Year: 2026

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Cryptococcal Meningitis Claims Many Lives in SA – Stopping it won’t be Easy

On By ModernMedia

Cryptococcal meningitis is a serious fungal infection causing inflammation of the lining of the brain. (Photo: Pixabay)

By Elri Voigt for Spotlight

One of the top killers of people living with HIV in South Africa is a fungal infection. In this Spotlight special briefing, we unpack what we know about this dangerous disease called cryptococcal meningitis, why it remains so deadly, and what we can do about it.

Someone who is diagnosed with HIV today could live a relatively healthy and normal life. That is providing that they are consistently taking the antiretroviral treatment that successfully suppresses the virus in their bodies.

Roughly four out of every five people living with HIV in South Africa are on treatment. The remaining one in five, or 20%, represents around 1.6 million people who could potentially get very ill from a virus that is attacking their immune system, leaving them at risk of complications and opportunistic infections.

The best-known HIV-related opportunistic infection is tuberculosis, comfortably the top killer of people with HIV in South Africa. The second top killer of people with HIV, at least according to most estimates, originates from the environment around us. Around 19% of HIV-related deaths were attributed to this illness in a 2022 modelling study. Despite the many lives this illness has claimed, it has lurked chronically under the radar, much more so than TB, which itself has been somewhat in the shadows.

A fungus that is all around us

“Cryptococcal meningitis is a serious fungal infection causing inflammation of the lining of the brain (meninges),” explains Dr Richard Lessells. He is an infectious diseases clinical researcher at the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) at the University of KwaZulu-Natal (UKZN).

Cryptococcal meningitis is caused by one of two fungi – Cryptococcus neoformans or Cryptococcus gattii. The former is responsible for most infections in people. The fungus is found all around us, particularly in rotting trees and wood, the soil and bird droppings. The tiny fungal spores are routinely inhaled by humans.

In most people, the immune system takes care of the spores and eventually controls it, explains Lessells. The fungus only starts causing problems when the immune system is weakened and not able to contain it. When that happens, the fungus spreads to the bloodstream, from where it can spread all over the body. While it can cause disease in other places, like in the lungs or on the skin, the most common place the fungus heads to is the brain and its lining. This lining, which consists of three membrane layers that cover and protect the brain and spinal cord, is called the meninges.

Classic symptoms of cryptococcal meningitis include headache, stiff neck, light sensitivity, fever, confusion, and nausea and vomiting. The symptoms can eventually be debilitating, with one patient quoted in literature saying that a previous gunshot wound hurt less than his headache. The inflammation in the meninges causes a dangerous build-up of pressure in the skull – called raised intracranial pressure – which explains the severity of the headaches.

Two disease states

When the fungus spreads from the lungs to the rest of the body, it doesn’t immediately cause inflammation in the brain or lead to severe illness. At this early stage, it is possible to stop the infection from spreading to the central nervous system, if it is detected and treated.

The key is a blood test, explains Professor Graeme Meintjes, an infectious diseases specialist based at the University of Cape Town and Clinical Professor of Infectious Diseases at Queen Mary University of London. The test, called a cryptococcal antigen test (CrAg), looks for a complex sugar molecule found in the cell wall of the fungus. When the test detects the sugar molecule in the blood, that person has what is called cryptococcus antigenemia – meaning the antigen is present in the body.

“They would then be treated pre-emptively with antifungal medication, essentially to prevent them from progressing from the antigenemia to the meningitis,” Meintjes says. Fluconazole, the drug used for this early treatment, is cheap, widely available, and works well.

If someone is not treated in time, the fungus spreads to the central nervous system – specifically the brain – and causes dangerous inflammation in the lining of the brain. When it gets to this stage, the infection is called cryptococcal meningitis. It is diagnosed by doing a CrAG test on spinal fluid obtained through a lumbar puncture, explains Lessells.

The key difference between the two disease states is that symptoms only manifest once cryptococcus antigenaemia has progressed to cryptococcal meningitis.

Someone who has cryptococcal meningitis needs to be admitted to hospital. This is because the drugs used to treat it will only start helping to control the dangerous inflammation after a few days. In the meantime, the build-up of intracranial pressure needs to be reduced through daily lumbar punctures during the first few days in hospital, says Lessells. The drugs themselves can also cause some dangerous side effects that need to be monitored closely and managed.

“Cryptococcal meningitis is associated with very high early mortality. GERMS-SA surveillance in South Africa has shown in-hospital mortality in routine care to be between 30-40% for the past 20 years,” points out Lessells. GERMS-SA is a national, population-based laboratory surveillance programme led by the National Institute for Communicable Diseases (NICD). It monitors bacterial, fungal, and parasitic infections across South Africa through a network of laboratories and sentinel hospital sites.

Screening the right people

Since waiting for cryptococcal meningitis symptoms to appear is a losing strategy, the focus has been on proactively identifying and offering CrAg screening to people at high risk of the condition.

In South Africa, says Lessells, cryptococcal meningitis most commonly affects people living with HIV, especially those with advanced HIV disease. This is a state where the virus is not under control in the body and the number of important immune cells called CD4 cells are dangerously low, at less than 200 cells/mm3. CD4 cells are a type of white blood cell important for a well-functioning immune system. A CD4 count above 500 is generally considered to be healthy.

But cryptococcal meningitis can also affect organ transplant recipients, people undergoing cancer treatment or those taking steroids. “Very occasionally, it can affect people with no apparent immunocompromising condition,” adds Lessells.

Either way, people with advanced HIV are the most obvious group to target with screening efforts. In 2025, there were about 7.8 million people living with HIV in South Africa, according to estimates from Thembisa, the leading mathematical model of HIV in the country. Of those, roughly 530 000 had advanced HIV, with a CD4 count of less than 200. This group of around half-a-million people are at highest risk of cryptococcal meningitis.

