s more sensitive to freezing," he explained. In fact, the manufacturer recommends discarding any vaccine exposed to freezing temperatures.

In the study, the investigators attached data loggers to 54 vaccine refrigerators in 13 Community Health Centers in the Harris County Hospital District of Houston. The centers provide approximately 580,000 outpatient visits each year to an indigent population.

The loggers sampled the refrigerator temperature every minute for at least 6 days. Data from the first hour were discarded to allow the logger’s temperature to equilibrate.

The centers’ own procedure for cold chain monitoring consisted of twice-daily readings from approved digital thermometers during weekday work hours, as mandated by the Centers for Disease Control and Prevention.

The investigators obtained data on the incidence of pertussis in the district for the years 2005-2009 from the City of Houston Health Department.

Results showed that 48% of refrigerators maintained temperature in the correct range (2?C to 8?C), Dr. McColloster reported. But 19% experienced cold temperatures (0.1?C to 1.9?C) and 24% experienced freezing ones (0?C or lower). The remaining 9% had temperatures rising into the warm range (greater than 8?C), but this usually was so transient that it was unlikely to alter temperature of the vaccine itself, he said.

Among the refrigerators with freezing temperatures, the average time spent at freezing was 2 hours per day. Freezing usually occurred on nights and over weekends.

Across the six health regions within the district, the percentage of refrigerators in the region having freezing temperatures for more than 2 hours daily ranged from 14% to 80%. And the average annual pertussis rate ranged from 2.9 to 6.3 cases per 100,000 population.

The higher the percentage of refrigerators in a region experiencing freezing temperatures for more than 2 hours daily, the higher the pertussis rate for that region (r = 0.76, P less than .05), Dr. McColloster reported.

Establishing causation will require freezing the vaccine and then testing its immunogenicity in animals, or assessing pertussis immune status in patients who have received vaccines from refrigerators experiencing freezing, he acknowledged.

To address the problem, there are several possible solutions, according to Dr. McColloster. DTaP vaccine vials could be affixed with temperature-sensitive labels that show immediately if they have been frozen. Also, clinics could use refrigerators that do not permit staff to manually adjust the temperature.

Dr. McColloster said he did not have any conflicts of interest related to the study.

Freezing DTaP Vaccine Linked to Rise in Pertussis