Sexually Transmitted Diseases (4th edition) (III)

I read the first nine chapters of this very long book a while back, and I decided to have another go at it. I have now read chapters 10-18, the first seven of which deal with ‘Profiles of Vulnerable Populations’ (including chapters about: Gender and Sexually Transmitted Diseases (10), Adolescents and STDs Including HIV Infection (11), Female Sex Workers and Their Clients in the Epidemiology and Control of Sexually Transmitted Diseases (12), Homosexual and Bisexual Behavior in Men in Relation to STDs and HIV Infection (13), Lesbian Sexual Behavior in Relation to STDs and HIV Infection (14) (some surprising stuff in that chapter, but I won’t cover that here), HIV and Other Sexually Transmitted Infections in Injection Drug Users and Crack Cocaine Smokers (15), and STDs, HIV/AIDS, and Migrant Populations (16)), and the last two of which deal with ‘Host Immunity and Molecular Pathogenesis and STD’ (Chapters about: ‘Genitourinary Immune Defense’ (17) and ‘Normal Genital Flora’ (19 as well as ‘Pathogenesis of Sexually Transmitted Viral and Bacterial Infections’ (19) – I have only read the first two chapters in that section so far, and so I won’t cover the last chapter here. I also won’t cover the content of the first of these chapters, but for different reasons). The book has 108 chapters and more than 2000 pages, so although I’ve started reading the book again I’m sure I won’t finish the book this time either. My interest in the things covered in this book is purely academical in the first place.

You can read my first two posts about the book here and here.

Some observations and comments below…

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“A major problem when assessing the risk of men and women of contracting an STI [sexually transmitted infection], is the differential reporting of sexual behavior between men and women. It is believed that women tend to underreport sexual activity, whereas men tend to over-report. This has been highlighted by studies assessing changes in reported age at first sexual intercourse between successive birth cohorts¹⁵ and by studies that compared the numbers of sex partners reported by men and by women.¹⁰,¹³,¹⁶, ¹⁷, ¹⁸ […] There is widespread agreement that women are more frequently and severely affected by STIs than men. […] In the studies in the general population that have assessed the prevalence of gonorrhea, chlamydial infection, and active syphilis, the prevalence was generally higher in women than in men […], with differences in prevalence being more marked in the younger age groups. […] HIV infection is also strikingly more prevalent in women than in men in most populations where the predominant mode of transmission is heterosexual intercourse and where the HIV epidemic is mature […] It is generally accepted that the male-to-female transmission of STI pathogens is more efficient than female-to-male transmission. […] The high vulnerability to STIs of young women compared to young men is [however] the result of an interplay between psychological, sociocultural, and biological factors.³³”

“Complications of curable STIs, i.e., STIs caused by bacteria or protozoa, can be avoided if infected persons promptly seek care and are managed appropriately. However, a prerequisite to seeking care is that infected persons are aware that they are infected and that they seek treatment. A high proportion of men and of women infected with N. gonorrhoeae, C. trachomatis, or T. vaginalis, however, never experience symptoms. Women are asymptomatic more often than men. It has been estimated that 55% of episodes of gonorrhea in men and 86% of episodes in women remain asymptomatic; 89% of men with chlamydial infection remain asymptomatic and 94% of women.⁶⁶ For chlamydial infection, it has been well documented that serious complications, including infertility due to tubal occlusion, can occur in the absence of a history of symptoms of pelvic inflammatory disease.⁶⁵”

“Most population-based STD rates underestimate risk for sexually active adolescents because the rate is inappropriately expressed as cases of disease divided by the number of individuals in this age group. Yet only those who have had intercourse are truly at risk for STDs. For rates to reflect risk among those who are sexually experienced, appropriate denominators should include only the number of individuals in the demographic group who have had sexual intercourse. […] In general, when rates are corrected for those who are sexually active, the youngest adolescents have the highest STD rates of any age group.⁵”

“Although risk of HPV acquisition increases with number of partners,⁶⁷,⁷⁴,⁷⁵ prevalence of infection is substantial even with limited sexual exposure. Numerous clinic-based studies,⁷⁶,⁷⁷ supported by population-based data, indicate that HPV prevalence typically exceeds 10% among young women with only one or two partners.⁷¹”

“while 100 years ago young men in the United States spent approximately 7 years between [sexual] maturation and marriage, more recently the interval was 13 years, and increasing; for young women, the interval between menarche and marriage has increased from 8 years to 14. […] In 1970, only 5% of women in United States had had premarital intercourse by age 15, whereas in 1988, 26% had engaged in intercourse by this age. However, in 1988, 37% of never married 15-17-year-olds had engaged in intercourse but in 2002, only 30% had. Comparable data from males demonstrated even greater declines — 50% of never married 15-17-year-olds reported having had intercourse in 1988, compared with only 31% in 2002⁹⁹”

