Antibiotic resistance tends to stabilise over time, according to a study published April 3, 2025 in the open-access journal PLOS Pathogens by Sonja Lehtinen from the University of Lausanne, Switzerland, and colleagues.
Antibiotic resistance is a major public health concern, contributing to an estimated 5 million deaths per year. Understanding long-term resistance patterns could help public health researchers to monitor and characterise drug resistance as well as inform the impact of interventions on resistance.
In this study, researchers analysed drug resistance in more than 3 million bacterial samples collected across 30 countries in Europe from 1998 to 2019. Samples encompassed eight bacteria species important to public health, including Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.
They found that while antibiotic resistance initially rises in response to antibiotic use, it does not rise indefinitely. Instead, resistance rates reached an equilibrium over the 20-year period in most species. Antibiotic use contributed to how quickly resistance levels stabilised as well as variability in resistance rates across different countries. But the association between changes in drug resistance and antibiotic use was weak, suggesting that additional, yet unknown, factors are at play.
The study highlights that continued increase in antibiotic resistance is not inevitable and provides new insights to help researchers monitor drug resistance.
Senior author Francois Blanquart notes: “When we looked into the dynamics of antibiotic resistance in many important bacterial pathogens all over Europe and in the last few decades, we often found that resistance frequency initially increases and then stabilises to an intermediate level. The consumption of the antibiotic in the country explained both the speed of initial increase and the level of stabilisation.”
Senior author Sonja Lehtinen summarises: “In this study, we were interested in whether antibiotic resistance frequencies in Europe were systematically increasing over the long-term. Instead, we find a pattern where, after an initial increase, resistance frequencies tend to reach a stable plateau.”
A medical breakthrough could result in the first treatment for rare but serious diseases in which genetic defects disrupt cellular energy production. Researchers at the University of Gothenburg have identified a molecule that helps more mitochondria function properly.
Mitochondrial diseases caused by POLG mutations vary in severity. In young children, these diseases can quickly result in brain damage and life-threatening liver problems while others suffer muscle weakness, epilepsy, and organ failure later in childhood. POLG mutations recently received media attention when Prince Frederik of Nassau in Luxembourg died in March 2025 at just 22 years of age.
The POLG gene regulates the production of DNA polymerase gamma, an enzyme that copies mitochondrial DNA. Without it, the mitochondria cannot function normally and, as a result, fail to provide the cell with energy.
A breakthrough
Maria Falkenberg and Claes Gustafsson, professors at Sahlgrenska Academy at the University of Gothenburg, have led the work behind the study now being published in the journal Nature.
“We demonstrate that the molecule PZL-A can restore the function of mutated DNA polymerase gamma and improve the synthesis of mitochondrial DNA in cells from patients. This improves the ability of the mitochondria to provide the cell with energy,” says Maria Falkenberg.
“This is a breakthrough as for the first time we can demonstrate that a small molecule can help improve the function of defective DNA polymerase. Our results pave the way for a completely new treatment strategy,” says Claes Gustafsson.
From lab to medication
More than twenty years of basic research led to the discovery of PZL-A. The molecule was identified following the analysis of hundreds of chemical compounds in collaboration with Pretzel Therapeutics, where another one of the lead authors of the study, Simon Giroux, has led the chemical development of the molecule. So far, the molecule has been studied in cells from patients as well as in animal models.
Sebastian Valenzuela, a doctoral student at Sahlgrenska Academy, has analysed the molecule’s structure, including by means of cryo-electron microscopy.
“We demonstrate exactly where the molecule binds, between two separate chains of the enzyme. The binding site is extremely specific, which helps us understand how the enzyme works and how we can influence it,” says Sebastian Valenzuela, first author of the study.
Pretzel Therapeutics has just embarked on phase I studies with a refined version of the molecule in order to test its safety on healthy volunteers. Since a lack of mitochondrial DNA is also seen in other mitochondrial, age-related, and neurodegenerative diseases, substances similar to PZL-A may gain broader therapeutic use.
