Worrisome Infection Eludes a Leading Children’s Vaccine: Streptococcus pneumoniae antibiotic resistant

[Guest guest]

Worrisome Infection Eludes a Leading Children’s Vaccine

By LAURA BEIL

http://www.nytimes.com/2008/10/14/health/14vacc.html

A highly drug-resistant germ has become a common cause of meningitis,

pneumonia and other life-threatening conditions in young children. The

culprit — a strain of strep bacteria — can conquer almost all

antibiotics in pediatrics, and has dodged a vaccine otherwise credited

with causing the number of serious infections in children to plummet.

Since 2000, American toddlers have been immunized against Streptococcus

pneumoniae, or pneumococcus, an organism that preys largely on children

younger than 5 and the elderly. Pneumococcal meningitis can be fatal,

and survivors are often left with deafness and other lifelong

neurological problems.

And by most measures, the vaccine has worked: by 2002, rates of

infection from these bacteria had dropped as much as 80 percent in some

places. But progress has now stalled, and infection with a particular

type of pneumococcus, Serotype 19A, is steadily rising.

“It’s very much a concern,†said Bernard Beall, a pneumococcal expert at

the federal Centers for Disease Control and Prevention. Last year, in

The Journal of the American Medical Association, pediatricians described

an outbreak of Serotype 19A ear infections in Rochester that could be

cured only by surgically implanting tubes, or by turning to adult

medicines not yet tested for safety in children.

A greater worry, however, is the frequency of meningitis, pneumonia and

bloodstream infections from Serotype 19A. Since 2001, rates of these and

other invasive pneumococcal diseases have crept upward, to more than 10

per 100,000 children from about 2 per 100,000. A fourfold increase in

life-threatening infections has also occurred among the elderly.

The vaccine, Prevnar, is aimed at seven types of bacteria that were

responsible for 70 to 80 percent of pneumococcal illness during the

1990s. Because pneumococci come in 91 forms, experts have worried from

the start whether bacteria that were just as deadly, but not wiped out

by the vaccine, might move in as opportunists when the competition

suddenly vanished.

“Nature abhors a vacuum,†said Dr. Black of Cincinnati Children’s

Hospital. Indeed, almost all pneumococcal infections among American

children today are caused by versions not covered by the vaccine, and

19A is leading the way. “People hoped against hope it wouldn’t happen,â€

he said.

The vaccine’s manufacturer, Wyeth, says it has been working quickly to

develop a new product to counter 19A and five other pneumococcal

variations, along with the original seven. The company will release

results of the first large studies of the newer version this month at an

infectious disease meeting in Washington.

“There was no point where we said to ourselves, ‘We missed it, we need

to put in 19A,’ †said Emilio A. Emini, head of vaccine research and

development for Wyeth. The company was always prepared to remake the

product, he said.

Once a new vaccine demonstrates that it can protect against

pneumococcus, it must work its way through the approval process —

passing tests of effectiveness and safety — before it can be licensed.

Researchers will also try to determine whether young children who have

been immunized with the old Prevnar should be revaccinated to protect

themselves from 19A.

The remodeling of a vaccine so soon after its approval is highly

unusual, but so was the effort to tackle pneumococcus.

The bacteria live in the nose and throat, usually as microbial

freeloaders of no consequence. Occasionally — often after a simple viral

infection — pneumococci slip into inner areas of the body and cause

disease. Weaker immune systems in the very young and the very old leave

them most vulnerable. (The pneumonia shot in older people includes 19A,

but many elderly people have not received the immunization.)

Not all of the 91 incarnations of pneumococcal bacteria are dangerous.

They developed so much variety by mingling in the back of the throat,

exchanging genetic material as eagerly as children trading Halloween

candy. The variation in genes slightly alters how the bacteria function

and how they are received by the immune system.

For vaccine manufacturers, pneumococci’s diversity presented a

challenge: how to teach the immune system to recognize a target that may

look a little different from child to child. “This is the most complex

biological product ever made,†Dr. Emini said.

Serotype 19A was around in the 1990s, though uncommon, and the vaccine

includes a similar version called 19F. The hope in 2000 was that 19F

looked enough like 19A to set off an immune reaction. It did not.

Experts say it is hard to know what role the introduction of Prevnar may

have played in the rise of the bacteria, which was gaining momentum in

some countries before the vaccine’s adoption. For example, researchers

from GlaxoKline, which is introducing its own pneumococcal vaccine,

reported last month that Serotype 19A became more common in Belgium from

2001 to 2004 — years when pneumococcal vaccination was rare in that

country. Similar reports have emerged from China, South Korea and Israel.

Pneumococci ebb and flow in natural cycles, and some types have gained a

survival advantage by growing resistant to a host of drugs. The vaccine

may have simply amplified natural trends..

“I don’t think anyone can tell you the relative contributions of these

factors,†said Dr. Sheldon L. Kaplan of Texas Children’s Hospital in

Houston. This summer, he and his colleagues described a growing number

of cases of drug-resistant mastoiditis, an infection of an inner-ear

bone, from 19A.

Experts are now watching to see how forcefully the organism will spread

before the new immunization arrives. Wyeth says it hopes to file an

application with the Food and Drug Administration in 2009.

Disease experts also wonder what organisms like 19A mean for the future

of pneumococcal infections. Public health experts once hoped the

infection could be defeated, but it now appears that pneumococci may be

playing a game of cat and mouse.

“The pneumococcus has shown an extraordinary ability to evolve to our

strategies,†said Dr. Beall of the C.D.C.

Yet he and others are quick to say that immunization remains highly

effective, even if it leaves some children behind. “This is not a

failure of the vaccine,†said Dr. H. McCracken Jr. of the

University of Texas Southwestern Medical Center at Dallas. Even with the

rise of 19A, children are much less likely to become ill from

pneumococcal infections.

Dr. McCracken hopes that researchers will one day avoid threats like 19A

entirely by developing a vaccine that primes the immune system to

recognize some element common to all 91 types of pneumococci — in the

way a quiche, an omelet and a custard pie are all versions of eggs. But

until such an immunization comes along, he said, pediatricians will be

forced to battle the pneumococcus as they always have, by trying to stay

one strain ahead of its game.

<?>