Sexually Transmitted Diseases (4th edition)

…by King Holmes, P. Sparling, Walter Stamm, Peter Piot, Judith Wasserheit, Lawrence Corey, Myron Cohen (…and many others: “This edition welcomes new editors Myron Cohen, Larry Corey, and Heather Watts, and 119 new authors”).

I thought that since I brought up my recent doctor’s appointment (not STD-related in any way…) in my last post, I should update you on that stuff here before getting to the book blogging. It was good news all around: There was nothing unusual about the EKG, I do not have microalbuminuria and my Hba-1c was 0.070 (/53) [relevant link to Danish readers]. HDL cholesterol was higher- and LDL and total cholesterol levels, as well as triglycerides, were much lower than required, and the BP was 123/82. I’m always a little concerned about the BP values because they’re sort of the ‘weakest link’ when it comes to my regular test results, but it’s nowhere near high enough to justify any kind of pharmacological intervention at this point.

Back to the book: I’ve read roughly the first 100 pages (Introduction and Overview as well as Part 1 – i.e. the first 5 chapters), and I like it so far. Some good stuff from the first part of the book:

1. “The prevalence, of persistent vaginal and cervical infections are remarkably high in young women; and the incidence, and prevalence, of the chronic STIs are exceptionally high in adults, with seroprevalence increasing steadily with advancing age for infections caused by HIV, syphilis, hepatitis B, and especially, HSV-2 and the genital types of HPV. It is therefore, undoubtedly true that a very large proportion of patients seen by clinicians of all disciplines—perhaps the majority of all adults in the world—have one or more STIs.”

2. “Cohort studies demonstrate condom effectiveness against STI acquisition, not only vs. HIV, but also vs. HSV, gonorrhea, and chlamydial and vaginal infections, and specifically against HPV infection—refuting earlier concerns that condoms did not prevent HPV acquisition.” (that condoms do seem to offer protection against HPV was news to me. Later on in the book the protection offered is made more explicit: “Even for human papilloma virus, which can be transmitted without exposure of mucosal surfaces, condoms have been found to reduce the risk of acquisition by 70%.28“)

3. One major effect of the introduction of penicillin […] was loss of public health interest in STD control. Public spending on STD control declined throughout the world, and these diseases became a low priority.24 For example, India developed the capacity to manufacture its own penicillin in 1954, after which the state governments of India turned their attention to other health problems.40

One significant exception to this trend was China. Partly because the Chinese had blamed STDs on foreign occupation of China and foreign cultural decadence, the Communist government adopted STD control as one of its major policy initiatives immediately after its 1949 political victory. In a campaign that included widespread public relations efforts through plays, radio programs, and small discussion groups, the government undertook a massive screening and treatment program including vocational rehabilitation for former female sex workers. By 1964, the government claimed to have eliminated STDs, a statement that is impossible to verify but widely accepted as a general indication of a very low Chinese prevalence rate. The long-term effects of the campaign are, however, less clear. Because STDs were represented as a social evil and sign of decadence, Chinese patients tried to avoid public hospitals, which charged STD patients to punish them for their having acquired these diseases. Social stigma became a major problem. Furthermore, the medical specialty of venereology was no longer practiced and taught after 1960s. With the liberalization of employment policies in 1989 and the subsequent development of an enormous migrant labor population (between 50 and 120 million people), rates of STDs began to increase, with insufficient medical resources and ability to respond.41

4.”Historically, prevention is the neglected aspect of STD control programs. Moral reformers have often asserted their control over prevention efforts by defining STD prevention as a problem of morality. Whether led by church groups themselves or by charitable organizations, these efforts focused on fear-based messages about the consequences of immorality (death, disfigurement, infertility, shame) along with representations of happy family life with abundant, healthy offspring as a consequence of correct moral choices..24

This approach seldom focused on the structural factors which influence sexual behavior, such as long-term labor migration which keeps spouses separated, population displacement, and lack of economic opportunities for young females. […] Not until the threat of HIV/AIDS emerged during the 1980s, when a fatal STD with no cure threatened the lives of millions, did governments begin to invest substantial resources into systematically studying behavioral science approaches to changing behavior.”

