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Africa

Africa: On World Meningitis Day, Too Many People Are Dying of Cryptococcal Meningitis in Africa

todayOctober 7, 2024 2

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Improving outcomes for patients requires urgent efforts to reduce the price of treatments and increase access to drugs.

When Zikhona, a young woman from New Crossroads in Cape Town, arrived at Khayelitsha Hospital, she thought she was going to die. She was in severe pain, had an excruciating, crippling headache, a stiff neck, and was almost blind. She was diagnosed with cryptococcal meningitis – a disease she never heard of before. Fortunately, she received treatment in time and survived.

But many people don’t not have this chance. Every year, around 180,000 people with HIV die from cryptococcal meningitis – 135,000 of them in sub-Saharan Africa.

As an HIV clinician and researcher, I have witnessed first-hand the devastation brought by this disease. And I am outraged, because I know that most of these deaths could be avoided. Many people with cryptococcal meningitis die simply because they aren’t diagnosed or can’t access the treatment that could save their life.

Cryptococcal meningitis is not only the second-leading cause of death for people living with HIV in Africa, but it is also one of the most painful ways to die.

Cryptococcal meningitis is caused by a fungus called cryptococcus neoformans, commonly found in soil and bird droppings. Most people will inhale this fungus at some point in their lives without ever getting sick. But for those with weakened immune systems due to advanced HIV (previously called AIDS) the fungus can be deadly. Once the infection takes hold, it often leads to meningitis, an inflammation of the brain coverings causing swelling around the brain and spinal cord. The excruciating headaches that Zikhona experienced were a sign that the infection had spread to the lining of her brain.

Despite its impact, cryptococcal meningitis is a neglected disease. It remains largely unnoticed, underdiagnosed, and untreated in people with HIV – leading to a death rate as high as 70% in Africa. Yet with early diagnosis and proper treatment, the death toll can be reduced to 30%.

So why are so many people still dying? The main reason: poor access to diagnosis and life-saving treatment.

Why can’t people with cryptococcal meningitis access the treatment they need?

The World Health Organisation recommends a treatment regimen of a single high dose of liposomal amphotericin B (LAmB), followed by 14 days of flucytosine and fluconazole. But here’s the problem: two of these three drugs – LAmB and flucytosine – are often unavailable in Africa.

LAmB is priced beyond the reach of many low- and middle-income countries (LMICs). Our latest research found that LMICs pay significantly more than high-income countries (HICs), despite shouldering a higher burden of HIV. For example, Brazil pays USD 215 per vial, while Japan and the UK pay USD 51 and USD 99, respectively. Such high prices discourage countries from prioritising LAmB, despite its superior efficacy, reduced toxicity, and ease of use. Of the 4.18 million vials of LAmB sold in 2021, only 28% went to LMICs.

Efforts to secure LAmB at lower prices have been made, with Gilead – the main supplier – once offering it at a ‘no-profit’ price of USD 16.25 per vial in certain LMICs. However, access has been limited by delivery delays, supply shortages, and complex reporting requirements. In January 2024, Gilead increased its ‘no-profit’ price by 40%.

LAmB’s complex structure makes it difficult to manufacture. Only two generic versions exist, and their manufacturers have also prioritised large and lucrative markets in HICs. Most LMICs continue to rely on the more toxic amphotericin B deoxycholate, which is harmful to human cells and can cause serious damage to the kidneys.

The second drug in the WHO-recommended treatment regimen, flucytosine, is not registered or available in most African countries. Like LAmB, unaffordability and unavailability are the main barriers to access.

And even where it is available, flucytosine is difficult to use. It must be taken every six hours and comes in the forms of tablets. Patients with cryptococcal meningitis are often unconscious when they arrive at the hospital, requiring healthcare staff to crush the tablets for administration via nasogastric tube, despite this method not being approved.

Ending this unacceptable neglect

Improving outcomes for neglected cryptococcal meningitis patients requires urgent efforts to reduce the price of LAmB, develop a more patient-friendly formulation of flucytosine, and increase access to both drugs.

One immediate step must be to boost LAmB production capacity in LMICs. My organisation, the Drugs for Neglected Diseases initiative (DNDi), in collaboration with Unitaid and the Clinton Health Access Initiative, is seeking expressions of interest from potential new generics manufacturers to provide LAmB at affordable prices. But these manufacturers will need additional incentives, like volume guarantees, which means that countries and stakeholders must coordinate regionally to register, procure, finance, and deliver any new generic product.