Setback re: Gonorrhea PEP & Vaxx

[SirBillybob]

Updated/revised DoxyVAC trial results a year later; reduced benefit from DoxyPEP and negligible benefit from Bexsero vaccine.

https://www.poz.com/article/meningococcal-vaccine-significantly-reduce-gonorrhea-risk

[+ nycman]

1 hour ago, SirBillybob said:

Updated/revised DoxyVAC trial results a year later; reduced benefit from DoxyPEP and negligible benefit from Bexsero vaccine.

https://www.poz.com/article/meningococcal-vaccine-significantly-reduce-gonorrhea-risk

Actually, it looks like the results aren’t so bad. I mean, DoxyPEP had very good reduction in chlamydia and syphilis rates, and a significant (although not great) reduction in gonorrhea rates. Unfortunately, I predict wide spread DoxyPEP use will soon lead to near universal doxycycline resistance in gonorrhea, making it useless for gonorrhea prevention. And although the meningitis vaccine didn’t show a great reduction in gonorrhea, there appears to be some. Not bad for vaccine that wasn’t targeted at gonorrhea. I think people got a little too excited about the early results from this trial. Nonetheless, I think it shows a real gonorrhea vaccine might be feasible.

Overall, I’d chalk this up as good, although not great news. 

[SirBillybob]

Let me pose this question. At a certain point virtually everybody sexually active and with a similar risk profile to DoxyVAC eligible study participants and receiving doxycycline PEP will eventually get breakthrough gonorrhea infection that requires standard treatment, treatment that is currently very effective. It’s just a question of when, simply because incident rates are quite high, albeit less frequently compared to no DoxyPEP. According to your own risk tolerance, what is the temporal frequency of breakthrough gonorrhea infection, say, in months, that would for you satisfactorily maintain the ‘worth it’ factor for DoxyPEP uptake? In other words, what is the period of time that you require to stave off gonorrhea infection such that DoxyPEP has enough value to pursue it?

Edited April 28 by SirBillybob

[+ nycman]

11 hours ago, SirBillybob said:

In other words, what is the period of time that you require to stave off gonorrhea infection such that DoxyPEP has enough value to pursue it?

At this point, I would put any prevention of gonorrhea by DoxyPEP into the category of "lucky side effect that won’t last". I’d still consider DoxyPEP for prevention of chlamydia and syphilis though. Since gonorrhea is already largely resistant to doxycycline, I don’t see the real harm in driving its doxycycline resistance to 100%. 

Although that doesn’t take into account, the idea that by selecting gonorrhea that is resistant to doxycycline, you are also selecting gonorrhea that is resistant to other drugs, and thus driving up antimicrobial resistance across-the-board. Certainly it’s going to be an interesting experiment to watch, because I don’t think DoxyPEP is going away anytime soon.
 

A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance - PMC

WWW.NCBI.NLM.NIH.GOV

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Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing...

 

Edited April 28 by nycman

[marylander1940]

On 4/27/2024 at 5:25 PM, SirBillybob said:

Updated/revised DoxyVAC trial results a year later; reduced benefit from DoxyPEP and negligible benefit from Bexsero vaccine.

https://www.poz.com/article/meningococcal-vaccine-significantly-reduce-gonorrhea-risk

 

On 4/28/2024 at 7:58 AM, nycman said:

At this point, I would put any prevention of gonorrhea by DoxyPEP into the category of "lucky side effect that won’t last". I’d still consider DoxyPEP for prevention of chlamydia and syphilis though. Since gonorrhea is already largely resistant to doxycycline, I don’t see the real harm in driving its doxycycline resistance to 100%. 

Although that doesn’t take into account, the idea that by selecting gonorrhea that is resistant to doxycycline, you are also selecting gonorrhea that is resistant to other drugs, and thus driving up antimicrobial resistance across-the-board. Certainly it’s going to be an interesting experiment to watch, because I don’t think DoxyPEP is going away anytime soon.
 

A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance - PMC

WWW.NCBI.NLM.NIH.GOV

---

Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing...

