Seminar Series Report: Cryptococcal meningitis – treatment, prevention and advocacy

News article 7 Oct 2016

LSTM’s seminar series continued with a talk from Dr Angela Loyse and Professor Tom Harrison from St George’s University of London. Their presentation entitled: Cryptococcal meningitis – treatment, prevention and advocacy, was introduced by LSTM’s Professor Shabbar Jaffar.

Dr Loyse opened by discussing the global burden of cryptococcal meningitis, which is caused by a fungus. It mainly affects people with a supressed immune system, particularly those with HIV. The highest burden is in sub-Saharan Africa with an estimated one million cases occurring globally. She explained the process of infection with Cryptococcus spores residing in the soil which are inhaled. While many will experience no symptoms, in those with a supressed immune system the spores can reactivate causing a number of problems such as bone and lung disease, skin infections and most commonly meningitis.

She continued that the high mortality associated with the disease, which accounts for around 20-25% of HIV deaths, is due to late presentation with HIV-infection and inadequate access to antifungal drugs and diagnostic tests. Dr Loyse explained that due to the uptake of anti-retroviral therapies (ARTs) for the treatment of HIV many would expect that the associated drops in cases of cryptococcal meningitis seen in North America and Europe will be replicated imminently in sub-Saharan Africa. However she talked about why this is not likely to be the case in the African setting for a number of reasons including high drop-out rates from care and lack of availability of suitable drugs.

Unlike other forms of meningitis, the symptoms of cryptococcal meningitis can take a number of weeks to fully develop, meaning that a patient may have subclinical meningitis in advance of the onset symptoms. The advent of a new point of care, lateral flow crypotococcal antigen assay has been proven to be accurate and can detect the infection at the early stages, making it medically and economically beneficial to initiate prompt pre-emptive treatment. She also talked about the development of second generation assays which can indicate the level of antigen present to give an early indication of prognosis.

Dr Loyse went on to talk about the current treatment regimens and the problems faced due to length of treatment and the lack of availability of some drugs in sub-Saharan Africa. She talked through a number of potential alternatives and then Professor Harrison went on to look at a number of currently active studies across Africa which are investigating different length, doses and combinations of drugs and their affect in comparison to the current gold standard of treatment, which is two weeks of amphotericin B followed by eight weeks of fluconazole.

He concluded by emphasising the need for further antifungal therapies that could be bundled with additional drugs and tests used to treat other associated infections, such as TB, as well as looking at mechanisms to promote adherence support for late stage HIV sufferers. Professor Harrison talked through two main studies ACTA, which is taking place across four countries, within nine hospitals, and the AMBITION trial. AMBITION looks specifically at ambisome, which is a liposomal formulation of amphotericin B that is less toxic but has a similarly long half-life which results in good levels of the drug in the brain. The trial will examine the efficacy of reducing length of treatment for cyrptococcal meningitis with this formulation, given that one big dose of ambisome has been as effective against visceral leishmaniasis as longer treatments with smaller, multiple doses.

A recording of the seminar can be found here: