Cryptococcal Screening in Patients With HIV

While many in the field of infectious disease research and medicine have noted the decline in new investigators and practitioners entering the workforce, the HIV Medicine Association and the Infectious Disease Society of America (IDSA) Foundation have teamed up to do something about it. Over the summer, they announced a program to fund 15 medical students in the U.S. for clinical learning and research projects, each to be paired with an experienced mentor to support the student's research area of interest.

This is the second in a series of interviews with a mentor/mentee pair.

We spoke with Russell Kempker, M.D., M.Sc., associate professor in the Division of Infectious Diseases at the Emory University School of Medicine. His research focus is in the areas of drug-resistant tuberculosis and HIV-related opportunistic infections, including cryptococcal disease.

His mentee, Kristin Harrington, is a third-year M.D./Ph.D. student at Emory University, with a Ph.D. focus in epidemiology. She is working towards a career as a clinician-scientist in infectious diseases.

Russell Kempker, M.D., M.Sc.
Russell Kempker, M.D., M.Sc.
Jack Kearse

Jeanine Barone: Why is screening for cryptococcal infection so important in this population?

Russell Kempker: The route of acquiring cryptococcal infection for most patients is through inhalation, and then the organism works its way into the bloodstream and eventually into the central nervous system (CNS). There is a window of time, and thus, opportunity, from when the Cryptococcus gets into the bloodstream until it migrates into the CNS, and this is precisely the time when screening is so valuable. If we can catch patients early in the course of infection when they have few-to-no symptoms and the Cryptococcus in the blood, then we can initiate early treatment with a well-tolerated medicine (fluconazole) and prevent progression to cryptococcal meningitis [CM], which can be a devastating infection.

JB: Is screening in the U.S. recommended?

RK: There are no strong recommendations indicating all patients with advanced HIV in the U.S. should be screened for cryptococcal antigenemia (presence of the antigen or foreign protein in the blood) from either the most recent IDSA or U.S. [Department of Health and Human Services] guidelines. The IDSA guidelines (which are from 2010) do suggest that an aggressive screen-and-treat strategy may be warranted in certain high-incidence locales, which is not further defined. Essentially, we need more data on the utility of cryptococcal screening here in the U.S. to help inform screening strategy policies.

JB: What criteria should be used to determine who should be screened?

RK: The easiest and most useful way to determine whether an HIV-positive patient should be screened for cryptococcal antigenemia is based on their CD4 count. Most guidelines and experts would suggest a CD4 cut off of either less than 100 or 150 cells/mm3 to determine who should be screened. Given cryptococcal organisms are found all over the U.S., geographic location is not particularly important in determining who should be screened.

JB: Is cryptococcal infection still a problem in the U.S.?

RK: Cryptococcal infection is still a major problem among patients living with HIV in the U.S., especially for those with advanced disease and low CD4 counts. Cryptococcal meningitis is the most common cause of fungal meningitis in the U.S., and the average length and cost of a hospitalization for cryptococcal meningitis is estimated to be greater than $100,000 and greater than 70 days, respectively. As evident by these numbers, CM cases are incredibly hard to treat, requiring the use of very toxic and hard to tolerate medicines and, in many cases, requiring some neurosurgical intervention to help control high intracranial pressure. Some recent data has also found the rates of asymptomatic cryptococcal antigenemia among patients with a CD4 count less 100 cells/mm3 to be much higher than expected, at approximately 3%.

JB: What is the best screening assay?

RK: The main two assays used are a latex agglutination assay, and more recently, the lateral flow assay has been introduced. Both tests are sensitive and specific and, thus, high performing. At our hospital, we are currently in the process of switching to the lateral flow assay as it offers a few potential advantages, including a rapid turnaround time of 10-15 minutes, low cost, easy to perform, and can detect a lower number of organisms and, thus, may be able to detect antigenemia earlier.

JB: What are the long-term consequences of cryptococcal infection?

RK: The major long-term consequences of cryptococcal meningitis are mainly related CNS damage and can include blindness, vertigo, motor deficits, and cognitive dysfunction, among other deficits. These can lead to severe disability and may require intense rehabilitation to manage.

JB: What are some of your key findings on cryptococcal infection among people with HIV/AIDS?

RK: Preliminary results from our cryptococcal screening project at Grady Memorial Hospital show a high prevalence of cryptococcal antigenemia among patients screened, approximately 4%. This includes both outpatients and patients hospitalized. When we perform a complete data analysis, we will be able to provide more details about disease prevalence and to compare test performance between the lateral flow assay and latex agglutination test.

Kristin Harrington
Kristin Harrington
Emory University School of Medicine

JB [to Harrington]: Why did you decide to focus on cryptococcal infection?

Kristin Harrington: One of the main reasons is that, despite the number of individuals that are affected by CM worldwide and the lasting repercussions it can have on individuals, there is relatively little research in the field. Additionally, the research is mostly done outside the United States due to the fewer number of overall CM cases in comparison with other countries like, for example, Uganda. Being in a city like Atlanta, where we do see more cases than in most U.S. cities, presents a unique opportunity to study CM.

JB: How do you think being involved in this project will inform your clinical experience or research interests?

KH: During the course of our study, I will be able to work in preventative health in an underserved setting with the same population that I will be working with during my clinical rotations. Additionally, it will also allow me to have longitudinal clinical exposure to a complicated disease in the dynamic field of HIV. In terms of my research interests in infectious diseases and epidemiology, this project will serve as an applied experience in utilizing epidemiological methods to analyze this patient population, as well as the introduction of a new diagnostic test.

JB: What do you think could get your peer group more interested in working in the field of HIV?

KH: I think that the field of ID [infectious disease] is unique in that you are also very much immersed in the social and political issues affecting your patients. Many infectious diseases affect individuals in society that are also affected by things like poverty and homelessness, as well as social stigma. For those working in the field of ID and HIV, battling these issues is just as important as battling the infection for an individual. So, if someone already has an interest in these social issues, the field of HIV would certainly present a challenging opportunity.

In terms of gaining more interest in working in the field of HIV, I think education is a very important part of this. The field of HIV research and clinical practice is incredibly dynamic and is changing constantly. Everyone could always be more informed of the opportunities that exist to work in the field of HIV, and how HIV affects an individual's health outside the realm of ID. For example, another one of my research projects is looking at pulmonary pathologies in people living with HIV, and my mentors are in specialties outside ID.

This transcript has been lightly edited for clarity.

Jeanine Barone is a scientist and journalist with an eclectic background. She's a nutritionist and exercise physiologist who regularly writes about travel, health, fitness, and food for numerous top-tier publications. Jeanine enjoys active travel, especially long-distance cycling and cross-country skiing.