Determining HIV-associated cryptococcal disease with clinic-based, point-of-care screening in Durban, South Africa.
In August, I traveled to Durban, South Africa to collect pilot data for a study of diagnostics and to set up a new study related to cryptococcal infections, a common cause of HIV-related mortality.
The global burden of cryptococcal meningitis (CM) is estimated at 958,000 cases and 625,000 deaths per year, making CM a leading cause of AIDS-related mortality. The vast majority of CM occurs among HIV-infected people with advanced immunosuppression or within 3 months of antiretroviral therapy (ART) initiation. In sub-Saharan Africa, an estimated 7-19% of HIV-infected adults have asymptomatic cryptococcal antigenemia (CrAg) at the time of HIV diagnosis, and circulating CrAg predicts onset of CM and mortality. These antigens appear weeks before the onset of neurological symptoms, and among those with circulating antigens oral anti-fungal therapy (fluconazole) reduces the risk of CM and death. Thus, early detection of CrAg and prophylactic anti-fungal therapy might improve health outcomes, but few laboratories in resource-limited settings (RLS) have had the ability to expeditiously test for CrAg in serum.
In the first study, I worked with Ms. Julia Kleene (pictured below), a medical student at Stony Brook School of Medicine, to conduct testing of stored urine samples from a previous cohort (photos below). In one long, exhausting day we managed to test approximately 800 urine samples using a rapid test for cryptococcal antigens. This study was the first assessment of cryptoccocal antigen prevalence in the KwaZulu-Natal Province. We tested participants with a wide range of CD4 counts. We found about 10% prevalence of cryptococcosis among newly-diagnosed HIV-infected adults, and the results did not differ among people with higher CD4 counts, which is contrary to most other studies. The results formed the basis for pilot data related to a K23 grant application and are currently being prepared for publication.
In the second study, I used the time to set up a new longitudinal study to determine the impact of clinic-based screening for cryptococcal infections at the time of HIV diagnosis. During my visit, we were able to hire a local research assistant and a local research nurse. We spent time at our clinical site arranging the flow of the participants through the stages of the study, preparing documents, and meeting with various research partners. The study then started enrollment on September 12, and to date we have already enrolled over 200 participants.
The location of this study is the iThembalabantu Clinic in Umlazi, a township of Durban with over 1.2 million people and a very high burden of HIV and TB. The clinic offers HIV testing, counseling, and treatment, and has a pharmacy to dispense ART (first and second line regimens) and therapy for opportunistic infections. The clinic is staffed by 2 full-time physicians, 10 nurses, 4 HIV counselors, and a cadre of community health workers. Each day, clinic counselors test 30-40 adults for HIV, of whom an average of 36% are HIV-infected, and clinicians provide comprehensive care for >100 HIV-infected people. The results of these studies will help inform future studies of point-of-care CrAg screening in South Africa, as well as other resource-limited settings, to help prevent AIDS-related mortality.
The travel funds provided an essential opportunity for me to travel to Durban to collect pilot data for my K23 application, and at the same time to lay the groundwork to initiate a new prospective clinical study. I have very grateful to Partners for the Global Health Center of Expertise travel grant to help support my clinical research projects. I would definitely recommend this funding opportunity to other clinical fellows.