WASHINGTON, D.C. Acellular pertussis vaccines may have more drawbacks than benefits for developing countries, according to Mark Kane, MD, of the World Health Organization (WHO). He spoke at the National Institutes of Health Pertussis Conference here.
Although clinical trials demonstrated that diphtheria-tetanus-acellular pertussis (DTaP) vaccines are safe, effective and less reactogenic than vaccines containing whole cell pertussis (DTP), their practical use may be limited to industrialized countries, said Kane.
In developing countries, DTaP vaccines may have no real advantage over whole cell products. The new vaccines have several serious drawbacks: higher cost, complex production with patented components, and no significant advantage in efficacy.
Acellular vaccines are expected to cost more than whole cell vaccines for a variety of reasons.
"They are newer products; the older whole cell vaccines are produced in factories that have long been paid off," Kane said. "They produce lower yields, in general. Some of the products and processes are protected intellectual property. There may be a shorter pay back period to recoup research and development costs, capital expenditures, and to pay for clinical trials, licensing and marketing. Maybe within a very short time DTaP will be replaced by combination vaccines and other products that will require more expenditures for research and development. Finally, there is the higher cost of quality control for some of these products."
Sixty producers of DTP supply 42 countries, making the whole cell vaccine relatively inexpensive, Kane said. The United Nations Children's Fund (UNICEF) currently purchases DTP for about 8 cents per dose. Fully immunizing a child according to the Expanded Program on Immunizations (EPI) schedule one dose of bacille Calmette-Guérin, three doses of DTP, three doses of oral polio vaccine and one dose of measles vaccine costs UNICEF 60 cents.
"We don't know how much acellular pertussis vaccines might cost UNICEF, but let's assume that they cost 60 cents per dose. ... At 60 cents per dose, it would essentially triple the amount of money UNICEF would have to spend and raise to supply that vaccine," Kane said. "This money is not available. We can see from our experience with trying to introduce new antigens such as hepatitis B vaccine that it is extremely difficult to raise money to purchase vaccines for children in the developing world."
The desire to purchase more expensive vaccines with limited resources may create competition among various programs, Kane said. For example, money may be taken away from polio or measles eradication campaigns.
"The issue is in a world of constrained resources, is using acellular pertussis vaccines a cost-effective way for the developing world to move forward," Kane asked.
There is no clear evidence that, in developing countries, the advantages of acellular pertussis vaccines justify their additional cost. Globally, pertussis morbidity has declined 85% to 90% over the past 15 years, said WHO's Artur Galazka, MD.
"A declining trend is much more accentuated in developing countries, especially in the second half of the 1980s when immunization coverage with the primary series of DTP vaccine exceeded 60%," Galazka said. "Data show that immunization with the conventional DTP vaccine had been remarkably effective in preventing pertussis."
It is unclear whether acellular vaccines would be more effective than whole cell vaccines in controlling disease.
"Is it best to pay a lot of money to switch from whole cell to acellular vaccines, which actually may not change the number of deaths that occur from pertussis in the world, or would those resources be better spent on [purchasing] additional antigens, such as Haemophilus influenzae type b or hepatitis B vaccines, for the countries that haven't been able to introduce those vaccines yet?"
We have to think about cost-effectiveness, which is usually measured in cost per year of life gained. It may actually be that the switch to acellular vaccines, which may have a little lower efficacy than whole cell vaccines, may not buy any more years of life gained at a very substantial increase in cost. If you put those numbers into a cost-effectiveness evaluation you get actually a negative result," Kane said.
The lower reactogenicity of acellular pertussis vaccines may offset their cost, but concerns over adverse events are unique to developed countries.
"The DTP reactogenicity issue is not generally seen as a major problem in developing countries. It may be that parents and health providers are more tolerant of minor side effects or there are fewer lawyers living in a less litigious society, but it has been our experience over many years in the EPI that the reactogenicity of DTP is not a major issue in these countries," Kane said.
Related to cost is the equally important concern that acellular vaccines require a more complicated production process, with some components protected as intellectual property. Although 60 producers currently are qualified to make whole cell vaccine, few will be able to make acellular products, Kane said.
WHO encourages local vaccine production to lessen dependence on foreign donations, provided the facilities meet certain standards. A switch to acellular vaccines will put many local producers out of business or require that they enter into joint ventures with outside manufacturers.
"Actually, few local producers are attractive partners for industrial producers," Kane said. "Many local producers are inefficient local government departments: they have small, fixed budgets; they are not allowed to hire and fire people; salaries are low, making it difficult to retain skilled people; they may have very weak management and no cost accounting they may not have any idea how much it costs them to make DTP. They may have weak or no national control authority and weak quality control assurance. Many of these local producers will not be able to make acellular pertussis vaccines."
Another concern for developing countries is the future of DTP-based combination vaccines. Combinations based on DTaP have been problematic, but whether whole-cell combinations will continue to be pursued for use in either developing or industrialized countries is uncertain.
WHO is meeting with regional and country representatives to create criteria and guidelines so individual countries can decide which strategy to use, Kane said.
You can express your views on this article, or other relevant themes, in the Infectious Diseases in Children Specialty Forums.