 

Can we please blend all threads about this subject?

 

[SirBillybob]

Re: thread merging. Thanks for inserting the year-old topic. I had been aware of it. I consciously started the new topic as it is specific to the one bacterial STI [gonorrhea] most concerning for its increasing standard treatment failure rate, as well as adds vaccination concepts (eg, Bexsero) not included in the previous discussion but that had been referenced in at least one other thread on the board. Moreover, the previous topic discussion is antimicrobial resistance focused and requires unpacking the merits and liabilities of DoxyPEP alone across a broader range of viral and bacterial diseases. There are also several separate threads more relevant to gonorrhea alone over the past year, including vaccination as mentioned, newly emerging first-in-class oral treatment medications, and acute disseminated gonococcal disease. Anybody wishing a more integrative reading experience is advised to use the search term ‘gonorrhea’ on the board. 

Edited April 29 by SirBillybob

[+ APPLE1]

My biggest concern at this point is for the speed at which the DoxyPREP regimen may accelerate the resistance of chlamydia and syphilis.

Obviously, it is a bit of a summary article and not a not a journal article on the research data, but I am gathering that while chlamydia remained relatively constant, starting at 88% with the initial DoxyPREP trial and 89% a year in, syphilis was initially 87% and fell to 79% a year in.

If the big picture observations are that:

- DoxyPREP only reduces gonorrhea infection rate by 33%;

-studies show evidence that vaccination with meningococcal B by itself reduce gonorrhea by 30 - 50%;

-current scientific theory tells us that short bursts of antibiotics contribute resistance;

-antibiotics take a toll on body systems; and

-we already know that Benzathine Penicillin G is already a better treatment for syphilis than doxycycline

I would place my faith in vaccination for gonorrhea, treat syphilis with the superior antibiotic, and treat both gonorrhea and chlamydia with a FULL course of Doxycycline as needed.

And of course, pray to the pharmaceutical and profit gods for vaccines specific for all three!

[SirBillybob]

9 hours ago, APPLE1 said:

If the big picture observations are that:

- DoxyPREP only reduces gonorrhea infection rate by 33%;

-studies show evidence that vaccination with meningococcal B by itself reduce gonorrhea by 30 - 50%

I would place my faith in vaccination for gonorrhea, treat syphilis with the superior antibiotic, and treat both gonorrhea and chlamydia with a FULL course of Doxycycline as needed.

And of course, pray to the pharmaceutical and profit gods for vaccines specific for all three!

The conference paper indicates that Bexsero risk reduction dropped from 22% to 16% when analyzing cumulative GC infections, that is, new recurrences as opposed to first infection exclusively. There has been some chatter that a large Bexsero trial has since been cancelled but I have not been able to figure out if that relates to the ongoing large U Alabama study, the smaller Australian study, or a proposal not yet formally registered. I think that a viable vaccine is not on the proximal horizon. 

That said, the revised DoxyPEP analysis excluded a second set of analyses incorporating recurrences; the total incidence appears to add about 25% more cases to first infection incidence. My sense is that GC risk reduction will have dropped from the revised 33% to a less meaningful degree, particularly since the proportional hazards curves eventually intersect following a parallel rather than widening gap. If this omission was intentional, disingenuous even, perhaps it is moot given that I doubt any forthcoming DoxyPEP product monograph will include indication for GC prophylaxis.

I think you mean Ceftriaxone with possibly Azithromycin or Doxycycline added for standard GC treatment.

—-
This brings us to recent data on standard Ceftriaxone effectiveness embedded in Innoviva’s Zoliflodacin noninferiority trial (mentioned in an earlier thread) and now GSK’s Gepotidacin noninferiority trial. The two new oral formulations and current standard treatment are showing around 90% cure rates, and these first-in-class developments are being framed as exciting. Well, no. It’s not a good time to acquire gonorrhea infection. 

 

Edited April 30 by SirBillybob

[+ nycman]

5 minutes ago, SirBillybob said:

It’s not a good time to acquire gonorrhea infection. 

 

Was there ever a "good" time?……grin