Garlic for Yeast Infections? Probably Best To Skip It
Cryptococcal Meningitis Treatment Enters Phase 2 Clinical Trial
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A new, easier-to-administer and patient-friendly sustained-release formulation of flucytosine, a medicine used to treat cryptococcal meningitis, has entered Phase II clinical trials in Malawi and Tanzania. The trial is being conducted by the not-for-profit research organization Drugs for Neglected Diseases initiative (DNDi) and its partners.
'As HIV funding cuts threaten to undo decades of progress in Africa, treatment interruptions are already threatening to push thousands into advanced HIV disease (AHD),' said Dr Luis Pizarro, Executive Director of DNDi. 'Essential AHD services have been disrupted, and stockouts of life-saving medicines like flucytosine are looming. Amidst this unprecedented crisis in multilateral cooperation, we must continue developing new treatment options for people living with HIV/AIDS and urgently strengthen international scientific collaborations.'
Cryptococcal meningitis is caused by the fungus Cryptococcus neoformans, found in soil and bird droppings, and is a major health threat to people with weakened immune systems. Those with advanced HIV are particularly at risk. It often begins with severe headaches, fever, nausea, and vomiting—progressing to neck stiffness, confusion, and, in late stages, coma due to inflammation of the brain and spinal cord. In Africa, where access to timely treatment is limited, the disease kills up to 70% of those who get it.
'When people with HIV can't access effective treatment, they risk developing advanced HIV disease—and that opens the door to deadly infections like cryptococcal meningitis,' said Dr Justine Odionyi, Head of HIV Disease at DNDi. 'In 2023 alone, AIDS-related illnesses killed 390,000 people in Africa. Cryptococcal meningitis claimed 130,000 of those lives—deaths driven by treatment gaps. Now, with funding cuts, even more people will be left without care. More lives will be lost. It's a terrifying reality.'
Lack of access to timely diagnosis and treatment is a major reason why cryptococcal meningitis remains so deadly. Across many countries, point-of-care CD4 testing—important for identifying people with advanced HIV—is in short supply. There are also growing shortages of cryptococcal antigen lateral flow assay (CrAg LFA) tests, which are recommended for routine screening in people living with HIV with low CD4 count. With fewer diagnostic tools available and a shrinking health workforce, linking patients to life-saving AHD care will become harder by the day. Unless urgent action is taken, continued disruptions to the AHD care package will result in hundreds of thousands of preventable deaths.
Flucytosine, an effective and key component of the World Health Organization's first-line treatment regimen for cryptococcal meningitis, is difficult to administer in overburdened, resource-limited settings. It must be taken every six hours, which can lead to missed doses. Additionally, many patients arrive at the hospital already in a coma, forcing healthcare staff to crush the tablets and administer them via nasogastric tube, a method not formally approved but often the only available option.
'We were already struggling with limited supplies of flucytosine across many countries. Now, with the HIV funding cuts, the situation is becoming worse. Widespread stockouts are just around the corner. Without this life-saving drug, preventable deaths are inevitable,' added Dr Odionyi.
The open-label, randomized Phase II study for the new sustained-release flucytosine formulation will include 72 adult participants in Tanzania and Malawi. It simplifies dosing from four times to twice daily. It comes in pellet form, making it easier to take with water or through a nasogastric tube, and is suitable for outpatient self-administration. Participants will be divided into two groups: one will receive the current regimen of flucytosine every six hours for 14 days, while the other will receive the new sustained-release version—6000 mg taken twice daily.
'In 2023, around 12,000 people in Malawi died from AIDS-related illnesses. The need for faster diagnostic testing and simpler, more practical treatment options has never been more urgent,' said Dr Cecilia Kanyama, Principal Investigator for the study at the University of North Carolina Project in Malawi. 'The current flucytosine formulation is difficult to administer, which has impacted treatment outcomes for years. We're hopeful this new formulation will be easier to use and lead to better outcomes for our patients.'
'In Tanzania, around 1.4 million people depend on antiretroviral therapy to manage HIV. We've been telling people HIV is no longer a death sentence—if you can access and stay on treatment,' said Prof. Sayoki Mfinanga, Global Coordinating Investigator at the National Institute for Medical Research (NIMR) in Tanzania. 'But with supply chains under threat, that progress is at risk. We urgently need innovative, simpler treatments to protect those with advanced HIV and stop unnecessary loss of life.'
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Everything You Need To Know About Meningitis
Meningitis can occur due to a viral, bacterial, or fungal infection and requires emergency medical treatment. Symptoms may include stiff neck, sleepiness, and headache, among others.
Meningitis is an inflammation of the fluid and three membranes (meninges) surrounding your brain and spinal cord.
