Human Ecology and Behavior and Sexually Transmitted Bacterial Infections KING K

Home , Chlamydia, Chlamydia (genus), Chlamydia trachomatis, Lymphogranuloma venereum

Proc. Natd. Acad. Sci. USA Vol. 91, pp. 2448-2455, March 1994 Colloquium Paper

This paper was presented at a colloquium entited "Changes in Human Ecology and Behavior: Effects on Infectious Diseases," organized by Bernard Roikman, held September 27 and 28, 1993, at the National Academy ofSciences, Washington, DC. Human ecology and behavior and sexually transmitted bacterial infections KING K. HOLMES Department of Medicine and Center for AIDS and Sexually Transmitted Diseases, University of Washington, Seattle, WA 98122

ABSTRACT The three direct determinants of the rate of 1,000,000- spread of sexually diseases (STDs) are sexual behaviors, the mean duration of Infectiosness, and the wean 100 DE0 i e of sexual ission of each STD. Underlying ecological and behaviral factors that operate hugh one or more of these direct dermiants Lie on a ontiuum, ranging 0(Y from those most promte back to those more remote (in time or me m) from the direct determinants. Most remote and least modifiabl are the- of economic develop- stages 0 ment that even today y patter of sexual 0. 10- behavior. Next are the ditribution and changing patterns of Reubli ofChna177199 bimate, hygiene, and p density; the giobal population e n and stages of the demographic tansition; and ongo- '77 '78 '79 '80 '81 '82 '83 '84 '85 '86 '87 '88 '89 ing -hanges in human physiology (e.g., menarche at younger Year More on the and culture (e.g., later marriae). proximate FIG. 1. Trends in reported sexually transmitted diseases, Peoples continuum are war, mi , and travel; and current policies Republic of China, 1977-1989. for e o developet and social welfare. Most recent or modifible are t o and commercial product develop- nity randomization trials of improved STD control for HIV ment (e.g., oral contraceptives); checumcision, condom, sper- World micide, and contreaption practices; patterns ofIllicit drug use prevention are planned or under way in Africa, the at I e seual behaviors; and the accessbit, quality, Health Organization (12) and U.S. Agency for International and me of ED health care. These underlying factors help Development (13) identify treatment ofbacterial STDs as one explain why the curable ba l STDs are epidemic In devel- ofthree available public health strategies (along with condom oplu es and why the United States Is the only- Indus- promotion and sexual behavior change) for preventing sexual trialie country that has failed to control bacterial STDs transmission ofHIV. Ironically, our own country, possessing during the AIDS era. resources and technical capabilities for control of bacterial STD, has not applied the same balanced strategy within our The four major bacterial sexually transmitted diseases borders. Neither promotion of condom use nor control of (STDs), gonorrhea, chlamydial infection, syphilis, and chan- bacterial STDs has been aggressively pursued within the croid, all rank together with human immunodeficiency virus United States during the AIDS era. (HIV) infection among the top 25 diseases causing loss of Our failure to implement effective programs for preventing healthy days oflife in a representative high prevalence urban heterosexual HIV transmission may stem from the wide- area of sub-Saharan Africa (1). The prevalence of bacterial spread but misguided belief that heterosexual AIDS is not a STDs in many developing countries is extremely high (2). In problem in the United States (14). Even as national surveil- China and Thailand, where national STh surveillance sys- lance showed that heterosexually acquired AIDS increased tems do exist, major epidemics of bacterial STDs have faster than AIDS in other risk groups every single year for the occurred in recent years (Figs. 1 and 2). In contrast, every past 9 years, ultimately becoming the principal form ofAIDS Western industrialized country but one has eradicated chan- in women, we have allowed STD control to deteriorate in the croid as an endemic disease and dramatically reduced the United States. Better definition of the ecologic and behav- incidence of gonorrhea and syphilis during the AIDS era. ioral determinants of the emergence of the bacterial STDs- Many are bringing chlamydia under control. Only the United all curable-provides the basic conceptual framework for States allowed gonorrhea, syphilis, and chancroid to go out rethinking prevention and control of STD/HIV in the 1990s. of control during the AIDS era, as summarized elsewhere in The following discussion begins with current epidemio- this issue by Wasserheit (3), and the United States has failed the to implement a country-wide chlamydia control program. logic models of STD, then hihlhts available data on Beyond the extensive morbidity caused directly by these three direct determinants of the rate of spread of STD, and four STDs, all represent risk factors for heterosexual trans- finally, examines key ecologic and behavioral factors that mission ofHIV (4-8). STD may increase heterosexual trans- operate through these direct determinants to explain the mission of HIV by producing genital inflammation in HIV- emergence of the four major bacterial STDs in developing infected persons, thereby enhancing shedding of HIV in countries and in subpopulatiops of the United States. The genital secretions (9-11), or by producing genital inflamma- discussion compares causal factors in developing countries tion in individuals who are sexually exposed to HIV, thereby and in the United States and indicates how these factors enhancing susceptibility to HIV acquisition. While commu- operate at the population level and at the individual level. 