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Bacterial vaginosis

Bacterial vaginosis-associated bacterium (Gardnerella) may after all have a role in the aetiology of non-gonococcal urethritis

28 Apr, 17 | by Leslie Goode, Blogmaster

The question of the aetiology of ‘non-gonococcal’ or ‘non-specific’ urethritis (NGU/NSU) has been a hot topic of debate in this journal and its predecessors since before 1951, when it was officially acknowledged in the Chief Medical Officer’s report as an independent category of infection (Oriel (STI)). More recently, a number of infectious agents have been recognized as potentially responsible (Hallen & Wallin (STIs); Moi & Moghaddam (STIs)).  But it would be misleading to suggest that, even today, the aetiological question has been altogether resolved.

The controversial hypothesis that bacterial vaginosis (BV) associated bacteria (i.e. Gardnerella) might have a role – proposed in 2001 in an STI editorial by a former editor (Shamanesh (STIs)) – seems to have raised its head once again in a recent animal-based study, Gilbert & Lewis (G&A). Results from studies that have tested for the presence of these – amongst other – bacterial agents seem not to have been particularly favourable to the hypothesis (Manhart & Fredericks (STI); Froelund & Jensen (STIs)).  It must be borne in mind, however, that ‘fastidious growth requirements make G. vaginalis unrecoverable, or at least unidentifiable, under conditions most often used by clinical microbiology labs for the culture and identification of potential uropathogens’ (G&A, p.11).

G&A hypothesize G. vaginalis operates indirectly in the case of NSU by triggering the emergence of Escherichia coli from reservoirs in the bladder of the pre-infected individual.  In this way repeated sexual contact could, they suggest, lead to recurrent UTI infections by an infection that is not itself sexually transmitted.  This theory of ‘covert pathogenesis’ is tested by exposing mice with latent E-coli infection – i.e. mice that had been transurethrally pre-infected but were now negative for bacteriuria – to repeated doses of G. vaginalis or Lactobacillus crispatus.  It was found that double exposure to G.v. triggered E-coli bacteriuria while exposure to L.c.  did not.  Furthermore, G.v. exposed mice had neutrophilic infiltrates, confirming the presence of active UTI.  In sacrificed mice, G.v. was also found to have induced bladder epithelial exfoliation and apoptosis in the bladder epithelium.

The theory of covert pathogenesis is intriguing – not least because it overrides any hard-and-fast distinction been sexually-related and non-sexually-related UTIs.  But, assuming it turns out to be correct, it also has practical implications.  The conventional paradigm assumes that the pathogen present at time of clinical presentation is the main driver of disease.  Given the alarming rise of multi-drug resistant E-coli, the authors point to the potential benefit of preventing UTI and sequelae (e.g. pyelonephritis) by targeting the organism that triggers the infection (i.e. G. vaginalis) rather than the pathogen that causes the symptoms.


Susceptibility of heterosexual sub-Saharan women to HIV could be the result of cervicovaginal microbiome characteristics

30 Jan, 17 | by Leslie Goode, Blogmaster

Could part of the explanation for the apparent susceptibility of sub-Saharan African heterosexual women to HIV infection (eight-fold that of males) lie in the bacterial flora of their female genital tract (FGT)?

Studies published in STI journal have considered the relationship between a certain state of the FGT bacterial microbiome – especially the depletion of lactobacillus (Francis & Grosskurth/STIs) – and the susceptibility to BV (Antonio & Hillier/STIs; Hardy & Crucitti/STIs; Francis & Grosskurth/STIs; Haggerty & Ness/STIs), to pelvic inflammatory disease (Haggerty & Ness/STIs), and to other STIs (Francis & Grosskurth/STIs).  Others have observed the prevalence of Lactobacillus in the healthy FGT microbiome (Madhivanan & Krupp/STIs), and considered the impact on the FGT lining of practices of vaginal douching (Balkus & McClelland/STIs), hormonal contraception (Verwijs & Wijgert/STIs), and sexual debut (Jespers & Crucitti/STIs).

Highly relevant to all these discussions is a recently published study by Gosmann & Anahtar of a prospective cohort of 236 young HIV-negative women participating in the South African Ragon Institute’s FRESH study (Females Rising through Educations, Support and Health) in Kwa-Zulu Natal. The researchers were able to follow up their cohort for a total of 198.2 person-years, in the course of which 31 participants acquired HIV.  The researchers distinguish four ‘cervicotypes’ in respect to FGT bacterial flora; then determine their prevalence along with their association with ‘HIV target cells’ (i.e. activated CD4 T cells expressing the HIV co-receptor CCR5) and HIV acquisition.

The four cervicotypes correspond to the dominance of Lactobacillus crispatus and of Lactobacillus iners (CT1 and CT2, respectively), the preponderance of Gardnerella vaginalis (CT3), and a biome showing a far more diverse range of bacterial types (CT4).  Strikingly, the first two cervicotypes (CT1 and CT2) account for only 10% and 32% of women in the cohort; while, among white women in Western countries, the proportion showing Lactobacillus dominance would be c.90%.  The other 58% fall into the categories of high diversity communities with low Lactobacillus abundance (CT3 and CT4).  More interestingly still, none of the 31 HIV sero-conversions took place among the 10% of women with CT1-type bacterial flora.  Rather, sero-conversions were fairly evenly distributed among the other three cervicotypes, with some diminution of relative incidence in the CT2 category (i.e. nine sero-conversions, as opposed to 10 and 12 in CT3 and CT4 respectively).  Researchers observed a 17-fold increase in HIV target cells in women with a CT4-type cervico-vaginal microbiome as against those with CT1-type, and elevated levels of chemokines MIP-α and MIP-β which attract CCR5 expressing cells in women with diverse FGT bacterial communities.

Sadly, regimens aiming to restore Lactobacillus crispatus dominance (e.g. antibiotics or probiotic vaginal suppositories) show significant recurrence rates.  However, modifiable biological and behavioural factors may play a considerable role on Lactobacillus depletion in sub-Saharan African women (e.g. vaginal washing; antibiotic use; recent Trichomonas and HSV-2).  If so, then, as Baeten & McClelland/STIs point out, this would suggest the possibility of effective intervention strategies to reduce HIV transmission by improving vaginal health.

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