The most common causes of meningitis are viral and bacterial infections. Other causes may include:
Some viral and bacterial meningitis are contagious. They can be transmitted by coughing, sneezing, or close contact.
The symptoms of viral and bacterial meningitis can be similar in the beginning. However, bacterial meningitis symptoms are usually more severe. The symptoms also vary depending on your age.
Viral meningitis symptoms
Viral meningitis may cause:
Bacterial meningitis symptoms
Bacterial meningitis symptoms develop suddenly. They may include:
Seek immediate medical attention if you experience these symptoms. Bacterial and viral meningitis can be deadly. There's no way to know if you have bacterial or viral meningitis just by judging how you feel. A doctor needs to perform tests to determine which type you have.
Fungal meningitis symptoms
Symptoms of fungal meningitis resemble the other types of this infection. These may include:
Chronic meningitis symptoms
Chronic meningitis symptoms are similar to other forms but may develop more slowly.
Viruses that cause colds, cold sores, flu, and diarrhea can also cause viral meningitis.
Bacterial meningitis typically spreads from a severe infection in a nearby area of the body. For example, bacteria from a severe ear infection or sinus infection can enter the bloodstream and travel to the brain or spinal cord.
Meningitis becomes more common in children as they grow older and reach high school and college ages. Symptoms of viral and bacterial meningitis in children are similar to symptoms in adults. These include:
Having Neisseria meningitidis, one bacterial cause of meningitis, in your bloodstream may cause a faint rash.
Bacteria from a meningococcal meningitis infection reproduce in the blood and target cells around the capillaries. Damage to these cells leads to capillary damage and mild blood leaks. Depending on your skin color, this shows up as a faint pink, red, or purple rash. The spots may resemble tiny pinpricks and are easily mistaken for bruises.
People with darker skin may have a harder time seeing a meningitis rash. Lighter areas of skin, such as the palms of hands and the inside of the mouth, may show signs of a rash more easily.
As the infection worsens and spreads, the rash can become more visible. The spots usually grow darker and larger.
Though meningitis refers to inflammation of the fluid and membranes around the brain and spinal cord, experts categorize it based on the type of infection that causes it.
Viral meningitis
Viral meningitis is the most common type of meningitis. Viruses in the Enterovirus category cause about 52% of cases in adults and 58% in infants, more commonly during the summer and fall. Viruses include:
Though viruses in the Enterovirus category cause about 10 to 15 million infections per year, only a small percentage of people who get them develop meningitis.
Other viruses can also cause meningitis. These may include:
Viral meningitis typically goes away without treatment. However, some causes do need treatment.
Bacterial meningitis
Bacterial meningitis is contagious and caused by infection from certain bacteria. It can be fatal if left untreated. About 1 in 10 people who get bacterial meningitis die, and 1 in 5 have serious complications. This can be true even with proper treatment.
Common bacterial causes include:
Pneumococcal meningitis
Pneumococcal meningitis is a rare but serious and life threatening form of bacterial meningitis.
About 40% of people carry bacteria called Streptococcus pneumoniae in their throat and the back of the nose. These bacteria are responsible for common illnesses like pneumonia, sinus infections, and ear infections.
Symptoms of pneumococcal meningitis can include:
Fungal meningitis
Fungal meningitis is rare. It occurs when a fungus enters the body and spreads from the bloodstream to the brain or spinal cord.
People with a weakened immune system are more likely to develop it. This includes people with cancer or HIV.
Common funguses related to fungal meningitis include:
Parasitic meningitis
Parasitic meningitis is less common than viral or bacterial meningitis. It's caused by parasites in dirt, feces, and on some animals and food, like:
One type of parasitic meningitis is rarer than others. It's called eosinophilic meningitis (EM). Three main parasites are responsible for EM. These include:
Parasitic meningitis is not passed from person to person. Instead, these parasites enter an animal or hide out on food that a human then eats. An infection may occur if the parasite or parasite eggs are infectious when ingested.
Amebic meningitis is a very rare type of parasitic meningitis that causes a life threatening infection.
It occurs when one of several types of ameba enters the body through the nose. The most commonly recognized species is Naegleria fowleri. Infection can occur while swimming in lakes, rivers, or ponds that contain these amoebas. The parasite can destroy brain tissue and may eventually cause hallucinations, seizures, and other serious symptoms.
Non-infectious meningitis
Non-infectious meningitis is not an infection. Instead, it is inflammation caused by other medical conditions or treatments, including:
Chronic meningitis
Doctors call meningitis chronic if the inflammation lasts longer than 4 weeks. Causes can include:
Treating the underlying cause (i.E., managing rheumatoid arthritis) may help relieve chronic meningitis.