2448 Downloaded by guest on September 30, 2021 Colloquium Paper: Holmes Proc. Natl. Acad. Sci. USA 91 (1994) 2449 patterns of sexual mixing in poor urban areas may contribute to rapid spread of STDs. In summary, STD prevalence and incidence in a particular sociogeographic setting is determined by factors that influence (3, those that influence sexual behaviors (mean rate of partner change in the population, variance in rate of change, and patterns of partner mixing), and those that influence D (availability and use of good STD health care). The next section elaborates on the definition and current status of ecologic factors that most closely influence each of these three direct determinants of Ro. '80 Year Global Health Care and the Duration of Infectiousness of Bacterial STDs FIG. 2. Trends in reported bacterial sexually transmitted diseases, Thailand, 1%7-1992 (from the National Ministry of Health of The quality, accessibility, and use of health care services Thailand). GC, gonorrhea; NGU, nongonococcol urethritis; LGV, the lymphogranuloma venereum. determine the average duration of infectiousness of bacterial STD. Early diagnosis and treatment, therefore, Epidemiologic Models of STD represent primary prevention of new infections and secondary prevention of complications. Models of STD epidemiology draw on the concept of "core Developing Countries. Bacterial STDs predominate among groups" of individuals who can maintain the spread of an adult clinical consultations, disproportionately affecting STD within a larger population. Various authors have defined those who cannot afford private care. Because early diagno- "core groups" differently, for example, referring to those sis and treatment of STD have not been a high priority in the with repeated STDs, those living in high-prevalence areas, public health sector until now, many bypass the formal those with high-risk lifestyles (e.g., sex workers and their private and public health care systems for STD treatment. clients), or those with prevalence rates of STDs so high as to Men with urethritis often go directly to pharmacies, and often "preempt" the introduction of new infection into their group receive inappropriate, yet costly, therapy. (15, 16). Women with bacterial STDs may not develop genital Core groups (17-19) have also been defined in terms of symptoms and would never undergo routine screening for transmission of STDs and three principle determinants of the these infections in developing countries; those who develop rate of STD have been delineated. The reproductive symptoms may not seek or find medical care; those who seek of spread or bimanual exams in rate, is the initial rate of secondary cases of STD arising and find care seldom receive speculum Ro, the least countries; where such exams are done, from a new case. At Ro > 1, the STD spreads; at Ro < 1, it developed out. The three determinants of the rate of spread are the microscopy and specific tests for gonorrhea, chlamydial dies are available. average risk of infection per exposure or efficiency of trans- infection, and Haemophilus ducreyi rarely Although official policies require testing pregnant women for mission ((3); the average rate of sexual partner change within who do average duration of the syphilis, many receive no prenatal care, and those the population (c); and the (D) without Effective and for individuals with the STD. Thus = often slip through syphilis screening. infectious period Ro STD are now included on the x c x D. relatively inexpensive drugs list but seldom reach care When the population prevalence of an STD is at equilib- international essential drug primary clinics that serve women. For those very select few infected rium, then Ro = 1 and c = 11,/D. Based upon published or values for and D, Brunham and Plummer (20) have women who might develop symptoms, seek care, be exam- probable ined, have tests performed or receive a correct syndromic estimated values for the mean rate of partner change (c) diagnosis, and receive effective therapy, treatment of the required to sustain transmission of different bacterial STD. male partner is not attempted, and reinfection is likely. Without health care, D is large, and rates of partner change Thus absence of the necessary clinical, laboratory, phar- required for sustained transmission are highest for chancroid macy, and public health infrastructure results in a very long and syphilis, lowest for chlamydial infection, and intermedi- average duration of infectiousness for bacterial STD. When ate for gonorrhea. With early diagnosis and treatment, D combined with high-risk sexual behaviors and efficient trans- decreases, and the rate of partner change required to sustain mission, very high equilibrium prevalence rates result. transmission increases. In developing countries and poor The United States. There are several thousand public STD urban areas with poor access to early treatment and pro- clinics in the United States, some free standing as categorical longed infectiousness, lower rates of partner change sustain metropolitan STD clinics, often serving predominantly men; spread of bacterial STDs. some integrated with family planning clinics serving predom- Subsequent work by Anderson (19) demonstrated that the inantly women; some integrated with community or health greater the variance in rate of partner change within the department primary care clinics. Prior to the 1970s, STD population, the greater the calculated value ofRo. Those with clinics emphasized treatment and partner notification for highest rates of partner change (the "core group") contribute syphilis and treatment of gonorrhea in