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Biomedical Interventions Ch03.qxd 3/5/07 5:11 PM Page 60 3 Biomedical Interventions Stuart Berman, M.D., Sc.M., and Mary L. Kamb, M.D., M.P.H. Biomedical interventions for STD are not new. In fact, the 19th century discoveries related to syphilis in large part presaged the biomedical model of intervention. Three major discoveries at the dawn of the 20th century set the stage for subsequent medical advances: the identification of Treponema pallidum as organism responsible for syphilis; a complement fixation blood test that could diagnose the presence of the organism; and the identification by Paul Ehrlich of an arsenical, salvarsan (though not the magic bullet hoped for), that could kill the organism (1). Subsequently, the availability of penicillin and the publication of Surgeon General Thomas Parran’s “Shadow on the Land” con- tributed to the national effort to control syphilis transmission, supported by the National Venereal Disease Control Act (1938), the model for modern public health interventions based on the biomedical model. However, as this book demonstrates, the array of available interventions aimed at preventing and con- trolling sexually transmitted infections (STIs) now include many other non- medical approaches. Nevertheless, in many ways biomedical interventions are still the critical mainstay of prevention, and new biomedical approaches are constantly being evaluated and added to the armamentarium. In considering biomedical interventions, we have found that the Anderson- May equation, R = bcd, serves as a useful framework (2). In this construct, R, the reproductive number, is the average number of secondary cases associated with an index case; b is the measure of transmissibility, given exposure; c is the average number of susceptibles exposed during the period of infectivity; and d is the average period of infectivity. Although biomedical interventions may affect any of these transmission parameters, two of these, d—duration of infectivity, and b—transmissibility, are most directly affected and are the focus of this chapter. Some aspects of c are addressed by biomedical inter- ventions (e.g., vaccines); however, this parameter is primarily affected by sexual behaviors that are addressed elsewhere in this book. Reducing d—Duration of Infectivity Reducing duration of infection (i.e., affecting d) is the most obvious and his- torically most common means by which biomedical interventions reduce transmission. Case identification and prescribed antibiotic treatment of STD Behavioral Interventions for Prevention and Control of Sexually Transmitted Diseases. 60 Aral SO, Douglas JM Jr, eds. Lipshutz JA, assoc ed. New York: Springer Science+ Business Media, LLC; 2007. Ch03.qxd 3/5/07 5:11 PM Page 61 3 Biomedical Interventions 61 infection clears infection and renders the index case noninfectious—achieving “prevention” by reducing the period of infectivity, and thus reducing preva- lence. Although case identification and treatment is the biomedical interven- tion that probably comes to mind first, there are a variety of other biomedical approaches that can reduce duration of infectivity. STD screening of asympto- matic populations can identify unrecognized infections and allow treatment of cases that would otherwise have been missed. “Mass treatment” of an entire at-risk population—regardless of symptoms or behavioral risks—is a strategy that aims to reduce STD prevalence in the entire community. In addition to prescribed treatment approaches, nonprescribed approaches such as traditional therapies and folk remedies have been used to attempt to reduce symptoms and eliminate disease (and thereby infectivity). The various approaches and contexts by which biomedical interventions affect d are addressed here primarily for the curable STDs targeted by national control programs, typically for syphilis, gonorrhea, and chlamydia. However, some therapeutic approaches aimed at viral STDs such as herpes simplex virus (HSV) and human immunodeficiency virus (HIV) may also affect duration of infectivity, and these are commented on as relevant. Case Identification and Prescribed Antibiotic Treatment There are few more established, fundamental biomedical interventions than the antibiotic treatment of infectious disease. In fact, the landmark paper in 1944 promoting use of penicillin to treat syphilis (a disease that was already a public health priority) and gonorrhea was among the first published applica- tions of the drug (3,4). The availability of this powerful and effective antibi- otic therapy was a revolutionary advance that changed medical management of STDs and other communicable diseases forever, as antibiotic treatment not only prevented adverse consequences in the individual, but also affected disease transmission, incidence, and