Stories From the Field:


Early detection and prevention of cryptococcal disease using blood based immunological assays

Bjorn Corleis, PhD, Graduate Research Assistant at the Ragon Institute of MGH, MIT, and Harvard, received an MGH Global Health Travel Award and traveled to Harare, Zimbabwe to further his ongoing work on HIV/Cryptococcal Meningitis with the University of Zimbabwe College of Health Sciences.

The MGH Global Health Travel Award allowed me to travel to Harare, Zimbabwe and continue my ongoing collaborations with the University of Zimbabwe. This work would have been impossible without the support by MGH Global Health. Project background: Cryptococcus neoformans is a ubiquitous environmental fungal pathogen that causes disseminated disease, in particular meningoencephalitis (CM), among severely immunocompromised HIV patients. Early detection of cryptococcal antigenemia in asymptomatic patients enrolling in antiretroviral therapy (ART) programs could provide an opportunity to mitigate Cryptococcus-associated mortality after the initiation of ART. Determining host immune defects that correlate with reactivation and dissemination will allow for improved risk stratifications.

Project aims during my stay:
This was my 3rd visit in Harare. During my last visits I implemented a new immunological assay to support the efforts to better understand CM in people living with HIV and to develop new clinical tests. The specific goals for this visit were to
1. Further improve and extend the immunological assays for early diagnosis of CM
2. Provide training for these assays and lab equipment to new lab members
3. Move forward with the goal to establish a new area of research in the lab (HIV/TB co-infection)

Progress report:
1. The previous immunological assay was designed to broadly (non-specifically) characterize the immune response of blood T cells obtained from patients with HIV and with or without CM. During my visit we extended the assay and established antigen specific activation of blood T cells from patients in the same cohort. In particular, we started to look at T cell responses to cryptococcal- and tuberculosis antigen. The first results looked very promising and we decided that this assay should be done routinely for all future experiments. In addition, the assay turned out to be useful for another project in the lab where the investigators study the impact of Kaposi sarcoma on the immune response to bacterial infection in people living with HIV.
2. I was able to provide training in tissue culture technique, immunological assays and flow cytometry to 2 new lab members in the department of medicine at the University of Zimbabwe. The 2 lab members are now able to perform these assays independently.
3. I made great progress to develop new projects in the department. I had meetings with several Professors of the department, including the deputy dean to discuss the implementation of a project which aims to investigate the role of lung tissue resident T cells in a protective response against tuberculosis in the context of HIV. We finalized a protocol to be submitted to the ethical committee of the University. I found pulmonologists and students who are interested to work on this new project and received a verbal confirmation by the deputy dean of the department that this project is of great interest.

Future plans:
I will continue my efforts to support ongoing research in the department of medicine. I stay in contact with lab members in Harare by montly skype calls and email. I’m very excited about the opportunity to be the main prinicpal investigtor of a new research project with a focus on HIV/TB co- infection. I currently apply for faculty position and funding in order to be able to move this project to the next step. The research in Zimbabwe will be very important for my future career in academia and I’m very grateful that the MGH global health travel award helped to support the ground work for this.