Each type of meningitis has a slightly different cause, but each ultimately acts in the same way:
A bacterium, fungus, virus, or parasite spreads through the body (via the bloodstream, nerve endings, or even a dormant reactivation in the nervous system) until it reaches the brain or spinal cord. There, it spreads within the lining or fluids around these vital body parts and starts developing into a more advanced infection.
Non-infectious meningitis results from a physical injury or other condition; it doesn't involve an infection.
Some groups may have an increased risk of meningitis. This can include:
People with weakened immune systems
Certain health conditions and treatments can weaken your immune system. These include:
Community living
Meningitis often spreads more easily if people live or work in close quarters, such as:
Pregnancy
Pregnancy can increase the risk of listeriosis, an infection caused by the Listeria bacteria, which can result in meningitis.
Age
Children under 5 may have an increased risk of viral meningitis, while infants have a higher risk of bacterial meningitis. Older adults can also be at an increased risk of infections that can cause meningitis.
Working with animals
People who work closely with animals may have an increased risk of Listeria infection.
Vaccines are available for several types of bacterial meningitis, including meningococcal meningitis, caused by Neisseria meningitidis. These include:
Meningococcal conjugate (MenACWY) vaccine
The meningococcal conjugate, or MenACWY vaccine (often called by brand names such as Menactra, Menveo, and MenQuadfi) features a vaccine that targets four of the most common types of bacterial serotypes. It lasts longer and offers greater protection, especially if you maintain booster shots.
Serogroup B meningococcal (MenB) vaccine
The Serogroup B meningococcal, or MenB, vaccine targets one specific strain and has a much shorter protection window. The CDC recommends that anyone 10 years old or older at an increased risk for meningococcal disease get the MenB vaccine.
Vaccine side effects
Depending on the vaccine, these side effects usually improve in 1 to 5 days.
While viral meningitis is more common, bacterial meningitis can be more dangerous if not diagnosed and treated quickly.
Special conditions
While most younger children and adults do not need a meningitis vaccine, the CDC recommends it for the following conditions:
If you fall into any of the categories above, it's best to talk with a doctor about vaccination for meningitis.
Meningitis in adults
The risk of several forms of meningitis decreases after young adulthood. Once a young adult ages out of school and university, getting meningitis is less likely.
However, older individuals who are living with underlying diseases or health conditions that weaken the immune systems can be at greater risk. The risk is especially higher in older adults in assisted living facilities.
Teachers, healthcare professionals, and day care staffers also have an elevated risk.
Not all types of meningitis are contagious. Fungal, parasitic, and non-infectious meningitis are not contagious.
Viral meningitis is contagious. It's spread through direct contact with body fluids, including mucus, feces, and saliva. Droplets of infected fluid can spread by sneezing and coughing. You can get viral meningitis without coming into direct contact with someone who has it.
Bacterial meningitis, the most serious form of meningitis, can also be contagious, especially if it's meningococcal meningitis. It can spread through extended contact with someone who has it. It typically spreads in locations where people are in close quarters.
While it's difficult to prevent all types of meningitis, you may be able to prevent bacterial meningitis, the most common and serious type, with vaccines.
If you're at an elevated risk for meningitis due to your age, job, or overall health, consider talking with a doctor about your options for vaccination.
You may be able to reduce your risk of meningitis by:
Certain practices may also support your overall immune system health and reduce your risk of illness that could lead to meningitis. This can include:
Meningitis is an inflammation of the fluid and three membranes surrounding the brain and spinal cord. Meningitis can occur when fluid surrounding these membranes becomes infected.
Meningitis can result from viral, bacterial, or fungal infections.
Some forms of meningitis can be dangerous or fatal if not treated quickly.
Vaccines for bacterial meningitis are available for pre-teens and teens, as well as anyone who may be at a higher risk of developing the condition.
New Treatment For Deadly HIV-linked Meningitis Enters Phase II Trial.
HIV sensitisation. [Courtesy]
There is hope in the fight against cryptococcal meningitis, the second leading cause of death in patients with advanced HIV (previously called AIDS), as scientists work around the clock to release new medicine to treat the disease.
This comes amid a cut of donor funding with the signing of stop-work order by U.S. President Donald Trump, a move likely to increase cases of cryptococcal meningitis leading to deaths.
Scientists from the Drugs for Neglected Diseases Initiative (DNDI) and partners have launched a Phase II trial in Malawi and Tanzania to develop a simpler, patient-friendly treatment for cryptococcal meningitis.
"When people with HIV can't access effective treatment, they risk developing advanced HIV disease—and that opens the door to deadly infections like cryptococcal meningitis,' said Dr Justine Odionyi, Head of HIV Disease at DNDI.