The National HIV treatment guidelines recommend that people living with HIV should be offered CrAg screening if they present with a blood test showing a CD4 count of less than 200. But the catch is that often people with advanced HIV disease are not accessing healthcare services or only accessing services once they are already very ill. In 2025, around 42 000 of the adults living with HIV who started taking treatment that year had a CD4 count of less than 200, according to Thembisa. This is over 20% of the total number of people who started taking treatment that year.

“Cryptococcal meningitis is essentially a marker for the gaps in our HIV programme,” says Liliwe Shuping, an epidemiologist at the NICD.

“If a patient gets cryptococcal meningitis, it usually means they fell through the cracks of the healthcare system; either they were never tested for HIV, they were lost to follow-up, or their treatment failed without being caught,” she says.

She describes cryptococcal meningitis as “almost exclusively a disease of advanced HIV, untreated HIV, or failed HIV care”.

There are thus two layers to the problem: First, too many people with HIV are not in care and end up developing advanced HIV, and second, even when people are visiting health facilities, they are not always screened in time.

“At the primary healthcare level, there are still challenges with implementation of the CrAg screening programme,” says Lessells. The laboratory component works well, but then he says there are the usual problems of a healthcare worker seeing the result, acting on the result, being able to contact the patient to recall them to the facility, and then referral to a higher level of care for lumbar puncture.

Unfortunately, people do fall through the cracks. Similarly, he suggests there are sometimes avoidable delays at hospital level when it comes to doing lumbar puncture. For example, some doctors might wait for a CT scan of the brain, which is not always necessary and can lead to delays.

At least some of these challenges should be reduced with the latest National HIV treatment guidelines, which address these issues with more information and clarified referral pathways, Lessells says. For example, the guidelines include a chapter on managing advanced HIV, among others covering how to screen for, diagnose and manage cryptococcal meningitis. It also spells out the requirement for automatic CrAg testing for people with CD4 counts below 200.

The big picture – what the data tells us

Some good news from the GERMS-SA report is that there has been a decline of about 11% in reported cryptococcal meningitis cases from 2023 to 2024. There has also been a drop in cryptococcal meningitis incidence over the last six years, says Shuping.

The annual number of recorded cases dropped from about 6 000 in 2018 to 4 000 in 2023, decreasing by about one third overall, says Shuping. This is based on the Public Health Bulletin study on data from 2018 to 2023. The authors caution that the decline in cases could be due to the potential impact of strengthening public health interventions or may reflect an under-detection of cases. Either way, these numbers reflect only confirmed cases. Modelling suggests real cryptococcal meningitis incidence may be several times what is being reported.

Shuping cautions that despite the reduction in reported cases, cryptococcal meningitis is still killing many people living with HIV.

The in-hospital mortality rate for cryptococcal meningitis “has not meaningfully improved,” she points out. Despite treating fewer cases over time, she says that a patient who develops cryptococcal meningitis today has roughly the same high risk of dying in hospital as they did six years ago.

In general, Meintjes explains that brain infections have a high mortality. Even with the best treatment options and under clinical trial settings, around a quarter of patients die despite treatment.

Quality of care matters. Lessells says that while drug treatment generally receives the most attention, it is only one component of the clinical management of cryptococcal meningitis. Monitoring and reducing intracranial pressure and preventing and monitoring side effects from the drugs are vital. In a setting where resources are stretched thin, healthcare workers are overwhelmed and facilities don’t always follow the best practises, he says quality of care can fall, contributing to “stubbornly high mortality rates”.

High mortality despite new drug

Given the serious side effects associated with some medicines used to treat cryptococcal meningitis, there was great optimism in 2022 when an old anti-fungal medicine called flucytosine was approved for use in the country to the treat the illness.

This followed the AMBITION trial, where researchers found that combining flucytosine with two other powerful drugs (liposomal amphotericin B – an IV infusion and fluconazole – an oral medication) improved patient treatment. Meintjes explains that the combination of the three drugs was not “better” than the previous regimen as there were similar mortality rates between the two arms, but it was safer and had far fewer side effects.

Meintjes says that today the first choice for the treatment of cryptococcal meningitis is a single infusion of liposomal amphotericin B, then 14 days of fluconazole plus flucytosine.

The second choice, that has similar mortality outcomes to the first but has more side effects, is seven days of another form of amphotericin B plus flucytosine and fluconazole.

The third-choice regimen is 14 days of amphotericin B plus fluconazole. Meintjes says that the outcomes for this regimen are not as good as with the first two.

After the initial treatment, regardless of which regimen was used, patients then have to take a maintenance dose of fluconazole for at least another year to completely eradicate the fungus. If the fungus is not entirely gone from the body, it can cause disease again in the future. Patients living with HIV also need to be started on antiretroviral therapy around four weeks after the meningitis diagnosis, which helps prevent a relapse.

Best drugs not always in stock

One reason the approval of flucytosine, and the improved treatment regimens it enables together with liposomal amphotericin B, hasn’t yet resulted in better outcomes is that patients simply aren’t always getting the drugs.

“[O]ften we’re in a situation where we have to use the third choice because neither liposomal amphotericin B nor flucytosine are available and that’s associated with worse outcomes,” says Meintjes.

Jessica Burry, a pharmacist and technical officer working on advanced HIV with Unitaid, concurs. “I think what it comes down to is if you don’t have access to liposomal amphotericin B and flucytosine, then you don’t have the gold standard of treatment…and it’s shown quite clearly that mortality rates are much higher in those groups [that don’t have access to these drugs],” she says.

There are several reasons why a drug might not be in stock at the clinic or hospital where it is needed. Often in South Africa, medicines have been in stock in central depots, but not available at all health facilities. A further challenge with medicines for cryptococcal meningitis is that the volumes are comparatively low, and pharmacies may thus be reluctant to hold onto too much stock for fear it might expire.

While such distribution problems have no doubt played a role in limiting access to cryptococcal meningitis medicines, sourcing a reliable supply from manufacturers appears to have been a greater stumbling block in recent years. In this regard, public health imperatives are up against some tough economic realities.