The cancellation of PEPFAR funding to South Africa could cause between 150 000 and 295 000 additional HIV infections by the end of 2028. This is unless the South African government covers some of the defunded services.
These are the preliminary findings of a new modelling study commissioned by the National Health Department to look into the impact of PEPFAR funding cuts in South Africa. It was authored by researchers at the University of Cape Town (UCT) and University of the Witwatersrand (WITS). PEPFAR is a multi-billion dollar US initiative that supports HIV-related services globally, but which has been significantly slashed by the Trump administration since February.
The research on South Africa comes at the same time that a separate modelling study was published in The Lancet which found that the discontinuation of PEPFAR could cause an additional 1-million HIV infections among children in sub-Saharan Africa by 2030. This would lead to the deaths of about 500 000 children according to the study, while over 2-million others would be left orphaned.
On 20 January, newly-elected US president Donald Trump issued an executive order which suspended virtually all US foreign development assistance for 90 days pending a review. As a result, US-backed aid programmes were brought to a standstill across the world, including in South Africa. While a waiver was published which supposedly allowed some PEPFAR-related activities to continue, this had a limited effect in practice.
Since then, some US grants have resumed, while others have been cancelled. The value of all terminated grants comes to tens of billions of dollars globally. In South Africa, numerous awards have been cancelled from PEPFAR, which had provided roughly R7.5-billion to non-profit organisations in the country in 2024. These organisations primarily used the money to hire and deploy health workers in government clinics, or to operate independent health facilities. Many of these have now been forced to close.
While there are still some active PEPFAR grants in South Africa, it’s unclear how much longer these will be retained, as many are only approved until September. The new study focusing on South Africa models what would happen if all PEPFAR funding was eliminated.
Up to 65 000 additional deaths expected by 2028
In 2024 roughly 78% of all people who had HIV in South Africa were on antiretroviral (ARV) treatment. This figure has been steadily rising over time. By 2026, it was expected to climb to 81%, according to Dr Lise Jamieson, lead author of the local modelling study.
But this trend will be reversed if the entire PEPFAR programme is cancelled and the government fails to step in. ARV coverage among people with HIV would drop to 70% by 2026, according to the study. Under the model’s more pessimistic scenario, the figure would drop even lower – to 59% by 2026.
This is partly because some people living with HIV in South Africa get their ARVs directly from PEPFAR-funded drop-in centres. If these centres close down, some patients may stop taking their ARVs. Indeed, this is precisely what happened after one centre in Pretoria stopped providing services.
The loss of PEPFAR funds could also hinder the health system’s capacity to get newly-infected people on HIV treatment. For instance, PEPFAR-funded organisations had employed nearly 2000 lay counsellors across South Africa who tested people for HIV. Without these staff, fewer people will be diagnosed and get started on treatment.
Not only will ARV coverage drop due to the cuts, but HIV prevention services will also be affected, according to the study. For instance, PEPFAR-funded drop-in sites had been providing people with pills that prevent HIV, called pre-exposure prophylaxis (PrEP). These services were targeted at groups most likely to contract and transmit HIV, like sex workers. According to the new modelling study, the full termination of PEPFAR would lead to as much as a 55% reduction in PrEP coverage for female sex workers by 2026.
Because of factors like these, the researchers estimate that the PEPFAR cuts would cause between 56 000 and 65 000 additional HIV-related deaths in South Africa by 2028. By 2045, this would increase to between 500 000 and 700 000 deaths.
Nearly 90% of USAID contracts terminated in South Africa
All of these results only hold if the South African government fails to step in, according to Jamieson. The modelling study finds that to cover all PEPFAR services from 2025 to 2028, the government would need to spend an extra R13 to 30-billion in total.