5. “STI/HIV are not spread randomly. Unprotected sex with an infected partner is by far the most important risk factor for STI/HIV infection.1,9 This in turn is influenced by prevalence and distribution of infection in a population, as well as the behavior of an individual and his/her partners.

Economic deprivation, low education, economic inequality, and economically driven migration and mobility have all been found to be associated with the risk of STI/HIV infection.10, 11, 12 […] processes associated with development such as increases in disposable income and increases in mobility among certain groups and not others are associated with increased risk.10,18 Professions involving high mobility and extended periods away from families, such as migrant labor, serving in the military, driving trucks, or working as sailors are also associated with augmented risk.”

6. “The primary mechanism through which STI contribute to mortality is through mortality associated with HIV. And with an estimated median survival time, a little above 9 years from HIV infection to death in developing countries in the absence of antiretroviral therapy, HIV has had a dramatic impact on adult mortality.25,37 [I’ve written about these numbers before here on the blog, but the 9 year time frame was news to me. Note that it’s age-dependant: “most infected [at birth or as a result of breast-feeding] children, in absence of antiretroviral therapy, will develop AIDS and die before their fifth birthday”. There’s a lot more in the book about this stuff if you’re interested.] […]

7. “Data on cost-effectiveness [of interventions] are extremely limited and a function of the scarcity of both effectiveness and cost data. The best available data are for health facility-based interventions such as syndromic STI management, screening of blood for transfusion, and prevention of MTCT. The data on cost-effectiveness of behavioral, community, and structural interventions are far weaker. […] the position taken in the current chapter is that estimates of the cost-effectiveness of STI interventions are highly variable, reflecting both the great heterogeneity in environments as well as the great heterogeneity in the efficiency of service delivery:

The health benefit in terms of numbers of disability-adjusted, discounted, healthy life years saved by curing or preventing a case of syphilis varies from 3 years in a person who has ceased all sexual activity to as many as 161 years in a sex worker with two partners a day. The cost of treating that prostitute for syphilis varies from US$ 5 to US$ 100. Thus the cost per disability adjusted life year (DALY) of syphilis treatment can range from 100/3 or US$ 33 per DALY to 5/161 or less than a US$ 0.05 per DALY. As we learn more about the complexities of delivering STI treatment services and take into account the diversity of risk behavior, the ease with which STI interventions can be ascribed a simple cost-effectiveness ratio has declined. […]

Almost by definition, there is more to be gained by changing the behavior of people with high levels of risk behavior than by changing that of an equivalent number of people with lower levels of risk behavior. However, the difference in the effectiveness between the two falls as epidemics become more generalized, such that in heavily affected countries prevention interventions are likely to become extremely cost-effective even when targeted to individuals with relatively low levels of risk behavior. Consequently, countries with low-level and concentrated epidemics should emphasize interventions that are targeted to individuals at especially high risk of becoming infected or transmitting the virus, whereas countries with generalized epidemics should also invest heavily in interventions that target entire populations or population subgroups. Thus, any determination of the likely effectiveness and cost-effectiveness of specific interventions in particular circumstances requires an accurate understanding of the stage and nature of the national epidemic.”

8. “The natural history of an infection is the relationship between that infection and disease and associated patterns of infectiousness. In understanding this natural history, individuals can be divided between mutually exclusive categories and the flows between them illustrated schematically in flow diagrams. Figure 3-1 shows the assumptions frequently made about a range of the key STIs in such flow diagrams.”


(click to view full size)

9. “Those with many sexual partners can drive the incidence of an STI in the population and have been described as a “core group”.48 Axiomatically, for a sexually transmitted disease (STD) to exist there must be individuals with sufficient sexual partners to transmit infection to more than one other person.49 If interventions could reliably prevent infection in these individuals, the STI could be eliminated. Studies of risk behaviors and the distribution of STIs have attempted to identify the characteristics of those within the core group as a target for interventions. […]

The lower the incidence of an STI in a population, the more it will be concentrated in those with higher risk behaviors. If the behaviors placing individuals at risk are similar then those most at risk of one STI would be the same as those most at risk of another infection. We would expect infections with a higher combined transmission probability and duration to not only be more widespread, but to also be found in those with STIs with a lower combined reproductive potential.52 If this is not the case as has been suggested in some observations,53 potential explanations include the acquisition of immunity against one infection, different likelihoods of receiving treatment, and different risk behaviors placing individuals at risk. […]