Lessells says that, because flucytosine is an anti-fungal mainly used to treat cryptococcal meningitis, there isn’t much demand for the drug across the world, since many countries very rarely deal with the illness. This, he says, ties into the systemic problem with global drug supplies for rare diseases or rare conditions, where you’ve got a small number of manufacturers and problems in the manufacturing process that then lead to global supply chain problems.

How such dynamics have played out with flucytosine and liposomal amphotericin B is worth a closer look. As often is the case with such questions of medicines access, the picture gets fuzzier before it becomes clearer.

Flucytosine shortages

“During 2026, the availability of flucytosine has been constrained, requiring available stock to be carefully managed and distributed to facilities based on clinical need,” Foster Mohale, spokesperson for the National Department of Health tells Spotlight. He says that there was a global supply problem and that the stockouts were not due to procurement issues at the department. A shortage of flucytosine has also affected several other countries.

Flucytosine is on the Essential Medicines List (EML), which is a list of medicines that are considered vital for the health of the country, like antiretrovirals or insulin. The health department undertakes to supply medicines on the EML to the public health sector, normally via tenders.

Two pharmaceutical companies, Viatris and Macleods, have registered flucytosine with the South African Health Products Regulatory Authority (SAHPRA) for use in South Africa.

Flucytosine was previously procured by the state in terms of a tender awarded to Viatris in 2023. According to Mohale, uptake from provincial health departments was poor, and in July 2024 some expired stock had to be written off. A few months later, the department issued a notice to confirm there was stock and that healthcare facilities should place orders based on their needs.

A new tender was advertised in 2025, but according to Mohale, no “responsive bids” were received. The health department then approached Viatris to supply flucytosine via a Request for Quotation (RFQ). The RFQ process is when the state obtains a quotation on a price when an essential medicine is not available from a contracted tenderer, either because no tender was awarded or the product is out of stock, explains UKZN pharmaceutical sciences expert Dr Andy Gray. This form of procurement, he says, is not unusual.

Viatris initially accepted the RFQ but then informed the department in March 2026 that it was “unable to supply due to manufacturing and global supply constraints”. Macleods was then approached by the health department and is now supplying the drug in terms of a new RFQ. The plan is to issue a new tender when it makes sense to do so. (You can read the health department’s full response here).

Price fluctuations

There have also been challenges with access to another important cryptococcal meningitis medicine. Historically, many low-and-middle income countries have struggled to access liposomal amphotericin B because of the price, says Burry.

Gilead Sciences, the pharmaceutical company that owned the patent for liposomal amphotericin B (which it acquired when purchasing a company called NeXstar Pharmaceuticals) had made it available at an access price for some low-and-middle income countries starting in 2018. It has also taken steps to make the drug more widely available to treat another infection called leishmaniasis through a long-standing partnership with the World Health Organization (WHO).

Initially, it appeared that South Africa was exempt from this access price due to an exclusive distributor agreement Gilead had with some companies. In South Africa, the distributor was Key Oncologics, which at the time had priced the drug for sale in the private healthcare sector at just under $200 a vial (about R2 880 at the time) – a price the health department could not afford when Spotlight first reported on the issue in 2022.

When asked about access to the drug and this agreement, both Gilead and Key Oncologics provided short statements which you can read here and here.

Key Oncologics then did end up supplying the health department with the drug in 2023, through the Gilead Access Programme, explains Mohale, when it was contracted to supply an estimated 5 860 vials at around R600 per vial over two years. That R600 price tag was used to support the inclusion of the drug on the EML and Adult Hospital Level Standard guidelines. There were initially some supply issues as demand for the drug increased, but Mohale says that was resolved when production and supply volumes were adjusted.

Under the current three-year tender, Key Oncologics is contracted to supply an estimated 166 056 vials at R1 167.48 per vial. Although, Mohale adds that following engagements with Gilead and Key Oncologics, the price has been reduced to R1 035 per vial. This is still substantially higher than the previous price of R600. Mohale says the department’s understanding is that South Africa is no longer eligible for the lower access price since a generic alternative has been registered in the country. (You can read the health department’s full response here.)

How outcomes can be improved

As we’ve seen in this Spotlight special briefing, South Africa has made substantial progress against cryptococcal meningitis, but the fungal infection nevertheless continues to cause suffering and death. The reasons for the disease’s continued toll on people living with HIV are varied and complex, but three issues stand out.

First, there is the fact that far too many people living with HIV in South Africa are not on antiretroviral treatment and are thus at increased risk of developing cryptococcal meningitis. As with our HIV response more generally, the priority here must simply be to help more people with HIV to start and stay on antiretroviral treatment. Special attention needs to be paid to finding and supporting the subset of people who don’t go to the clinic or the hospital until they are very ill.

Second, we need to get better at diagnosing infection early, ideally before the development of full-on cryptococcal meningitis. Automatic CrAg testing for people with low CD4 counts is the right move – it needs to be backed up with a push for greater healthcare worker awareness to respond quickly to a positive test.

And third, there is the question of having the best treatments available where they are needed. There was much optimism a few years ago over the introduction of new safer treatments with fewer side effects, but issues with drug supply has dampened the mood considerably since then. The good news, for now at least, is that the national supply of the most important medicines seems to have stabilised. As we know from experience, however, having the medicines in the country does not always mean they are available in the right health facilities when needed.

Ultimately, in all three of these areas much will depend on how well our public healthcare system is, or is not, functioning. As Lessells puts it: “We have the right approach to prevention, diagnosis and management of cryptococcal meningitis. Our guidelines are informed by the best evidence (including clinical trial evidence generated in Africa by African research teams). It’s really about broader health systems strengthening so that we can realise the benefits of this.”

*Reviewed by Professor Graeme Meintjes and Dr Richard Lessells. Spotlight takes full responsibility for any errors.

This special briefing is part of a series by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.

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Can SA’s New Director-General for Health Turn Around a Struggling Department?

On By ModernMedia
Dr Thembisile Xulu is the newly-appointed Director General of the National Department of Health. (Photo: Denvor de Wee/Spotlight)

By Marcus Low

Dr Thembisile Xulu is South Africa’s sixth permanent Director-General of health since the dawn of democracy. How will she measure up against her predecessors?

