Hormonal contraceptives are associated with altered cervical immunity, dependent on the presence of genital tract infections

Past studies have shown an association between hormonal contraceptives and risk of HIV-1 infection, as well as between genital tract infection and acquisition of HIV-1. The types of hormonal contraceptives that have been associated with increased risk of HIV include progestin injectable depot medroxyprogesterone acetate (DMPA) and combined estrogen-progestin oral contraceptives (COC). Untreated cervical pathogens such as Trichomonas vaginalis, Neisseria gonorrhoeae, Chlyamydia trachomatis, Candida albicans, and genital herpesvirus 2 also contribute to increased risk of HIV. In a study recently published in mBio by the American Society for Microbiology, researchers investigated the combined effects of hormonal contraceptives and genital tract infections on risk level of HIV.

The participants of this study were 633 HIV-negative women and 199 HIV-positive women, all of whom live in Uganda or Zimbabwe. It was found that more than half the study participants were positive for herpes. Cases of herpes were evenly distributed among women with chlamydia, candidiasis, and bacterial vaginosis. However, herpes was significantly more common among women positive for T. vaginalis or gonorrhea. As for contraceptives, women with asymptomatic infections were mainly COC users (65%) followed by DMPA users (60%). Symptomatic infections were most common in the group that did not use hormonal contraceptives.  

To test for risk factors of HIV, the researchers looked at certain immune system response components. It was found that HIV was associated with higher levels of two immune components known as RANTES and BD2. RANTES was seen to be increased among combined estrogen-progestin oral contraceptive users whom were also associated with herpes and abnormal vaginal microbiota. BD2 was seen increased among COC and non-HC users by T. vaginalis infection and among DMPA users by herpes, candidiasis, and bacterial vaginosis.

As is common in all processes of life, there seem to be many factors that contribute to HIV infection. Changes in the immune system caused by hormones, like contraceptive hormones, and genital bacteria composition may combine to influence vulnerability to HIV infection. This study is important, because the more knowledge scientists have about women’s reproductive health, the greater the possibility that we can develop treatment and prevention plans for infections.

Bacterium identified that may be associated with cervicitis

Cervicitis is an inflammation of the uterine cervix of women. This condition is known to be associated with many different infections, such as Chlamydia trachomatis or Neisseria gonorrhoeae, however the true cause of the inflammation is still unclear. Researchers in Seattle, Washington performed a study, recently published by the journal Sexually Transmitted Diseases, to determine whether it is an imbalance of the vaginal and/or cervical microbiome that is at the root of the problem. The study’s aim was to look at the associations of bacteria with cervicitis in two different groups of women, to see if the results of each group agree.

At a clinic in Seattle, vaginal and cervical samples were collected from a group of predominantly young white women that agreed to the study. Of the 210 women from the clinic, only 14 were identified as having cervicitis based on certain identification criteria. A parallel control study was performed in Mombasa, Kenya with the hopes that the gathered information would either refute or confirm the results of the Seattle group. The Seattle results showed that women with cervicitis were more likely to have Mageeibacillus indolicus in the cervix and vagina than women without the condition. The bacteria Lactobacillus jensenii was the only species that was more present in women without than with cervicitis.

The Kenyan study did not show that M. indolicus was more present in women with cervicitis. In fact, the bacterium was more common in women without the condition. While the results of this study are confusing, because the Kenyan study seems to disprove the results of the Seattle study, it important to keep in mind the flaws of this study as a whole. There were many factors not taken into consideration during analysis, such as birth control intake and viral infections. Additionally, the criteria of cervicitis diagnosis were most-likely different in Seattle and Kenya, and there were very few women in the study that even had the condition. Regardless of the flaws, this study still gave good results which could lead scientists too look further into M. indolicus and L. jensenii for their contribution to cervical health. 

Sometimes-pathogenic Neisseria are constantly invoking immune response in humans

Fluorescent antibody stain of Neisseria gonorrhoeae.

Bacteria from the genus Neisseria exist as normal commensals in greater than 95% of adults.  That being said, two strains, Neisseria meningitides (a cause of bacterial meningitis) and Neisseria gonorrhoeae (the cause of gonorrhea),are known pathogens, although these too can often asymptomatic.  A new study published last week in Science suggests that although asymptomatic, Neisseria may always be inducing an autoimmune response, via a metabolite they are constantly producing and releasing into the environment. 

Using genetic approaches, scientists from the University of Toronto identified the inflammation-inducing metabolite as heptose-1,7-bisphosphate (HBP), which prior to the study had not been implicated as causing an immune response.  To prove its effect, the researchers injected the metabolite into mice and showed that these mice displayed inflammation almost immediately.  The scientists recognized that this metabolite is actually produced by many bacteria, and wondered if these others were causing harm as well.  Using mouse studies though, they demonstrated that other bacteria do not release it from their cells into the environment, so these bacteria only induce a response when they are lysed.  Thus far only Neisseria have been shown to produce and release this metabolite, which is important because it means as long as they are growing they are constantly producing an immune response. 

The scientists also discovered the immune pathway by which HMP triggers a response: the TRAF-interacting protein with forkhead-associated domain (TIFA).  Interestingly, it has been known for many years that infection with N. meningitidis or N. gonorrhoeae increases HIV shedding and transmission, but the reason was still a mystery.  The scientists figured out this connection when they recognized that HIV actually use the TIFA pathway to reproduce.  They observed that these bacteria invoke the TIFA response via HBP, which gives the HIV the proper cells it needs to replicate.

Given what we know about the effects of chronic inflammation and its effects on many diseases these findings could be very important.  Perhaps there is no such thing as a nonpathogenic Neisseria, and its existence in ‘healthy’ guts may not be so healthy after all.