Introduction
Largely because of the HIV epidemic, interest in STIs has increased over the past two decades. During that time, the epidemiology of STIs has changed in developing countries, partly as a result of modifications in STI case management approaches and partly because of behavioral changes in response to the HIV epidemic. At the same time, advances in STI prevention have enhanced understanding of the intricacies of STI transmission dynamics and the role of interventions in the control of STIs. However, what has not changed is as significant as what has changed: the epidemiology of STIs still differs substantially in the industrial countries and the developing world. The sociocultural and economic contexts in developing countries influence the epidemiology of STIs and help make them an important public health priority.
Incidence and prevalence rates of STIs are generally high in both urban and rural populations and vary considerably across areas. Because diagnosis and treatment of STIs are often delayed, inadequate, or both, rates of STI complications are also high in developing countries. Those complications include pelvic inflammatory disease, ectopic pregnancy, and chronic abdominal pain in women; adverse pregnancy outcomes, including abortion, intrauterine death, and premature delivery; neonatal and infant infections and blindness in infants; infertility in both men and women; urethral strictures in men; genital malignancies, such as cancer of the cervix uteri, vulva, vagina, penis, and anus; arthritis secondary to gonorrhea and chlamydia; liver failure and liver cancer secondary to hepatitis B or human T cell lymphotropic virus type I; and central nervous system disease secondary to syphilis (Holmes and Aral 1991; Meheus, Schulz, and Cates 1990; van Dam, Dallabetta, and Piot 1999). Thus, STI sequelae affect mostly women and children.
In developing countries, high levels of STIs and high rates of complications and sequelae result largely from inadequacies in health service provision and health care seeking (Aral and Wasserheit 1999). STI care is provided by a large variety of health care providers, many of whom are poorly trained in STI case management, and the quality of care they provide is often less than desirable (Moses and others 1994; WHO 1991). Health care seeking for STIs is frequently inadequate, particularly among women (van Dam 1995), because of the low levels of awareness regarding sexual health, the stigmatization associated with genital symptoms, and the asymptomatic nature of many STIs. A study in Nairobi, Kenya, found that 42 percent of patients had been symptomatic for more than a week before coming to a clinic and that 23 percent had been symptomatic for more than two weeks (Moses and others 1994).
Setting up good-quality STI services is considerably more difficult in resource-poor settings than elsewhere. Variables that affect the duration of infectiousness include adequacy of health workers' training, attitudes of health workers toward such marginalized groups as sex workers, patient loads at health centers, availability of drugs and clinic supplies, and costs of care (Moses and others 2002). Thus, improvements pertaining to all these factors would greatly improve STI-related services, help reduce the duration of infectiousness, and decrease the incidence of STIs (Aral 2002a). However, in many countries in the developing world, worsened economic conditions and the increasing burden of HIV/AIDS have negatively affected these variables. For example, in South Africa, the ratio of hospital beds to population declined from 6.5 per 1,000 in 1976 to 2.3 in 1996; during 1999, approximately 300 professionally trained nurses left the country each month; and student enrollments in nursing school declined from 12,282 in 1996 to 10,398 in 1999 (Aral 2002a).
Sexual behaviors also contribute to the STI burden in developing countries. These behaviors are heavily influenced by the sociocultural, economic, and political contexts, which in the past two decades have deteriorated at an accelerated rate in many areas. Societal change has included rising levels of inequality within countries, growing inequality between countries, increased levels of globalization, increased proportions of people who live in cultures they were not born in, and a larger proportion of the world's population living in postconflict societies (Aral 2002a). One effect of these changes is an increase in multipartner sexual activity, which in turn increases the rate at which infected and susceptible individuals are sexually exposed to each other and consequently the rate at which STIs spread.
Changes in STI Epidemiology, Management, and Prevention Since 1993
Since 1993, STI epidemiology and management have evolved interactively, particularly in developing countries. Technological advances in diagnosis, screening, and treatment; evaluation and widespread implementation of new case-management algorithms; and changes in risk behaviors in response to the AIDS epidemic have all influenced the dynamic typology of STIs (Wasserheit and Aral 1996).
The introduction of nucleic acid amplification tests, which have improved the sensitivity and expanded the repertoire of usable specimens, has heralded a new era in STI diagnosis. The use of urine and vaginal swabs in diagnosis has enabled providers to supply diagnostic and screening services outside traditional clinical facilities and has greatly enhanced the coverage of outreach activities (Schachter 2001). Unfortunately, many of these tests are currently too expensive for routine use in developing countries. Single-dose oral azithromycin has improved the treatment of several bacterial STIs (Lau and Qureshi 2002), but quinolones are apparently becoming ineffective for gonorrhea in some locations (Donovan 2004).