In recent months, we’ve been keeping an especially close eye on the media statements following the twice-monthly meetings of South Africa’s cabinet. Then last week, we finally spotted the line we had been waiting for – the announcement of South Africa’s new Director-General (DG) for Health. 

The name of the country’s sixth permanent DG since 1994 was a familiar one. Back in 2020, Spotlight interviewed Dr Thembisile Xulu when she was appointed CEO of the South African National AIDS Council (SANAC) – the national body established by Cabinet to coordinate South Africa’s response to HIV, Tuberculosis, and Sexually Transmitted Infections. 

In moving from the job of SANAC CEO to health DG, Xulu follows in the footsteps of Dr Sandile Buthelezi, who was CEO of SANAC from 2017 to 2020 and DG for Health from 2020 to early 2026, when he was suspended along with two other senior officials in the department. 

Prior to her time at SANAC, Xulu worked at the non-profit Right to Care for around a decade and a half. She is a medical doctor and has a master’s degree in public health. As far as we can tell, she is well liked in healthcare circles.

A huge task

The job facing Xulu is a daunting one. 

First, she will have to sort out problems within the department itself. As we pointed out in an editorial published in April, the department hasn’t gotten a clean audit in any of the last five years. The Digital Vibes scandal and the suspension of several senior officials earlier this year relating to another matter paints a bleak picture. While we know there are several committed and capable people working in the department, organisationally it seems to be exhibiting all the classic signs of chronic dysfunction and a lack of effective leadership. 

Maybe the most urgent task facing Xulu then is simply to turn the health department into a more professional organisation. This will require strong leadership and management skills, but it will also require her to more effectively protect the department from whatever the political whims of the day may be. Ultimately, a DG that always says, “yes Minister”, isn’t actually doing the Minister, or the public, any favours. 

But it won’t be easy. When the DG job was advertised back in March, the advert did not open by referencing the Constitution or the National Health Act, as one might expect, but by stating that the DG will be responsible for implementing the Presidential Social Compact for transformation of the health sector. The last health compact, signed in 2024, was a controversial document that did not get buy-in from several key business and healthcare worker organisations. That the job advert starts by referencing the compact rather than the relevant laws, seems an ominous sign for the DG’s chances of building a more capable, less politicised, department. 

Second, getting the department’s house in better order will help with what is of course Xulu’s main job – helping to address the country’s many health challenges. Top of the list is the chronic shortages of healthcare workers in the public sector. We have seen an important policy document and some extra funds for healthcare workers, but the incisive leadership and sustained commitment and planning needed to really get on top of the problem has been absent. 

There is a worrying pattern whereby government looks into a problem, maybe a committee of some sort is set up, the intentions are all good, but then everything stalls once some implementation challenge or political complication arises. We need a DG who does not allow important health issues to drift in this way, but who has the focus and determination to find workable solutions and to see them through. 

And then there is NHI

The NHI Act might currently be tangled up in a thicket of litigation, but whatever happens in the courts, NHI will be a big part of the DG’s work in the coming years (DGs are appointed for five years at a time). This may take the form of implementing some elements of the current NHI Act, or working with a revised Act, we just don’t know at this stage. 

But there will be many other bread and butter issues besides NHI demanding Xulu’s attention. In our analysis, the department has badly dropped the ball on urgent issues such as healthcare worker shortages, the regulation of private healthcare, and improving the quality of public healthcare services in areas such as mental health, diabetes, and hypertension. Hopefully under the new DG, the department will find ways of better addressing these issues in parallel with its work on NHI. 

A chance at renewal

There is some reason for optimism. With the appointment of Xulu as DG, and that of Dr Nonhlanhla Ndlovu before that as the department’s HIV czar, new people are now in two of the most important positions in the department. Such leadership changes offer a unique opportunity for organisational renewal. 

Spotlight has requested an interview with Xulu and we hope to get some time with her once she’s been in the job for a few weeks. We will ask her the tough questions, but we will also be fair and give her time. After all, we all want to see a health department and a health system that works. 

– Low is editor of Spotlight

This article was first published by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.

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Study Identifies Potentially Harmful Drug Combinations Prescribed to Older Adults

On By ModernMedia
Photo by Kampus Production

A new Ontario-wide study reveals that common medications, from statins to iron supplements, are quietly setting off prescribing cascades that leave older adults unknowingly taking drugs to treat side effects of other drugs.

The research, published in BMJ and led by Paula Rochon, a clinician scientist at Sinai Health and professor of medicine at the University of Toronto’s Temerty Faculty of Medicine, has revealed that certain drug combinations are a common but unrecognised contributor to drug related harm at the population level and add unnecessary costs to the healthcare system. 

A potentially inappropriate prescribing cascade (PIPC) happens when a medication’s side effect gets mistaken for a new health problem, leading to another prescription that may not have been needed in the first place. One common example flagged in the study involves non-steroidal anti-inflammatory drugs (NSAIDs). Commonly prescribed for pain, these drugs are associated with a rise in blood pressure, which can lead to a new prescription for high blood pressure, rather than a second look at the original pain medication. Older adults are especially vulnerable to this pattern because they’re more likely to be on multiple medications at once, due to having multiple conditions, making it harder for both patients and clinicians to trace a new symptom back to an existing drug.

“These sequences of events are common but often missed in clinical practice,” says Rochon, who serves as the director of research at the Weston and O’Born Centre for Mature Women’s Health at Sinai Health. “Knowing what medications you are taking, when they were started and for what indication is important in order to identify possible prescribing cascades that may be problematic.”

The study brought together an interdisciplinary, international team of collaborators and leaders in drug prescribing and geriatric medicine research from the United States, Belgium, Italy, Israel and Ireland, along with Sinai Health researchers and U of T professors Vasily Giannakeas and Nathan Stall, geriatrician Christina Reppas-Rindlisbacher and research staff Wei Wu and Joyce Li.

