ABSTRACT: Increasing sexually transmitted disease rates demand attention: Syphilis is re-emerging and new data suggest outbreaks cycle every decade. New tests make screening for chlamydia and gonorrhea easier.
CME OBJECTIVE: The reader will better appreciate the rationale for routine screening for sexually transmitted diseases and understand clinical sequelae, screening options, and therapeutic choices.
Edward W. Hook III, MD, grants/research support Becton, Dickinson and Co.; Gen-Probe, Inc.; consultant Abbott Molecular Diagnostics; honoraria Gen-Probe, Inc., Becton, Dickinson and Co. William Geisler, MD, honoraria Pfizer Inc.
Hot on the hunt for hidden dynamics of sexual disease transmission, UAB infectious disease expert Edward W. Hook III, MD, takes a stand. "Prevention has always been a neglected stepchild for funding," he says. "While biomedical research is critical, epidemics will increase unless we address epidemiologic analysis and behavioral changes with more impact than we are doing now," adds Hook, who directs the UAB Center for Social Medicine and Sexually Transmitted Diseases (STDs). He also serves as medical director of the Jefferson County Health Department's active STD Control Program.
In Hook's view, syphilis transmission, which researchers have just begun to fully understand, is entirely controllable.
"Syphilis is a fascinating disease, and rates are highest in the Southeast. From a public health perspective, it should be readily managable, but despite four large-scale attempts over the last 50 years, syphilis has not been eradicated. Each time the public health infrastructure reduced incidence, a decade later, rates skyrocketed."
Oscillating Endemic Syphilis
"We now know syphilis transmission follows an undulant course, based on a composite of endogenous biological factors — natural partially protective immunity — and exogenous environmental issues, including public awareness programs and social phenomena, such as crack cocaine and crystal methamphetamine 'epidemics,'" he continues. "No one has yet successfully combined these factors into a single predictor."
In the January issue of Nature (2005; 433:417-421), investigators reported that in the United States, "Repeated epidemics of syphilis...have followed roughly 10-year cycles. This new analysis, based on case report data collected from 68 cities since 1941, suggests natural oscillations in disease incidence are linked to host immunity rather than changes in sexual behavior. Current synchronized outbreaks may be due to a buildup of nonimmune individuals, rather than a return to unsafe sexual behavior."
Also, populations at risk have changed on multiple occasions, recently propelling syphilis from a largely homosexual disease to a threat to minority heterosexual couples, particularly women, which parallels the evolution of the HIV/AIDS epidemic. Although Alabama ranks 13th nationally for incidence of primary and secondary syphilis, Birmingham is only 38th on a list of US cities, a tribute to Jefferson County's vigorous public health system, Hook notes.
Parallels in Chlamydia and Gonorrhea
Hook says a recent Journal of the American Medical Association article (2002;287: 726-733) regarding undiagnosed, usually unsuspected gonococcal and sexually transmitted urogenital chlamydial infections in Baltimore should alarm primary care physicians. The authors reported nearly 1 in 12 adults in a sample population tested for STDs had a previously undiagnosed gonococcal or chlamydial infection. Based on these findings, they estimated the number of Baltimore adults with undiagnosed infections exceeded the number diagnosed and treated during the same years.
"This article tells us patients with gonorrhea or chlamydia are not always symptomatic, and asymptomatic infections are much more common than health-care practitioners realize," Hook explains.
According to the Centers for Disease Control and Prevention (CDC), the chlamydia diagnosis rate in Alabama per 100,000 adults in 2000 was 350.7; in Birmingham it was 547.7. For gonorrhea, rates were 276.0 per 100,000 adults in Alabama and 459.1 in Birmingham. These numbers are higher than national rates and have risen since 1999.
"Combined, chlamydia and gonorrhea are the main preventable causes of pelvic inflammatory disease, which in turn is the major preventable cause of infertility and ectopic pregnancy in the country," UAB STD specialist William M. Geisler, MD, MPH, says, noting at least 4 million Americans develop sexually transmitted chlamydia each year at a cost of $2.5 billion to the health-care system.