men. Subsequently, disproportionately to STD transmission. In populations STD clinics introduced several new services, such as gon- where a few persons have many partners, the high variance orrhea culture testing of women, partner notification for in partner change effects a high rate of STD transmission. gonorrhea, and vaginal speculum and bimanual pelvic exam- Thus, for example, the crack cocaine epidemic, with frequent ination. Uniform guidelines were developed by the Centers exchange of sex for drugs by a few individuals, has a for Disease Control for treating conditions poorly managed potentially big influence on STD transmission. earlier, such as nongonococcal urethritis, mucopurulent cer- Patterns of partner mixing also influence Ro. At low mean vicitis, bacterial vaginosis, and pelvic inflammatory disease. rates of partner change, Ro is highest when those with many Most recently, STD clinics have also expanded services for partners tend to have sex nonrandomly with others who viral STD, including counseling and testing for HIV, and themselves have many partners (21). Such "assortative" some provide cervical Pap smears. Downloaded by guest on September 30, 2021 2450 Colloquium Paper: Holmes Proc. Nadl. Acad. Sci. USA 91 (1994) Principal failings ofour public STDclinics during the AIDS 15-19 years old who were sexually experienced, from 28.6% era include the inability to provide (i) sufficient access for all in 1970 to 51.5% in 1988, including an increase among white persons seeking health care (22), a problem worsened acutely teenagers from 44.1% to 51.5% during the AIDS era from by the added burden of HIV testing and counseling; (ii) 1985 to 1988. Similarly, the General Social Survey collected hepatitis B vaccination of high-risk groups to reduce spread limited data annually from 1988 to 1990 on sexual behaviors of the first vaccine-preventable STD; and (iii) nationwide of U.S. adults (33), providing perhaps the best comparison diagnostic testing for Chlamydia trachomatis infection or yet available ofrecent sexual behaviors ofmales and females, partner notification for chlamydial infection or related syn- with data stratified by age, race, and marital status. Results dromes. help explain age and race disparities in rates ofbacterial STD Prior to 1992, only 1 of 10 regions in the United States, in the United States and suggest that >22.5 million U.S. region X, received federal funds for a region-wide chlamydia adults had 2 or more sex partners during the preceding year, screening program (23). About 150 family planning clinics in with an estimated 4.8 million having had 5 or more partners. the Pacific Northwest began selective chlamydia screening in The 1990 National AIDS Behavioral Surveys (34) assess 1988. Chlamydia prevalence has since declined by >50% in HIV-related sexual risk behaviors. Most recently, from the women throughout the region. A few other areas, such as landmark 1990 National Survey of Men (NSM-I), a series of Wisconsin, where chlamydia control programs were also five articles by Tanfer and coworkers (70-74), concerning begun, replicated this experience. Screening is particularly sexual behaviors of men 20-39 years old, appeared in Family effective in reducing transmission of chlamydial infection, Planning Perspectives, March/April 1993. Age and race/ because of the often silent nature and long duration of ethnicity differences in numbers ofsexual partners paralleled infectiousness. age and race/ethnicity disparities in bacterial STD rates in In summary, inadequate health services for STD treatment the United States and the General Social Survey results (33). provide an obvious explanation for the high rates ofbacterial We await results of the national survey of female sexual STDfound in developing countries and in the inner cities and behavior from the same group. rural south of the United States. However, disproportion- These trends in heterosexual behavior over the last decade ately high rates of viral STD that are little influenced by contrast with the well-documented dramatic decline in unsafe medical treatment indicate the importance of other ecologic sexual behavior among homosexual/bisexual men, which and behavioral determinants in these same settings. strikingly cut rates of early syphilis and rectal gonorrhea. Prior to 1982, syphilis in the United States predominantly Trends and Patterns of Sexual Behaviors involved homosexual or bisexual men (35). Subsequently, the incidence of syphilis and gonorrhea in gay men plummeted, Developing Countries. Demographic data and ethnographic although several cities now see growing numbers of young research suggest progressive liberalization ofsexual behavior gay men with rectal gonorrhea. during the 19th and 20th centuries (24, 25), as a result of Overall, sexual attitudes and behaviors became steadily colonial and economic development, urbanization, popula- more liberal in the United States throughout the 20th century. tion growth, and other factors discussed below. These With oral contraception in the early 1960s came partial changes probably best explain the subsequent epidemic elimination ofthe double standard of sexual behavior ofmen spread of HIV and other ST~s. Because of the HIV epi- and women. The sexual revolution extended to homosexual demic, qualitative behavioral research and formal sexual and bisexual men at the same time. During the 1970s and behavioral surveys have been undertaken recently in many 1980s, an increasing percentage of young women had pre- countries. None approach the size of the sexual behavior marital intercourse, and recent birth cohorts have had more surveys recently completed in the United Kingdom (26), partners than earlier cohorts. During the