With the expertise of 12 international panellists specialising in internal medicine, geriatric medicine and clinical pharmacology, the research team previously created a list of 65 PIPCs. Using this list and population-level prescription data from ICES, Ontario’s health data institute, the researchers examined each PIPC against three factors: how common the initial drug was in the population, how often it was followed by the second drug, and how strong the link was between the two. That analysis allowed them to pinpoint the 24 potentially inappropriate prescribing cascades most commonly seen in the population and with a potential to cause harm.

Seeing the pattern behind every prescription 

For Rochon, the findings highlight a gap that opens quietly, one prescription at a time. “Our concern is that so often these conversations between the health care prescriber and the patient are being missed, so people don’t recognise the sequences of events and that they are connected to one another,” she said.

Closing that gap means physicians need to think about medication history at every visit, not just what a patient is currently taking, but why each drug was started in the first place, and whether the next one was really needed.

The work also carries a particular weight for mature women, as they tend to live with more chronic conditions than men over their lifetime. Mature women are prescribed more drug therapies, and experience more adverse drug events. By being on multiple medications at once, they are more exposed to the risk that a drug’s side effect gets mistaken for a new diagnosis rather than traced back to its source.

The team’s findings point to promising next steps.

The first involves technology. Automated clinical decision support tools could flag a prescribing cascade in real time and prompt a second look before a new prescription is added. This information could be leveraged in one of several automated ways to help clinicians be aware of these potentially inappropriate prescribing cascades at the point of care. 

Next is optimising the role of pharmacists as part of the care team and more directly integrating them into the prescribing process alongside physicians. Their expertise can help identify these potentially inappropriate prescribing cascades for further evaluation.

Original written by Jayda Ayriss

Source: University of Ontario

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Novel Immunotherapy Leads to Complete Regression of Liver Cancer in a Child

On By ModernMedia
Photo by CDC on Unsplash

A new report in the New England Journal of Medicine by researchers at Baylor College of Medicine, Texas Children’s Hospital and Seattle Children’s describes a complete regression of hepatoblastoma, the most common paediatric liver cancer, in a 3-year-old treated with a novel immunotherapy. The patient is enrolled in the CARE study (NCT04715191), a first-in-human, Phase 1 trial evaluating glypican-3-specific chimeric antigen receptor (GPC3-CAR) T cells armed with interleukin-15 and -21 (IL15 and IL21).

The child initially presented with a large primary liver tumour and metastases in the lungs. Prior to enrolment in the CARE study, the patient was treated with three lines of chemotherapy and underwent complete resection of the primary liver tumour and two lung metastases. His cancer was no longer responsive to chemotherapy, and a new lung metastasis recurred after surgery when he was enrolled on the CARE study.

The immunotherapy was engineered from the patient’s own cells at the Good Manufacturing Practices laboratories at the Center for Cell and Gene Therapy using two vectors: one encoding the second-generation GPC3-CAR and the second encoding IL15, IL21 and the inducible caspase 9 safety switch, which Center for Cell and Gene Therapy investigators previously showed controlled CAR T expansion.

Two infusions were administered eight weeks apart in the outpatient setting. A partial response was observed after the first infusion, and imaging showed complete resolution of the metastatic disease after the second infusion. No dose-limiting toxicities or cytokine release syndrome occurred. Complete regression continues one year after treatment.

“This case demonstrates that a durable complete response in a chemotherapy-resistant solid tumour can be achieved entirely in the outpatient setting without systemic toxicity,” said first author Dr David Steffin, associate chief of cellular therapy and bone marrow transplant at Texas Children’s and associate professor of paediatrics – haematology and oncology in the Center for Cell and Gene Therapy at Baylor.

“This study provides evidence that these novel CAR T cells may be a safe and effective modality for hepatoblastoma and highlights the need for further assessment in patients with GPC3+ solid tumors,” said corresponding author Dr Andras Heczey, principal investigator at Seattle Children’s and professor of pediatrics in hematology-oncology at the University of Washington School of Medicine. Heczey was at Baylor and Texas Children’s at the time of research.

Source: Baylor College of Medicine

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Trial Testing Out-of-Body Experiences Produces Unexpected Twist

On By ModernMedia
Photo by Bruce Christianson on Unsplash

A test to determine if people who report out-of-body experiences could identify objects in another room produced results no better than chance, but afterward something strange happened: Two participants described, unprompted, researchers’ locations and activities behind closed doors.

The participants’ unexpected observations were not part of the trial’s predefined outcome measures and therefore can’t be considered evidence for out-of-body experiences, or OBEs, UVA Health investigators say. But the unexplained results may help researchers design better, more effective ways to evaluate the potential validity of a phenomenon that has been reported for decades.

“I hope this study encourages researchers to think creatively about how we test these experiences. The unexpected findings give us a potentially useful new direction, but they also need to be tested prospectively and under rigorous conditions before we can know what they mean,” said researcher Marina Weiler, PhD, of the University of Virginia School of Medicine’s Division of Perceptual Studies. “For me, the most important takeaway is that unexpected findings can sometimes help us ask better questions. We now have a specific idea that can be tested in future experiments, and that is exactly what science should do.”

Understanding Out-of-Body Experiences

In the recent trial, conducted in Brazil, 21 participants attempted to identify a random object on a laptop screen in another room. Of the 21, 10 reported having an out-of-body experience, and 13 provided target descriptions. (The 13 included participants who had not reported leaving their bodies but said they could see images on an internal “mental screen” or the like.)

The descriptions the participants gave of the objects on the laptop screen did not prove statistically more accurate than what could be expected from guessing. But during interviews afterward, one participant described how a researcher in another room, behind closed doors, had been seated on the left looking at a laptop screen while another researcher was farther back reading a book. Another participant described how a researcher had been seated on the right, taking notes, while a second was sitting on the left at the computer.

Trial records confirmed both descriptions were correct at the time of the participants’ sessions. Further, there was no way the participants could have seen the researchers, according to the trial organizers.