"Nationally, Birmingham ranks 19th for reported cases of chlamydia and 17th for gonorrhea among cities larger than 200,000; Alabama ranks 6th for chlamydia and 3rd for gonorrhea," he says. "However, these are only the infections we diagnose. If the number of undiagnosed infections is higher than those diagnosed, as the JAMA article suggests, then the prevalence of these STDs in our area is much higher.
"Although chlamydia and gonorrhea are extremely widespread, and if undetected, can have severe consequences, most people are unaware of the risks and assume, 'If I had an STD, I would know it.' This belief is a fallacy," Geisler says.
It is up to clinicians to screen for STDs, Hook adds. "Routine testing should be a regular part of health care for men and women under age 30," he says. "This includes adolescents; rates of both diseases are highest in 15- to 19-year-old girls."
Both Hook and Geisler stress that increasing physician awareness of the asymptomatic prevalence of chlamydia and the benefits of screening can decrease the spread of this costly disease. A landmark study in the Journal of Adolescent Health (2001;28:204-210) reported only 32% of physicians surveyed routinely screened asymptomatic, sexually active adolescents during routine gynecologic visits.
And, several new urine-based nucleic acid amplification tests (NAATs) are now available to make gonorrhea and chlamydia screening easier and more accurate. "For some patients, NAATs can be performed on a first-voided urine specimen, and in women, can also be done on a self-collected vaginal swab. So, a pelvic exam may not be necessary for all women, and a urethral swab is no longer always needed for men," Geisler says.
These tests are now readily available to most health-care providers. "Because chlamydia and gonorrhea are often asymptomatic, yet cause significant morbidity, physicians should routinely screen for these infections and make every effort to ensure partners of infected patients also get treatment," he says.
Effective Treatments
Recommended antibiotic regimens for syphilis, chlamydia, and gonorrhea are published in the CDC STD Treatment Guidelines (MMWR. 2002;51[No. RR-6]). A single dose of 2.4 million units of benzathine penicillin administered intramuscularly is recommended for primary, secondary, and early latent syphilis. For late latent syphilis or syphilis of unknown duration, the same dose of benzathine penicillin is given weekly for a total of three doses. For neurosyphilis, 18 to 24 million units of aqueous penicillin G is given intravenously, administered at 3 to 4 million units every 4 hours, for 10 to 14 days.
For nonpregnant HIV-negative patients with penicillin allergy, 100 mg of oral doxycycline twice daily may be given for 14 days in primary, secondary, and early latent syphilis and for 28 days in late latent syphilis. Doxycycline should not be used for syphilis in pregnant women or for people who have neurosyphilis; if these patients have a penicillin allergy, they should be desensitized. Azithromycin is being investigated as an alternative agent for syphilis, however, it is not currently recommended as front-line treatment. Recommendations regarding posttreatment follow up also can be found in the CDC STD Treatment Guidelines.
For uncomplicated chlamydial infections, recommended antibiotic regimens include 1 g of oral azithromycin in a single dose or 100 mg of oral doxycycline twice daily for 7 days. Both regimens are equally efficacious and well tolerated. For uncomplicated gonorrhea, recommended regimens include either a single 125 mg intramuscular dose of ceftriaxone or a single 400 mg dose of oral ofloxacin, 250 mg of levofloxacin, or 500 mg of ciprofloxacin. Because of rising fluoroquinolone resistance among gonococcal strains detected in persons in California and Hawaii, and also among men who have sex with men in large cities, intramuscular ceftriaxone may be better in these clinical settings. Fluoroquinolone or doxycycline use is contraindicated in pregnant women.
Partner notification and treatment also is being explored to decrease reinfection rates. "Researchers are investigating promising interventions, such as offering medication or a prescription for patients' partners, in hopes of breaking the cycle of infections," Hook concludes.
For more information
Dr. Edward Hook
Dr. William Geisler
1.800.UAB.MIST
mist@uabmc.edu
Published in UAB Insight, Summer 2005