By David N. Leff

AIDS imposes a death sentence on its victims; syphilis, usually just a life sentence.

And as HIV spreads its epidemic around the world, it drags along syphilis — until now on the decline in the U.S. — as an opportunistic infection of AIDS.

From its emergence in 1493, as described by physicians in Spain, syphilis sowed AIDS-like terror among Europeans. They called it with a shudder "the great pox," or "the French (or Italian, or Spanish) evil." People tended to blame Christopher Columbus for importing the sexually transmitted disease from his crews' contacts with Amerindians in the lands he discovered.

Molecular geneticist George Weinstock, at the University of Texas Health Science Center, in Houston, questions laying this rap on the New World Indians. He pointed out that Treponema pallidum, the spirochete that causes syphilis, is genomically indistinguishable from two related but non-venereal pathogens: Yaws, caused by T. pertenue, lurks in equatorial Africa; pinta (T. carateum), in Central and South America.

The Texas scientist speculates that those 15th-century explorers may have brought the yaws or pinta spirochete back to Europe, where the harsh climate made it mutate into the T. pallidum of syphilis.

Until the mid-20th century, syphilis raged in the U.S., causing the majority of blindness and insanity among Americans, plus much cardiovascular disease. In the 1930s, it was regarded as the nation's No. 1 public health problem. One in 20 American recruits called up for World War II was infected.

Aside from widespread quackery, the only standard "cures" were agonizing mercury vapor and arsenic.

Then, in the immediate aftermath of the war, in the late 1940s, came penicillin, which quickly and thoroughly wipes out the infection when caught early enough. The other good news is that T. pallidum, which makes its living entirely by infecting Homo sapiens — no animal reservoirs need apply — hasn't yet caught on to developing antibiotic resistance against penicillin.

The bad news is that the spirochete does resist growing in culture dishes. This in vitro evasion makes it almost impossible to study, which explains why there is no anti-syphilis vaccine — yet.

Condoms Can't Cover All The Syphilitic Lesions

Even the safe (or safer) sex that helps prevent HIV infection falls down on the job of warding off syphilis. Although the majority of the spirochete's initial hallmark skin lesions — chancres — erupt on male and female genitalia, they can rapidly proliferate to other bodily targets, such as the mouth. Because these skin ulcers are brimful of T. pallidum bacteria, even a chaste kiss can spread the disease. Condoms can't encompass all the spreading genital sores.

Weinstock is one of the lead authors (among 34 in all) of a paper in today's Science, dated July 17, 1998. It reports the "Complete genome sequence of Treponema pallidum, the syphilis spirochete."

Its senior author is molecular biologist J. Craig Venter, founder-director of TIGR — The Institute for Genomic Research, in Rockville, Md. Of the 14 microbial genomes sequenced in the past four years, TIGR is responsible for half.

T. pallidum, a corkscrew-shaped spirochete measuring about one-fourth of a micrometer wide by five to ten micrometers long, turns out, the DNA-mappers determined, to have a circular chromosome of 1,138,006 base pairs. It carries 1,041 predicted coding sequences.

"Mechanisms of T. pallidum pathogenesis are poorly understood," the paper pointed out. "No known virulence factors have been identified and the outer membrane is mostly lipid with a paucity of proteins. Consequently, existing diagnostic tests for syphilis are suboptimal and no vaccine against T. pallidum is available."

But completion of the pathogen's DNA sequence bids fare to overcome these long-standing obstacles.

"The new genetic map of T. pallidum should make it easier for scientists to fill some remaining gaps in detection, treatment and prevention," said Penelope Hitchcock, chief of the sexually transmitted diseases branch at NIAID — the National Institute of Allergy and Infectious Diseases.

"A major problem for researchers," she added, "has been the inability to grow the organism in the laboratory. The genetic map identifies genes that are present or absent in the bacterium's metabolic pathways. This critical information will allow us to develop better drugs, a continuous laboratory system, and a specific diagnostic test for congenital syphilis."

Infection Even Unto The Next Generation

This neonatal form of the disease can occur when an untreated woman (who may not even know she has the infection) becomes pregnant.

About one-fourth of such babies are miscarried. Another fourth die soon after birth, and the remaining half may be born with skin rashes, pneumonia and skeletal abnormalities. If untreated, such infants face syphilitic blindness, deafness, and liver and nervous-system disorders.

During the latest periodic mini-outbreak of syphilis, in the late 1980s and early 1990s, congenital syphilis affected 3,000 infants a year.

A companion article in today's Science bears the title, "Elimination of syphilis in the United States." Its authors, Michael St. Louis and Judith Wasserhelt, are with the Center for Disease Control's National Center for HIV, STD and TB Prevention.

The authors point out that "in 1997 blacks outnumbered whites 40-to-one in reporting syphilis," adding, "This extraordinary differential in a disease that is so susceptible to basic medical care — in its infectious stage, it is treatable with a single dose of antibiotics — is one of the most glaring examples of existing gaps in minority health status."

They invoke a "window of opportunity" favoring an elimination campaign without delay: "As of 1997, we were in a period of the lowest incidence ever reported: 3.2 cases per 100,000 people, [concentrated] in just 31 (1 percent) of the 3,115 U.S. counties" —nearly all in the Southern states.

"The U.S. Public Health Service is once again targeting syphilis for national elimination," the co-authors observed, and estimated "such an effort would require at least $25 million annually for five years, matched by a parallel allocation of state and local resources.

"This would be not only a cost-effective but a cost-saving enterprise," they concluded, "as compared with the $80 million annual cost of syphilis treatment alone." *