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New research analyzing an online survey of 1,633 respondents found 15% recent use of doxycycline post- and pre-exposure prophylaxis (doxyPEP/PrEP) among men who have sex with men (MSM), transgender and gender diverse people in the Netherlands according to a recent study published by Eurosurveillance. These data highlight an increase in the informal use of doxyPEP/PrEP, with 65% of the participants intending to use it in the future. Currently, doxyPEP/PrEP is not recommended or actively promoted by healthcare professionals in the Netherlands. Informal use i.e. without a prescription by a healthcare professional, could contribute to antimicrobial resistance (AMR) and changes in the microbiome.

The use of doxyPEP has been shown to be an effective method in the prevention against sexually transmitted infections (STIs) in MSM, transgender and gender diverse persons. Clinical trials of doxyPEP have shown significant reductions in syphilis and chlamydia, with additional potential to reduce incidence of other bacterial STIs such as chlamydia and gonorrhea

However, the public health implications of the widespread use of doxyPEP are subject to current debate. The administration of doxyPEP to specific individuals could prevent a substantial number of STIs and lower antibiotic use, particularly among those who repeatedly have STIs.

Informal doxyPEP/PrEP use associated with HIV PrEP use, sexualized drug use and perception of safety

As highlighted by this paper and an accompanying editorial by Lyons et al., the prescription of doxyPEP to many sexually active individuals poses the risk of a substantial population-level increase in overall antibiotic consumption and an increase in AMR.

Teker et al. reviewed data from a cross-sectional study gathered from an online survey among MSM, transgender and gender diverse persons of 18 years of age or older. The survey focused on previous use of doxyPEP or doxyPrEP awareness and intention to use it. Participants were recruited through advertisements at the Centre for Sexual Health in Amsterdam, the Netherlands, as well as dating apps (Grindr), Instagram, Facebook, Facebook Messenger and targeted Instagram accounts.

In the study, 23% of participants reported having ever used doxyPEP/PrEP and 15% reported having used doxyPEP/PrEP in the six months prior to the survey. Respondents informing about recent use were more likely to report living with HIV or frequently using oral HIV PrEP in the six months before taking the survey. They were also more likely to report a history of bacterial STIs, having a higher number of sexual partners, and a higher frequency of engaging in chemsex and in group sex during that period.

Doxycycline was the most used antibiotic reported in this study, with 46% of the participants reporting using it recently as PEP, 29% of recent PEP users using it as PrEP and 25% using it as a combination of both. 

Overall, the intention to use doxyPEP/PrEP was very high among the study population, with more than half of the participants (65%) expressing intention to use. More than two thirds of respondents (72%) were willing to pay for doxyPEP/PrEP if it became formally available, indicating a potential demand for the drug among the study population and beyond. 

It was also found that doxyPEP/PrEP was primarily obtained from countries outside of the Netherlands or through prescriptions, with participants paying on average €30 for the drug.

Additional determinants for both informal use of doxyPEP/PrEP and high intention to use included using oral HIV PrEP or living with HIV, receiving advice from others to use doxyPEP/PrEP and perceiving doxyPEP/PrEP as an effective and safe method of STI prevention.

Potential antimicrobial resistance risks from lack of monitoring

The impact of prophylactic antibiotic use on AMR was highlighted in the study as there are uncertainties regarding the long-term adverse effects of doxyPEP/PrEP use. Teker et al. emphasize the potential harms of doxycycline effectiveness and AMR risks, as summarised in previous studies including in the United States. 

They also cite its potential effects on the gut microbiome, which need to be studied further. If doxyPEP is implemented in country-wide clinical guidance, it would be vital to monitor both individual and population-level resistance to doxycycline.

Lack of awareness on the extent of informal use of doxyPEP/PrEP makes it difficult to monitor and implement appropriate public health stewardship. This leads to difficulties in detecting overuse, misuseand adverse effects including AMR development and effects on microbiome composition.

A study has shown that neurons or nerve cells continue to form well into late adulthood in the brain’s hippocampus, which manages memory—a finding that presents compelling new evidence about the human brain’s adaptability.

Neurogenesis—a process whereby new neurons are created—is said to continue throughout one’s life, even as the rate is considered to slow down with age.

However, researchers from Karonlinska Institutet in Sweden said the extent and significance of neurogenesis is still debated with no clear evidence of cells that precede new neurons—or ‘neural progenitor cells’—actually existing and dividing in adults.

“We have now been able to identify these cells of origin, which confirms that there is an ongoing formation of neurons in the hippocampus of the adult brain,” Jonas Frisen, professor of stem cell research, Karolinska Institutet, who led the research published in the journal Science.

The team used carbon dating methods to analyse DNA from brain tissue, which made it possible to determine when the cells were formed. Tissue samples of people aged 0 to 78 were obtained from international biobanks, they said.

The results showed that cells that precede the forming of new neurons in adults are similar to those mice, pigs and monkeys, with differences in genes which are active.

The researchers also found large differences between individuals—some adult humans had many neural progenitor cells, others hardly any at all.

Frisen added that the study is an “important piece of the puzzle in understanding how the human brain works and changes during life”, with implications for developing regenerative treatments in neurodegenerative and psychiatric disorders.

A steady loss of neurons resulting in an impaired functioning and eventually cell death is said to drive neurodegenerative disorders, which affects the hippocampus, among other brain regions. Risks of the disorders are known to heighten with age.

For the study, the researchers used a method called ‘single-nucleus RNA sequencing’, which looks at activity of a gene in a cell’s nucleus.

This was combined with machine learning (a type of AI) to discern varied stages of how neurons develop, from stem cells to immature neurons, many of which were in the division phase, the team said.

“We analysed the human hippocampus from birth through adulthood by single-nucleus RNA sequencing. We identified all neural progenitor cell stages in early childhood,” they wrote.

“In adults, using antibodies against the proliferation marker Ki67 and machine learning algorithms, we found proliferating neural progenitor cells,” the authors wrote.

“The results support the idea that adult neurogenesis occurs in the human hippocampus and add valuable insights of scientific and medical interest,” the study said.