AIDS era, gay men France (27), or the United States (see below), but generali- decreased risky sexual behaviors, but some young gay men zations are possible. Invariably the rate of change of sex now resume such behaviors. Surveys through 1990-1991 do partners for men exceeds that for women. In six African not suggest dramatic reduction in multipartner, casual, or countries surveyed in 1988-1990, the percentage of respon- risky sex among heterosexuals, though more recent data are dents who had engaged in casual or commercial sex in the last urgently needed. Cocaine-associated risky sexual behavior 12 months ranged from 8 to 44% for men, and 2-17% for has emerged since 1985 as a major factor in the spread of women, with the percent of men engaging in such behavior bacterial STD. 2-4 times higher than the percent of women in five of the countries (28). In Asia and Latin America, scattered general Determinants of Efficiency of Transmission of STD population surveys indicate even higher differences in pro- portions ofmen and women en ng in casual or commercial Three factors determine efficiency of STD transmission: the sex. These gender differences in sexual behaviors in Asia and size of the microbial inoculum, the susceptibility ofthe host, Latin America also exceed gender differences in the indus- and the infectious virulence ofthe pathogen (e.g., the ID50 for trialized countries (26, 27). a given host). The stage of infection at exposure influences The United States. Despite recent interference from Con- inoculum size, with highest inocula during early infection, gress, several methodologically sound surveys of sexual with lesions or exudate. Continued sexual activity despite behavior have been conducted in the United States. Zelnik symptoms of STD can reflect lack of knowledge about STD, and Kantner (29) studied adolescent sexual behavior in lack of access to care, dependence on income from commer- national probability samples in 1971, 1976, and 1979, docu- cial sex, or use oftoxic drugs. The inoculum is reduced by use menting steadily increasing rates ofpremarital intercourse by of condoms or microbicidal agents (e.g., spermicides) and, teenaged females throughout the 1970s. The National Survey conceivably, by vaginal douching. Cultural differences in of Adolescent Males (30, 31) found that from 1988 to 1991, condom and spermicide use undoubtedly influence STD 17.5- to 19.0-year-old males experienced a significantly transmission. Finally, just as other STDs influence genital younger mean age of first intercourse and a significant HIV shedding, genital infection or inflammation caused by increase, from 2.0 to 2.6, in the mean number of sexual one STD pathogen (e.g., gonorrhea) might also influence partners over the past 12 months, with no increase in fre- genital shedding of another bacterial STD pathogen (e.g., quency ofcondom use. The 1973, 1976, 1982, and 1989 cycles chlamydia) (36). of the National Survey on Family Growth (32) showed a Host susceptibility to chancroid, and perhaps to syphilis continuing increase in the proportion of female teenagers and gonorrhea, is reduced by male circumcision (37). Tradi- Downloaded by guest on September 30, 2021 Colloquium Paper: Holmes Proc. Natl. Acad. Sci. USA 91 (1994) 2451 tional male circumcision practices probably protect some believe all clinical and epidemiological differences between populations against these STDs. Male circumcision is less venereal syphilis of adults and endemic syphilis in children, common in U.S. blacks (37) and Hispanics than in whites, and perhaps even between syphilis and yaws, reflect ecologic creating an increased risk for these infections in blacks and factors and sexual behaviors, rather than essential differ- Hispanics. ences in pathogenicity of Treponema pertenue (the cause of Cervical ectopy, which decreases with advancing age and yaws) and the variants of Treponema pallidum associated increases with oral contraceptive use, increases susceptibil- with endemic syphilis of children or venereal syphilis of ity to chlamydial infection, and perhaps to gonorrhea. Very adults. young sexually active women and oral contraceptive users Similarly, poor hygiene, flies, and crowding characterize with ectopy are particularly susceptible to chlamydial infec- the epidemiologic niche for ocular trachoma strains of C. tion. Early average onset of intercourse among females or trachomatis (serovars A, B, Ba, and C) while sexually high rates of oral contraceptive use probably foster rapid transmitted LGV strains of C. trachomatis now require transmission of chlamydial infection. tropical developing country settings, whereas genital sero- Variations in infectious virulence of Neisseria gonor- vars D-K of C. trachomatis cause urethral and cervical rhoeae may influence efficiency of transmission of gonor- infections throughout the world. rhea. Certain strains ofN. gonorrhoeae are resistant to fecal Modern studies have not sufficiently addressed the effec- acids, and are more prevalent among homosexual men, tiveness of hygiene or use of antiseptics in preventing trans- probably because of more efficient transmission by rectal mission or acquisition of chancroid or syphilis in high-risk intercourse (38). Other strains that tend to cause dissemi- populations. nated gonococcal infection, with bacteremia and tenosyno- "Socio-Geographic Space" and Bacterial STDs. The influ- vitis, are highly susceptible to fecal acids, and uncommon in ence ofgeography, crowding, and hygiene on transmission of gay men, perhaps explaining why disseminated gonococcal the endemic treponematoses, chlamydia, and chancroid infection has been relatively uncommon among gay men. somewhat presages current concepts