Box 14 Vaccine Resistant Pathogens

Vaccines typically instruct the human immune system to recognize a pathogen and destroy it. In some circumstances, the pathogen can alter its surface properties to make it less responsive to the immune system. For example, the malaria parasite frequently changes its surface; consequently, the human immune system is always a step behind the parasite. In other cases, the pathogen species exists in many varieties. Shortly after the U.S. anthrax scare of 2001, considerable concern arose because the bacterial strain used in the attacks, the Ames strain, was relatively resistant to the available vaccines.

Vaccines for Streptococcus pneumoniae (also known as pneumococ-cus) illustrate the principle of replacement.29 This organism, which causes pneumonia, otitis media (middle ear infection), sinusitis, and meningitis, colonizes the nasopharynx of 50% of children and about 2.5% of adults. Two types of vaccine are available, one prepared against polysaccharides of 23 pneumococcal strains and the other against a nontoxic diphtheria protein conjugated to polysaccharide from 7 strains of S. pneumoniae. The former reduces the impact of disease, whereas the latter also eliminates colonization by the pathogen. Because more than 90 strains (serotypes) of S. pneumoniae have been identified, neither vaccine was expected to provide full coverage. Nevertheless, the 7-strain vaccine reduced invasive pneumococcal disease by more than 70%. The fraction of antibiotic-resistant pneumococci also dropped. However, elimination of vaccine strains as colonizers created an ecological niche for nonvaccine strains. As a result, serotype 19A, which was rare before the vaccine became available, replaced vaccine strains. In some cases, capsular switching occurred between a vaccine strain (serotype 4) and a nonvaccine strain (serotype 19A) due to genetic recombination. The resulting strains have virulence properties of serotype 4 with low sensitivity to the vaccine (serotype 19A).

Another serious example concerns the pertussis vaccine. Before vaccination began in the 1940s, pertussis (whooping cough) was a major cause of infant death. In the 1990s, pertussis began a resurgence in countries where most of the population had been vaccinated. Some of the resurgence was due to waning vaccine-induced immunity among the elderly, who increasingly were stricken with whooping cough. However, in Holland between 1989 and 2004, a new strain of Bordetella pertussis, the causative agent, replaced the old one among children, and the number of whooping cough cases increased. The new strain appears to be more virulent and produces more toxin than the old one.30

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