Does the use of antibiotics for bacterial vaginosis during pregnancy reduce the risk of preterm birth?

Bacterial vaginosis (BV) is an inflammatory disease that is defined as a vaginal microbiome that is not dominated by Lactobacilli.  This abnormal vaginal flora is associated with preterm birth and miscarriage.  A recent study showed that women’s vaginal microbiomes shift frequently during pregnancy, but that the amount of time spent with a flora not dominated by Lactobacillus was associated with the length of the pregnancy, i.e. the less time spent with Lactobacillus the shorter the pregnancy.  Considering these studies, doctors may want to begin screening the vaginal microbiome during pregnancy, and treating BV (which is currently done through antibiotics).  Strategies such as that one have not yet been rigorously studied, so their efficacy is still unknown.  Last week a study out of Japan performed a study that showed little improvement in preterm birth risk by monitoring and treating BV during pregnancy.  The results were published in Nature Scientific Reports.

The researchers measured the microbiomes of 1,735 pregnant women and split them into two groups.  Women in the intervention group that had BV were given antibiotics, whereas women in the control group, whether they had BV or not, proceeded as normal through their pregnancy.  Women in both groups had their vaginal microbiomes sampled at various time points throughout the pregnancy. The first group would have their BV status verified, and placed on antibiotics. In both groups, approximately 10% of the women had preterm birth at around 30 weeks gestational age.  There was no significant difference in these rates between the two groups, meaning that administration of antibiotics did not appear to prevent preterm birth.  Even though the antibiotics did not prevent preterm birth, the researchers noted that regardless of group, women who entered preterm birth did have abnormal vaginal flora compared to women who went full term, supporting the notion that BV is highly correlated with preterm birth.  They noted that many of the women who entered preterm labor did not have BV at the initial time of screening, but acquired BV at some point during pregnancy. 

This paper supports the idea that BV may cause preterm birth, however it cannot recommend universal screening for BV in pregnant women for two reasons.  First, the antibiotics did not appear to affect the rates of preterm birth, and second many of the women who had preterm birth only had abnormal flora after initial screening.  Perhaps a better strategy would be to constantly monitor BV status throughout pregnancy.  In addition, there will soon be healthier and more effective methods to treat BV than antibiotics, which are only shown to have a transient effect on BV and disrupt the rest of the microbiome.

New probe developed to detect specific bacteria associated with bacterial vaginosis

Confocal laser scanning images with 400x magnification of G.vaginalis biofilm in 2 vaginal slides (A and B) in a superimposed image: vaginal epithelial cells in blue and G. vaginalis specific PNA-probe in red. A: vaginal sample with dispersed bacteria; B: vaginal sample with bacteria in biofilm.

Bacterial vaginosis (BV) is a topic we have previously covered on the blog, because of its significance to women’s health. BV is a change in women’s vaginal bacterial composition, in which bacteria that are usually associated with health are at a decreased presence in comparison to BV-associated bacteria. BV is such an issue because it causes a biofilm to form that increase susceptibility HIV and other sexually transmitted infections. BV also has negative effects on pregnancy and is a threat to women of reproductive age. Clearly this is an important topic of research, and was the focus of an article recently published by PLOS ONE.

BV is usually characterized by the presence of Gardnerella vaginalis and Atopobium vaginae. A.vaginae has previously been shown to be much more common than G. vaginalis in BV patients. In the PLOS ONE study, researchers focused on finding the best way to detect these two bacteria in vaginal samples. Samples were taken from 119 women in Rwanda, between the ages of 18 and 35 years old. After testing multiple different probes that had been developed by the researchers, they found that something called the PNA FISH is a very good tool for detecting bacteria in biofilms. Through this study the scientists were able to detect that higher quantities of G. vaginalis and A. vaginae are associated with bacterial biofilms. Almost half the samples containing G. vaginalis also contained A. vaginae, whereas all of the samples that contained A. vaginae were also positive for G. vaginalis.

With the data collected, the researchers hypothesize that G. vaginalis is a main cause of vaginal biofilms when it is high enough in concentration. Hopefully with the discovery of effective probes, much more can be discovered about bacterial vaginosis.    

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. 

New contraceptive vaginal ring does not increase risk of vaginal infections

The Nuvaring, a type of vaginal ring.

A newly developed contraceptive device that consists of a vaginal ring that is meant to be used for an entire year is currently under development.  As part of this device’s safety trials the scientists who developed the device monitored how it would impact the vaginal microbiome.  The vaginal microbiome is critical to vaginal health, and certain changes to the vaginal flora are associated with bacterial vaginosis (BV), yeast infections, and other vaginal diseases.  Implanting devices will certainly affect the vaginal microbiome, but fortunately, the scientists determined that the device did not increase the likelihood of getting a vaginal microbiome-mediated disease.  They published their results last week in PLoS ONE.