The choice of sexual partners of an individual will have a large influence on whether or not they are exposed to someone infected. The choice of sexual partners will depend upon the contexts in which potential couples meet, for instance, schools, church groups, beer halls, and family gatherings and how they relate. Studies show that individuals tend to choose sexual partners, particularly spouses, who are similar with respect to social and demographic variables such as age, education and income.47,49 Such a choice will lead to assortative (like-with-like) sexual mixing within the population with respect to the specific variables. […] Assortative mixing restricts the spread of STIs but helps maintain chains of infection within high-risk groups. Thus if mixing were assortative, an STI would be more likely to invade rapidly and persist within a population but would also be less likely to spread widely. In contrast, random mixing would spread infection from high- to low-risk individuals who are dead ends for the infection.”

10. “The basic reproductive number (R0) is a measure of the potential for the spread of an infection and can be defined for STIs as the average number of infections caused by one infectious individual entering an entirely susceptible population.69 The key components determining the value of the basic reproductive number are those discussed above: the transmission likelihood (β), the contact rate (c ) and the duration of infectiousness (D), with, in a simple, illustrative model, the product of these three being the basic reproductive number: R0 = βcD.69 The value of R0 determines: the chances of an epidemic when an infection enters a population; the rate of spread of the epidemic; the endemic level of infection, and the effort required to bring the infection under control. An important distinction has to be drawn between the basic reproductive number, R0, which measures the potential for spread in a naive population, and the effective reproductive number, Rt, which changes depending on the experience of infection in the population.70 This effective reproductive number is the number of new infections caused by an average infection at a given time, t, which at time zero equals the basic reproductive number. Once some contacts are already infected or immune, the effective reproductive number is reduced and is the product of the basic reproductive number and the fraction of contacts remaining susceptible. When an infection successfully invades a population its prevalence will initially grow exponentially, until it saturates and the effective reproductive number falls. […] the greater the value of R0, the higher predicted prevalence of infection and immunity. In the case of STIs, where there is heterogeneity of risk, contacts are concentrated in a small fraction of the population and infection saturates long before it would in a homogenous population. […]

The pattern of spread of the epidemic and its subsequent progress to an endemic level depends upon the duration of infection and the role of acquired immunity […] For a short-lived infection with no acquired immunity, such as gonorrhea, we can expect a steady state to be reached quickly. If death or acquired immunity reduces the susceptible pool, the prevalence of infection can fall until the resupply of susceptibles through newly susceptible individuals entering the population either balances the losses or builds up over time to cause new epidemics. The associated declines in prevalence could be confused for the impact of interventions but are the natural course of the epidemic. In the case of syphilis, acquired or concomitant immunity can explain the long-term cycles in incidence observed in US case reports.10 In the case of HIV, declines in prevalence can reflect earlier declines in incidence caused by saturation.73″ 

11. “To reduce the incidence of STI infection interventions must alter the reproductive potential of the infection. Shortening the infectious period, reducing the contact rate, or reducing the transmission probability, all reduce the basic reproductive number of infection, while introducing artificial immunity through vaccination would reduce the proportion of the population susceptible and thereby reduce the effective reproductive number. Reducing the basic reproductive number has a nonlinear impact on the endemic prevalence of infection […] heterogeneity in risk plays a key role in the epidemiology of STIs. In populations with a distribution of risk, small reductions in risk can have a large impact in a lower risk group while having little impact in higher risk groups.75 Thus, initially interventions can have a large impact, but as their intensity is increased it generates diminishing returns, as infection is removed from low-risk sections of the population and becomes more concentrated. […]

The relative success of different STIs is likely to have changed in response to treatment, with chancroid, syphilis, and gonorrhea becoming relatively less common if their symptoms are more likely to receive attention. Similarly within microbial populations, treatment is likely to provide a selective advantage to organisms that generate negligible symptoms, more so than organisms that have partial drug resistance. Over time, we might expect the pathogenicity of curable STIs to decline unless there is a correlation between symptoms and transmissibility, which is hypothetically likely if disease is associated with larger bacterial colonies and transmission depends upon the infectious dose of bacteria. However, if interventions through screening target both asymptomatic and symptomatic infections, then selection is likely to favor organisms that transmit more readily, with a concomitant shorter duration of infection in the absence of treatment.77 Similarly, drug resistance becomes a better adaptive strategy if both symptomatic and asymptomatic infections are rapidly treated through active screening.”