It’s unlikely that the government will cough up this amount, but according to Jamieson the National Health Department is taking steps to identify and support certain key services that were defunded by PEPFAR. She is hopeful that the results may not be as drastic as what the study suggests.
Another caveat is that the modelling study estimated what would happen if South Africa lost all of its PEPFAR funding. But at least for now, there are still some grants reaching beneficiaries in the country.
PEPFAR funds are primarily distributed by two US agencies – the US Agency for International Development (USAID) and the US Centres for Disease Control and Prevention (CDC). While both agencies paused funding after the initial suspension order in late-January, the CDC resumed its funding roughly two weeks later. This was after a US federal court ruled that the Trump administration could not freeze congressionally appropriated funds.
CDC grants only appear to be active until September (at least for South African beneficiaries), though uncertainty remains about this.
USAID has taken a much harder line – funding was suspended from late January. By late-February, the agency moved from pausing funds to issuing termination notices to most of its beneficiaries.
In South Africa, roughly 89% of all USAID funding has been cancelled. The value of all cancelled funds comes to about US$261-million (R5.2-billion). Only five other countries have faced larger cuts in absolute terms (see all country-level estimates here). Spotlight and GroundUp have confirmed that at least some of the remaining 11% of USAID funding has once again begun flowing to beneficiaries in the country.
Thus, a small amount of USAID funding is trickling into South Africa, while CDC funds have largely been retained in full. Though it’s unclear for how much longer.
While Australia was busy defending the Pharmaceutical Benefits Scheme against threats from the United States in recent weeks, another issue related to the supply and trade of medicines was flying under the radar.
Buried on page 19 of the Trump’s administration’s allegations of barriers to trade was a single paragraph related to Australia’s access to generic medicines. These are cheaper alternatives to branded medicines that are no longer under patent.
The US is concerned about how much notice their drug companies have that Australia will introduce a generic version of their product. Once a single generic version of a medicine is listed on the PBS, the price drops. The US argues that lack of advance notice is a barrier to trade.
There is pressure for Australia to emulate aspects of the US system, where drug companies can delay generic copies of their medicines by 30 months.
If the US plays hardball on this issue, perhaps in return for other concessions, this could delay Australia’s access to cheaper generic drugs.
It would also mean significant pressure on Australia’s drug budget, as the government could be forced to pay for the more expensive branded versions to ensure supply.
What’s the current process?
Drug companies use patents to protect their intellectual property and prohibit other manufacturers from copying the drug. The standard patent term in Australia is 20 years, but the time a product is protected by patents can be extended in a number of ways. When patents expire, other companies are able to bring generic versions to market.
A generic manufacturer wanting to market its drug in Australia must apply to the Therapeutic Goods Administration (TGA) for regulatory approval. Before approval is granted, the generic company must provide a certificate to the TGA that states either:
a) that the product will not infringe a valid patent, or
b) that it has notified the patent-holder of its intention to market the product.
The certificate can be provided after the TGA has evaluated the generic – before it grants approval.
If the generic company chooses option “a”, the manufacturer of the patented product may not find out the competing product is going to be launched until after the TGA has approved it.
The patent-holder can then apply for a court order to temporarily stop the generic from coming to market, while legal battles are fought over patent-related issues.
However, if the first generic has already launched and been added to the PBS, it triggers an automatic 25% price drop. This affects all versions of the drug, including the patented product.
In Australia, patented drug companies that try to delay generics by taking legal action without good reason can face penalties and be required to pay compensation.
Patented drug companies don’t like this system. They want to know as early as possible that a generic is planning to launch so they can initiate legal action and prevent or delay generic entry and the associated price reductions.
Is Australia’s system consistent with our trade obligations?
Australia introduced its patent notification system at the request of the US, to comply with the Australia-US Free Trade Agreement (AUSFTA). The World Trade Organization doesn’t require patent notification.
The report also mentions US concerns about the potential for penalties and compensation when a patent owner takes legal action against a generic company.
