An exploratory pilot study evaluating the supplementation of standard antibiotic therapy with probiotic lactobacilli in south African women with bacterial vaginosis

Abstract

Background To reduce acquisition and relapse of bacterial vaginosis (BV), lactobacilli must be maintained in the vaginal microbiome. Probiotic lactobacilli may aid this purpose. We investigated whether vaginal probiotics (containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869) would result in vaginal colonisation with lactobacilli in women with and without BV. Methods This prospective, partially randomised, exploratory pilot study was conducted in Soweto, South Africa. Thirty-nine sexually-active, HIV negative women were enrolled from October 2014 to May 2016 into three arms. Women who did not have BV (Group 1, n = 13) self-administered probiotic capsules vaginally once daily for 30 days, then once a week until Day 190. Women diagnosed with BV were randomized into Group 2 (n = 12) or Group 3 (n = 14) and treated with the triple oral antibiotic combination for vaginal discharge syndrome per South African guidelines (cefixime 400 mg stat, doxycycline 100 mg BD for 7 days and metronidazole 2 g stat). Immediately after antibiotic treatment, women in Group 2 self-administered probiotic capsules vaginally once daily for 30 days then vaginally once a week until Day 190. Women in Group 3 were not given lactobacilli. Results During the study, L. rhamnosus DSM 14870 or L. gasseri DSM 14869, were isolated in 5/13 (38.5%) women in Group 1 compared to 10/12 (83.3%) women in Group 2 (p = 0.041). The 1-month and 6-month BV cure rates were similar (P > 0.05) between Group 2 (42 and 25%) compared to Group 3 (36 and 25%). In Group 2, no correlation was observed between the frequency of isolation of the two Lactobacillus strains and the 1-month or 6-month cure rate. Conclusions Supplementation with vaginal probiotic capsules resulted in colonisation of the vagina by the Lactobacillus strains (L. rhamnosus DSM 14870 and L. gasseri DSM 14869) contained in the capsules. We observed low initial cure rates of BV after a stat dose of metronidazole and that the probiotic did not improve BV cure rates or alleviate recurrence which could be due to treatment failure or very limited power of the study. Trial registration Registered at the Pan African Clinical Trial Registry (www.pactr.org) on April 13, 2018 (retrospectively registered). Trial identification number: PACTR201804003327269.

Lactobacilli Expressing Broadly Neutralizing Nanobodies against HIV-1 as Potential Vectors for HIV-1 Prophylaxis?

“…Previous studies have already shown the potential of lactobacilli for delivery of microbicides against HIV-1/SHIV infection including antibody fragments [ 41 , 75 ], the chemokine RANTES [ 76 ], cyanovirin [ 77 ] and two-domain CD4 [ 36 ] in vitro and in animal models. Here we chose L. rhamnosus DSM 14870 as vector, because this strain is already a constituent of EcoVag ® vaginal capsules for treatment of bacterial vaginosis and has been shown to colonize the human vagina [ 45 , 47 , 48 ]. Furthermore, the genome of this strain has been completely sequenced and does not contain antibiotic resistance genes ensuring its safety for clinical applications [ 46 ].…”

“…Such preventive products are inexpensive to produce, stable at higher temperatures and easy to applicate at home and thus very promising for developing countries. Further, we have previously shown that L. rhamnosus DSM 14870 could transiently colonize the vagina of women and that weekly administration could increase the persistence of the bacteria on mucosal surfaces [ 47 , 48 ]. It is thus likely that vaginal capsules containing the recombinant lactobacilli would need to be administered on a regular basis to maintain their population level.…”

“…Here, we express our most potent HIV-neutralizing nanobody, VHHA6, in Lactobacillus rhamnosus DSM 14870, a strain, which has been well characterized and which is already in clinical use as a constituent of vaginal capsules (EcoVag, Bifodan A/S, Hundested, Denmark) for treatment of bacterial vaginosis. Furthermore, this strain was previously shown to effectively colonize the human vagina [ 45 , 46 , 47 , 48 ]. After showing protection from mucosal HIV-1 infection in a humanized mouse model by soluble VHHA6 produced in E. coli in a proof-of-concept study, we expressed VHHA6 from recombinant L. rhamnosus DSM 14870, both in a soluble and in a surface covalently anchored form.…”

Testing the regulatory framework in South Africa – a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis

“…As the microbial composition of the lower female genital tract (FGT) in health and dysbiosis may be geo-adapted, with regional differences in diet, vaginal insertion, hygiene practices and host genetics possibly shaping these [ 19 – 21 ], it is critical to conduct trials in South Africa to test the effectiveness of probiotics for vaginal health in a local context. While randomized controlled trials (RCTs) assessing the effects of probiotics on BV management have been performed in several other African countries [ 22 , 23 ], only one exploratory pilot study has recently been performed in South Africa, although with a European product that is not locally available [ 24 ].…”

Results from the first South African Health Products Regulatory Authority-approved randomised trial evaluating supplementation of standard antibiotic therapy with a commercially available probiotic in South African women with bacterial vaginosis

“…However, there is clinical equipoise as to whether adjunctive probiotics improve BV cure and/or recurrence rates, as a recent meta-analysis (15) concluded that adjunctive probiotics may improve BV cure rates but that there is currently not enough high-quality clinical evidence to support this approach as superior to antibiotic treatment alone. While randomized controlled trials (RCTs) assessing the effects of probiotics on BV management have been performed in several African countries (16,17), only one exploratory pilot study has recently been performed in South Africa (18). As the microbial composition of the lower female genital tract (FGT) in health and dysbiosis may be influenced by regional factors, including diet, vaginal insertion, hygiene practices and possibly host genetics (19)(20)(21), it is important to conduct such trials in South African women to evaluate the effectiveness of probiotics for vaginal health in a local context.…”