That has prompted Weiler and her collaborators to propose that the targets provided during OBE trials may play important roles in determining outcomes. It’s possible, they suggest, that memorable, distinctive or emotionally engaging targets may be easier for participants to visualise. Researchers conducting future trials may want to supplement the traditional targets with other unseen details that participants might notice, such as having a researcher wear a distinctive or colorful item of clothing while behind closed doors. 

If participants could recall such items without seeing or being told about them, that might bolster the case for out-of-body remote viewing.

“I hope these findings encourage us to think more deeply about what they might mean for our understanding of consciousness and, ultimately, the nature of reality. If studies demonstrate that people can obtain accurate information that they could not have accessed through their ordinary senses, we would have to reconsider some of our assumptions about the relationship between consciousness, perception and the physical world,” Weiler said. “At its deepest level, this research is not only asking whether out-of-body experiences are real. It is asking what we mean by ‘real’ in the first place, and whether our current understanding of reality is broad enough to account for everything human consciousness can experience.”

Findings Published

The researchers have published their findings in the peer-reviewed journal Explore. The research team consisted of Weiler, Damon Abraham, David J.P. Acunzo and Niffe Hermansson. The researchers have no financial interest in the work.

Source: University of Virginia Health

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Should Adults with Autoimmune Rheumatic Conditions Receive Updated COVID Vaccines?

On By ModernMedia
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In an Arthritis & Rheumatology analysis of data on 60 980 US adults with autoimmune rheumatic conditions who developed COVID between December 2020 and August 2024, those who received booster or updated (2023-2024) COVID vaccines were less likely to be hospitalised for COVID compared to those who received only the initial series vaccines or who were unvaccinated.

Compared with no vaccination, completion of the initial series, booster vaccination, and updated vaccination were associated with 41%, 71%, and 69% lower adjusted odds of COVID-related hospitalisation, respectively. Among patients who had received only the initial vaccine series versus booster/updated vaccine, the absolute risk reduction was 5.6%.

“Our findings provide important real-world evidence that updated vaccines continue to offer substantial protection in this medically vulnerable population,” said corresponding author Maria I. Danila, MD, MSc, MSPH, of the University of Alabama at Birmingham. “These results underscore the need for continued efforts by clinicians, policymakers, and patient advocacy groups to help ensure that these patients remain current with updated COVID vaccines,” added first author Lesley E. Jackson, MD, MSPH, also of the University of Alabama at Birmingham.

Source: Wiley

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Too Much Nighttime Light Alters Cardiac Structure and Function

On By ModernMedia
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Exposure to light during the nighttime is linked to important and potentially harmful changes to the structure and function of the heart, according to a study of more than 11 000 people published in the European Heart Journal today (Thursday).

The research was led by Professor Lu Qi from Tulane University, New Orleans, USA. He said: “Previous observational studies have linked nighttime light exposure with a higher risk of cardiovascular disease, but little is known about the related cardiac structure and functional changes. We carried out this research to find out what happens to the heart over time when people are exposed to too much light at nighttime.”

The research included 11 071 people who are part of the UK Biobank study. All participants wore a light sensor on their wrists for seven days to measure light levels over night. Three years later, participants were given a cardiac MRI scan to carefully examine the structures and functions of the heart.

Researchers compared people who were exposed to light levels of more than three lux with people exposed to almost no light at night.

This showed that people with high exposure to nighttime light had thickening of the wall of the left ventricle (one of the chambers of the heart), reducing the space inside of the chamber. There were signs that the heart muscle’s ability to flex during a heartbeat was reduced. This is an early indicator of heart dysfunction. Researchers also found changes in the right ventricles and left atria (two other chambers of the heart).

Professor Qi said: “This is the first study of its kind, and it shows that exposure to higher levels of light at nighttime is linked to cardiac remodelling. This is where the structure and function of the heart changes and we typically see it in response to chronic stress or injury to the heart. It’s our body’s way of adapting to that stress, but ultimately it weakens the heart and can lead to heart failure.

“Light pollution has emerged as a new risk factor for cardiovascular disease. Our findings, together with evidence from other studies, suggest that reduction of nighttime light exposure should be considered as one of the potential strategies for preventing heart disease by clinicians and policy makers.”

In an accompanying editorial Professor Thomas Münzel from University Medical Center Mainz, Germany and colleagues said: “It is time for clinicians, particularly those managing patients with heart failure or atrial fibrillation, to start asking about the sleep environment: how dark the bedroom is, whether the patient works night shifts, and how much screen use occurs after sunset. The advice is simple and inexpensive: blackout curtains, warm-coloured bedside lighting, and covering the small standby LEDs on household electronics. From a public health perspective, the implications are larger still. Light pollution is one of the few environmental hazards that cities can control directly and affordably. Shielded fixtures, warm-spectrum bulbs, and dimming or motion-activated streetlights are already available, energy-efficient, and climate-friendly.

“Ultimately, this study is more than an interesting observation. It provides a crucial link between what satellites already show us, i.e. a planet glowing ever brighter at night, and the clinical reality unfolding inside our chests: hearts that are becoming stiffer, weaker, and less efficient. The relationship is biologically coherent, the effect sizes are clinically meaningful, and the dose–response is unambiguous: more light, worse outcomes. The takeaway is clear, darkness deserves recognition as a vital sign, as essential to cardiovascular health as blood pressure control and clean air.”

Source: European Society of Cardiology

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Psychiatrists Agree on a Diagnosis in Only 55% of Cases, New Study Finds

On By ModernMedia
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When psychiatrists assess the same patient, they agree on the diagnosis in only about half of cases, according to a new study from the University of Copenhagen. The findings raise concerns about potential misdiagnosis, inappropriate treatment, and errors in psychiatric research.

In the 1970s, psychiatric diagnoses were marked by considerable uncertainty and disagreement. Since then, organisations such as the American Psychiatric Association and the World Health Organization (WHO) have worked to develop standardised diagnostic criteria that psychiatrists around the world can use.

These efforts have shaped modern psychiatry by establishing common, criteria-based systems for diagnosing mental disorders across institutions and national borders.

