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.