12. “An estimated 1.9 million people (1.3-2.6 million) are living with HIV in North America and in Western and Central Europe.

In high-income countries, where the great majority of people who need antiretroviral treatment do have access to it, people living with HIV are staying healthy and surviving longer than infected people elsewhere. Widespread access to life-extending antiretroviral treatment kept the number of AIDS deaths at between 19,000 and 42,000 in 2005. However, prevention efforts are not keeping pace with the changing epidemics in several countries. Sex between men is the most common route of infection in Australia, Canada, Denmark, Germany, Greece, and the United States. Patterns of HIV transmission are changing with an increasing proportion of people becoming infected through unprotected heterosexual intercourse. In Belgium, Norway, and the UK, the increase in heterosexually transmitted infections is dominated by people from countries with generalized epidemics, predominantly sub-Saharan Africa. In the United States, about half of newly reported infections are among African Americans who represent 12% of the population. […] Drug injecting accounted for more than 10% of all reported HIV infections in Western Europe in 2002 (in Portugal it was responsible for over 50% of cases). In Canada and the United States, about 25% of HIV infections are attributed to drug injecting.”

13. “The incidence, prevalence, and population distribution of sexually transmitted infections (STIs) are largely determined by the complex interplay of dynamically changing demographic, economic, social, and behavioral forces and the response of the health system to emergent STI morbidity patterns. Over the past 3 decades, overall incidence and prevalence of bacterial STI, in particular gonorrhea, syphilis, chancroid, and chlamydial infections have declined in the United States, Western Europe, and many developing countries, to their lowest levels since World War II. Declines in bacterial STI in developing countries are attributed to the widespread implementation of syndromic management and to a large-scale shift to safer sexual behaviors in response to the HIV epidemic. Despite such remarkable declines, rates of some bacterial STI are still high and/or increasing in some subpopulations […] During the past decade prevalences of viral STI, particularly genital herpes infections (HSV), appear to have increased in many countries […] Diagnosis, management, and control of viral STIs have changed drastically over the past decade. The introduction of new diagnostic technologies has increased recognition of viral STI, improved sensitivity in identification of bacterial STI, and expanded the repertoire of usable specimens. The use of urine and vaginal swabs has greatly expanded coverage of screening services and has led to the availability of true population-based estimates of the prevalences of STIs.1 […] In all societies, for many reasons discussed in this chapter, STIs tend to concentrate in certain populations including urban, poor, and minority populations, with highest rates among sexually active adolescent females followed by adolescent and young adult men. This pattern is particularly pronounced in western industrialized countries where effective prevention and control efforts result in concentrated STI morbidity. During the past decade commercial sex has become an increasingly important factor in STI transmission6,7 in many areas of the world including the United States and Western Europe.”

14. “Trajectories whereby STI epidemics evolve differ for different types of population-pathogen interactions.30, 31, 32 Whereas highly infectious, short duration bacterial STIs—for instance, gonorrhea—depend on the presence of core groups marked by multiple sex partnerships (often of short duration) for their spread, less infectious, long duration viral STIs—for example, herpes simplex virus (HSV) or human papillomavirus (HPV) infections—are less dependent on multiple partnerships of short duration or on short gaps between partnerships. Thus, the pattern of spatial and population distribution of various STIs differs markedly. Syphilis and gonorrhea tend to be concentrated in individuals with multiple partnerships and in populations with highly connected sexual networks; whereas genital chlamydial infections, genital herpes, and genital HPV infections are much more ecumenically, widely distributed across the entire population.33

15. “The most recent updated estimates for prevalence and incidence of STIs globally are provided by the WHO.47 These estimates suggest that of 340 million new cases of gonorrhea, syphilis, chlamydial infection, chancroid, and trichomoniasis STIs in 1999 under 10% occurred in North America and Western Europe; over 90% of new infections were in developing countries (Table 5-1). In 1999, the overall estimated number of new cases of chlamydia, gonorrhea, and syphilis infections among 15-49-year-old men and women totaled over 166 million with close to 92 million cases of chlamydial infection, 62.35 million cases of gonorrhea, and 11.76 million cases of syphilis (Table 5-2). In addition, there were an estimated 173.46 million cases of trichomoniasis.

