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In the present narrative review, the probiotic effects of vaginal Lactobacillus spp. are described in detail, covering the importance of the differential production of lactic acid, the lactic acid D/L isoforms, the questionable in vivo effect of hydrogen peroxide, as well as bacteriocins and other core proteins produced by vaginal Lactobacillus spp. Moreover, the microbe–host interaction is explained with emphasis on the vaginal mucosa. To understand the crucial role of Lactobacillus spp. dominance in the vaginal microbiota, different dysbiotic states of the vagina are explained including bacterial vaginosis and aerobic vaginitis. Finally, this review takes on the therapeutic aspect of live lactobacilli in the context of bacterial vaginosis. Until recently, there was very low-quality evidence to suggest that any probiotic might aid in reducing vaginal infections or dysbiosis. Therefore, clinical usage or over the counter usage of probiotics was not recommended. However, recent progress has been made, moving from probiotics that are typically regulated as food supplements to so-called live biotherapeutic products that are regulated as medical drugs. Thus, recently, a phase 2b trial using a Lactobacillus crispatus strain as a therapeutic add-on to standard metronidazole showed significant reduction in the recurrence of bacterial vaginosis by 12 weeks compared to placebo. This may constitute evidence for a brighter future where the therapeutic use of lactobacilli can be harnessed to improve women’s health.

Background The primary objective of this study was to investigate if extended antibiotic treatment against bacterial vaginosis (BV) together with adjuvant lactobacilli treatment could cure BV and, furthermore, to investigate factors that could cause relapse. Methods In all, 63 consecutive women with bacterial vaginosis diagnosed by Amsel criteria were offered a much more aggressive treatment of BV than used in normal clinical practice with repeated antibiotic treatment with clindamycin and metronidazole together with vaginal gelatine capsules containing different strains of lactobacilli both newly characterised and a commercial one (10 9 freeze-dried bacteria per capsule). Oral clindamycin treatment was also given to the patient's sexual partner. Results The cure rate was 74.6% after 6 months. The patients were then followed as long as possible or until a relapse. The cure rate was 65.1% at 12 months and 55.6% after 24 months. There was no significant difference in cure rate depending on which Lactobacillus strains were given to the women or if the women were colonised by lactobacilli. The most striking factor was a new sex partner during the follow up period where the Odds Ratio of having a relapse was 9.3 (2.8-31.2) if the patients had a new sex partner during the observation period. Conclusions The study shows that aggressive treatment of the patient with antibiotics combined with specific Lactobacillus strain administration and partner treatment can provide long lasting cure. A striking result of our study is that change of partner is strongly associated with relapse of BV. Trial registration ClinicalTrials.gov: NCT01245322

Background The aim of this study was to investigate the colonisation by lactobacilli and clinical outcome in women with bacterial vaginosis (BV) and recurrent vulvovaginal candidiasis (R-VVC) receiving antibiotic or anti-fungal treatment in combination with the probiotic EcoVag® capsules. Methods A total of 40 Scandinavian women diagnosed with BV or VVC on the basis of Amsel’s criteria or clinical symptoms were consecutively recruited in two pilot open label clinical trials. In trial I, women with BV were treated with clindamycin and metronidazole followed by vaginal EcoVag® capsules, containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869, for 5 consecutive days after each antibiotic treatment. In trial II, women were recruited in three groups as follows: women with BV receiving clindamycin and metronidazole treatment together with a prolonged administration of EcoVag® (10 consecutive days after each antibiotic treatment followed by weekly administration of capsules for next four months), women with R-VVC receiving extended fluconazole and EcoVag® treatment, and women receiving extended fluconazole treatments only. The difference in frequency of isolation of EcoVag® strains or other lactobacilli between groups was compared by Fisher’s exact test. Results The 6-month cure rate for BV was 50 % in trial I while both the 6- and 12-month cure rates were 67 % in trial II. The 6- and 12-month cure rates for VVC were 100 % and 89 % in women receiving fluconazole and EcoVag®, and 100 % and 70 % in women receiving fluconazole only. The frequency of isolation of any Lactobacillus species during the course of the study was associated with cure of BV in trial I and II, whereas the frequency of isolation of EcoVag® strains was significantly associated with the cure of BV in trial II only. As previously observed, a change in sexual partner was associated with relapse of BV with an Odds ratio of 77 (95 % CI: 2.665 to 2225). Conclusions The study suggests that the treatment with antibiotics or anti-fungal medication in combination with EcoVag® capsules provide long-term cure against BV and R-VVC as compared to previous reports. Trial registration ClinicalTrials.gov NCT02295579 . Registered November 20, 2014

