Drug-Resistant Bacterium Strikes Soldiers Fighting in Iraq

An unusually drug-resistant bacterial infection among  soldiers who served in the Middle East first showed up in 2003 when a handful of cases were identified in military hospitals. By October 2005, more than 300 cases had been reported, sending military physicians scrambling. The bacterium, Acinetobacter baumannii, is similar to a strain that was a common source of infection among U.S. soldiers in the Vietnam War. But this variant of the bacterium has evolved so much resistance to antibiotics that to combat it doctors must rely on drugs that haven't been widely used in decades.

Like Staphylococcus, another common pathogen, A. baumannii poses the biggest threat to hospitalized patients whose immune systems are already weakened by injury or illness. The bacterium can live on the skin and survive for weeks on dry surfaces, so it infiltrates and lingers in hospitals, poised to colonize new patients. A ward of soldiers wounded by land mines, mortar fire, or bombs may be especially vulnerable to infection.

"Once it has established itself, it is difficult to eliminate," says Colonel Bruno Petrucelli, one of the U.S. Army's senior epidemiologists.

At least five patients have died because symptoms of their illness were aggravated by the infection, despite their receiving intravenous antibiotic treatment.
"What makes this special is that we can run out of drugs that we can count on," says Petrucelli. "There's always that fear that we're running out of options, that this organism is going to grow and there is nothing that's going to knock it down."  —Susan Kruglinski

HIV Attacks the Gut First

For more than a decade, scientists have tracked the insidious progression of HIV by measuring the amount of virus in a patient's blood. Over a period of years, the replication of the virus gradually and steadily destroys the immune system's defenses—or so it was thought.

In April two studies of simian immunodeficiency virus, a kin of HIV that infects monkeys, reported that the virus swiftly infects and decimates key immune cells in the gut within days, not years, of infection. "This basically changes our whole view of the pathogenesis of HIV infection," says Daniel Douek, chief of the Human Immunology Section at the National Institutes of Health's Vaccine Research Center.

Virologists have long known that HIV infects and kills CD4+ T cells, which mediate the body's immune response to viruses. What has emerged over the past few years is that the virus thrives not only in the blood and the lymph system but also in mucosal tissues, which are rich in immune cells. The mucosae line parts of the body, such as the mouth, nose, and rectum, that are exposed to the environment. The gut, the largest of the mucosal tissues, harbors most of the body's CD4+ T cells.

"What we now know is that within the first few weeks of infection, probably two to three weeks, the majority of those cells are depleted by HIV infection," says Douek. During that early stage of infection, about half the T cells in the gut can be wiped out in just four days.

The findings have profound implications for the control of HIV infection. They not only underscore the importance of starting antiretroviral therapy very early in the infection but also highlight the need for a vaccine that can protect mucosal surfaces. —Apoorva Mandavilli

Vaccine Protects Against Cervical Cancer

Each year cervical cancer kills about 250,000 women around the world, most of them in developing regions without basic health care. Since the 1980s, when scientists discovered that human papillomavirus plays a role in nearly all cases of cervical cancer, researchers have worked to create a vaccine. This year they succeeded. In October Merck completed a study showing that its vaccine, Gardasil, was 100 percent effective in protecting a group of more than 5,000 women.

Of the 30 strains of papillomavirus that can be sexually transmitted, about half can provoke the cellular changes that lead to cancer. Gardasil protects against two strains responsible for 70 percent of all cervical cancer cases and another two that cause noncancerous genital warts. The vaccine includes one key viral protein—not enough of the virus to cause infection but enough for the body to react and create immunity. GlaxoSmithKline has developed a similar vaccine that protects against the two cancer-provoking strains.

If the vaccines get approval from the FDA, the next formidable obstacle will be getting them to those who need them most. The vaccine will not protect the 75 percent of sexually active adults who are already infected with the virus. The biggest pool of those who can be helped are young boys and girls. But some researchers worry that religious and conservative groups will speak out against vaccinating children because they fear it might condone sexual activity.

Laura Koutsky, an epidemiologist at the University of Washington who led the studies on Gardasil, says that the abstinence-only message doesn't protect children who ignore it. And even if a child abstains from early sexual activity, she is still unprotected, Koutsky says: "Your child may abstain until marriage, but her partner might not. You don't know what that partner will bring to the marriage."