A major recent advance in STI prevention is the early success of a prophylactic, monovalent human papillomavirus (HPV) type 16 vaccine (Koutsky and others 2002); HPV vaccines may be able to help prevent genital and anal cancers in the foreseeable future. Researchers are evaluating multivalent vaccines for preventing moderate to severe cervical dysplasia as well. Other advances include easier episodic treatment of genital herpes (Strand and others 2002) and the use of suppressive therapy to reduce the transmission of genital herpes to regular partners (Corey and others 2004). In a related development, a prophylactic vaccine against herpes simplex virus type 2 (HSV-2) has shown limited efficacy in that it has proved partly effective for HSV-seronegative women, but not for men or herpes simplex virus type 1 (HSV-1) seropositive women (Stanberry and others 2002). Prevention successes of the recent past include STI sequelae, such as pelvic inflammatory disease and cervical cancer. A randomized controlled trial showed that selective screening of women for Chlamydia trachomatis significantly reduced the incidence of pelvic inflammatory disease (Scholes and others 1996).
Widespread implementation of syndromic management as an approach to STI case management has apparently had a considerable effect on the epidemiology of STIs, particularly in resource-poor settings (King Holmes and Michael Alary, personal communication, May 15, 2003).
In some developing countries, including Cambodia, the Dominican Republic, and Thailand, sexual risk behaviors have been changing over the past decade. In Uganda, for example, the age of sexual debut has increased, the frequency of sex with casual partners has decreased, and the use of condoms has increased (Stoneburner and Low-Beer 2004). During the 1990s, demographic and health surveys in 29 developing countries asked individuals if they had done anything to avoid AIDS (Low-Beer and Stoneburner 2003): almost 80 percent of men and 50 percent of women surveyed reported that they had. Specific behavior changes reported included increased monogamy, reduced number of partners, avoidance of sex workers, and increased condom use.
By contrast, in developed countries, recent years have seen behavior changes in the opposite direction; for example, in many European countries and in the United States, risk behaviors among men who have sex with men have increased significantly (CDC 2004; L. Doherty and others 2002). In addition, Gremy and Beltzer (2004) report declines in condom use among heterosexual adult populations in Europe. Investigators attribute increases in risk behaviors to the introduction and availability of antiretroviral therapy for HIV infection and the difficulties in sustaining preventive behaviors in the long term, referred to as prevention fatigue. Some researchers speculate that the widespread introduction of antiretroviral therapy in developing countries may have a similar disinhibitory effect on sexual behaviors and that changes in sexual behavior may offset the beneficial effect of antiretroviral therapy (Blower and others 2001; Blower and Farmer 2003; Blower and Volberding 2002; Over and others 2004).
Advances in STI prevention in recent decades have enhanced understanding of transmission dynamics and the role of interventions. Investigators have articulated the following five emergent insights about STI epidemiology and prevention over the past two decades:
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Populations consist of many diverse subpopulations, and each population-level epidemic trajectory consists of many distinct subpopulation epidemic trajectories (Pisani and others 2003). The epidemic trajectories of specific STIs differ depending on when and where the infection was introduced; the natural history and transmissibility of the infection; the structure of sexual networks; the demographic, economic, social, and epidemiological context; and the state of the health system (Aral and others 2005).
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Temporal dimensions are important in relation to STI epidemiology (Aral and Blanchard 2002). At the individual level, concurrency of partnerships and gaps between partnerships are risk factors for the acquisition and transmission of STIs (Adimora and others 2002; Agrawal, Gillespie, and Foxman 2001; Kraut and Aral 2001). At the population level, investigators have described the evolution of STI epidemics through sometimes predictable phases, characterized by changing patterns in the distribution and transmission of STI pathogens within and between subpopulations (UNAIDS and WHO 2000; Wasserheit and Aral 1996).
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Sexual networks are important in the transmission dynamics of STIs at the population level, and position in a sexual network is important in the transmission and acquisition of STIs at the individual level (Morris 2004).
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Trajectories whereby STI epidemics evolve differ for different types of population-pathogen interactions (Aral 2002a; Blanchard 2002; Garnett 2002). Whereas highly infectious, short-duration bacterial STIs—for instance, gonorrhea—depend on the presence of core groups marked by multiple sex partnerships of short duration for their spread, less infectious, long-duration viral STIs—for example, HSV—depend on the presence of multiple partnerships of longer duration.
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Interactions among sexually transmitted pathogens affect STI epidemic trajectories at the population level (Wasserheit 1991). The inconsistent findings of three landmark randomized community trials evaluating the effect of STI treatment on HIV transmission (Grosskurth and others 1995; Kamali and others 2003; Wawer and others 1999) can be accounted for by the complex, multifactorial, multilevel, and phase-specific nature of STI epidemics (Orroth 2003).