ofthe social and spatial concentrations of STD, and the spread of these infections Ecologic Factors Influencing the Emergence of along social networks and spatial contiguity or transportation Bacterial STD links (41-44). Rothenberg (41) and others (45) documented geographic clustering of high gonorrhea incidence in a few Having considered the three direct determinants of the rate urban census tracts. An impact on AIDS and STD of short- of spread of bacterial STD, we next consider underlying sighted policies for public services-not only public health ecologic factors that have influenced the emergence of bac- services but also fire control, housing, and others-has been terial STD. inferred by Wallace (43), who decried how planned reduction Historical Stages of Economic Development. As the econ- in capacity to contain urban fires led to spreading urban omy evolved from hunting to agriculture to industry, patterns decay, and the physical and social "ghettoization" of the of sexual behavior, reproduction, moral codes, and religion Bronx. While sexual behaviors and health care most directly presumably adapted. With the transition from hunting to determine the rate of introduction and removal of bacterial agriculture, children became economic assets at an early age, STDs in the population, the patterns ofintroduction, spread, the family became the unit ofproduction, and land became a and removal within and between communities are determined valuable commodity to be passed on from father to son. Early by social networks and spatial factors, influenced by urban/ marriage, monogamy, and multiple births were reinforced by community planning and services. religion and moral codes (39). In sociobiological terms War, Travel, and Migration. Quinn (46) discusses these "greaterpredictability offood in space and time promotes the factors separately in this issue as determinants of the spread evolution of territoriality. When the resources are dense and of HIV infection. They equally influence spread of bacterial easily defensible, and when food is the limiting resource, the STD. The possible contribution ofepidemic urban decay and optimum strategy is the double defense-by means of the resulting migration described by Wallace (43) to the reemer- monogamous pair bond" (40). gence of gonorrhea, syphilis, and chancroid in the United With the industrial revolution in Europe and North Amer- States provides one example. Global examples include the ica, the family unit fragmented, as parents and children left epidemic increases in gonorrhea and syphilis in the industri- the home and village to find work in cities, children no longer alized countries during and after World Wars I and II and in were economic assets, marriage was delayed, secular insti- the United States during and after the Vietnam War, and the tutions began to replace religious and moral codes, and rapid global spread of two types of (3-lactamase-encoding premarital and extramarital sex became more common. This plasmids in gonococci from separate regional foci in Asia and scenario is replayed conspicuously today in the emerging Africa in the 1970s. The resurgence of reported STDs in countries throughout Asia, Latin America, and Africa. China (Fig. 1) accompanied reopening of the country to Geography, Crowding, and Hygiene. Climate, crowding, foreign visitors, movement ofthe male work force within the and hygiene profoundly influence the epidemiology of the country to industrial centers, and reemergence of a commer- nonvenereal treponematoses of childhood (yaws, pinta, and cial sex industry in response. Similarly, the growth of the endemic syphilis). Crowding, primitive conditions, and poor commercial sex industry in Thailand accompanied increased hygiene have characterized settings permitting spread of military, work-related, and tourist travel and urbanization, all endemic syphilis, typically within family units, and yaws of which fueled epidemic STD (Fig. 2). Indeed the classic persists in some developing tropical countries. At one time, tendency of one country to attribute STD epidemics to endemic syphilis was a problem even in Northern Europe and another country (e.g., syphilis, as both "The French Dis- North America, disappearing as living conditions improved. ease" in Italy and "The Italian Disease" in France at the end The WHO/UNICEF-coordinated global program for eradi- of the 15th century) generally reflects changing behaviors in cation of the endemic treponematosis in the 1950s and 1960s both countries during periods of war, migration, or increased greatly reduced yaws prevalence throughout the developing travel. world. Endemic syphilis was eradicated in Bosnia, and pinta The Demographic and Epidemiologic Transitions. Fig. 3 disappeared in Latin America. The next generations were contrasts the age distribution ofthe population of the world's rendered fully susceptible to adult syphilis, as immunity from developing regions with that ofthe industrialized countries in the childhood treponematoses no longer occurred and sexual 1980 and shows projected growth to the year 2000. Young behaviors became more liberal. Many tremonematologists people predominate now in developing regions and will Downloaded by guest on September 30, 2021 2452 Colloquium Paper: Holmes Proc. Nati. Acad. Sci. USA 91 (1994)

Developing Regions Male -80 3M Female 1980 - 3.3 billion 70 I 2000 - 4.8 billion -60 I r//A VIZA 50 I, I V." 40 I V,,,,,, I Vaczzzz ,,, 30 A/// 20 10 O- I E6yzzzzA 300 250 200 1io 16o 50 0 50 100 150 200 250 300 Population in Millions Population in Millions

FIG. 3. World population by age and sex for 1980 and projected for the year 2000 for developed and developing regions (United Nations).

