Childhood vaccine saves lives, but may lead to other infections
Since it was put on the market in February 2000, a childhood vaccine called Prevnar has reduced the rates of certain serious bacterial infections by 75 percent in American children.
But the bacterium it protects against -- pneumococcus, which causes bloodstream infections, meningitis, pneumonia, ear infections and other diseases -- is a wily organism. It comes in over 90 different strains, and Prevnar covers just the seven most common. Since the introduction of Prevnar, there has been a slow but definite rise in infections caused by strains not covered by the vaccine, and there are concerns that this trend may continue.
''I think this is a very good vaccine," said Dr. Gordon Schutze, a professor of pediatrics at the University of Arkansas for Medical Sciences. ''But I'm concerned because we're seeing a rise in disease caused by strains not covered by the vaccine."
Pneumococcus -- which is also referred to as Streptococcus pneumoniae -- was first identified in 1881, and has been a scourge of humanity since long before that.
Studies have shown that roughly half of all children carry pneumococcus in their noses and throats at any one time. It's mostly harmless, but when the bacterium is inhaled into the lungs, or gets into the bloodstream, it can cause serious illness.
Prior to 2000, pneumococcus was responsible for close to 200,000 hospitalizations and several thousands deaths annually in the United States in both children and adults. The rates have dropped since the introduction of Prevnar -- one recent study in Michigan showed a 50 percent reduction in hospitalizations in young children since 2002 due to the vaccine -- but pneumococcus continues to be one of the most important causes of infectious disease worldwide.
Children receive Prevnar in three doses at 2 months, 4 months and 6 months of age, followed by a booster dose at about a year old. The latest federal data shows that about two-thirds of American infants are receiving all of their doses on time.
The only previously approved vaccine against pneumococcus -- called the pneumococcal polysaccharide vaccine, which is still given to high-risk adults -- is not effective in infants and young children. While Prevnar is very effective in infants and young children, it only protects against a limited number of strains because it stimulates an immune response against pneumococci's outer shell, which varies from strain to strain.
Prevnar seems to be reducing pneumococcal disease not just in children but in adults as well because children are now less likely to pass on the bacterium to others. This so-called ''herd effect" has been a somewhat unexpected benefit of the vaccine.
According to Dr. Cynthia Whitney of the US Centers for Disease Control and Prevention, serious diseases such as meningitis and bloodstream infections due to strains of pneumococci not covered by Prevnar have risen by about 50 percent since its introduction, though the amount of disease due to these strains is still low. The rise has been more substantial for less-serious diseases such as ear infections and pneumonia. The strains not covered by Prevnar seem to be better at causing these less-serious diseases for reasons that are not entirely clear.
Recent studies have also found that strains of pneumococci not covered by Prevnar multiply in the noses and throats of children after they are given the vaccine. Although Prevnar reduces the amount of the seven strains it covers, other strains completely fill in the gap -- so the total amount of pneumococcus found in children's noses and throats is not reduced by vaccination.
This ''replacement" phenomenon is something that occurs commonly throughout nature. For example, when timber companies chop down the largest trees in a forest, it creates room for smaller trees and bushes to increase in number. Likewise, when doctors give antibiotics to treat an infection, new bacteria that are resistant to the antibiotic quickly fill in the space left by the susceptible bacteria.
And it is not just other strains of pneumococcus that are filling in the gaps. New evidence is showing that ear infections due to other species of bacteria are on the rise now that ear infections caused by pneumococcus have decreased. This may make it necessary to treat ear infections with different antibiotics than those currently used because the bacteria filling in the gaps are not always susceptible to the currently used antibiotics.
According to experts, extensive replacement has not happened with other widely used vaccines, likely because many other bacteria exist in only a small number of disease-causing varieties.
The rise in nonvaccine strains of pneumococci has been especially concerning in high-risk patients -- those with HIV or sickle-cell disease, for instance -- whose immune systems are weaker.
Dr. Stephen Pelton, a pediatric infectious disease physician at Boston Medical Center, explained that the strains not covered by Prevnar are weaker than the strains that are covered. Therefore, high-risk patients -- who have weaker immune systems -- are most susceptible to these less-virulent strains that healthy people usually can fight off.
The rise in nonvaccine strains of pneumococcus is likely to continue. ''We do need to keep our eyes on the nonvaccine type disease in case it starts becoming more of a problem," Whitney said.
Experts say that the best way to curb such a rise would be to develop new vaccines to cover more strains. This will be especially important for the developing world where, according to Pelton, pneumococcal strains not included in Prevnar have always been a more important cause of disease than in the United States.
Wyeth Pharmaceuticals, which makes Prevnar, is currently working on a product that would cover 13 total strains of pneumococci -- six more than the current version. And
According to Pelton, researchers are also developing vaccines that would cover all 90 strains of pneumococci. Several groups are working on a vaccine that would stimulate a response against a protein common to all strains. The best candidate proteins are hidden inside the outer shell, however, and the immune system has trouble recognizing these proteins when pneumococcus enters the body. ''I think we can ultimately win the race [against pneumococci]," Schutze said. ''But I think we'll probably have to do better than covering seven strains. I think we'll have to find a vaccine that covers 20 strains or so."