prevalence. Gonorrhea Classically, antibiotic treatment was primarily provided to those persons pre- senting with symptoms; in terms of gonorrhea, male urethritis was the typical presenting complaint, and was one of first demonstrated uses for penicillin (5). The treatment was highly effective—symptoms were relieved and in addition, infection was cured; the reduction in infectivity could be clearly demonstrated by microbiologic culture. In fact, treatment of gonococcal urethritis with an appropriate antibiotic has been demonstrated to eliminate infectivity in a mat- ter of hours (6). Treatment for gonorrhea has been observed to be so effective that some experts recommend that only therapies with greater than 95% effi- cacy would meet an acceptable standard of care (7). However, maintaining that rate of efficacy has been challenging since N. gonorrhoeae has proved quite nimble at acquiring antimicrobial resistance (8). In fact, evolving antibiotic resistance over time has resulted in substantial changes in the antibiotic regi- mens recommended for treatment of gonorrhea. As resistance emerged to penicillin and tetracycline, these drugs were no longer sufficiently effective, and have ceased to be recommended in most national STD guidelines (9). Currently, as an increasing percentage of N. gonorrhoeae strains have demon- strated resistance to quinolone antibiotics, this class of drug treatment is also becoming less relevant even in the United States. As of 2005, resistance has Ch03.qxd 3/5/07 5:11 PM Page 62 62 Stuart Berman and Mary L. Kamb reached high enough levels in certain settings or subpopulations that quinolone use for gonorrhea is no longer recommended in several western states includ- ing Hawaii and California, or among men who have sex with men regardless of location (10,11). In such situations, cephalosporins are the primary treat- ment recommended for gonorrhea, and although clinical failures have been reported and low levels of resistance to some cephalosporin preparations have been observed (12), resistance has not as yet been documented to ceftriaxone. If widespread antimicrobial resistance to ceftriaxone were to develop, gonor- rhea treatment options would be severely limited (13). Although antibiotic treatment of gonorrhea has been observed to be highly effective at the individual level, the broader public health benefit of treating symptomatic disease—primarily males who present with urethritis—is less obvious. The community trial conducted in Mwanza, Tanzania, during the early 1990s found that increased access to and quality of symptomatic STD treatment was associated with a 49% reduction in prevalence of male sympto- matic urethritis compared with control communities, although prevalence of gonorrhea among women attending antenatal clinics in the treatment and con- trol communities did not differ (14). Furthermore, evidence from mathemati- cal models has demonstrated the importance of providing prompt treatment to men and women with symptoms (15). Given reports of increasing delays in obtaining services in genitourinary medicine clinics in Britain, modelers eval- uated the public health impact of such compromise. The models indicated that when disease incidence is elevated, if access is limited a “vicious” cycle can be set in motion, whereby “inadequate treatment capacity leads to many untreated infections, generating further high incidence and high demand and thus maintaining the inadequacy of services” (15). Additionally, other data support the concept that compromises in treatment efficacy can also have pop- ulation-level public health impact, as at least one gonorrhea outbreak was attributed to prevalence of antibiotic resistant gonorrhea (16). How effective is case identification and treatment of gonorrhea in control- ling disease prevalence? In the United States, rates of gonorrhea disease did not decline dramatically until three years after a national gonorrhea control program, with broadly applied culture-based screening for gonorrhea among women, was launched in 1972 (17). Rates of gonorrhea continued to decline over the next 25 years, although the relative contributions of behavior change, partner notification, and screening are unknown (Fig. 1). However, some experts estimated that the gonorrhea prevention program—which relies pri- marily on antibiotic treatment—had shortened duration of gonorrhea infectiv- ity by 70% (18). Syphilis Assessing the role of case identification and treatment regarding prevention of syphilis transmission is somewhat more challenging than for gonorrhea. As is the case for gonorrhea, studies that document the effectiveness of penicillin are historic—before the era of randomized trials. But, additionally, evidence of antimicrobial efficacy is challenging to gather
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