Besides, in rare cases the virus can be spread by any sexual contact, even touching, so abstaining from intercourse does not always prevent transmission. "Using the same flawed logic, we should eliminate Pap smears because they're looking for the same sexually transmitted disease this vaccine prevents," Koutsky says. She is confident that parents' concerns will outweigh philosophical issues. "You know, I just hope most people would rather give a vaccine like this than watch their daughters struggle with abnormal Pap smears and cervical cancer."—Rebecca Skloot

FDA: Over The Counter Warning

For decades, the Food and Drug Administration endorsed over-the-counter painkillers as largely safe and effective. But in April the agency warned that the medicines might carry a risk of heart attack, stroke, and gastrointestinal problems—and requested that manufacturers' packaging provide information on the product's risk. 

The debate over painkiller safety began in the late 1990s when competition for the arthritis market erupted between Merck's Vioxx and Pfizer's Celebrex. The new drugs, which target the COX-2 enzyme, were seen as better than traditional painkillers like aspirin because they don't have gastrointestinal side effects. But as early as 1997, researchers began warning that the drugs increase the risk of heart attack.

On September 30, 2004, Merck withdrew Vioxx after trial results unquestionably showed that the drug increased the risk of heart attack and stroke. The FDA began scrutinizing all nonsteroidal anti-inflammatory drugs, a group that includes COX-2 inhibitors and over-the-counter painkillers.

On April 7 reports of adverse skin reactions and heart problems prompted the FDA to ask Pfizer to withdraw Bextra, another COX-2 inhibitor, and to include a warning about the health risks for Celebrex. It also asked for a similar label for over-the-counter ibuprofen drugs, such as Motrin and Advil, and for naproxen (Aleve) and ketoprofen (Orudis, Actron).

Eric Topol, chairman of cardiovascular medicine at the Cleveland Clinic, says labeling all painkillers is "absurd." Although he had questioned Vioxx's safety, Topol contends that the more generic warning is an overreaction. Traditional anti-inflammatories such as ibuprofen and naproxen have been widely used for more than a decade, Topol says. "If there were any significant risks—life-threatening risks—with these drugs, we would know about it by now."

Garret FitzGerald, director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania, adds that the FDA's European counterpart has said there is not enough information to change how the public uses the over-the-counter drugs.

Meanwhile, Merck is facing more than 7,000 lawsuits from Vioxx users and their families. At the end of the first lawsuit, a Texas jury in August awarded $253.4 million in damages to the family of 59-year-old Robert Ernst, who died in 2001 after taking Vioxx for eight months. In the second Vioxx-related suit, Merck won against 60-year-old Frederick Humeston, who suffered a heart attack after taking Vioxx for knee pain for two months. The jury found that Merck had not been misleading or fraudulent in selling Vioxx.

If the FDA and Merck had both acknowledged the problems when they first appeared, says Topol, Vioxx might still be on the market and prescribed only for people who respond well to it and who understand the risks. The result of the Vioxx scare, he says, is that people are left with a lot of uncertainty. "Who do they believe?" he asks. "Not the companies, not the FDA. It didn't need to be like this."  —Apoorva Mandavilli

Gene Therapists Break Through Blood Barrier

Scientists have now crossed the biggest barrier to the delivery of therapeutic genes: the blood vessels. In a series of studies this year, molecular geneticists at the University of Pittsburgh School of Medicine used a harmless virus to ferry new genes through the bloodstream, across blood vessel walls, and into almost every muscle cell in the bodies of hamsters bred to have human genetic diseases. "We've never seen such a dramatic therapeutic effect," says Xiao Xiao, head of the research team.

This is the first time anyone has been able to deliver genes efficiently through blood-vessel walls without the aid of wall-weakening drugs or vessel-distending pressure. Xiao's team first used AAV8, a strain of adeno-associated virus, to carry a gene for a marker, green fluorescent protein, into an unprecedented number of muscle cells. Then they showed they could deliver genes to repair deteriorated muscles and reverse congestive heart failure.

The technique holds the greatest potential for treating diseases like muscular dystrophy, in which billions of far-flung cells need new DNA. As for worries about harmful effects, researchers say AAV8 isn't likely to disrupt healthy genes, a side effect that stalled a promising gene-therapy trial for an immune-deficiency disorder in 2002. Xiao is optimistic about the clinical applications but cautions, "Hamster to a human—that's a long way to go!"  —Jessica Ruvinsky