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Cryptococcal meningitis persists in Botswana, despite high antiretroviral coverage – aidsmap

A study of cryptococcal meningitis incidence in people with HIV in Botswana shows that incidence has halved since 2015 and that the decline is correlated to increased antiretroviral coverage. But the study found that men were more likely to be diagnosed with cryptococcal meningitis than women and that illness related to advanced HIV remains a substantial problem despite achieving near-universal treatment coverage.

Writing in Clinical Infectious Diseases, Dr James Milburn of the Botswana Harvard AIDS Institute Partnership and colleagues say that cryptococcal meningitis data can be used to evaluate progress in tackling advanced HIV.

Cryptococcal meningitis and advanced HIV

Advanced HIV disease refers to a CD4 count below 200 (advanced immunodeficiency) or severe HIV-related symptoms and AIDS-defining opportunistic infections. The development of HIV-related symptoms can be prevented by early HIV diagnosis and treatment.

Glossary

advanced HIV

A modern term that is often preferred to ‘AIDS’. The World Health Organization criteria for advanced HIV disease is a CD4 cell count below 200 or symptoms of stage 3 or 4 in adults and adolescents. All HIV-positive children younger than five years of age are considered to have advanced HIV disease.

cryptococcosis

A type of fungal infection usually affecting the membrane around the brain, causing meningitis. It can also affect the lungs and chest.

meningitis

Inflammation of the outer lining of the brain. Potential causes include bacterial or viral infections.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Advanced HIV is not just a sign of late presentation for care. It can also be a consequence of loss from care; people with HIV suffer a rapid CD4 cell decline after stopping treatment and may soon become vulnerable to opportunistic infections.

A modelling analysis published in 2022 estimated that 4.3 million people worldwide were living with advanced HIV (defined as a CD4 count below 200) in 2020 and that 580,000 people with HIV died from AIDS-defining illnesses in the same year. And last month, a World Health Organization study estimated almost two million people are living with advanced HIV in Africa, more than half already diagnosed with HIV but either untreated or virally unsuppressed despite treatment.

Since the World Health Organization recommended antiretroviral treatment for everyone as soon as possible after HIV diagnosis in 2015 guidance, most countries have adopted ‘treat all’ policies that seek to streamline care and speed up treatment initiation. These policies are intended to limit HIV transmission and reduce HIV-related illness through earlier diagnosis and treatment.

But the prevalence of advanced HIV is hard to track because CD4 counts – until recently the most reliable indicator of advanced HIV – are being carried out less regularly in low- and middle-income countries. Programme implementation of ‘treat all’ guidelines has tended to emphasise viral load testing and viral suppression as the goal of treatment, with less priority given to CD4 testing.

In the absence of CD4 count data, national HIV programmes need to consider other measures that can show the extent of advanced HIV and the impact of progress towards the 90-90-90 goals on illness and death related to advanced HIV.

Few high-HIV prevalence countries have national systems that can produce reliable data on mortality or causes of death. Knowing what proportion of deaths is due to advanced HIV remains challenging, so programmes need a reliable surrogate. Without measurement, there is likely to be little action to reduce the burden of death and illness caused by advanced HIV.

Cryptococcal meningitis remains one of the most common causes of death in people with HIV in Africa and is estimated to account for one in five deaths in people with HIV globally.

As the majority of people with symptoms of cryptococcal meningitis – severe headache, neck pain and fever – will present to a healthcare facility, information on the number of positive tests for cryptococcal infection provides a more reliable indicator of the incidence of advanced HIV-related illness than the monitoring of disseminated tuberculosis or pneumocystis jirovecii pneumonia. These conditions often have non-specific symptoms that are missed until too late or are undiagnosed due to lack of equipment or clinical inexperience in differentiating the symptoms.

However, there is a lack of information about the impact of antiretroviral treatment expansion on the incidence of cryptococcal meningitis, one of the easier opportunistic infections to monitor at a national level. Cryptococcal meningitis can be diagnosed using a cryptococcal antigen (CrAg) lateral flow test, a dipstick test that detects cryptococcal antigen in a sample of cerebrospinal fluid in less than 15 minutes. This testing method means faster diagnosis compared to laboratory culture or microscopy, although it still requires insertion of a needle into the spine (lumbar puncture) to obtain a sample of cerebrospinal fluid.