This report reflects long-standing concerns of the US pharmaceutical industry. In March, its drug makers trade association wrote to the US trade representative complaining that “lack of adequate notification” is an unfair trade practice. It argued this creates uncertainty for patent-holders, prevents resolution of patent challenges before generics enter the market, and penalises patented-drug companies for trying to protect their rights.
Medicines Australia, which represents the Australian subsidiaries of many big patented drug makers, echoes these concerns.
What does the US want instead?
The US patent notification system is much more favourable to the patented drug companies than Australia’s.
In the US, the generic company must notify the patented drug company within 20 days of filing an application for approval.
Then, within 45 days of receiving the notification, the patent-holder can ask the regulator to impose a 30-month delay on approval for the generic.
This means there is an automatic 30-month delay on the launch of the generic, unless patents expire in the meantime or the court decides earlier that valid patents aren’t being infringed.
What could happen if Australia bowed to pressure from the US?
Changing Australia’s system to be more like the US would delay generics entering the market in Australia and keep the price of drugs higher for longer.
The quicker generics can be added to the PBS, the less the government pays. When the first generic is listed on the PBS, a 25% price cut is applied to all versions of the product, including the patented version.
Over time, as more generics get added, prices continue to fall. Having plenty of generic competition can eventually result in prices lower than the PBS co-payment, resulting in savings for consumers.
In the longer term, lost savings from timely listing of generics on the PBS would reduce value for money and add cost pressure.
In time, it could also delay savings for consumers from drugs priced below the PBS co-payment.
Both major parties are saying they won’t use the PBS as a bargaining chip in negotiations with the US over tariffs. They also need to resist pressure to slow down access to generic drugs.
Shoulders are, in many ways, a marvel. One shoulder has four separate joints, packed with muscles, that allow us to move our arm in eight different major ways, giving us the most degrees of freedom of any joint in the body. We can swim, toss, hug, and even punch because of the movement our shoulders enable.
But the same complexity that allows us such motion also presents opportunities for pain when something goes wrong. Another complication: shoulders change as we age, and new types of injuries come with it. Clinical practitioners face the daunting task of keeping up on the latest developments to treat a range of injuries as wide as Michael Phelps’ wingspan.
“It’s not that shoulder problems are unique to one particular age or for one particular group of individuals, but rather that they can arise throughout our lifetime,” said Paul Salamh, visiting associate professor of rehabilitation sciences at Tufts University School of Medicine. “Because we ask our shoulders to do so much, they’re vulnerable to a wide range of issues.”
It can also be a challenge for health care providers to keep up with all of the latest evidence-based research on treating shoulder injuries. That’s why Salamh served as the lead author on two recently published papers, the research for which was conducted while he worked at the University of Indianapolis, about efforts to help coalesce this information and make it easier for everyone to understand.
In a paper published recently in the International Journal of Sports Physical Therapy, Salamh and other researchers conducted a systematic review of 19 papers on shoulder injuries. That review included four studies encompassing 7802 athletes in baseball, handball, swimming, tennis, cricket, American football, and also multi-sport athletes and people in the military. The reason to focus on athletes, Salamh said, was because the rate of shoulder and elbow pain in athletes in these “overhead” sports is increasing. A 2022 study estimated that nearly 11% of athletes between the ages of 5 to 18 years old experience a shoulder injury.
Overall, the research team found five risk factors for athletes developing shoulder pain, two that can’t be changed (local and regional musculoskeletal pain) and three that can (range of motion, strength, and training load).
These findings are supportive of a drilling-down approach to risk factors specific to body region, sport, and where applicable, position played in that sport, said Salamh. “There is a lot that can be looked at specifically in each sport. For example, the range of motion that would predispose a swimmer to a shoulder injury is different than that for someone playing lacrosse,” he said, adding that the same is true with strength of muscle or muscle groups within a particular sport.