“Infection with herpes simplex type 2 (HSV-2) is extremely common among FSWs [female sex workers], and because HSV-2 infection increases the likelihood of both HIV acquisition in HIV-uninfected individuals, and HIV transmission in HIV-infected individuals, HSV-2 infection plays a key role in HIV transmission dynamics.¹⁰⁰ Studies of FSWs in Kenya,⁶⁷ South Africa,¹⁰¹ Tanzania,³⁶ and Mexico⁷² have found HSV-2 prevalences ranging from 70% to over 80%. In a prospective study of HIV seronegative FSWs in Nairobi, Kenya, 72.7% were HSV-2 seropositive at baseline.⁶⁷ Over the course of over two years of observation […] HSV-2 seropositive FSWs were over six times more likely to acquire HIV infection than women who were HSV-2 seronegative.”

“Surveys in the UK¹³³ and New Zealand¹³⁴ found that approximately 7% of men reported ever paying for sex. A more recent telephone survey in Australia found that almost 16% of men reported having ever paid for sex, with 1.9% reporting that they had paid for sex in the past 12 months.¹³⁵ Two national surveys in Britain found that the proportion of men who reported paying women for sex in the previous 5 years increased from 2.0% in 1990 to 4.2% in 2000.¹⁴ A recent review article summarizing the findings of various surveys in different global regions found that the median proportion of men who reported “exchanging gifts or money for sex” in the past 12 months was approximately 9-10%, whereas the proportion of men reporting who engaged in “paid sex” or sex with a sex worker was 2-3%.¹³⁶”

“There are currently around 175-200 million people documented as living outside their countries of birth.³ This number includes both voluntary migrants, people who have chosen to leave their country of origin, and forced migrants, including refugees, trafficked people, and internally displaced people.⁴ […] Each year about 700 million people travel internationally with an estimated 50 million originating in developed countries traveling to developing ones.⁹⁸ […] Throughout history, infectious diseases of humans have followed population movements. The great drivers of population mobility including migration, economic changes, social change, war, and travel have been associated with disease acquisition and spread at individual and population levels. There have been particularly strong associations of these key modes of population mobility and mixing for sexually transmitted diseases (STDs), including HIV/AIDS. […] Epidemiologists elucidated early in the HIV/AIDS epidemic that there was substantial geographic variability in incidence, as well as different risk factors for disease spread. As researchers better understood the characteristics of HIV transmission, its long incubation time, relatively low infectivity, and chronic disease course, it became clear that mobility of infected persons was a key determinant for further spread to new populations.⁶ […] mobile populations are more likely to exhibit high-risk behaviors”

“Studies conducted over the past decade have relied on molecular techniques to identify previously noncultivable organisms in the vagina of women with “normal” and “abnormal” flora. […] These studies have confirmed that the microflora of some women is predominated by species belonging to the genus Lactobacillus, while women having BV [bacterial vaginosis] have a broad range of aerobic and anaerobic microorganisms. It has become increasingly clear that even with these more advanced tools to characterize the microbial ecology of the vagina the full range of microorganisms present has yet to be fully described. […] the frequency and concentration of many facultative organisms depends upon whether the woman has BV or Lactobacillus-predominant microflora.³⁶ However, even if “normal” vaginal microflora is restricted to those women having a Lactobacillus-dominant flora as defined by Gram stain, 46% of women are colonized by G. vaginalis, 78% are colonized by Ureaplasma urealyticum, and 31% are colonized by Candida albicans.³⁶ […] Nearly all women are vaginally colonized by obligately anaerobic gram-negative rods and cocci,³⁶ and several species of anaerobic bacteria, which are not yet named, are also present. While some species of anaerobes are present at higher frequencies or concentrations among women with BV, it is clear that the microbial flora is complex and cannot be defined simply by the presence or absence of lactobacilli, Gardnerella, mycoplasmas, and anaerobes. This observation has been confirmed with molecular characterization of the microflora.²⁶, ²⁷, ²⁸, ²⁹, ³⁰, ³¹, ³², ³³, ³⁴, ³⁵”

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Vaginal pH, which is in some sense an indicator of vaginal health, varies over the lifespan (I did not know this..): In premenarchal girls vaginal pH is around 7, whereas it drops to 4.0-4.5 in healthy women of reproductive age. It increases again in post-menopausal women, but postmenopausal women receiving hormone replacement therapy have lower average vaginal pH and higher numbers of lactobacilli in their vaginal floras than do postmenopausal women not receiving hormone replacement therapy, one of several findings indicating that vaginal pH is under hormonal control (estrogen is important). Lactobacilli play an important role because those things produce lactic acid which lowers pH, and women with a reduced number of lactobacilli in their vaginal floras have higher vaginal pH. Stuff like sexual intercourse, menses, and breastfeeding all affect vaginal pH and -microflora, as does antibiotic usage, and such things may play a role in disease susceptibility. Aside from lowering pH some species of Lactobacilli also play other helpful roles which are likely to be important in terms of disease susceptibility, such as producing hydrogen peroxide in their microenvironments, which is the kind of stuff a lot of (other) bacteria really don’t like to be around: “Several clinical studies conducted in populations of pregnant and nonpregnant women in the United States and Japan have shown that the prevalence of BV is low (4%) among women colonized with H₂O₂-producing strains of lactobacilli. By comparison, approximately one third of women who are vaginally colonized by Lactobacillus that do not produce H₂O₂ have BV.⁴⁵, ⁴⁶, ⁴⁷“.