In developing countries, passive surveillance of STI morbidity is particularly inadequate. However, in recent years the epidemiology of STIs in sub-Saharan Africa is better defined based on large population-based prevalence surveys. The results of these surveys have confirmed the high prevalences of STIs even in rural populations, for example, syphilis (5-10% of adults infected), vaginal trichomoniasis (20-30% of women), and bacterial vaginosis (up to 50% of women). Syphilis has been estimated to cause 490,000 stillbirths and neonatal deaths per year in Africa—a figure similar to the number of children dying of HIV/AIDS worldwide.48

16. “Data on gonococcal antimicrobial resistance across the EU are not comprehensive. Plasmid-mediated resistance to penicillin and tetracycline had increased in Europe during the early 1990s. Sporadic resistance to fluoroquinolones was also documented in the early 1990s, mainly imported from South East Asia.52 […] Recently, increases in fluoroquinolone resistance have been reported in many countries in Europe. In Denmark, the laboratory-confirmed percentage of gonococci with fluoroquinolone resistance increased from 0% to 27% in 1999, 17% of the strains were resistant to both penicillin and fluoroquinolones.52 […] By early 2004, fluoroquinolones were no longer recommended in the United States as first-line treatment for MSM, and by early 2007, were no longer recommended as first-line treatment of gonorrhea in any group.86

17. “Chlamydia trachomatis is still the most prevalent sexually transmitted bacterial infection in North America and Europe.52,54 It is difficult to describe temporal trends in the incidence of chlamydial infection because of the large proportion of asymptomatic infections; the increasing use of increasingly sensitive diagnostic tests, with expansion of chlamydia screening activities in Europe and the United States; the increased emphasis on case reporting by providers; and the improvements in the information systems for reporting. In many European countries, case reporting of genital chlamydial infections is not mandatory; consequently, relatively little information is available from national surveillance sources. […]

In a recent study,122 U.S. women aged 14-49 participating in the National Health and Examination Survey (NHANES) cycles 2001-2004 provided self-collected vaginal swabs; vaginal fluids extracted from the swabs were evaluated for Trichomonas vaginalis using polymerase chain reaction (PCR). The overall prevalence of T. vaginalis was 3.1%; it was highest among non-Hispanic blacks (13.3%) and lower among Mexican Americans (1.8%) and non-Hispanic whites (1.3%). […]

Viral STIs are not notifiable in most European countries and relatively limited temporal trend data have been published.52 Genital HSV infection is the most common ulcerative STI in the UK and the United States. However, many patients with genital herpes do not perceive or recognize symptoms of the infection, and clinical case-reports grossly underrepresent the true incidence of genital herpes as reflected by serologic testing for antibody to HSV-2. […] HSV-2 prevalence appears to be higher in Northern Europe and in North America than in Western and Southern Europe. The highest prevalence of HSV-2 infection was found among women in Greenland, reaching 57% among 20-26-year olds and 74% in 25-39-year olds. In Scandinavia, HSV-2 prevalence was relatively higher than in other areas of Europe—15-35% among women between 25 and 35 years of age.124 […] The most recent data on HSV-2 seroprevalence in the United States were collected in a stratified random sample of the United States population through the NHANES during 1988 through 1994 and 1999 through 2004.126 Persons between ages 14 and 49 were included in the analyses. The overall age-adjusted HSV-2 seroprevalence was to 21.0% in the period 1988-1994, decreasing to 17.0% in 1999-2004, representing a relative decline of 19% between the two surveys. […] The seroprevalence of HSV-1 also decreased from 62% to 57.7% between the two surveys—a relative decrease of 6.9%. […]

