That's a Lot of Ambisome!

A post by Melanie Nicol

Greetings readers! We are still on a bit of a high regarding our safari trip. This is my third time on a safari and my second time in Murchison but that did not make the trip any less awe-inspiring. I am so blessed to have the opportunity to experience something that many will never get to do.

Although we planned for the long weekend since I knew June 3rd, Martyrs' Day was a public holiday in Uganda, it was only last week we learned that Eid al-Fitr, the end of Ramadan, would also fall this week.  We found out late last evening that Eid was today (June 4th) meaning we actually have a 4-day weekend. Apparently the day that Eid will fall on is not known ahead of time so we could not have planned for this anyway. Since most of the sites and partners that we would be working with today have a holiday, we made today a "project day". We have been working in a local coffee shop, Endiro Cafe, which is a local little Mzungu Haven within walking distance of the Minnesota House. We got here a little after 10. Around 1pm it started pouring rain- 2 hours later it hasn't let up. We may be stuck here for quite awhile. There is food, coffee, internet, and electricity so we are all happy campers though :)

As you've read in the students posts- they have been rotating through a couple of different locations and experiences during their time here. One of those rotations is with the meningitis team at Kiruddu Hospital. I have previously described some about the cryptococcal meningitis research team in a previous post (see Mushroom Meningitis of Uganda). Observing this team is a great example for the students to see integration of clinical care and clinical research.  Although to some extent this is true in the U.S. (i.e. for many difficult to treat pediatric cancers standard of care is to enroll in a clinical trial so they have access to the newest treatment advances). I think in some ways this integration is especially true in resource limited settings.

Since last year, there have been many updates on the meningitis research projects. It is an exciting time for the meningitis team. Many new drugs and formulations will be tested over the coming months-years. Currently, Kampala is a site for the AMBITION-CM (link) which is investigating a single high-dose liposomal amphotericin compared to the standard 7 days of de-oxycholate amphotericin.

Member of study team prepares the Ambisome

That's a lot of Ambisome

The next trial to be underway here is the ENACT study which is going to investigate an oral formulation of amphotericin. If successful, this would be a great boost to clinical care as currently amphotericin can only be given IV- infusion related reactions are common. Lastly a clinical trial investigating a new oral "first-in-class" antifungal. New classess of antifungal medications are sorely needed so this study also has the potential to have great impact on the drug development pipeline.

As for my own research with the meningitis team, the autopsy study is still underway. Our first manuscript describing antiretroviral penetration in brain tissue was recently accepted in Clinical Translational Science (will add link when available). We confirmed that CSF is not a good surrogate for brain exposure AND we confirmed that drug penetration (into CSF) is higher in individuals with meningitis, something that has long been suspected but never shown with these drugs in humans. We have now developed a pretty extensive tissue bank and investigations related pharmacokinetics and pharmacodynamics in brain tissue are underway. We are hoping we can identify regimens (both anti-HIV and antifungal) that will be able to erradicate viral and fungal reservoirs in all regions of the central nervous system.

I can't believe it but tomorrow is my last day in Kampala! I have been very impressed with how the students have quickly learned their way around and feel comfortable leaving them in the hands of Prosperity and my collaborators