No Evidence That Combined DTP-HBV-Hib Vaccine Works Better

There is no evidence that giving infants a combination vaccine for diphtheria (D), tetanus (T), pertussis (P), hepatitis B (HBV), and Haemophilus influenza type B (Hib) protects them as effectively as separate vaccines, according to the results of a new Cochrane review.

Although the World Health Organization (WHO) recommends adding the Hib vaccination to the DTP-HBV vaccines, no data support this immunization practice, the review authors found.

“Despite its use in accordance with the WHO recommendation in several countries, no systematic review of the effectiveness and safety of the combined vaccine is available. We decided to compare the outcomes from the combined vaccine and the separate injections for the combined vaccine’s suitability to be used in national immunization programs,” said lead review author Edna Bar-On, PhD.

“Combined vaccines, if they work well, have several potential advantages. These include the benefit of minimizing the number of injections and consequently patient discomfort. There’s also a potential savings in supplies, syringes and health care worker time,” said Samir Shah, MD, a pediatric infectious diseases physician at the Children’s Hospital of Pennsylvania. He had no connection with the review.

Using data from 18 studies involving 10,374 children, Bar-On and her colleagues examined use of the DTP-HBV-Hib vaccine and the separate DTP-HBV and Hib. Two of the studies took place in the United States.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

“The results of this review should be viewed with caution, mostly as an indication that high-quality data are lacking,” said Bar-On, of Rabin Medical Center in Petah-Tiqva, Israel.

There was no difference between the combined vaccine and the separate vaccines regarding the immune response, although two large studies showed a lower level of immunization in the combined vaccine. These two studies changed the statistical analysis results, Bar-On said.

In addition, some minor side effects, such as pain and redness around the injection site, were more common in children who received the combined vaccine, although the number of serious side effects was comparable between the combined and separate vaccines.

“Although no difference was found between combined and separate vaccines in our adverse events meta-analysis, we cannot base conclusions upon nine studies with a relatively small sample of 4,932 participants,” Bar-On said.

“Since WHO has approved the regimen of a combination vaccine, it’s not unreasonable to use it if it facilitates administration and allows you to cover more people with the vaccine,” Shah said.

“Part of the risk-benefit analysis includes evaluating safety issues. In the studies reviewed here, there does not seem to be any difference in safety, so that’s a critical point,” Shah said.

“Ideally, what this study had hoped to address was whether the incidence of these diseases changes when using the combined vaccine. Unfortunately, none of the studies contained enough information to address that primary outcome,” Shah said.

There simply is not enough information to for a clear understanding of the benefits or the differences between the combination vaccine and the standalone Hib vaccine, Shah said.

Anytime a new vaccine goes on the market, post-marketing surveillance is an important part of the safety process, Shah said. “One of the key parts of evaluating this vaccine is to monitor the immunization over time. That will give us a more clear picture of whether this is an optimal strategy.”

Currently, the Centers for Disease Control and Prevention recommends that infants receive an initial dose of HBV vaccine at birth, followed by a second dose at one to two months, and a third dose between six to 18 months. Children should get five doses of the DTaP vaccine, usually at 2, 4, 6, and 15 to 18 months and four to six years. The dosage schedule for the Hib vaccine varies depending on the brand, but generally, children should be vaccinated at two, four, six, and 12 to 15 months of age.

The study authors received support from Rabin Medical Center and the National Institute for Health Policy and Health Services Research, both in Israel.