Data from Botswana

To assess the impact of its ‘treat all’ policy on the incidence of cryptococcal meningitis, Botswana’s national HIV treatment programme reviewed laboratory reports between 2015 and 2022. Botswana has one of the highest levels of antiretroviral treatment coverage in the world and reached the UNAIDS 95-95-95 target for diagnosis, treatment and viral suppression in 2022.

In this study, a case of cryptococcal meningitis was defined as a positive CrAg result (86% of diagnoses in 2022), a positive cerebrospinal India ink stain or a positive culture of Cryptococcus neoformans from cerebrospinal fluid. Data on cases were collected from national electronic records for laboratory tests.

Between 2015 and 2022, 1744 cases of cryptococcal meningitis were diagnosed in Botswana in 1440 people with HIV (15% of cases were recurrences more than 14 days after an initial diagnosis). Almost two-thirds (65%) of cases occurred in men, the median age at diagnosis was 38 years and the median CD4 count at diagnosis (within six months of diagnosis) was 48 cells.

National incidence halved between 2015 and 2022, from 15 cases per 100,000 person-years to 7.4 cases per 100,000 person-years. When the population at risk was restricted to people with HIV, the incidence also halved, falling from 92 cases to 49 cases per 100,000 between 2015 and 2022.

Incidence was three times higher in men than in women (11.2 vs 4 per 100,000) in 2022.

Every 5% increase in antiretroviral coverage was associated with a 2.5 per 100,000 person-years decrease in incidence. However, when the analysis was restricted to the two national referral hospitals, as these sites had longitudinal data from prior to 2015, there was no difference in the rate of decline in cryptococcal meningitis cases after the implementation of the Treat-All policy in January 2017.

The study authors say that further research is needed to establish whether cryptococcal meningitis is still a frequent cause of illness or death in people with advanced HIV.

A neglected disease?

In a recent editorial commentary in The New England Journal of Medicine, researchers from three major institutions in the field of global health say that advanced HIV is in danger of becoming a neglected disease due to the focus on viral suppression as the key metric of treatment success.

A lack of research on tools to diagnose and treat opportunistic infections is accompanied by “a shrinking ability to diagnose the problem,” say the authors. Laboratory capacity to carry out CD4 count monitoring is declining, but “we believe that donors should continue supporting CD4 testing for diagnosing advanced HIV and guiding diagnosis and treatment of opportunistic infections,” they conclude.

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Harry Potter star Daniel Radcliffe makes rare comment on fallout with JK Rowling over her transgender views – Sky News

Daniel Radcliffe has responded to the fallout with Harry Potter author JK Rowling over her views on the transgender community for the first time since 2020, saying: “It makes me really sad”.

Rowling, who has always denied being transphobic, has been widely condemned in recent years for her views on transgender rights, having claimed that she would rather go to jail than refer to a trans person by their preferred pronouns.

Radcliffe, who became a worldwide star after playing schoolboy wizard Harry in the blockbuster adaptations of the novels, said in an interview with US magazine The Atlantic he has had no direct contact with the writer throughout the controversy.

“It makes me really sad, ultimately,” he said, “because I do look at the person that I met, the times that we met, and the books that she wrote, and the world that she created, and all of that is to me so deeply empathic.”

The 34-year-old actor first expressed his support for the trans community in response to Rowling’s stance back in June 2020 when she took issue with the phrasing of a headline for an opinion article about healthcare equality, titled Opinion: Creating a more equal post-COVID-19 world for people who menstruate.

Her response to it on social media – “‘People who menstruate’. I’m sure there used to be a word for those people. Someone help me out. Wumben? Wimpund? Woomud?” – sparked a debate and ongoing criticism of her views.

Radcliffe waded into the controversy at the time in a blog post for the LGBT suicide prevention charity The Trevor Project, writing that while Rowling “is unquestionably responsible for the course my life has taken… as a human being, I feel compelled to say something at this moment”.