However, a new study, led by researchers at the University of Copenhagen, suggests that major challenges remain. In the study, 1038 psychiatrists and physicians working in psychiatry from 19 countries were presented with nine written patient case descriptions. Each participant was assigned two cases and asked to determine the most appropriate diagnosis.

The results surprised the researchers.

“Our study shows that when two psychiatrists diagnose the same patient, they will agree only 55% of the time. We consider that worryingly low. In fact, it is similar to the levels reported in some of the studies conducted in the 1970s, which prompted the development of standardised diagnostic criteria in the first place,” says Professor and Consultant Psychiatrist Julie Nordgaard.

“This is not about psychiatrists doing a poor job. Rather, it reflects the fact that, despite the existence of diagnostic systems, clinicians continue to differ in how they interpret symptoms and which features they consider most important. We need a greater degree of consensus, otherwise patients risk receiving changing diagnoses and treatments,” she adds.

Same symptoms, different diagnoses

The study found substantial variation in diagnostic agreement across different mental disorders. Diagnoses within the schizophrenia spectrum proved particularly challenging.

“Cases that could be diagnosed either as schizophrenia or schizotypal disorder generated especially high levels of disagreement. In many of these cases, agreement among participants was well below 50%,” says PhD candidate Mateo Boberg, the study’s first author.

According to Boberg, one reason is that symptoms frequently overlap across psychiatric disorders. For example, obsessive thoughts may occur in both obsessive-compulsive disorder (OCD) and schizophrenia.

“These are not random errors. There is a clear pattern to the disagreements. This likely reflects the fact that diagnostic categories are not as clearly defined as we have assumed, when experienced psychiatrists can interpret the same symptom presentations so differently.”

Diagnostic uncertainty undermines research

Disagreement about diagnoses is an obvious concern for patients. But the researchers argue that diagnostic uncertainty also threatens the reliability of some kinds of psychiatric research¸ explains Professor Mads Gram Henriksen:

“In research, it is essential that we know exactly what we are studying. If a considerable part of participants enrolled in a study on treatment of personality disorders actually suffer from schizophrenia, the study’s results become difficult to interpret. Which condition is the treatment having – or not having – an effect on? Personality disorders or schizophrenia?”

The researchers argue that progress in psychiatric research risks remaining limited until there is a clearer and more widely shared understanding of what mental disorders are and how they can be distinguished from one another. Greater diagnostic agreement, they say, is a prerequisite for the breakthroughs needed to improve patient care.

“WHO’s ICD-10 diagnostic system, which participants in the study used to assess the cases, contains more than 200 diagnoses, a complexity that may contribute to uncertainty. At the same time, many psychiatric conditions are inherently multifaceted,” says Julie Nordgaard and concludes:

“In our view, it is necessary to take a step back and develop more precise descriptions of psychiatric disorders so that clinicians can distinguish them more clearly. It may also be necessary to reduce the number of diagnostic categories.”

The study, Reliability of Psychiatric Diagnoses in the 21st Century, has been published in Frontiers in Psychiatry.

Source: University of Copenhagen

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The Bias in Medical Research: Africa Carries a Huge Disease Burden but Is Missing from Clinical Trials

On By ModernMedia

Bamba Gaye, MD, MPH, MSc, PhD, Emory University

Modern medicine prides itself on being a universal science, built on evidence from clinical trials.

But there’s a bias in medical research. While Africa accounts for roughly 25% of the global disease burden and 19% of the global population, the continent’s people are largely invisible in some clinical trials.

The scale of the erasure is revealed in a landmark study of 2,472 randomised controlled trials globally published between 2019 and 2024.

I led this team of researchers, who scrutinised the world’s most influential medical publications to quantify African representation. They included the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, Nature Medicine, and the British Medical Journal. There were also three leading cardiovascular journals in the study: Circulation, the European Heart Journal and the Journal of the American College of Cardiology.

I am a physician-scientist working at the intersection of cardiometabolic epidemiology and biomedical data science. I also focus on large-scale population studies in Africa and data-driven cardiovascular prevention.

Randomised controlled trials are a cornerstone of evidence-based medicine. Introduced in the mid-20th century, they rigorously evaluate the safety and effectiveness of treatments by randomly assigning participants to different groups. This is done to minimise bias. Trials like these have been central to major medical breakthroughs, from cardiovascular therapies to vaccines. They continue to guide clinical decisions and the development of new treatments worldwide.

What we discovered

Our findings show a profound imbalance in the global clinical research landscape. Across the five most prestigious general medical journals, only 3.9% of trials were conducted exclusively in Africa. In cardiovascular health, the numbers drop to a statistical whisper. Of the major trials published in leading cardiology journals, just two studies (0.6%) were conducted solely on African soil.

This is a crisis of scientific accuracy. When clinical trials exclude African populations, they produce evidence that lacks “external validity”. This refers to how well the results of a study can be generalised beyond the participants. It asks whether findings from a clinical trial will still hold true when applied to different populations, settings, or real-world conditions.

Without that validity, doctors are essentially conducting unmonitored experiments on millions of patients every day.

Modern medicine cannot claim to be universal if entire populations remain invisible in the evidence base. Biology, health systems and disease patterns are not identical across the world.

The gap and why it matters

Many treatments used across the continent are based on evidence generated in non-African populations, raising concerns about their applicability.

Moreover, most Africa-based trials still focus on infectious diseases, despite the rising burden of non-communicable diseases such as cardiovascular disease.

Emerging evidence shows that genetics, environment and diet can radically alter how a body responds to a drug. It therefore makes no medical sense that an entire continent is left out of the trial net.

There’s also evidence showing that certain treatments have different safety profiles in Black patients. Diabetes and gout are just two examples. So are certain common blood pressure medications, such as angiotensin-converting enzyme (ACE) inhibitors. Research shows that they carry a three- to four-fold higher risk of severe, life-threatening side effects in people of African descent compared to other populations.

When clinical trials exclude populations, doctors are forced to extrapolate findings from one population and apply them to another.

