Return of the Clap

Gonorrhea colony, as seen under a microscope Image: Juergen Berger/Photo Researchers, Inc.

Mark Pandori was worried. It was 2008, and he had just read the latest in a string of reports from Japan. The articles all described patients infected with a particular strain of gonorrhea that was less susceptible than usual to an important class of antibiotics. Pandori, director of the laboratory at the San Francisco Department of Public Health, knew that gonorrhea had become resistant to other antibiotics in past decades. Each time, the resistance seemed to arise in Asia and spread to California. He wondered if something new was heading across the Pacific.

The latest report from Japan described a test that could identify resistant strains of bacteria by isolating and amplifying the culprit gene. Pandori tried the procedure on 54 samples of gonorrhea bacteria collected that year from men in San Francisco. Five samples, or 9 percent, contained the altered gene. When he analyzed the bacteria in the lab, he found that they?like the Japanese strains?possessed partial resistance to cephalosporins, the only antibiotics that still work reliably and inexpensively against gonorrhea.

Pandori and his research partner at the time, a health department epidemiologist named Pennan Barry, were alarmed and baffled. No physicians in the state had reported any difficulties treating patients with gonorrhea. Cephalosporin resistance had apparently infiltrated California without anyone noticing. Perhaps it had started spreading across the country as well.

Last summer a surveillance network run by the Centers for Disease Control and Prevention confirmed their fears. Using a different test, the CDC demonstrated that up to 1.4 percent of 5,900 gonorrhea bacterial samples from around the U.S. had diminished susceptibility to cephalosporins, meaning they would succumb only to unusually high doses. A New England Journal of Medicine editorial published in February said the occurrence of that partial resistance increased 17 times between 2006 and 2011. ?The threat of untreatable gonorrhea is emerging rapidly,? the editorial warned.

That threat is troubling for two reasons. First, gonorrhea is abundant: it is the second-most reported infectious disease in the U.S., with more than 600,000 new cases a year. Second, if untreated, it can cause widespread organ damage, pelvic inflammatory disease and infertility. Making matter worse, our current methods for tracking and controlling gonorrhea are actually contributing to the spread of resistant disease.

A Slow But Steady Spread
Gonorrhea is the first of the major sexually transmitted diseases (STDs) to tiptoe to the threshold of untreatability. True, chlamydia, which infects 426 of every 100,000 people in the country every year, is more common, and cases of syphilis, which doubled in incidence between 2000 and 2010, are growing faster. But syphilis infects only 4.5 of every 100,000 people, and neither chlamydia nor syphilis has developed significant resistance to antibiotics.

Gonorrhea, in contrast, has been developing defenses against drug treatment for decades. The latest news from Japan and California is making the disease a priority for public health planners?a status it has not known since before Alexander Fleming and the discovery of penicillin. Once antibiotics became abundant and inexpensive, gonorrhea and syphilis seemed like solved problems.

Neither infection was vanquished, however. Gonorrhea, in particular, held on by borrowing DNA from other bacteria to construct new microbiological defenses. It steadily gained resistance against entire classes of antibiotics: first the penicillins in the 1960s, then the tetracyclines in the 1980s, and Cipro and its chemical cousins, known as fluoroquinolones, in the 1990s. By 2000 the only class of drugs that could provide what public health strategies rely on?something that is inexpensive, delivered in a single dose and works well enough to obviate follow-up appointments?was the cephalosporins.

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