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Other than for papillomaviruses, there is a paucity of whole-genome sequences for bacteriophages and eukaryote-infecting viruses isolated from the female genital tract. Here, we report the genome sequences of 16 microviruses, 3 anelloviruses, 2 polyomaviruses, 1 genomovirus, and 1 caudovirus that were identified in vaginal secretion samples from adolescents in South Africa.

Background: Psychiatric disorders are associated with an increased risk of metabolic diseases, including obesity. The aim of this study was to determine whether genetic variants associated with severe mental illness (individually or combined in polygenic risk scores) have significant associations with adipose tissue biology. Methods: Adipose phenotypes, clinical and genetic data from was available from the participants of the GENiAL study. Summary statistics from the Psychiatric Genomic Consortium genome-wide association study meta-analyses were used to calculate polygenic risk scores for major depressive disorder, bipolar disorder and schizophrenia. Individual genetic variants associated with major depressive disorder, bipolar disorder and schizophrenia were cross referenced for associations with adipose phenotypes – specifically adipocyte morphology (sample N=895), adipocyte number (sample N=896), spontaneous (sample N=856) and stimulated lipolysis (sample N=875). We used R to carry out linear regression with adjustment for age, sex, population structure and body mass index (BMI; where appropriate). Results: There was no evidence that genetic variation associated with psychiatric disorders (individually or combined in polygenic risk scores) had significant effects on any adipose phenotypes. Conclusions: This study suggests that genetic variation associated with major depressive disorder, bipolar disorder and schizophrenia does not have direct effects on adipocytes.

Background: \ud The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. \ud \ud Methods: \ud Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. \ud \ud Results: \ud Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. \ud \ud Conclusion: \ud Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag-specific CD4+ T cell proliferation and interferon gamma (IFN-γ) production. Vaccine-specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme-Linked Immunosorbent assay (ELISA). MDSC frequency in mother-infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN-γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC-mediated suppression of vaccine Ag-specific IFN-γ responses should be explored further, and considered when evaluating candidate infant vaccines.

Vroue van Afrika-afkoms is meer vatbaar vir bakteriële vaginose (BV) in vergelyking met Europese vroue. Beide mikrobiese diversiteit (soos met BV) sowel as spesifieke bakteriële taksa speel ‘n rol in seksuele en reproduktiewe gesondheid insluitende MIV vatbaarheid. Die moontlike rol van geografi ese ligging en etnisiteit op die verhouding tussen mikrobiese samestelling en seskuele en reproduktiewe gesondheid bly egter onbekend. In hierdie studie vergelyk ons dus die vaginale mikrobiota van 16–22-jarige swart, HIV-negatiewe Suid-Afrikaanse vroue van twee geografies-uiteenlopende liggings, beide lae-inkomste, hoë bevolkingsdigtheidsgemeenskappe, een in Kaapstad, en een in Johannesburg. Vaginale mikrobiese profiele is bepaal met behulp van 16S rRNS volgordebepaling van laterale muur deppers. Ons pas permutasie variansieanalise (PERMANOVA) toe en vind statisties betekenisvolle assosiasies tussen vaginale mikrobiese samestelling en geografiese ligging (p=0.02), asook met liggaamsmassa-indeks (LMI) (p=0.015) en menslike papilloomvirus (MPV) risikotipe (p=0.005), maar nie met die voorkoms van een of meer seksueel-oordraagbare infeksies (SOI’s) (p=0.053) of met hormonale kontrasepsie verbruik nie. (p=0.4) Geografiese ligging was ‘n statisties betekenisvolle determinant van mikrobiese samestelling, ongeag verskille in LMI, SOI status en MPV-risiko tipes tussen Kaapstad en Johannesburg vroue. Geografiese ligging, LMI en MPV-risiko verduidelik gesamentlik 10% van die variansie in mikrobiese samestelling, met ‘n groot persentasie van onbekende oorsprong. Verskeie taksa het statisties betekenisvol verskil in terme van frekwensie of relatiewe vlakke van voorkoms tussen die geografiese liggings. Ons resultate stel voor dat MIV profi laktiese metodes wat die vaginale

Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota. DNA was extracted from vaginal lateral wall, saliva and supragingival plaque samples from 94 adolescent females (aged 15&ndash, 19 years). 16S rRNA gene sequencing of the V4 hypervariable region was performed for analysis of the oral and vaginal microbiota and BV status was determined by Nugent scoring. The core oral microbiota was predominately comprised of Firmicutes followed by Proteobacteria and Bacteroidetes. The salivary microbiota of participants with BV was more diverse than those with lactobacillus-dominated communities (p = 0.030). PD-associated bacterial species, including Prevotella intermedia and Porphyromonas endodontalis were enriched in the supragingival microbiota of women with non-optimal vaginal communities compared to those with Lactobacillus-dominant communities, while Pseudomonas aeruginosaand Prevotella intermedia were enriched in the saliva of women with non-optimal vaginal microbiota. These data suggest a relationship between oral and vaginal dysbiosis, warranting further investigation into whether they are casually related.

Both maternal microbiota and helminth infection may alter offspring immunity but the relationship between these is underexplored. We hypothesized that maternal helminth exposure prior to pregnancy has lasting consequences on offspring intestinal microbiota and consequent immunity. Female BALB/c adult mice were infected with 500L3 Nippostrongylus brasiliensis (N brasiliensis). Infection was cleared by ivermectin treatment, and mice were mated 3 weeks post-infection (NbM). Control mice were not infected but were exposed to ivermectin (NvM). We analysed maternal gut microbiota during pregnancy, breastmilk microbiota and offspring faecal microbiota and immunity 2 weeks after delivery. During pregnancy, NbM (Mothers previously infected with Nippostrongylus brasiliensis) displayed significantly altered stool bacterial communities (R2 = .242; P = .001), with increased abundance of Enterococcaceae versus NvM (Naive mothers). Similarly, we observed a profound impact on breastmilk microbiota in NbM vs NvM. Moreover, NbM pups showed significantly altered gut microbial communities at 14 days of age versus those born to NvM with increased relative abundance of Coriobacteriaceae and Micrococcaceae. These changes were associated with alterations in pup immunity including increased frequencies and numbers of activated CD4 T cells (CD4 + CD44hi) in NbM offspring spleens. Taken together, we show that preconception helminth infections impact offspring immunity possibly through alteration of maternal and offspring microbiota.

BackgroundDuring pregnancy, the vaginal microbiota is relatively stable. However, African women have more diverse vaginal microbiota than their European counterparts, in addition to high human immunodeficiency virus (HIV) prevalence and risk of adverse birth outcomes. Although HIV is associated with alterations in vaginal microbiota and inflammation in nonpregnant women, these relationships are underexplored in pregnant women.MethodsIn this study, we characterize the vaginal microbiota and immune factors in pregnant African women who were HIV-uninfected (n = 314) versus HIV-infected (n = 42). Mucosal samples were collected once at the enrollment visit (between 15 and 35 weeks of gestation) and women were followed until delivery.ResultsVaginal microbial communities of pregnant women with HIV were significantly more diverse than women without HIV (P = .004), with community structure also differing by HIV status (P = .002, R2 = 0.02). Human immunodeficiency virus infection was also associated with increased risk of preterm birth (PTB) (31% versus 15.3%; P = .066). In a multivariate analysis, HIV infection was independently associated with diverse vaginal community state type (CST)-IVA (P = .005) and CST-IVB (P = .018) as well as PTB (P = .049). No association between HIV status and cytokine concentrations was found.ConclusionsLongitudinal studies with accurate gestational age assessment would be important to confirm these relationships.