The study also highlights a dangerous lag between global research funding and the evolving reality of African health. The new data show that nearly 76% of trials conducted exclusively in Africa focused on infectious diseases. But the continent is undergoing a massive epidemiological shift. Non-communicable diseases – heart disease, stroke, and diabetes – now account for about 38% of all deaths in many African nations.

The middle class in Africa has tripled to 300 million people from roughly 100 million people in the early 2000s. More people are now living long enough with lifestyles that increase the risk of chronic conditions such as heart disease, diabetes, and hypertension. Consequently, there is a growing need and market for long-term treatments that manage these diseases, rather than short-term therapies for infections. Yet cardiovascular trials continue to be discouraged.

Even within the continent, the data show deep “black holes” of information. South Africa accounted for over 62% of all trials conducted on the continent. Central Africa, a region that’s home to more than 180 million people, was virtually non-existent in the global research record. It contributed less than 3% of the continent’s limited trial output. Possible reasons include South Africa’s decades of cumulative investment, seen in stronger academic hubs, research governance, experienced trial units, and more established sponsor relationships. Other regions face barriers like fewer resourced research institutions, less access to trial platforms, and sometimes language and publication issues that can reduce visibility in top-tier journals.

The inequity extends into the hierarchy of science itself. Even when African sites are included in large, multicontinental trials, they are often relegated to the role of “recruitment hubs” rather than scientific partners. Our study found that African scientists led only 3.6% of multicontinental trials that included an African site.

Towards a new era of African science

Africa should not simply be a location where studies are conducted.

It must be a place where research is conceived, led and interpreted. The current model creates a cycle of external dependence where international institutions manage the funding and the data. This leaves local research systems fragile and unable to translate evidence into national policy.

There is need for “ring-fenced” funding for African-led research, the development of regional trial networks, and a mandate for medical journals to report on the diversity of trial populations.

There are signs of a rising momentum. Organisations like Alliance for Medical Research in Africa are working to equip a new generation of African investigators. Africa must create a research ecosystem that is too important for the global community to ignore.

Bamba Gaye, MD, MPH, MSc, PhD, Adjunct professor, Emory University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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“People Are Crying Out for Help,” Says SADAG, with 460 Suicide Attempts a Day in SA

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Every day in South Africa, an estimated 23 people die by suicide, while another 460 attempt suicide.

The impact is particularly concerning among younger people. Globally, suicide is the third-leading cause of death among people aged 15 to 29, according to the World Health Organization’s (WHO) latest estimates.[1] The South African Depression and Anxiety Group (SADAG) is also seeing the extent of the need first-hand as its helplines currently receive between 2 500 and 3 000 calls a day, with around one in four serious suicide-related calls.[2]

“People are crying out for help, and the calls we receive every day show us just how many people are struggling,” says SADAG’s Operations Director Cassey Chambers. “For us to make a meaningful difference and prevent suicides, we can’t just intervene at the point of crisis. People need help recognising the warning signs to make it easier to talk openly about suicide and know where they can turn for help. We need families, friends, schools, workplaces and communities to understand that talking about suicide is crucial and that asking someone directly if they are struggling can open the door to getting them the support they need.”

Every conversation counts

This World Suicide Prevention Day (10 September), Cipla is partnering with SADAG to encourage more of these conversations before someone reaches crisis point. The initiative supports SADAG’s 2026 World Suicide Prevention Day campaign, Every Conversation Counts, which provides South Africans with practical resources to help them understand what to say, how to respond and where to find support.[3]

As part of the campaign, Cipla is introducing the Postcard Wall of Hope, an interactive activation where members of the public can write and share messages of encouragement and support for people they may never meet.

“Sometimes, a few words can mean more than we realise. The Postcard Wall* of Hope is about sharing those words while they can still reach someone, reminding them that their life matters and that it is okay to speak about how they are feeling,” says Paul Miller, CEO of Cipla Africa.

Members of the public can read a postcard, take one that speaks to them or write a message for somebody else to find.

“You don’t have to know who will eventually read your postcard or what they may be going through,” says Miller. “It could simply remind someone that they matter or encourage them to keep going and reach out. The Wall is a way of showing that our words don’t only have to come when it is too late. We can use them now to start conversations and remind people that support is available.”

When to start the conversation

SADAG advises people to take changes in a loved one’s behaviour seriously. Warning signs can include talking about death or suicide, withdrawing from loved ones, risky or self-harming behaviour, giving away personal belongings or a sudden change in mood after a period of depression.[4]

“Importantly, asking somebody directly about suicide does not increase their likelihood of attempting it. SADAG encourages people to ask directly if they are thinking about suicide, listen without judgement and encourage them to seek professional help,” adds Cassey Chambers.

Starting a conversation doesn’t mean you need to know exactly what to say or have all the answers. It can begin with noticing that somebody isn’t themselves and asking how they are really doing. “What matters is that we don’t allow our fear of saying the wrong thing to stop us from saying anything at all,” concludes Miller.

Help is available

Anyone experiencing emotional distress, or concerned about someone they know, can contact SADAG for free telephonic counselling and support:

  • Cipla Mental Health Helpline: 0800 456 789 – free, 24-hour counselling
  • Cipla Mental Health WhatsApp: 076 882 2775 – daily, 08:00–17:00
  • For more mental health and suicide-prevention resources, visit the SADAG website: https://www.sadag.org

*The Postcard wall will be launched during Mental Health month in October as malls in Cape Town, Johannesburg and Durban.

References

[1] World Health Organization (2025), *Suicide worldwide in 2021: Global health estimates*. WHO reports suicide as the third-leading cause of death globally among people aged 15–29.

[2]South African Depression and Anxiety Group (SADAG), World Suicide Prevention Day 2026 media information.

[3] South African Depression and Anxiety Group (SADAG), *Every Conversation Counts: World Suicide Prevention Day 2026*.

[4] South African Depression and Anxiety Group (SADAG), *Understanding Suicide*, suicide warning signs and guidance on supporting somebody who may be suicidal.