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Hopes that tamoxifen could improve survival for a deadly form of fungal meningitis have been dashed by the results of a clinical trial conducted by University of Oxford researchers and published today in eLife.

Typical spherical to oval cells of Cryptococcus neoformans, with extensive capsules and a budding daughter cell © Phan Hai Trieu

The study finds that adding tamoxifen to standard antifungal treatment was no better at speeding up the clearance of fungal infection from the spinal fluid of people with meningitis. More patients who received tamoxifen had evidence of conduction disturbances in their hearts, although there was no difference in the rates of severe side effects between study groups. 

Cryptococcal meningitis is a leading cause of death in people with HIV, but also affects those without HIV, regardless of whether they are immunocompromised. Most infections are caused by a fungus called Cryptococcus neoformans (C. neoformans) and occur in low-income tropical settings. The gold-standard treatment is a combination of three drugs: flucytosine and amphotericin B initially, followed by fluconazole. Yet, even on this gold-standard therapy, a third of patients die within 10 weeks of being diagnosed. Moreover, the drug flucytosine is severely restricted by availability and cost, meaning it is rarely used where the disease burden is highest.

Co-first author Nguyen Thi Thuy Ngan, Clinician at the Department of Tropical Medicine, Cho Ray Hospital, and the Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam, said: 'Tamoxifen has shown antifungal activity against various yeasts in the lab; we subsequently showed that it acts synergistically with amphotericin against two-thirds of clinical Cryptococcus isolates from our archive. As a well-understood, off-patent, cheap and widely available medicine, it was a promising candidate for treating cryptococcal meningitis.'

Read the full story on the University of Oxford website

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