A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia.

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

Starting to have sexual intercourse is associated with increases in cervicovaginal immune mediators in young women: a prospective study and meta-analysis.

Background: Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in changes to immune mediators in the cervicovaginal tract that contribute to this risk. Methods: We collected cervicovaginal lavages from Kenyan AGYW in the months before and after first penile-vaginal sexual intercourse and measured the concentrations of 20 immune mediators. We compared concentrations pre- and post-first sex using mixed effect models. We additionally performed a systematic review to identify similar studies and combined them with our results by meta-analysis of individual participant data. Results: We included 180 samples from 95 AGYW, with 44% providing only pre-first sex samples, 35% matched pre and post, and 21% only post. We consistently detected 19/20 immune mediators, all of which increased post-first sex (p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1ß, IL-2, and CXCL8). Effects remained similar after excluding samples with STIs and high Nugent scores. Concentrations increased cumulatively over time after date of first sex, with an estimated doubling time of about 5 months.Our systematic review identified two eligible studies, one of 93 Belgian participants, and the other of 18 American participants. Nine immune mediators were measured in at least two-thirds of studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (p<0.05 for six mediators, most prominently IL-1α, IL-1ß, and CXCL8). Conclusions: Cervicovaginal immune mediator concentrations were higher in women who reported that they started sexual activity. Results were consistent across three studies conducted on three different continents. Funding: This research was funded by R01 HD091996-01 (ACR), by P01 AI 030731-25 (Project 1) (AW), R01 AI116292 (FH), R03 AI154366 (FH) and by the Center for AIDS Research (CFAR) of the University of Washington/Fred Hutchinson Cancer Research Center AI027757.

Contraceptive rings promote vaginal lactobacilli in a high bacterial vaginosis prevalence population: A randomised, open-label longitudinal study in Rwandan women.

BACKGROUND: Hormonal contraception has been associated with a reduced risk of vaginal dysbiosis, which in turn has been associated with reduced prevalence of sexually transmitted infections (STIs), including HIV. Vaginal rings are used or developed as delivery systems for contraceptive hormones and antimicrobial drugs for STI and HIV prevention or treatment. We hypothesized that a contraceptive vaginal ring (CVR) containing oestrogen enhances a lactobacilli-dominated vaginal microbial community despite biomass accumulation on the CVR's surface. METHODS: We enrolled 120 women for 12 weeks in an open-label NuvaRing® study at Rinda Ubuzima, Kigali, Rwanda. Vaginal and ring microbiota were assessed at baseline and each ring removal visit by Gram stain Nugent scoring (vaginal only), quantitative PCR for Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae, and fluorescent in situ hybridization to visualize cell-adherent bacteria. Ring biomass was measured by crystal violet staining. RESULTS: Bacterial vaginosis (BV) prevalence was 48% at baseline. The mean Nugent score decreased significantly with ring use. The presence and mean log10 concentrations of Lactobacillus species in vaginal secretions increased significantly whereas those of G. vaginalis and presence of A. vaginae decreased significantly. Biomass accumulated on the CVRs with a species composition mirroring the vaginal microbiota. This ring biomass composition and optical density after crystal violet staining did not change significantly over time. CONCLUSIONS: NuvaRing® promoted lactobacilli-dominated vaginal microbial communities in a population with high baseline BV prevalence despite the fact that biomass accumulated on the rings.

A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa.

In cross-sectional studies increased vaginal bacterial diversity has been associated with vaginal inflammation which can be detrimental for health. We describe longitudinal changes at 5 visits over 8 weeks in vaginal microbiota and immune mediators in African women. Women (N = 40) with a normal Nugent score at all visits had a stable lactobacilli dominated microbiota with prevailing Lactobacillus iners. Presence of prostate-specific antigen (proxy for recent sex) and being amenorrhoeic (due to progestin-injectable use), but not recent vaginal cleansing, were significantly associated with microbiota diversity and inflammation (controlled for menstrual cycle and other confounders). Women (N = 40) with incident bacterial vaginosis (Nugent 7-10) had significantly lower concentrations of lactobacilli and higher concentrations of Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia, at the incident visit and when concentrations of proinflammatory cytokines (IL-1ß, IL-12p70) were increased and IP-10 and elafin were decreased. A higher 'composite-qPCR vaginal-health-score' was directly associated with decreased concentrations of proinflammatory cytokines (IL-1α, IL-8, IL-12(p70)) and increased IP-10. This longitudinal study confirms the inflammatory nature of vaginal dysbiosis and its association with recent vaginal sex and progestin-injectable use. A potential role for proinflammatory mediators and IP-10 in combination with the vaginal-health-score as predictive biomarkers for vaginal dysbiosis merits further investigation.

Prevalence and correlates of bacterial vaginosis in different sub-populations of women in sub-Saharan Africa: a cross-sectional study.

BACKGROUND: Clinical development of vaginally applied products aimed at reducing the transmission of HIV and other sexually transmitted infections, has highlighted the need for a better characterisation of the vaginal environment. We set out to characterise the vaginal environment in women in different settings in sub-Saharan Africa. METHODS: A longitudinal study was conducted in Kenya, Rwanda and South-Africa. Women were recruited into pre-defined study groups including adult, non-pregnant, HIV-negative women; pregnant women; adolescent girls; HIV-negative women engaging in vaginal practices; female sex workers; and HIV-positive women. Consenting women were interviewed and underwent a pelvic exam. Samples of vaginal fluid and a blood sample were taken and tested for bacterial vaginosis (BV), HIV and other reproductive tract infections (RTIs). This paper presents the cross-sectional analyses of BV Nugent scores and RTI prevalence and correlates at the screening and the enrolment visit. RESULTS: At the screening visit 38% of women had BV defined as a Nugent score of 7-10, and 64% had more than one RTI (N. gonorrhoea, C. trachomatis, T. vaginalis, syphilis) and/or Candida. At screening the likelihood of BV was lower in women using progestin-only contraception and higher in women with more than one RTI. At enrolment, BV scores were significantly associated with the presence of prostate specific antigen (PSA) in the vaginal fluid and with being a self-acknowledged sex worker. Further, sex workers were more likely to have incident BV by Nugent score at enrolment. CONCLUSIONS: Our study confirmed some of the correlates of BV that have been previously reported but the most salient finding was the association between BV and the presence of PSA in the vaginal fluid which is suggestive of recent unprotected sexual intercourse.