become even more predominant. Furthermore, the percent- Menarche generally occurs later in developing countries, but age of the world's population living in urban areas will grow earlier in urban than in rural areas. This progressively earlier from 37% in 1985 to 45% by the year 2000 and to 61% by 2025 sexual maturation and the progressively delayed mean age of (47); in developing countries, this urban migration selectively marriage greatly extends the duration of time that premarital involves young adults, typically young men. This will further intercourse can occur, making social, cultural, and religious markedly increase the relative numbers of young adults proscriptions less effective than in the past. within cities, creating even a larger predominance of young Soca and Economic Development Polie DevInng men in cities (48). Countries. The low status of women and economic develop- Declining birth rates plus increasing life expectancy is ment policies that move the male work force away from producing a demographic transition to an older population in families and communities into urban industrial centers con- Western industrialized countries. This leads in turn to an tribute to the epidemics of STD/HIV in many developing epidemiologic transition, in which aging of the population, countries (24, 48, 51). The relatively poor educational op- improved economic and health infrastructures, and declining portunities for women leave them ill-prepared for economic rates of death from childhood communicable diseases result survival outside of marriage, especially after child-bearing. in older average age at death and growing morbidity from This problem, where coupled with the emergence ofurban or noncommunicable diseases of adults. periurban male slums, fosters casual and commercial sex and However, in developing countries, especially in Africa and a new generation of urban or periurban teenagers with one South Asia, birth rates remain high, and child survival available parent (who may be a sex worker) and without a improves due to successes of the extended. program on stabilizing extended family or community. immunization, use of oral rehydration solution treatment for In summary, interrelated factors, including separation of diarrhea, and improved care of acute respiratory infection. families with male urban migration, low status of women, Rapidly growing numbers of children who survive cause a increasing urban, periurban, and interurban prostitution, a sustained and disproportionate surge in the size of the demographic transition characterized by growing and desta- adolescent and young adult age groups, both in absolute bilizing excesses of teenagers and young adults no longer numbers and relative to the size ofthe older population. The success survival programs and comparative failure of ofchild No--in-Hsp,a rm family planning programs in sub-Saharan Africa and South Asia have led to an unanticipated stage in the epidemiologic transition (49), the epidemic of communicable diseases of -****'J--~* adolescents and young adults (i.e., STDs/AIDS). Fig. 4 shows the age distribution of the population of the 25-44-. United States in 1990 for blacks, Hispanics of any race, and non-Hispanic whites. The proportion ofblacks and Hispanics 45 -64 - 65-79 from 5 to 24 years old substantially exceeds that ofwhites, so that the age pyramid for these U.S. minorities lies interme- 8F. diate between that of the developing regions and that of 0) 10 20 30 42.; 3 I C'- 220 3030 40 industrialized countries. Pa~~~~~~~~..Celi - -r-T1 Ages ofSexual Maturation and of Marriage. The average age of sexual maturation declined steadily during the 19th and 20th FIG. 4. Distribution ofthe population ofthe United States by age, century in industrialized countries. In the Nordic countries, race, and Hispanic origin in 1990 [Bureau of the Census (1990); average age at menarche was about 16 years in the mid to late Census of Population; General Population Characteristics (1990); 19th century, falling steadily to 13 by the mid 20th century (50). Census of Population CP-1-1;17-24]. Downloaded by guest on September 30, 2021 Colloquium Paper: Holmes Proc. Natl. Acad. Sci. USA 91 (1994) 2453 under the regulatory influence ofa nuclear or extended family Mental Health Epidemiological Catchment Area Program, or community, and war, migration, and travel, have fostered Robins (56) found that the proportion meeting criteria for changes in sexual behavior and epidemics of STD in devel- adolescent antisocial conduct disorder had increased from oping countries during the 20th century. Many similarities are 0.5% of females and 6% of males in the oldest (65+) cohort, evident in the United States. to 13% of females and 36% of males in the youngest (18-29) A "Synergism of Pagues": STD/HIV, Teen Pregnancy, cohort. Nationally, with =1,000,000 admissions per year of Violence, and Cocaine Use. In the United States, bacterial adolescents into juvenile detention facilities, the average STDs, such as gonorrhea, syphilis, and chancroid, concen- number ofadolescents in detention is '.125,000, at an average trate in black and Hispanic populations, particularly among cost of about $40,000 per detainee per year. teenagers. The enormous disparity between blacks and The crack epidemic contributes to the related epidemics of whites in annual rates of gonorrhea and syphilis has actually violence, child abuse and neglect, and the resulting place- grown since 1985. Because this disparity largely depends ment of children in foster care. The epidemic of freebase upon basic structural disparities in socioeconomic attainment (later crack) cocaine use appeared as early as 1982 in the and in access to health care, it is not surprising that the Bahamas (57), where it was temporally and epidemiologically determinants of the STD epidemic in the United States and associated with major epidemics of HIV and genital ulcer in developing countries are similar. Race and ethnicity should disease, including chancroid, syphilis, and lymphogranuloma be viewed not as risk factors per se but as risk markers for a venereum, caused by the L2 strain of C. trachomatis (un- more complex set of underlying socioeconomic, cultural, published data). Crack use spread throughout the United political, behavioral, and environmental risk factors. States during the mid 1980s. Although the estimated number Specifically, the nature of the demographic transition in of current cocaine users dropped from a peak of 5.8 million black and Hispanic U.S. populations, a steeply rising pro- in 1985 to 1.3 million in 1992 (58), the number ofweekly users portion of children being born to unmarried mothers, frag- has not fallen since 1985. The estimated number of emer- mentation of the family and community, counter-productive gency room encounters for cocaine use increased rapidly social welfare policies, and a unique form of commercial sex from 1983 to 1989 (Fig. 5). After an encouraging decline in related to use of crack cocaine have been the prime deter- 1990, the numbers shot up again in 1991 and 1992 (59). These minants of changing sexual behaviors; and the failure of the encounters presumably reflect those cocaine users getting public health infrastructure to cope with rising rates of STD into most difficulties with the drug. Further, the percentage has worsened the problem in the United States. of cocaine users seen in emergency rooms who acknowl- In 1991, 1.2 million U.S. children born to unmarried edged use by smoking increased from 41% in 1990 to 53% in mothers represented 28% of all births. This included 68% of 1992, and as the "purity" of street cocaine rose from 58% in all births to black women, up from 26% in the 1960s; 41% of 1990 to 74% in 1992, the number ofemergency room encoun- births to Hispanic mothers; and 17% of births to white ters for cocaine overdose rose by 47%. women, ranging up to 44% of white women in poverty (52). The epidemics of teenage antisocial behaviors and crack The overall birth rates and pregnancy rates for U.S. teenag- use clearly promote the epidemic spread ofbacterial STD. In ers in 1990 exceeded those ofmost developing countries (52). juvenile detention populations, the combined prevalence of In 1990, 521,000 births to U.S. women 15-19 years of age gonorrhea and chlamydial infection typically averages .20%o represented a 20%o increase from 1986 to 1990 in rate ofbirths in girls. Gonorrhea is now linked to membership in street to teenaged women. Birthrates per 1000 women 15-19 years gangs (60). Crack use is directly related to syphilis, gonor- of age in 1990 were 42.5 for non-Hispanic white, 100.3 for rhea, and chancroid, as well as HIV infection (61). Crack use black, and 116.2 for Hispanic women (53). leads to several STD risk behaviors, including exchange of Trends in statistics for child neglect and abuse and in sex for drugs or money (62). placement of children in foster home care provide further New Technology and Product Development. Epidemic in- evidence of family fragmentation. Nationally, 2.2 million creases in gonorrhea and other STD in industrialized coun- children were referred to child protective services in 1986, tries closely followed the introduction oforal contraceptives, and an estimated 270,000 children nationally were in foster which liberalized the sexual behavior of women, increased care (54), a 223% increase since 1976. The urban situation the efficiency of sexual transmission of chlamydial infection is worst. Reports of child abuse or neglect totaled 52,504 and perhaps of gonorrhea, and decreased condom use for in New York City alone in 1992, and the number of children contraception. On the other hand, family planning programs in foster homes in New York City increased from ==18,000 in are now lowering fertility rates and slowing population 1985 to nearly 50,000 in 1992 (data from Management and growth, even where economic progress is slow (63), and this Analysis, Child Welfare Administration, Human Resources ultimately should slow STD spread. Administration, City of New York). Children commonly Development of fluoroquinolones and new oral cepholo- transfer from one family to another in the foster care system, sporins has made oral therapy for gonorrhea and chancroid some having been placed in 10 or more homes, precluding consistency in family values or approaches to child rearing. . - -- - In a disturbing recent article entitled "The Coming of the a) White Underclass," Murray (55) argues that this extraordi- nary increase in births to young poor single women and the LU 100.000-I- C resulting family fragmentation are due to social welfare D 80,000 - policies that encourage single parenthood, policies that are E 6 - the root cause of the growing problem with antisocial behav- z 60.000 ior in young people in the United States. 40.000- Ca Not surprisingly, multiple interrelated epidemics ofbehav- E ioral and emotional problems now converge in U.S. adoles- * 20,000- cents, with the epidemics of STD/HIV accompanied by LUEnJ ;..il ,a1, I concurrent epidemics of gang-related crime and violence, 1978 1980 1982 1984 1986 1988 1990 1992 drug use involving teenagers, sustained high rates of teen Year pregnancies, and increasing rates of live births to teenage FIG. 5. Estimated number of emergency room encounters for girls. In an analysis of retrospective data from successive cocaine use in the United States from 1978 to 1992 [from the U.S. birth cohorts of adults studied in the National Institute of Drug Abuse Warning Network (DAWN) surveillance system] (59). Downloaded by guest on September 30, 2021 2454 Colloquium Paper: Holmes Proc. Natl. Acad. Sci. USA 91 (1994)

