Could Chlamydia treatment failure be the result of genital contamination from persistent gut infection

The persistence of Chlamydia trachomatis  (Ct) infection in treated patients is generally attributed either to re-infection or poor treatment adherence.  To some, however, the evidence has suggested the operation of an additional factor – such as treatment failure (STIs/ Goetz & Bruisten; STIs/ Pitt & Ison; STIs/ Horner).

A recent study (Rank & Yeruva (R&Y)) develops an interesting hypothesis, based on evidence of Ct. infection in the gastro-intestinal (GI) tract of mice.  This supports the possibility that Ct. persistence in humans might be a result of ongoing Ct. infection of the gut, and re-infection of the genital via the lower GI tract (Yeruva & Rank).  According to R&Y’s research on animals, Ct. of the GI tract does not elicit an inflammatory response, and never resolves.  It provokes an immune response – but not at a level that would cure the GI infection.  The orthodoxy states that Ct. found in the human GI tract is “non-replicating”.  R&Y claim this not based on evidence.  So they see nothing to exclude the possibility that, in humans, as in mice, treatment failure may be due to auto-innoculation from the lower GI tract.

This hypothesis is highly relevant to discussion of Ct. persistence in this journal, which has arisen around such questions as: whether persistence is due to some factor other than re-infection or poor adherence, such as anti-microbial resistance (STIs/ Goetz & Bruisten; STIs/ Pitt & Ison); how important that factor is, and what it means for Chlamydia screening programs (STIs/ Regan & Hocking).  If R&Y’s hypothesis proves valid for humans as for mice, then that other factor – or, at least, some element of it – is explained, and would certainly need to be taken account of when modelling the effectiveness of screening programs.

The idea that persistence of Ct. in humans results from contamination from persistent GI tract infection seems to be a new one in the STI literature (though apparently cases have been documented by the veterinary literature in numerous animals as early as the 1950s).  It is certainly worthy of further investigation, given the implications that it would have, if proven, for diagnosis and management of human Ct. infection.  In that event, it would be necessary to consider, for example, what importance to attach to the clearing Ct. from the GI tract – and, supposing this to be necessary, how this would affect the nature and duration of treatment given for genital Ct..  In treating rectal Ct., for example, treatment with Azithromycin (≤13%) has been claimed to be inadequate (STIs/ Drummond & Donovan), while Hathorn & Goold find treatment with doxycycline to be a more effective alternative (STIs/ Hathorn & Goold).

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