In a paper published recently in the Journal of Manual and Manipulative Therapy, Salamh and a team of researchers addressed a decade’s worth of research on the risk factors, aetiology, diagnosis, and management of frozen shoulder, an inflammatory condition that causes unrelenting stiffness and pain in the shoulder that can last for years.
For this paper, 14 international experts discussed and identified possible risk factors for the condition and symptoms that most often lead to a diagnosis. They also examined 33 different treatment options and categorised them into effectiveness for treating frozen shoulder in its earlier stages when pain is more prominent than stiffness, and later stages, when stiffness is a bigger problem than pain.
“The treatment we would intervene with varies significantly depending on the stage of the condition,” Salamh said. “Depending on where they are in this process, we could be doing something that could be more painful and create more problems for individuals than be helpful.”
Overall, Salamh hopes that these types of papers and future research can lead to better understanding of what this unique joint requires to stay healthy along the course of our lives. “We want to take the complexity of the shoulder and not simplify it but make it more manageable and digestible for patients, clinicians, and researchers,” he said.
Heavy drinkers who have eight or more alcoholic drinks per week have an increased risk of brain lesions called hyaline arteriolosclerosis, signs of brain injury that are associated with memory and thinking problems, according to a study published on April 9, 2025, online in Neurology®, the medical journal of the American Academy of Neurology (AAN).
Hyaline arteriolosclerosis is a condition that causes the small blood vessels to narrow, becoming thick and stiff. This makes it harder for blood to flow, which can damage the brain over time. It appears as lesions, areas of damaged tissue in the brain.
“Heavy alcohol consumption is a major global health concern linked to increased health problems and death,” said study author Alberto Fernando Oliveira Justo, PhD, of University of Sao Paulo Medical School in Brazil. “We looked at how alcohol affects the brain as people get older. Our research shows that heavy alcohol consumption is damaging to the brain, which can lead to memory and thinking problems.”
The study included 1781 people who had an average age of 75 at death. All had brain autopsies. Researchers examined brain tissue to look for signs of brain injury including tau tangles and hyaline arteriolosclerosis. They also measured brain weight and the height of each participant. Family members answered questions about participants’ alcohol consumption. Researchers then divided the participants into four groups: 965 people who never drank, 319 moderate drinkers who had seven or fewer drinks per week; 129 heavy drinkers who had eight or more drinks per week; and 368 former heavy drinkers.
Researchers defined one drink as having 14 grams of alcohol, which is about 350mL of beer, 150mL of wine or 45mL of distilled spirits. Of those who never drank, 40% had vascular brain lesions. Of the moderate drinkers, 45% had vascular brain lesions. Of the heavy drinkers, 44% had vascular brain lesions. Of the former heavy drinkers, 50% had vascular brain lesions.
After adjusting for factors that could affect brain health such as age at death, smoking and physical activity, heavy drinkers had 133% higher odds of having vascular brain lesions compared to those who never drank, former heavy drinkers had 89% higher odds and moderate drinkers, 60%.
Researchers also found heavy and former heavy drinkers had higher odds of developing tau tangles, a biomarker associated with Alzheimer’s disease, with 41% and 31% higher odds, respectively. Former heavy drinking was associated with a lower brain mass ratio, a smaller proportion of brain mass compared to body mass, and worse cognitive abilities.
No link was found between moderate or heavy drinking and brain mass ratio or cognitive abilities. Justo noted that, in addition to brain injuries, impaired cognitive abilities were observed only in former drinkers. Researchers also found that heavy drinkers died an average of 13 years earlier than those who never drank.
“We found heavy drinking is directly linked to signs of injury in the brain, and this can cause long-term effects on brain health, which may impact memory and thinking abilities,” said Justo. “Understanding these effects is crucial for public health awareness and continuing to implement preventive measures to reduce heavy drinking.”
A limitation of the study was that it did not look at participants before death and did not have information on the duration of alcohol consumption and cognitive abilities.