He added: “Transgender women are women. Any statement to the contrary erases the identity and dignity of transgender people and goes against all advice given by professional health care associations who have far more expertise on this subject matter than either Jo or I.”

Radcliffe told The Atlantic: “Obviously Harry Potter would not have happened without her, so nothing in my life would have probably happened the way it is without that person. But that doesn’t mean that you owe the things you truly believe to someone else for your entire life.”

Last month, Rowling reignited the row with the Harry Potter stars, hitting out at “celebs” who she said have “used their platforms to cheer on the transitioning of minors” – after the Cass Review found there is “remarkably weak evidence” to support gender treatments for children.

One person replied to her post on X, writing: “Just waiting for Dan and Emma to give you a very public apology… safe in the knowledge that you will forgive them…”

Rowling responded: “Not safe, I’m afraid. Celebs who cosied up to a movement intent on eroding women’s hard-won rights and who used their platforms to cheer on the transitioning of minors can save their apologies for traumatised detransitioners and vulnerable women reliant on single sex spaces.”

In response, Radcliffe told The Atlantic: “I will continue to support the rights of all LGBTQ people, and have no further comment than that.”

Emma Watson, who played Hermione Granger in the Harry Potter films, and Rupert Grint, known for his portrayal of Ron Weasley in the series, have also been outspoken in support of transgender people.

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Explainer-The Eta Aquariid meteor shower: When is it and what to expect? – CNA

Meteors will be streaking across the sky as Earth passes through dusty debris in space left by Halley’s Comet in the annual Eta Aquariid meteor shower, with peak activity in early May.

Here is an explanation of this meteor shower.

WHAT IS A METEOR?

Meteors are space rocks and other material that burn up as they plummet through Earth’s atmosphere, leaving a bright streak in the sky. They also are called shooting stars or falling stars, though they are not stars. Comets can be a source of meteor showers because they cast off dust and debris as they orbit the sun. Meteor showers happen annually or at regular intervals when our planet, during its orbit of the sun, journeys through trails of such debris.

WHY IS IT CALLED THE ETA AQUARIID METEOR SHOWER?

It gets its name because the origination point in the sky – called the radiant – for the debris that burns up in the atmosphere is in the constellation Aquarius – the “water bearer” – and close to Eta Aquarii, one of the constellation’s brightest stars and one of the four stars that comprise the top of its “water jar.” Eta Aquarii and the other stars in the constellation have nothing to do with causing the meteors.

WHEN AND WHERE CAN YOU VIEW THE METEOR SHOWER?

According to the American Meteor Society, the Eta Aquariids are active from April 16-May 27, with the highest meteor rates from May 1-10 and the peak on May 5. The meteors can be seen during pre-dawn hours in both the Northern and Southern hemispheres. The Southern Hemisphere offers an advantage because the Aquarius constellation is situated higher in the sky than in the Northern Hemisphere. Experts recommend viewing the shower in the darkest skies possible because most of the meteor activity is faint. During the peak, about 30 meteors can be viewed each hour, according to NASA.

WHAT DOES HALLEY’S COMET HAVE TO DO WITH THIS?

Comets are icy remnants from the time of the solar system’s formation, made up of rock, dust and ices. As they orbit nearer the sun, they release dust and gases. Halley’s Comet, named for English astronomer Edmond Halley (1656-1742) who studied it, is considered the most famous one. It takes a 76-year orbital lap around the sun. It was last seen in Earth’s skies in 1986 and will return in 2061, according to NASA. Debris released by Halley’s Comet causes the Eta Aquariid meteor shower. The Orionid meteor shower that peaks in mid-October each year also is driven by debris from Halley’s Comet.

HOW QUICKLY DO THESE METEORS TRAVEL?

According to NASA, Eta Aquariid meteors are particularly speedy, moving at about 148,000 miles per hour (238,000 km per hour) into Earth’s atmosphere. Such quickly moving meteors can produce glowing “trains” lasting for seconds to minutes. The American Meteor Society said meteor rates are expected to be enhanced this year by debris being perturbed by the gas giant planet Jupiter in a direction closer to Earth.

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‘Frankenstein’ mice with brain cells from rats raised in the lab – Livescience.com

In an experiment reminiscent of “Frankenstein,” scientists found that rat brain cells can fill in for lost neurons in mice, even allowing the host rodents to sniff out sweets.

