The fungal form of meningitis is rare and is usually caused by fungus spreading through blood to the spinal cord. It leads to more than 600,000 deaths in
Africa every year and is responsible for 20% of HIV/AIDS-related
deaths globally, suggests the U.S. Centers for Disease Control and
An existing medicine could help curb these numbers, but its
cost has been a barrier to access in some places. Now, scientists report
in the ACS journal Organic Process Research & Development
a more affordable way to make the drug.
‘A more affordable way to make the antifungal flucytosine, used to treat a fungal form of meningitis, has been reported by scientists.’
The antifungal flucytosine has been available to patients in the
U.S. for decades. In 2011, the World Health Organization (WHO)
recommended that patients with Cryptococcal meningitis
infection of particular concern to people with HIV/AIDS, take
flucytosine in combination with amphotericin B as a first line of
Flucytosine is now on WHO's Core List of Essential Medicines.
However, the drug is not registered for use in many African countries,
according to the non-profit Doctors without Borders, and where it is
available, many patients can't afford it. Currently, making the drug
requires a multiple-step process that involves fluorination,
chlorination, amination and hydrolysis from uracil.
To help slash
flucytosine's price tag and improve its availability, Graham Sandford
and colleagues at Durham University in the U.K. wanted to come up with a
simpler, lower cost way to make the drug.
The researchers developed a one-step technique to make flucytosine
out of readily available, naturally occurring cytosine. Their process
involved simultaneously pumping inexpensive fluorine gas and a solution
of cytosine in formic acid through a steel tube. This fluorinated all of
the starting cytosine, and the researchers were able to isolate high
yields of the resulting flucytosine by recrystallization.
researchers say the method should be simple to scale up for
manufacturing and could help lower the drug's cost. The one-step method
has been successfully developed to pilot-scale by industrial
collaborators Sanofi-Aventis and La Maison Européenne des Procédés
Innovants in France.