Epidemiology and Control
The epidemiology of STI pathogens, the local prevention and care infrastructure, and the cultural and sociopolitical context vary considerably within and across developing countries. At the same time, health care delivery for STIs varies by type of institution and location, although inadequate resources are universal in the developing world, as are recordkeeping, data management, and data analysis. The limited data that are available suggest that STIs are a major public health burden in the developing world. Although the prevalence and incidence of bacterial STIs have apparently declined because of expanded syndromic management, changes in sexual behavior, and death of high-risk populations, the prevalence and incidence of viral STIs seem to have increased over the past decade.
Syndromic Management
Health systems can use three different approaches to manage patients presenting with symptoms suggestive of an STI. First, etiology-based management relies on identifying causative microorganisms or detecting specific antibodies. It requires costly and often technically complex laboratory diagnosis, trained personnel, quality assurance programs, and infrastructure. Second, clinical diagnosis-based management is rapid, inexpensive, and requires less infrastructure than etiology-based management; however, clinical diagnosis is often inaccurate, may miss multiple infections, and may result in undertreatment or overtreatment. Third, syndromic management, which is based on the recognition of a constellation of clinical signs and symptoms, is inexpensive, can be standardized, and can be used by both physicians and paramedical personnel, though it often results in some overtreatment. Nevertheless, syndromic management has been recommended as a realistic approach for managing symptomatic patients in developing countries (Over and Piot 1993). Implementation issues associated with the syndromic management approach involve inadequate local evaluation of treatment algorithms because of a lack of local data, inconsistencies in implementation, and inadequate monitoring (Dallabetta, Gerbase, and Holmes 1998; Hawkes and Santhya 2002; WHO 2001b).
Limitations of the syndromic management approach include the inability to directly target the subclinical STI pool, the variability of STI symptoms and signs, the potential for wasting antibiotics, the risk of promoting drug resistance, and the unintended consequence of decreasing the skill levels of health care providers (Dallabetta Gerbase, and Holmes 1998; Donovan 2004). Moreover, syndromic management tends to undermine STI surveillance efforts because cases are managed and treated in the absence of a specific clinical or laboratory diagnosis (O'Farrell 2002).
Role of Core Groups and Bridge Populations
Core groups—that is, groups of individuals who have large numbers of sex partners who themselves have large numbers of sex partners—play an important role in the spread and persistence of STIs and are characterized by a high prevalence of STIs. Examples of core groups include sex workers, drug users, truck drivers, and bar girls. Because a case treated or prevented in a core group member tends to prevent that person from infecting several others, interventions that target core groups tend to be more effective and more cost-effective than interventions that target the general population (Ainsworth and Over 1997; Over 1999; Over and Piot 1993). In situations in which a high prevalence of STIs is concentrated in core groups, so-called bridge populations (individuals who have sexual links with members of both high- and low-prevalence subpopulations) may play an important role in disseminating infection from core groups to the general population (Aral 2000; Aral and others 1999; Gorbach and others 2000; Morris and others 1996).
Several variables influence the relative importance of core groups in the spread of STIs, including the characteristics of the specific pathogen, such as its transmissibility and duration of infectiousness; the phase of a particular epidemic; and the duration of sexual partnerships among those involved in multipartner sexual activity (Aral 2002a, 2002b; Blanchard 2002; Garnett 2002; Wasserheit and Aral 1996). The role of core groups in STI dissemination tends to be greater during the initial and later phases of epidemics, when infection is highly concentrated in small, high-risk subpopulations, than during the middle phases of epidemics, when infection tends to be widely spread across subpopulations. The importance of core groups appears to be greater in populations in which most people are involved in sexual activity with a single partner and only a small minority of people engage in short-term sexual partnerships with a large number of sex partners (Laumann and Youm 1999).
Antibiotic Use and Drug Resistance
Antibiotic use is unregulated in many developing countries, and antibiotics are frequently misused and overused, which results in drug resistance. Resistance to antimicrobial drugs is increasing mortality and morbidity from infectious diseases (Hart and Kariuki 1998). STIs are among the most frequently occurring infections worldwide, with more than 76 percent estimated to occur in the developing world (WHO 2001a). Neisseria gonorrhoeae has shown great versatility in developing resistance to antimicrobial drugs, including sulfonamides, penicillins, and tetracycline. Fluoroquinolones such as ciprofloxacin and ofloxacin have proved highly effective in treating gonorrhea, but after widespread and often inappropriate use of fluoroquinolones, resistant N. gonorrhoeae has emerged. In some areas, such resistance leaves third-generation cephalosporins as the only predictably effective antibiotic treatment for gonorrhea.
STIs and HIV/AIDS
Because HIV is a sexually transmitted infection, people who are infected with another STI also tend to be at increased risk of HIV infection and vice versa. However, beyond this correlation resulting from common risk behaviors, STIs and HIV may facilitate each other's transmission.