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation., Hormonal contraception may alter women’s susceptibility to HIV. Here, the authors report the results of a randomized clinical trial substudy assessing the effects of injectable Net-En, oral contraceptives (COC) and Nuvaring on vaginal microbiota and cytokines, associating COC with lower microbial diversity and Nuvaring with increased inflammation.

crAssphages are a broad group of diverse bacteriophages in the order Caudovirales that have been found to be highly abundant in the human gastrointestinal tract. Despite their high prevalence, we have an incomplete understanding of how crAssphages shape and respond to ecological and evolutionary dynamics in the gut. Here, we report genomes of crAssphages from feces of one South African woman and three infants. Across the complete genome sequences of the South African crAssphages described here, we identify particularly elevated positive selection in RNA polymerase and phage tail protein encoding genes, contrasted against purifying selection, genome-wide. We further validate these findings against a crAssphage genome from previous studies. Together, our results suggest hotspots of selection within crAssphage RNA polymerase and phage tail protein encoding genes are potentially mediated by interactions between crAssphages and their bacterial partners.

Background Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. Results In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. Conclusion Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity. Electronic supplementary material The online version of this article (10.1186/s40168-018-0511-7) contains supplementary material, which is available to authorized users.

Young South African women, from resource-poor communities, face several sexual and reproductive health challenges. Here we describe the vaginal microbiota and sexually transmitted infection (STI) prevalence of 102; 16–22-year-old, HIV-negative South African women from a low-income, high-population-density community in Cape Town (CPT). Vaginal microbiota were profiled using 16S rRNA amplicon sequencing; bacterial vaginosis (BV) status was established using Nugent scoring and STIs were determined by multiplex polymerase chain reaction. STIs were common, with 55% of women having at least one STI; 41% were infected with high-risk human papilloma virus (HPV) and a further 28% with low-risk HPV; 44% were infected with Chlamydia, 16% of whom had at least one additional STI. Similarly, BV rates were very high, with 55% of women classified as BV-positive (Nugent score ≥7), 7% as BV-intermediate (Nugent score 3–6) and 38% as BV-negative (Nugent 0–2). Group B Streptococcus (Streptococcus agalactiae), the leading cause of neonatal sepsis, was present in 25% of BV-positive women and 28% of BV-negative women, and was significantly more abundant among BV-negative women. Both Chlamydia infection and BV may adversely affect reproductive health and place these women at additional risk for HIV acquisition. The high abundance of Prevotella amnii, in particular, may increase HIV risk, given its inflammatory capacity. Laboratory-based testing for STIs (Chlamydia and Gonorrhoeae in particular) appear to be warranted in this community, together with further monitoring or treatment of BV.Research correlation: This article is the original version, of which an Afrikaans translation was made available to provide access to a larger readership, available here: https://doi.org/10.4102/satnt.v36i1.1495

OpsommingJong Suid-Afrikaanse vroue uit hulpbron-arm gemeenskappe staar verskeie uitdagings in die gesig in terme van hulle seksuele en reproduktiewe gesondheid. Hier beskryf ons die voorkoms van vaginale mikrobiota en seksueel oordraagbare infeksies (SOI’s) onder 102; 16–22-jarige MIV-negatiewe Suid-Afrikaanse vroue uit ’n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad. Vaginale mikrobiota is met behulp van 16S rRNA amplikon volgorde-bepaling geprofileer; bakteriese vaginose (BV) status is met behulp van ’n Nugent-telling vasgestel; en SOI’s is deur middel van ’n multipleks polimerase kettingreaksie bepaal. SOI’s was algemeen, met 55% van die vroue wat ten minste een SOI gehad het; 41% wat met hoë-risiko menslike papillomavirus (MPV) besmet was, en ’n verdere 28% wat met laerisiko-MPV besmet was; 44% van die vroue was met Chlamydia besmet waarvan 16% een of meer addisionele SOI gehad het. BV persentasies was ook baie hoog met 55% van die vroue wat as BV-positief (Nugent-telling ≥7) geklassifiseer is, 7% as BV-intermediêr (Nugent-telling 3–6), en 38% as BV-negatief (Nugent-telling 0–2). Streptococcus (Streptococcus agalactiae), die grootste oorsaak van neonatale sepsis, was teenwoordig in 25% van die BV-positiewe vroue en 28% van die BV-negatiewe vroue, en was dus meer onder BV-negatiewe vroue. Chlamydia-infeksie sowel as BV kan reproduktiewe gesondheid nadelig beïnvloed en verhoog hierdie vroue se risiko vir die verkryging van MIV. Die voorkoms van veral Prevotella amnii kan die MIV-risiko verhoog as gevolg van sy inflammatoriese kapasiteit. Laboratorium-gebaseerde toetsing vir SOI’s (veral Chlamydia en Gonorrhoeae) blyk in hierdie gemeenskap geregverdig te wees, tesame met verdere monitering en/of behandeling van BV.Navorsing korrelasie: Hierdie artikel is die vertaalde weergawe en is beskikbaar gestel om ‘n breër lesersgroep te bereik. Die oorspronklike Engelse artikel is beskikbaar hier: https://doi.org/10.4102/satnt.v36i1.1484