Behavioral Risk Factors for Exposure to an FTmransmnission Infected Partner :-4 L::;oaZcatand tonsi - Choice of high risk partner AnnL.al pap -- Number of partners Antiviral therap, Sexual practices Prophylaxis vs Frequency of intercourse opportunistic infections Sexual Ex.proure_ Activity toSTD Health Care Acces _L Quality. Jtilization

- Effective mean rate of Host Susceptibiit acquiring new sex Sexual practices (esp Early diagriosis and partners* anatomic site exposed) curative treatment - Patterns of partner mixing - Male circumcision Health care access. Cervical ectopy -:T- ..a. _ utilization, quality Presence of other STD and - Mean efficiency of - Contraceptive method F ...... 1. sexual transmission Immunity acqUired from Q~omnp'466'atcons' previous infection. vaccine Virulence of STO Ecologic - Genetic factors Pathogens - Local microbial flora lI D5 holding host Determinants ? Stage of menstrual cycle susceptibility of Population or pregnancy constant) Prevalence of STD Risk Factors Influencing Efficiency of Transmission

FIG. 6. Overview of ecologic, microbial, and behavioral determinants of individual risk of acquisition and complication of STDs. *, Effective mean rate of acquiring new sex partners in the population = (mean rate of new partners + SD2/mean rate).

more feasible, even through pharmacies, possibly contribut- the modem global emergence of STD and AIDS. These ing to the recent decline in cases reported from STD clinics underlying factors must be addressed as public health pro- in Thailand (Fig. 2). grams are strengthened. As summarized in Fig. 6, for any individual, the risk of Eclogic and Behavioral Determinants of Complications and exposure to an STD depends upon the ecological (i.e., Sequeflae of Bacterial STDs sociogeographic) setting in which partners are chosen as well as upon the individual's own sexual behaviors (such as choice The many complications ofbacterial STD result from extension ofpartner within that setting and frequency ofpartner change from lower to upper genital tract; bacteremia; pregnancy or and sexual practices). A woman who lives and works in the puerperal infectious morbidity; congenital or perinatal trans- Bronx (where bacterial STDs are out ofcontrol) and has only mission; or inmunopathologic host responses. Good health one sexual partner may have much higher risk ofexposure to care access, quality, and utilization provide secondary preven- a bacterial STD than a woman who has 10 sex partners in tion of these complications. Other behaviors also influence Sweden (where bacterial STDs are under excellent control) complications. For example, vaginal douching is associated (69). The risk factors influencing risk of acquiring an STD by with increased risk of pelvic inflammatory disease (64, 65), is the exposed individual, when summed across individuals, more common among black women (65, 66), and may contrib- define the mean efficacy of transmission for the population. ute to high rates ofpelvic immatory disease and its sequellae At the individual level, health care behaviors influence risk of in black women. Conversely, oral contraception use seems to complications, as well as risk of further transmission. Clear decrease the risk ofpelvic inflammatory disease among women understanding and clear thinking about the populational and with cervical chlamydial infection (67). individual determinants of STD/HIV transmission and com- HIV infection may influence the risk and severity ofpelvic plications are required for developing, prioritizing, and im- inflmmatory disease among women with gonorrhea and may plementing public health strategies for disease prevention. increase the risk of neurologic complications of syphilis (68). Fortunately, many of these strategies are now well under- Finally, variation in the bacterial STD pathogens themselves stood and formulated by international agencies (12). Imple- influences disease manifestations. For example, strains of N. mentation of effective programs for sexual behavior change, gonorrhoeae that require arginine, hypoxanthine, and uracil condom promotion, and STD treatment still represents a for growth accounted for a high proportion of cases of formidable technical and economic challenge for developing gonorrhea in the United States and Europe during the 1960s countries. However, in the United States, the technical skills and 1970s and caused most cases of gonococcal bacteremia. are available, and only a small fraction of funds currently For unknown reasons, these strains have nearly disappeared spent on AIDS and other complications of STD would be from the United States, and disseminated gonococcal infec- required for more effective control ofbacterial STD. There is tion has become a rare disease. no longer any conceivable rationalization for not proceeding.

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