The vaginal microbiomes of 120 women using the device were measured over the course of a year.  There were no significant increase in the rates of BV over the course of the year.  In addition, the levels of Lactobacilli, which are associated with a healthy vagina, and Gardnerella vaginalis, which has been associated with BV, remained relatively unchanged over the course of treatment.  In addition, measurements on the actual surface of the vaginal ring matched the overall vagina quite well in terms of microbial colonization. In both cases, Lactobacilli dominated.

Any fluid or device inserted into the vagina should be considered for its effect on the vaginal microbiome, for example, douching is associated with BV.  Fortunately, this safety study showed that the vaginal ring did not increase rates of disease, so women out there using a vaginal ring for contraception need not be too concerned that their ring is negatively impacting their vaginal health.

Bacterial vaginosis associated bacteria may increase a women’s risk for miscarriage

Bacterial infections or even slight imbalances can be damaging at many difference locations in the human body. One that should be taken seriously in bacterial vaginosis, which is an infection in females where a healthy bacterial balance is taken over by bacteria such as Gardnerella vaginalis, Ureaplasma urealyticum, and Mycoplasma hominis to name a few. Meanwhile, the presence of Lactobacillus crispatus and Lactobacilus iners would be characteristic of a normal vaginal microbiome. In a study out of Philidelphia, Pa that was recently published by Maternal and Child Health Journal, researchers inspected a possible connection between bacterial vaginosis and pregnancy miscarriages.

          A total of 418 pregnant women were included in the study. 65% of the women were African American, 27% were Hispanic, and 4% were Caucasian. Women were eligible if they were seeking treatment prior to 14 days of gestation, if they were not pregnant with multiples, and if there were no issues in terms of ectopic or molar pregnancy. Swabs were collected from the women and analyzed. During this study, 74 women experienced a miscarriage, while 344 delivered at term.

          It was found that the group of women who had miscarriages were older than those who did not. Women with high concentrations of Bacterial Vaginosis-Associated Bacterium 3 (BVAB3) before 2 weeks gestation had a 20% increased chance of miscarriage. On the other hand, for each one unit increase in Leptotrichia/Sneathia species concentration, risk of miscarriage decreased by 20%, and for that of Megasphaera phylotype 1-like species risk decreased by 19%. The implications of this type of research could be very beneficial to women everywhere. More knowledge like this could hopefully one day lead doctors towards even better care for pregnant women. Ideally, with more research into this area, the prevalence of miscarriages could be lowered. 

Study suggests penile microbiome can transmit bacterial vaginosis by sexual intercourse

Bacterial vaginosis (BV) is a microbiome-based disease characterized by a lack of Lactobacillus in the vagina.  We have covered this disease with multiple blog posts and encourage any interested readers to search for these blogs to learn more.  One outstanding question regarding BV is how sexual intercourse affects the disease.  One prevailing thought is that the penis can actually be colonized by BV-associated bacteria, and that through sexual intercourse it can be spread between partners.  A new paper published last week in mBio suggests this is true.

The researchers measured the penile microbiomes of 165 uncircumcised, black men from Uganda, as well as diagnosing BV status in their female partners.  The BV status was measured by Nugent score, which is a bacterial staining technique that basically measures the amount of anaerobic bacteria in the vagina (non-Lactobacilli).  The stain produces a score between 1-7 with 1 being healthiest and 7 being least healthy (mostly anaerobic bacteria).  After measuring the penile microbiomes, the scientists were able to be categorize them into 7 different community state types (CST1-7).  These community state types varied from 1 to 7 in terms of both overall abundance and composition, with CST1 having the lowest density of bacteria and the lowest diversity while CST7 had the highest density and the highest diversity of bacteria.

The scientists compared the female partner’s BV status with the men’s community state type, and noted that having a CST1-7 on the penile microbiome corresponded with a higher likelihood of the female partner being diagnosed with BV.  Two genera of bacteria, Corynebacterium and Staphylococcus, on the penile microbiome were associated with healthy vaginal flora, whereas Dialister, Mobiluncus, Prevotella, and Porphyromonas were associated with BV.  Interestingly penises that included Lactobacillus and Gardnerella, genera associated with healthy vaginas and BV vaginas, respectively, were not statistically associated with BV status.  Overall, men with CST4-7 were significantly more likely to have a sexual partner with BV, and had more BV associated bacteria colonizing their penises.  In addition, men with more than one sexual partner were more likely to have CST4-7, and again, their partners more likely to have BV.

It appears that men’s penises, especially uncircumcised ones, can be vectors for bacterial transmission.  This simple fact should make us reconsider BV as an STD, and actually fits in well with another that has shown promiscuity is a risk for BV.  It is likely that circumcision and condom would decrease BV transmission rate, as they do other STDs, but until a paper comes out that studies this connection no one can say for sure.