My interest in the things covered in this book is as mentioned purely academical, but I’m well aware that some of the stuff may not be as ‘irrelevant’ to other people reading along here as it is to me. One particularly relevant observation I came across which I thought I should include here is this:

“The lack of reliable plenotypic methods for identification of lactobacilli have led to a broad misunderstanding of the species of lactobacilli present in the vagina, and the common misperception that dairy and food derived lactobacilli are similar to those found in the vagina. […] Acidophilus in various forms have been used to treat yeast vaginitis.¹⁴⁴ Some investigators have gone so far as to suggest that ingestion of yogurt containing acidophilus prevents recurrent Candida vaginitis.¹⁴⁵ Nevertheless, clinical studies of women with acute recurrent vulvovaginitis have demonstrated that women who have recurrent yeast vaginitis have the same frequency and concentration of Lactobacillus as women without recurrent infections.¹⁴⁶ […] many women who seek medical care for chronic vaginal symptoms report using Lactobacillus-containing products orally or vaginally to restore the vaginal microflora in the mistaken belief that this will prevent recurrent vaginitis.¹⁴⁷ Well-controlled trials have failed to document any decrease in vaginal candidiasis whether orally or vaginally applied preparations of lactobacilli are used by women.¹⁴⁸ Microbial interactions in the vagina probably are much more complex than have been appreciated in the past.”

As illustrated above, there seems to be some things ‘we’ know which ‘people’ (including some doctors..) don’t know. But there are also some really quite relevant things ‘we’ don’t know a lot about yet. One example would be whether/how hygiene products mediate the impact of menses on vaginal flora: “It is unknown whether the use of tampons, which might absorb red blood cells during menses, may minimize the impact of menses on colonization by lactobacilli. However, some observational data suggests that women who routinely use tampons for catamenial protection are more likely to maintain colonization by lactobacilli compared to women who use pads for catamenial protection”. Just to remind you, colonization by lactobacilli is desirable. On a related and more general note: “Many young women use vaginal products including lubricants, contraceptives, antifungals, and douches. Each of these products can alter the vaginal ecosystem by changing vaginal pH, altering the vaginal fluid by direct dilution, or by altering the capacity of organisms to bind to the vaginal epithelium.” There are a lot of variables at play here and my reading of the results indicate that it’s not always obvious what is actually the best advice. For example an in this context large (n=235) prospective study about the effect of N-9, a compound widely used in contraceptives, on vaginal flora “demonstrated that N-9 did have a dose-dependent impact on the prevalence of anaerobic gram-negative rods, and was associated with a twofold increase in BV (OR 2.3, 95% CI 1.1-4.7).” Using spermicides like those may on the one hand perhaps decrease the likelihood of getting pregnant and perhaps lower the risk of contracting a sexually transmitted disease during intercourse, but on the other hand usage of such preparations may also affect the vaginal flora in a way which may make users more vulnerable to sexually transmitted diseases by promoting E. coli colonization of the vaginal flora. On a more general note, “The impact of contraceptives on the vaginal ecosystem, including their impact on susceptibility to infection, has not been adequately investigated to date.” The book does cover various studies on different types of contraceptives, but most of the studies are small and probably underpowered, so I decided not to go into this stuff in more detail. An important point to take away here is however that there’s no doubt that the vaginal flora is important for disease susceptibility: “longitudinal studies [have] showed a consistent link between increased incidence of HIV, HSV-2 and HPV and altered vaginal microflora […] there is a strong interaction between the health of the vaginal ecosystem and susceptibility to viral STIs.” Unfortunately, “use of probiotic products for treatment of BV has met with limited success.”

I should note that although multiple variables and interactions are involved in ‘this part of the equation’, it is of course only part of the bigger picture. One way in which it’s only part of the bigger picture is that the vaginal flora plays other roles besides the one which relates to susceptibility to sexually transmitted disease – one example: “Studies have established that some organisms considered to be part of the normal vaginal microflora are associated with an increased risk of preterm and/or low birth weight delivery when they are present at high-density concentrations in the vaginal fluid”. (And once again the lactobacilli in particular may play a role: “high-density vaginal colonization by Lactobacillus species has been linked with a decreased risk of most adverse outcomes of pregnancy”). Another major way in which this stuff is only part of the equation is that human females have a lot of other ways to defend themselves as well besides relying on bacterial colonists. If you don’t like immunology there are some chapters in here which you’d be well-advised to skip.