Browsing by Author "Balle, Christina"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    Open Access
    Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents
    (Multidisciplinary Digital Publishing Institute, 2023-03-15) Happel, Anna-Ursula; Balle, Christina; Havyarimana, Enock; Brown, Bryan; Maust, Brandon S.; Feng, Colin; Yi, Byung H.; Gill, Katherine; Bekker, Linda-Gail; Passmore, Jo-Ann S.; Jaspan, Heather B.; Varsani, Arvind
    The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex). The DNA virome included single-stranded (Anelloviridae, Genomoviridae) and double-stranded DNA viruses (Adenoviridae, Alloherpesviridae, Herpesviridae, Marseilleviridae, Mimiviridae, Polyomaviridae, Poxviridae). We identified 110 unique, complete HPV genomes within two genera (Alphapapillomavirus and Gammapapillomavirus) representing 40 HPV types and 12 species. Of the 40 HPV types identified, 35 showed positive co-infection patterns with at least one other type, mainly HPV-16. HPV-35, a high-risk genotype currently not targeted by available vaccines, was the most prevalent HPV type identified in this cohort. Bacterial taxa commonly associated with bacterial vaginosis also correlated with the presence of HPV. Bacterial vaginosis, rather than HPV, was associated with increased genital inflammation. This study lays the foundation for future work characterizing the vaginal virome and its role in women’s health.
  • Thumbnail Image
    Item
    Open Access
    Effects of hormonal contraceptives on the female genital tract microbiota in South African adolescents
    (2018) Balle, Christina; Jaspan, Heather; Passmore, Jo-Ann; Lennard, Katie
    Background Young women in sub-Saharan Africa are disproportionally affected by HIV and often rely on injectable hormonal contraception (HC) to prevent unintended pregnancies. However, HC might affect HIV-1 risk through changes in the female genital tract (FGT) microbiota. We examined the impact of three different HC methods on the adolescent female genital tract microbiota and related cytokine and HIV target cell levels at the cervical mucosa in a randomized, crossover trial. Study design and methods 131 adolescent females aged 15 to 19 from Cape Town were enrolled into a randomized, crossover study. The participants were randomized into three study arms: 1. progestin-only injectable norethisterone enanthate (Net-En), 2. combined oral contraceptive pills (COCPs) or 3. combined contraceptive vaginal ring (CCVR) for 16 weeks. Participants then switched to one of the other HC options for a final four months. Vaginal samples were collected at baseline, crossover and exit. STI testing and Nugent scoring were performed at all study visits. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing, cytokine concentrations were measured by Luminex and CD4+ T cells analysed by flow cytometry. Results Using fuzzy clustering, three major female genital tract bacterial community types were identified. Two of these were dominated by Lactobacillus species (L. crispatus and L. iners, respectively) and the third was comprised of a diverse group of anaerobic bacteria associated with bacterial vaginosis (BV). In an intention-to-treat analysis at crossover, participants randomized to COCP had a significantly less diverse vaginal microbiota compared to participants randomized to either Net-En or CCVR. The same was observed in an according to protocol analysis at crossover. Using differential abundance testing and random forest analyses, we found that species associated with BV and risk of HIV were significantly more abundant in, and predictive of, participants on Net-En (e.g. Prevotella, Sneathia and Dialister) or CCVR (e.g. Prevotella, Mycoplasma and Parvimonas) compared to COCP while L. iners was more common in the COCP group. Cytokine concentrations were positively associated with a diverse vaginal community and with specific bacterial taxa associated with BV and increased risk of HIV including species enriched in participants on Net-En and NuvaRing. In contrast, there were no association of the frequencies of CD4+ T cells expressing CCR5+ with the vaginal community or BV status. There was likewise no significant association with BV or diversity with Th17 cell frequency, yet BVassociated bacteria were more abundant in participants with higher frequencies of Th17 cells. Conclusions Our data generated from a randomized study suggests that COCPs use may exert a positive influence on genital health through an increase in lactobacilli and a decrease in BV-associated bacterial taxa with an accompanying decrease in overall bacterial diversity, vaginal pH and cytokine levels. In contrast, the vaginal microbiota of participants on Net-En and NuvaRing have increased levels of bacteria associated with BV and HIV risk and increased cytokine levels. We did not observe any association of the frequencies of CD4+ T cells expressing CCR5 or Th17-like cells with the vaginal community, BV status or HC use.
  • Thumbnail Image
    Item
    Open Access
    Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents
    (2021-11-23) Happel, Anna-Ursula; Balle, Christina; Maust, Brandon S; Konstantinus, Iyaloo N; Gill, Katherine; Bekker, Linda-Gail; Froissart, Rémy; Passmore, Jo-Ann; Karaoz, Ulas; Varsani, Arvind; Jaspan, Heather
    The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact.
  • Thumbnail Image
    Item
    Open Access
    The association between the oral and vaginal microbiome of young South African women
    (2019) Esra, Rachel; Jaspan, Heather; Balle, Christina
    Bacterial vaginosis (BV) and periodontal disease (PD) are conditions characterised by reduction of healthy bacterial communities in the vaginal and oral microbiomes respectively. Both BV and PD are associated with an increased risk of preterm labour and negative birth outcomes, yet it is unknown whether PD and BV are independent risk factors or may be interrelated. Understanding the health risks associated with pregnancies in young women is critical for developing new preventative interventions and for informing guidelines. Current knowledge of what constitutes a healthy microbiome is largely based on North American studies and may not be applicable to the South African population. This study characterises the oral and vaginal microbiome of South African female adolescents and investigates the association between alterations in oral bacterial diversity and BV in young South African women. DNA was extracted from matched lateral vaginal wall, saliva and periodontal samples and V4 16S sequencing was performed using MiSeq technology. The composition of the core oral microbiome of South African female adolescents was found to be similar to descriptive studies published in other populations. We additionally report a description the vaginal microbiome that is in agreement with previous studies in the South African population. PD-associated bacterial species were enriched in the oral microbiome of women with clinically diagnosed BV and in those with Lactobacillus iners dominant vaginal community types (VCTs) compared to asymptomatic women and those with L. crispatus dominated VCTs respectively. While this data provides evidence in support of a relationship between oral and vaginal dysbiosis, it unclear in which compartment bacterial dysbiosis would originate, should the association holds true.