Additionally, she said many patients arrive at the hospital already in a coma, forcing healthcare staff to crush the tablets and administer them via nasogastric tube, a method not formally approved but often the only available option.
'We were already struggling with limited supplies of flucytosine across many countries. Now, with the HIV funding cuts, the situation is becoming worse. Widespread stockouts are just around the corner.
Without this life-saving drug, preventable deaths are inevitable,' added Dr Odionyi.
The easier-to-administer and patient-friendly sustained-release formulation of flucytosine is the one under development.
Flucytosine, an effective and key component of the World Health Organisation (WHO) first-line treatment regimen for cryptococcal meningitis, is difficult to administer in overburdened, resource-limited settings.
The current formulation must be taken every six hours, which can lead to missed doses.
The open-label, randomised Phase II study for the new sustained-release flucytosine formulation will include 72 adult participants in Tanzania and Malawi.
It simplifies dosing from four times to twice daily. It also comes in pellet form, making it easier to take with water or through a nasogastric tube, and is suitable for outpatient self-administration.
Participants have been divided into two groups: one will receive the current regimen of flucytosine every six hours for 14 days, while the other will receive the new sustained-release version—6000 mg taken twice every day.
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After completion of the study, the results will be submitted to the WHO for review, and the drug will be distributed to respective countries to help in the treatment of cryptococcal meningitis, a leading cause of death in people with advanced HIV disease, after Tuberculosis (TB).
In Kenya, at least 1.4 million people are living with HIV, with at least 20,000 deaths reported annually.
"The need for faster diagnostic testing and simpler, more practical treatment options has never been more urgent,' said Dr Cecilia Kanyama, Principal Investigator for the study at the University of North Carolina Project in Malawi.
'The current flucytosine formulation is difficult to administer, which has impacted treatment outcomes for years. We're hopeful this new formulation will be easier to use and lead to better outcomes for our patients.'
DNDI is developing the sustained-release flucytosine formulation in partnership with Mylan Laboratories Limited, India (a Viatris Company), the National Institute for Medical Research, Tanzania; the University of North Carolina Project, Lilongwe, Malawi; the Luxembourg Institute of Health; St George's, University of London; and FARMOVS.
"As HIV funding cuts threaten to undo decades of progress in Africa, treatment interruptions are already threatening to push thousands into advanced HIV disease (AHD)," Dr Luis Pizarro, Executive Director of DNDI, said in a statement.
Pizarro said essential AHD services have been disrupted, and stockouts of life-saving medicines like flucytosine are looming.
"Amidst this unprecedented crisis in multilateral cooperation, we must continue developing new treatment options for people living with HIV/AIDS and urgently strengthen international scientific collaborations," added the researcher.
Cryptococcal meningitis is caused by the fungus Cryptococcus neoformans, found in soil and bird droppings, and is a major health threat to people with weakened immune systems.
Those with advanced HIV are particularly at risk.
The disease presents with severe headaches, fever, nausea, and vomiting, progressing to neck stiffness, confusion, and, in late stages, coma due to inflammation of the brain and spinal cord.
In Africa, where access to timely treatment is limited, the disease kills up to 70 per cent of those who get it.
In 2023 alone, AIDS-related illnesses killed 390,000 people in Africa, with Kenya recording 20,000 deaths.
Cryptococcal meningitis claimed 130,000 of those lives, deaths driven by treatment gaps.
Scientists worry that with funding cuts, more people will be left without care, with multiple deaths.
Lack of access to timely diagnosis and treatment is a major reason why cryptococcal meningitis remains so deadly.
Across many countries, point-of-care CD4 testing—important for identifying people with advanced HIV—is in short supply.
There are also growing shortages of cryptococcal antigen lateral flow assay (CrAg LFA) tests, which are recommended for routine screening in people living with HIV with low CD4 count.
With fewer diagnostic tools available and a shrinking health workforce, linking patients to life-saving AHD care will become harder by the day.
Unless urgent action is taken, continued disruptions to the AHD care package will result in hundreds of thousands of preventable deaths.
"We've been telling people HIV is no longer a death sentence—if you can access and stay on treatment,' said Prof Sayoki Mfinanga, Global Coordinating Investigator at the National Institute for Medical Research (NIMR) in Tanzania.
"But with supply chains under threat, that progress is at risk. We urgently need innovative, simpler treatments to protect those with advanced HIV and stop unnecessary loss of life.'
This clinical trial is financially supported by the second European and Developing Countries Clinical Trials Partnership (EDCTP2) programme supported by the European Union (grant RIA2018CO-2516), with additional funding from the UK National Institute for Health and Care Research (Department of Health and Social Care).
The trial is also supported by the Swiss Agency for Development and Cooperation (SDC), Switzerland; Médecins Sans Frontières International, and other private foundations and individuals.
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