While splicing rat and mouse brains together may sound odd, this work aims to build a basis for understanding how mammal brains develop, said Kristin Baldwin, a neuroscientist at Columbia University and the lead author of a new study describing the experiment.

Baldwin and her team’s study, which was published in the journal Cell alongside a second study from collaborators at the University of Texas (UT) Southwestern, shows that the rat brain cells introduced into a mouse brain pick up cues from their new environment. These cells develop in the same time frame as nearby mouse brain cells, communicating with them and even adjusting their size to match.

“The host is controlling at least two aspects: the size and also the developmental speed,” said Jun Wu, a molecular biologist at the UT Southwestern Medical Center and the lead author of the second study. “That’s very interesting and suggests the microenvironment has influence on the pace, as well as the size, of the donor cell.”

The study led by Baldwin focuses on how networks form in a hybrid mouse-rat brain, while the study led by Wu focuses more on replacing an entire brain region with transplanted cells. The research could lead to other cross-species brain tissue, helping scientists study brain development and disease and potentially develop new treatments for people.

Baldwin’s team first used bacterial toxins to either kill or silence brain cells in developing mouse embryos. They started when the developing embryo was just a hollow ball of 100 to 200 cells, called a blastocyst, and targeted cells involved in sensing scents. Into these blastocysts, they also injected stem cells from rats, using a type of cell capable of developing into many cell types.

They then implanted the altered blastocysts into mouse mothers and allowed the embryos to develop. They found that the rat cells developed apace with the mouse cells, filling in for the killed or silenced cells in the scent-sensing centers of the brain. Completely wiping out the mouse cells and replacing them with rat cells led to some odd-looking anatomy, Baldwin told Live Science, but the mouse’s sense of smell still worked completely normally.

The fact that the different neurons foraged a network together and gave rise to fairly normal behavior is promising, Baldwin said. There are hopes right now for treating brain diseases, such as Parkinson’s or Alzheimer’s, with donated or lab-grown cells that would replace the diseased cells in patients’ brains.

Similar donations of brain tissue are a long way off — but there’s a need to ensure that neuron transplants of that sort could actually lead to functional brain networks.

This microscopic image shows mouse and rat brain cells interspersed in tissue and labeled in red, blue and green — This image shows the “olfactory switchboard” of a mouse, meaning a region of the brain that processes scents. Rat cells are labeled with red and yellow while mouse cells are labeled in green. (Image credit: Ben Throesch)

“You could say, ‘We can replace the cells that make dopamine and they will make dopamine,'” Baldwin told Live Science. Dopamine is a chemical messenger that’s dramatically depleted in Parkinson’s. “But what are they doing to the information processing in that part of the brain?” Baldwin added. “Are they participating in the right way, and could we improve that?”

Wu’s study focused on replacing an entire region of the mouse brain with rat cells. The team used the gene-editing technique CRISPR to shut down a gene that triggers the development of the mouse forebrain in the womb. They replaced this large brain region with rat cells, and 60% of the cells in the mature mice ended up being of rat origin. Despite their hybridized brains, the mice acted like typical lab mice.

“We show that up to 60% of cells that are coming from a different species in the forebrain doesn’t really dramatically alter the behavior of the host recipient,” Wu told Live Science.

No one’s planning to put human neurons in mouse brains. That would raise far more ethical issues than growing hybrid rodent-rodent brains, because the brains could cross a threshold and become “too human.” In any case, it would be far more technically difficult to achieve, Wu said. There have been attempts to grow other human organs in animals — for instance, scientists grew human kidneys inside pig embryos — but brain tissue would be another matter.

Researchers could theoretically apply these techniques to hybridize the brains of different monkey species. This could make it easier to genetically tweak the primates to model aspects of human diseases; that’s because different gene-modification techniques tend to be tried and tested in specific species and aren’t always easy to use across species.

Such work in monkeys might be more relevant to people, as many diseases that humans get don’t affect mice or rats, Baldwin noted. But it would raise its own ethical questions.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line “Health Desk Q,” and you may see your question answered on the website!