Background Bacterial vaginosis (BV), which is highly prevalent in the African population, is one of the most common vaginal syndromes affecting women in their reproductive age placing them at increased risk for sexually transmitted diseases including infection by human immunodeficiency virus-1. The vaginal microbiota of a healthy woman is often dominated by the species belonging to the genus Lactobacillus namely L. crispatus, L. gasseri, L. jensenii and L. iners, which have been extensively studied in European populations, albeit less so in South African women. In this study, we have therefore identified the vaginal Lactobacillus species in a group of 40 African women from Soweto, a township on the outskirts of Johannesburg, South Africa. Methods Identification was done by cultivating the lactobacilli on Rogosa agar, de Man-Rogosa-Sharpe (MRS) and Blood agar plates with 5% horse blood followed by sequencing of the 16S ribosomal DNA. BV was diagnosed on the basis of Nugent scores. Since some of the previous studies have shown that the lack of vaginal hydrogen peroxide (H 2 O 2 ) producing lactobacilli is associated with bacterial vaginosis, the Lactobacillus isolates were also characterised for their production of H 2 O 2 . Results Cultivable Lactobacillus species were identified in 19 out of 21 women without BV, in three out of five women with intermediate microbiota and in eight out of 14 women with BV. We observed that L. crispatus, L. iners, L. jensenii, L. gasseri and L. vaginalis were the predominant species. The presence of L. crispatus was associated with normal vaginal microbiota (P = 0.024). High level of H 2 O 2 producing lactobacilli were more often isolated from women with normal microbiota than from the women with BV, although not to a statistically significant degree (P = 0.064). Conclusion The vaginal Lactobacillus species isolated from the cohort of South African women are similar to those identified in European populations. In accordance with the other published studies, L. crispatus is related to a normal vaginal microbiota. Hydrogen peroxide production was not significantly associated to the BV status which could be attributed to the limited number of samples or to other antimicrobial factors that might be involved.

The vaginal macrobiota (VMB) is a complex and delicate balance between different bacterial species and is normally dominated by Lactobacillus species. Under the effect of hormonal changes, behavioral or sexual activity VMB could lose this balance resulting in diseases. Bacterial vaginitis (BV) is one of the most common vaginitis affecting women and is defined as an increase in proportion of anaerobic bacteria and a reduction or absence of lactobacilli. BV has been linked with increased risk of acquiring sexually transmitted diseases (STDs) including infection by human immunodeficiency virus type-1 (HIV-1). Vulvovaginal Canadianism (VVC) is the second most common cause of vaginitis after BV, which is recognized by an overgrowth of yeast mainly belonging to the genus Candida and albicans species. The standard clinical treatment for these conditions prescribes antibiotics (clindamycin and/or metronidazole) and anti fungal (fluconazole). This thesis focuses on investigating clinical interventions for the treatment of BV and VVC and attempting to express neutralizing antibody fragments in Lactobacillus against HIV-1 for future applications.An extended antibiotic treatment with clindamycin and metronidazole together with adjutant lactobacilli was tested in order to achieve long lasting cure and reduce relapse of BV (paper I). Five different combinations of Lactobacillus strains were tested which included newly characterized strains (paper I) and the commercial EcoVag® capsules (a mixture of L.gasseri DSM 14869 and L. rhamnosus DSM 14870). The cure rate was 74.6% after six months and 65.1% after 12 months. No significant difference was observed in cure rates depending on whether the women were colonized by any of the given strains. However, change of sexual partner was significantly associated with relapse of BV. The results were further confirmed in another clinical trial (paper II, trial I).We subsequently assessed the efficacy of a prolonged treatment with EcoVag® lactobacilli in combination with similar antibiotic treatment in BV patients (paper II, trial II). The cure rate was 66.7% and 62.5% after six months and 12 months respectively and was comparable to that in paper I. Prolonged treatment with lactobacilli did not significantly improve the colonization by EcoVag® strains. Overall colonization by any lactobacilli and by EcoVag strains was associated with cure of BV. Once again change of sexual partner was associated with relapse of BV. We also tested for the first time, a combination of EcoVag® and anti-fungal for treatment of recurrent VVC and evaluated if lactobacilli can colonize women when the microbiota is not disturbed by antibiotics. All the women were cured of VVC after six months and 87.5% remained cured after 12 months. EcoVag® strains colonized more in the presence of prior antibiotic treatment in BV patients and in women with VVC who were not colonized by Lactobacillus in the beginning of the study.The VMB has been extensively studied in European and American populations albeit less so in the African population. Therefore we have identified the vaginal Lactobacillus species in a group of 40 women in South Africa (paper III). We found that the vaginal Lactobacillus species identified were similar to those in other populations, suggesting that the strategies utilizing probiotic and engineered Lactobacillus could be applied in Africa.

Oil Marketing Companies (OMCs)ensure efficient supply chain management to deliver petroleum products to retail outlets in time and at an optimized cost. Terminals are an essential component in the supply chain and distribution network of petroleum products for retail outlets and consumers of petroleum products. These terminals have large capacities to store products distributed using trucks, railway wagons, or barges. Optimizing operations of the terminal leads to reducing the operational cost of OMCs.