Author(s): Wood, Lianna F; Brown, Bryan P; Lennard, Katie; Karaoz, Ulas; Havyarimana, Enock; Passmore, Jo-Ann S; Hesseling, Anneke C; Edlefsen, Paul T; Kuhn, Louise; Mulder, Nicola; Brodie, Eoin L; Sodora, Donald L; Jaspan, Heather B | Abstract: Background:Exclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding. Methods:We performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay. Results:A total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in EBF infants. Conclusions:These data suggest that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

Young African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously ( Prevotella , Sneathia , Aerococcus , Fusobacterium , and Gemella ) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, Prevotella amnii , Prevotella pallens , Parvimonas micra , Megasphaera , Gardnerella vaginalis , and Atopobium vaginae and decreased frequencies of Lactobacillus reuteri , Lactobacillus crispatus , Lactobacillus jensenii , and Lactobacillus iners ). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection.

Rationale – There is limited evidence about the effect of climate on blood pressure management of people living with and cared for hypertension in Sub-Sahara Africa. We investigate the relationship between outdoor temperature and blood pressure in a primary care setting with limited control of indoor climate in Cape Town, South Africa. Method – The study uses blood pressure data from 2494 participants screened and enrolled for entry in the SMS-text Adherence (StAR) trial study. Participants’ data were matched with outdoor temperature and air quality data using the nearest hour of enrolment. Individuals were included in this study if they were recruited during the study’s screening period (June 2012 to November 2014) and the clinic’s operating hours (7h00 and 17h00). Result - 72% of participants enrolled for the trial were female and had a BMI of 31 kg/m2 . There was an inter-subject variation of blood pressure between participants enrolled in winter and spring. Those enrolled in winter (June – July) and in the morning (07h00-10h00) when temperatures were generally low, had a higher mean blood pressure compared to those enrolled during spring (September - November) and in the afternoons (≥13h00). Mean outdoor temperature during the trial period was 16.7°C (min: 3.7°C –max: 30.7°C) with lowest temperatures recorded in June. Both outdoor temperature and blood pressure were found to be associated with nitrogen dioxide (NO2) and sulphur dioxide and (SO2) and therefore may be confounded by them. In a multivariate analysis controlling for air pollution, humidity and several leading cardiovascular risk factors, it was observed that a 10°C increase in outdoor temperature was associated with 7.5mmHg (95% CI: 3, 82 - 11, 18) change in systolic blood pressure. This association is modified by age, BMI and the time of the day. Those 65 years and older, with a low BMI and those enrolled in the morning (7h00 – 10h00) had the greatest change in blood pressure due to outdoor temperature Conclusion –The study shows an inverse association between outdoor temperature and clinic-based blood pressure in a primary care setting in South Africa. Given the fact that clinic-based blood pressure measures are used to direct the management of hypertension, greater attention needs to be given to environmental factors which may affect it. This may become of greater clinical relevance with changes in the climate and extreme weather patterns, including extensive smog