iiinova — where your digital self keeps evolving

Michael Marks @drmichaelmarks.bsky.social · 02/10/2026

Thanks @benvyle.bsky.social for hosting us @thelovetankcic.bsky.social to discuss community co-creation, participation, engagement and qualitative research as part of out collaborative projects focused on the control of syphilis in the UK.

A photo of a group of people in a line. In the centre they are holding up postcards about syphilis.

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Michael Marks @drmichaelmarks.bsky.social · 08/08/2026

Doesnt really make sense to just directly use Tanzania data as a prior as they have very different absolute effect sizes. But if you take the relative effect from Tanzania as the basis for a beta-binomial prior the net is still similar - there is about a 50% chance that the NNT is 1000 or less.

A graph showing the posterior distribution of a bayesian analysis showing the probability that Vitamin D decreases the absolute risk of TB by at least 0.1% in absolute terms.

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Michael Marks @drmichaelmarks.bsky.social · 08/08/2026

Here is the Mongolia data quickly re-analysed with a Bayesian model and a beta-binomial prior centred on null. Plotted probability there is a 0.1%, 0.2%, 0.3% absolute risk reduction in TB disease (NNT 1000, 500, 333). <50% chance NNT is 1000 & only a 8.7% chance that is as low as 333.

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Michael Marks @drmichaelmarks.bsky.social · 04/08/2026

I attach a copy of the letter I have on several occasions sent to journals when they publish yet another of these trials.

The image shows a letter discussing the failure of Vitamin D to improve health outcomes in a large number of trials. It concludes:

Outside of the trial setting, a wide range of observational studies have reported Vitamin D to have strong associations with a wide range of clinical outcomes. This has been accompanied by basic science studies which have demonstrated pleiotropic effects, in particular on immune responses, which provide plausible mechanisms by which Vitamin D might ultimately influence clinical outcomes.

Despite this observational and basic science data, the consistent message of randomised controlled trials is that vitamin D based interventions have little if any discernible health impact. What can explain this disconnect between basic science, observational studies and the results repeatedly observed in trials? Potentially, the association of Vitamin D and poor outcomes is true but our interventions do not sufficiently impact on VItamin D and it's downstream mediators to have a health impact. Secondly, we are targeting only a single molecule amongst a complex milieu of other important mediators. Just like trying to 'stop sepsis' by targeting activated protein C we may well be merely playing around the edges of a larger system and unable to impact the ultimate clinical outcome.

Or perhaps Vitamin D's association are simply not causal. Given the diverse range of diseases targeted by Vitamin D in trials, and the consistently negative findings of these studies, this option appears to warrant consideration. Whatever the reason, the research community has now committed several millions of dollars repeatedly testing the hypothesis that vitamin D modification will have significant health impact. The repeated failure of this strategy does not reflect well on science funding. We should take time to reflect and consider how we ended up here.

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Michael Marks @drmichaelmarks.bsky.social · 19/06/2026

Bridget Freyne presenting CARES-1 trial: The first new trial for congenital syphilis treatment in 30 years & the first ever trial of a non-penicillin treatment for congenital syphilis. Super excited to be part of the team for this trial & looking forward to results over next 12-24 months.

Presenter stood in front of a slide describing the design of the CARE-1 trial.

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Michael Marks @drmichaelmarks.bsky.social · 18/02/2026

Next up hearing about the creation of an incredible (and I suspect unique) birth cohort of Palestinian refugees pubmed.ncbi.nlm.nih.gov/38414543/ Allows linkage of health & education data in this cohort & to explore (sadly) a wide range of exposures including the impact of conflict on outcomes. 4/n

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Michael Marks @drmichaelmarks.bsky.social · 18/02/2026

At @lshtm.bsky.social workshop on administrative data for early life exposures. Wonderful opening Bethania Almedia CIDACS with a paper from 1946 on 'Record Linkage' to generate the Book of Life which still feels highly relevant today. pmc.ncbi.nlm.nih.gov/articles/PMC... 1/n

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Michael Marks @drmichaelmarks.bsky.social · 13/01/2026

Wiping clean the last year of grant applications & preparing for this one. As always grateful to a stellar group of colleagues & collaborators who keep the show on the road.

A whiteboard showing a list of projects that were applied for in 2025

A whiteboard showing plans for 2026 projects.

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Michael Marks @drmichaelmarks.bsky.social · 07/01/2026

Out @lancetmicrobe.bsky.social & led @amberbarton.bsky.social We used WGS to look at Treponema population dynamics during community MDA for yaws tinyurl.com/bd6zu6xm Intriguingly found sublineage associated w longer ulcer duration & lower antibody titres. Whether occurs in syphilis needs exploring

The image shows two box and whisker plots. The left hand plot shows the duration of peoples ulcers stratified by sub-lineage and demonstrates that one of these sub-lineages has a longer duration of ulcers than the others. The right hand plot shows the titre of treponemal antibodies stratified by sub-lineage and demonstrates that the same sub-lineage is also associated with much lower antibody titres than the others.

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Michael Marks @drmichaelmarks.bsky.social · 03/01/2026

As ever from Lorenzo, @nicolelieberman.bsky.social & the team at @uwnews.uw.edu a great paper showing variation in Penicillin Binding Proteins in T.pallidum do not appear to impact susceptibility - consistent with what we have observed clinically for 50+ years. journals.lww.com/stdjournal/a...

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Michael Marks @drmichaelmarks.bsky.social · 02/01/2026

We found extremely low levels in semen in our cohort study during the 2022 pandemic & (caveat emptor) always below the level at which we could culture it (see also Table S3 in the Supplementary). www.thelancet.com/journals/lan...

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Michael Marks @drmichaelmarks.bsky.social · 28/12/2025

Don't worry I think your position is common (especially in USA). Nagoya is a globally agreed set of rules about ensuring protection of rights related to genetic/biological resources. The USA is not a signatory unlike nearly all European, African, Asian and South American governments (see map).

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Michael Marks @drmichaelmarks.bsky.social · 11/12/2025

Super proud of my student Philippe Ndzomo awarded PhD today at University of Yaounde. His work focused on the emergence of Hameophilus ducreyi as a cause of cutaneous ulcers in Cameroon & Globally pubmed.ncbi.nlm.nih.gov/40338972/ pubmed.ncbi.nlm.nih.gov/39961439/ pubmed.ncbi.nlm.nih.gov/38150487/

The student and members of his team wearing formal academic gowns as he is awarded his PhD.

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Michael Marks @drmichaelmarks.bsky.social · 09/12/2025

Incredible retirement talk by Prof. Paul Fine @lshtm.bsky.social Career dedicated to global health, critical enquiry & passion for training next generation in UK & esp Malawi where he left huge legacy. Privilege spend 10+yrs at same institution & humbling to know its not even 1/3 time hes been here.

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Michael Marks @drmichaelmarks.bsky.social · 02/12/2025

Congratulations to Burrell St Sexual Health: First UK patient into SOS Global - Evaluating mucosal shedding of spirochetes in heterosexual individuals with syphilis. Great collaboration led by Melbourne Sexual Health Centre focused on understanding syphilis transmission.

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Michael Marks @drmichaelmarks.bsky.social · 22/11/2025

Great event at the Red Run for World Aids Day - a bracing, wet, windy but highly enjoyable 10km. Still accepting final donations for an excellent cause - @thelovetankcic.bsky.social

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Michael Marks @drmichaelmarks.bsky.social · 13/11/2025

Fabulous meeting in Zimbabwe @thruzim.bsky.social for PROMISE Trial Investigating STI screening in 12,000 women in antenatal care thruzim.org/hiv-srh-1/promise Great team across clinical, stats, economics, social science, genomics & basic science to allow us to tackle a wide range of questions

A photo of a group of people who make up many of the people working on the PROMISE study.

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Michael Marks @drmichaelmarks.bsky.social · 10/11/2025

Two syphilis/STI related UK PhD Studentships with our group: Evaluating near-patient syphilis tests with @uclglobalhealth.bsky.social inyurl.com/aw9sapma deadline 5th Dec 2025 Mathematical models to understand partner notification tinyurl.com/2re7xasj deadline 14th Jan 2026 Please do share

A picture of the spirochete that causes Treponema pallidum

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Michael Marks @drmichaelmarks.bsky.social · 22/10/2025

A beautiful example of why when assessing growth of a pathogen in a cell culture line that you need to know if the drug is actually just killing the cell line. For example T.pallidum doesn't grow in culture when you use ivermectin BUT that's because ivermectin is killing the cell line.

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Michael Marks @drmichaelmarks.bsky.social · 22/10/2025

There is exciting progress in identifying human cell lines which could replace rabbit cells in the culture model & could therefore more accurately recapitulate human syphilis infection.

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Michael Marks @drmichaelmarks.bsky.social · 22/10/2025

We can use the in-vitro cultivation system to explore the pathogenesis of T.pallidum. This is helping us understand the interactions between epithelial cells and the pathogen which is critical to transmission and pathogenesis. Slowly slowly itching towards vaccines...

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Michael Marks @drmichaelmarks.bsky.social · 22/10/2025

The schema developed by Sheila Lukehart (queen of syphilis immunology) highlights the key role of cellular immune responses alongside humoral responses in controlling and clearing T.pallidum.

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Michael Marks @drmichaelmarks.bsky.social · 22/10/2025

Kicking off day 3 Shanghai Syphilis Symposium. There is still a huge amount we can learn from the historic studies to inform our understanding of syphilis immunology and vaccine development.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

BPG is made up of lots of crystals of penicillin bound to Benzathine. These slowly release penicillin into the blood - so we have a long period of absorption from IM into the blood and then a short elimination half life in the circulation.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

The lack of evidence means there is massive variation around the world in how asymptomatic infants with congenital syphilis are managed globally. We need clearer guidelines informed by well done diagnostic and therapeutic studies.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

At one end of the congenital syphilis spectrum are those infants who have symptomatic disease. These children can be severely unwell and we need drugs that can be easily and safely administered to sick neonates.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

There remains a depressingly high gap in many LMIC settings between uptake of HIV testing and syphilis testing in Antenatal Care. And it's not an issue of cost because this is a cheap and hugely cost effective intervention. It's an issue around political will, prioritisation and sustained support.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Introducing a new diagnostic test is not enough to address issues - for syphilis RDTs even though they gave a quicker test turn around it required a full health system intervention for that to be accompanied by an increased uptake of Syphilis treatment

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Fundamental health system barriers remain as the major challenge to the implementation of diagnostics. If we don't fix this then no matter how good your new syphilis test is you will still run in to major road blocks in implementing and improving care pathways.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Pregnant women with syphilis are also shedding from their mucosa in a similar fashion to what has been demonstrated in MSM populations.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Neurosyphilis criteria vary from country to country. A classic example of the absence of a reference standard to guide diagnostic pathways & inform management.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

We can leverage social network structure to distribute self-testing kits to contacts & there is evidence this is a more effective method than simply asking individuals to refer their contacts for facility based testing.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

There are multiple different ways we can deliver syphilis serological testing. There is good RCT data that self testing models can result in an increase in the uptake of testing - especially amongst first time testers - and (in China at least) was cheaper than facility based testing.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Rapid clearance of T.pallidum from non-lesion mucosal sites following treatment - so regardless of importance for transmission treatment will be highly effective at rendering individuals non-infectious.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Highlighting that amongst asymptomatic individuals there can still be a lot of mucosal shedding of T.pallidum. Can we use this to inform staging of clinical cases? What does it mean for transmission dynamics? Lots still to learn about this.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

A reminder that the clinical spectrum of Congenital Syphilis is wide and that there are distinct and only partly overlapping requirements for diagnostic needs in each place. Unlikely a single test can answer all these needs.

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Michael Marks @drmichaelmarks.bsky.social · 21/10/2025

Day 2 of the Shanghai International Syphilis Symposium. Bridget Freyne highlighting the inadequacies of current surveillance definitions and mechanisms for congenital syphilis. Algorithms are either to complex for LMIC implementation OR likely result in over investigation in HICs.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

There are a series of gaps that need to be addressed if we want to identify viable alternative therapeutics to benzathine penicillin for syphilis treatment.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

We also need alternative drugs for several different manifestations of syphilis AND also think about how we can improve partner notification and treatment. We know poor partner notification uptake is associated with worse pregnancy outcomes - tackling this point is especially challenging.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

The @who.int recently published global STI research priorities - better tests and very importantly implementation research on their optimal deployment was the number one identified priority.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

What are the evidence gaps we need to address to move forward the development of syphilis vaccines. We really need to understand some fairly basic elements - What does protection look like - Who do we need to vaccinated for maximum impact - Which technologies should we leverage for vaccine design

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

Highlighting the all too familiar story that pregnant women and children are often left out of treatment studies & the regulatory framework is often not supportive of addressing this critical gap.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

The region suffers (as many so) with ongoing testing and treatment gaps. In some countries the legal framework doesn't allow a syphilis rapid test to be performed by front line staff. So you have to send blood to a lab where they then do the test - turn around 3-7 days: not so rapid!

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

Latin America is now often considered a middle-higher income country but this is accompanied by extreme income inequality. These inequalities are also seen in syphilis where indigenous people have much higher rates of syphilis than the broader population prevalence.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

MSM remain key population for syphilis epidemics - reflecting transmission dynamics but also structural & society barriers and context. MSM are often earlier adopters of new biomedical interventions so working closely with this population can help us learn a lot how these tools are best deployed

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

Yes we need new tools BUT we can make a huge step forward by improving our deployment of existing strategies and strengthening syphilis control at all levels of the health system

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

We also need to strengthen the treatment pipeline - this should include improving the supply, targeting and dosing of Benzathine Penicillin as well as identifying alternative therapies.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

Testing in the ANC setting remains much too low - closing this gap needs to be a major focus if we want to achieve Elimination of Congenital Syphilis. There are also several areas where new tests could help move the field forward - most notably (I think) simplifying the diagnosis for infants.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

Changing tack to global target of Elimination of Mother to Child Transmission of Syphilis where the largest burden of morbidity and mortality is. Vital for this to be integrated into alongside HIV and Hepatitis B. 21 countries have now achieved the WHO target but globally progress remains limited.

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Michael Marks @drmichaelmarks.bsky.social · 20/10/2025

More work to be done but is there potential that understanding tprK deep sequencing can help us better unpick transmission networks given how conserved the core genome is?

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