Genital HPV infections are the most prevalent STIs in the United States and in the world. HPV infections other than those causing genital warts (usually types 6 and 11) are nearly always subclinical, not recognized by the infected individual. By screening for HPV DNA every 3 months, using PCR amplification tests, the cumulative incidence of genital HPV infections in one study was 43% over a 3-year period in one study of sexually active female University students127 and 32% over a 2-year period in another.128 […] A recent pooled analysis showed the age standardized prevalence of all types of HPV infection to vary 20-fold among different regions of the world.130 The prevalence of high risk types of the virus was 18% in sub-Saharan Africa, 5% in Asia, 10% in South America, and 4% in Europe. The prevalence of HPV infection is highest among young women and appears to drop-off with increasing age.131 […] Risk factors for HPV infection include increased number of sex partners, increased number of male partners’ lifetime partners, a short-time interval between meeting a partner and engaging in sexual intercourse, increased age difference between partners, and current smoking.128 […] Based on these preliminary findings from cohort studies, and together with data from national surveys of sexual behavior […] it is not unlikely that the majority of adults in the United States, perhaps three-quarters, have been infected with one or more types of genital HPV.”

18. “Worldwide, more men than women report multiple partnerships except in some industrialized countries, where the proportions of men and women who report multiple partnerships are similar.10 The mean age difference between married men and women is lower in industrialized countries (1.9 in Australia and 2.2 in United States) than in developing countries; data are not available on age differences between sex partners. According to a recent review153 of estimates of lifetime, prevalence of men having had sexual intercourse with other men is lower in industrialized countries (6% in the UK and 5% in France) than in most other regions of the world. Rates of condom use are generally higher in industrialized countries than in developing countries, especially in women.10 The increase in condom use in recent years has also often been more substantial in industrialized countries; the only exception to this pattern is France where women have reported declining condom use in more recent years.”

19. “Historically, the predominant focus of STI epidemiology has been on the attributes and behaviors of individuals, and on the risk of acquiring, rather than of transmitting infection. This approach is consistent with the approaches of clinical medicine, chronic disease epidemiology, and psychology. However, when considered as the “sole” or “main” focus, it appears to be inconsistent with STI transmission dynamics190 and it has been increasingly challenged in recent years. The new paradigm includes at least three principles: that one person’s health outcome is highly dependent on other person’s health outcomes;191,192 that transmission of infection and its prevention is at least as important and perhaps more important than acquisition of infection and its prevention—thus focusing attention on infected individuals and the role they play in the spread of infection; that characteristics of sex partners and partner selection processes are an important component of risk determination—thereby focusing on behaviors of sex partners as well.186

20. “The inadequacy of the STD health service infrastructure and the resulting preventable increment in duration of infectiousness is a major reason why the United States has the highest rates of STIs among developed countries.”

21. “In the light of all these considerations, it is obvious that in evaluating behavioral interventions to prevent STIs, and HIV, data from randomized controlled trials are particularly important, the choice of outcome measure is critical, and the outcome measure of choice is the appropriate biomedical measure of the STI or STIs of interest.264,270

Most evaluations of behavioral interventions to date have employed less rigorous study designs and behavioral outcome measures. A systematic review of computerized abstracts from International AIDS conferences between 1989 and 1992 showed that only 10 of 15,946 abstracts reported on randomized controlled trials of behavioral interventions.264 Two subsequent critical reviews of behavioral interventions in general and behavioral interventions for young people reported similar findings.271,272 These reviews also indicated that many behavioral intervention studies focused only on determinants of behavior such as knowledge, beliefs, and attitudes as outcome measures. […] In the past 2 decades a number of behavioral intervention trials have been conducted including those mentioned above. Many of these studies showed efficacy in reducing risky behaviors, and a smaller number showed efficacy in reducing incidence of bacterial STI in study subjects. Interestingly, to date, no cluster randomized trial of behavioral interventions (where at least one arm of the study represented a behavioral intervention) has showed significant impact at the population level.”


December 6, 2012 - Posted by | Books, Demographics, Epidemiology, Health Economics, Immunology, Infectious disease, Medicine, Microbiology, Pharmacology

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